Role of craniofacial phenotypes in the response to oral appliance therapy for obstructive sleep apnea

alexandrossfakianakis shared this article with you from Inoreader Role of craniofacial phenotypes in the response to oral appliance therapy for obstructive sleep apnea via Journal of Oral Rehabilitation Abstract Background Mandibular advancement device (MAD) is a good alternative for patients with obstructive sleep apnea (OSA). However, the treatment response varies among individuals. Objective This study aimed to explore the role of craniofacial features in the response to MADs to improve prognostication and patient selection. Methods The retrospective trial contained 42 males aged 41.5±9.0 years, and with an apnea-hypopnea index (AHI) of 21.5±13.8 events/h. According to the mandibular plane angle, participants were divided into three groups: low angle (n=13), average angle (n=14), and high angle (n=15). Under monitor of home sleep testing, adjustable MADs were used to titrate the mandible forward from 0 mm with an increment of 0.5 mm every day. The polysomnography outcomes, mandibular protrusion amounts, changes in upper airway MRI measurements, and nasal resistance were compared among three groups. Results The normalization rate (AHI < 5 /h) was 92.3%, 57.1%, and 46.7% respectively in the low, average, and high angle groups (p=0.027). The effective protrusion where AHI was reduced by half was 20 (11.3~37.5) %, 31.3 (23.6~50) %, and 50 (36.9~64.9) % of the maximal mandibular protrusion, in the low, average, and high angle groups (p=0.004). Multivariate logistic regression revealed that increased gonion angle (OR=0.878) and baseline AHI(OR=0.868) can reduce the probability of normalization. Conclusion The high mandibular plane angle might be an unfavorable factor to MAD treatment and more protrusion was needed to achieve a 50% reduction in AHI. Vertical craniofacial pattern (gonion angle) and baseline AHI constituted the model for predicting the effect of MADs. View on Web

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Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma

alexandrossfakianakis shared this article with you from Inoreader Single-cell transcriptomic analyses provide insights into the cellular origins and drivers of brain metastasis from lung adenocarcinoma via Neuro-Oncology Advance Access Abstract Background Brain metastasis (BM) is the most common intracranial malignancy causing significant mortality, and lung cancer is the most common origin of BM. However, the cellular origins and drivers of BM from lung adenocarcinoma (LUAD) have yet to be defined. Methods The cellular constitutions were characterized by single-cell transcriptomic profiles of 11 LUAD primary tumor (PT) and 10 BM samples (GSE131907). Copy number variation (CNV) and clonality analysis were applied to illustrate cellular origins of BM tumors. Brain metastasis-associated epithelial cells (BMAECs) were identified by pseudotime trajectory analysis. By using machine-learning algorithms, we developed the BM-index representing the relative abundance of BMAECs in the bulk RNA-seq data, indicating high risk of BM. Therapeutic drugs targeting BMAECs were predicted based on the drug sensitivity data of cancer cell lines. Results Differences in macrophage s and T cells between PTs and BMs were investigated by single-cell RNA (scRNA) and immunohistochemistry and immunofluorescence data. CNV analysis demonstrated BM was derived from subclones of PT with a gain of chromosome 7. We then identified BMAECs and its biomarker, S100A9. Immunofluorescence indicated strong correlations of BMAECs with metastasis and prognosis evaluated by the paired PT and BM samples from Peking Union Medical College Hospital (PUMCH). We further evaluated the clinical significance of BM-index and identified 7 drugs that potentially target BMAECs. Conclusions This study clarified possible cellular origins and drivers of metastatic LUAD at single cell level, and laid a foundation for early detections of LUAD patients with a high risk of BM. View on Web

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GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data

alexandrossfakianakis shared this article with you from Inoreader GBMdeconvoluteR accurately infers proportions of neoplastic and immune cell populations from bulk glioblastoma transcriptomics data via Neuro-Oncology Advance Access Abstract Background Characterising and quantifying cell types within glioblastoma (GBM) tumours at scale will facilitate a better understanding of the association between the cellular landscape and tumour phenotypes or clinical correlates. We aimed to develop a tool that deconvolutes immune and neoplastic cells within the GBM tumour microenvironment from bulk RNA sequencing data. Methods We developed an IDH wild-type (IDHwt) GBM-specific single immune cell reference consisting of B cells, T cells, NK cells, microglia, tumour associated macrophages, monocytes, mast and DC cells. We used this alongside an existing neoplastic single cell-type reference for astrocyte-like, oligodendrocyte- and neuronal-progenitor like and mesenchymal GBM cancer cells to create both marker and gene signature matrix-based deconvolution tools. We applied single-cell resolution imaging mass cytometry (IMC) to ten IDHwt GBM samples, five paired primary and recur rent tumours, to determine which deconvolution approach performed best. Results Marker based deconvolution using GBM tissue specific markers was most accurate for both immune cells and cancer cells, so we packaged this approach as GBMdeconvoluteR. We applied GBMdeconvoluteR to bulk GBM RNAseq data from The Cancer Genome Atlas and recapitulated recent findings from multi-omics single cell studies with regards associations between mesenchymal GBM cancer cells and both lymphoid and myeloid cells. Furthermore, we expanded upon this to show that these associations are stronger in patients with worse prognosis. Conclusions GBMdeconvoluteR accurately quantifies immune and neoplastic cell proportions in IDHwt GBM bulk RNA sequencing data and is accessible here: https : // gbmdeconvoluter.leeds.ac.uk View on Web

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Does baseline EEG activity differ in the transition to or from a chronic pain state?

alexandrossfakianakis shared this article with you from Inoreader Does baseline EEG activity differ in the transition to or from a chronic pain state? via Pain Practice Abstract Background and aim Identifying EEG brain markers might yield better mechanistic insights into how chronic pain develops and could be treated. An existing longitudinal EEG study gave us the opportunity to determine whether the development of pain is accompanied by less alpha power—ie, a 'relaxed' brain state—and vice versa. Methods Five-minute resting EEG with the eyes open was measured 2 times in 95 subjects at T0 (baseline) and T1 (6 months later). Based on the Short-Form Health Survey and Brief Pain Inventory questionnaire, subjects were divided into 4 groups: staying pain-free (n = 44), developing chronic pain (n = 8), becoming pain-free (n = 15), and ongoing chronic pain (n = 28). The EEG data of 14 electrodes were analyzed by multilevel regression. Results The group that developed chronic pain demonstrated less power in the lower-frequency bands over time during the resting state EEG, whereas the transition to a pain-free state had the opposite pattern. Thus, the a priori hypothesis was confirmed. Conclusions Transitions in pain states are linked to a change in baseline EEG activity. Future research is needed to replicate these results in a larger study sample and in targeted clinical populations. Further, these results might be beneficial in optimizing neurofeedback algorithms for the treatment of chronic pain. View on Web

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Spinal cord stimulation and return to work of patients with failed back surgery syndrome

alexandrossfakianakis shared this article with you from Inoreader Spinal cord stimulation and return to work of patients with failed back surgery syndrome via Pain Practice Abstract Objectives Chronic pain has a substantial negative impact on work-related outcomes, which underlines the importance of interventions to reduce the burden. Spinal cord stimulation (SCS) efficiently relieves pain in specific chronic pain syndromes and is recommended for treating failed back surgery syndrome (FBSS) or post-surgical chronic back pain that is refractory to other treatments. To examine the impact of SCS in patients with FBSS on the return to work (RTW), we determined the RTW rate and the factors positively associated with the RTW. Materials and Methods Among 106 patients with FBSS who benefitted from SCS at a single institution in France between September 1999 and March 2010, we retrospectively included 59 who had stopped work at the time of SCS because of disability or sick leave and evaluated the RTW (rate and predictors, estimating odds ratios [ORs] and 95% confidence intervals [CIs]). Results The mean (SD) post-surgery follow-up for the 59 patients (34 men; mean [SD] age 46.9 [7.4] years) was 7.5 (3.6) years (range 5–15). The RTW rate was 30.5%, with a median [IQR] recovery time of 5.5 months [3–8.5]. RTW was improved with functional improvement evolution (OR 1.1, 95% CI [1.01–1.1], p=0.02) and was reduced with unemployment > 3 years (OR 0.1, 95% CI [0.01-0.7], p=0.02). Conclusions Our protocol for SCS for patients with FBSS, including a strict selection of patients and a multidisciplinary approach, led to good results, especially for the RTW. RTW should be a therapeutic goal, directly affecting indirect costs related to FBSS. View on Web

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Pediatric autoimmune myelofibrosis: Experience from a large pediatric tertiary care center

alexandrossfakianakis shared this article with you from Inoreader Pediatric autoimmune myelofibrosis: Experience from a large pediatric tertiary care center via Pediatric Blood & Cancer Abstract Autoimmune myelofibrosis (AIMF) is a rare disorder characterized by cytopenias and autoimmunity, with characteristic bone marrow findings that include lymphocytic infiltration and fibrosis. AIMF is described predominantly in adult populations who have systemic lupus erythematosis (SLE), with scant pediatric cases described mainly in older adolescents with SLE. Here, we described the largest single-center pediatric experience of pediatric autoimmune myelofibrosis (PAIMF) series, demonstrating both similarities and distinctions from the adult experience. Patients overall respond well to steroid therapy, but these patients were significantly younger, infrequently carried a diagnosis of SLE, and causative genetic lesions were identified in many cases. View on Web

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Significant neutralizing escapes of Omicron and its sub‐lineages in SARS‐CoV‐2‐infected individuals vaccinated with inactivated vaccines

alexandrossfakianakis shared this article with you from Inoreader Significant neutralizing escapes of Omicron and its sub‐lineages in SARS‐CoV‐2‐infected individuals vaccinated with inactivated vaccines via Journal of Medical Virology Abstract In China, most SARS-CoV-2-infected individuals had been vaccinated with inactivated vaccines. However, little is known about their immune resistances to the previous variants of concerns (VOCs) and the current Omicron sub-lineages. Here, we collected convalescent serum samples from SARS-CoV-2-infected individuals during the ancestral, Delta and Omicron BA.1 waves, and evaluated their cross-neutralizing antibodies (nAbs) against the previous VOCs and the current Omicron sub-lineages using VSV-based pseudoviruses. In the convalescents who had been unvaccinated and vaccinated with two doses of inactivated vaccines, we found infections from either the ancestral or the Delta strain elicited moderate cross-nAbs to previous VOCs, but very few cross-nAbs to the Omicron sub-lineages, including BA.1, BA.2, BA.3 and BA.4/5. The individuals who had been vaccinated with two doses of inactivated vaccines before Omicron BA.1 infection had moderate nAbs to Omicron BA.1, but weak cross-nAbs to the other Omicron sub-lineages. While three doses of inactivated vaccines followed Omicron BA.1 infection induced elevated and still weak cross-nAbs to other Omicron sub-lineages. Our results indicate that the Omicron sub-lineages show significant immune escape in the previously SARS-CoV-2-infected individuals and thus highlights the importance of vaccine boosters in this population. This article is protected by copyright. All rights reserved. View on Web

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Developmental Outcomes in Children Born to Women with Possible Subclinical Rubella Exposures During Pregnancy

alexandrossfakianakis shared this article with you from Inoreader Developmental Outcomes in Children Born to Women with Possible Subclinical Rubella Exposures During Pregnancy via Journal of Medical Virology Abstract This study investigated outcomes of children born to women who seroconverted to rubella immune during pregnancy. In a prior 2012-2013 study of 296 women who were rubella non-immune, 26 (8.8%) seroconverted to rubella immune during pregnancy. These same women and their now 8-9 years-old children were queried as to the children's developmental health. After removing exclusions and those lost to follow-up, the total response rate was 115/204 (56.4%). Three sets of twins in the non-immune group increased the total to 118. The seroconversion group had more autism (12.5% versus 3.9%, P=.19), ADHD (37.5% versus 18.6%, P=.10), and any developmental disability (43.8% versus 31.4%, P=.39) but none showed a statistical difference between the two groups. Compared to Autism and Developmental Disabilities Monitoring data, the seroconversion group had a greater prevalence of autism (OR 6.07, P=0.051, nonsignificant); and to data derived from the National Health Interview Survey, a nonsignificant higher odds of autism (OR 5.57, P=0.060), higher odds of ADHD (OR 5.65, P=0.0027) and of an y developmental disability (OR 3.59, P=0.014).The non-immune group also demonstrated a statistically significant increase for both ADHD and any developmental disability, but not for autism. This article is protected by copyright. All rights reserved. View on Web

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Immune‐dysregulation in subacute sclerosing panencephalitis: an exploratory case‐control study

alexandrossfakianakis shared this article with you from Inoreader Immune‐dysregulation in subacute sclerosing panencephalitis: an exploratory case‐control study via Journal of Medical Virology ABSTRACT Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurological condition caused by a defective measles virus. It is postulated that immune-dysregulation might result in persistent infection (immune evasion) as well as initiation of autoimmune phenomenon (via natural killer cells) leading to panencephalitis. The primary objective was to study the pattern of immune dysregulation in cases with SSPE. The secondary objective was to assess the correlation between the measured immunological variables and disability/death at 6 months. This was an exploratory case-control study conducted at a tertiary-care referral-facility from January 2020 to September 2021. Thirty consecutive patients fulfilling the Dyken's criteria for SSPE and 30 age-and-sex-matched healthy controls were enrolled. Immunological profile constituted by lymphocyte subset analysis, immunoglobulin levels and complement levels were done in all cases and controls. Cases were staged as per Jabbour's system; disability was assessed using the modified Rankin Scale (mRS). Patients with SSPE had a mean age of 14.76 years (± 6.9 years). There were 25 males and 5 females; 6.7% cases belonged to Jabbour's first stage, 40% to second stage and 53.3% to third stage. At least 1/4th had evidence of measles vaccination. Levels of absolute lymphocyte count, B-cells, T cells, helper T-cells and cytotoxic T-cells were significantly higher in cases. IgG, IgM and IgE levels were significantly higher while IgD levels were significantly lower in cases. At baseline, 13.3% of cases had a mRS score of 0-2 and 86.7% had a score of 3-6; at 6 months 10% had a mRS score 0-2 (favourable outcome) while 90% had a mRS score 3-6 (poor outcome). Higher IgE levels were found to significantly correlate with favourable outcome. Immune-dysregulation may play a significant role in shaping one's response to measles infection as well as in determining vaccine-efficacy. This article is protected by copyright. All rights reserved. View on Web

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A hepatitis B virus core antigen‐based virus‐like particle vaccine expressing SARS‐CoV‐2 B and T cell epitopes induces epitope‐specific humoral and cell‐mediated immune responses but confers limited protection against SARS‐CoV‐2 infection

alexandrossfakianakis shared this article with you from Inoreader A hepatitis B virus core antigen‐based virus‐like particle vaccine expressing SARS‐CoV‐2 B and T cell epitopes induces epitope‐specific humoral and cell‐mediated immune responses but confers limited protection against SARS‐CoV‐2 infection via Journal of Medical Virology Abstract The hepatitis B virus core antigen (HBcAg) tolerates insertion of foreign epitopes and maintains its ability to self-assemble into virus-like particles (VLPs). We constructed a ∆HBcAg-based VLP vaccine expressing three predicted SARS-CoV-2 B and T cell epitopes and determined its immunogenicity and protective efficacy. The recombinant ∆HBcAg-SARS-CoV-2 protein was expressed in E. coli, purified, and shown to form VLPs. K18-hACE2 transgenic C57BL/6 mice were immunized intramuscularly with ∆HBcAg VLP control (n=15) or ∆HBcAg-SARS-CoV-2 VLP vaccine (n=15). One week after the 2nd booster and prior to virus challenge, five ∆HBcAg-SARS-CoV-2 vaccinated mice were euthanized to evaluate epitope-specific immune responses. There is a statistically significant increase in epitope-specific IgG response, and statistically higher IL-6 and MCP-1 expression levels in ∆HBcAg-SARS-CoV-2 VLP-vaccinated mice compared to ∆HBcAg VLP controls. While not statistically sign ificant, the ∆HBcAg-SARS-CoV-2 VLP mice had numerically more memory CD8+ T-cells, and 3/5 mice also had numerically higher levels of IFN-γ and TNF. After challenge with SARS-CoV-2, ∆HBcAg-SARS-CoV-2 immunized mice had numerically lower viral RNA loads in the lung, and slightly higher survival, but the differences are not statistically significant. These results indicate that the ∆HBcAg-SARS-CoV-2 VLP vaccine elicits epitope-specific humoral and cell-mediated immune responses but they were insufficient against SARS-CoV-2 infection. This article is protected by copyright. All rights reserved. View on Web

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