bluuebunny/crossref_metadata_2025 huggingface dataset:
Degrees of Acceptance
Authors: Dinges Alexander
Published: November 2021

While many authors distinguish belief from acceptance, it seems almost universally agreed that no similar distinction can be drawn between degrees of belief, or credences, and degrees of acceptance. I challenge this assumption in this paper. Acceptance comes in degrees and acknowledging this helps to resolve problems in at least two philosophical domains. Degrees of acceptance play vital roles when we simplify our reasoning, and they ground the common ground of a conversation if we assume context probabilism, i.e., that the common ground must be represented with probability spaces rather than possible worlds.
Assessing predictors of rheumatoid arthritis-associated interstitial lung disease using quantitative lung densitometry
Authors: Alevizos Michail K , Danoff Sonye K , Pappas Dimitrios A , Lederer David J , Johnson Cheilonda , Hoffman Eric A , Bernstein Elana J , Bathon Joan M , Giles Jon T
Published: November 2021

Objective

To assess predictors of subclinical RA-associated interstitial lung disease (RA-ILD) using quantitative lung densitometry (qLD).

Methods

RA patients underwent multi-detector row CT scanning at baseline and after an average of 39 months. Scans were analysed with qLD for the percentage of lung parenchyma with high attenuation areas (%HAA: the percentage of voxels of –600 to –250 Hounsfield units). Additionally, a pulmonary radiologist calculated an expert radiologist scoring (ERS) for RA-ILD features. Generalized linear models were used to identify indicators of baseline %HAA and predictors of %HAA change.

Results

Baseline %HAA was assessed in 193 RA patients and 106 had repeat qLD assessment. %HAA was correlated with ERS (Spearman’s rho = 0.261; P < 0.001). Significant indicators of high baseline %HAA (>10% of lung parenchyma with high attenuation) included female sex, higher pack-years of smoking, higher BMI and anti-CCP ≥200 units, collectively contributing an area under the receiver operator curve of 0.88 (95% CI 0.81, 0.95). Predictors of %HAA increase, occurring in 49% with repeat qLD, included higher baseline %HAA, presence of mucin 5B (MUC5B) minor allele and absence of HLA-DRB1 shared epitope (area under the receiver operator curve = 0.69; 95% CI 0.58, 0.79). The association of the MUC5B minor allele with %HAA change was higher among men and those with higher cumulative smoking. Within the group with increased %HAA, anti-CCP level was significantly associated with a greater increase in %HAA.

Conclusions

%HAA, assessed with qLD, was linked to several known risk factors for RA-ILD and may represent a more quantitative method to identify RA-ILD and track progression than expert radiologist interpretation.
Continuous positive airway pressure and adverse cardiovascular events in obstructive sleep apnea: are participants of randomized trials representative of sleep clinic patients?
Authors: Reynor Ayesha , McArdle Nigel , Shenoy Bindiya , Dhaliwal Satvinder S , Rea Siobhan C , Walsh Jennifer , Eastwood Peter R , Maddison Kathleen , Hillman David R , Ling Ivan , Keenan Brendan T , Maislin Greg , Magalang Ulysses , Pack Allan I , Mazzotti Diego R , Lee Chi-Hang , Singh Bhajan
Published: November 2021

Study Objectives

Randomized controlled trials (RCTs) have shown no reduction in adverse cardiovascular (CV) events in patients randomized to continuous positive airway pressure (CPAP) therapy for obstructive sleep apnea (OSA). This study examined whether randomized study populations were representative of OSA patients attending a sleep clinic.

Methods

Sleep clinic patients were 3,965 consecutive adults diagnosed with OSA by in-laboratory polysomnography from 2006 to 2010 at a tertiary hospital sleep clinic. Characteristics of these patients were compared with participants of five recent RCTs examining the effect of CPAP on adverse CV events in OSA. The percentage of patients with severe (apnea-hypopnea index, [AHI] ≥ 30 events/h) or any OSA (AHI ≥ 5 events/h) who met the eligibility criteria of each RCT was determined, and those criteria that excluded the most patients identified.

Results

Compared to RCT participants, sleep clinic OSA patients were younger, sleepier, more likely to be female and less likely to have established CV disease. The percentage of patients with severe or any OSA who met the RCT eligibility criteria ranged from 1.2% to 20.9% and 0.8% to 21.9%, respectively. The eligibility criteria that excluded most patients were preexisting CV disease, symptoms of excessive sleepiness, nocturnal hypoxemia and co-morbidities.

Conclusions

A minority of sleep clinic patients diagnosed with OSA meet the eligibility criteria of RCTs of CPAP on adverse CV events in OSA. OSA populations in these RCTs differ considerably from typical sleep clinic OSA patients. This suggests that the findings of such OSA treatment-related RCTs are not generalizable to sleep clinic OSA patients.

Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial, https://clinicaltrials.gov/ct2/show/NCT00519597, ClinicalTrials.gov number, NCT00519597.

Usefulness of Nasal Continuous Positive Airway Pressure (CPAP) Treatment in Patients with a First Ever Stroke and Sleep Apnea Syndrome, https://clinicaltrials.gov/ct2/show/NCT00202501, ClinicalTrials.gov number, NCT00202501.

Effect of Continuous Positive Airway Pressure (CPAP) on Hypertension and Cardiovascular Morbidity-Mortality in Patients with Sleep Apnea and no Daytime Sleepiness, https://clinicaltrials.gov/ct2/show/NCT00127348, ClinicalTrials.gov number, NCT00127348.

Continuous Positive Airway Pressure (CPAP) in Patients with Acute Coronary Syndrome and Obstructive Sleep Apnea (OSA) (ISAACC), https://clinicaltrials.gov/ct2/show/NCT01335087, ClinicalTrials.gov number, NCT01335087.
Investigating a potential format effect with two-column proofs
Authors: Alarfaj Maryam , Sangwin Chris
Published: November 2021

The current study aims to explore the impact of the two-column format in writing simple mathematical arguments. That is to say, a structured method of presenting a mathematical proof or argument by using a tabular layout with two columns. The underlying goal of the research reported in this paper is to inform understanding of how to effectively assess students’ proof construction, particularly online. In this paper, we report the results of an experiment designed to test the hypothesis that students provide more justifications when using the two-column format in writing mathematical proofs. The participants were 80 first year undergraduate mathematics students at the University of Edinburgh who were enrolled in a calculus course. The findings supported this hypothesis: overall frequency of justification were higher in the two-column condition compared with the traditional condition. This is due to the format structure where students are expected to justify each line in the statements’ column with a corresponding explanation in the justification column. However, as a side effect of increasing the amount of justifications, students in the two-column group generated more non-explanation statements which we classed as paraphrasing. A secondary outcome was our use and further development of the coding scheme.
Impact of COVID-19 Infection on Neonatal Birth Outcomes
Authors: Vizheh Maryam , Allahdadian Maryam , Muhidin Salut , Valiani Mahboubeh , Bagheri Khadijeh , Borandegi Forogh , Ghasimi Golnaz
Published: November 2021

Introduction

There is limited data on newborns born to mothers with COVID-19 infection. This multicenter cohort study aimed to investigate the clinical characteristics and outcomes of neonates born to mothers with and without COVID-19 infection to fill a gap in the literature review.

Methods

The medical records of all neonates in Isfahan, Iran, between October 2020 and March 2021, were retrospectively reviewed.

Results

Among the 600 neonates in this study, 255 (42.5%) were in the infected group and 345 (57.5%) were assigned to the control group as they were born to non-infected mothers. In the infected group, sepsis, fever and pneumothorax were detected in 3 (1.2%), 3 (1.2%) and 4 (1.6%) neonates, respectively, compared with no case in the control group. In the infected group, neonatal respiratory distress (NRDS) (32, 12.5%) was significantly higher than the control group (27, 10.6%). Asphyxia in the infected group was 22(6.4%), compared with 19 (5.5%), in the control group. Preterm labor (PTL) (55, 21.65%), premature rupture of membranes (PROMs) (24, 9.4%) and intra-uterine growth retardation (IUGR) (15, 5.9%) were significantly higher in women with COVID-19 (45, 13.0%, 4, 1.2% and 7, 2.0%, respectively). Low birth weight (LBW) accounted for 42 (16.5%) neonates in the infected group and 25 (7.2%) in the control group (p < 0.05). Of the 255 neonates born to infected mothers, 38 (14.9%) were admitted to the Neonatal Intensive Care Unit (NICU), compared with 31 out of 345 (9.0%) in the control group (p < 0.05). RT-PCR test results were positive in two newborns (0.8%), one of whom died of necrotizing enterocolitis.

Conclusion

As a result of maternal COVID-19 infections, neonates experienced higher rates of sepsis, fever, pneumothorax, asphyxia and NRDS in addition to PTL, PROMs, IUGR, and LBW.
CoVizu: Rapid analysis and visualization of the global diversity of SARS-CoV-2 genomes
Authors: Ferreira Roux-Cil , Wong Emmanuel , Gugan Gopi , Wade Kaitlyn , Liu Molly , Baena Laura Muñoz , Chato Connor , Lu Bonnie , Olabode Abayomi S , Poon Art F Y
Published: November 2021

Phylogenetics has played a pivotal role in the genomic epidemiology of severe acute respiratory syndrome coronavirus 2, such as tracking the emergence and global spread of variants and scientific communication. However, the rapid accumulation of genomic data from around the world—with over two million genomes currently available in the Global Initiative on Sharing All Influenza Data database—is testing the limits of standard phylogenetic methods. Here, we describe a new approach to rapidly analyze and visualize large numbers of SARS-CoV-2 genomes. Using Python, genomes are filtered for problematic sites, incomplete coverage, and excessive divergence from a strict molecular clock. All differences from the reference genome, including indels, are extracted using minimap2 and compactly stored as a set of features for each genome. For each Pango lineage (https://cov-lineages.org), we collapse genomes with identical features into ‘variants’, generate 100 bootstrap samples of the feature set union to generate weights, and compute the symmetric differences between the weighted feature sets for every pair of variants. The resulting distance matrices are used to generate neighbor-joining trees in RapidNJ that are converted into a majority-rule consensus tree for each lineage. Branches with support values below 50 per cent or mean lengths below 0.5 differences are collapsed, and tip labels on affected branches are mapped to internal nodes as directly sampled ancestral variants. Currently, we process about 2 million genomes in approximately 9 h on 52 cores. The resulting trees are visualized using the JavaScript framework D3.js as ‘beadplots’, in which variants are represented by horizontal line segments, annotated with beads representing samples by collection date. Variants are linked by vertical edges to represent branches in the consensus tree. These visualizations are published at https://filogeneti.ca/CoVizu. All source code was released under an MIT license at https://github.com/PoonLab/covizu.
The story of a rock-star: multilocus phylogeny and species delimitation in the starred or roughtail rock agama,Laudakia stellio(Reptilia: Agamidae)
Authors: Karameta Emmanouela , Lymberakis Petros , Grillitsch Heinz , Ilgaz Çetin , Avci Aziz , Kumlutaş Yusuf , Candan Kamil , Wagner Philipp , Sfenthourakis Spyros , Pafilis Panayiotis , Poulakakis Nikos
Published: November 2021

Situated at the junction of three continents, Europe, Asia and Africa, the Eastern Mediterranean is an ideal region to study the effects of palaeogeography, ecology and long human presence on animal evolution. Laudakia stellio (Squamata: Agamidae) is found across this region and offers an excellent opportunity for such studies. The high morphological variation across their range suggests that these lizards might represent a species complex. This is the first study exploring their evolutionary history, using molecular markers and individuals from all described subspecies. We employed the latest phylogenetic and species-delimitation methods to identify all distinct evolutionary lineages, their genetic variation and divergence times. The phenotypical diversity of L. stellio matches its genetic differentiation: almost all subspecies correspond to well-supported retrieved subclades and additional distinct lineages representing intermediate morphs have been retrieved. ‘Laudakia stellio’ represents three distinct evolutionary entities that diverged during the Plio-Pleistocene transition, which we propose as distinct species. One includes Greek and Turkish populations, as well as cryptic Anatolian lineages. The second comprises all other Near East populations and the third is endemic to Cyprus. Our results indicate a role of humans in shaping present distribution patterns, and highlight the importance of the Aegean, Anatolia and the Levant as glacial refugia and diversity hotspots.
An Analysis of the Evidence Underpinning the American Academy Orthopaedic Surgery Pediatrics Clinical Practice Guidelines
Authors: Batioja Kelsi L.E. , Nguyen Tiffany , Anderson J. Michael , Detweiler Byron , Checketts Jake , Torgerson Trevor , Hartwell Micah , Vassar Matt
Published: November 2021

Background:

Randomized control trials (RCTs) serve as evidentiary support for recommendations underpinning clinical practice guidelines (CPGs) with the goal of optimizing patient care. A knowledge gap exists within scientific literature when evaluating the quality of RCTs used as evidence in the American Academy of Orthopaedic Surgery (AAOS) pediatric CPGs. We aim to evaluate the reporting quality and risk of bias in RCTs underlying AAOS Pediatric CPG recommendations.

Methods:

We located all AAOS Pediatric CPGs. We then extracted all RCTs from the CPG reference sections. All included RCTs were evaluated using the Consolidated Standards of Reporting Trials (CONSORT) checklist and Cochrane Collaboration risk of bias assessment tool (RoB 2.0). Descriptive statistics were recorded, and bivariate analysis was used to account for variance in CONSORT scores. A Mann-Whitney U test was completed to compare CONSORT studies published before and after 2010.

Results:

Three CPGs and 23 RCTs met inclusion criteria. Mean CONSORT adherence was 69.8% (21.6/31). The lowest adhered to CONSORT items were 10, 23, and 24, while items 2a, 13a, and 18 displayed the highest adherence. Ten RCTs (43.5%, 10/23) had “low” risk of bias, 5 RCTs (21.7%, 5/23) were of “some concerns,” and 8 RCTs (34.8%, 8/23) received a “high” designation for risk of bias. There were no statistically significant associations in the bivariate regression analysis or Mann-Whitney U test.

Conclusions:

Our results suggest that CONSORT adherence within RCTs used as evidence in AAOS Pediatric CPGs is substandard—relying on evidence that, in some cases, is >20 years old. Many of the RCTs cited as supporting evidence have a “high” risk of bias. Altogether, these CPGs may need to be updated or expanded to include more recent evidence relevant to pediatric orthopaedic surgery.
Identification of Aggravation-Predicting Gene Polymorphisms in Coronavirus Disease 2019 Patients Using a Candidate Gene Approach Associated With Multiple Phase Pathogenesis: A Study in a Japanese City of 1 Million People
Authors: Tanimine Naoki , Takei Daisuke , Tsukiyama Naohumi , Yoshinaka Hisaaki , Takemoto Yuki , Tanaka Yuka , Kobayashi Tsuyoshi , Tanabe Kazuaki , Ishikawa Nobuhisa , Kitahara Yoshihiro , Okimoto Mafumi , Shime Nobuaki , Ohge Hiroki , Sugiyama Aya , Akita Tomoyuki , Tanaka Junko , Ohdan Hideki
Published: November 2021

IMPORTANCE:

The pathology caused by the coronavirus disease 2019 is mediated by host-mediated lung inflammation, driving severity, and mortality. Polymorphisms in genes encoding host inflammation and immune-related molecules may be associated with the development of serious pathologies, and identifying such gene polymorphisms may lead to the identification of therapeutic targets.

OBJECTIVES:

We attempted to identify aggravation-predicting gene polymorphisms.

DESIGN:

We use a candidate gene approach associated with multiple phase pathogenesis in coronavirus disease 2019 patients among a cohort in Hiroshima, a city with a population of 1 million, in Japan. DNA samples from the study populations were genotyped for 34 functional polymorphisms from 14 distinct candidate genes, which encode proteins related to viral cell entry, regulation of viral replication, innate immune modulators, regulatory cytokines, and effector cytokines.

SETTING AND PARTICIPANTS:

Three core hospitals providing different services for patients with coronavirus disease 2019 under administrative control. A total of 230 patients with coronavirus disease 2019 were recruited from March 1, 2020, to March 31, 2021.

MAIN RESULTS AND MEASUREMENTS:

Among the 14 genes, we found rs1131454 in OAS1 and rs1143627 in IL1B genes as independent genetic factors associated with disease severity (adjusted odds ratio = 7.1 and 4.6 in the dominant model, respectively). Furthermore, we investigated the effect of multiple phase pathogenesis of coronavirus disease 2019 with unbiased multifactor dimensionality reduction analysis and identified a four-gene model with rs1131454 (OAS1), rs1143627 (IL1B), rs2074192 (ACE2), and rs11003125 (MBL). By combining these polygenetic factors with polyclinical factors, including age, sex, higher body mass index, and the presence of diabetes and hypertension, we proposed a composite risk model with a high area under the curve, sensitivity, and probability (0.917, 96.4%, and 74.3%, respectively) in the receiver operating characteristic curve analysis.

CONCLUSIONS AND RELEVANCE:

We successfully identified significant genetic factors in OAS1 and IL1B genes using a candidate gene approach study as valuable information for further mechanistic investigation and predictive model building.
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.
Reducing Nurse Practitioner Turnover in Home Based Primary Care
Authors: Hughes Ashley , Keys Yolanda , Peck Jessica , Garcia Theresa
Published: November 2021

Access to healthcare is challenging for both Veterans and the nation's general population. To keep up with national primary healthcare needs, the Department of Veteran Affairs (VA) implemented Home Based Primary Care (HBPC). After a structure remodel at a Texas VA medical center, 40% of nurse practitioners (NPs) left the HBPC department in one year. The Anticipated Turnover Scale and the Misener NP Job Satisfaction Scale were administered online (n = 7), and results were used to complete a program evaluation. Forty-three percent of participants indicated intent to leave, and 56% of answers indicated job dissatisfaction. Seven categories were identified to mitigate voluntary turnover: Recognition; Shared governance; Orientation; Full practice authority; Collaboration; Organizational workflow maps; and Mentoring. Implementation of recommendations resulting from this project may help retain NPs in both VA and non-VA organizations, reduce organizational costs, support optimal patient outcomes, and increase access to healthcare.
Experiences of Families with Adult Home Invasive Mechanical Ventilation Patients
Authors: Nayeri Dehghan , Bahramnezhad Fatemeh , Asgari Parvaneh
Published: November 2021

Adult home mechanical ventilation (HMV) represents a small but growing vulnerable population in the community. Caring for these patients exposes families to many positive and negative experiences. This study aimed to synthesize the existing qualitative research that examined family members' experiences of caring for adult patients using HMV. Medline, PubMed, CINAHL, Scopus, and Web of Science were searched for qualitative studies conducted with family caregivers of adult patients receiving HMV. Thematic synthesis was conducted to interpret the findings. The GRADE-CERQual approach was used to assess the level of confidence. After completion of the screening process, 11 studies were included. The main theme from the meta-synthesis was the Experience of changing as a person. Families' experiences were divided into three stages over time: (1) Mixed feelings, (2) Challenging, and (3) Continuity. Family experiences illustrate that teamwork with an interprofessional approach based on patient and family needs is required to deliver care, improve clinical outcomes, reduce adverse experiences, and increase family satisfaction.
Developing a Standardized Method for Clinical Staff Training, Education, and Competency
Authors: Siju Jemilat , Orekoya Grace , Vernet Eumenide , Anagboso Uzoma
Published: November 2021

Clinical skill competency maintenance is a regulatory and quality requirement, making it top priority for healthcare organizations. Staff having the proper clinical competencies to provide high-quality care begins with nursing orientation and continues with the maintenance of annual skill competency. Building a robust training and clinical competency program requires collaboration between nursing education and nursing leadership. This project describes a model for nursing orientation and continued training in an ambulatory care setting.
Histologic Diagnosis of Inflammatory Bowel Diseases
Authors: Kővári Bence , Báthori Ágnes , Friedman Mark S. , Lauwers Gregory Y.
Published: November 2021

Inflammatory bowel disease, including ulcerative colitis and Crohn disease, is an idiopathic chronic inflammatory condition of the gastrointestinal tract. Since neither the clinical manifestations nor the morphologic features of inflammatory bowel disease are pathognomonic alone, the differential diagnosis to consider is relatively broad, and it relies on the synthesis of clinical, endoscopic, and microscopic features. Long-held histologic diagnostic principles include recognizing structural and inflammatory features of chronicity, that is, architectural distortion, basal plasmacytosis, and expansion of the lamina propria lymphoplasmacytic infiltrate. In addition, evaluation of the neutrophilic inflammation and related crypt and epithelial destruction is essential to gauge the activity of the disease. Nevertheless, these features can be difficult to confirm in special settings, including at the inception of the disease or in partially treated cases. This review will explore the classic morphologic features of ulcerative colitis and Crohn disease, followed by a detailed discussion of atypical and diagnostically challenging presentations and a brief review of the clinical aspects necessary for the daily practice of pathologists.
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

Background

Birt-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.

Methods

Targeted 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.

Results

Six 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.

Conclusion

Pathogenic 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

Importance

Lower-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.

Objective

To 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.

Design

We 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 Measure

The 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.

Results

We 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 Relevance

Our 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 points

Question

Lower-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?

Findings

Utilizing 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.

Meaning

Our 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

Recently, 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

The 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

Background

Within 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.

Methods

Forty-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.

Results

Among 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.

Discussion

The 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

Connecting 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

Many 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 Implementation

decoupleR 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).

Contact

Julio 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

With 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

For 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

Whole-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.