Unconscious integration: Current evidence for integrative processing under subliminal conditions

alexandrossfakianakis shared this article with you from Inoreader Unconscious integration: Current evidence for integrative processing under subliminal conditions via British Journal of Psychology Abstract Integrative processing is traditionally believed to be dependent on consciousness. While earlier studies within the last decade reported many types of integration under subliminal conditions (i.e. without perceptual awareness), these findings are widely challenged recently. This review evaluates the current evidence for 10 types of subliminal integration that are widely studied: arithmetic processing, object-context integration, multi-word processing, same-different processing, multisensory integration and 5 different types of associative learning. Potential methodological issues concerning awareness measures are also taken into account. It is concluded that while there is currently no reliable evidence for subliminal integration, this does not necessarily refute 'unconscious' integration defined through non-subliminal (e.g. implicit) approaches. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

In-utero exposure to antibiotics and risk of colorectal cancer

alexandrossfakianakis shared this article with you from Inoreader In-utero exposure to antibiotics and risk of colorectal cancer in a prospective cohort of 18 000 adult offspring via International Journal of Epidemiology - Advance Access Abstract Background Incidence rates of colorectal cancer (CRC) are increasing among younger adults and in mid-life, implicating exposures in early life as risk factors. We examined the association between in-utero exposure to antibiotics and risk of CRC in adult offspring. Methods The Child Health and Development Studies is a prospective cohort of women receiving prenatal care between 1959 and 1966 in Oakland, California, with deliveries through June 1967. Diagnosed conditions and all prescribed medications were abstracted from mothers' medical records beginning 6 months prior to pregnancy through delivery. We identified mothers who received antibiotics in pregnancy, including penicillins, tetracyclines, short-acting sulfonamides and long-acting sulfonamides. Diagnoses of CRC in adult (age ≥18 years) offspring were ascertained through 2021 by linkage with the California Cancer Registry. Co x proportional models were used to estimate adjusted hazard ratios (aHR), with follow-up accrued from birth through cancer diagnosis, death or last contact. Results Of 18 751 liveborn offspring, about 15% (n = 2635) were exposed in utero to antibiotics: 5.4% (n = 1016) to tetracyclines, 4.9% (n = 918) to penicillins, 4.2% (n = 785) to short-acting sulfonamides and 1.5% (n = 273) to long-acting sulfonamides. Compared with offspring not exposed, associations between in-utero exposure and CRC in adult offspring were: aHR 1.03 (95% CI 0.32, 3.31) for tetracyclines; aHR 1.12 (95% CI 0.35, 3.58) for penicillins; aHR 0.83 (95% CI 0.20, 3.42) for short-acting sulfonamides; and aHR 4.40 (95% CI 1.63, 11.88) for long-acting sulfonamides. Conclusion Our findings support an association between in-utero exposure to long-acting sulfonamides and CRC in adulthood. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Perspectives on Adherence from the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach with 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment

alexandrossfakianakis shared this article with you from Inoreader Perspectives on Adherence from the ACTG 5360 MINMON Trial: A Minimum Monitoring Approach with 12 Weeks of Sofosbuvir/Velpatasvir in Chronic Hepatitis C Treatment via Clinical Infectious Diseases Advance Access Abstract Background With the advent of efficacious oral Direct-acting antivirals (DAAs) for hepatitis C virus(HCV), identification of characteristics associated with adherence is critical to treatment success. We examined correlates of sub-optimal adherence to HCV therapy in a single-arm, multinational, clinical trial. Methods ACTG A5360 enrolled HCV treatment-naïve persons without decompensated cirrhosis from 5 countries. All participants received a 12-weeks course of sofosbuvir/velpatasvir at entry. In-person visits occurred at initiation and week 24, sustained virologic response (SVR) assessment. Adherence at week 4 was collected remotely and was dichotomized optimal (100%, no missed doses) versus sub-optimal (<100%). Correlates of sub-optimal adherence were explored using logistic regression. Results 400 participants enrolled; 399 initiated treatment; 395/397 (99%) reported completing at week 24.. Median age was 47 year s with 35% female. Among the 368 reporting optimal adherence at week 4 SVR was 96.5% (95% CI [94.1%, 97.9%]) vs. 77.8% (95% CI [59.2%, 89.4%]) p-value < 0.001. In the multivariate model age < 30 years and being a US participant were independently associated with early sub-optimal adherence. Participants < 30 years were 7.1 times more likely to have early sub-optimal adherence compared to their older counterparts. Conclusion Self-reported optimal adherence at week 4 was associated with SVR. Early self-reported adherence could be used to identify those at higher risk of treatment failure and may benefit from additional support. Younger individuals < 30 years may also be prioritized for additional adherence support. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cancer-associated SMARCAL1 loss-of-function mutations promote alternative lengthening of telomeres and tumorigenesis in telomerase-negative glioblastoma cells

alexandrossfakianakis shared this article with you from Inoreader Cancer-associated SMARCAL1 loss-of-function mutations promote alternative lengthening of telomeres and tumorigenesis in telomerase-negative glioblastoma cells via Neuro-Oncology Advance Access Abstract Background Telomere maintenance mechanisms are required to enable the replicative immortality of malignant cells. While most cancers activate the enzyme telomerase, a subset of cancers use telomerase-independent mechanisms termed alternative lengthening of telomeres (ALT). ALT occurs via homology directed-repair mechanisms and is frequently associated with ATRX mutations. We previously showed that a subset of adult GBM patients with ATRX-expressing ALT-positive tumors harbored loss-of-function mutations in the SMARCAL1 gene, which encodes an annealing helicase involved in replication fork remodeling and the resolution of replication stress. However, the causative relationship between SMARCAL1 deficiency, tumorigenesis, and de novo telomere synthesis is not understood. Methods We used a patient-derived ALT-positive GBM cell line with native SMARCAL1 deficiency to investigate the role of SMARCAL1 in ALT-mediated de novo telomere synthesis, replication stress, and gliomagenesis in vivo. Results Inducible rescue of SMARCAL1 expression suppresses ALT indicators and inhibits de novo telomere synthesis in GBM and osteosarcoma cells, suggesting that SMARCAL1 deficiency plays a functional role in ALT induction in cancers that natively lack SMARCAL1 function. SMARCAL1-deficient ALT-positive cells can be serially propagated in vivo in the absence of detectable telomerase activity, demonstrating that the SMARCAL1-deficient ALT phenotype maintains telomeres in a manner that promotes tumorigenesis. Conclusions SMARCAL1 deficiency is permissive to ALT and promote gliomagenesis. Inducible rescue of SMARCAL1 in ALT-positive cell lines permits the dynamic modulation of ALT activity, which will be valuable for future studies aimed at understanding the mechanisms of ALT and identifying nov el anti-cancer therapeutics that target the ALT phenotype. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Merkelzellkarzinom

alexandrossfakianakis shared this article with you from Inoreader Merkelzellkarzinom via Laryngo-Rhino-Otologie Laryngorhinootologie DOI: 10.1055/a-1949-3751 Das Merkelzellkarzinom ist ein aggressiver neuroendokriner Tumor, welcher durch schnelles Wachstum und frühzeitige Metastasierung charakterisiert ist. Das mediane Erkrankungsalter liegt zwischen 75–80 Jahren. Mit Zunahme des durchschnittlichen Bevölkerungsalters tritt der einstmals seltene Tumor immer häufiger auf. Neben den klassischen Therapiesäulen Chirurgie, Strahlentherapie und Chemotherapie spielt die Immunonkologie au ch beim Merkelzellkarzinom eine zunehmend wichtige Rolle. [...] Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany Article in Thieme eJournals: Table of contents  |  Abstract  |  Full text View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Impact of air pollutants on influenza−like illness outpatient visits under COVID−19 pandemic in the sub−center of Beijing, China

alexandrossfakianakis shared this article with you from Inoreader Impact of air pollutants on influenza−like illness outpatient visits under COVID−19 pandemic in the sub−center of Beijing, China via Journal of Medical Virology Abstract Objective This study aimed to explore the association between air pollutants and outpatient visits for influenza−like illnesses (ILI) under the coronavirus disease 2019 (COVID−19) stage in the sub−center of Beijing. Methods The data on ILI in the sub−center of Beijing from 1 January 2018 to 31 December 2020 were obtained from the Beijing Influenza Surveillance Network. A generalized additive Poisson model was applied to examine the associations between the concentrations of air pollutants and daily outpatient visits for ILI when controlling meteorological factors and temporal trend. Results A total of 171,943 ILI patients were included. In the pre−COVID−19 stage, an increased risk of ILI outpatient visits was associated to a high air quality index (AQI) and the high concentrations of particulate matter less than 2.5 (PM2.5), particulate matter 10 (PM10), sulphur dioxide (SO2), nitrogen dioxide (NO2), and carbon monoxide (CO), and a low concentration of ozone (O3) on lag0 day and lag1 day, while a higher increased risk of ILI outpatient visits was observed by the air pollutants in the COVID−19 stage on lag0 day. Except for PM10，the concentrations of other air pollutants on lag1 day were not significantly associated with an increased risk of ILI outpatient visits during the COVID−19 stage. Conclusion The findings that air pollutants had enhanced immediate effects and diminished lag-effects on the risk of ILI outpatient visits during the COVID−19 pandemic, which is important for the development of public health and environmental governance strategies. This article is protected by copyright. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Torque teno virus (TTV): a gentle spy virus of immune status, predictive marker of seroconversion to COVID‐19 vaccine in kidney and lung transplant recipients

alexandrossfakianakis shared this article with you from Inoreader Torque teno virus (TTV): a gentle spy virus of immune status, predictive marker of seroconversion to COVID‐19 vaccine in kidney and lung transplant recipients via Journal of Medical Virology Abstract To date, no comprehensive marker to monitor the immune status of patients is available. Given that Torque teno virus (TTV), a known human virome component, has previously been identified as a marker of immunocompetence, it was retrospectively investigated whether TTV viral load may also represent a marker of ability to develop antibody in response to COVID-19-BNT162B2 vaccine in solid organ transplant recipients (SOT). Specifically, 273 samples from 146 kidney and 26 lung transplant recipients after successive doses of vaccine were analyzed. An inverse correlation was observed within the TTV copy number and anti-Spike IgG antibody titer with a progressive decrease in viremia the further away from the transplant date. Analyzing the data obtained after the second dose, a significant difference in TTV copy number between responsive and non-responsive patients was observed, considering a 5 log10 TTV copies/ml threshold to discriminate between the two groups. Moreover , for 86 patients followed in their response to the second and third vaccination doses a 6 log10 TTV copies/ml threshold was used to predict responsivity to the booster dose. Although further investigation is necessary, possibly extending the analysis to other patient categories, this study suggests that TTV can be used as a good marker of vaccine response in transplant patients. This article is protected by copyright. All rights reserved. View on Web

Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.