bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contemporary use of antimicrobial prophylaxis for surgical patients
Authors: Dias Priyanthi , Patel Akshaykumar , Rook William , Edwards Mark R. , Pearse Rupert M. , Abbott Tom E.F. 
Published: November 2021

BACKGROUND
Antimicrobial prophylaxis is commonly used to prevent surgical site infection (SSI), despite concerns of overuse leading to antimicrobial resistance. However, it is unclear how often antimicrobials are used and whether guidelines are followed.

OBJECTIVES
To describe contemporary clinical practice for antimicrobial prophylaxis including guideline compliance, the rate of postoperative infection and associated side effects.

DESIGN
A prospective, multicentre, observational cohort study.

SETTING
Twelve United Kingdom National Health Service hospitals.

PARTICIPANTS
One thousand one hundred and sixteen patients, aged at least 18 years undergoing specific colo-rectal, obstetric, gynaecological, urological or orthopaedic surgical procedures.

EXPOSURE
Compliance with guidelines for antimicrobial prophylaxis.

OUTCOMES
The primary outcome was SSI within 30 days after surgery. Secondary outcomes were number of doses of antimicrobials for prophylaxis and to treat infection, incidence of antimicrobial-related side effects and mortality within 30 days after surgery. Data are presented as number with percentage (%) or median with interquartile range [IQR].
Results of logistic regression analyses are presented as odds ratio/rate ratio (OR/RR) with 95% confidence intervals (95% CIs).

RESULTS
1102 out of 1106 (99.6%) patients received antimicrobial prophylaxis, which was compliant with local guidelines in 929 out of 1102 (84.3%) cases. 2169 out of 51 28 (42.3%) doses of antimicrobials were administered as prophylaxis (median 1 [1 to 2] dose) and 2959 out of 5128 (57.7%) were administered to treat an infection (median 21 [11 to 28] doses). 56 patients (5.2%) developed SSI. Antimicrobial prophylaxis administered according to local guidelines was not associated with a lower incidence of SSI compared with administration outside guidelines [OR 0.90 (0.35 to 2.29); P
= 0.823]. 23 out of 1072 (2.2%) patients experienced a side effect of antimicrobial therapy. 7 out of 1082 (0.6%) patients died. The median hospital stay was 3 [1 to 5] days.

CONCLUSION
Antimicrobial prophylaxis was administered for almost all the surgical procedures under investigation. However, this was not always compliant with guidelines. Further research is required to determine whether the amount of prophylactic antimicrobials could be safely and effectively reduced without increasing the incidence of SSI.
Chryseobacterium endalhagicum sp. nov., isolated from seed of leguminous plant
Authors: Zhang Xiaobo , Guo Xingyan , Kahaer Mayina , Tian Tingting , Sun Yuping 
Published: November 2021

A Gram-stain-negative, yellow-pigmented bacterium, designated as L7T, was isolated from seeds of Alhagi sparsifolia Shap., a leguminous plant that grows in northwest PR China. Strain L7T was found to be non-flagellated, non-spore forming rods which can grow at 10–37 °C, pH 6.0–8.5 and in 0–3 % (v/w) NaCl concentration. The 16S rRNA gene sequence analysis showed that strain L7T belongs to the genus

Chryseobacterium

with sequence similarities to

Chryseobacterium vietnamense

GIMN1.005T (98.1%),

C. bernardetii

NCCTC13530T (98.0%),

C. vrystaatense

LMG 22846T (97.9%),

C. nakagawai

NCTC13529T (97.7%),

C. shigense

DSM 17126T (97.6%) and

C. rhizosphaerae

RSB3-1T (97.5%). The average nucleotide identity of strain L7T to 31 reference strains were 78.6–85.6 %, lower than the species delineation threshold of 95 %. MK-6 was the only respiratory quinone of L7T and major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C16 : 1
ω7c and/or C16 : 1
ω6c, isoC17 : 1
ω9c and/or C16 : 0 10-methyl. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminophospholipids, two unidentified aminolipids, three unidentified glycolipids and two unidentified lipids. The G+C content of the genome was 38.58 mol%. On the basis of polyphasic taxonomy analyses in this study, strain L7T is considered to represent a novel species in the genus

Chryseobacterium

, for which the name Chryseobacterium endalhagicum sp. nov. is proposed. The type strain is L7T (=MCCC 1K05687T=JCM 34506T)
Genetic Insight into Birt-Hogg-Dubé syndrome in Indian patients reveals novel mutations in FLCN
Authors: Ray Anindita , Chattopadhyay Esita , Singh Richa , Bera Arnab , Sarma Mridul , Munot Mahavir , Desai Unnati , Rajan Sujeet , Prabhudesai Pralhad , Prakash Ashish K. , Chowdhury Sushmita Roy , Bhowmick Niladri , Dhar Raja , Udwadia Zarir F. , Dey Atin , Mitra Subhra , Joshi Jyotsna M , Ghosh Saurabh , Maitra Arindam , Roy Bidyut 
Published: November 2021

AbstractBackgroundBirt-Hogg-Dubé syndrome (BHDS) is a rare monogenic condition mostly associated with germline mutations at FLCN. It is characterized by either one or more manifestations of primary spontaneous pneumothorax (PSP), skin fibrofolliculomas and renal carcinoma. Here, we comprehensively studied germline mutations in BHDS patients and asymptomatic members from 15 Indian families.MethodsTargeted amplicon NGS and Sanger sequencing was performed to detect germline mutations at FLCN in 31 clinically diagnosed patients and 74 asymptomatic family members. Functional effects and protein-protein interaction of FLCN variants were evaluated in-silico and molecular docking method. Family-based association study between pathogenic mutations and BHDS was also performed. Germline mutations at genes associated with phenotypically similar diseases were also addressed in few families.ResultsSix different types of pathogenic FLCN mutations were observed in the patients. Two of them: 11-nucleotide deletion (c.1150_1160delGTCCAGTCAGC) and splice acceptor mutation (c.1301-1G>A), were novel mutations. Two unreported Clinvar pathogenic mutations: stop-gain (c.634C>T) and 4-nucleotide duplication (c.1329_1332dupAGCC), and known mutations: hotspot mutation (c.1285delC) and splice donor mutations (c.1300+1G>A) were also detected. All these mutations greatly affected the protein stability and FLCN-FNIP2 protein interaction. Family-based association studies suggested pathogenic FLCN mutations are significantly associated with BHDS. Two pathogenic SNPs, rs1801133 and rs138189536, at MTHFR, associated with Homocystinuria, were found in one family.ConclusionPathogenic mutations at FLCN may play key roles in deregulating metabolic pathways leading to disease pathogenesis. Instead of FLCN mutations, MTHFR pathogenic SNPs were also detected in clinically diagnosed BHDS patients, therefore, genetic evaluation is necessary to avoid confounding diagnosis.
Lightweight Mobile Automated Assistant-to-physician for Global Lower-resource Areas
Authors: Zhang Chao , Zhang Hanxin , Khan Atif , Kim Ted , Omoleye Olasubomi , Abiona Oluwamayomikun , Lehman Amy , Olopade Christopher O. , Olopade Olufunmilayo I. , Lopes Pedro , Rzhetsky Andrey 
Published: November 2021

AbstractImportanceLower-resource areas in Africa and Asia face a unique set of healthcare challenges: the dual high burden of communicable and non-communicable diseases; a paucity of highly trained primary healthcare providers in both rural and densely populated urban areas; and a lack of reliable, inexpensive internet connections.ObjectiveTo address these challenges, we designed an artificial intelligence assistant to help primary healthcare providers in lower-resource areas document demographic and medical sign/symptom data and to record and share diagnostic data in real-time with a centralized database.DesignWe trained our system using multiple data sets, including US-based electronic medical records (EMRs) and open-source medical literature and developed an adaptive, general medical assistant system based on machine learning algorithms.Main outcomes and MeasureThe application collects basic information from patients and provides primary care providers with diagnoses and prescriptions suggestions. The application is unique from existing systems in that it covers a wide range of common diseases, signs, and medication typical in lower-resource countries; the application works with or without an active internet connection.ResultsWe have built and implemented an adaptive learning system that assists trained primary care professionals by means of an Android smartphone application, which interacts with a central database and collects real-time data. The application has been tested by dozens of primary care providers.Conclusions and RelevanceOur application would provide primary healthcare providers in lower-resource areas with a tool that enables faster and more accurate documentation of medical encounters. This application could be leveraged to automatically populate local or national EMR systems.Key pointsQuestionLower-resource areas like many countries in Africa are suffering from severe disease burdens, how can we utilize the modern health system in developed countries to help ease it?FindingsUtilizing AI technology with large data sets from US, we developed a smart diagnosis assistance help primary healthcare providers in lower-resource areas document demographic and medical sign/symptom data and to record and share diagnostic data in real-time with a centralized database. The assistance system has been tested in Pakistan and proven to be effective.MeaningOur application would provide primary healthcare providers in lower-resource areas with a tool that enables faster and more accurate documentation of medical encounters.
Cohort study of Covid-19 vaccine effectiveness among healthcare workers in Finland, December 2020 - October 2021
Authors: Poukka Eero , Baum Ulrike , Palmu Arto A. , Lehtonen Toni O. , Salo Heini , Nohynek Hanna , Leino Tuija 
Published: November 2021

AbstractRecently, Covid-19 vaccine effectiveness has decreased especially against mild disease due to emergence of the Delta variant and waning protection. In this register-based study among healthcare workers in Finland, the vaccine effectiveness of two-dose mRNA vaccine series against SARS-CoV-2 infection decreased from 82% (95% CI 79-85%) 14-90 days after vaccination to 53% (43-62%) after 6 months. Similar trend was observed for other series. Waning was not observed against Covid-19 hospitalization. These results facilitate decision-making of booster doses for healthcare workers.
A genome-wide association analysis of loss of ambulation in dystrophinopathy patients suggests multiple candidate modifiers of disease severity
Authors: Flanigan Kevin M. , Waldrop Megan A. , Martin Paul T. , Alles Roxane , Dunn Diane M. , Alfano Lindsay N. , Simmons Tabatha R. , Moore-Clingenpeel Melissa , Burian John , Seok Sang-Cheol , Weiss Robert B. , Vieland Veronica J. 
Published: November 2021

AbstractThe major determinant of disease severity in patients with severe Duchenne muscular dystrophy (DMD) or milder Becker muscular dystrophy (BMD) is whether their dystrophin gene (DMD) mutation disrupts the mRNA reading frame or allows expression of a partially functional protein. However, even in the complete absence of dystrophin, variability in disease severity is observed, and candidate gene studies have implicated several genes as possible modifiers. Our previous genome-wide association study (GWAS) for age at loss of ambulation (LOA) in DMD provided confirmation for the role of genetic modifiers of TGF-β signaling in disease progression. Here we present the largest genome-wide search to date for loci influencing disease severity in DMD patients. Availability of subjects for such studies is still quite limited, leading to modest sample sizes, which present a challenge for GWAS design. We have therefore taken special steps to minimize heterogeneity within our dataset at the DMD locus itself, taking a novel and conservative approach to mutation classification to effectively exclude the possibility of residual dystrophin expression. We have also utilized statistical methods that are well adapted to smaller sample sizes, including the use of a novel linear regression-like residual for time to ambulatory loss and the application of evidential statistics for the GWAS approach. Based on the resulting sample size of N = 419 patients, we have identified multiple potential candidate genetic modifier loci. In a companion paper to this one, we use a systematic bioinformatic pipeline to implicate specific genes within these loci as potential DMD modifiers.
Antibodies in Serum and MENSA Predict Non-recurrence in Primary Clostridioides difficile infection
Authors: Haddad Natalie S. , Nozick Sophia , Kim Geena , Ohanian Shant , Kraft Colleen S. , Rebolledo Paulina A. , Wang Yun , Wu Hao , Bressler Adam , Thi Le Sang Nguyet , Kuruvilla Merin , Cannon L. Edward , Lee F. Eun-Hyung , Daiss John L. 
Published: November 2021

ABSTRACTBackgroundWithin eight weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no validated biomarkers predictive of recurrence during primary infection. This study demonstrates the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence.MethodsForty-six hospitalized CDI patients were enrolled at Emory University Hospitals. Serum and MENSA samples prepared during weeks 1, 2, and 4 following symptom-onset were measured for antibodies specific for ten C. difficile antigens.ResultsAmong the 46 C. difficile-infected patients, nine (19.5%) experienced recurrence within eight weeks of primary infection. Among the 37 non-recurrent patients, 23 had anti-C. difficile MENSA antibodies specific for any of the three toxin antigens: TcdB-CROP, TcdBvir-CROP, and/or CDTb. Positive MENSA responses occurred within the first week post-symptom onset, including six patients who never seroconverted. A similar trend was observed in serum responses, but they peaked later and identified fewer patients (19/37). In contrast, none of the patients who subsequently recurred after hospitalization produced antibodies specific for the three C. difficile toxin antigens. IgA antibodies for the toxin antigens demonstrated the greatest predictive power for protection from recurrence.DiscussionThe development of IgG and/or IgA antibodies for three C. difficile toxins in serum and/or MENSA has prognostic potential. These immunoassays measure nascent immune responses that reduce the likelihood of recurrence. Early identification of patients at-risk for recurrence can reduce costs and morbidity.
Identification of residue inversions in large phylogenies of duplicated proteins
Authors: Pascarelli Stefano , Laurino Paola 
Published: November 2021

AbstractConnecting protein sequence to function is becoming increasingly relevant since high-throughput sequencing studies accumulate large amounts of genomic data. In order to go beyond the existing database annotation, it is fundamental to understand the mechanisms underlying functional inheritance and divergence. If the homology relationship between proteins is known, can we determine whether the function diverged?In this work, we analyze different possibilities of protein sequence evolution after gene duplication and identify “residue inversions”, i.e., sites where the relationship between the ancestry and the functional signal is decoupled. Residues in these sites are masked from being recognized by other prediction tools. Still, they play a role in functional divergence and could indicate a shift in protein function. We develop a method to specifically recognize residue inversions in a phylogeny and test it on real and simulated datasets. In a dataset built from the Epidermal Growth Factor Receptor (EGFR) sequences found in 88 fish species, we identify 19 positions that went through inversion after gene duplication, mostly located at the ligand-binding extracellular domain.Our work uncovers a rare event of protein divergence that has direct implications in protein functional annotation and sequence evolution as a whole. The developed method is optimized to work with large protein datasets and can be readily included in a targeted protein analysis pipeline.
decoupleR: Ensemble of computational methods to infer biological activities from omics data
Authors: Badia-i-Mompel Pau , Vélez Jesús , Braunger Jana , Geiss Celina , Dimitrov Daniel , Müller-Dott Sophia , Taus Petr , Dugourd Aurelien , Holland Christian H. , Ramirez Flores Ricardo O. , Saez-Rodriguez Julio 
Published: November 2021

AbstractSummaryMany methods allow us to extract biological activities from omics data using information from prior knowledge resources, reducing the dimensionality for increased statistical power and better interpretability. Here, we present decoupleR, a Bioconductor package containing computational methods to extract these activities within a unified framework. decoupleR allows us to flexibly run any method with a given resource, including methods that leverage mode of regulation and weights of interactions. Using decoupleR, we evaluated the performance of methods on transcriptomic and phospho-proteomic perturbation experiments. Our findings suggest that simple linear models and the consensus score across methods perform better than other methods at predicting perturbed regulators.Availability and ImplementationdecoupleR is open source available in Bioconductor (https://www.bioconductor.org/packages/release/bioc/html/decoupleR.html). The code to reproduce the results is in Github (https://github.com/saezlab/decoupleR_manuscript) and the data in Zenodo (https://zenodo.org/record/5645208).ContactJulio Saez-Rodriguez atpub.saez@uni-heidelberg.de.
Genome-wide analysis of DNA methylation reveals selection signatures of grass carp during the domestication
Authors: Li Yichao , Fu Bing , Zhang Junming , Xie Jun , Wang Guangjun , Jiang Peng , Tian Jingjing , Li Hongyan , Xia Yun , Yu Ermeng 
Published: November 2021

ABSTRACTWith the rapid development of aquaculture, more and more fish species from wild environments are artificially domesticated and cultured. In the process of domestication, the fish develop some adaptations and phenotypic traits, namely selection signatures. However, it is still unclear about the biological process underlying these selection signatures. Here, we used grass carp (Ctenopharyngodon idellus), an aquaculture fish with the largest production worldwide, to detect its selection signatures and investigate the roles of DNA methylation in the emergence of selection signatures during domestication based on whole-genome bisulfite sequencing technology. Our results showed that domesticated grass carp demonstrated four selection signatures, including growth and metabolism, immunity, foraging and learning behaviors, and 38 candidate genes were associated with these traits. 16 of candidate genes, such as IGF-1, GK, GYS1, etc., were found to play major roles in the growth and metabolism. Immunity signature was related to 11 of candidate genes, including MHCI, MHCII, C1QA, etc. The GRM1, TAS1R1 and TAS1R3 genes were essential for the adaptation of domesticated grass carp to commercial feed in artificial rearing condition. The C-FOS, POMC and CBP genes might be responsible for the acquisition of novel feeding habits and contribute to faster growth indirectly by enhancing food intake. These findings would provide new insights to expand our understanding on the role of DNA methylation in shaping physiological phenotypes in fish, and also contribute to efficient breeding of aquaculture stocks and restocking programs.
Direct addition of poly-lysine or poly-ethylenimine to the medium, a simple alternative to plate pre-coating
Authors: Faussner Alexander , Deininger Matthias , Weber Christian , Steffens Sabine 
Published: November 2021

AbstractFor most cell culture experiments, it is indispensable that the cells are firmly anchored to the culture plates, tolerating several rinsing steps, and withstanding shear forces or temperature changes without detaching. For semi-adherent cells such as the very common HEK 293 cells, this could so far be obtained only by time-consuming plate pre-coating with cationic polymer solutions. We report here, that i) pre-coating with the cheaper poly-ethylenimine (PEI) works as well as the commonly used poly-D-lysine (PDL), but more importantly and novel ii) that simple direct addition of either PEI (1.5 μg/ml) or PDL (2 μg/ml) to the cell culture medium results in strongly anchored HEK 293 cells, indistinguishable from ones seeded on pre-coated plates. Therefore, the replacement of plate pre-coating by direct addition of either PEI or PDL gives comparable excellent results, but is highly labour-, time-, and cost-efficient. Interestingly, additional experiments in this context showed that strong cell attachment requires only cationic polymers but not fetal calf serum added to the medium. Fetal calf serum is, however, of course required for further maintenance and growth of the cells.
A comparative analysis of current phasing and imputation software
Authors: Marino Adriano De , Mahmoud Abdallah Amr , Bose Madhuchanda , Bircan Karatuğ Ozan , Terpolovsky Andrew , Bamunusinghe Varuna , Khan Umar , Novković Biljana , Yazdi Puya G. 
Published: November 2021

AbstractWhole-genome data has become significantly more accessible over the last two decades. This can largely be attributed to both reduced sequencing costs and imputation models which make it possible to obtain nearly whole-genome data from less expensive genotyping methods, such as microarray chips. Although there are many different approaches to imputation, the Hidden Markov Model remains the most widely used. In this study, we compared the latest versions of the most popular Hidden Markov Model based tools for phasing and imputation: Beagle 5.2, Eagle 2.4.1, Shapeit 4, Impute 5 and Minimac 4. We benchmarked them on three input datasets with three levels of chip density. We assessed each imputation software on the basis of accuracy, speed and memory usage, and showed how the choice of imputation accuracy metric can result in different interpretations. The highest average concordance rate was achieved by Beagle 5.2, followed by Impute 5 and Minimac 4, using a reference-based approach during phasing and the highest density chip. IQS and R2 metrics revealed that IMPUTE5 obtained better results for low frequency markers, while Beagle 5.2 remained more accurate for common markers (MAF>5%). Computational load as measured by run time was lower for Beagle 5.2 than Impute 5 and Minimac 4, while Minimac utilized the least memory of the imputation tools we compared. ShapeIT 4, used the least memory of the phasing tools examined, even with the highest density chip. Finally, we determined the combination of phasing software, imputation software, and reference panel, best suited for different situations and analysis needs and created an automated pipeline that provides a way for users to create customized chips designed to optimize their imputation results.