bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bacteria of the order Burkholderiales are original environmental hosts of type II trimethoprim resistance genes (dfrB)
Authors: Kneis David , Tskhay Faina , de la Cruz Barron Magali , Berendonk Thomas U 
Published: December 2024

Abstract
It is consensus that clinically relevant antibiotic resistance genes have their origin in environmental bacteria, including the large pool of primarily benign species. Yet, for the vast majority of acquired antibiotic resistance genes, the original environmental host(s) has not been identified to date. Closing this knowledge gap could improve our understanding of how antimicrobial resistance proliferates in the bacterial domain and shed light on the crucial step of initial resistance gene mobilization in particular. Here, we combine information from publicly available long- and short-read environmental metagenomes as well as whole-genome sequences to identify the original environmental hosts of dfrB, a family of genes conferring resistance to trimethoprim. Although this gene family stands in the shadow of the more widespread, structurally different dfrA, it has recently gained attention through the discovery of several new members. Based on the genetic context of dfrB observed in long-read metagenomes, we predicted bacteria of the order Burkholderiales to function as original environmental hosts of the predominant gene variants in both soil and freshwater. The predictions were independently confirmed by whole-genome datasets and statistical correlations between dfrB abundance and taxonomic composition of environmental bacterial communities. Our study suggests that Burkholderiales in general and the family Comamonadaceae in particular represent environmental origins of dfrB genes, some of which now contribute to the acquired resistome of facultative pathogens. We propose that our workflow centered on long-read environmental metagenomes allows for the identification of the original hosts of further clinically relevant antibiotic resistance genes.
Effectiveness of work-based educational interventions for antimicrobial stewardship: a systematic review
Authors: Langdridge Darren , Virhia Jennika , McMullan Rachel , Banks Duncan , Biard Olivier , Charitonos Koula , Alunyo Jimmy Patrick , Kagoya Enid Kawala , Olupot-Olupot Peter 
Published: December 2024

Abstract

Background
The pressing need for better antimicrobial stewardship (AMS) is invariably reliant on educational interventions in some form.

Objectives
To evaluate the effectiveness of post-qualification educational interventions for AMS behaviour change among health professionals.

Methods
Seven databases were searched for articles published between 2013 and 2024 for post-qualification educational interventions aimed at health professionals to improve AMS. Randomised controlled trials (RCTs) and quasi-experimental designs such as non-randomised trials, controlled and non-controlled before and after studies, and qualitative studies were considered eligible. The quality of studies was assessed using Cochrane Effective Practice and Organization of Care (EPOC) criteria for RCTs and interrupted time series designs, and the Mixed Methods Appraisal Tool (MMAT) for all other studies. Data were extracted, analysed for effectiveness, and synthesised narratively. Registration: PROSPERO international prospective register of systematic reviews (PROSPERO 2023 CRD42023447115).

Results
Forty-six studies were included in the review, with six meeting the EPOC criteria. The remaining forty were assessed using the MMAT. The overall risk of bias for the six studies meeting the EPOC criteria was low, but risk of bias was high for studies assessed using the MMAT. Overall, there was some evidence that formal education alone was effective in this context, but only limited evidence about what type of educational intervention, for which profession, is most effective.

Conclusions
Our review provided an in-depth examination of post-qualification AMS interventions. We found studies were heterogeneous and quality of evidence relatively poor. High quality studies focused on establishing key components of effective educational interventions are required.
Toward an artificial intelligence code of conduct for health and healthcare: implications for the biomedical informatics community
Authors: Payne Philip R O , Johnson Kevin B , Maddox Thomas M , Embi Peter J , Mandl Kenneth D , McGraw Deven , Saria Suchi , Adams Laura 
Published: December 2024

Abstract

Introduction
The rapid advancement of artificial intelligence (AI) has led to significant transformations in health and healthcare. As AI technologies continue to evolve, there is an urgent need to establish a unified framework that guides the design, implementation, and evaluation of AI-driven interventions across individual and population health contexts.

Approach
In response to this need, the National Academy of Medicine (NAM) has initiated the development of an AI code of conduct (AICC) through its Digital Health Action Collaborative. This code of conduct is grounded in shared principles and commitments, aiming to actualize ethical and effective AI practices within the broader health and healthcare ecosystem. Given its specialized expertise and insight, the biomedical informatics (BMI) community plays a pivotal role in shaping and applying these guidelines.

Recommendations
We, as members of the AICC Steering Committee and the NAM Digital Health Action Collaborative, urge BMI educators, researchers, and practitioners to engage actively in refining and implementing the AICC. This involvement is critical to ensuring that the code is robust, applicable, and continuously improved to meet the evolving challenges facing health and healthcare.
Development, deployment, and continuous monitoring of a machine learning model to predict respiratory failure in critically ill patients
Authors: Lam Jonathan Y , Lu Xiaolei , Shashikumar Supreeth P , Lee Ye Sel , Miller Michael , Pour Hayden , Boussina Aaron E , Pearce Alex K , Malhotra Atul , Nemati Shamim 
Published: December 2024

Abstract

Objectives
This study describes the development and deployment of a machine learning (ML) model called Vent.io to predict mechanical ventilation (MV).

Materials and Methods
We trained Vent.io using electronic health record data of adult patients admitted to the intensive care units (ICUs) of the University of California San Diego (UCSD) Health System. We prospectively deployed Vent.io using a real-time platform at UCSD and evaluated the performance of Vent.io for a 1-month period in silent mode and on the MIMIC-IV dataset. As part of deployment, we included a Predetermined Changed Control Plan (PCCP) for continuous model monitoring that triggers model fine-tuning if performance drops below a specified area under the receiver operating curve (AUC) threshold of 0.85.

Results
The Vent.io model had a median AUC of 0.897 (IQR: 0.892-0.904) with specificity of 0.81 (IQR: 0.812-0.841) and positive predictive value (PPV) of 0.174 (IQR: 0.148-0.176) at a fixed sensitivity of 0.6 during 10-fold cross validation and an AUC of 0.908, sensitivity of 0.632, specificity of 0.849, and PPV of 0.235 during prospective deployment. Vent.io had an AUC of 0.73 on the MIMIC-IV dataset, triggering model fine-tuning per the PCCP as the AUC was below the minimum of 0.85. The fine-tuned Vent.io model achieved an AUC of 0.873.

Discussion
Deterioration of model performance is a significant challenge when deploying ML models prospectively or at different sites. Implementation of a PCCP can help models adapt to new patterns in data and maintain generalizability.

Conclusion
Vent.io is a generalizable ML model that has the potential to improve patient care and resource allocation for ICU patients with need for MV.
A dynamic customized electronic health record rule based clinical decision support tool for standardized adult intensive care metrics
Authors: Cucchi Eric W , Burzynski Joseph , Marshall Nicholas , Greenberg Bruce 
Published: December 2024

Abstract

Objectives
Many routine patient care items should be reviewed at least daily for intensive care unit (ICU) patients. These items are often incompletely performed, and dynamic clinical decision support tools (CDSTs) may improve attention to these daily items. We sought to evaluate the accuracy of institutionalized electronic health record (EHR) based custom dynamic CDST to support 22 ICU rounding quality metrics across 7 categories (hypoglycemia, venothromboembolism prophylaxis, stress ulcer prophylaxis, mechanical ventilation, sedation, nutrition, and catheter removal).

Design
The dynamic CDST evaluates patient characteristics and patient orders, then identifies gaps between active interventions and conditions with recommendations of evidence based clinical practice guidelines across 22 areas of care for each patient. The results of the tool prompt clinicians to address any identified care gaps. We completed a confusion matrix to assess the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of the dynamic CDST and the individual metrics.

Setting
Tertiary academic medical center and community hospital ICUs.

Subject
Customized Clinical Decision Support Tool.

Measurements and Main Results
The metrics were evaluated 1421 times over 484 patients. The overall accuracy of the entire dynamic CDST is 0.979 with a sensitivity of 0.979, specificity of 0.978, PPV 0.969, and NPV 0.986.

Conclusions
A customized, EHR based dynamic CDST can be highly accurate. Integrating a comprehensive dynamic CDST into existing workflows could improve attention and actions related to routine ICU quality metrics.
Development of an indigestible dietary protein index to investigate the effects of dietary protein content in postweaned pigs
Authors: de Oliveira Marllon J K , Babatunde Olufemi O , Rodrigues Lucas A , Erinle Taiwo J , Htoo John K , Mendoza S Maria , Columbus Daniel A 
Published: December 2024

Abstract
Proteolytic fermentation induces negative effects on gut health and function, which may affect pig performance. The objective was to conduct a meta-analysis to develop an index of dietary indigestible dietary protein (IDP) to investigate growth performance outcomes of mixed-sex weanling pigs (average body weight of 7.59 kg). Eighty-nine articles reporting growth performance variables [average daily gain (ADG), average daily feed intake (ADFI), gain:feed ratio (GF), initial (IBW), and final body weight] in pigs fed different dietary protein (DP) content (from 12% to 33.6%) and protein sources (plant and animal) were included. DP and IDP index was calculated in all experiments using a common database, with the IDP index defined as the difference between total DP and standardized ileal digestible DP. A DP- and an IDP-based model were developed to predict the ADG, GF, and ADFI (by their relationship) of weaning pigs using a multivariable linear mixed model regression approach with estimates of variable effects obtained using the residual maximum likelihood method. Based on a stepwise manual forward selection, significant predictor variables with improvement of at least 2 points in the Bayesian information criterion were included in the final regression model. Statistical significance was set at P ≤ 0.05 and a trend at P &lt; 0.10. Initial exploratory analysis of the database showed a quadratic increase (P &lt; 0.01) in the IDP index with increasing inclusion of plant protein sources in diet formulation and a linear decrease (P &lt; 0.01) in the IDP index with increasing synthetic amino acid inclusion. Regarding the models, the DP-based model could not account for the inclusion of protein sources compared to the IDP-based model. There was a tendency for DP to positively affect (P &lt; 0.10) ADG and GF. Increasing the IDP index tended to negatively impact (P &lt; 0.10) ADG while reducing (P &lt; 0.05) ADFI. Using a practical and hypothetical feed formulation simulation, the final regression models predicted the expected negative impact of a high IDP index on newly weaned pig performance when compared to a low IDP diet. The IDP-based model predicted a stronger negative effect of high IDP when compared to the DP-based model. Results indicate that IDP may be an improved and more reliable index to investigate the impact of DP on pig performance in the postweaning phase.
Commentary for: a lipid scramblase TMEM41B is involved in the processing and transport of GPI-anchored proteins
Authors: Hirayama Hiroto 
Published: December 2024

Abstract
Glycosylphosphatidylinositol (GPI) anchoring is a conserved post-translational modification in eukaryotes. This modification allows acceptor proteins to be expressed at the cell surface as GPI-anchored proteins (GPI-APs), which play critical roles in various biological processes. It has been proposed that remodelling of GPI after transferring acceptor proteins, including the PGAP1-dependent deacylation of GPI-inositol, functions as a checkpoint for transporting mature GPI-APs from the endoplasmic reticulum (ER) to the Golgi. A previous study identified several factors involved in regulating PGAP1-dependent GPI-inositol deacylation, including proteins associated with the calnexin cycles, SELT and CLPTM1. A recent report by Cao et al., revealed that the loss of TMEM41B, an ER-resident lipid scramblase, rescues the defect in GPI-inositol deacylation in SELT-KO cells. Further investigation demonstrated that TMEM41B is essential for the efficient transport of both GPI-APs and transmembrane proteins from the ER to the Golgi. The study also found that PGAP1 proteins accumulate in the ER of TMEM41B-KO cells, suggesting that perturbations in the ER-membrane lipid integrity stabilize PGAP1 proteins, thereby enhancing the PGAP1 activity within the ER. These findings highlight that defects in TMEM41B impact two distinct processes: (i) the transport of GPI-APs from the ER to the Golgi, and (ii) the deacylation of GPI-APs.
An activating calcium-sensing receptor variant with biased signaling reveals a critical residue for Gα11 coupling
Authors: Benson Matthew R , Wyatt Rachael A , Levine Michael A , Gorvin Caroline M 
Published: December 2024

Abstract
Autosomal dominant hypocalcemia (ADH) is due to enhanced calcium-dependent signaling caused by heterozygous gain-of-function (GOF) variants in the CASR gene (ADH1) or in the GNA11 gene, encoding Gα11 (ADH2). Both ADH1 and ADH2 are associated with hypocalcemia and normal or inappropriately low levels of circulating PTH. ADH1 patients typically manifest hypercalciuria, while ADH2 is associated with short stature in approximately 42% of cases. We evaluated a 10-yr-old boy with hypoparathyroidism and short stature. Biochemical analyses revealed hypocalcemia, hyperphosphatemia, and inconsistent hypercalciuria. Genetic analyses revealed a de novo heterozygous p.Leu723Arg variant in CASR. We characterized the expression of recombinant WT and Leu723Arg calcium-sensing receptor (CaSR) proteins in HEK293 cells and assessed G protein activation in vitro by CaSR using bioluminescence resonance energy transfer. Transient expression studies showed the Leu723Arg variant was normally expressed but resulted in a significantly lower EC50 for extracellular calcium activation of G11 but not other G proteins (ie, Gi, Gq, Gs). The Leu723Arg substitution has a novel GOF phenotype that leads to biased CaSR activation of G11 signaling, suggesting that residue 723 specifies activation of G11 but not other G proteins. Similar studies of a previously described CaSR variant associated with hypoparathyroidism and short stature, Leu616Val, showed no changes in any G protein pathways, indicating it is likely to be a benign variant. Given the preferential activation of G11 by the Leu723Arg CaSR variant, we propose that the patient’s short stature shares a similar basis to that in patients with ADH2 due to GOF variants in GNA11.
Cardiovascular outcomes of romosozumab treatment—real-world data analysis
Authors: Tsur Anat , Cahn Avivit , Levy Ludmila , Pollack Rena 
Published: December 2024

Abstract
Romosozumab is a potent treatment for osteoporosis, with significant effects on bone density and fracture prevention. This study evaluated the cardiovascular safety of romosozumab in a real-world cohort of postmenopausal women at high fracture risk. We retrospectively evaluated postmenopausal women who initiated treatment with romosozumab between January 1, 2020, and June 30, 2023. We examined the occurrence of a major adverse cardiovascular event (MACE) across two distinct segments during the treatment period and after its conclusion. After applying inclusion and exclusion criteria, 847 women were followed for a median of 729 days (IQR: 445-1060). The incidence rate of MACE was 24.0 (95% CI 17.7-32.5) per 1000 person-years during the study period. The change in the rate of MACE from 0-90 days and 90-365 days post-treatment initiation was 0.04 and 0.06 events per 1000 days, respectively. The difference in the rate between these intervals was not statistically significant (p = .09). After 1 yr of treatment, the slope of MACE increased to 0.10, differing significantly from the preceding 12 mo on treatment (p&lt;.001). The incidence of MACE was higher in those with a background of previous cardiovascular disease or diabetes at all timepoints, as expected. The consistency in event rates during treatment suggests that romosozumab is not associated with an increase in MACE in postmenopausal women. This finding challenges reports suggesting an increase in cardiovascular events within the first year of romosozumab treatment.
A novel method for long-term ventilation recording of prawns and shrimps (Decapoda: Dendrobranchiata, Caridea) across molting cycle
Authors: Xie Jia-Min , Tsai Meng-Li , Chen Tsen-Chien , Wu Wen-Yi 
Published: December 2024

Abstract
We developed a novel method for real-time recording of scaphognathite pumping in prawns using a 27-gauge, stainless-steel injection needle bent at three right angles as a recording electrode. This electrode was implanted into the inner side of the carapace at the anterior end of the gill chamber. During pumping, the small frictional contact between the scaphognathite and the electrode generated electrical signals that served as indicators of scaphognathite activity. The electrical signals accurately differentiated between forward and reverse pumping and the various scaphognathite pumping patterns reported in the literature. The electrode and the wire did not interfere with the prawns’ movements or molting, enabling prolonged recording periods, including across molting cycles.
Development of a panel of SNP loci in the emblematic southern damselfly (Coenagrion mercuriale) using a hybrid method: pitfalls and recommendations for large-scale SNP genotyping in a nonmodel endangered species
Authors: Lévêque Agathe , Arnaud Jean-François , Vignon Vincent , Mazoyer Clément , Godé Cécile , Duputié Anne 
Published: December 2024

Abstract
Genomic markers are essential tools for studying species of conservation concern, yet nonmodel species often lack a reference genome. Here we describe a methodology for identifying and genotyping thousands of SNP loci in the southern damselfly (Coenagrion mercuriale), a bioindicator of freshwater stream quality classified as near-threatened, with locally declining populations. We used a hybrid approach combining reduced representation sequencing and target enrichment. First, we identified putative SNP loci using ddRADseq and de novo assembly. Then, single primer enrichment technology targeted 6000 of these SNPs across 1920 individuals. Challenges encountered included sequence recapture failure, coverage depth discrepancies, and aberrant FIS values. We provide recommendations to address such issues. After multiple filtering steps, 2092 SNPs were retained and used to analyze the genetic structure of 131 individuals belonging to 11 populations in France, comparing central and marginal populations. Genetic differentiation was lower among central populations, with no sign of inbreeding. As compared with microsatellite loci, SNPs exhibited greater resolution in detecting fine-scaled genetic structure, and identifying putative hybrids in adjacent populations. In this study, we emphasize the difficulties of large-scale SNP genotyping in nonmodel species via a hybrid method that ultimately did not offer the expected cost and time-saving compared with classical ddRAD approaches. However, SNPs showed greater power than previously available markers in identifying conservation units or admixture events, and the panel of reusable probes we describe here offers the potential to improve conservation efforts through future diachronic studies or finer estimations of key parameters like effective population size.
“Covering For Our City Blight”: Kudzu and Public Health in Atlanta, 1979-1994
Authors: Reilly Kenneth 
Published: December 2024

Abstract
Kudzu, a perennial climbing vine and invasive species to the American South, occupied a unique space in the city of Atlanta, Georgia as a danger to public health from the late 1970s to the early 1990s. This article examines why municipal authorities understood the vine as a threat to public health. Kudzu’s ability to smother surfaces allowed it to conceal murdered people and serve as a habitat for rats, snakes, and mosquitos, making it a direct threat to public safety in the eyes of public health authorities. Kudzu also grew extensively in vacant lots where city officials were trying to promote the city as progressive and prosperous. The city council voted in support of an ordinance against extensive growths of the vine, but eradication produced its own challenges: kudzu removal was expensive, and permanent eradication required large investments in time. Unhoused people also relied on the vine for shelter, which meant that eradication directly affected their safety. Examining how municipal authorities framed kudzu as a threat to public health, this article demonstrates that the vine’s status as a health risk lay in how it unintentionally clashed with the promoted image of Atlanta as a business-friendly city with harmonious relationships among its citizens.