bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evolutionary history of cotranscriptional editing in the paramyxoviral phosphoprotein gene
Authors: Douglas Jordan , Drummond Alexei J , Kingston Richard L 
Published: March 2021

Abstract
The phosphoprotein gene of the paramyxoviruses encodes multiple protein products. The P, V, and W proteins are generated by transcriptional slippage. This process results in the insertion of non-templated guanosine nucleosides into the mRNA at a conserved edit site. The P protein is an essential component of the viral RNA polymerase and is encoded by a faithful copy of the gene in the majority of paramyxoviruses. However, in some cases, the non-essential V protein is encoded by default and guanosines must be inserted into the mRNA in order to encode P. The number of guanosines inserted into the P gene can be described by a probability distribution, which varies between viruses. In this article, we review the nature of these distributions, which can be inferred from mRNA sequencing data, and reconstruct the evolutionary history of cotranscriptional editing in the paramyxovirus family. Our model suggests that, throughout known history of the family, the system has switched from a P default to a V default mode four times; complete loss of the editing system has occurred twice, the canonical zinc finger domain of the V protein has been deleted or heavily mutated a further two times, and the W protein has independently evolved a novel function three times. Finally, we review the physical mechanisms of cotranscriptional editing via slippage of the viral RNA polymerase.
Detection of Four New Tomato Viruses in Serbia Using Post Hoc High-Throughput Sequencing Analysis of Samples From a Large-Scale Field Survey
Authors: Vučurović Ana , Kutnjak Denis , Mehle Nataša , Stanković Ivana , Pecman Anja , Bulajić Aleksandra , Krstić Branka , Ravnikar Maja 
Published: March 2021

Tomato production worldwide is affected by numerous plant virus species. The early and accurate detection of viruses is a critical step for disease control. However, the simultaneous detection of the most known tomato viruses can be difficult because of the high number and diversity of tomato-infecting viruses. Here, we have identified four new viruses in Serbia by applying target-independent small RNA high-throughput sequencing (HTS). HTS was applied on pools of samples and separate samples, in total comprising 30 tomato samples that exhibited (severe) virus-like symptoms and were collected in Serbia during three annual surveys (2011 to 2013). These samples had previously tested negative for the presence of 16 tomato viruses using targeted detection methods. Three divergent complete genome sequences of Physostegia chlorotic mottled virus were obtained from different localities, indicating for the first time that this virus is widespread in Serbia and might represent an emergent viral pathogen of tomato. The tomato torrado virus was detected at one locality with devastating yield losses. The southern tomato virus was detected at two localities, and the spinach latent virus was detected at one locality. In addition, we detected the presence of one already-known virus in Serbia, the tomato spotted wilt orthotospovirus. All the HTS results were subsequently confirmed by targeted detection methods. In this study, the successful application of post hoc HTS testing of a limited number of pooled samples resulted in the discovery of new viruses. Thus, our results encourage the use of HTS in research and diagnostic laboratories, including laboratories that have limited resources to resolve disease etiology.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Surgical Prevention of Weight Regain and Type 2 Diabetes Recurrence in 3 Different Bariatric Operations and Their Differential Long-Term Outcome
Authors: Steffen Rudolf , Horber Fritz F. 
Published: March 2021

Introduction:
Comparative data on long-term outcomes of mechanistically different bariatric operations are scarce.

Methods:
In this prospective, observational study, consecutive patients with severe obesity were studied using a predefined reoperation algorithm to determine long-term health outcomes after bariatric surgery (BS): adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGB), or biliopancreatic diversion (BPD). All patients were assessed for mortality, postoperative weight loss, rate of reoperation, comorbidities, and quality of life (QoL) 8 years after surgery.

Results:
Between 1996 and 2008, 2364 Swiss patients, with a mean body mass index of 43 ± 7 kg/m2 (mean ± SD) underwent AGB (n = 1404), RYGB (n = 790), or BPD (n = 170). Two thousand two hundred twenty-eight (94%) were followed for 8 years after BS. Eight-year mortality of the whole study group was 34.3 per 104 person-years. Percent excessive weight loss at 8 years was 56.7 ± 1.4% (95% confidence interval) in AGB, 62.5 ± 2.4% in RYGB and 64.8+-3.0% in BPD. The rate of major reoperation was highest in AGB and significantly lower in RYGB and BPD (63.4 vs 54.3 vs 47.2 per 103 person-years, P < 0.001). Remission of comorbidities was observed across all 3 groups, with key improvement (P < 0.01) in esophagitis in the RYGB group, and type 2 diabetes (T2D) (>60%) in procedures involving duodenal exclusion. Total improvement in QoL was similar between the 3 types of operations but was strongly correlated with weight loss preservation (P < 0.001).

Conclusions:
BS, at the expense of a high reoperation rate but low procedural mortality, considerably improves the QoL and results in sustained remission of comorbidities, especially T2D using a predefined reoperation algorithm developed to prevent weight regain and operation-specific complications.
Forehead and Hairline Surgery for Gender Affirmation
Authors: Pansritum Kamol 
Published: March 2021

Background:
With the improvement of the results of surgical treatment for facial transformation globally, many female transgender individuals seek surgical management for their faces, especially the forehead and hairline. These are critical aspects in the surgical management of the frontonasal-orbital area because the anatomy of the frontal sinuses is complicated and shows a high variation.

Methods:
The author presents a grid method to measure the boundary of the frontal sinus in the female transgender forehead contouring and reconstruction. The surgical technique of forehead set back and simultaneous hairline advancement is described.

Results:
Between January 2015 and December 2017, there were 23 cases of forehead and hairline feminization procedures by the author. Patient age was between 20 and 74 years (mean 32.56). There were 11 Asians and 12 White patients. Eleven patients underwent supraorbital ridge contouring, and 12 underwent forehead reconstruction. Hairline advancement was simultaneously performed in 9 patients, and 3 underwent forehead augmentation at the supraorbital ridge. The postoperative follow-up time ranged from 3 weeks to 18 months.

Conclusions:
The key to the success of forehead contouring surgery in female transgender patients is the precise measurement of the boundary of the frontal sinus. This technique offers a practical way to estimate the frontal sinus sizes and shapes to avoid intraoperative complications and reduces the possibility of surface irregularity.
Effects of Slowness, Frailty, Insufficient Intake, and Delirium in Patients Following Cardiac Surgery
Authors: Teng Chiao-Hsin , Hsu Ron-Bin , Chi Nai-Hsin , Wang Shoei-Shen , Chen Yih-Sharng , Chen Ssu-Yuan , Chen Cheryl Chia-Hui 
Published: March 2021

Background
Slow gait, frailty, insufficient postoperative caloric intake, and delirium, although seemingly distinct, can appear simultaneously in patients who underwent cardiac surgery.

Objectives
The aim of this study was to evaluate how these 4 factors overlap and how they individually and cumulatively affect cardiac surgery outcomes.

Methods
The effects of slowness (gait speed <0.83 m/s), frailty (≥3/5 Fried criteria), insufficient postoperative intake (<800 kcal/d), and delirium (defined by the Confusion Assessment Method) on hospital length of stay (LOS) and 3-month mortality were analyzed in 308 adult patients.

Results
Slowness, frailty, insufficient intake, and delirium affected 27.5%, 29.5%, 31.5%, and 13.3% of participants, respectively; only 42.2% (130/308) were free from these risks. Risk overlap was prevalent, as 26.3% (n = 81) had 2 or more risk factors. The most obvious overlap was in delirium (80% of delirious participants had other risks), suggesting that delirium cannot be managed in isolation. Individually, whereas slowness was associated only with longer LOS, frailty, insufficient intake, and delirium all led to longer LOS and higher mortality. When equally weighting each risk factor to analyze their cumulative effects, LOS increased by 4.4 days (95% confidence interval, 3.0–5.7) and 3-month mortality increased by 2.6-fold (95% confidence interval, 1.4–4.6), with each risk factor added, independent of participants' educational level, body mass index, and risk for cardiac surgery (EuroSCORE II ≥6).

Conclusions
Because a clinical overlap of slowness, frailty, insufficient postoperative intake, and delirium was evident in patients who underwent cardiac surgery, and risk of death and longer hospital stay increased with each factor added, care should be revised to consider these overlapping factors to maximize patient outcomes.
A Case of Self-Cannibalism
Authors: Aras Neriman 
Published: March 2021

Abstract
Self-mutilation is a behavior often associated with various psychiatric diseases, and it has various risk factors. Self-cannibalism, an extremely rare form of self-mutilation, can also be observed in the absence of psychosis and substance abuse. This study reports a case of self-cannibalism with multiple risk factors including history of substance use, previous self-mutilation actions, suicidal attempts, antisocial personality disorder, imprisonment, and active symptoms associated with untreated schizophrenia.
Physician, Protect Thyself
Authors: MacIntyre Michael R. , Appel Jacob M. 
Published: March 2021

Abstract
Modern psychiatric practice requires the use of the Internet, and the current pandemic has accelerated the adoption of technology in clinics. Psychiatrists receive significant education on protecting patient privacy and medical information when using these tools. However, they receive little training regarding protecting their own personal privacy in the Internet era. Private information, often without one's knowledge, is frequently available online and accessible by patients. The work of physicians and psychiatrists creates additional unique vulnerabilities to privacy. Given the essential nature of the Internet in modern clinical practice, physicians should understand how to monitor and protect personal privacy and safety online. We provide advice to minimize vulnerability to a privacy breach, with a focus on areas unique to psychiatrists and psychiatric practice. We review the literature on physician safety online and offer guidance to get started.
Regional spread of blaNDM-1-containing Klebsiella pneumoniae Sequence Type 147 in post-acute care facilities
Authors: Lapp Zena , Crawford Ryan , Miles-Jay Arianna , Pirani Ali , Trick William E. , Weinstein Robert A. , Hayden Mary K. , Snitkin Evan S. , Lin Michael Y. 
Published: March 2021

AbstractBackgroundCarbapenem-resistant Enterobacterales (CRE) harboring blaKPC have been endemic in Chicago-area healthcare networks for more than a decade. During 2016-2019, a series of regional point prevalence surveys identified increasing prevalence of blaNDM-containing CRE in multiple long-term acute care hospitals (LTACHs) and ventilator-capable skilled nursing facilities (vSNFs). We performed a genomic epidemiology investigation of blaNDM-producing CRE to understand their regional emergence and spread.MethodsWe performed whole-genome sequencing on NDM+ CRE isolates from four point-prevalence surveys across 35 facilities (LTACHs, vSNFs, and acute care hospital medical intensive care units) in the Chicago area and investigated the genomic relatedness and transmission dynamics of these isolates over time.ResultsGenomic analyses revealed that the rise of NDM+ CRE was due to the clonal dissemination of an ST147 Klebsiella pneumoniae strain harboring blaNDM-1 on an IncF plasmid. Dated phylogenetic reconstructions indicated that ST147 was introduced into the region around 2013 and likely acquired NDM around 2015. Analyzing genomic data in the context of patient transfer networks supported initial increases in prevalence due to intra-facility transmission in certain vSNFs, with evidence of subsequent inter-facility spread to connected LTACHs and vSNFs via patient transfer.ConclusionsWe identified a regional outbreak of blaNDM-1 ST147 that began in and disseminated across Chicago area post-acute care facilities. Our findings highlight the importance of performing genomic surveillance at post-acute care facilities to identify emerging threats.
An automated Dashboard to improve laboratory COVID-19 diagnostics management
Authors: Maury Emma , Boldi Marc-Olivier , Greub Gilbert , Chavez Valérie , Jaton Katia , Opota Onya 
Published: March 2021

AbstractBackgroundIn response to the CoVID-19 pandemic, our microbial diagnostic laboratory located in a university hospital has implemented several distinct SARS-CoV-2 RT-PCR systems in a very short time. Thanks to our automated molecular diagnostic platform, more than 140’000 SARS-CoV-2 RT-PCR tests were achieved over 12 months, with peaks higher than 1’500 daily tests. A dashboard was developed to give access to Key Performance Indicators (KPIs) to improve laboratory operational management.MethodsRT-PCR data extraction of four respiratory viruses – SARS-CoV-2, influenza A and B and RSV – from our laboratory information system (LIS), was automated. Important KPIs were identified and the visualization was achieved using an in-house dashboard based on the open-source language R (Shiny). Information is updated every 4 hours.ResultsThe dashboard is organized into three main parts. The “Filter” page presents all the KPIs, divided into five sections: i) general and gender-related indicators, ii) number of tests and positivity rate, iii) cycle threshold and viral load, iv) test durations, and v) not valid results. Filtering allows to select a given period, a dedicated instrument, a given specimen, or a requester for instance. The “Comparison” page allows a custom charting of all the available variables, which represents more than 182 combinations. The “Data” page gives the user access to the raw data in table format, with the possibility of filtering, allowing for a deeper analysis and data download in Excel format.ConclusionsThe dashboard, that gives a rapid access to a huge number of up-to-date information, represents a reliable and user-friendly tool improving the decision-making process, resource planning and quality management. The dashboard represent an added value for diagnosric laboratories during a pandemic, where rapid and efficient adaptation is mandatory.
Derivation of stationary distributions of biochemical reaction networks via structure transformation
Authors: Hong Hyukpyo , Kim Jinsu , Al-Radhawi M Ali , Sontag Eduardo D. , Kyoung Kim Jae 
Published: March 2021

AbstractLong-term behaviors of biochemical reaction networks (BRNs) are described by steady states in deterministic models and stationary distributions in stochastic models. Unlike deterministic steady states, stationary distributions capturing inherent fluctuations of reactions are extremely difficult to derive analytically due to the curse of dimensionality. Here, we develop a method to derive analytic stationary distributions from deterministic steady states by transforming BRNs to have a special dynamic property, called complex balancing. Specifically, we merge nodes and edges of BRNs to match in- and out-flows of each node. This allows us to derive the stationary distributions of a large class of BRNs, including autophosphorylation networks of EGFR, PAK1, and Aurora B kinase and a genetic toggle switch. This reveals the unique properties of their stochastic dynamics such as robustness, sensitivity and multi-modality. Importantly, we provide a user-friendly computational package, CASTANET, that automatically derives symbolic expressions of the stationary distributions of BRNs to understand their long-term stochasticity.
Cell-type-specific meQTL extends melanoma GWAS annotation beyond eQTL and informs melanocyte gene regulatory mechanisms
Authors: Zhang Tongwu , Choi Jiyeon , Dilshat Ramile , Einarsdóttir Berglind Ósk , Kovacs Michael A , Xu Mai , Malasky Michael , Chowdhury Salma , Jones Kristine , Bishop D Timothy , Goldstein Alisa M , Iles Mark M , Landi Maria Teresa , Law Matthew H , Shi Jianxin , Steingrímsson Eiríkur , Brown Kevin M 
Published: March 2021

AbstractWhile expression quantitative trait loci (eQTL) have been powerful in identifying susceptibility genes from genome-wide association studies (GWAS) findings, most trait-associated loci are not explained by eQTL alone. Alternative QTLs including DNA methylation QTL (meQTL) are emerging, but cell-type-specific meQTL using cells of disease origin has been lacking. Here we established an meQTL dataset using primary melanocytes from 106 individuals and identified 1,497,502 significantcis-meQTLs. Multi-QTL colocalization using meQTL, eQTL, and mRNA splice-junction QTL from the same individuals together with imputed methylome-wide and transcriptome-wide association studies identified susceptibility genes at 63% of melanoma GWAS loci. Among three molecular QTLs, meQTLs were the single largest contributor. To compare melanocyte meQTLs with those from malignant melanomas, we performed meQTL analysis on skin cutaneous melanomas from The Cancer Genome Atlas (n = 444). A substantial proportion of meQTL probes (45.9%) in primary melanocytes are preserved in melanomas, while a smaller fraction of eQTL genes is preserved (12.7%). Integration of melanocyte multi-QTL and melanoma meQTL identified candidate susceptibility genes at 72% of melanoma GWAS loci. Beyond GWAS annotation, meQTL-eQTL colocalization in melanocytes suggested that 841 unique genes potentially share a causal variant with a nearby methylation probe in melanocytes. Finally, melanocytetrans-meQTL identified a hotspot for rs12203592, acis-eQTL of a transcription factor, IRF4, with 131 candidate target CpGs. Motif enrichment and IRF4 ChIPseq analysis demonstrated that these target CpGs are enriched in IRF4 binding sites, suggesting an IRF4-mediated regulatory network. Our study highlights the utility of cell-type-specific meQTL.
ExploringLeishmania-Host Interaction with Reactome, a Database of Biological Pathways and Processes
Authors: Murillo Julieth , Jassal Bijay , Gómez Maria Adelaida , Hermjakob Henning 
Published: March 2021

AbstractLeishmaniasis is a parasitic disease with a wide range of clinical manifestations. Multiple aspects of theLeishmania-host interaction, such as genetic factors and modulation of microbicidal functions in host cells, influence pathogenesis, disease severity and treatment outcome. How do scientists contend with this complexity? Here, we work towards representing detailed, contextual knowledge onLeishmania-host interactions in the Reactome pathway database to facilitate the extraction of novel mechanistic insights from existing datasets. The Reactome database uses a hierarchy of abstractions that allows for the incorporation of detailed contextual knowledge on biological processes matched to differentially expressed genes. It also includes tools for enhanced over-representation analysis that exploits this extra information. We conducted a systematic curation of published studies documenting different aspects of theLeishmania-host interaction. The “Leishmaniainfection pathway” included four sub-pathways: phagocytosis, killing mechanisms, cell recruitment, andLeishmaniaparasite growth and survival. As proof-of-principle of the usefulness of the released pathway, we used it to analyze two previously released transcriptomic datasets of human and murine macrophages infected withLeishmania. Our results provide insights on the participation of ADORA2B signaling pathway in the modulation of IL10 and IL6 in infected macrophages. This work opens the way for other researchers to contribute to, and make use of, the Reactome database.ImportanceLeishmaniasis is a neglected disease infectious disease which affects more than 1.5 million people annually. Many researchers in the field apply -omic technologies to dissect the basis of clinical and therapeutic outcomes and access drug targetable features in the host-parasite interaction, among others. However, getting mechanistic insights from -omics data to such end is not an easy task. The most common approach is to use the -omics data to inquire pathways databases. The retrieved list of pathways often contains vague names that lack the biological context. In this study, we worked to create theLeishmaniainfection pathway in the Reactome database. With two practical examples from transcriptomics and microarray data, we demonstrated how this pathway facilitates the analysis of such data. In both datasets, we found a common mechanism of IL10 and IL6 production that the authors did not advert in their previous analysis, providing proof-of-principle of the tool’s enhanced potential for knowledge extraction.Leishmaniainfection pathway is in its first version, and must be expanded to cover the current knowledge base of theLeishmania-host interaction. We strongly encourage contributions from domain experts for the completion ofLeishmaniainfection pathways.
Macrophage-derived cholesterol contributes to therapeutic resistance in prostate cancer
Authors: El-Kenawi Asmaa , Dominguez-Viqueira William , Liu Min , Awasthi Shivanshu , Keske Aysenur , Steiner KayLee K. , Noel Leenil , Dhillon Jasreman , Gillies Robert J. , Yamoah Kosj , Yu Xiaoqing , Koomen John , Gatenby Robert A. , Ruffell Brian 
Published: March 2021

AbstractTumor-associated macrophages are key immune cells associated with cancer progression. Here we sought to determine the role of macrophages in castration-resistant prostate cancer (CRPC) using a syngeneic model that reflected the mutational landscape of the disease. A transcriptomic analysis of CRPC tumors following macrophage depletion revealed lower molecular signatures for steroid and bile acid synthesis, indicating potential perturbation of cholesterol metabolism. Since cholesterol is the precursor of the five major classes of steroid hormones, we reasoned that macrophages were regulating androgen biosynthesis within the prostate tumor microenvironment. Indeed, macrophage depletion reduced the levels of androgens within prostate tumors and restricted androgen receptor (AR) nuclear localizationin vitroandin vivo. Macrophages were cholesterol rich and had the ability to transfer cholesterol to tumor cellsin vitro, and AR nuclear translocation was inhibited by activation of Liver X Receptor (LXR)-β, the master regulator of cholesterol homeostasis. Finally, combining macrophage depletion with androgen deprivation therapy increased survival, supporting the therapeutic potential of targeting macrophages in CRPC.