bluuebunny/crossref_metadata_2025 huggingface dataset:
Smoking history and adherence to cancer-related recommendations in a primary care setting
Authors: Zoorob Roger J , Mejia Maria C , Matas Jennifer , Wang Haijun , Salemi Jason L , Levine Robert
Published: December 2021

Public health prevention efforts have led to overall reductions in mortality from screening-preventable cancers. We explored cancer screening behaviors of smokers, former smokers, and nonsmokers among patients of large primary care practices to discover the relationship between smoking status and previous adherence to the United States Preventive Services Task Force breast, cervical, and colorectal cancer screening recommendations. Our descriptive study of electronic medical record data included 6,029 established primary care patients. Multi-predictor log-binomial regression models yielded prevalence ratios (PRs) and 95% confidence intervals (CIs) to determine associations between smoking status and the likelihood of nonadherence. All models were adjusted for race/ethnicity, age, insurance, primary care specialty, number of comorbidities, and sex. Smoking history was obtained from all participants in January 2020. Current smokers accounted for 4.8%, while 22.7% were former smokers, and 72.5% were never smokers. Current smokers (compared to never smokers) were 63% more likely to be mammogram nonadherent (PR: 1.63, 95% CI: 1.31 to 2.02), 26% more likely to be Pap smear nonadherent (PR: 1.26, 95% CI: 1.04 to 1.53), and 39% more likely to be colonoscopy nonadherent (PR: 1.39, 95% CI: 1.16 to 1.66). Current smokers and former Powered by Editorial Manager and ProduXion Manager from Aries Systems Corporation smokers had on average 2.9 comorbidities while never smokers had on average 2.1 comorbidities. Our findings showed that current smokers experienced significantly lower rates of cancer screening compared to never smokers. Further research is needed to investigate and identify best practices for increasing cancer screening uptake in this population.
Knowledge, attitudes, and practices: a quantitative assessment of hospital physicians and medical interns treating snakebite envenomation in Rwanda
Authors: Schurer Janna M , Hirwa Elise M , Masimbi Ornella , Nduwayezu Richard
Published: December 2021

Background

Snakebite envenomation (SBE) is a serious and potentially life-threatening condition that most often targets rural, subsistence-based farmers in sub-Saharan Africa. Rwanda is home to 13 venomous and medically important snake species. Those bitten are known to seek care from traditional healers and/or formal health facilities. No information is available on patient management at government health facilities.

Methods

This quantitative evaluation aimed to characterize knowledge, attitudes and practices related to snakebite management in Rwanda. Target respondents included physicians working at hospitals with the highest SBE caseload and medical interns. Respondents were asked to complete questionnaires on paper or online through Qualtrics.

Results

Overall, 105 physicians and 171 interns agreed to participate. Our findings suggest that overall knowledge scores were low for both groups (mean 49.4%, minimum–maximum 31.3–70.8%). Respondents were keen to receive SBE training but often lacked essential supplies needed to adhere to recommended guidelines for SBE management. One-third of respondents (34.8%) believed that traditional healers could manage SBE successfully and two-thirds (66.3%) felt that black stone therapy was an appropriate first aid practice.

Conclusions

These findings indicate a clear need for improved curricula related to SBE, enhanced supply chain management and practical mechanisms for supporting clinicians.
Deletion of ApoE Leads to Intervertebral Disc Degeneration via Aberrant Activation of Adipokines
Authors: Zhou Yachuan , Chen Xiaoqian , Tian Qinglu , Zhang Jun , Wan Mian , Zhou Xin , Xu Xin , Cao Xu , Zhou Xuedong , Zheng Liwei
Published: December 2021

Study Design.

Animal experiment: a mouse model of intervertebral disc (IVD) degeneration induced by deletion of apolipoprotein E (apoE).

Objective.

The aim of this study was to investigate the role and mechanism of apoE on the process of IVD degeneration.

Summary of Background Data.

Abnormal lipid metabolism has been demonstrated to be closely related to IVD degeneration, a common chronic degenerative joint disease. ApoE, a component of apolipoproteins, plays a crucial role in lipid transportation and metabolic balance. But the relationship between apoE and IVD degeneration remains largely unknown.

Methods.

ApoE knockout (KO) mouse was employed to investigate the progressive disc degeneration. The changes of vertebral bone and intervertebral disc space were measured by micro-computed tomography (micro-CT). The histo-morphological changes of cartilage endplate (CEP) and underlying signals were tested using immunohistochemistry and immunofluorescence staining.

Results.

The deletion of apoE gene accelerated the lumbar spine degeneration. Compared with WT mice, apoE KO mice showed reduced IVD space and increased vertebral bone mass. The progressive CEP degeneration was further found with cartilage degradation and endplate sclerosis in apoE KO mice. The deletion of apoE stimulated abnormal CEP bone remodeling and activation of adipokines signals.

Conclusion.

The deletion of apoE gene induced abnormal activation of adipokines signals, thus contribute to the CEP degeneration.

Level of Evidence.

N/A
Mini-Bronchoalveolar Lavage for Diagnosing Coronavirus Disease 2019–Associated Invasive Pulmonary Aspergillosis
Authors: Vanbellinghen Manon C. , Atasever Burak , van der Spoel Hans J. I. , Bouman Catherine C. S. , Altenburg Josje , van Dijk Karin
Published: December 2021

Objectives:

To evaluate the yield of mini-bronchoalveolar lavage compared with that of directed bronchoalveolar lavage in critically ill patients with suspected coronavirus disease 2019–associated pulmonary aspergillosis.

Design:

A retrospective cohort study.

Setting:

The ICU of the Amsterdam University Medical Centers.

Patients:

Patients with confirmed coronavirus disease 2019 screened for coronavirus disease 2019–associated pulmonary aspergillosis.

INTERVENTIONS:

Mini-bronchoalveolar lavage and/or directed bronchoalveolar lavage.

Measurements and Main Results:

In total, 76 patients were included, 20 of whom underwent bronchoalveolar lavage, 40 mini-bronchoalveolar lavage, and 16 both mini-bronchoalveolar lavage and bronchoalveolar lavage. The percentage of samples with one or more positive Aspergillus detecting test (galactomannan, culture, polymerase chain reaction) did not differ significantly between bronchoalveolar lavage and mini-bronchoalveolar lavage (16.7% vs 21.4%). However, in mini-bronchoalveolar lavage samples, this was more frequently driven by a positive polymerase chain reaction than in bronchoalveolar lavage samples (17.9% vs 2.8%; p = 0.030). In 81% of patients (13/16) with both mini-bronchoalveolar lavage and bronchoalveolar lavage, the test results were in agreement. In 11 of 12 patients (92%) with first a negative mini-bronchoalveolar lavage, the subsequent bronchoalveolar lavage sample was also negative.

Conclusions:

We found a similar percentage of positive test results in mini-bronchoalveolar lavage and bronchoalveolar lavage samples in patients with suspected coronavirus disease 2019–associated pulmonary aspergillosis. Our findings indicate that mini-bronchoalveolar lavage could be a useful tool for coronavirus disease 2019–associated pulmonary aspergillosis screening in ICU patients.
Perfusion Monitoring During Oculoplastic Reconstructive Surgery: A Comprehensive Review
Authors: Berggren Johanna V. , Stridh Magne , Malmsjö Malin
Published: December 2021

Purpose:

Knowledge of how blood perfusion is affected during and after reconstructive surgery is of great importance to predict the survival of grafts and flaps. When commonly used reconstructive procedures were developed a century ago, they were based on empirical observations of clinical outcome.

Methods:

This is a comprehensive literature review that summarizes the current state of knowledge regarding microvascular perfusion monitoring during oculoplastic procedures.

Results:

Over the years, a number of techniques for perfusion monitoring have been developed as an attempt to be more objective than clinical examination using traditional methods such as observations of skin temperature, turgor, color, smell, and capillary refill time. There are limited publications regarding microvascular perfusion monitoring during reconstructive procedures in the periocular area. Modern laser-based techniques have been attractive due to their noninvasive nature.

Conclusions:

Today, modern, noninvasive techniques are available to monitor perfusion during and after surgery. This has increased our knowledge on the perfusion in common oculoplastic surgery procedures. A detailed understanding of how blood perfusion is affected will hopefully allow the improvement of surgical techniques for better clinical outcome.
Talaromyces saxoxalicus sp. nov., isolated from the limestone walls of the Old Cathedral of Coimbra, Portugal
Authors: Trovão João , Soares Fabiana , Tiago Igor , Portugal António
Published: December 2021

Fungi are one of the main agents of stone biodeterioration worldwide, since they strongly interfere with its integrity, aesthetical and structural natural properties. During an experimental survey aimed to isolate fungal species contributing to the biodeterioration of the limestone walls of the Old Cathedral of Coimbra (Portuguese unesco World Heritage site), a Talaromyces species that could not be identified to any currently known species in this genus was isolated. Molecular phylogenetic analysis of the internal transcribed spacer, β-tubulin and RNA polymerase II subunit 2, placed this fungus in Talaromyces sect. Purpurei, while also pointing at its phylogenetic distinction from the remaining species in this section. Thus, a novel species, Talaromyces saxoxalicus sp. nov., is here proposed. Moreover, considering the isolation source of this fungus and in an attempt to understand its contribution to the overall stone monument biodeterioration, the species's in vitro biodeteriorative potential was also evaluated. The results highlighted that the species exhibited an in vitro biodeteriorative ability (calcium oxalate crystal formation), highlighting its potential deteriorative profile.
Accuracy of an amplicon-sequencing nanopore approach to identify variants in tuberculosis drug-resistance-associated genes
Authors: Mariner-Llicer Carla , Goig Galo A. , Zaragoza-Infante Laura , Torres-Puente Manuela , Villamayor Luis , Navarro David , Borras Rafael , Chiner-Oms Álvaro , Comas Iñaki
Published: December 2021

A rapid and accurate diagnostic assay represents an important means to detect

Mycobacterium tuberculosis

, identify drug-resistant strains and ensure treatment success. Currently employed techniques to diagnose drug-resistant tuberculosis include slow phenotypic tests or more rapid molecular assays that evaluate a limited range of drugs. Whole-genome-sequencing-based approaches can detect known drug-resistance-conferring mutations and novel variations; however, the dependence on growing samples in culture, and the associated delays in achieving results, represents a significant limitation. As an alternative, targeted sequencing strategies can be directly performed on clinical samples at high throughput. This study proposes a targeted sequencing assay to rapidly detect drug-resistant strains of

M. tuberculosis

using the Nanopore MinION sequencing platform. We designed a single-tube assay that targets nine genes associated with drug resistance to seven drugs and two phylogenetic-determining regions to determine strain lineage and tested it in nine clinical isolates and six sputa. The study’s main aim is to calibrate MinNION variant calling to detect drug-resistance-associated mutations with different frequencies to match the accuracy of Illumina (the current gold-standard sequencing technology) from both culture and sputum samples. After calibrating Nanopore MinION variant calling, we demonstrated 100% agreement between Illumina WGS and our MinION set up to detect known drug resistance and phylogenetic variants in our dataset. Importantly, other variants in the amplicons are also detected, decreasing the recall. We identify minority variants and insertions/deletions as crucial bioinformatics challenges to fully reproduce Illumina WGS results.
Genetic Sex Validation for Sample Tracking in Clinical Testing
Authors: Hu Jianhong , Korchina Viktoriya , Zouk Hana , Harden Maegan V. , Murdock David , Macbeth Alyssa , Harrison Steven M. , Lennon Niall , Kovar Christie , Balasubramanian Adithya , Zhang Lan , Chandanavelli Gauthami , Pasham Divya , Rowley Robb , Wiley Ken , Smith Maureen E. , Gordon Adam , Jarvik Gail P. , Sleiman Patrick , Kelly Melissa A , Bland Sarah T. , Murugan Mullai , Venner Eric , Boerwinkle Eric ,   the eMERGE III consortium, Prows Cynthia , Mahanta Lisa , Rehm Heidi L. , Gibbs Richard A. , Muzny Donna M.
Published: December 2021

Background

Next generation DNA sequencing (NGS) has been rapidly adopted by clinical testing laboratories for detection of germline and somatic genetic variants. The complexity of sample processing in a clinical DNA sequencing laboratory creates multiple opportunities for sample identification errors, demanding stringent quality control procedures.

Methods

We utilized DNA genotyping via a 96-SNP PCR panel applied at sample acquisition in comparison to the final sequence, for tracking of sample identity throughout the sequencing pipeline. The 96-SNP PCR panel’s inclusion of sex SNPs also provides a mechanism for a genotype-based comparison to recorded sex at sample collection for identification. This approach was implemented in the clinical genomic testing pathways, in the multi-center Electronic Medical Records and Genomics (eMERGE) Phase III program

Results

We identified 110 inconsistencies from 25,015 (0.44%) clinical samples, when comparing the 96-SNP PCR panel data to the test requisition-provided sex. The 96-SNP PCR panel genetic sex predictions were confirmed using additional SNP sites in the sequencing data or high-density hybridization-based genotyping arrays. Results identified clerical errors, samples from transgender participants and stem cell or bone marrow transplant patients and undetermined sample mix-ups.

Conclusion

The 96-SNP PCR panel provides a cost-effective, robust tool for tracking samples within DNA sequencing laboratories, while the ability to predict sex from genotyping data provides an additional quality control measure for all procedures, beginning with sample collections. While not sufficient to detect all sample mix-ups, the inclusion of genetic versus reported sex matching can give estimates of the rate of errors in sample collection systems.
Neural Readout of a Latency Code in the Active Electrosensory System
Authors: Perks Krista E. , Sawtell Nathaniel B.
Published: December 2021

The latency of spikes relative to a stimulus conveys sensory information across modalities. However, in most cases it remains unclear whether and how such latency codes are utilized by postsynaptic neurons. In the active electrosensory system of mormyrid fish, a latency code for stimulus amplitude in electroreceptor afferent nerve fibers (EAs) is hypothesized to be read out by a central reference provided by motor corollary discharge (CD). Here we demonstrate that CD enhances sensory responses in postsynaptic granular cells of the electrosensory lobe, but is not required for reading out EA input. Instead, diverse latency and spike count tuning across the EA population gives rise to graded information about stimulus amplitude that can be read out by standard integration of converging excitatory synaptic inputs. Inhibitory control over the temporal window of integration renders two granular cell subclasses differentially sensitive to information derived from relative spike latency versus spike count.
Transcriptomic responses of the human kidney to acute injury at single cell resolution
Authors: Hinze Christian , Kocks Christine , Leiz Janna , Karaiskos Nikos , Boltengagen Anastasiya , Skopnik Christopher Mark , Klocke Jan , Hardenberg Jan-Hendrik , Stockmann Helena , Gotthardt Inka , Obermayer Benedikt , Haghverdi Laleh , Wyler Emanuel , Landthaler Markus , Bachmann Sebastian , Hocke Andreas C. , Corman Victor , Busch Jonas , Schneider Wolfgang , Himmerkus Nina , Bleich Markus , Eckardt Kai-Uwe , Enghard Philipp , Rajewsky Nikolaus , Schmidt-Ott Kai M.
Published: December 2021

Background

Acute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood.

Methods

We performed single-nuclei transcriptomics, bulk transcriptomics, molecular imaging studies, and conventional histology on kidney tissues from 8 individuals with severe AKI (stage 2 or 3 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria). Specimens were obtained within 1-2 hours after individuals had succumbed to critical illness associated with respiratory infections, with 4 of 8 individuals diagnosed with COVID-19. Control kidney tissues were obtained post-mortem or after nephrectomy from individuals without AKI.

Results

High-depth single cell-resolved gene expression data of human kidneys affected by AKI revealed enrichment of novel injury-associated cell states within the major cell types of the tubular epithelium, in particular in proximal tubules, thick ascending limbs and distal convoluted tubules. Four distinct, hierarchically interconnected injured cell states were distinguishable and characterized by transcriptome patterns associated with oxidative stress, hypoxia, interferon response, and epithelial-to-mesenchymal transition, respectively. Transcriptome differences between individuals with AKI were driven primarily by the cell type-specific abundance of these four injury subtypes rather than by private molecular responses. AKI-associated changes in gene expression between individuals with and without COVID-19 were similar.

Conclusion

The study provides an extensive resource of the cell type-specific transcriptomic responses associated with critical illness-associated AKI in humans, highlighting recurrent disease-associated signatures and inter-individual heterogeneity. Personalized molecular disease assessment in human AKI may foster the development of tailored therapies.
Shape variability of the central sulcus in the developing brain: a longitudinal descriptive and predictive study in preterm infants
Authors: de Vareilles H , Rivière D , Sun Z , Fischer C , Leroy F , Neumane S , Stopar N , Eijsermans R , Ballu M , Tataranno ML , Benders MJNL , Mangin JF , Dubois J
Published: December 2021

Despite growing evidence of links between sulcation and function in the adult brain, the folding dynamics, occurring mostly before normal-term-birth, is vastly unknown. Looking into the development of cortical sulci in babies can give us keys to address fundamental questions: what is the sulcal shape variability in the developing brain? When are the shape features encoded? How are these morphological parameters related to further functional development?

In this study, we aimed to investigate the shape variability of the developing central sulcus, which is the frontier between the primary somatosensory and motor cortices. We studied a cohort of 71 extremely preterm infants scanned twice using MRI – once around 30 weeks post-menstrual age (w PMA) and once at term-equivalent age, around 40w PMA –, in order to quantify the sulcus’s shape variability using manifold learning, regardless of age-group or hemisphere. We then used these shape descriptors to evaluate the sulcus’s variability at both ages and to assess hemispheric and age- group specificities. This led us to propose a description of ten shape features capturing the variability in the central sulcus of preterm infants. Our results suggested that most of these features (8/10) are encoded as early as 30w PMA. We unprecedentedly observed hemispheric asymmetries at both ages, and the one captured at term-equivalent age seems to correspond with the asymmetry pattern previously reported in adults. We further trained classifiers in order to explore the predictive value of these shape features on manual performance at 5 years of age (handedness and fine motor outcome). The central sulcus’s shape alone showed a limited but relevant predictive capacity in both cases. The study of sulcal shape features during early neurodevelopment may participate to a better comprehension of the complex links between morphological and functional organization of the developing brain.

Highlights

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Shape features can be isolated to describe quantitatively the development of the central sulcus.

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Most shape characteristics of the central sulcus are already encoded at 30 weeks of post-menstrual age (w PMA) in preterm newborns.

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The central sulcus shows subtle hemispheric asymmetries as soon as 30w PMA.

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The early shape of the central sulcus can help predicting handedness and fine motor outcome at 5 years of age.
An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by several therapeutic monoclonal antibodies
Authors: VanBlargan Laura A. , Errico John M. , Halfmann Peter J. , Zost Seth J. , Crowe James E. , Purcell Lisa A. , Kawaoka Yoshihiro , Corti Davide , Fremont Daved H. , Diamond Michael S.
Published: December 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic resulting in millions of deaths worldwide. Despite the development and deployment of highly effective antibody and vaccine countermeasures, rapidly-spreading SARS-CoV-2 variants with mutations at key antigenic sites in the spike protein jeopardize their efficacy. Indeed, the recent emergence of the highly-transmissible B.1.1.529 Omicron variant is especially concerning because of the number of mutations, deletions, and insertions in the spike protein. Here, using a panel of anti-receptor binding domain (RBD) monoclonal antibodies (mAbs) corresponding to those with emergency use authorization (EUA) or in advanced clinical development by Vir Biotechnology (S309, the parent mAbs of VIR-7381), AstraZeneca (COV2-2196 and COV2-2130, the parent mAbs of AZD8895 and AZD1061), Regeneron (REGN10933 and REGN10987), Lilly (LY-CoV555 and LY-CoV016), and Celltrion (CT-P59), we report the impact on neutralization of a prevailing, infectious B.1.1.529 Omicron isolate compared to a historical WA1/2020 D614G strain. Several highly neutralizing mAbs (LY-CoV555, LY-CoV016, REGN10933, REGN10987, and CT-P59) completely lost inhibitory activity against B.1.1.529 virus in both Vero-TMPRSS2 and Vero-hACE2-TMPRSS2 cells, whereas others were reduced (∼12-fold decrease, COV2-2196 and COV2-2130 combination) or minimally affected (S309). Our results suggest that several, but not all, of the antibody products in clinical use will lose efficacy against the B.1.1.529 Omicron variant and related strains.
Modified forms of easyCLIP
Authors: Porter Douglas F , Garg Raghav M , Meyers Robin M. , Miao Weili , Ducoli Luca , Zarnegar Brian J , Khavari Paul A
Published: December 2021

The easyCLIP protocol describes a method for both normal CLIP library construction and the absolute quantification of RNA cross-linking rates, data which could be usefully combined to analyze RNA-protein interactions. Using these cross-linking metrics, significant interactions could be defined relative to a set of random non-RBPs. The original easyCLIP protocol did not use index reads, required custom sequencing primers, and did not have an easily reproducible analysis workflow. This short paper attempts to amend these deficiencies. It also includes some additional technical experiments and investigates the usage of alternative adapters. The results here are intended to allow more options to easily perform and analyze easyCLIP.
Unraveling the roles of Mast4 in amelogenesis via regulating DLX3 and stem cell maintenance of mouse incisors
Authors: Lee Dong-Joon , Kim Pyunggang , Kim Hyun-Yi , Park Jinah , Lee Seung-Jun , An Haein , Heo Jin Sun , Lee Min-Jung , Ohshima Hayato , Mizuno Seiya , Takahashi Satoru , Jung Han-Sung , Kim Seong-Jin
Published: December 2021

Asymmetric division of stem cells allows for maintenance of the cell population and differentiation for harmonious progress. Developing mouse incisors allows for examination of how the stem cell niche employs specific insights into essential phases. Microtubule-associated serine/threonine kinase family member 4 (Mast4) knockout (KO) mice showed abnormal incisor development with weak hardness as the apical bud was reduced and preameloblasts were shifted to the apical side, resulting in Amelogenesis Imperfecta. In addition, Mast4 KO incisors showed abnormal enamel maturation, and stem cell maintenance was inhibited as amelogenesis accelerated. Distal-Less Homeobox 3 (DLX3), known to be a critical factor Tricho-Dento-Osseous (TDO) syndrome, is considered to be responsible for Amelogenesis Imperfecta in humans. MAST4 directly binds to DLX3 and induces phosphorylation at three residues within the nuclear localization sites (NLS) that promote the nuclear translocation of DLX3. MAST4-mediated phosphorylation of DLX3 ultimately controls the transcription of DLX3 target genes, which are carbonic anhydrase and ion transporter genes involved in the pH regulation process during ameloblast maturation. Taken together, our data reveal a novel role of MAST4 as a critical regulator of ameloblast maturation, which controls DLX3 transcriptional activity.
Prevalence and time trend of congenital heart defects: a registry-based study in Iran
Authors: Molapour Hossein , Dastgiri Saeed , Esmaeili Elham Davtalab
Published: December 2021

Introduction

Congenital Heart Defects (CHD) are one of the most common types of congenital anomalies affecting nearly one percent of births every year. The aim of this study was to report the prevalence and time trend of CHD in the northwest of Iran between 2000 and 2019.

Methods

Since 2000, infants born with birth defects have been registered in Tabriz Registry of Congenital Anomalies (TRoCA). For this study, the information and data of newborns with CHD (n=1084) were collected using the TRoCA registry system.

Results

Over the two decades, the prevalence rate of CHD in the northwest of Iran was 3.7 per 1000 live births (95 percent CI: 34.9 to 39.4). The prevalence rate of CHD during the first decade (2000-09) and the second (2010-19) were estimated 2.8 (95 percent CI: 2.5 to 2.9) and 5.9 (95 percent CI: 5.4 to 6.4) per 1000 live births, respectively.

Conclusion

The prevalence rate of CHD in the TRoCA registry area showed an increasing trend indicating methodological improvement in the facilities and diagnosis techniques. It would therefore seem essential to concentrate on the primary prevention activities to reduce the burden of these defects.
The tryptophan catabolite or kynurenine pathway in schizophrenia: meta-analysis reveals dissociations between central, serum and plasma compartments
Authors: Almulla Abbas F. , Vasupanrajit Asara , Tunvirachaisakul Chavit , Al-Hakeim Hussein K. , Solmi Marco , Verkerk Robert , Maes Michael
Published: December 2021

The tryptophan catabolite (TRYCAT) pathway is implicated in the pathophysiology of schizophrenia (SCZ) since the rate-limiting enzyme indoleamine-dioxygenase (IDO) may be induced by inflammatory and oxidative stress mediators. This systematic review searched PubMed, Web of Science, and Google Scholar for papers published from inception until August 2021 and meta-analyzed the association between SCZ and TRYCATs in the central nervous system (CNS) and peripheral blood. We included 61 studies comprising 2813 patients and 2948 healthy controls. In the CNS we found a significant (p<0.001) increase in the kynurenine/tryptophan (KYN/TRP) (standardized mean difference, SMD=0.769, 95% confidence interval, CI: 0.456; 1.082) and kynurenic acid (KA)/KYN+TRP (SMD=0.697, CI:0.478-0.917) ratios, KA (SMD=0.646, CI: 0.422; 0.909) and KYN (SMD=1.238; CI: 0.590; 1.886), while the 3OH-kynurenine (3HK) + KYN-3-monooxygenase (KMO)/KYN ratio was significantly reduced (SMD=-1.089, CI: -1.682; -0.496). There were significant differences between KYN/TRP, (KYN+KA)/TRP, (3HK+KMO)/KYN, KA, and KYN levels among the CNS and peripheral blood, and among serum and plasma KYN. The only useful peripheral marker of CNS TRYCATs findings was the increased KYN/TRP ratio in serum (SMD=0.211, CI: 0.056; 0.366, p=0.007), but not in plasma. There was no significant increase in a neurotoxic composite score based on KYN, 3HK, and picolinic, xanthurenic, and quinolinic acid. SCZ is accompanied byincreased IDO activity in the CNS and serum, and reduced KMO activity and a shift towards KA production in the CNS. This CNS TRYCATs profile indicates neuroprotective, negative immunoregulatory and anti-inflammatory effects. Peripheral blood levels of TRYCATs are dissociated from CNS findings except for a modest increase in serum IDO activity.
Prolonged Detection of SARS CoV2 RNA in Extracellular Vesicles in Nasal Swab RT-PCR Negative Patients
Authors: Subudhi P. Debishree , Rooge Sheetalnath , Thangariyal Swati , Goswami Sivang , Agarwal Reshu , Gupta Ekta , Baweja Sukriti
Published: December 2021

Background

There is a prolonged RT-PCR positivity seen in COVID-19 infected patients up to 2-3 months. We aim to investigate the presence of viral particles inside Extracellular vesicles (EV) and its role in underlying liver disease patients.

Methods

SARS CoV2 nasal RT-PCR positive n=78 {n=24(66.6%) chronic liver disease (CLD); n=52 (81.3%) non-liver disease} were studied. SARS CoV2 patients were also followed up for day (d) 7, 14 and 28. Extracellular vesicles were isolated using differential ultracentrifugation. SARS CoV2 RNA was measured using qRT-PCR by Altona Real Star kit.

Results

In baseline RT-PCR positive patients, SARS-CoV2 RNA inside the EV was present in 64/74 (82%) patients with comparable viral load between VTM and EV (mean 1CT – 0.033±0.005 vs. 1CT – 0.029±0.014, p=ns). On follow-up at day 7, of the 24 patients negative for COVID19, 10 (41%) had persistence of virus in the EV (1CT – 0.028±0.004) and on day 14, 14 of 40 (35%) negative RT-PCR had EVs with SARS CoV2 RNA (1CT – 0.028±0.06). The mean viral load decreased at day7 and day14 in nasal swab from baseline (p=0.001) but not in EV. SARS-CoV2 RNA otherwise undetectable in plasma, was found to be positive in EV in 12.5% of COVID19 positive patients. Interestingly, significantly prolonged and high viral load was found in EV at day 14 in CLD-COVID19 patients compared to COVID19 alone (p=0.002). The high cellular injury was seen in CLD-COVID19 infected patients with significant high levels of EV associated with endothelial cells and hepatocytes than COVID19 alone (p=0.004; 0.001).

Conclusion

Identification of SARS-CoV2 RNA in EV, in RT-PCR negative patients indicates persistence of infection for and likely recurrence of the infection. EV associated RNA may determine the clinical course of subjects with undetectable SARS-CoV2 virus and this may also have relevance in management of chronic liver disease patients.
A Single Dose of COVID-19 mRNA Vaccine Induces Airway Immunity in COVID-19 Convalescent Patients
Authors: Martinuzzi Emanuela , Benzaquen Jonathan , Guerin Olivier , Leroy Sylvie , Simon Thomas , Ilie Marius , Hofman Véronique , Allegra Maryline , Tanga Virginie , Michel Emeline , Boutros Jacques , Maniel Charlotte , Sicard Antoine , Glaichenhaus Nicolas , Czerkinsky Cecil , Blancou Philippe , Hofman Paul , Marquette Charles
Published: December 2021

Background

Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and hence virus shedding. Preclinical and clinical studies have shown that a parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior infection compared to two injections of a parenteral vaccine. We investigated whether this was also the case for a COVID-19 mRNA vaccine.

Methods

Twenty-three COVID-19 convalescent patients and 20 SARS-CoV-2-naive subjects were vaccinated with respectively one and two doses of the Pfizer-BioNTech COVID-19 RNA vaccine. Nasal Epithelial Lining Fluid (NELF) and plasma were collected before and after vaccination and assessed for Immunoglobulin (Ig)G and IgA to Spike and for their ability to inhibit the binding of Spike to its ACE-2 receptor. Blood was analyzed one week after vaccination for the number of Spike-specific Antibody Secreting Cells (ASCs) with a mucosal tropism.

Results

In COVID-19 convalescent patients, a single dose of vaccine amplified pre-existing Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after two vaccine doses

Conclusion

This study showed that a parenteral booster injection of a COVID-19 RNA vaccine promoted stronger mucosal immune responses in COVID-19 convalescent patients compared to SARS-CoV-2 naive subjects who had received a first vaccine dose.
Categorical working memory codes in human visual cortex
Authors: Yan Chang , Christophel Thomas B. , Allefeld Carsten , Haynes John-Dylan
Published: December 2021

Working memory contents are represented in neural activity patterns across multiple regions of the cortical hierarchy. It has remained unclear to which degree this reflects a specialization for different levels of abstraction. Here, we demonstrate that for color stimuli categorical codes are already present at the level of extrastriate visual cortex (V4 and VO1). Interestingly, this categorical coding was observed during working memory, but not during perception.
seGMM: a new tool to infer sex from massively parallel sequencing data
Authors: Liu Sihan , Zeng Yuanyuan , Chen Meilin , Zhang Qian , Wang Lanchen , Wang Chao , Lu Yu , Guo Hui , Bu Fengxiao
Published: December 2021

Inspecting concordance between self-reported sex and genotype-inferred sex from genomic data is a significant quality control measure in clinical genetic testing. Numerous tools have been developed to infer sex for genotyping array, whole-exome sequencing, and whole-genome sequencing data. However, improvements in sex inference from targeted gene sequencing panels are warranted. Here, we propose a new tool, seGMM, which applies unsupervised clustering (Gaussian Mixture Model) to determine the gender of a sample from the called genotype data integrated aligned reads. seGMM consistently demonstrated > 99% sex inference accuracy in publicly available (1000 Genomes) and our in-house panel dataset, which achieved obviously better sex classification than existing popular tools. Compared to including features only in the X chromosome, our results show that adding additional features from Y chromosomes (e.g. reads mapped to the Y chromosome) can increase sex classification accuracy. Notably, for WES and WGS data, seGMM also has an extremely high degree of accuracy. Finally, we proved the ability of seGMM to infer sex in single patient or trio samples by combining with reference data and pinpointing potential sex chromosome abnormality samples. In general, seGMM provides a reproducible framework to infer sex from massively parallel sequencing data and has great promise in clinical genetics.
Supramolecular assembly of chloroplast NAD(P)H dehydrogenase-like complex with photosystem I from Arabidopsis thaliana
Authors: Su Xiaodong , Cao Duanfang , Pan Xiaowei , Shi Lifang , Liu Zhenfeng , Dall’Osto Luca , Bassi Roberto , Zhang Xinzheng , Li Mei
Published: December 2021

Cyclic electron transport/flow (CET/CEF) in chloroplasts is a regulatory mechanism crucial for optimization of plant photosynthetic efficiency. CET is catalyzed by a membrane-embedded NAD(P)H dehydrogenase-like (NDH) complex containing at least 29 protein subunits and associating with photosystem I (PSI) to form the NDH-PSI supercomplex. Here we report the 3.9 Å resolution structure of Arabidopsis thaliana NDH-PSI (AtNDH-PSI) supercomplex. We have constructed structural models for 26 AtNDH subunits, among which 11 subunits are unique to chloroplast and stabilize the core part of NDH complex. In the supercomplex, one NDH can bind up to two PSI-LHCI complexes at both sides of its membrane arm. Two minor LHCIs, Lhca5 and Lhca6, each present in one PSI-LHCI, interact with NDH and contribute to the supercomplex formation and stabilization. Our results showed structural details of the supercomplex assembly and provide molecular basis for further investigation of the regulatory mechanism of CEF in plants.
AliSim: A Fast and Versatile Phylogenetic Sequence Simulator For the Genomic Era
Authors: Ly-Trong Nhan , Naser-Khdour Suha , Lanfear Robert , Minh Bui Quang
Published: December 2021

Sequence simulators play an important role in phylogenetics. Simulated data has many applications, such as evaluating the performance of different methods, hypothesis testing with parametric bootstraps, and, more recently, generating data for training machine-learning applications. Many sequence simulation programs exist, but the most feature-rich programs tend to be rather slow, and the fastest programs tend to be feature-poor. Here, we introduce AliSim, a new tool that can efficiently simulate biologically realistic alignments under a large range of complex evolutionary models. To achieve high performance across a wide range of simulation conditions, AliSim implements an adaptive approach that combines the commonly-used rate matrix and probability matrix approach. AliSim takes 1.3 hours and 1.3 GB RAM to simulate alignments with one million sequences or sites, while popular software Seq-Gen, Dawg, and INDELible require two to five hours and 50 to 500 GB of RAM. We provide AliSim as an extension of the IQ-TREE software version 2.2, freely available at www.iqtree.org, and a comprehensive user tutorial at http://www.iqtree.org/doc/AliSim.
Declining population sizes and loss of genetic diversity in commercial fishes: a simple method for a first diagnostic
Authors: Petit-Marty Natalia , Min Liu , Tan Iris Ziying , Chung Arthur , Terrasa Bàrbara , Guijarro Beatriz , Ordines Francesc , Ramírez-Amaro Sergio , Massutí Enric , Schunter Celia
Published: December 2021

Exploited fish species may have or are experiencing declines in population sizes coupled with a decrease in genetic diversity. This can lead to the loss of adaptive potential to face current and future environmental changes. However, little is known about this subject while research on it is urgently needed. Thus, this study aims to answer a simple, even naive question, given the complexity of the subject: Could we use a simple method to obtain information on the loss of genetic diversity in exploited fish species? We investigated the use of the levels of genetic diversity in the widely used genetic marker Cytochrome C Oxidase subunit I (COI) mitochondrial gene. Estimates of genetic diversity in COI were obtained for populations of seven fish species with different commercial importance from the East China Sea. These estimates were contrasted against a large dataset of fish species distributed worldwide (N=1426), a dataset of East-Asian fish species (N=118), two farmed species with expected low genetic diversity, and four long-term managed species from the Mediterranean Sea. We found that estimates of genetic diversity in COI match the expectations from theoretical predictions, known population declines, and fishing pressures. Thus, the answer to our question is affirmative and we conclude that estimates of genetic diversity in COI provide an effective first diagnostic of the conservation status of exploited fish species. This simple and cost-effective tool can help prioritize research, management, and conservation on species with suspected loss of genetic diversity potentially eroding their adaptive potential to global change.
Anti-inflammatory and neuroprotective activity of Viphyllin a standardized extract of β-caryophyllene from black pepper (Piper Nigrum L) and its associated mechanisms in mouse macrophage cells and Human Neuroblastoma SH-SY5Y cells
Authors: Gouthamchandra Kuluvar , Venkataramana Sudeep Heggar , Sathish Anusha , Amritharaj  , Basavegowda Lingaraju Harakanahalli , Puttaswamy Naveen , Kodimule Shyam Prasad
Published: December 2021

Oxidative stress breeds various chronic lifestyle ailments including inflammatory conditions and neurodegenerative diseases. β-caryophyllene natural bicyclic sesquiterpene, obtained from various plants sources found to be effective against inflammation and neuroprotection. In this study, we have evaluated the protective effect of Viphyllin, a standardized extract of β-caryophyllene from black pepper against inflammation induced by lipopolysaccharide in RAW264.7 macrophage cells and mechanisms involved in hydrogen peroxide (H2O2)-challenged oxidative stress in human neuroblastoma SH-SY5Y cells. Viphyllin demonstrated the anti-inflammatory activity by subsiding the release of the pro-inflammatory intermediaries like NO, cytokines, interleukins, and protein expression levels of cyclooxygenase (COX-2) and inducible nitric oxide synthase (iNOS). In addition, Viphyllin suppressed the extracellular signal-regulated kinase (ERK). c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) phosphorylation. On the other hand, Viphyllin showed neuroprotective effect against neuronal oxidative damage caused by H2O2. Viphyllin lessened the expression B-cell lymphoma-2 (Bcl-2), B-cell lymphoma-2-associated X protein (BAX), cleaved caspase-9, and PARP-1 proteins associated with apoptosis. Our results indicate that Viphyllin ameliorated LPS-mediated inflammation in macrophages by regulating inflammation and Viphyllin exerted remarkable anti apoptotic effect against neuronal damage challenged by H2O2. Altogether, Viphyllin could be potential functional food ingredient for inflammation and neurodegenerative diseases.
Interferon-gamma mediates skeletal muscle lesions through JAK/STAT pathway activation in inclusion body myositis
Authors: Hou Cyrielle , Periou Baptiste , Gervais Marianne , Berthier Juliette , Baba-Amer Yasmine , Souvannanorath Sarah , Malfatti Edoardo , Relaix Fréderic , Bencze Maximilien , Authier François Jérôme
Published: December 2021

Dysimmune and Inflammatory Myopathies (DIMs) are acquired idiopathic myopathy associated with immune response dysregulation. Inclusion Body Myositis (IBM), the most common DIMs, is characterized by endomysial infiltrates of cytotoxic T lymphocytes CD8, muscle type II-interferon (IFNγ) signature, and by the lack of response to immunomodulatory therapies. We showed that IBM was pathologically characterized by the presence of chronic degenerative myopathic features including myofiber atrophy, fibrosis, adipose involution, and the altered functions of skeletal muscle stem cells. Here, we demonstrated that protracted systemic exposure to IFNγ delayed muscle regeneration and led to IBM-like muscular degenerative changes in mice. In vitro, IFNγ treatment inhibited the activation, proliferation, migration, differentiation, and fusion of myogenic progenitor cells and promoted their senescence through JAK-STAT-dependent activation. Finally, JAK-STAT inhibitor, ruxolitinib abrogated the deleterious effects of IFNγ on muscle regeneration, suggesting that the JAK-STAT pathway could represent a new therapeutic target for IBM.
Alterations in human gut microbiome composition and metabolism after exposure to glyphosate and Roundup and/or a spore-based formulation using the SHIME® technology
Authors: Mesnage Robin , Calatayud Marta , Duysburgh Cindy , Marzorati Massimo , Antoniou Michael N
Published: December 2021

Despite extensive research into the toxicology of the herbicide glyphosate, there are still major unknowns regarding its effects on the human gut microbiome. As a step in addressing this knowledge gap, we describe for the first time the effects of glyphosate and a Roundup glyphosate-based herbicide on infant gut microbiota using SHIME technology, which mimics the entire gastrointestinal tract. SHIME® microbiota culture was undertaken in the presence of a concentration of 100 mg/L (corresponding to a dose of 1.6 mg/kg/day) glyphosate and the same glyphosate equivalent concentration of Roundup, which is in the range of the US chronic reference dose, and subjected to molecular profiling techniques to assess outcomes. Roundup and to a lesser extent glyphosate caused an increase in fermentation activity, resulting in acidification of the microbial environment. This was also reflected by an increase in lactate and acetate production concomitant to a decrease in the levels of propionate, valerate, caproate and butyrate. Ammonium production reflecting proteolytic activities was increased by Roundup exposure. Global metabolomics revealed large scale disturbances in metabolite profiles, including an increased abundance of long chain polyunsaturated fatty acids (n3 and n6). Although changes in bacterial composition measured by qPCR and 16S rRNA sequencing were less clear, our results suggested that lactobacilli had their growth stimulated as a result of microenvironment acidification. Co-treatment with the spore-based probiotic formulation MegaSporeBiotic reverted some of the changes in short-chain fatty acid levels. Altogether, our results suggest that glyphosate can exert effects on human gut microbiota at permitted regulatory levels of exposure, highlighting the need for epidemiological studies aimed at evaluating the effects of glyphosate herbicides on human gut microbiome function.
Systemic and intra-amygdala administrations of midazolam reverse anxiety-like behavior induced by cohabiting with a cagemate in chronic pain condition
Authors: Carmona Isabela Miranda , de Oliveira Paulo Eduardo Carneiro , Baptista-de-Souza Daniela , Canto-de-Souza Azair
Published: December 2021

The affective component of pain may be shared among conspecifics through emotional contagion, a form of empathic expression. In this sense, reverberation of negative emotions could generate distress behavioral responses, such as pathological anxiety. Evidences reported that amygdala and its benzodiazepine receptors are involved in perception of pain in others. However, relatively little is known about the neural processes underlying emotional contagion induced by pain observation. In the present study, we investigated the effects of midazolam, an allosteric GABAergic receptor agonist, in anxiety-like behaviors induced by cohabitation with cagemate submitted to sciatic nerve constriction. For this purpose, we administrated systemic (0.5, 1.0 and 2.0 mg/kg) and intra-amygdala midazolam injections (3.0 and 30.0 nmol) in observer cagemates before elevated plus-maze (EPM) evaluation. We found that mice subjected to nerve constriction and their observer cagemates increased anxiety-like behavior in the EPM. Further, systemically (1.0 and 2.0 mg/kg) and intra-amygdala administration of midazolam (3.0 and 30 nmol) reverse this anxiogenic effect. Collectively, these results suggest that social interaction with a cagemate under chronic pain produces anxiety-like responses that could be blocked through midazolam application.