bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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.
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

ABSTRACTBackgroundNext 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.MethodsWe 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 programResultsWe 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.ConclusionThe 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

SUMMARYThe 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

AbstractBackgroundAcute 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.MethodsWe 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.ResultsHigh-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.ConclusionThe 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

AbstractDespite 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-Shape features can be isolated to describe quantitatively the development of the central sulcus.-Most shape characteristics of the central sulcus are already encoded at 30 weeks of post-menstrual age (w PMA) in preterm newborns.-The central sulcus shows subtle hemispheric asymmetries as soon as 30w PMA.-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

ABSTRACTSevere 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

AbstractThe 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

AbstractAsymmetric 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

AbstractIntroductionCongenital 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.MethodsSince 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.ResultsOver 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.ConclusionThe 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

AbstractThe 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.