bluuebunny/crossref_metadata_2025 huggingface dataset:
Biogeography of Lentibacter algarum, description of a new strain isolated from the North Sea and emended genus and species descriptions
Authors: Hahnke Sarah , Giebel Helge-Ansgar , Freese Heike M. , Moraru Cristina , Tindall Brian J. , Simon Meinhard , Brinkhoff Thorsten
Published: July 2024

A new heterotrophic, aerobic alphaproteobacterium, designated strain SH36 (=DSM 23330=LMG 25292), was obtained from a seawater sample collected in the open North Sea during a phytoplankton bloom. Analysis of the 16S rRNA gene sequence revealed affiliation of strain SH36 to the species Lentibacter algarum (family Roseobacteraceae), showing 100 and 99.9 % sequence similarity to the 16S rRNA genes of the strains L. algarum ZXM098 and ZXM100T. Digital DNA–DNA hybridization of strain SH36 with the type strain of L. algarum showed 98.0 % relatedness, confirming that strain SH36 can be classified within the same species. All three L. algarum strains were compared by physiological, morphological, chemotaxonomic, and genotypic characteristics. The strains showed only minor differences in the composition of fatty acids and polar lipids, but considerable physiological differences. Comparison of the 16S rRNA gene sequence of SH36 with sequences present in GenBank revealed that phylotypes with ≥98.65 % sequence identity to the type strain of L. algarum were found at different marine and estuarine locations of temperate and subtropic regions. Furthermore, by using a specific PCR approach L. algarum was detected throughout annual cycles at the offshore station at Helgoland Roads in the German Bight, indicating that this species is a permanent member of the microbial community in the North Sea.
Communicating and disseminating One Health: successes of the One Health European Joint Programme
Authors: Taylor Emma , Artursson Karin , Busani Luca , Callegari Arnaud , Cantlay Jennifer , Caniça Manuela , Campling Elaine , Gavier-Widén Dolores , van de Giessen Arjen , Itier David , Imberechts Hein , Roest Hendrik-Jan , Jestin André , de Juan Lucia , Jokelainen Pikka , Kaesbohrer Annemarie , Lindberg Ann , Mantovani Alberto , Mølbak Kåre , van der Poel Wim H.M. , Poirier Aurore C. , Sepe Ludovico P. , Morabito Stefano , Whitehouse Jack , Horton Daniel L. , La Ragione Roberto
Published: July 2024

The application of a One Health approach recognizes that human health, animal health, plant health and ecosystem health are intrinsically connected. Tackling complex challenges associated with foodborne zoonoses, antimicrobial resistance, and emerging threats is imperative. Therefore, the One Health European Joint Programme was established within the European Union research programme Horizon 2020. The One Health European Joint Programme activities were based on the development and harmonization of a One Health science-based framework in the European Union (EU) and involved public health, animal health and food safety institutes from almost all EU Member States, the UK and Norway, thus strengthening the cooperation between public, medical and veterinary organizations in Europe. Activities including 24 joint research projects, 6 joint integrative projects and 17 PhD projects, and a multicountry simulation exercise facilitated harmonization of laboratory methods and surveillance, and improved tools for risk assessment. The provision of sustainable solutions is integral to a One Health approach. To ensure the legacy of the work of the One Health European Joint Programme, focus was on strategic communication and dissemination of the outputs and engagement of stakeholders at the national, European and international levels.
Cross-modal interaction of Alpha Activity does not reflect inhibition of early sensory processing: A frequency tagging study using EEG and MEG
Authors: Brickwedde M. , Limachya R. , Markiewicz R. , Sutton E. , Postzich C. , Shapiro K. , Jensen O. , Mazaheri A.
Published: July 2024

Selective attention involves prioritizing relevant sensory input while suppressing irrelevant stimuli. It has been proposed that oscillatory alpha-band activity (∼10 Hz) aids this process by functionally inhibiting early sensory regions. However, recent studies have challenged this notion. Our EEG and MEG studies aimed to investigate whether alpha oscillations serve as a ‘gatekeeper’ for downstream signal transmission. We first observed these effects in an EEG study and then replicated them using MEG, which allowed us to localize the sources.

We employed a cross-modal paradigm where visual cues indicated whether upcoming targets required visual or auditory discrimination. To assess inhibition, we utilized frequency-tagging, simultaneously flickering the fixation cross at 36 Hz and playing amplitude-modulated white noise at 40 Hz during the cue-to-target interval.

Consistent with prior research, we observed an increase in posterior alpha activity following cues signalling auditory targets. However, remarkably, both visual and auditory frequency tagged responses amplified in anticipation of auditory targets, correlating with alpha activity amplitude. Our findings suggest that when attention shifts to auditory processing, the visual stream remains responsive and is not hindered by occipital alpha activity. This implies that alpha modulation does not solely regulate ‘gain control’ in early sensory areas but rather orchestrates signal transmission to later stages of the processing stream.
Testing the causal impact of amyloidosis on total Tau using a genetically informative sample of adult male twins
Authors: Gillespie Nathan A. , Neale Michael C. , Panizzon Matthew S. , McKenzie Ruth E. , Tu Xin M. , Xian Hong , Reynolds Chandra A. , Lyons Michael J. , Rissman Robert A. , Elman Jeremy A. , Franz Carol , Kremen William S.
Published: July 2024

INTRODUCTION

The amyloid cascade hypothesis predicts that amyloid-beta (Aβ) aggregation drives tau tangle accumulation. We tested competing causal and non-causal hypotheses regarding the direction of causation between Aβ40 and Aβ42 and total Tau (t-Tau) plasma biomarkers.

METHODS

Plasma Aβ40, Aβ42, t-Tau, and neurofilament light chain (NFL) were measured in 1,035 men (mean = 67.0 years) using Simoa immunoassays. Genetically informative twin modeling tested the direction of causation between Aβs and t-Tau.

RESULTS

No clear evidence that Aβ40 or Aβ42 directly causes changes in t-Tau was observed; the alternative causal hypotheses also fit the data well. In contrast, exploratory analyses suggested a causal impact of the Aβ biomarkers on NFL. Separately, reciprocal causation was observed between t-Tau and NFL.

DISCUSSION

Plasma Aβ40 or Aβ42 do not appear to have a direct causal impact on t-Tau. In contrast, Aβ aggregation may causally impact NFL in cognitively unimpaired men in their late 60s.
Treatment Outcome in Patients With Spinal Neurocysticercosis: A Systematic Review of Published Cases and Case Series
Authors: Garg Ravindra Kumar , Rizvi Imran , Nigam Harish , Pandey Shweta , Uniyal Ravi
Published: July 2024

Background

Spinal neurocysticercosis is a rare central nervous system infection caused by the larval form of theTaenia soliumtapeworm. Due to its rarity, most knowledge is derived from isolated case reports.

Objectives

This systematic review aims to evaluate existing case reports and observational studies to provide a comprehensive overview of the disease’s clinical presentation, and treatment outcomes.

Methods

Adhering to PRISMA guidelines, a search was conducted across multiple databases including PubMed, Scopus, Embase, and Google Scholar. Case reports, case series, and observational studies were included. The review is registered with PROSPERO (CRD42024496957).

Results

The search yielded 163 records describing 197 patients. Symptoms ranged from one week to over three years, with the most common being paraparesis or quadriparesis (61%) and back pain. Treatment modalities varied. with a combination of surgery and cysticidal drugs being the most preferred (45.2%) treatment. Surgery was done in 77% (152/197) of cases. In 45 % of cases (89/197) cysticidal drugs were given following surgery. Medical treatment alone was given to 22% (43/197) of patients.

The majority of cases (92%) irrespective of treatment modality showed clinical improvement. Post-operative complications caused three deaths.

Conclusions

We noted that surgery followed by cysticidal drugs was the most preferred treatment. Medical treatment alone was given to many patients. Clinical improvement was observed in most cases, regardless of the treatment option used. The use of cysticidal drugs could eliminate the need for surgery in many spinal neurocysticercosis patients.

Key message

Most spinal neurocysticercosis patients improve clinically with surgery and cysticidal drugs, the most common treatment. Medical management alone also benefits many, suggesting potential to reduce surgical intervention with effective drug therapy.
Analyzing the Factor Structure and Sleep Quality of Pittsburgh Sleep Quality Index in Indian Information Technology Sector
Authors: Chatterjee Arindam , Dutta Arijit , Chaudhuri Rimu
Published: July 2024

The Pittsburgh Sleep Quality Index (PSQI) has gained widespread acceptance as a useful tool to measure sleep quality. In order to formulate the diagnosis process, it is essential that we understand the factor structure inherent in the PSQI data. In this work, we seek to estimate such a structure with a focus on the Indian Information Technology (IT) workers. We have used Confirmatory Factor Analysis (CFA) and the Exploratory Factor Analysis (EFA) for this purpose. Instead of using random imputation to handle the frequently occurring missing values, we have used more sophisticated techniques thereby improving the accuracy of our results. We have also used the Multi layer perceptron based method to see how we can classify the sleep quality of the sampled population. We have discovered that, contrary to the general perception, most Indian IT employees have sleep quality belonging to good and very good classes.

Author summary

Arindam Chatterjee - Curently Assistant Professor of Computer Science and Engineering, Heritage Institute of Technology, Kolkata. Arindam has almost 16 years of teaching and research experience. In past he has worked in the industry for eight years. Area of academic interest is Impact of Information Technology on Indian Financial and Social sectors.

Rimu Chaudhuri -Currently Professor of Economics, Heritage Business School, Kolkata. Rimu is having teaching experience of almost 16yrs and research experience of 20 yrs. Area of academic / research interest is Entrepreneurship Development and for last couple of years Rimu is working in the field of Gender and Environment Sustainability. Last couple of years Rimu has worked extensively on Social Impact of IT. Rimu is also the President of Institution’s Innovation Council of Heritage Business School.

Arijit is a software engineer at Bloomberg LP, with a Master’s degree in Computer Science from the University of Florida. He specializes in creating and maintaining low-latency, high-performant, and robust backend applications. Arijit has a keen interest in Distributed Systems and Software Development. Currently, he contributes his expertise to the ESG (Environmental, Social, and Governance) sector, managing proprietary datasets and developing services that handle millions of requests per day. His work ensures efficient and reliable data management in a high-demand environment.
Symptom Cluster Profiles among Community-residing Older Adults with Heart Failure: Findings from the U.S. Health and Retirement Study
Authors: Wang Zequan , JEON Sangchoon , TOCCHI Christine , CONLEY Samantha , WALSH Stephen , KIM Kyounghae , CHYUN Deborah , REDEKER Nancy Schmieder
Published: July 2024

Background

The incidence of heart failure (HF) rises significantly as people age due to the accumulated influence of risk factors in cardiovascular structure and function. Among older adults with HF, symptoms are manifested in clustered symptoms. Few studies have addressed symptoms specifically in older adults with HF and most have been conducted with small samples. The aims of this study were to (1) describe symptom cluster profiles in older adults with HF in a nationally representative sample of community-dwelling older adults; and (2) determine the associations between demographic and clinical characteristics and membership in symptom cluster profiles.

Methods

A secondary analysis was conducted using data from the Health and Retirement Study. Fatigue, shortness of breath, pain, swelling, depressive symptoms, and dizziness were measured. Latent class analysis was used to identify symptom cluster profiles. Bivariate associations and multinomial logistic regression were used to determine the associations between symptom cluster profiles and demographic and clinical characteristics.

Results

The sample included 690 participants. Three symptom cluster profiles were identified [high-burden, low-burden, and cardiopulmonary-depressive]. Age, gender, BMI, marital status, alcohol consumption, diabetes, lung disease, and arthritis were significantly different across the three profiles. People in the high-burden and cardiopulmonary-depressive profiles, compared to those in low-burden, had higher odds of having lung disease and arthritis, yet lower odds of higher alcohol consumption.

Conclusions

Older adults with HF residing in the community experienced distinct symptom cluster profiles. Research is needed to identify and test targeted interventions for specific symptom cluster profiles.
Population Performance and Individual Agreement of Coronary Artery Disease Polygenic Risk Scores
Authors: Abramowitz Sarah A. , Boulier Kristin , Keat Karl , Cardone Katie M. , Shivakumar Manu , DePaolo John , Judy Renae , Kim Dokyoon , Rader Daniel J. , Ritchie Marylyn D. , Voight Benjamin F. , Pasaniuc Bogdan , Levin Michael G. , Damrauer Scott M.
Published: July 2024

Importance

Polygenic risk scores (PRSs) for coronary artery disease (CAD) are a growing clinical and commercial reality. Whether existing scores provide similar individual-level assessments of disease liability is a critical consideration for clinical implementation that remains uncharacterized.

Objective

Characterize the reliability of CAD PRSs that perform equivalently at the population level at predicting individual-level risk.

Design

Cross-sectional Study.

Setting

All of Us Research Program (AOU), Penn Medicine Biobank (PMBB), and UCLA ATLAS Precision Health Biobank.

Participants

Volunteers of diverse genetic backgrounds enrolled in AOU, PMBB, and UCLA with available electronic health record and genotyping data.

Exposures

Polygenic risk for CAD from previously published PRSs and new PRSs developed separately from the testing cohorts.

Main Outcomes and Measures

Sets of CAD PRSs that perform population prediction equivalently were identified by comparing calibration and discrimination (Brier score and AUROC) of generalized linear models of prevalent CAD using Bayesian analysis of variance. Among equivalently performing scores, individual-level agreement between risk estimates was tested with intraclass correlation (ICC) and Light’s Kappa, measures of inter-rater reliability.

Results

50 PRSs were calculated for 171,095 AOU participants. When included in a model of prevalent CAD, 48 scores had practically equivalent Brier scores and AUROCs (region of practical equivalence = 0.02). Across these scores, 84% of participants had at least one score in both the top and bottom risk quintile. Continuous agreement of individual risk predictions from the 48 scores was poor, with an ICC of 0.351 (95% CI; 0.349, 0.352). Agreement between two statistically equivalent scores was moderate, with an ICC of 0.649 (95% CI; 0.646, 0.652). Light’s Kappa, used to evaluate consistency of assignment to high-risk thresholds, did not exceed 0.56 (interpreted as ‘fair’) across statistically and practically equivalent scores. Repeating the analysis among 41,193 PMBB and 50,748 UCLA participants yielded different sets of statistically and practically equivalent scores which also lacked strong individual agreement.

Conclusions and Relevance

Across three diverse biobanks, CAD PRSs that performed equivalently at the population level produced unreliable individual risk estimates. Approaches to clinical implementation of CAD PRSs must consider the potential for discordant individual risk estimates from otherwise indistinguishable scores.
Rationale of acupuncture for stabilizing blood pressure fluctuation during total laparoscopic hysterectomy (ASBP): a parallel grouped, randomized clinical trial
Authors: Lee Joohyun , Roh Ju-Won , Han Kyung-Hee , Kim Min-Jeong , Na Young Jeong , Yun Bo Seong , Lee Jee Young
Published: July 2024

Introduction

Reducing blood pressure fluctuations during surgery is a significant goal for anesthesiologists. Acupuncture may be a non-invasive intervention to reduce blood pressure fluctuations but has not yet been studied. This study aims to determine whether acupuncture can be used to reduce blood pressure fluctuations during surgery, especially in the early stages.

Methods and analysis

This is a prospective, single-center, randomized controlled clinical trial with a parallel-group design. Thirty adult patients scheduled to undergo total laparoscopic hysterectomy are eligible. Participants who consent will be randomly assigned in a 1:1 ratio to the acupuncture or placebo group. They will be followed up for at least 14 days to assess the safety of the intervention, general anesthesia, and surgery. We will compare the differences between the highest and lowest mean blood pressures from anesthesia induction to the post-incision period as the primary endpoint. As secondary outcomes, systolic, diastolic, and mean blood pressures will be compared at each pre-determined time point. Incidence of hypotension, hypertension, tachycardia, and bradycardia will be counted separately. The use of remifentanil at the early stage of surgery, the rate of surgical discontinuation, and the length of hospital stay will be assessed as surrogate indicators of stable general anesthesia and surgical procedures. For patient-reported outcomes, Spielberger’s State-Trait Anxiety Inventory and EuroQoL-5 Dimensions–5 Levels will evaluate the change in anxiety and overall quality of life. Another non-pharmacological intervention may contribute to surgery by maintaining blood pressure within a stable range during the early postoperative period.

Ethics and dissemination

The study will be conducted in accordance with the Declaration of Helsinki, and approved by the Institutional Review Board of CHA Ilsan Medical Center (ICHA 2022-11-010, date of approval 2023-01-03). This study was registered atClinicaltrials.gov(registration identifier:NCT05720884) and CRiS (registration identifier: KCT0009149). The publication is scheduled for December 2025. Data deposition is scheduled to occur.

Strengths and limitations of this study

Reducing blood pressure fluctuation is important during surgical process.

Considering pharmacological interactions, non-pharmacological interventions are preferable for managing blood pressure fluctuation.

Acupuncture has some potential for stabilizing blood pressure.
National Assessment on the Frequency of Pain Medication Prescribed for Intrauterine Device Insertion Procedures within the Veterans Affairs Health Care System
Authors: Ware Anna D. , Blumke Terri L. , Hoover Peter J. , Veigulis Zach P. , Ferguson Jacqueline M. , Pillai Malvika , Osborne Thomas F.
Published: July 2024

Background

The intrauterine device (IUD) is a highly effective form of long-acting reversible contraception, widely recognized for its convenience and efficacy. Despite its benefits, many patients report moderate to severe pain during and after their IUD insertion procedure. Furthermore, reports suggest significant variability in pain control medications, including no adequate pain medication. The aim of this evaluation was to assess the pharmaceutical pain medication types, proportions, and trends related to IUD insertion procedures within the Veterans Health Administration (VHA).

Methods

IUD insertion procedures documented in the VA electronic health record were assessed from 1/1/2018 to 10/13/2023. Descriptive statistics described patient and facility characteristics while annual trends were assessed using linear regression.

Results

Out of the 28,717 procedures captured, only 11.4% had any form of prescribed pain medication identified. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) were the most frequently prescribed pain medication category (8.3%), with ibuprofen being the most common pain medication overall (6.1%). Over the assessment period, there was an average annual increase of 0.52% (p=0.038) of procedures with prescribed pain medication, increasing from 10.3% in 2018 to 13.3% in 2023.

Conclusions

Although IUD insertion procedures have been seeing an increase in prescribed pain medication, the overall proportion remains disproportionality low relative to the pain experienced. Additionally, when pain interventions were initiated, they disproportionally utilized medication that have been shown to be ineffective. The intent of the work is that the information will help guide data driven pain medication strategies for patients undergoing IUD insertion procedures within the VHA.
A machine learning approach to predict mortality and pulmonary hypertension severity in newborns with congenital diaphragmatic hernia
Authors: Conte Luana , Amodeo Ilaria , De Nunzio Giorgio , Raffaeli Genny , Borzani Irene , Persico Nicola , Griggio Alice , Como Giuseppe , Colnaghi Mariarosa , Fumagalli Monica , Cascio Donato , Cavallaro Giacomo
Published: July 2024

Prenatal prediction of postnatal outcomes in newborns with congenital diaphragmatic hernia (CDH) remains challenging, especially for mortality and neonatal persistent pulmonary hypertension (PPHN). Despite the increasing utilization of advanced artificial intelligence (AI) technologies in the neonatal field, this study is pioneering in exploring AI methodologies in the context of CDH. It represents an initial attempt to implement a Machine Learning (ML) system to predict postnatal mortality and PPHN severity, using prenatal and early postnatal data as input variables. We enrolled 50 patients with isolated left-sided CDH from singleton pregnancies and retrospectively collected clinical and imaging variables from fetal ultrasound (US) and shape features extracted from magnetic resonance imaging (MRI), combined with gestational age and birth weight. A supervised ML model for predicting mortality and PPHN severity was developed, achieving good accuracy (88% for mortality prediction and 82% for PPHN) and sensitivity (95% for mortality and 85% for PPHN). The area under the curve (AUC) of the ROC curve was 0.88 for mortality and 0.82 for PPHN predictions. Our results may lead to novel AI applications in the neonatal field, focusing on predicting postnatal outcomes based on prenatal data, ultimately improving prognostic assessments and intervention strategies for such a complex disease.

Clinical Trial Registration

The trial was registered at ClinicalTrials.gov with IdentifierNCT04609163

What is Known

prenatal prediction of postnatal mortality and severity of pulmonary hypertension in CDH newborns remains challenging and largely based on imaging through the volumetric assessment of fetal lungs.

What is New

developing a ML system for predicting PPHN severity and mortality risk based on the integrated assessment of prenatal and early postnatal variables is feasible, with good accuracy.
A randomized controlled trial of postbiotic administration during antibiotic treatment increases microbiome diversity and enriches health associated taxa
Authors: Schluter Jonas , Matheis Fanny , Ebina Wataru , Jogia William , Sullivan Alexis P. , Gordon Kelly , Fanega de la Cruz Elbert , Victory-Hays Mary E. , Heinly Mary Joan , Diefenbach Catherine S. , Peled Jonathan U. , Foster Kevin R. , Levitt Aubrey , McLaughlin Eric
Published: July 2024

Antibiotic-induced microbiome injury, defined as a reduction of ecological diversity and obligate anaerobe taxa, is associated with negative health outcomes in hospitalized patients, and healthy individuals who received antibiotics in the past are at higher risk for autoimmune diseases. No interventions are currently available that effectively target the microbial ecosystem in the gut to prevent this negative collateral damage of antibiotics. Here, we present the results from a single-center, randomized placebo-controlled trial involving 32 patients who received an oral, fermentation-derived postbiotic alongside oral antibiotic therapy for gastrointestinal (GI)-unrelated infections. Postbiotics comprise complex mixtures of metabolites produced by bacteria during fermentation and other processes, which can mediate microbial ecology. Bacterial ecosystem alpha diversity, quantified by the inverse Simpson index, during the end of the antibiotic course was significantly higher (+40%) across the 16 postbiotic-treated patients compared with the 16 patients who received a placebo, and the postbiotic was well-tolerated. Secondary analyses of 157 stool samples collected longitudinally revealed that the increased diversity was driven by enrichment in health-associated microbial genera: obligate anaerobe Firmicutes, in particular taxa belonging to the Lachnospiraceae family, were higher in treated patients; conversely,Escherichia/Shigellaabundances, which comprise pathobionts and antimicrobial-resistant strains, were reduced in postbiotic-treated patients at the end of their antibiotic course and up to 10 days later. Taken together, these results indicate that postbiotic co-administration during antibiotic therapy could support a health-associated gut microbiome community and may reduce antibiotic-induced microbiome injury.
Optimal annual COVID-19 vaccine boosting dates following previous booster vaccination or breakthrough infection
Authors: Townsend Jeffrey P. , Hassler Hayley B. , Dornburg Alex
Published: July 2024

COVID-19 booster vaccinations mitigate transmission and reduce the morbidity and mortality associated with infection. However, the optimal date for booster administration remains uncertain. Geographic variation in infection rates throughout the year make it challenging to intuit the best yearly booster administration date to effectively prevent infection, and also challenging to provide best guidance in how to alter booster administration in response to a breakthrough infection. Therefore, we leverage longitudinal antibody and reinfection probabilities with spatiotemporal projections of COVID-19 incidence to develop a geographically-informed approach to optimizing the timing of booster vaccination. Additionally, we assess the delay in booster vaccination that is warranted following breakthrough infections whenever they occur during the year, enabling an approach that acknowledges and respects diverse immune statuses, thereby addressing a substantial barrier to uptake. Our results provide guidance for individual decision-making and healthcare provider recommendations, as well as optimal public health policies.

Significance Statement

COVID-19 booster vaccinations are pivotal in reducing disease transmission. However, optimal schedules that would most successfully mitigate adverse health outcomes have not been rigorously determined. Spatial and temporal surges of infections, including breakthrough infections, challenge the implementation of effective boosting strategies. We leverage antibody data and incidence projections to develop a geographically-informed schedule for yearly booster administration and quantify appropriate delays in booster vaccination post-breakthrough infection, thereby accounting for immune status and enhancing vaccination inclusivity. Our findings offer crucial information for individual decision making, healthcare provider guidance, and policy aimed at optimizing the impact of booster vaccination on public health.
Physician experiences of electronic health records interoperability and its practical impact on care delivery in the English NHS: A cross-sectional survey study
Authors: Li Edmond , Lounsbury Olivia , Hasnain Mujtaba , Ashrafian Hutan , Darzi Ara , Neves Ana Luisa , Clarke Jonathan
Published: July 2024

Background

The lack of interoperability has been a well-recognised limitation associated with the use of electronic health records (EHR). However, less is known about how it manifests for frontline NHS staff when delivering care, how it impacts patient care, and what are its implications on care efficiency.

Objectives

(1) To capture the perceptions of physicians regarding the current state of EHRs interoperability, (2) to investigate how poor interoperability affects patient care and safety and (3) to determine the effects on care efficiency in the NHS.

Methods

An online survey was conducted to explore how physicians perceived the routine use of EHRs, its effects on patient safety, and impact to care efficiency in NHS healthcare facilities. Descriptive statistics was used to report any notable findings observed.

Results

A total of 636 NHS physicians participated. Participants reported that EHR interoperability is rudimentary across much of the NHS, with limited ability to read but not edit data from within their organisation. Negative perceptions were most pronounced amongst specialties in secondary care settings and those with less than one year of EHR experience or lower self-reported EHR skills. Limited interoperability prolonged hospital stays, lengthened consultation times, and frequently necessitated repeat investigations to be performed. Limited EHR interoperability impaired physician access to clinical data, hampered communication between providers, and was perceived to threatened patient safety.

Conclusion

As healthcare data continues to increase in complexity and volume, EHR interoperability must evolve to accommodate these growing changes and ensure the continued delivery of safe care. The experiences of physicians provide valuable insight into the practical challenges limited interoperability poses and can contribute to future policy solutions to better integrate EHRs in the clinical environment.

Public Interest/Lay Summary

Limited interoperability between EHR systems has been a longstanding problem since the technology’s introduction in NHS England. However, little research has been done to understand the extent of this problem from the perspective of physicians and the challenges it poses.

This study surveyed 636 physicians across England to better understand limited EHR interoperability. Most participants reported that interoperability between NHS facilities was inadequate. Consequences of this included increased duration of hospital stays, lengthened consultation times, and more redundant diagnostic tests performed. Limited interoperability hindered communication between NHS workers and threatened care quality and patient safety. As more healthcare technologies are incorporated into the NHS, gaining greater insight from physicians is critical to finding solutions to address these problems.
Parvalbumin interneuron ErbB4 controls ongoing network oscillations and olfactory behaviors in mice
Authors: Hu Bin , Geng Chi , Guo Feng , Liu Ying , Wang Ran , Chen You-Ting , Hou Xiao-Yu
Published: July 2024

Parvalbumin (PV)-positive interneurons modulate the processing of odor information. However, less is known about how PV interneurons dynamically remodel neural circuit responses in the olfactory bulb (OB) and its physiological significance. This study showed that a reinforced odor discrimination task up-regulated the activity of ErbB4 kinase in mouse OB. ErbB4 knock-out in the OB impaired dishabituation of odor responses and discrimination of complex odors, whereas odor memory or adaptation had no alteration in mice. RNAscope analysis demonstrated that ErbB4-positive neurons are localized throughout the OB, whereas within the internal and external plexiform layers, ErbB4 mRNA are largely expressed in PV-positive interneurons. ErbB4 knock-out in PV interneurons disrupted odor-evoked responses of mitral/tufted cells, and led to increased power in the ongoing local field potential in awake mice. We also found a decrease in the frequency of miniature inhibitory postsynaptic currents and deficits in stimulus-evoked recurrent and lateral inhibition onto mitral cells, suggesting broad impairments in inhibitory microcircuit following PV-ErbB4 loss. Similarly, ErbB4 ablation in OB PV interneurons disrupted olfactory discrimination and dishabituation in mice. These findings provide novel insights into the role of PV-ErbB4 signaling in inhibitory microcircuit plasticity, ongoing oscillations, and OB output, which underlies normal olfactory behaviors.
Re-analysis of mobile mRNA datasets highlights challenges in the detection of mobile transcripts from short-read RNA-Seq data
Authors: Paajanen Pirita , Tomkins Melissa , Hoerbst Franziska , Veevers Ruth , Heeney Michelle , Thomas Hannah Rae , Apelt Federico , Saplaoura Eleftheria , Gupta Saurabh , Frank Margaret , Walther Dirk , Faulkner Christine , Kehr Julia , Kragler Friedrich , Morris Richard J.
Published: July 2024

Short-read RNA-Seq analyses of grafted plants have led to the proposal that large numbers of mRNAs move over long distances between plant tissues, acting as potential signals. The detection of transported transcripts by RNA-Seq is both experimentally and computationally challenging, requiring successful grafting, delicate harvesting, rigorous contamination controls and data processing approaches that can identify rare events in inherently noisy data. Here, we perform a meta-analysis of existing datasets and examine the associated bioinformatic pipelines. Our analysis reveals that technological noise, biological variation and incomplete genome assemblies give rise to features in the data that can distort the interpretation. Taking these considerations into account, we find that a substantial number of transcripts that are currently annotated as mobile are left without support from the available RNA-Seq data. Whilst several annotated mobile mRNAs have been validated, we cannot exclude that others may be false positives. The identified issues may also impact other RNA-Seq studies, in particular those using single nucleotide polymorphisms (SNPs) to detect variants.
The minimal number of genes needed to identify a tumor
Authors: Gil Gabriel , Gonzalez Augusto
Published: July 2024

We demonstrate that the global state of a Gene Regulatory Network[1]may be labeled by a few genes in spite of the fact that there are thousands of genes participating in it. For example, the expression values of only 3 genes are enough to discriminate between a tissue sample coming from a normal lung or a lung adenocarcinoma. We follow a pragmatic procedure, dependent on the sample set, but which is expected to become exact for large enough sets of samples. The proof relies on a scheme for the construction of perfect classification panels of genes[2], inspired by rough set theory[3].
A review of co-occurrence and hybridization as neglected factors in studies of Syrian WoodpeckerDendrocopos syriacusand Great Spotted WoodpeckerDendrocopos major
Authors: Bakai Antonii , Gorman Gerard , Kajtoch Łukasz
Published: July 2024

Some species of woodpecker (Picidae), such as in the genusDendrocopos, are known to occasionally hybridize. The distribution, biology and ecology of the Syrian Woodpecker (D. syriacus) and the Great Spotted Woodpecker (D. major) are fairly well-known (less so in the case of Syrian), but these closely related species are seldom treated together in studies. This review summarizes the published data on these species in order to evaluate the omissions and inaccuracies in research and surveys on their sympatric populations. As research that deals with both species together is scant, the need to examine interactions, both antagonistic and hybridization, is advisable in order to properly understanding their ecology, ethology, breeding biology and demography.
SAVANA: reliable analysis of somatic structural variants and copy number aberrations in clinical samples using long-read sequencing
Authors: Elrick Hillary , Sauer Carolin M , Espejo Valle-Inclan Jose , Trevers Katherine , Tanguy Melanie , Zumalave Sonia , De Noon Solange , Muyas Francesc , Cascao Rita , Afonso Angela , Amary Fernanda , Tirabosco Roberto , Giess Adam , Freeman Timothy , Sosinsky Alona , Piculell Katherine , Miller David T , Faria Claudia C , Elgar Greg , Flanagan Adrienne M , Cortes-Ciriano Isidro
Published: July 2024

Accurate detection of somatic structural variants (SVs) and copy number aberrations (SCNAs) is critical to inform the diagnosis and treatment of human cancers. Here, we describe SAVANA, a computationally efficient algorithm designed for the joint analysis of somatic SVs, SCNAs, tumour purity and ploidy using long-read sequencing data. SAVANA relies on machine learning to distinguish true somatic SVs from artefacts and provide prediction errors for individual SVs. Using high-depth Illumina and nanopore whole-genome sequencing data for 99 human tumours and matched normal samples, we establish best practices for benchmarking SV detection algorithms across the entire genome in an unbiased and data-driven manner using simulated and sequencing replicates of tumour and matched normal samples. SAVANA shows significantly higher sensitivity, and 9- and 59-times higher specificity than the second and third-best performing algorithms, yielding orders of magnitude fewer false positives in comparison to existing long-read sequencing tools across various clonality levels, genomic regions, SV types and SV sizes. In addition, SAVANA harnesses long-range phasing information to detect somatic SVs and SCNAs at single-haplotype resolution. SVs reported by SAVANA are highly consistent with those detected using short-read sequencing, including complex events causing oncogene amplification and tumour suppressor gene inactivation. In summary, SAVANA enables the application of long-read sequencing to detect SVs and SCNAs reliably in clinical samples.
Resistance of estrogen receptor function to BET bromodomain inhibition is mediated by transcriptional coactivator cooperativity
Authors: Zhang Sicong , Roeder Robert G.
Published: July 2024

The Bromodomain and Extra-Terminal Domain (BET) family of proteins are critical chromatin readers that bind to acetylated histones through their bromodomains to activate transcription. Here, we reveal that bromodomain inhibition fails to repress oncogenic targets of estrogen receptor due to an intrinsic transcriptional mechanism. While bromodomains are necessary for the transcription of many genes, BRD4 binds to estrogen receptor binding sites and activates transcription of critical oncogenes independently of its bromodomains. BRD4 associates with the Mediator complex and disruption of Mediator complex reduces BRD4’s enhancer occupancy. Profiling changes in the post-initiation RNA polymerase II (Pol II)-associated factors revealed that BET proteins regulate interactions between Pol II and elongation factors SPT5, SPT6, and PAF1 complex, which associate with BET proteins independently of their bromodomains and mediate their transcription elongation effect. Our findings highlight the importance of bromodomain-independent functions and interactions of BET proteins in the development of future therapeutic strategies.
Cross-view graph neural networks for spatial domain identification by integrating gene expression, spatial locations with histological images
Authors: Liu Songyan , Guo Yin , Zhang Zixuan , Zhang Shuqin , Li Limin
Published: July 2024

The latest developments in spatial transcriptomics technology provide an unprecedented opportunity for in situ elucidation of tissue structure and function. Spatial transcriptomics can provide simultaneous, multi-modal, and complementary information, including gene expression profiles, spatial positions, and histological images. Despite these capabilities, current methodologies often fall short in fully integrating these multi-modal datasets, thereby limiting their ability to fully understand tissue heterogeneity. In this study, we propose XVGAE (cross-view graph autoencoders), a novel approach that integrates gene expression data, spatial coordinates, and histological images to identify spatial domains. XVGAE constructs two distinct graphs: a spatial graph from spatial coordinates and a histological graph from histological images, and these graphs enable XVGAE to learn specific representations for each view and propagate information between them using cross-view graph convolutional networks. The experiments on benchmark datasets of the human dorsolateral prefrontal cortex show demonstrate that the XVGAE could achieve better clustering accuracy than state-of-the-art methods, and further experiments on four real spatial transcriptomics datasets on different sequencing platforms show that the XVGAE could identify biologically meaningful spatial domains with smoother boundary than other methods.
Scenarios for the emergence of new miRNA genes in the plantArabidopsis halleri
Authors: Pavan Flavia , Lacoste Eléanore , Castric Vincent , Legrand Sylvain
Published: July 2024

MicroRNAs (miRNAs) are central players of the regulation of gene expression in Eukaryotes. The repertoires of miRNA genes vary drastically even among closely related species, indicating that they are evolutionarily labile. However, the processes by which they originate over the course of evolution and the nature of their progenitors across the genome remain poorly understood. Here we analyzed miRNA genes inArabidopsis halleri, a plant species where we recently documented a large number of species-specific miRNA genes, likely to represent recent events of emergence. Analysis of sequence homology across the genome indicates that a diversity of sources contributes to the emergence of new miRNA genes, including inverted duplications from protein-coding genes, rearrangements of transposable element sequences and duplications of preexisting miRNA genes. Our observations indicate that the origin from protein-coding genes was less common than was previously considered. In contrast, we estimate that almost half of the new miRNA genes likely emerged from transposable elements. Miniature inverted transposable elements (MITE) seem to be particularly important contributors to new miRNA genes, with the Harbinger and Mariner transposable element superfamilies representing disproportionate sources for their emergence. We further analyzed the recent expansion of a miRNA family derived from MuDR elements, and the duplication of miRNA genes formed by two hAT transposons. Overall, our results illustrate the rapid pace at which new regulatory elements can arise from the modification of preexisting sequences in a genome, and highlight the central role of certain categories of transposable elements in this process.
NPMc+ and Flt3-ITD cooperation promotes a new oncogenic HSC state that supports transformation and leukemia stem cell maintenance
Authors: Colombo Emanuela
Published: July 2024

NPMc+ and FLT3-ITD are the most frequently co-occurring mutations in Acute Myeloid Leukemia (AML). Cellular and molecular mechanisms of their cooperation are largely unknown. We investigated their effects on pre-leukemic and leukemic hematopoietic stem cells (HSCs) in mouse models that recapitulate the human disease. Both oncogenes increase proliferation of pre-leukemia HSCs, however, only NPMc+ extends self-renewal, by preventing depletion of quiescent HSCs. Quiescent HSCs include dormant and active HSCs, which are dynamic and alternative phenotypic states supporting, respectively, self-renewal and regenerative haematopoiesis. Analyses of the dormant and active transcriptional programs showed that NPMc+ stimulates the dormant-to-active transition but also enforces dormancy, thus allowing dormant HSCs to be replenished. Co-expression of NPMc+ and Flt3-ITD induces a new phenotypic state of quiescent HSCs whereby dormancy and activity co-exist at single-cell level. This new state likely supports in vivo proliferation of self-renewing HSCs and rapid selection of leukemia initiating cells. Pharmacological inhibition of the TGFb cell-dormancy pathway reduces self-renewal of leukemia SCs and prolongs mouse survival allowing to conclude that enforcement of HSC dormancy is a critical determinant of unrestricted self-renewal during leukemia development and represents a target for novel anti-leukemic strategies.
The role of dietary patterns in the polarization of angiogenic uterine Natural Killer cells during murine pregnancy
Authors: Salles Evila Lopes , Zavan Bruno , Marcelino Rodolfo Cabral , Chagas Pablo Shimaoka , do Amarante-Paffaro Andrea Mollica , Woodham Padmashree Chaudhury , Baban Babak , Paffaro Junior Valdemar Antonio
Published: July 2024

Uterine Natural Killer (uNK) cells, predominant leukocytes in mouse and human pregnant uteruses, play crucial roles in angiogenesis and pregnancy protection. In mice, DBA lectin-reactive uNK cells expressing Gal-N-Ac sugar exhibit angiogenic functions essential for pregnancy maintenance. This study compares the impact of different nutritional imbalances on mouse pregnancy and the activation of angiogenic DBA+ uNK cells to safeguard against pregnancy complications. High Fat (HF), High Carbohydrate (HC), High Protein (HP), and Food Restriction (FR) diets were administered from gestation day (GD) 1 to GD10 or until parturition. HF and HC diets led to reduced expression of DBA-identified N-acetyl-D-galactosamine, akin to LPS-induced inflammation, and decreased uNK perforin levels. Additionally, HF and HC diets resulted in elevated endometrial cleaved caspase-3 and decreased smooth muscle alpha-actin, causing blood vessel wall thinning without jeopardizing pregnancy term. FR impaired uNK differentiation, manifesting as an “all-or-none” phenomenon with 50% pregnancy failure. Our findings highlight the intricate relationship between nutritional imbalances and mouse pregnancy outcomes. Notably, high-fat diets elicited pronounced responses from DBA+ uNK cells, while high-protein diets had relatively weaker effects. This study underscores the importance of comprehending uNK cell dynamics in maintaining pregnancy homeostasis under diverse dietary conditions, paving the way for elucidating molecular mechanisms governing these interactions. By shedding light on these complex relationships, this research offers valuable insights for improving maternal and fetal health in the context of nutritional interventions during pregnancy.
The axillary lymphoid organ - an external, experimentally accessible immune organ in the zebrafish
Authors: Castranova Daniel , Kenton Madeleine I. , Kraus Aurora , Dell Christopher W. , Park Jong S. , Galanternik Marina Venero , Park Gilseung , Lumbantobing Daniel N. , Dye Louis , Marvel Miranda , Iben James , Taimatsu Kiyohito , Pham Van , Willms Reegan J. , Blevens Lucas , Robertson Tanner F. , Hou Yiran , Huttenlocher Anna , Foley Edan , Parenti Lynne R. , Frazer J. Kimble , Narayan Kedar , Weinstein Brant M.
Published: July 2024

Lymph nodes and other secondary lymphoid organs play critical roles in immune surveillance and immune activation in mammals, but the deep internal locations of these organs make it challenging to image and study them in living animals. Here, we describe a previously uncharacterized external immune organ in the zebrafish ideally suited for studying immune cell dynamicsin vivo, the axillary lymphoid organ (ALO). This small, translucent organ has an outer cortex teeming with immune cells, an inner medulla with a mesh-like network of fibroblastic reticular cells along which immune cells migrate, and a network of lymphatic vessels draining to a large adjacent lymph sac. Noninvasive high-resolution imaging of transgenically marked immune cells can be carried out in the lobes of living animals, and the ALO is readily accessible to external treatment. This newly discovered tissue provides a superb model for dynamic live imaging of immune cells and their interaction with pathogens and surrounding tissues, including blood and lymphatic vessels.

Teaser

A newly characterized external zebrafish lymphoid organ provides a powerful model for live imaging of immune cell dynamics