Contributions of biotic and abiotic processes to the presence of an aggregate hierarchy in three different mineral soils in an experimental incubation study

Abstract

Purpose

This study aims to investigate the presence of aggregate hierarchy during the decomposition of rice straw in a subtropical soil (Ultisol) with large quantities of Fe and Al oxides and in two temperate soils with a large amount of montmorillonite (Vertisol) or with less organic matter but a large content of CaCO₃ (Inceptisol) and to explore the relationship between relative contributions of biotic and abiotic processes in soil aggregation and the presence of aggregate hierarchy.

Materials and methods

A 120-day incubation experiment with or without ¹³C-labeled straw was conducted in the above-mentioned three soils previously sieved at < 0.25 mm (i.e., without macroaggregates). During incubation, the aggregate size distribution, aggregate associated organic C (OC), straw-derived ¹³C, soil respiration, soil microbial biomass C and N, and phospholipid fatty acids were measured several times.

Results and discussion

At the end of each experiment, both macro- and microaggregates were present. Higher OC and ¹³C concentrations in macroaggregates than in the fractions < 0.25 mm were observed within the first 15 days in all three soils. However, after 60 days, only the Vertisol could still show a slightly higher OC concentration in the macroaggregates. Same as the temperate Vertisol and Inceptisol, more macroaggregates could form by organic binding agents than by inorganic binding agents in the Ultisol at the early incubation stage. While similar to the subtropical Ultisol, macroaggregates could also mainly form by inorganic binding agents than by organic binging agents in the Vertisol and Inceptisol at the later stage. Despite the microbial community structure being different from each other, the macroaggregation was significantly related to the microbial biomass and activity in all three soils at the early incubation stage.

Conclusions

A high degree of aggregate hierarchy can present in all three soils at the early decomposition stage of rice straw, while at the later stage, no aggregate hierarchy or only a small degree of aggregate hierarchy can present in the Ultisol and Inceptisol or in the Vertisol. Consequently, instead of soil type, the expression of aggregate hierarchy is essentially determined by the relative contributions of biotic and abiotic processes or of organic and inorganic binding agents in soil aggregation.

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A novel dynamic distraction external fixator for proximal interphalangeal joint fracture dislocation

Journal of International Medical Research, Ahead of Print.


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The learning curve in blind bedside postpyloric placement of spiral tubes: data from a multicentre, prospective observational study

Journal of International Medical Research, Ahead of Print.


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Mitral valve blood cyst occlusion of the aortic valve leading to syncope: detection by transthoracic and contrast echocardiography

Journal of International Medical Research, Ahead of Print.


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Comparative study of urethroplasties to reduce urethral strictures in patients with severe hypospadias

Journal of International Medical Research, Ahead of Print.


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Citric acid and itaconic acid accumulation: variations of the same story?

Abstract

Citric acid production by Aspergillus niger and itaconic acid production by Aspergillus terreus are two major examples of technical scale fungal fermentations based on metabolic overflow of primary metabolism. Both organic acids are formed by the same metabolic pathway, but whereas citric acid is the end product in A. niger, A. terreus performs two additional enzymatic steps leading to itaconic acid. Despite of this high similarity, the optimization of the production process and the mechanism and regulation of overflow of these two acids has mostly been investigated independently, thereby ignoring respective knowledge from the other. In this review, we will highlight where the similarities and the real differences of these two processes occur, which involves various aspects of medium composition, metabolic regulation and compartmentation, transcriptional regulation, and gene evolution. These comparative data may facilitate further investigations of citric acid and itaconic acid accumulation and may contribute to improvements in their industrial production.

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Mapping orbital changes upon electron transfer with tunnelling microscopy on insulators

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Risk assessment of frost damage to sugar beet simulated under cold and semi-arid environments

Abstract

In the semi-arid climatic conditions, water shortage is a key factor to generate crop production. Planting in autumn and winter and using precipitation can help cope with the problem. But in the semi-arid areas with cold winter, frost is another limited factor affecting crop production. For this purpose, in the present study, a simple and universal crop growth simulator (SUCROS) model was used to estimate the potential yield of sugar beets and frost damage from 1993 to 2009 for four autumn sowing dates (2 October, 17 October, 1 November, and 16 November) and two spring dates (6 March and 6 May) in eight locations (Birjand, Bojnord, Ghaen, Mashhad, Torbat-e Heydarieh, Neyshabor, Torbat-e Jam, and Ghochan) of the Khorasan province in northeastern Iran as a semi-arid and cold area. There was a large variability between locations and years in terms of frost damage. The crop failure from frost for the autumn sowing dates ranged from 62.5 to 100% at Neyshabor and Ghochan, respectively. Although autumn sowing dates performed better than spring sowing dates in terms of fresh storage organ yield (~ 109.9 t ha⁻¹ vs. ~ 78.4 t ha⁻¹), the risk of frost stress under autumn sowing dates was high at all studied locations. To maximize potential yield and minimize frost risk, sugar beet farmers under semi-arid and frost-prone conditions in the world such as Khorasan province should choose optimum sowing dates outside the high frost risk period to avoid crop damage. The last frost day under these areas normally happened between the 15th and 28th of February, after which no frost events occurred. Accordingly, it is recommended to farmers to sow sugar beet after the period during which no frost risk for sugar beet occurred.

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A case of human pancreatic eurytremiasis

Abstract

This study provides the first comprehensive imaging report of human pancreatic eurytremiasis. A 43-year-old man with obstructive jaundice and a pancreatic tumor was referred for diagnosis and treatment. Serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase were elevated. Computed tomography (CT) revealed a multilocular cystic lesion with delayed enhanced area in the pancreas head. On magnetic resonance imaging, the tumor was hyperintense on diffusion-weighted image, and the apparent diffusion coefficient value of the tumor was lower than that of the normal pancreatic parenchyma. Positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-d-glucose integrated with computed tomography (¹⁸F-FDG PET/CT) revealed abnormally increased uptake of ¹⁸F-FDG in the tumor. A subtotal stomach-preserving pancreaticoduodenectomy was performed on the preoperative diagnosis of pancreatic carcinoma accompanied by branch duct-type intraductal papillary mucinous neoplasm. Multifocal granulomatous lesions with necrotic areas including many parasite eggs were seen on the histology. The final diagnosis was pancreatic eurytremiasis.

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MicroRNA-143 is Associated With Pathological Complete Response and Regulates Multiple Signaling Proteins in Breast Cancer

Technology in Cancer Research &Treatment, Volume 18, Issue , January 2019.


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Inhalation cancer risk estimation of source-specific personal exposure for particulate matter–bound polycyclic aromatic hydrocarbons based on positive matrix factorization

Abstract

In previous studies, inhalation cancer risk was estimated using conventional risk assessment method, which was normally based on compound-specific analysis, and cannot provide substantial data for source-specific particulate matter concentrations and pollution control. In the present study, we applied an integrated risk analysis method, which was a synthetic combination of source apportionment receptor model and risk assessment method, to estimate cancer risks associated to individual PAHs coming from specific sources. Personal exposure particulate matter samples referring to an elderly panel were collected in a community of Tianjin, Northern China, in 2009, and 12 PAH compounds were measured using GC-MS. Positive matrix factorization (PMF) was used to extract the potential sources and quantify the source contributions to the PAH mixture. Then, the lung cancer risk of each modeled source was estimated by summing up the cancer risks of all measured PAH species according to the extracted source profile. The final results indicated that the overall cancer risk was 1.12 × 10⁻⁵, with the largest contribution from gasoline vehicle emission (44.1%). Unlike other risk estimation studies, this study was successful in combining risk analysis and source apportionment approaches, which allow estimating the potential risk of all source types and provided suitable information to select prior control strategies and mitigate the main air pollution sources that contributing to health risks.

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Antidepressant based on party drug gets backing from FDA advisory group

Antidepressant based on party drug gets backing from FDA advisory group

Antidepressant based on party drug gets backing from FDA advisory group, Published online: 13 February 2019; doi:10.1038/d41586-019-00559-2

Esketamine could soon be approved for use in people, although questions remain about its efficacy and potential for abuse.

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Four decades of the coexistence of beech and spruce in a Central European old-growth forest. Which succeeds on what soils and why?

Abstract

Aims

The dynamics of forests dominated by European beech (Fagus sylvatica) and Norway spruce (Picea abies) have been studied intensively. However, mainly due to a lack of long-term data, little is known about how these dynamics interact with soil conditions. In an old-growth spruce-beech forest with high soil diversity we studied how the development of tree populations differs among different soils.

Methods

Data from tree censuses carried out in 1972, 1996 and 2010 in the Boubín Primeval Forest in the Czech Republic were combined with detailed soil sampling to assess the relative abundance of beech and spruce and the role of the main drivers of population dynamics (tree growth, mortality and recruitment) in changes with respect to soils.

Results

The spatial distribution of populations of the two species primarily reflected a gradient of soil hydromorphism, with beech dominating drier soils and spruce dominating wetter soils. Over the 38 years, beech expanded on all major soils, yet the most important drivers differed. The only driver acting in favour of spruce on certain terrestrial soils was its faster radial growth. However, the effect was weaker than the effect of drivers that prioritized beech, mainly tree mortality. Fine-scale mortality (deaths of individual trees) was more significant on terrestrial soils, while the effect of coarse-scale mortality (deaths from a single severe windstorm event) increased towards hydromorphic soils. Certain soils (Histosols and Albic Podzols) diverged from the general trends because of their different disturbance regimes and specific tree–soil interactions.

Conclusions

Soils play an important role in the dynamics of an old-growth spruce-beech forest. Their physical and chemical properties together with specific disturbance regimes determine fine-scale differences in tree species composition. At the same time, soils themselves are affected by trees, e.g. through acidification. The current expansion of beech is expected to continue on terrestrial soils but will probably slow down with increasing soil wetness.

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Uptake of rare earth elements by citrus plants from phosphate fertilizers

Abstract

Background and Aims

Rare earth elements (REE) are a group of the periodic table formed by 17 chemical elements (lanthanoids plus yttrium and scandium). They have been used in different field applications. In agriculture, they can be found in some phosphate fertilizers at levels one or two orders of magnitude higher than those found in normal agricultural soils. Citrus plants are known to present high levels of REE when compared to most other species, however, there is little information about bioavailability of REE in phosphate fertilizers for citrus plants. This work focuses on the study of REE behavior by the application of increasing doses of single superphosphate fertilizer in Rangpur lime (Citrus limonia Osbeck) plants in a greenhouse study.

Methods

The technique used was instrumental neutron activation analysis (INAA).

Results

The results showed that the fertilizer has caused significant increases in the content of REE in the citrus plant tissues, with higher concentrations in leaves than in branches. The highest substrate-leaf transfer factor was observed for La (0.0047), though the concentrations in the plants followed the same order found in the substrate, i.e. Ce > La > Sm > Eu > Sc.

Conclusion

There was an increase of rare earth elements concentrations in Rangpur lime plants by superphosphate fertilizer application.

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Visualization and quantification of root exudation using 14 C imaging: challenges and uncertainties

Abstract

Background and aims

Root exudation is an important carbon (C) and energy source for soil microorganisms but quantifying its spatial distribution is challenging. We tested whether ¹⁴C imaging (analogue of previous autoradiography) can be used to quantitatively estimate the spatial distribution of root exudates in the rhizosphere.

Methods

First, the attenuation coefficient of ¹⁴C β⁻ rays in soil and in water was measured and expected gradients of ¹⁴C in the rhizosphere were modelled. Secondly, barley plants were pulse labelled in ¹⁴CO₂ atmosphere and the origin (roots or root exudation) and locations of ¹⁴C signal in soil were detected with imaging.

Results

The attenuation coefficient of ¹⁴C was 148 cm⁻¹ for soil and 67 cm⁻¹ for water, corresponding to a maximum distance that ¹⁴C β⁻ rays pass through a dry soil of 0.37 mm. Based on the measured coefficients we calculated the effect of exudation intensity, root radius and root position on the imaged ¹⁴C signal. The distribution of the imaged signal was strongly affected by: a) ¹⁴C activity in the root, b) root radius, c) distance from the root surface to the imaging screen, d) amount of root exudates in the soil, and e) presence of an air gap (or a region with high porosity) between the soil and the imaging screen.

Conclusions

Neglecting the effects of these factors (a-e) may cause biases in the estimation of root exudates using ¹⁴C imaging of the rhizosphere. The ¹⁴C imaging approach should therefore be accompanied by accurate measurement of these factors and calculation of the β⁻ ray transmission through the soil.

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A unique aluminum resistance mechanism conferred by aluminum and salicylic-acid-activated root efflux of benzoxazinoids in maize

Abstract

Background and aims

Although aluminum (Al) exclusion via root exudation of organic matters is a common resistance mechanism adopted by many plant species, whether root exudation of benzoxazinoids, such as hydroxamic acids (HAs), confers Al resistance remains unclear.

Methods

We performed physiological characterization for an Al-resistant maize cultivar TY and a sensitive maize cultivar ZD.

Results

First, Al exposure induced HA exudation from the root tip of TY, but not from ZD. Second, HAs formed non-toxic Al chelation complexes in vitro and exogenous HAs alleviated root damage and improved root growth under Al stresses. Third, both Al and exogenous salicylic acid (SA) treatments induced accumulation of endogenous SAs in the root apices of TY, which in turn enhanced root HA exudation and Al resistance in TY. Furthermore, an SA biosynthesis inhibitor significantly decreased Al resistance in TY and abolished the beneficial effects of exogenous SA on Al resistance, suggesting a key role of the endogenous SAs in induction of Al resistance. Finally, it was the root-tip HA exudation but not the root-tip HA contents that determined Al resistance in maize.

Conclusion

We have revealed a unique Al exclusion mechanism underlying Al resistance via Al and SA-mediated root HA efflux in maize.

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Naked oats biochar-supported nanoscale zero-valent iron composite: effects on Cd immobilization and enzyme activities in Ulansuhai River sediments of China

Abstract

Purpose

This investigation aimed to synthesize biochar-supported nanoscale zero-valent iron (BC-nZVI) to immobilize cadmium (Cd) in contaminated sediments of shallow grass-type rivers in typical cold and arid regions in northern China and reduce the bioavailability of Cd. Besides, the influence of multiple factors on the immobilization effect was discussed. In particular, the effects of the addition of humic acid (HA) on the fraction of Cd and enzyme activities were investigated.

Materials and methods

In this study, BC-nZVI was synthesized and all materials were characterized by field emission scanning electron microscopy (FESEM), energy dispersive spectrometer (EDS), x-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR). The remediation effect of BC-nZVI on Cd-contaminated sediments was evaluated through sequential extraction experiments. Batch tests such as experiments of iron-to-carbon ratio, dosage, and incubation time were examined; the effect of HA concentration on Cd immobilization was highlighted, and corresponding enzyme activities (catalase, urease, and alkaline phosphatase) were tested for further illustration.

Results and discussion

BC-nZVI could immobilize Cd efficiently, with the maximum residual percentage of Cd increasing by 19.57 to 81.98% after 35 days of incubation, at 1:3 iron-to-carbon ratio and 0.05 g dosage. Sequential extraction experiments indicated that most labile fractions of Cd were transformed into stable fraction. When 10 and 20 mg kg⁻¹ HA were added, immobilization was enhanced, and residual fraction increased to 89.43% and 88.70%, respectively. Meanwhile, exclusive of catalase, the activities of urease and alkaline phosphatase were enhanced with increased incubation time.

Conclusions

This study proved that BC-nZVI has a significant effect on Cd immobilization. The addition of HA greatly promoted the immobilization of Cd and enzyme activities in sediments. In conclusion, BC-nZVI is an effective substance that can be used to remediate sediments contaminated with heavy metals.

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STEP as a Useful Tool to Screen for Diabetes-Specific Health-Related Problems in Community-Based Geriatric Patients- An Exploratory Secondary Analysis of Cross-Sectional Data

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0803-0362

Background and Aims Comprehensive geriatric assessments are established tools for the identification of health problems in the elderly. So far, little is known about tailoring and targeting to facilitate their application. As a starting point for a tailored assessment of patients with diabetes, a highly prevalent health condition, we aimed to assess if the Standardized Assessment of Elderly People (STEP) is able to identify relevant differences in self-reported health problems between diabetic and non-diabetic patients. Patients and Methods We performed a secondary analysis of a cross-sectional study including 1007 adults (aged 65 and older) from 28 German general practices, evaluating the feasibility and usefulness of the self-administered STEP version. For this exploratory study we re-analysed the data and compared patients with and without diabetes. Results Out of 940 patients included in the secondary analysis, 248 (26.4%) had diabetes. Compared to non-diabetic patients, geriatric diabetic patients reported more often problems in activities of daily living, physical problems typically associated with diabetes such as urinary incontinence, visual impairment, mood disturbances, as well as the use of medical or social services. Most of our results were stable after adjusting for age, sex and body mass index. Conclusion We conclude that the self-administered version of the STEP tool may be used to screen for health problems typically associated with diabetes. Our results may guide the development of a tailored STEP-version specifically for diabetic patients. Further research might evaluate the adoption and usefulness of such a tool in every-day general practice.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Association of the PNPLA2, SCD1 and Leptin Expression with Fat Distribution in Liver and Adipose Tissue From Obese Subjects

Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0829-6324

The expansion of adipose tissue is regulated by insulin and leptin through SREBP-1c, up-regulating lipogenesis in tissues by SCD1 enzyme, while ATGL enzyme is key in lipolysis. The research objective was to evaluate the expression of SREBF1, SCD1, PNPLA2, and LEP genes in hepatic-adipose tissue, and related them with the increment and distribution of fat depots of individuals without insulin resistance. Thirty-eight subjects undergoing elective cholecystectomy with liver and adipose tissue biopsies (subcutaneous-omental) are included. Tissue gene expression was assessed by qPCR and biochemical parameters determined. Individuals are classified according to the body mass index, classified as lean (control group, n=12), overweight (n=11) and obesity (n=15). Abdominal adiposity was determined by anthropometric and histopathological study of the liver. Increased SCD1 expression in omental adipose tissue (p=0.005) and PNPLA2 in liver (p=0.01) were found in the obesity group. PNPLA2 decreased expression in subcutaneous adipose tissue was significant in individuals with abdominal adiposity (p=0.017). Anthropometric parameters positively correlated with liver PNPLA2 and the expression of liver PNPLA2 with serum leptin. SCD1 increased levels may represent lipid storage activity in omental adipose tissue. Liver PNPLA2 increased expression could function as a primary compensatory event of visceral fat deposits associated to the leptin hormone related to the increase of adipose tissue.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Antidepressant based on party drug gets backing from FDA advisory group

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Young bats rely on Mum for real-estate advice

Young bats rely on Mum for real-estate advice

Young bats rely on Mum for real-estate advice, Published online: 13 February 2019; doi:10.1038/d41586-019-00544-9

Offspring are shown to the best bat boxes and tree holes, but receive no assistance when it comes to self-catering.

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Young bats rely on Mum for real-estate advice

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Revision Stapes Surgery: A Novel Technique of Overcoming Erosion of the Long Process of Incus Using Hydroxylapatite Cement and Shape Memory Piston

Background: Stapes surgery is performed to treat hearing loss in patients with otosclerosis. Erosion of the long process of incus can occur postoperatively and requires demanding revision surgery to further improve the hearing. The authors describe a novel method of performing revision stapes surgery where there is erosion of the long process of incus. Methods: A retrospective case series analysis of a database of revision stapes operations performed by one surgeon between July 2013 and December 2017 at a tertiary center was carried out. 26 cases were identified where there was significant erosion of long process of incus. The ossicular chain in these cases was reconstructed using a novel technique of using cement to fix the piston prosthesis to the incus remnant. The full technique is described herein. The pre- and postoperative audiometric data were analyzed. Results: Mean preoperative air bone gap (ABG) was 29.3 dB and mean postoperative ABG was 9.9 dB. Of the 22 patients with recorded postoperative masked bone conduction thresholds, 16 had ABG closure to

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The Natural History of Hearing Loss in Pendred Syndrome and Non-Syndromic Enlarged Vestibular Aqueduct

Introduction: The aim was to investigate the progress of hearing loss over time in a cohort of pendred syndrome and non-syndromic enlarged vestibular aqueduct (PS/NSEVA) with one or two confirmed pathogenic variations in SLC26A4. Study Design: Retrospective cohort study. Subjects and Methods: At our tertiary referral center, a retrospective search of all patients with enlarged vestibular aqueduct, hearing loss and SLC26A4 mutations yielded 103 individuals by March 2017, 96 of whom had records of hearing levels; both an early audiometry and the latest between 3 and 668 months follow-up. Pure-tone average (PTA; average of thresholds at 0.5, 1, 2 and 4 kHz) was calculated for both ears at time 1 and time 2. Neonatal screening results were retrieved. Results: Eighty-seven (87) individuals had biallelic (M2) and 16 had monoallelic alterations (M1) in their SLC26A4. On average, the PTA progressed to 80 dB HL by the age of 6 years for the entire cohort, and 3.2 years for the biallelic (M2) affected individuals. 25% of the cohort was screened in the neonatal screening program; of these 42% had "passed" at least monaurally. Audiometric profiles related to age show faster deterioration in high frequencies than in low frequencies. Conclusion: In patients with PS/NSEVA and SLC26A4 mutations, the average hearing loss progresses to 80 dB HL by the age of 6 years. For biallelic (M2) affected individuals it was 3.2 years. Although hearing levels reached severe to profound during childhood, almost 1/2 had passed neonatal hearing screening, at least monaurally, emphasizing the need for close follow-up.

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Accessory Auricle Deformity of Eustachian Tube

No abstract available

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Book Review: Color Atlas of Endo-Otoscopy: Examination-Diagnosis-Treatment, by Mario Sanna et al.; Thieme Publishers, 2017.

No abstract available

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An Assessment of the Change in Compliance of Observational Otology and Audiology Studies With the STROBE Statement Guidelines: A Systematic Review

Objectives: Observational studies often represent the best available evidence for surgical practice. Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations were generated in 2007 with the aim of improving the quality of reporting. This study was designed to assess whether publication of STROBE guidelines has improved the quality of reporting in observational otology and audiology studies. Data Sources: EMBASE and MEDLINE were searched using a comprehensive keyword search developed in conjunction with a scientific librarian. Study Selection: English language papers from six Otorhinolaryngology journals during two 6-month periods (2005 and 2016) were evaluated. Data Extraction: Two reviewers independently analyzed papers according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Data Synthesis: Percentage scores for the two periods were compared using Mann–Whitney U test. Conclusions: Forty and 42 studies were returned for the 2005 and 2016 periods, respectively. The mean percentage of STROBE items that were met improved between 2005 and 2016 (58, 76%, respectively; p 

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Hybrid Music Perception Outcomes: Implications for Melody and Timbre Recognition in Cochlear Implant Recipients

Objective: To examine whether or not electric–acoustic music perception outcomes, observed in a recent Hybrid L24 clinical trial, were related to the availability of low-frequency acoustic cues not present in the electric domain. Study Design: Prospective, repeated-measures, within-subject design. Setting: Academic research hospital. Subjects: Nine normally hearing individuals. Intervention: Simulated electric–acoustic hearing in normally hearing individuals. Main Outcomes Measures: Acutely measured melody and timbre recognition scores from the University of Washington Clinical Assessment of Music Perception (CAMP) test. Results: Melody recognition scores were consistently better for listening conditions that included low-frequency acoustic information. Mean scores for both acoustic (73.5%, S.D. = 15.5%) and electric–acoustic (67.9%, S.D. = 21.2%) conditions were significantly better (p  0.05). Conclusion: Recipients of hybrid cochlear implants demonstrate music perception abilities superior to those observed in traditional cochlear implant recipients. Results from the present study support the notion that electric–acoustic stimulation confers advantages related to the availability of low-frequency acoustic hearing, most particularly for melody recognition. However, timbre recognition remains more limited for both hybrid and traditional cochlear implant users. Opportunities remain for new coding strategies to improve timbre perception.

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Longitudinal Analysis of “Window Shade” Tympanoplasty Outcomes for Anterior Marginal Tympanic Membrane Perforations

Objectives: Although many techniques have been proposed for the repair of tympanic membrane perforations, few address the unique challenges presented by anterior marginal perforations. In these circumstances, traditional underlay and overlay techniques are often complicated by issues including blunting of the anterior tympanomeatal angle, graft lateralization, delayed healing, and reduced graft take rates. The "window shade" tympanoplasty technique described in this paper incorporates several aspects of the underlay and overlay techniques to address these issues. Study Design and Setting: A retrospective chart review was conducted at an academic medical center, of all patients who underwent window shade tympanoplasty from 1994 to 2016 by a single surgeon. Patients: A total of 412 patients aged 6 to 76 years old were included in the study. Patients who had undergone concomitant ossicular chain reconstruction were excluded from the hearing outcome portion of the analysis. Main Outcome Measures: Any patients observed to have residual postoperative perforations within the first 6 months after surgery were considered to have graft failure. Complications such as otorrhea, serous otitis media, epithelial pearls, and post-auricular infection were tabulated. Air-bone gap closure was also assessed. Results: Postoperative outcomes of 412 patients were assessed including graft take rate, complication rates, and air-bone gap closure. The graft take success rate was 94.2%. Overall complication rate was 4.6%. 82.6% of patients achieved air-bone gap closure within 10 dB. Conclusions: The results of this study further reinforce the success of the window shade technique in repairing anterior marginal tympanic membrane perforations.

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Modified-Power-Piston: Short-Incudial-Process-Vibroplasty and Simultaneous Stapedotomy in Otosclerosis

Objective: If mixed-hearing-loss (MHL) occurs in otosclerosis, hearing-aids (HA) in addition to conventional-stapedotomy (SDT) may be necessary. If otosclerosis progresses or technical or medical problems prevent use of HA, combining active-middle-ear-implants (AMEI) with SDT ("power-piston") may be considered. Previously, AMEI-coupling to the long-incudial-process was suggested. Here, a "modified-power-piston" surgery (mPP) coupling to the short-incudial-process was proposed, so no coupling over the positioned stapes-piston is required. We questioned whether mPP is as safe and effective as SDT. Methods: Otosclerotic patients with MHL and limited satisfaction with previously worn HA receiving mPP were retrospectively reviewed at two Austrian tertiary otologic referral centers. Patients, receiving stapedotomy, were case-matched for preoperative pure-tone averages (PTA), bone-conduction (BC-PTA), air-conduction (AC-PTA), and air-bone gap (ABG-PTA). Postoperative changes in BC-PTA and in AC-PTA and ABG-PTA were defined as safety- and as efficacy outcome parameter. Results: Of 160 patients, 14 received mPP and 14 stapedotomy. Preoperative findings were comparable (all p = 1.000). BC-PTA improved from 38.0 to 36.7 and from 37.1 to 36.9 dB-HL for mPP and SDT, respectively (Δ –1.3 versus –0.2 dB-HL; p = 0.077). AC-PTA improved from 66.8 to 47.1 and from 66.3 to 46.5 dB-HL for mPP and SDT, respectively (Δ –19.6 versus –19.7 dB-HL; p = 0.991). ABG-PTA improved from 28.8 to 10.4 and from 29.1 to 9.6 dB-HL for mPP and SDT, respectively (Δ –18.3 versus –19.5 dB-HL; p = 0.771). Conclusion: In otosclerosis with MHL and limited satisfaction with HA, mPP appeared as safe and effective as SDT and may be considered a treatment alternative in these patients.

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The Father of the Electrical Stimulation of the Ear

The Italian physicist Count Alessandro Volta, inventor of the electric battery, is considered the first scientist to have stimulated the ear with electricity, and the results of his experiments were presented in June 1800, at a meeting held by the Royal Society of London. Just recently, Mudry reported an electrical stimulation of the ear performed in 1748 by Benjamin Wilson (1721–1788), a British painter and scientist. After a thorough review of the literature available from the 18th century, we found that the first electrical stimulation of the ear was done in 1747, by a scientist in Bologna, Giuseppe Veratti.

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Temporal Modulation Detection in Children and Adults With Cochlear Implants: Initial Results

Objectives: The auditory experience of early deafened pediatric cochlear implant (CI) users is different from that of postlingually deafened adult CI users due to disparities in the developing auditory system. It is therefore expected that the auditory psychophysical capabilities between these two groups would differ. In this study, temporal resolving ability was investigated using a temporal modulation detection task to compare the performance outcomes between these two groups. Design: The minimum detectable modulation depth of amplitude modulated broadband noise at 100 Hz was measured for 11 early deafened children with a CI and 16 postlingually deafened adult CI users. Results: Amplitude modulation detection thresholds were significantly lower (i.e., better) for the pediatric CI users than for the adult CI users. Within each group, modulation detection thresholds were not significantly associated with chronologic age, age at implantation, or years of CI experience. Conclusions: Early implanted children whose auditory systems develop in response to electric stimulation demonstrate better temporal resolving abilities than postlingually deafened adult CI users. This finding provides evidence to suggest that early implanted children might benefit from sound coding strategies emphasizing temporal information.

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The Biomechanics of Lesion Formation in Endolymphatic Hydrops: Single and Double Hit Mechanisms

Background: The vestibular membranes of the cochlea and saccule are subject to two simultaneous constraints as they deform in endolymphatic hydrops. Boundary tethers impose a bulge-type constraint during pressure-induced transverse membrane displacement, while inherent elasticity imposes a stretch-type constraint during stress-induced longitudinal membrane distention. Objective: The aim of this study is to reconcile the effect of these dual constraints on membrane deformation. It is hypothesized that it is the interaction of these constraints that determines whether a stable membrane configuration can be achieved or progression to endolymphatic hydrops will occur. Methods: Reissner's membrane was modeled as a flat elastic ribbon that was bound along its lateral edges and subject to trans-mural pressure. The bulge and stretch constraints on membrane deformation were formulated mathematically. A graphic solution of the constraint functions was used to examine the nature of the interaction and determine how pressure and elasticity influence the hydropic process. Results: The graphic analysis shows how bulge and stretch phenomena interact to achieve an equilibrium point that satisfies both physical requirements. Nominal values of pressure and elasticity are projected to result in a stable membrane equilibrium in the precritical zone with the modest isolated increases in either parameter alone compatible with stability. However, a sufficiently large increase in either pressure or elasticity alone can constitute a single hit mechanism to exceed the critical point and destabilize the membrane. Moreover, simultaneous modest increases in both pressure and elasticity, neither of which would be sufficient in its own right, can be additive and constitute a double hit mechanism to destabilize the membranes as well. Finally, extreme values of pressure and elasticity that fail to intersect imply that no solution is feasible and that the affected membranes will fail immediately. Conclusions: Sufficiently large increases in either endolymphatic pressure or membrane elasticity alone can destabilize the membranes and constitute single hit mechanisms for inducing hydrops. Combined moderate increases in both trans-mural pressure and membrane elasticity can also destabilize the membranes and constitute a double hit mechanism for hydrops induction.

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Involvement of the Internal Auditory Canal in Subjects With Cochlear Otosclerosis: A Less Acknowledged Third Window That Affects Surgical Outcome

Objective: To investigate the effects of cavitating lesions involving the internal auditory canal (IAC) in subjects with cochlear otosclerosis with regard to poststapedotomy hearing outcome. Study Design: Retrospective study. Setting: Tertiary referral center. Patients: A retrospective chart review of 134 subjects with otosclerosis treated from January 2011 to June 2017 at Seoul National University Bundang Hospital was conducted. Sixteen subjects (23 ears) with temporal bone computed tomography (TBCT)-confirmed cochlear otosclerosis who underwent stapedotomy were included in the study. Main Outcome Measures: Pure tone audiometry (PTA) (i.e., air and bone conduction; AC and BC, respectively) thresholds and air–bone gap (ABG), measured at 6 months postoperatively were compared between cochlear otosclerosis with and without IAC involvement (IAC group and non-IAC group, respectively). Results: A total of 14 of 23 ears showed involvement of the IAC. There were no significant differences in age, side of otosclerosis, or preoperative hearing threshold between the two groups. The mean postoperative AC and BC thresholds and ABG of the IAC group were significantly poorer (45.7 dB, 33.8 dB, and 11.8 dB, respectively) than those of the nonIAC group (24.1 dB, 20.0 dB, and 4.1 dB, respectively). Conclusions: Cochlear otosclerosis with cavitating lesions involving the IAC showed significantly poorer postoperative audiological outcomes than those without any cavitating lesion. Cavitation extending to the IAC may act as a third window providing a route for sound energy shunting, and thus precluding successful hearing outcome in some subjects with cavitating otosclerosis after stapedotomy.

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Sequential versus Combination Treatment Using Steroids and Diuretics for Acute Low-Frequency Sensorineural Hearing Loss: A Noninferiority Trial

Objective: Acute low-frequency hearing loss (ALHL) is typically treated with combination therapy, including steroids and diuretics. To avoid unnecessary use of steroids we proposed a method of sequential administration using these two drugs, and compared the efficacy of our protocol with that of existing combination treatments. Methods: A prospective, randomized, open-label, single-blind, noninferiority clinical trial was conducted to investigate whether the effectiveness of sequential treatment is noninferior to that of combination treatment for ALHL. Ninety-two patients with ALHL received either steroids and diuretics simultaneously for 2 weeks (combination group), or diuretics for 2 weeks followed by steroids for another 2 weeks if they did not respond to diuretic treatment (sequential group). The primary outcome measure was a change in mean hearing threshold at three frequencies (125, 250, and 500 Hz) at 4 weeks after treatment. Results: The mean hearing threshold of the low frequencies improved 20.0 and 17.2 dB in the combination and the sequential group, respectively. The 95% lower confidence interval was −8.0 dB and noninferiority was established at p 

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American Neurotology Society Preliminary Program

No abstract available

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Long-term Changes in Musical Perception in Korean Cochlear Implant Patients

Objective: The purpose of this study was to assess the long-term changes in music perception among cochlear implant (CI) patients using the Korean version of the Clinical Assessment of Music Perception test and questionnaires for music listening. Methods: Twenty-seven CI patients participated in this study. Their music perception ability was evaluated using the Korean version of the Clinical Assessment of Music Perception test, which consisted of pitch discrimination, melody, and timbre identification. The test was conducted at least twice after CI. A questionnaire was also used to quantify listening habits (LH) and level of musical experience (LE). Results: The participants were divided into two groups according to the average of each test result from the first test. In the pitch discrimination test, the just-noticeable-difference limen values increased as the base frequency increased, and significant differences were observed between the results of 262 and 391 Hz (p = 0.006). In the good performance group, pitch discrimination in the second test did not significantly differ from the first test, but the pitch discrimination score significantly improved in the poor performance group. Similarly, timbre test results were significantly improved in the poor performance group. Neither group exhibited changes in the second test for melody identification. The scores for LH and LE significantly decreased postoperatively and did not recover during the follow-up period. Conclusions: Pitch discrimination and timbre identification improved in CI listeners who exhibited poor musical performance shortly after surgery. However, melody identification did not improve over time. LH and LE scores decreased after CI surgery without time-dependent improvement.

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Bilateral Cochlear Implants Using Two Electrode Lengths in Infants With Profound Deafness

Objective: The goal of this investigation was to determine if a short electrode in one ear and standard electrode in the contralateral ear could be an option for infants with congenital profound deafness to theoretically preserve the structures of the inner ear. Similarities in performance between ears and compared with a control group of infants implanted with bilateral standard electrodes was evaluated. Study Design: Repeated-measure, single-subject experiment. Setting: University of Iowa—Department of Otolaryngology. Participants: Nine infants with congenital profound bilateral sensorineural hearing loss. Intervention(s): Short and standard implants. Main Outcome Measure(s): Early speech perception test (ESP), children's vowel, phonetically balanced-kindergarten (PB-K) word test, and preschool language scales-3 (PLS-3). Results: ESP scores showed performance reaching a ceiling effect for the individual short and standard ears and bilaterally. The children's vowel and PB-K word results indicated significant (both p 

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Is Hard Failure Still a Common Indication for Revision Surgery in Adult Cochlear Implant Recipients?

Outcome Objectives: Review a 15-year, single institution experience with adult-cochlear implant (CI) revision surgery.Describe chronologic changes in the incidence of hard failure (HF), soft failure (SF), wound complications (WC), and magnet/device migration (MM). Study Design: Retrospective chart review. Setting: Single tertiary care center, 2001 to 2016. Patients: Adult CI recipients were assessed. Inclusion required ≥1 revision surgeries, operative note(s), and postrevision follow-up of 6 months. Interventions: Therapeutic/rehabilitative. Main Outcomes Measures: Indications for revision (HF, SF, WC, and MM) were tabulated. The incidence of each was compared between cohorts implanted before/after 2011. Additional outcomes included implant usage, explantation rates, and postrevision speech scores. Results: Four hundred thirty-two patients received 512 CIs. Of these, 30 patients required 38 revisions. Median time to revision was 24.5 months. Frequency by indication was HF (n = 14), SF (n = 12), WC (n = 8), and MM (n = 4). The overall revision rate was 7.4%. There was a significant decline in overall revisions for patients implanted before/after 2011 (10.4 versus3.5%; p = 0.009). No patients implanted after 2011 experienced a HF (p = 0.002). Patients with WC/MM had significantly shorter time to revision compared with patients with HF/SF (p = 0.04). The overall median follow-up was 24 months. Twenty-three of 30 patients are still using their revised CI. Patients revised for HF and MM achieved the best outcomes. Conclusion: 7.4% of adult CI recipients required revision surgery. Explantation/immediate reimplantation was an effective management strategy. While HF was the most common indication overall, no patients implanted after 2011 have suffered this complication. The overall revision rate has significantly declined since 2011.

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Grasshopper optimization algorithm–based approach for the optimization of ensemble classifier and feature selection to classify epileptic EEG signals

Abstract

Epilepsy is one of the most common neurological disease worldwide. It is diagnosed by analyzing a long electroencephalogram (EEG) recording in a clinical environment, which may be much prone to errors and a time-consuming task. In this paper, a methodology for the classification of an epileptic seizure is proposed for analyzing EEG signals. EEG signal is decomposed into intrinsic mode functions (IMFs) using empirical mode decomposition (EMD). A fusion, of the extracted non-linear and spike-based features from each of the IMF signals, is made. The parameters of five machine learning algorithms; k-nearest neighbor (k-NN), extreme learning machine (ELM), random forest (RF), support vector machine (SVM), and artificial neural network (ANN) are optimized, as well as a set of the significant features is chosen using grasshopper optimization algorithm (GOA). These classifiers with their optimized parameters are ensembled together for the classification of epileptic seizures. The results show that ensemble classifier performs better than individual classifier. A comparison of the proposed methodology with state of the art epileptic seizure detection techniques is also made for validation.

Graphical abstract

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High-flying pseudosatellites get their day in the sun

High-flying pseudosatellites get their day in the sun

High-flying pseudosatellites get their day in the sun, Published online: 12 February 2019; doi:10.1038/d41586-019-00561-8

Planes and airships that can soar through the stratosphere could enable new approaches to research.

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Neuroglial Differentiation and Neoplasms in Testicular Germ Cell Tumors Lack Immunohistochemical Evidence of Alterations Characteristic of Their CNS Counterparts: A Study of 13 Cases

Overgrowth of neuroglial tissue is rare in testicular germ cell tumors and mostly reported as isolated cases. We retrospectively reviewed 13 cases of testicular germ cell tumors from 2 institutions from 1995 to 2018. Hematoxylin and eosin slides were collected and reviewed. Immunohistochemistry was performed in all cases with available material. The series included 4 primary tumors and 9 metastases, including 8 retroperitoneal and 1 axillary lymph node (LN). The average age was 34 (range: 19 to 54). Five of the LN dissections were postchemotherapy, with one a recurrence 5 years after the initial diagnosis. The average tumor size for primary tumors was 5.15 cm (range: 1.7 to 7.3) and for metastases was 6.4 cm (range: 0.6 to 15). The largest size of the neuroglial component was 4.5 cm in the primary tumors and 7.5 cm in metastatic sites. The neuroglial component in the primary site was associated with pure teratoma (n=2) and with a mixed germ cell tumor (teratoma, seminoma, and embryonal carcinoma) (n=2). Cases involving LNs were associated with teratoma (n=4), seminoma (n=2), rhabdomyosarcoma (n=2), primitive neuroectodermal tumors (n=1), and high-grade sarcoma (n=1) (some with >1 other component). Two cases were pure glial tumor. Histologically, the neuroglial components included low-grade astrocytoma (n=3) (both with microcysts formation and pilocytic features), gemistocytic astrocytomas (n=3), anaplastic astrocytoma (n=2), ganglioglioma (n=1), glioblastoma (n=2), gliosarcoma (n=1), and developing central nervous system (CNS) (n=2). By immunohistochemistry, 13/13 (100%) cases were GFAP(+), 10/10 (100%) cases showed retained ATRX, 10/10 were IDH1 pR132H (−), 5/10 (50%) were p53 (+). A single case 1/10 (10%) was BRAF p.V600E (+), but a mutation was not identified by polymerase chain reaction. Follow-up was available in 6 patients; 4 were confirmed to have received chemotherapy with BEP; 1 had a local recurrence and the patient with gliosarcoma developed a lung metastasis morphologically similar to the gliosarcoma of the retroperitoneum. In conclusion, neuroglial differentiation and neoplasms are rare in testicular germ cell tumors and are most commonly associated with teratomas; they can be seen in primary and metastatic sites. They exhibit the full range of neuroglial differentiation including developing CNS to gliomas/glioneuronal tumors WHO grades I-IV. None of the cases showed results consistent with ATRX, IDH or BRAF alterations, suggesting they have different oncogenic mechanisms than their CNS counterparts.

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Novel PLAG1 Gene Rearrangement Distinguishes a Subset of Uterine Myxoid Leiomyosarcoma From Other Uterine Myxoid Mesenchymal Tumors

Genetic alterations in uterine myxoid leiomyosarcoma are unknown. We investigate the clinicopathologic features of 19 uterine tumors previously diagnosed as myxoid leiomyosarcomas in which tumoral RNA was subjected to targeted RNA sequencing. PLAG1, BCOR, BCORL1, HMGA2, and ALK break-apart fluorescence in situ hybridization (FISH) and BCOR, PLAG1, and ALK immunohistochemistry were performed in cases which failed or lacked fusions by sequencing. The diagnosis of myxoid leiomyosarcoma was confirmed in 15 cases after exclusion of 4 tumors with BCOR and ALK rearrangements. These 15 patients presented at a median age of 50 years with stage I (3), II (2), III (2), and IV (1) tumors, respectively; stage was unknown in 7 cases. Tumor size ranged from 10 to 24 cm. Matrix was myxoid in all tumors and also eosinophilic in 2. Cells were spindled, epithelioid, and both in 10, 2, and 3 tumors and showed mild, moderate, and severe nuclear atypia in 3, 8, and 4 tumors, respectively. Mitotic index ranged from

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SOX10, GATA3, GCDFP15, Androgen Receptor, and Mammaglobin for the Differential Diagnosis Between Triple-negative Breast Cancer and TTF1-negative Lung Adenocarcinoma

Triple-negative breast cancer (TNBC) patients have an increased risk of developing visceral metastases and other primary nonbreast cancers, particularly lung cancer. The differential diagnosis of TNBC metastases and primary cancers from other organs can be difficult due to lack of a TNBC standard immunoprofile. We analyzed the diagnostic value of estrogen receptor, progesterone receptor, human epidermal growth factor receptor, thyroid transcription factor-1 (TTF1), Napsin A, mammaglobin, gross cystic disease fluid protein 15 (GCDFP15), Sry-related HMg-Box gene 10 (SOX10), GATA-binding protein 3 (GATA3), and androgen receptor in a series of 207 TNBC and 152 primary lung adenocarcinomas (LA). All tested TNBCs were TTF1 and Napsin A-negative. When comparing TNBC and TTF1-positive or negative LA, SOX10 had the best sensitivity (62.3%) and specificity (100%) as a marker in favor of TNBC compared with LA, irrespective of TTF1 status (P

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Morphologic Overlap Between Inflammatory Myofibroblastic Tumor and IgG4-related Disease: Lessons From Next-generation Sequencing

Inflammatory myofibroblastic tumor (IMT), a locally aggressive neoplasm capable of metastasis, may show an immunoglobulin (Ig)G4-rich lymphoplasmacytic infiltrate. Prior reports suggest that storiform-fibrosis and obliterative phlebitis aid in the distinction of IMT from IgG4-related diseases. Herein, we highlight the morphologic overlap between the 2 diseases, and emphasize the importance of a multiplex fusion assay in the distinction of IgG4-related disease (IgG4-RD) from IMT. We identified 7 IMTs with morphologic and immunohistochemical features of IgG4-RD; 3 patients were originally diagnosed with IgG4-RD. Demographic, clinical and morphologic data was recorded. We also reevaluated 56 patients with IgG4-RD. We performed immunohistochemistry for IgG4, IgG, ALK, and ROS1. In situ hybridization for IgG4 and IgG was performed in selected cases. A multiplex next-generation sequencing–based RNA assay for gene fusions was performed to detect all known IMT-related gene fusions. All 7 IMTs showed a dense lymphoplasmacytic infiltrate and storiform-type fibrosis, with obliterative phlebitis noted in 3 cases. The neoplastic stromal cells constituted

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Pleomorphic and Florid Lobular Carcinoma In Situ Variants of the Breast: A Clinicopathologic Study of 85 Cases With and Without Invasive Carcinoma From a Single Academic Center

The natural history and optimal treatment of pleomorphic (PLCIS) and florid (FLCIS) lobular carcinoma in situ variants remains uncertain. We reviewed the clinicopathologic features and management of LCIS variants at our institution over a 20-year period. Of 85 cases (61 PLCIS, 24 FLCIS), 77% were associated with invasive carcinoma (84% lobular, 13% ductal/lobular, 3% ductal) and only 17% (9 PLCIS, 5 FLCIS) were pure. Most (81%) invasive carcinomas were grade 2, with all grade 3/pleomorphic invasive lobular carcinomas (ILC) associated with PLCIS, and all grade 1 tumors associated with FLCIS. PLCIS-associated invasive carcinomas were more often ER− (21%) or HER2+ (14%) than FLCIS-associated tumors (100% ER+, 6% HER2+). LCIS variants were unifocal and co-localized with invasive carcinoma in 20/20 selected spatially mapped cases, whereas classic LCIS (CLCIS) was multifocal with wider distribution (10/17). Of 21 pure LCIS variants on core biopsy, all represented the radiographic (95%) or palpable (5%) target. The excisional upgrade rate was similar for PLCIS (38%) and FLCIS (33%). Pure LCIS variants on core biopsy were often (20%) HER2+ and had a higher Ki-67-index than synchronous CLCIS (P=0.002). Lower ER expression in LCIS variants versus CLCIS was due to ER− apocrine PLCIS. ER and HER2 were consistently concordant between LCIS variants and upgraded ILC but discordant between synchronous CLCIS and LCIS variants in 5/14 (36%). Pure LCIS variants were excised to negative margins and frequently (58%) treated with endocrine but not radiation therapy without recurrences. In summary, PLCIS and FLCIS demonstrate features of direct precursor lesions warranting surgical excision.

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Napsin A, Hepatocyte Nuclear Factor-1-Beta (HNF-1β), Estrogen and Progesterone Receptors Expression in Arias-Stella Reaction

Background: The Arias-Stella reaction (ASR) can mimic endometrial clear cell carcinoma (ECCC) in small biopsies, especially when drug or pregnancy history is unknown. A panel of immunohistochemical markers comprising napsin A, hepatocyte nuclear factor-1-beta (HNF-1β), estrogen and progesterone receptors (ER, PR) has been found useful in confirming a diagnosis of ECCC. However, the detailed characterization of how expression of this combination of markers in the ECCC mimics ASR has yet to be thoroughly evaluated. Design: The frequency and extent of napsin A, HNF-1β, ER, and PR expression in ASR were assessed in a large series. For napsin A, any cytoplasmic staining was considered positive while only nuclear staining was deemed to be positive for HNF-1β, ER, and PR. Immunohistochemical histoscores based on the intensity and extent of staining were calculated. Results: Forty cases were gestational and 10 were nongestational ASR. In 19 (38%), the reaction was extensive and involved >50% of the glands. A stromal decidual change was found in 31 (77.5%) of the gestational and 3 (30%) of the nongestational cases. Napsin A was positive in all gestational and 8 of 10 (80%) nongestational ASR. All ASR showed HNF-1β expression. ER expression was reduced in 37 (92.5%) and lost in 3 (7.5%) gestational ASR, and reduced in 9 (90%) and lost in 1 (10%) of nongestational ASR. None of the ASR in our series expressed PR. Conclusions: Naspin A and HNF-1β were frequently expressed in both gestational and nongestational ASR, and ER expression was usually either reduced or loss. Interpretation of these markers in small biopsies containing atypical clear cells should be made with caution.

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Pearls and Pitfalls in Neoplastic Dermatopathology

No abstract available

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Comparison of Tumor Regression Grading of Residual Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Chemotherapy Without Radiation: Would Fewer Tier-Stratification Be Favorable Toward Standardization?

To assess whether the College of American Pathologists (CAP) and the Evans grading systems for neoadjuvant chemotherapy without radiation-treated pancreatectomy specimens are prognostic, and if a 3-tier stratification scheme preserves data granularity. Conducted retrospective review of 32 patients with ordinary pancreatic ductal adenocarcinoma treated with neoadjuvant therapy without radiation followed by surgical resection. Final pathologic tumor category (AJCC eighth edition) was 46.9% ypT1, 34.4% ypT2, and 18.7% ypT3. Median follow-up time was 29.8 months, median disease-free survival (DFS) was 19.6 months, and median overall survival (OS) was 34.2 months. CAP score 1, 2, 3 were present in 5 (15.6%), 18 (56.3%), and 9 (28.1%) patients, respectively. Evans grade III, IIb, IIa, and I were present in 10 (31.2%), 8 (25.0%), 7 (21.9%), and 7 (21.9%) patients, respectively. OS (CAP: P=0.005; Evans: P=0.001) and DFS (CAP: P=0.003; Evans: P=0.04) were statistically significant for both CAP and Evans. Stratified CAP scores 1 and 2 versus CAP score 3 was statistically significant for both OS (P=0.002) and DFS (P=0.002). Stratified Evans grades I, IIa, and IIb versus Evans grade III was statistically significant for both OS (P=0.04) and DFS (P=0.02). CAP, Evans, and 3-tier stratification are prognostic of OS and DFS.

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SSTR2a Is a Useful Diagnostic Marker for Follicular Dendritic Cells and Their Related Tumors

SSTR2a, a member of the somatostatin receptor family, has been used as a diagnostic marker of meningioma. However, the expression of SSTR2a in follicular dendritic cells (FDCs) and their related tumors has been poorly characterized. This study aimed to assess the potential diagnostic utility of measuring SSTR2a immunohistochemically in FDCs and their related tumors. We evaluated whole-tissue sections from 182 cases including 83 lymphoid reactive follicular hyperplasias, 17 follicular lymphomas, 18 follicular dendritic cell sarcomas (FDCSs), 6 inflammatory pseudotumor-like FDCSs, and 58 other histologic mimics. Immunohistochemistry for SSTR2a and other FDC markers (CD21, CD23, CD35, clusterin, and podoplanin) were performed in all 182 cases. Diffuse membrane immunoreactivity for SSTR2a in FDCs was observed in 100% of follicular lymphoma and FDCS cases and in 96.4% of the reactive follicular hyperplasias cases. Notably, the positive rate of SSTR2a in FDCSs was higher than that of CD21 (88.9%), CD23 (77.8%), CD35 (94.4%), clusterin (55.6%), and podoplanin (94.4%). All inflammatory pseudotumor-like FDCSs were negative for SSTR2a. The histologic mimics were negative for SSTR2a, except for 1 leiomyosarcoma case that showed focal (~10%) positive expression for SSTR2a. Overall, our findings indicate that SSTR2a is a highly sensitive and diagnostically useful marker for FDCs and FDCSs. Furthermore, immunohistochemistry for SSTR2a may be helpful to distinguish FDCSs from inflammatory pseudotumor-like FDCSs and other histologic mimics. Moreover, our findings suggest that SSTR2a may be a potential therapeutic target for treatment of FDCSs.

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Gray-zone Lymphoma Between cHL and Large B-Cell Lymphoma: A Histopathologic Series From the LYSA

Gray-zone lymphoma (GZL) with features intermediate between classic Hodgkin lymphoma (cHL) and large B-cell lymphoma (LBCL) was introduced as a provisional entity into the World Health Organization classification in 2008. However, as diagnostic criteria are imprecise, reliable identification of GZL cases remains challenging. Here, we describe the histopathologic features of 139 GZL cases from a retrospective Lymphoma Study Association (LYSA) study with the goal to improve classification accuracy. Inclusion criteria were based on literature review and an expert consensus opinion of the LYSA hematopathologist panel. We observed 86 cases with a morphology more closely related to cHL, but with an LBCL immunophenotype based on strong and homogenous B-cell marker expression (CD20 and/or CD79a, OCT2, BOB1, PAX5) on all tumor cells (cHL-like GZL). Fifty-three cases were morphologically more closely related to LBCL but harbored a cHL immunophenotype (LBCL-like GZL). Importantly, we observed a continuous morphologic and immunophenotypic spectrum within these 2 GZL categories. The majority of cases presented genetic immune escape features with CD274/PDCD1LG2 and/or CIITA structural variants by fluorescence in situ hybridization. Patients without mediastinal involvement at diagnosis (17%) were older than those with mediastinal tumors (median: 56 vs. 39 y). Cases associated with Epstein-Barr virus (24%) presented with similar patient characteristics and outcome as Epstein-Barr virus negative cases. In summary, we provide refined diagnostic criteria that contribute to a more precise pathologic and clinical characterization of GZL within a broad spectrum from cHL-like to LBCL-like disease.

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A Combined Morphologic and Molecular Approach to Retrospectively Identify KRAS-Mutated Mesonephric-like Adenocarcinomas of the Endometrium

An unusual subset of endometrial carcinoma, the mesonephric-like adenocarcinomas, are morphologically and molecularly similar to mesonephric carcinoma, characterized by KRAS mutation and lack of microsatellite instability. They also have a unique immunohistochemical profile and are usually positive for GATA-3, CD10, TTF-1, and negative for ER and PR. This study implemented a combined morphologic and molecular approach to retrospectively identify mesonephric-like carcinomas of the endometrium. KRAS-mutated microsatellite stable (MSS) endometrial carcinomas were identified from a database of 570 endometrial carcinomas that had undergone massively parallel sequencing. MSS tumors with canonical KRAS mutations that lacked features diagnostic of endometrioid carcinoma (including squamous or mucinous differentiation), were re-reviewed for morphologic features of mesonephric-like adenocarcinomas. Ninty-eight of 570 endometrial carcinomas (17%) harbored canonical KRAS mutations. Of the KRAS-mutated cases, 80 (82%) were MSS and 18 (18%) had microsatellite instability. Of the KRAS-mutated MSS cases with morphology review, 39/61 (64%) had squamous and/or mucinous differentiation while 22 (36%) lacked these histotype-defining features. Eight of these 22 had PTEN mutations and lacked morphologic features of mesonephric-like adenocarcinoma, leaving 14 cases with a possible mesonephric-like adenocarcinoma-like molecular profile that underwent detailed morphologic re-review. Ten of 14 had morphology typical of serous (3), carcinosarcoma (4), or endometrioid (3) carcinoma. In 4 cases, there was striking morphologic, immunophenotypic, and molecular resemblance to mesonephric carcinoma, leading to re-classification as mesonephric-like adenocarcinoma. Two of the 4 cases presented at an advanced stage, and a third case later developed distant metastases. On the basis of this retrospective study, KRAS-mutated mesonephric-like adenocarcinoma represents ∼1% of all endometrial carcinomas. Future prospective recognition of this unusual variant of endometrial carcinoma may be important given its possible aggressive nature.

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Cholangiolocellular Carcinoma With “Ductal Plate Malformation” Pattern May Be Characterized by ARID1A Genetic Alterations

Cholangiolocellular carcinoma (CLC) is a unique subtype of primary liver carcinoma, which sometimes coexists with hepatocellular carcinoma (HCC), cholangiocarcinoma and combined hepatocellular-cholangiocarcinoma (cHCC-CCA). "Ductal plate malformation" (DPM)-pattern of primary liver carcinoma, which resembles biliary lesions in Caroli disease and von Meyenburg complex, is sometimes associated with CLC. We examined genetic alterations of hTERT promoter (hTERT), IDH1 or 2 (IDH1/2), KRAS, ARID1A, PBRM1, ARID2, BAP1, p53 and their association with histologic features such as proportion of CLC and DPM-pattern in 77 patients with primary liver carcinoma diagnosed as cHCC-CCA or CLC. Primary liver carcinomas were histologically subdivided into 29 CLC-predominant (CLC component >80%), 31 with CLC (5% to 80%) and 17 without CLC (

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Molecular Profiling of Pheochromocytoma and Abdominal Paraganglioma Stratified by the PASS Algorithm Reveals Chromogranin B as Associated With Histologic Prediction of Malignant Behavior

Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGL, are believed to exhibit malignant potential—but only subsets of cases will display full-blown malignant properties. The Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) algorithm is a proposed histologic system to detect potential for aggressive behavior, but little is known regarding the coupling to underlying molecular genetics. In this study, a total of 92 PPGLs, previously characterized for susceptibility gene status and mRNA expressional profiles, were histologically assessed using the PASS criteria. A total of 32/92 PPGLs (35%) exhibited a PASS score ≥4, including all 8 cases with malignant behavior (7 with known metastases and 1 with extensively infiltrative local recurrence). Statistical analyzes between expressional data and clinical parameters as well as individual PASS criteria yielded significant associations to Chromogranin B (CHGB), BRCA2, HIST1H3B, BUB1B, and RET to name a few, and CHGB had the strongest correlation to both PASS and metastasis/local recurrence of all analyzed genes. Evident CHGB downregulation was observed in PPGLs with high PASS and overtly malignant behavior, and was also associated with shorter disease-related survival. This finding was validated using quantitative real-time polymerase chain reaction, in which CHGB expression correlated with both PASS and metastasis/local recurrence with consistent findings obtained in the TCGA cohort. Moreover, immunohistochemical analyses of subsets of tumors showed a correlation between high PASS scores and negative or weak CHGB protein expression. Patients with PPGLs obtaining high PASS scores postoperatively, also exhibited low preoperative plasma levels of CHGB. These data collectively point out CHGB as a possible preoperative and postoperative marker for PPGLs with potential for aggressive behavior.

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Histopathologic False-positive Diagnoses of Prostate Cancer in the Age of Immunohistochemistry

There are few studies into the rate and causes of histopathologic false-positive diagnosis of prostate cancer. Only 2 of these, including a previous one from our group, incorporate survival data. In addition, in none of the previous studies had immunohistochemistry (IHC) been originally requested on any of the misdiagnosed cases. Diagnostic biopsies (n=1080) and transurethral resection of prostate specimens (n=314) from 1394 men with clinically localized prostate cancer diagnosed in the United Kingdom but treated conservatively between 1990 and 2003 were reviewed by a panel of 3 genitourinary pathologists. Thirty-five cases were excluded for being potentially incomplete. Of the remaining 1359, 30 (2.2%) were reassigned to a nonmalignant category (26 benign and 4 suspicious for malignancy). IHC had been originally performed on 7 of these. The reasons for the errors were recorded on each case: adenosis (19), partial atrophy (3), prostatic intraepithelial neoplasia (2), seminal vesicle epithelium (1), and hyperplasia (1). Follow-up of these men revealed only one prostate cancer–related death, possibly due to unsampled tumor. In conclusion, a relatively small number of prostate cancer mimics were responsible for a large proportion of the false-positive prostate cancer diagnoses and the use of IHC did not prevent the overcall of benign entities as cancer in approximately a quarter of these cases. Targeting these mimics at educational events and raising awareness of the pitfalls in the interpretation of IHC in prostate cancer diagnosis, emphasizing that glands within a suspicious focus should be treated as a whole rather than individually, may be beneficial in lowering the rate of false-positive diagnosis.

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George M. Farrow, MD: A Tribute

No abstract available

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A Comprehensive Analysis of the Association Between Gleason Score at a Positive Surgical Margin and the Risk of Biochemical Recurrence After Radical Prostatectomy

Our objective was to identify the best of the existing definitions of Gleason score (GS) at a positive surgical margin (PSM) by validating them in our radical prostatectomy cohort. We analyzed 251 patients who had mixed (3+4, 3+5, 4+3 or 5+3) pathologic GS and PSM. We used 5 definitions to record GS at a PSM. Univariate and multivariate analyses were used to study the association between each definition and the risk of biochemical recurrence (BCR). We also tested the prognostic value of multivariate models including established predictors and each of the studied definitions of GS at a PSM. GS 3+3 was seen at a PSM in 57.4% of the cases and was more common in patients with lower overall GS. Over a median follow-up of 4.0 years 89 patients (35.5%) developed BCR. All of the definitions of GS at a PSM were independent predictors of the BCR-free survival. Most of them also improved the prognostic value of the multivariate models when added to the established parameters. The degree of improvement was similar for the most complex definition (full GS at a PSM) and the easiest to record binary definition (presence of Gleason 4/5 pattern at a PSM). We conclude that compared with the other possible options of reporting GS at a PSM, the presence of Gleason 4/5 pattern may be the most practical definition. It is at least as predictive as other definitions, may be the easiest to record and is the best studied of the existing alternatives.

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LMO2 Negative Expression Predicts the Presence of MYC Translocations in Aggressive B-Cell Lymphomas: Erratum

No abstract available

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OhmniLabs Uses Robots to Make Telepresence a Reality: Interview with CEO Thuc Vu

OhmniLabs uses robots to transform simple video calls into "telepresence," a more natural and immersive form of communication. The Santa Clara, California-based company designs rolling robots with a mounted display and hardware. A user can call in to the robot, connect, and move the robot around its space using a controller. While this might seem like a minor difference from traditional video callds, Co-Founder and CEO Dr. Thuc Vu, PhD points out that it actually changes the experience dra...

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Dinner with a CRISPR Connoisseur

The most exciting development in molecular biology in several years, CRISPR/Cas 9 gene editing technology has become prominent for all the wrong reasons of late. Far from the media storm, Richard Sherwood, Assistant Professor of Medicine at Harvard Medical School, Massachusetts, USA, is trying to improve the efficacy of the technology, which remains beset by problems. Donor templates, which are often used in conjunction with CRISPR/Cas9 to guide the cell to produce a desired edit, work ineffi...

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Versatile Microplate Sealing System

Set-up to quickly and securely seal 96-well deep well microplates as standard, the Autocapper is compatible with shallow well and several other plate formats (24-well, 48-well) using a range of supplied adapter blocks. Designed to meet the needs of laboratories for low to medium throughput microplate sealing, the Autocapper is compact and easy-to-use. With just a touch of a button, the powerful, yet smooth operating mechanism makes single action sealing of microplates quick and simple th...

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Role of compost biochar amendment on the (im)mobilization of cadmium and zinc for Chinese cabbage ( Brassica rapa L.) from contaminated soil

Abstract

Purpose

This study aims to assess the effect of amendment of an alkaline Zn, Cd-contaminated soil with compost of wheat straw biochar (CB) (4, 8, 12, and 18%) and sludge and different dosages of nitrogen. In addition, this study aimed to substantially mitigate the bioavailability of Zn and Cd for Chinese cabbage (Brassica rapa L.) from smelter-contaminated soils.

Materials and methods

This study was based on Chinese cabbage (B. rapa L.) growth for phytoremediation of soil toxic metals (TMs) (Zn and Cd) in different dosages of CB nitrogen (50, 150, 250, and 300 kg ha⁻¹) and soil (T1) alone as well as different nitrogen dosages (50-T18, 150-T19, 250-T20, and 300-T21 kg ha⁻¹) of chemical fertilizer (CF). The total and bioavailability of Zn and Cd were measured in shoot and root dry weight biomass, and soil in initial and after harvesting of Chinese cabbage. The chlorophyll content, pH, electrical conductivity, cation exchange capacity, and dissolved organic carbon content were measured to understand their role for plant growth and bioavailability of Zn and Cd. The phytoremediation of Zn and Cd was estimated by diethylene triamine pentaacetic acid (DTPA)-extractable method using smelter-contaminated soils amended with four different dosages of biochar.

Results and discussion

The CB application considerably reduced the DTPA-extractable Zn from contaminated soils, while in comparison to the control and CF treatment evidently mobilized the Zn in soil by approximately 4.17%. The maximum solubility of Zn of 23.46 and 26.78% was obtained with the control and CF-applied treatments in soils, respectively. The DTPA-extractable Cd concentration became elevated with increasing CB dosage, and a significantly higher Cd concentration was recorded in T6 compared to the control and chemical fertilizer-applied treatments. In the cases of higher dosages of CB, the Zn translocation in plants from soil was evidently reduced, but a lower CB amendment increased Zn levels by 5.15% in the shoot and 4.78% in the root, respectively. The changes in the soil EC, pH, and CEC by the amendment of CB could be the main reasons for the (im)mobilization of TMs in contaminated soil.

Conclusions

Finally, the results confirmed that the CB amendment, especially with 300 kg ha⁻¹ nitrogen, could reduce maximum bioavailability of Zn and Cd and the ecological risk of contaminated soil with TMs.

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Inducing therapeutic hypothermia via selective brain cooling: a finite element modeling analysis

Abstract

Therapeutic hypothermia is a treatment method to reduce brain injuries after stroke, especially for cerebral ischemia. This study investigates in the temperature distribution of the head within selective brain cooling (SBC). Anatomically accurate geometries based on CT images of head and neck regions are used to develop the 3D geometry and physical model for the finite element modeling. Two cooling methods, the direct head surface cooling strategy and the combination cooling strategy of both head and neck, are evaluated to analyze the inducing hypothermia. The results show that for direct head surface cooling, the scalp and skull temperatures decrease significantly as the blood perfusion rate is constrained, but it is hard to affect the brain core temperature. To achieve a lower cerebral temperature, combination cooling strategy of both head and neck is an effective method in improving deep brain cooling. In normal condition, the cerebral temperature is reduced by about 0.12 °C in 60 min of hypothermia, while the temperature drop is approximately 0.98 °C in ischemic condition.

Graphical abstract

In this study, the 3D geometry of the head and carotid artery model based on the computed tomography (CT) were derived separately and the corresponding investigations were conducted to validate the reliability of the model. Direct head surface cooling strategy and the combination cooling strategy of both the head and neck were numerically researched.

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[ASAP] Origin of the Immiscibility of Alkanes and Perfluoroalkanes

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b10745

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[ASAP] Unraveling the Impact of Halide Mixing on Perovskite Stability

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b11210

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[ASAP] Open-Air Alkylation Reactions in Photoredox-Catalyzed DNA-Encoded Library Synthesis

Journal of the American Chemical Society

DOI: 10.1021/jacs.9b00669

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[ASAP] Modulating Noncovalent Cross-links with Molecular Switches

Journal of the American Chemical Society

DOI: 10.1021/jacs.8b12762

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[ASAP] Solvent-Free Secondary Growth of Highly -Oriented MFI Zeolite Films from Anhydrous Synthetic Powder

Journal of the American Chemical Society

DOI: 10.1021/jacs.9b00018

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