bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological mechanisms of tuberculosis susceptibility in TB-infected individuals with type 2 diabetes mellitus: insights from mycobacterial growth inhibition assay and cytokine analysis
Authors: Dasan Bindu , Rajamanickam Anuradha , Pandiarajan Arul Nancy , Shanmugam Sivakumar , Nott Sujatha , Babu Subash 
Published: December 2024

ABSTRACT

Several studies have highlighted the increased risk of active tuberculosis (TB) in individuals with diabetes mellitus (DM), especially in TB-endemic regions. This dual burden poses significant challenges for TB control efforts. However, there is a lack of reliable laboratory tools to identify individuals at higher risk, and the immunological mechanisms underlying this susceptibility are poorly understood. In this study, we utilized the mycobacterial growth inhibition assay (MGIA) to assess immune response capacity against
Mycobacterium tuberculosis
(
M.tb
) in TB infection (TBI) in individuals with type 2 DM (T2DM) (
n
= 11) compared to those without type 2 DM (NDM) (
n
= 23). Additionally, we measured various cytokines using multiplex ELISA to understand the immune profile. Our findings revealed that TBI-T2DM individuals exhibited a lower capacity to inhibit
M.tb
growth compared to TBI-NDM, as evidenced by MGIA results (
P
= 0.0029). Cytokine analysis further demonstrated diminished production of key cytokines involved in protection, including type 1 (IFNγ, TNFα, IL-2), type 17 (IL-17A), and proinflammatory (IL-1α, IL-1β, IL-6, IL-12p70) cytokines in the TBI-T2DM group compared to TBI-NDM, upon
M.tb
infection. These findings suggest that MGIA holds promise as an
in vitro
marker for assessing
M.tb
immunological control in TBI individuals, particularly those with T2DM. The observed cytokine profile in TBI-T2DM individuals indicates a compromised immune response against
M.tb
activation, potentially explaining the heightened risk of active TB in this population.

IMPORTANCE
This study is important because it sheds light on the impaired immune response in individuals with type 2 diabetes mellitus (T2DM) who are infected with Mycobacterium tuberculosis (M.tb), offering critical insights into why they are at higher risk of developing active tuberculosis (TB). By demonstrating that T2DM individuals exhibit a weakened ability to control M.tb growth and a compromised cytokine profile, the research underscores the need for better diagnostic tools, such as the mycobacterial growth inhibition assay (MGIA), to identify those at greater risk of progression to active TB. The findings also highlight the importance of integrated care strategies for managing both T2DM and TB, particularly in TB-endemic regions, and point to the need for further research to develop more effective interventions tailored to this vulnerable population.
Using genomics to explore the epidemiology of vancomycin resistance in a sewage system
Authors: Jensen Emilie Egholm Bruun , Otani Saria , Liachko Ivan , Auch Benjamin , Aarestrup Frank M. 
Published: December 2024

ABSTRACT

VanHAX
-mediated glycopeptide resistance has been consistently high in one of the three main sewer systems in Copenhagen, Lynetten, for +20 years. To explore this for other glycopeptide resistance genes, and whether the colonization has resulted in establishment of multiple bacterial taxa, we mapped 505 shotgun metagenomic data sets from the inlet of three sewage treatment plants to 831 different glycopeptide resistance genes. Only
vanHAX
and
vanHBX
genes were differentially abundant in Lynetten. Analyses of eight contigs suggested limited variations in the flanking regions. Proximity ligation metagenomic analysis of 12 samples from Lynetten identified 441 and 5 paired reads mapping to
vanHAX
and
vanHBX
, respectively. The other end of these reads was mapped to generated metagenomic-assembled genomes and NCBI using BLAST.
vanHBX
could only be linked to the phylum level (Bacillota). Plasmid analysis of
vanHBX
Hi-C contigs showed that these were mainly located on plasmids reported found in enterococci species. Most
vanHAX
-linked reads could only be linked to phylum and class level, but some reads were assigned to
Enterococcus faecium
(7 reads),
Enterococcus faecalis
(4 reads),
Paenibacillus apiarius
(2 reads), and
Paenibacillus thiaminolyticus
(27 reads). Ten of the 20 Hi-C contigs-containing
vanHAX
were annotated as plasmid, all reported found in
Enterococcus
species. This study shows that while Hi-C technology is valuable for linking antimicrobial resistance genes to bacterial taxa, it suffers from challenges in reliably mapping the linked read to a genomic region with sufficient taxonomic information. Our results also suggest that over the +20 years of colonizing a sewer system,
vanHAX
has not become widespread across multiple taxa, remaining primarily in
E. faecalis
and
E. faecium
, with the exception of
Paenibacillus
.

IMPORTANCE

Long-term colonization of microbial communities with antimicrobial-resistant bacteria is expected to result in sharing of the resistance genes between several different bacterial taxa of the communities. We investigated microbiomes from a sewer, which have been colonized with glycopeptide-resistant bacteria harboring the mobile
vanHAX
gene cluster for a minimum of 20 years, using metagenomics sequencing and Hi-C. We found that despite the long-term presence in the sewer, the
vanHAX
genes have seemingly not disseminated widely.
Characterization of YdgH: a mediator of beta-lactam susceptibility in Enterobacterales
Authors: Lazarus Jacob E. , Waldor Matthew K. , Hooper David C. 
Published: December 2024

ABSTRACT

Beta-lactam antibiotics are often the treatment of choice for serious bacterial infections. In a previous screen for novel genetic mediators affecting beta-lactam susceptibility, we discovered that deletion of
ydgH
, a conserved gene of unknown function, leads to increased resistance to beta-lactams, as well as increased susceptibility to detergent compounds. Here, we further characterize YdgH in
Serratia marcescens, Enterobacter cloacae
, and
Escherichia coli
using a combination of biochemical and cell biological approaches. We find that YdgH fractionates with periplasmic proteins, and this periplasmic localization is necessary for its function. Using purified recombinant protein, we demonstrate that YdgH is a relatively compact, globular monomer. The YdgH polypeptide contains three tandem DUF1471 domains. In a Δ
ydgH
background, overexpression of polypeptides containing both the second and the third, but not the first DUF1471 domain, is necessary to rescue the deletion phenotype. To determine how YdgH function influences beta-lactam and detergent susceptibility, we tested several targeted hypotheses. We found that deletion of
ydgH
neither affects
ompC
or
ompF
transcript levels
,
nor does it alter the processing of lipopolysaccharide, nor does it activate the sigma E regulon alone or in combination with mutations in other periplasmic proteins. Finally, we delineate the results of a genetic screen for spontaneous mutants that complement the detergent susceptibility phenotype, the results of which may fuel the further studies that are necessary to determine the precise role YdgH plays in bacterial physiology.

IMPORTANCE

Beta-lactams such as penicillins and cephalosporins are the most commonly prescribed antibiotics for serious bacterial infections. Increasing antibiotic resistance threatens their effectiveness. We previously identified the uncharacterized gene
ydgH
as a modifier of beta-lactam susceptibility in Gram-negative bacteria. To begin to understand the specific role of YdgH, in this study, we perform initial characterizations of this protein. We also test hypotheses as to how the function of YdgH contributes to beta-lactam physiology.
Utilizing deep learning-based causal inference to explore vancomycin’s impact on continuous kidney replacement therapy necessity in blood culture-positive intensive care unit patients
Authors: Kang Min Woo , Kang Yoonjin 
Published: December 2024

ABSTRACT

Patients with positive blood cultures in the intensive care unit (ICU) are at high risk for septic acute kidney injury requiring continuous kidney replacement therapy (CKRT), especially when treated with vancomycin. This study developed a machine learning model to predict CKRT and examined vancomycin’s impact using deep learning-based causal inference. We analyzed ICU patients with positive blood cultures, utilizing the Medical Information Mart for Intensive Care III data set. The primary outcome was defined as the initiation of CKRT during the ICU stay. The machine learning models were developed to predict the outcome. The deep learning-based causal inference model was utilized to quantitatively demonstrate the impact of vancomycin on the probability of CKRT initiation. Logistic regression was performed to analyze the relationship between the variables and the susceptibility of vancomycin. A total of 1,318 patients were included in the analysis, with 41 requiring CKRT. The Random Forest and Light Gradient Boosting Machine exhibited the best performance, with Area Under Curve of Receiver Operating Characteristic Curve values of 0.905 and 0.886, respectively. The deep learning-based causal inference model demonstrated an average 7.7% increase in the probability of CKRT occurrence when administrating vancomycin in total data set. Additionally, that younger age, lower diastolic blood pressure, higher heart rate, higher baseline creatinine, and lower bicarbonate levels sensitized the probability of CKRT application in response to vancomycin treatment. Deep learning-based causal inference models showed that vancomycin administration increases CKRT risk, identifying specific patient characteristics associated with higher susceptibility.

IMPORTANCE
This study assesses the impact of vancomycin on the risk of continuous kidney replacement therapy (CKRT) in intensive care unit (ICU) patients with blood culture-positive infections. Utilizing deep learning-based causal inference and machine learning models, the research quantifies how vancomycin administration increases CKRT risk by an average of 7.7%. Key variables influencing susceptibility include baseline creatinine, diastolic blood pressure, heart rate, and bicarbonate levels. These findings offer insights into managing vancomycin-induced kidney risk and may inform patient-specific treatment strategies in ICU settings.
How often do parents administer medications to their children in hospital? A prospective direct observational study
Authors: Westbrook Johanna I , Li Ling , Badgery-Parker Tim , Fitzpatrick Erin , Mumford Virginia , Merchant Alison , Raban Magdalena Z 
Published: December 2024

Parents and carers play a critical role in supporting their children while in hospital. Multiple qualitative studies have explored parental involvement in the care of hospitalised children. Administration of medication to young children can be difficult and cause anxiety and stress for children. Parents are often willing and able to assist, yet little is known about how often parents are given responsibility for medication administration in hospital.We analysed data from a prospective direct observational study of nurses administering medication at a major paediatric referral hospital in Australia. Data from observations of 298 nurses preparing and administering 5137 medication doses to children on nine medical and surgical wards between 07:00 and 22:00 were analysed. Details of drugs administered, whether medications were left for parents/carers to administer, and if nurses observed the administration by parents, were recorded.Parents were at their child’s bedside during 89.7% (n=4610) of observed medication administrations. Parents gave 20.3% (n=1045) of medications. In 14.3% (n=733), medications were left with parents to administer without a nurse present. In 6.1% (n=312) of doses, medications were given to parents, but the administration was observed by a nurse. Parents were most likely to be given medications to administer to young children (1–5 years), and the medications most frequently administered were analgesics and anti-epileptics.Parents/carers are integrally involved in the administration of many medications to children in hospital. The extent of parents’ role and the impact on medication administration efficiency has been largely absent from the healthcare literature. Given that one in five medication doses is administered by parents, hospitals should recognise this contribution and consider if any additional support for parents is required.
Acute hepatitis of unknown aetiology in children: evidence for and against causal relationships with SARS-CoV-2, HAdv and AAV2
Authors: Gurdasani Deepti , Trent Mallory , Ziauddeen Hisham , Mnatzaganian Emmanuel , Turville Stuart , Chen Xin , Kunasekaran Mohana Priya , Chughtai Abrar Ahmad , Moa Aye , McEniery Julie , Greenhalgh Trisha , MacIntyre Chandini Raina 
Published: December 2024

BackgroundThe cause of acute paediatric hepatitis of unknown aetiology (2022) has not been established despite extensive investigation.ObjectiveTo summarise the evidence for and against a causal role for human adenovirus (HAdv), adeno-associated virus 2 (AAV-2) and SARS-CoV-2 in outbreaks of paediatric hepatitis in 2022.MethodsWe appraised and summarised relevant evidence for each of the Bradford Hill criteria for causality using quantitative (statistical modelling) and qualitative (narrative coherence) approaches. Each team member scored the evidence base for each criterion separately for HAdv, AAV-2 and SARS-CoV-2; differences were resolved by discussion. We additionally examined criteria of strength and temporality by examining the lagged association between SARS-CoV-2 positivity, respiratory HAdv positivity, positive faecal HAdv specimens and excess A&E attendances in 1–4 years for liver conditions in England.ResultsAssessing criteria using the published literature and our modelling: for HAdv three Bradford Hill criteria (strength, consistency and temporality) were partially met; and five criteria (consistency, coherence, experimental manipulation, analogy and temporality) were minimally met. For AAV-2, the strength of association criterion was fully met, five criteria (consistency, temporality, specificity, biological gradient and plausibility) were partially met and three (coherence, analogy and experimental manipulation) were minimally met. For SARS-CoV-2, five criteria (strength of association, plausibility, temporality, coherence and analogy) were fully met; one (consistency) was partially met and three (specificity, biological gradient and experimental manipulation) were minimally met.ConclusionBased on the Bradford Hill criteria and modelling, HAdv alone is unlikely to be the cause of the recent increase in hepatitis in children. The causal link between SARS-CoV-2, and to a lesser degree AAV-2, appears substantially stronger but remains unproven. Hepatitis is a known complication of multisystem inflammatory syndrome in children following COVID-19, and SARS-CoV-2 has been linked to increased susceptibility to infection post-COVID-19, which may suggest complex causal pathways including a possible interaction with AAV-2 infection/reactivation in hosts that are genetically susceptible or sensitised to infection.
Prevalence of domestic violence against pregnant women living in rural areas: systematic review and meta-analysis
Authors: Sulaimanova Gulnura , Yamaoka Yui , Bardella Inis Jane , Fujiwara Takeo 
Published: December 2024

BackgroundMany studies have demonstrated that pregnant women living in rural areas are more likely to experience domestic violence (DV). Systematic reviews on the prevalence and risk factors of DV among pregnant women have been conducted mainly in urban areas. Thus, there has been no determination of the global prevalence of DV among rural pregnant women. The objective of this study is to assess the prevalence and types of DV among rural pregnant women globally using systematic review and meta-analysis.MethodsThe Preferred Reporting Items for Systematic Review and Meta-Analysis expanded checklist for 2020 was employed. The Condition-Context-Population framework was used to determine the inclusion criteria. Fifteen studies met the inclusion criteria. The PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature and Scopus databases were searched for published articles through January 2023. Pooled prevalence and types of DV in rural pregnant women were assessed using the random effect model.ResultsDV against rural pregnant women was prevalent at 33.4% (95% CI 20.8 to 47.9%). Psychological violence was the most common with a prevalence of 34.2%, followed by physical violence (14.1%) and sexual violence (13.5%).ConclusionOne-third of pregnant women in rural areas are victims of DV. In rural pregnant women, the prevalence of DV is higher than overall global estimates. Policymakers, healthcare professionals and researchers must prioritise assessment and prevention of DV against pregnant women who reside in rural areas.
Examining causal relationships between educational attainment and type 2 diabetes using genetic analysis: findings from the EPIC-InterAct study through Mendelian randomisation
Authors: Macciotta Alessandra , Sacerdote Carlotta , Giachino Claudia , Di Girolamo Chiara , Franco Matteo , van der Schouw Yvonne T , Zamora-Ros Raul , Weiderpass Elisabete , Domenighetti Cloé , Elbaz Alexis , Truong Thérèse , Agnoli Claudia , Bendinelli Benedetta , Panico Salvatore , Vineis Paolo , Christakoudi Sofia , Schulze Matthias B , Katzke Verena , Bajracharya Rashmita , Dahm Christina C , Dalton Susanne Oksbjerg , Colorado-Yohar Sandra M , Moreno-Iribas Conchi , Etxezarreta Pilar Amiano , Sanchez María José , Forouhi Nita G , Wareham Nicholas , Ricceri Fulvio 
Published: December 2024

IntroductionObservational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such a relationship is causal. This study used genetic instruments for education to estimate the effect of education on T2D using the Mendelian randomisation (MR) approach.MethodsAnalyses have been conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study (more than 20 000 individuals), a case-cohort study of T2D nested in the EPIC cohort. Education was measured as Years of Education and Relative Index of Inequality. Prentice-weighted Cox models were performed to estimate the association between education and T2D. One-sample MR analyses investigated whether genetic predisposition towards longer education was associated with risk of T2D and investigated potential mediators of the association.ResultsMR estimates indicated a risk reduction of about 15% for each year of longer education on the risk of developing T2D, confirming the protective role estimated by observational models (HR 0.96, 95% CI 0.95 to 0.96). MR analyses on putative mediators showed a significant role of education on body mass index, alcohol consumption, adherence to the Mediterranean diet and smoking habits.ConclusionThe results supported the hypothesis that higher education is a protective factor for the risk of developing T2D. Based on its position in the causal chain, education may be antecedent of other known risk factors for T2D including unhealthy behaviours. These findings reinforce evidence obtained through observational study designs and bridge the gap between correlation and causation.
Cost-related non-adherence to medications among adults with asthma in the USA, 2011–2022
Authors: Hung Chun-Tse , Erickson Steven R , Wu Chung-Hsuen 
Published: December 2024

Background
Uncontrolled asthma is possibly caused by medication non-adherence, and financial hardship can be a major contributor to non-adherence. Since economic conditions and asthma management have changed over time, a comprehensive investigation of cost-related medication non-adherence (CRN) among adults with asthma is crucial.

Objective
To evaluate trends, prevalence and determinants of CRN, and its impact on asthma control among US adults with asthma.

Methods
Data from 2011 to 2022 National Health Interview Survey were used. Joinpoint regression analysis was used to evaluate trends in the prevalence of CRN. A multivariable logistic regression model was used to identify factors associated with CRN. Two additional multivariable logistic regression models were used to examine associations between CRN and asthma-related adverse events, including asthma attacks and emergency room (ER) visits for asthma.

Results
A total of 30 793 adults with asthma were included, representing 8.1% (19.38 million) of the US population. From 2011 to 2022, a declining trend in the prevalence of CRN among US adults with asthma was observed. Approximately every one in six adults with asthma was non-adherent to medications due to cost. Several factors, including demographics and comorbidities, were associated with CRN. Adults with asthma who had CRN were at an increased risk of experiencing asthma attacks (adjusted OR, 1.95; 95% CI 1.78 to 2.13) and ER visits for asthma (adjusted OR, 1.63; 95% CI 1.44 to 1.84).

Conclusion
Since asthma is one of the leading chronic diseases, the burden of cost-related non-adherence to medications highlights the need for appropriate policies and social supports to address such problems.
On the photon mass generation in Rarita–Schwinger QED
Authors: Ghasemkhani M. , Soleimani G. , Soto A. , Bufalo R. 
Published: December 2024

Abstract
This work examines the dynamical mass generation for the photon in Rarita–Schwinger QED. We focus our attention on the cases of

$$\omega =2,3$$

ω
=
2
,
3

dimensional spacetime. In these frameworks, it is well known that in the usual QED, the photon field (dynamically) acquires a gauge invariant mass (the Schwinger and Chern–Simons mass, respectively). We wish to scrutinize this phenomenon in terms of the Rarita–Schwinger fields. The presence of higher-derivative terms is shown as the leading contributions to the 1PI function

$$\langle AA \rangle $$

⟨
A
A
⟩

at one-loop order. We study the pole structure of the photon’s complete propagator to unveil the main effects of the Rarita–Schwinger fields on the photon’s mass. In addition, we present some remarks about the renormalizability of this model (in different dimensions) due to the presence of higher-derivative corrections at one-loop.
Geometric Embeddability of Complexes is ∃ℝ-complete
Authors: Abrahamsen Mikkel , Kleist Linda , Miltzow Tillmann 
Published: December 2024

We show that the decision problem of determining whether a given (abstract simplicial)
k
-complex has a geometric embedding in ℝ
d
is complete for the Existential Theory of the Reals for all
d
≥ 3 and
k
∈ {
d
-1,
d
} by reducing from pseudoline stretchability. Consequently, the problem is polynomial time equivalent to determining whether a polynomial equation system has a real solution. Moreover, this implies NP-hardness and constitutes the first hardness result for the algorithmic problem of geometrically embedding (abstract simplicial) complexes. This complements recent breakthroughs for the computational complexity of piece-wise linear embeddability [Matoušek, Sedgwick, Tancer, and Wagner, J. ACM 2018, and de Mesmay, Rieck, Sedgwick and Tancer, J. ACM 2020] and establishes connections to computational topology.