bluuebunny/crossref_metadata_2025 huggingface dataset:
Donation after cardiac death in heart transplantation: is there an ethical dilemma?
Authors: Cardounel Arturo , Julliard Walker
Published: December 2021

Purpose of review

In an attempt to address the organ shortages in heart transplantation, USA centres have begun utilizing donation after cardiac death (DCD) as an alternative to traditional donation after brain death (DBD). As this paradigm continues to expand, there is a need to address the medico-legal and ethical aspects of DCD donation, which is the focus of the current review.

Recent findings

Current protocols use criteria established by the Uniform Determination of Death Act (UDDA), which is explicit in defining the irreversibility of circulation and brain function in determining death. By the nature of DCD, the patient may not meet death criteria from a biological systems perspective of irreversibility, and thus, the moral dilemma ensues on whether removing vital organs violates our legal and moral obligations to the patient.

In the current article, we review the ethical issues raised with DCD and define DCD protocols and their ability to comply with established regulatory guidelines while respecting the wishes of patients and their surrogates through informed decisions making about organ donation and end-of-life care.
Exploring the Accuracy of Cited References in a Selected Data Set of Nursing Journal Articles
Authors: Nicoll Leslie H. , Oermann Marilyn H. , Carter-Templeton Heather , Wrigley Jordan , Owens Jacqueline K.
Published: December 2021

Accuracy of cited references in scholarly publications gives credit to original authors and offers information for readers to access sources for additional review. Errors in this foundational information can, at a minimum, create confusion and additional burden for consumers; at worst, these errors can make it impossible to locate the original work. For systematic and other types of reviews, finding relevant studies is critical for comprehensiveness and accuracy. The purpose of this study was to evaluate the accuracy of cited references in a curated data set of 100 articles from 100 different nursing journals. From these articles, a sample of references for analysis (n = 666) was created. From this total, only 8 references (1.3%) could not be retrieved at all. Small numbers of references (≤3%) had errors in the author name, journal title, article title, or year, but these did not prevent retrieval. These small numbers suggest that use of current technology including electronic databases and reference management software has improved overall accuracy in reference lists. An unexpected finding was the discovery of enhanced reference lists for online articles at publisher sites. These provide at least 1 and as many as 5 direct links to cited articles, thus increasing accuracy and ease of retrieval. Implications for authors, editors, and publishers are discussed.
Understanding the Associations Among Perceived Stress, Self-Control Skills, and Overeating in Asian Adolescents
Authors: Chuang Hsiao-Ling , Wang Ya-Fen
Published: December 2021

Objective:

Built on Rosenbaum's self-control theory, this study aimed to examine the mediating role of self-control skills in the relationship between perceived stress and overeating patterns among adolescents from an Asia-Pacific region.

Methods:

A cross-sectional study was used with a school-based, nonclinical sample of 195 adolescents. Participants completed self-report measures assessing study variables and demographic information such as body mass index (BMI) status for adolescents and their parents. Mediation analyses were conducted with Hayes' PROCESS macro modeling tool to assess self-control skills as the mediator of the relationships between perceived stress and each overeating pattern based on the regression-based bootstrapping method, adjusting for potential covariates.

Results:

The prevalence of overweight and obesity was approximately 18% in the current sample of adolescents. While controlling for age, sex, and standardized BMI, self-control skills mediated the effects of stress on emotional and external eating, but not on restrained eating; in addition, self-control skills partially mediated the relationship between perceived stress and an overall overeating tendency.

Conclusion:

Consistent with Rosenbaum's self-control theory, self-control skills were found to mediate the relationship between perceived stress and emotional and external eating. This study highlights the importance of prevention treatments developed to impart adolescents with self-control skills, decrease their perceived stress, and consequently, reduce their overeating patterns during this intense developmental period.
The efficacy of augmentative anti-rotational plating plus decortication and autogenic bone grafting for aseptic nonunion after intramedullary nailing of femoral shaft fracture
Authors: Li Yonggang , Xing Hanbing , Qi Xinchun , Liu Mingxing , Wang Zhiyong , Sang Xiguang
Published: December 2021

Background:

Femoral interlocking intramedullary (IM) nailing fixation is an effective method for the treatment of femoral shaft fractures. Aseptic nonunion of femoral shaft fracture after IM nailing is uncommon. Currently, the treatment for aseptic femoral shaft nonunion is controversial. The aim of this study was to investigate the clinical effect of augmentative antirotational plating plus decortication and autogenic bone grafting for aseptic femoral shaft nonunion after IM nailing failure.

Methods:

A retrospective study was conducted on 25 cases of aseptic femoral shaft fracture nonunion treated with IM nailing from January 2015 to August 2019. All patients were treated by leaving the nail in situ, debridement of nonunion sites, decortication, autogenous iliac bone grafting, and augmentative antirotational plating fixation. The time to fracture union and complications were recorded.

Results:

All patients were followed up for 12–18 months. The union rate after revision surgery was 100%. The average union time was 5.5 months (range, 4-10). Subjective pain symptoms had disappeared in all patients. There were no incision infections or internal fixator fatigue fractures. Average scores of the physical function and bodily pain components of the SF-36 were 95.5 (range, 91-98) and 94.1 (range, 90-97), respectively. No other obvious complications occurred postoperatively.

Conclusion:

Augmentative antirotational plating plus decortication and autogenic bone grafting is an excellent choice for treating femoral shaft fracture nonunion after IM nailing; this approach has an overall high union rate and few complications.
A Transformative Learning Experience for Senior Nursing Students
Authors: Revell Susan M. Hunter , Sethares Kristen A. , Chin Elizabeth Danells , Kellogg Marni B. , Armstrong Deborah , Reynolds Teresa
Published: December 2021

Background:

Research suggests that clinical practicums in hospital-based settings are important, even if condensed, to provide students with the opportunity for real-world learning experiences. Rational dialogue makes learning meaningful and empowers students to learn by reflecting on experiences.

Problem:

The COVID-19 pandemic minimized availability of traditional one-to-one mentorship practicums.

Approach:

This article describes the use of critical reflection on experiences in an undergraduate senior mentorship course to assess student learning through the thematic analysis of writing assignments. Guided by Mezirow's transformative learning theory, students completed a traditional group clinical practice, written reflective journals and virtual seminars focused on role development, and reflection on concurrent learning in clinical and simulation experiences.

Outcomes:

Transformative learning was evident in their writing. Student journals demonstrated themes of responding to change, discovering resilience, developing confidence, finding gratitude, embracing advocacy, and transforming and becoming.

Conclusions:

Through critical reflection, students recognized the opportunities mentorship afforded them, despite challenges.
Cognitively Based Compassion Training for HIV Immune Nonresponders—An Attention-Placebo Randomized Controlled Trial
Authors: Titanji Boghuma K. , Tejani Mehul , Farber Eugene W. , Mehta C. Christina , Pace Thaddeus W. , Meagley Kathryn , Gavegnano Christina , Harrison Timothy , Kokubun Caroline W. , Negi Satya Dev , Schinazi Raymond F. , Marconi Vincent C.
Published: December 2021

Objective:

Chronic inflammation is associated with increased morbidity and mortality for people with HIV (PWH). Psychological stress is an important contributor to this chronic inflammation. We hypothesized that a cognitively based compassion training (CBCT) approach could reduce inflammation and psychological stress in immune nonresponder PWH.

Design:

An attention-placebo randomized controlled trial design to evaluate the acceptability of CBCT among PWH and its effects on key aspects of stress and immune function compared with an active-attention control group (NCT02395289).

Methods:

This study was conducted at an HIV clinic in Atlanta, Georgia. Eligible individuals determined by (1) adherence to antiretroviral therapy for at least a year, (2) virologic suppression; and (3) stable CD4+ T-cell counts <350 cells/μL were randomized in a 2:1 ratio to either CBCT or control in 2 study periods: April–May, 2016, and September–December, 2016. Psychological measures and inflammatory biomarkers associated with HIV disease progression (IL-1β, TNF-α, sCD14, IL-6, and IL-10) were obtained for all study participants at baseline and at the time of study completion.

Results:

We found a significant association between CBCT practice time engagement and fold reduction in IL-6 and TNF-α levels. There was no association between CBCT practice time and other biomarkers markers assessed (IL-1β, sCD14, and IL-10). These changes were coincident with significant increases in self-reported psychological well-being and HIV disease acceptance and in benefits for CBCT participants. We also observed fewer instances of virologic failure for those in the CBCT arm compared with controls.

Conclusions:

CBCT is a novel and feasible nonmedication-based intervention that could reduce inflammation and psychological stress in PWH.
What will it take to meet UNAIDS targets for preexposure prophylaxis users?
Authors: Sullivan Patrick Sean , Siegler Aaron Julius
Published: December 2021

Purpose of review

Preexposure prophylaxis (PrEP) is a critical strategy to curb new HIV infections globally. National and global targets have been set for people starting PrEP. However, global PrEP initiations fell short of UNAIDS 2020 targets, and reflection is needed on how we set and meet targets for PrEP use.

Recent findings

Recent literature documents challenges to meeting ambitious goals for PrEP coverage in multiple phases of PrEP: PrEP initiations are limited by gaps in the identification of those who might benefit from PrEP. Conversely, getting PrEP to those who need it most is threatened by inaccurate risk perception and HIV and PrEP stigma. Once people are on PrEP, a substantial number discontinue PrEP in the first year (the ‘PrEP Cliff’), a finding that is robust across groups of PrEP users (e.g., women, men who have sex with men, transwomen) and across global prevention settings. Further, PrEP inequities – by which we refer to utilization of PrEP in a specific group that is not commensurate with their epidemic risk – threaten the overall population benefit of PrEP because those at highest risk of acquiring HIV are not adequately protected.

To realize global goals for PrEP utilization and impact, we must address multiple points of PrEP delivery programs that address not just PrEP starts, but also retention in PrEP and measurement and accountability to PrEP equity. We call for new approaches to better identify PrEP candidates, suggest additional research to address the known and consistent reasons for PrEP discontinuations, and advocate for metrics to measure and be accountable to PrEP equity.
Gracilibacillus suaedae sp. nov., an indole acetic acid-producing endophyte isolated from a root of Suaeda salsa
Authors: Huang Xiao-Xian , Xu Lian , Sun Ji-Quan
Published: December 2021

A Gram-stain-positive, facultatively anaerobic, spore-forming, motile with unipolar biflagella, rod-shaped, indole acetic acid-producing bacterium, named LD4P30T, was isolated from a root of Suaeda salsa collected in Inner Mongolia, northern China. Strain LD4P30T grew at pH 6.0–11.0 (optimum, pH 7.0), 10–40 °C (35 °C) and in the presence of 1–15% (w/v) NaCl (5%). The strain was positive for oxidase and negative for catalase. The major cellular fatty acids of strain LD4P30T were iso-C15:0, C15:1
ω5c and anteiso-C15:0; the major polar lipids were diphosphatidylglycerol and phosphatidylglycerol; and menaquinone-7 was the only respiratory quinone. The genomic DNA G+C content was 36.7 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain LD4P30T clustered with

Gracilibacillus thailandensis

TP2-8T,

Gracilibacillus saliphilus

YIM 91119T and

Gracilibacillus lacisalsi

BH312T, and showed 99.0, 98.9, 98.0 and <97.7% 16S rRNA gene similarity to

G. thailandensis

TP2-8T,

G. saliphilus

YIM 91119T,

G. lacisalsi

BH312T and all other current type strains, respectively. The digital DNA–DNA hybridization and average nucleotide identity based on blast values between strain LD4P30T and

G. saliphilus

YIM 91119T,

G. thailandensis

TP2-8T and

G. lacisalsi

BH312T were 44.9, 44.7 and 44.4%, and 91.1, 91.0 and 90.8%, respectively. Based on its phenotypic, physiological and phylogenetic characteristics, strain LD4P30T represents a novel species, for which the name Gracilibacillus suaedae is proposed. The type strain is LD4P30T (=CGMCC 1.17697T=KCTC 82375T).
Phosphitispora fastidiosa gen. nov. sp. nov., a new dissimilatory phosphite-oxidizing anaerobic bacterium isolated from anaerobic sewage sludge
Authors: Mao Zhuqing , Gräßle Fabian , Frey Jasmin , Franchini Paolo , Schleheck David , Müller Nicolai , Schink Bernhard
Published: December 2021

A new strictly anaerobic bacterium, strain DYL19T, was enriched and isolated with phosphite as the sole electron donor and CO2 as a single carbon source and electron acceptor from anaerobic sewage sludge sampled at a sewage treatment plant in Constance, Germany. It is a Gram-positive, spore-forming, slightly curved, rod-shaped bacterium which oxidizes phosphite to phosphate while reducing CO2 to biomass and small amounts of acetate. Optimal growth is observed at 30 °C, pH 7.2, with a doubling time of 3 days. Beyond phosphite, no further inorganic or organic electron donor can be used, and no other electron acceptor than CO2 is reduced. Sulphate inhibits growth with phosphite and CO2. The G+C content is 45.95 mol%, and dimethylmenaquinone-7 is the only quinone detectable in the cells. On the basis of 16S rRNA gene sequence analysis and other chemotaxonomic properties, strain DYL19T is described as the type strain of a new genus and species, Phosphitispora fastidiosa gen. nov., sp. nov.
Identification and application of plasmatic microRNA expression quantitative trait loci (miR-QTL) at first trimester of pregnancy
Authors: White Frédérique , Groleau Marika , Côté Samuel , Légaré Cécilia , Thibeault Kathrine , Clément Andrée-Anne , Hivert Marie-France , Bouchard Luigi , Jacques Pierre-Étienne
Published: December 2021

Background

MicroRNAs (miRNAs) are a class of small non-coding RNAs regulating gene expression. They are involved in many biological processes, including adaptation to pregnancy. The identification of genetic variants associated with gene expression, known as expression quantitative trait loci (eQTL), helps to understand the underlying molecular mechanisms and determinants of complex diseases. Using data from the prospective pre-birth Gen3G cohort, we investigated associations between maternal genotypes and plasmatic miRNA levels measured during the first trimester of pregnancy of 369 women.

Results

Assessing the associations between about 2 million SNPs and miRNA proximal pairs using best practices from the GTEx consortium, a total of 22,140 significant eQTLs involving 147 unique miRNAs were identified. Elastic-net regressions were applied to select the most relevant SNPs to build genetic risk scores (GRS) for each of these 147 miRNAs. For about half of the circulating miRNAs, the GRS captured >10% of the variance abundance. As a demonstration of the usefulness of the identified eQTLs and derived GRS, we used the GRSs as instrumental variables to test for association between the circulating levels of miRNAs quantified before the 16th week of pregnancy and the development of pregnancy complications (gestational diabetes [GDM] or pre-eclampsia [PE]) developing more than three months later on average. Using predicted miRNA levels derived from instrumental variables, we found 18 significant associations of miRNAs with potential support of causal inference for GDM or PE.

Conclusions

Our results represent a valuable resource to understand miRNA regulation and highlight the potential of genetic instruments in predicting circulating miRNA levels and their possible contribution in disease development.
Individual vaccine efficacy variation with time since mRNA BNT162b2 vaccination estimated by rapid, quantitative antibody measurements from a finger-prick sample
Authors: Vargas Matheus J. T. , Chandrasekhar Mithileshwari , Kwon Yong Je , Deijs Gerrit Sjoerd , Corazza Carsten Ma On Wong , Chai Angela (Wai Yin) , Binedell Rebecca L. , Jose Ellen , Govind Bhavesh , Huyet Laura , Patel Pooja K. , Reshef Gabrielle , Kumar Vijaya , Lowe Tiffany , Powell Robert J. , Jina Kieran C. , Walker Flynn C.W. , Talemaitoga Apisalome , Simpson M. Cather , Williams David E.
Published: December 2021

We show that an individual’s immune status to Covid-19 can be monitored through quantitative antibody measurements using a method based on centrifugal microfluidics, specifically designed for speed to result (20 min), high throughput (8 samples simultaneously) and accuracy from a finger-prick blood sample. Anti-Receptor Binding Domain (RBD) IgG concentration showed a log-normal distribution with mean decreasing with time following the second vaccination with mRNA BNT162b2 (Pfizer). Using a model for an individual’s antibody concentration-dependent vaccine efficacy allowed comparison with literature data on changing vaccine efficacy against symptomatic disease across a population. Even though the trial was small (n = 100) the computed population vaccine efficacy was in reasonable agreement with that obtained from a large population survey. The derived parameters for the vaccine efficacy model were in good agreement with those expected from previous studies and from a simple theoretical model. The results and modelling show that the major proportion of breakthrough infections are for people whose antibody concentration is in the tail of the distribution. The results provide strong support for personalized booster programmes that, by targeting people in the tail of the distribution, should be more effective at diminishing breakthrough infection and optimising booster dose supply than a program that simply mandates a booster at a specific post-vaccination time point.
RT-PCR/MALDI-TOF diagnostic target performance reflects circulating SARS-CoV-2 variant diversity in New York City
Authors: Hernandez Matthew M. , Banu Radhika , Gonzalez-Reiche Ana S. , Gray Brandon , Shrestha Paras , Cao Liyong , Chen Feng , Shi Huanzhi , Hanna Ayman , Ramírez Juan David , van de Guchte Adriana , Sebra Robert ,   Mount Sinai PSP Study Group, Gitman Melissa R. , Nowak Michael D. , Cordon-Cardo Carlos , Schutzbank Ted E. , Simon Viviana , van Bakel Harm , Sordillo Emilia Mia , Paniz-Mondolfi Alberto E.
Published: December 2021

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to circulate, multiple variants of concern (VOC) have emerged. New variants pose challenges for diagnostic platforms since sequence diversity can alter primer/probe binding sites (PBS), causing false-negative results. The Agena MassARRAY® SARS-CoV-2 Panel utilizes reverse-transcription polymerase chain reaction and mass-spectrometry to detect five multiplex targets across N and ORF1ab genes. Herein, we utilize a dataset of 256 SARS-CoV-2-positive specimens collected between April 11, 2021-August 28, 2021 to evaluate target performance with paired sequencing data. During this timeframe, two targets in the N gene (N2, N3) were subject to the greatest sequence diversity. In specimens with N3 dropout, 69% harbored the Alpha-specific A28095U polymorphism that introduces a 3’-mismatch to the N3 forward PBS and increases risk of target dropout relative to specimens with 28095A (relative risk (RR): 20.02; p<0.0001; 95% Confidence Interval (CI): 11.36-35.72). Furthermore, among specimens with N2 dropout, 90% harbored the Delta-specific G28916U polymorphism that creates a 3’-mismatch to the N2 probe PBS and increases target dropout risk (RR: 11.92; p<0.0001; 95% CI: 8.17-14.06). These findings highlight the robust capability of Agena MassARRAY® SARS-CoV-2 Panel target results to reveal circulating virus diversity and underscore the power of multi-target design to capture VOC.
Post-Vaccination Symptoms after A Third Dose of mRNA SARS-CoV-2 Vaccination in Patients with Inflammatory Bowel Disease
Authors: Li Dalin , Debbas Philip , Cheng Susan , Braun Jonathan , McGovern Dermot P.B. , Melmed Gil Y.
Published: December 2021

Symptoms after SARS-CoV-2 primary vaccination among patients with inflammatory bowel disease (IBD) are generally of similar frequency, severity, and duration to those reported in the general population. The symptom profile after a 3rd mRNA vaccine dose in the predominantly immune-compromised IBD population is unknown. We aimed to assess symptomology after a 3rd or booster dose of mRNA vaccination in adults with IBD. We surveyed participants of the Coronavirus Risk Associations and Longitudinal Evaluation in IBD (CORALE-IBD) post-vaccination registry for symptom frequency and severity after a 3rd mRNA vaccine dose in an observational cohort study. In total, 524 participants (70% female, mean age 45 years) reported a third dose of mRNA vaccination through October 11, 2021. Overall, 41% reported symptoms after a third dose, with symptoms generally more frequent and more severe among participants younger than 55 years. The most frequent postvaccination symptoms were injection site pain (39%), fatigue or malaise (34%), and headache (23%). These symptoms were all less frequently reported after dose 3 than after dose 2. Gastrointestinal symptoms were reported by 8.8%, which was slightly more frequent than after dose 2 (7.8%). Those with severe symptoms after dose 2 were more likely to have severe symptoms after dose 3. These findings can reassure the IBD patient and provider communities that the likelihood and distribution of symptoms after a third mRNA vaccine dose are generally similar to those after a second dose, and that the frequency of postvaccination symptoms after dose 3 are generally lower than after dose 2.
SEDRA: Selective Entry Dynamic Risk Assessment: A mathematical model to safely keep the borders open during Covid-19
Authors: de Gennaro Silvano , Lane Håkan
Published: December 2021

1.

The Covid-19 pandemic has brought the World to a near standstill for most of 2020 and 2021, causing chaos in international travel, driving many economies into the ground, particularly those largely based on tourism. The lack of standard tools to assist decision makers in structuring a coherent policy to allow foreign passengers into their county and the resulting panic-mode opening/closing the borders on every “new case” outburst or new variant “of concern”, have led several countries to costly and often meaningless decisions based on fear rather than science or logic. This study aims at providing a universal method to safely keep the borders open and allow conditional immigration to foreign passengers according to a “Risk Group” table that includes all the countries reporting data on their Covid-19 situation to the WHO and other organisms. The RG table is recalculated on a weekly basis according to a mathematical model described in this paper, dynamically assessing the status of the pandemic worldwide through the calculation of a “Safety Index” for each country. A prototype algorithm has been implemented in VBA/EXCEL and its results are published bi-weekly on a Github repository.
Machine learning quantification of amyloid deposits in histological images of ligamentum flavum
Authors: Wang Andy Y. , Sharma Vaishnavi , Saini Harleen , Tingen Joseph N. , Flores Alexandra , Liu Diang , Safain Mina G. , Kryzanski James , McPhail Ellen D. , Arkun Knarik , Riesenburger Ron I.
Published: December 2021

Background

Wild-type transthyretin amyloidosis (ATTRwt) is an underdiagnosed and potentially fatal disease. Interestingly, ATTRwt deposits have been found to deposit in the ligamentum flavum (LF) of patients with lumbar spinal stenosis prior to the development of systemic and cardiac amyloidosis. In order to study this phenomenon and its possible relationship with LF thickening and systemic amyloidosis, a precise method of quantifying amyloid deposits in histological slides of LF is critical. However, such a method is currently unavailable. Here, we present a machine learning quantification method with Trainable Weka Segmentation (TWS) to assess amyloid deposition in histological slides of LF.

Methods

Images of ligamentum flavum specimens stained with Congo red are obtained from spinal stenosis patients undergoing laminectomies and confirmed to be positive for ATTRwt. Amyloid deposits in these specimens are classified and quantified by TWS through training the algorithm via user-directed annotations on images of LF. TWS can also be automated through exposure to a set of training images with user-directed annotations, and then application to a set of new images without additional annotations. Additional methods of color thresholding and manual segmentation are also used on these images for comparison to TWS.

Results

We develop the use of TWS in images of LF and demonstrate its potential for automated quantification. TWS is strongly correlated with manual segmentation in the training set of images with user-directed annotations (R = 0.98; p = 0.0033) as well as in the application set of images where TWS was automated (R = 0.94; p = 0.016). Color thresholding was weakly correlated with manual segmentation in the training set of images (R = 0.78; p = 0.12) and in the application set of images (R = 0.65; p = 0.23).

Conclusion

TWS machine learning closely correlates with the gold standard comparator of manual segmentation and outperforms the color thresholding method. This novel machine learning method to quantify amyloid deposition in histological slides of ligamentum flavum is a precise, objective, accessible, high throughput, and powerful tool that will hopefully pave the way towards future research and clinical applications.
Evaluation of the Performance of Filmarray Blood Culture Identification Panel on Detecting Blood Cultures Containing Activated Carbon Powder
Authors: Chen Chen , He Shang , Wang Chengbin
Published: December 2021

Objective

The FilmArray Blood Culture Identification (BCID) panel is a rapid microfluidic PCR amplification microbial detection system. Several studies have evaluated its clinical performance on the basis of blood culture bottles containing resins. However, proportion of hospitals in China use bottles with carbon power, which the performance of FilmArray has not been fully investigated. Therefore, this study is conducted to explore the accuracy of the panel using blood culture bottles with carbon power.

Method

147 venous blood cultures containing carbon powder were used to assess the microbial and antibiotic resistance detection ability of the FilmArray panel. Outcomes were compared with results of the clinical combination method and their consistency was analyzed.

Results

FilmArray detected single microorganism in 121 samples, multiple microorganism in 9 cases and the consistency rate between the two methods was 90.6%. Among the 150 microorganisms detected, 85.1% (40/47) of staphylococcus contained the antibiotic resistant mecA gene, 15.3% (9/59) of Enterobacter detected the KPC gene, 7.7% (1/13) of Enterococcus has the vanA gene and the consistency with their clinical drug-resistant phenotypes were 93.6%, 86.4% and 100%, respectively.

Conclusion

The identification rate of the FilmArray BCID panel using venous blood cultures with activated carbon powder was highly consistent with the outcomes of previous researchers using non-carbon powder blood culture bottles. It is capable of providing rapid and reliable results in the detection of pathogens present in automated blood culture systems.
LEXAS: a web application for life science experiment search and suggestion
Authors: Ito Kei K , Tsuruoka Yoshimasa , Kitagawa Daiju
Published: December 2021

Motivation

In cellular biology, researchers design wet experiments by reading the relevant articles and considering the described experiments and results. Today, researchers spend a long time exploring the literature in order to plan experiments.

Results

To accelerate experiment planning, we have developed a web application named LEXAS (Life-science EXperiment seArch and Suggestion). LEXAS curates the description of biomedical experiments and suggests the experiments on genes that could be performed next. To develop LEXAS, we first retrieved the descriptions of experiments from full-text biomedical articles archived in PubMed Central. Using these retrieved experiments and biomedical knowledgebases and databases, we trained a machine learning model that suggests the next experiments. This model can suggest not only reasonable genes but also novel genes as targets for the next experiment as long as they share some critical features with the gene of interest.

Availability and implementation

LEXAS is available at https://lexas.f.u-tokyo.ac.jp/ and provides users with two interfaces: search and suggestion. The search interface allows users to find a comprehensive list of experiment descriptions, and the suggestion interface allows users to find a list of genes that could be analyzed along with possible experiment methods. The source code is available at https://github.com/lexas-f-utokyo/lexas.

Contact

ito-delightfully-kei@g.ecc.u-tokyo.ac.jp

Supplementary information

Supplementary data are available at Bioinformatics online.
Comprehensive Serological Profile and Specificity of Maternal and Neonatal Cord Blood SARS CoV-2 Antibodies
Authors: Boelig Rupsa C. , Chaudhury Sidhartha , Aghai Zubair H. , Oliver Emily , Manusco Francesca , Berghella Vincenzo , Bergmann-Leitner Elke
Published: December 2021

Objective

To describe the profile and specificity of maternal and neonatal cord-blood antibody profile in response SARS-CoV-2 virus exposure

Methods

This is a Prospective cohort study of delivering patients at Thomas Jefferson University Hospital from April 2020-February 2021. Primary objective was to describe unique maternal and fetal antibody epitope titers and specificity in those patients with COVID-19 history. Serologic profile assessed with a multiplex platform. Antigens used were: HA-trimer Influenza A (Hong Kong H3), spike trimers for SARS-CoV-2, SARS-CoV-1, MERS-CoV, and betacoronaviruses HKU-1 and OC43, as well as the spike N-terminal domain (NTD), spike receptor binding domain (RBD), and nucleocapsid protein (N; full length) for SARS-CoV-2.

Results

112 maternal samples and 101 maternal and cord blood pairs were analyzed. Thirty-seven had a known history of COVID-19 (positive PCR test) in the pregnancy and of those, 17 (47%) were diagnosed with COVID-19 within 30 days of delivery. Fifteen of remaining seventy-six (20%) without a known diagnosis had positive maternal serology. For those with history of COVID-19 we identified robust IgG response in maternal blood to CoV2 nucleocapsid (N), spike (S) full-length and S (RBD) antigens with more modest responses to the S (NTD) antigen. By contrast, the maternal blood IgM response appeared more specific to S (full-length), than N, S (RBD) or S (NTD) epitopes. There were significantly higher maternal and cord blood IgG response not just to CoV2 spike (p < 10−18), but also CoV1 spike (p < 10−9) and MERS spike (p < 10−8). By contrast, maternal IgM responses were more specific to CoV2 (p < 10−19), but to a lesser degree for CoV1 (p < 10−5), and no significant differences for MERS. Maternal and cord-blood IgG were highly correlated for both S and N (R2 = 0.96 and 0.94).

Conclusions

Placental transfer is efficient, with robust N and S responses. Both nucleocapsid and spike antibody responses should be studied for a better understanding of COVID-19 immunity. IgG antibodies are cross reactive with related CoV-1 and MERS spike epitopes while IgM, which cannot cross placenta to provide neonatal passive immunity, is more SARS CoV-2 specific. Neonatal cord blood may have significantly different fine-specificity than maternal blood, despite the high efficiency of IgG transfer.
The pneumonia severity index: assessment and comparison to popular machine learning classifiers
Authors: Wang Dawei , Willis Deanna R. , Yih Yuehwern
Published: December 2021

Pneumonia is the top communicable cause of death worldwide. Accurate prognostication of patient severity with Community Acquired Pneumonia (CAP) allows better patient care and hospital management. The Pneumonia Severity Index (PSI) was developed in 1997 as a tool to guide clinical practice by stratifying the severity of patients with CAP. While the PSI has been evaluated against other clinical stratification tools, it has not been evaluated against multiple classic machine learning classifiers in various metrics over large sample size. In this paper, we evaluated and compared the prediction performance of nine classic machine learning classifiers with PSI over 34720 adult (age 18+) patient records collected from 749 hospitals from 2009 to 2018 in the United States on Receiver Operating Characteristic (ROC) Area Under the Curve (AUC) and Average Precision (Precision-Recall AUC). Machine learning classifiers, such as Random Forest, provided a significant improvement (∼29% in PR AUC and ∼5% in ROC AUC) compared to PSI and required only 7 input values (compared to 20 parameters used in PSI). There were also statistically significant differences (p<0.05) between Random Forest and PSI among various races/ethnicities. Because of its ease of use, PSI remains a very strong clinical decision tool, but machine learning classifiers can provide better prediction accuracy performance. Comparing prediction performance across multiple metrics such as PR AUC, instead of ROC AUC alone can provide additional insight.

Key Messages

This work compared the prognostication accuracy performance of patient severity with Community Acquired Pneumonia (CAP) between Pneumonia Severity Index (PSI) and nine machine learning classifiers and found machine learning classifiers provided a significant improvement.
Genetic interactions drive heterogeneity in causal variant effect sizes for gene expression and complex traits
Authors: Patel Roshni A. , Musharoff Shaila A. , Spence Jeffrey P. , Pimentel Harold , Tcheandjieu Catherine , Mostafavi Hakhamanesh , Sinnott-Armstrong Nasa , Clarke Shoa L. , Smith Courtney J. ,   VA Million Veteran Program, Durda Peter P. , Taylor Kent D. , Tracy Russell , Liu Yongmei , Johnson Craig W. , Aguet Francois , Ardlie Kristin G. , Gabriel Stacey , Smith Josh , Nickerson Deborah A. , Rich Stephen S. , Rotter Jerome I. , Tsao Philip S. , Assimes Themistocles L. , Pritchard Jonathan K.
Published: December 2021

Despite the growing number of genome-wide association studies (GWAS), it remains unclear to what extent gene-by-gene and gene-by-environment interactions influence complex traits in humans. The magnitude of genetic interactions in complex traits has been difficult to quantify because GWAS are generally underpowered to detect individual interactions of small effect. Here, we develop a method to test for genetic interactions that aggregates information across all trait-associated loci. Specifically, we test whether SNPs in regions of European ancestry shared between European American and admixed African American individuals have the same causal effect sizes. We hypothesize that in African Americans, the presence of genetic interactions will drive the causal effect sizes of SNPs in regions of European ancestry to be more similar to those of SNPs in regions of African ancestry. We apply our method to two traits: gene expression in 296 African Americans and 482 European Americans in the Multi-Ethnic Study of Atherosclerosis (MESA) and low-density lipoprotein cholesterol (LDL-C) in 74K African Americans and 296K European Americans in the Million Veteran Program (MVP). We find significant evidence for genetic interactions in our analysis of gene expression; for LDL-C, we observe a similar point estimate although this is not significant, likely due to lower statistical power. These results suggest that gene-by-gene or gene-by-environment interactions modify the effect sizes of causal variants in human complex traits.
Gap genes are involved in inviability in hybrids between Drosophila melanogaster and D. santomea
Authors: Chang Wenhan , Kreitman Martin , Matute Daniel R.
Published: December 2021

Evolved changes within species lead to the inevitable loss of viability in hybrids. Inviability is also a convenient phenotype to genetically map and validate functionally divergent genes and pathways differentiating closely related species. Here we identify the Drosophila melanogaster form of the highly conserved essential gap gene giant (gt) as a key genetic determinant of hybrid inviability in crosses with D. santomea. We show that the coding region of this allele in D. melanogaster/D. santomea hybrids is sufficient to cause embryonic inviability not seen in either pure species. Further genetic analysis indicates that tailless (tll), another gap gene, is also involved in the hybrid defects. giant and tll are both members of the gap gene network of transcription factors that participate in establishing anterior-posterior specification of the dipteran embryo, a highly conserved developmental process. Genes whose outputs in this process are functionally conserved nevertheless evolve over short timescales to cause inviability in hybrids.
The genetic origin and architecture of sex determination
Authors: De Tisham
Published: December 2021

Here, I demonstrate that sex determination and sexual dimorphism across tree of life are deeply related to polyamine biochemistry in cells, especially to the synteny of genes: [SAT1-NR0B1], [SAT2-SHBG] and DMRT1. This synteny was found to be most distinct in mammals. Further, the common protein domain of SAT1 and SAT2 - PF00583 was shown to be present in the genome of the last universal common ancestor (LUCA). Protein domain-domain interaction analysis of LUCA’s genes suggests the possibility that LUCA had developed an immune defence against viruses. This domain-domain interaction analysis is the first scientific evidence indicating that viruses existed at least 3.5 billions years ago and probably co-existed with LUCA on early Hadean Earth.
Protein-protein interactions on membrane surfaces analysed using pull-downs with supported bilayers on silica beads
Authors: Andhare Devika S. , Khurana Himani , Pucadyil Thomas J.
Published: December 2021

Discovery-based proteomics workflows that identify novel interactors rely on immunoprecipitations or pull-downs with genetically-tagged bait proteins immobilized on appropriate matrices. But strategies to analyse protein interactions on a diffusible membrane surface combined with the practical ease of pull-downs remain unavailable. Such strategies are important to analyse protein complexes that mature in composition and stability because of diffusion-based encounter between participant proteins. Here, we describe a generic pull-down strategy to analyse such complexes using chelating lipid-containing supported bilayers formed on silica beads. These templates can display desired His-tagged bait proteins on a diffusible membrane surface. Using clathrin-mediated endocytosis as a paradigm, we find that the clathrin-binding adaptor protein epsin1 displayed as bait on these templates pulls down significantly higher amounts of clathrin from brain lysates than when immobilized on conventional matrices. Together, our results establish the potential of such templates as superior matrices for analysing protein-protein interactions and resultant complexes formed on membrane surfaces.
Healthy lifestyle, genetic risk, and incidence of cancer: A prospective cohort study of 13 cancer types
Authors: Byrne Stephanie , Boyle Terry , Ahmed Muktar , Lee Sang Hong , Benyamin Beben , Hyppönen Elina
Published: December 2021

Background

Genetic and lifestyle factors are related to the risk of cancer, but it is unclear whether a healthy lifestyle can offset genetic risk. Our aim was to investigate this for 13 cancer types using data from the UK Biobank prospective cohort.

Methods

In 2006-2010, participants aged 37-73 years were assessed and followed until 2015-2019. Analyses were restricted to those of European ancestries with no history of malignant cancer (n=195,822). Polygenic risk scores (PRSs) were computed for 13 cancer types and these cancers combined (‘overall cancer’), and a healthy lifestyle score was calculated from current recommendations. Relationships with cancer incidence were examined using Cox regression, adjusting for relevant confounders. Interactions between HLI and PRSs were assessed.

Results

There were 15,240 incident cancers during the 1,926,987 person-years of follow-up (median follow-up= 10.2 years). After adjusting for confounders, an unhealthy lifestyle was associated with a higher risk of overall cancer [lowest vs highest tertile hazard ratio (95% confidence interval) = 1.32(1.26, 1.37)] and eight cancer types. The greatest increased risks were seen for cancers of the lung [3.5(2.96,4.15)], bladder [2.03 (1.57, 2.64)], and pancreas [1.98 (1.54,2.55)]. Positive additive interactions were observed, suggesting a healthy lifestyle may partially offset genetic risk of colorectal, breast, and pancreatic cancers, and may completely offset genetic risk of lung and bladder cancers.

Conclusions

A healthy lifestyle is beneficial for most cancers and may offset genetic risk of some cancers. These findings have important implications for those genetically predisposed to these cancers and population strategies for cancer prevention.
Clinical features of UK Biobank subjects carrying protein truncating variants in genes implicated in schizophrenia pathogenesis
Authors: Curtis David
Published: December 2021

The SCHEMA consortium has identified ten genes in which protein truncating variants (PTVs) confer substantial risk of schizophrenia. Exome-sequenced participants in the UK Biobank who carried PTVs in these genes were studied to determine to what extent they demonstrated features of schizophrenia or had neuropsychiatric impairment. Following automated quality control and visual inspection of reads, 251 subjects were identified as having well-supported PTVs in one of these genes. The frequency of PTVs in CACNA1G was higher than had been observed in SCHEMA cases, casting doubt on its role in schizophrenia pathogenesis, but otherwise rates were similar to those observed in SCHEMA controls. Numbers were too small to allow formal statistical analysis but in general carriers of PTVs did not appear to have high rates of psychiatric illness or reduced educational or occupational functioning. One subject with a PTV in SETD1A had a diagnosis of schizophrenia. one with a PTV in HERC1 had psychotic depression and two subjects seemed to have developmental disorders, one with a PTV in GRIN2A and one with a PTV in RBCC1. There seemed to be somewhat increased rates of affective disorders among carriers of PTVs in HERC1 and RB1CC1. Carriers of PTVs did not appear to have subclinical manifestations of schizophrenia. Although PTVs in these genes can substantially increase schizophrenia risk, their effect seems to be dichotomous and most carriers appear psychiatrically well.

This research has been conducted using the UK Biobank Resource.
A phenotypic rescue approach identifies lineage regionalization defects in a mouse model of DiGeorge syndrome
Authors: Lania Gabriella , Franzese Monica , Noritaka Adachi , Bilio Marchesa , Russo Annalaura , D’Agostino Erika , Angelini Claudia , Kelly Robert G. , Baldini Antonio
Published: December 2021

TBX1 is a key regulator of pharyngeal apparatus (PhAp) development. Vitamin B12 treatment partially rescues aortic arch patterning defects of Tbx1+/- embryos. Here we show that it also improves cardiac outflow tract septation and branchiomeric muscle anomalies of Tbx1 hypomorphic mutants. At molecular level, the in vivo vB12 treatment let us to identify genes that were dysregulated by Tbx1 haploinsufficiency and rescued by treatment. We found that SLUG, encoded by the rescued gene Snai2, identified a population of mesodermal cells that was partially overlapping with but distinct from ISL1+ and TBX1+ populations. In addition, SLUG+ cells were mislocalized and had a greater tendency to aggregate in Tbx1+/- and Tbx1-/- embryos and vB12 treatment restore cellular distribution. Adjacent neural crest-derived mesenchymal cells, which do not express TBX1, were also affected, showing enhanced segregation from cardiopharyngeal mesodermal cells. We propose that TBX1 regulates cell distribution in core mesoderm and the arrangement of multiple lineages within the PhAp.
Positional motif analysis reveals the extent of specificity of protein-RNA interactions observed by CLIP
Authors: Kuret Klara , Amalietti Aram Gustav , Ule Jernej
Published: December 2021

Background

Crosslinking and immunoprecipitation (CLIP) is a method used to identify in vivo RNA– protein binding sites on a transcriptome-wide scale. With the increasing amounts of available data for RNA-binding proteins (RBPs), it is important to understand to what degree the enriched motifs specify the RNA binding profiles of RBPs in cells.

Results

We develop positionally-enriched k-mer analysis (PEKA), a computational tool for efficient analysis of enriched motifs from individual CLIP datasets, which minimises the impact of technical and regional genomic biases by internal data normalisation. We cross-validate PEKA with mCross, and show that background correction by size-matched input doesn’t generally improve the specificity of detected motifs. We identify motif classes with common enrichment patterns across eCLIP datasets and across RNA regions, while also observing variations in the specificity and the extent of motif enrichment across eCLIP datasets, between variant CLIP protocols, and between CLIP and in vitro binding data. Thereby we gain insights into the contributions of technical and regional genomic biases to the enriched motifs, and find how motif enrichment features relate to the domain composition and low-complexity regions (LCRs) of the studied proteins.

Conclusions

Our study provides insights into the overall contributions of regional binding preferences, protein domains and LCRs to the specificity of protein-RNA interactions, and shows the value of cross-motif and cross-RBP comparison for data interpretation. Our results are presented for exploratory analysis via an online platform in an RBP-centric and motif-centric manner (https://imaps.goodwright.com/apps/peka/). PEKA is available from https://github.com/ulelab/peka.