bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of supplementary private health insurance on out-of-pocket inpatient medical expenditure: evidence from Malaysia
Authors: Ng Rui Jie , Choo Wan Yuen , Ng Chiu-Wan , Hairi Noran Naqiah 
Published: February 2024

Abstract
The vital role of healthcare financing in achieving universal health coverage is indisputable. However, most countries, including Malaysia, face challenges in establishing an equitable and sustainable healthcare financing system due to escalating healthcare costs, an ageing population and a growing disease burden. With desirable pre-payment and risk pooling features, private health insurance (PHI) is considered an alternative financing option to reduce out-of-pocket (OOP) medical expenditure. However, ongoing theoretical and empirical debates persist regarding the adequacy of financial risk protection provided by PHI largely because it depends on its role, the benefit design and the regulations in place. Our study aimed to investigate the effect of supplementary PHI on OOP inpatient medical expenditure in Malaysia. Secondary data analysis was conducted using the Malaysian National Health and Morbidity Survey 2019 dataset. A total of 983 respondents with a history of inpatient hospitalization in the past 12 months were included in the study. Instrumental variable analysis using a two-stage residual inclusion was performed to address endogeneity bias, with wealth status and education level as the instrumental variables. Tobit regression model was used in the second stage considering the censored distribution of the outcome variable. Missing data were handled using multiple imputation. About one-fifth of the respondents had PHI. In this study, we found that having PHI significantly increased OOP inpatient medical expenditure in all three marginal effects. Additionally, age, residential location, ethnicity (citizenship), being covered by government guarantee letter, government funding and employer-sponsored health insurance were other significant factors associated with OOP inpatient medical expenditure. Our findings undermine a key justification to advocate PHI uptake among the population, with a need for the Malaysian government to reassess the role of PHI in healthcare financing and reconsider PHI subsidization policy. Regulations should also be strengthened to enhance the financial risk protection provided by PHI.
Lessons from the coronavirus pandemic: a review of how the disease spreads in indoor spaces
Authors: Abdin Taqui Ahmed Reda , Mahmoud Ayman Hassaan Ahmed 
Published: February 2024

Abstract
In the post-coronavirus era, it is important to understand how infections spread in the indoor environment. The modes of transmission that are of interest to this research are droplet-borne and airborne transmission. In these transmission cases, there is a dependency on air to transport pathogens. The buoyancy of pathogens depends on the mass of the particles or droplets, volume of the indoor space and air velocity. Understanding this is key to reaching a sound methodology for control. The case studies consist of two main groups: the first group is research based published prior to the onset of the pandemic, and the second group is based on studies of actual infection cases subsequent to the onset of the pandemic. When examining the cases, it is apparent that the three main factors that are constantly recurrent are population density, airflow rate and air recirculation. In a lot of cases, air stagnation and lack of air change are conclusive causative factors of infection transmission, while in a couple of cases, it was shown that infective agents can travel more than 3 m, another factor to be taken into consideration. When there is a total lack of airflow and air change, population density becomes the main causative factor. This research presents a set of guidelines for the ventilation of spaces in different types of indoor environment through exploring the role of the built environment in the transmission of infection and how building design can effect change on public health.
Safety, Tolerability, and Immunogenicity of an mRNA-Based Respiratory Syncytial Virus Vaccine in Healthy Young Adults in a Phase 1 Clinical Trial
Authors: Shaw Christine A , Mithani Runa , Kapoor Archana , Dhar Rakesh , Wilson Lauren , El Asmar Laila , Schnyder-Ghamloush Sabine , Schaefers Kristi , August Allison , Stoszek Sonia K , Chen Grace L 
Published: February 2024

Abstract

Background
Respiratory syncytial virus (RSV) presents a global health concern. A lipid nanoparticle–encapsulated mRNA-based RSV vaccine (mRNA-1345) that encodes the membrane-anchored RSV prefusion–stabilized F glycoprotein is under clinical investigation.

Methods
This phase 1 dose escalation study was based on a randomized, observer-blind, placebo-controlled design, and it assessed the safety and immunogenicity of mRNA-1345 in healthy adults aged 18 to 49 years. Participants were randomized to receive 1 dose of mRNA-1345 (50, 100, or 200 µg) or placebo or 3 doses of mRNA-1345 (100 µg) or placebo 56 days apart.

Results
mRNA-1345 was well tolerated at all dose levels. The most common solicited adverse reactions were pain, headache, fatigue, myalgia, or chills, which were all generally mild to moderate. At 1 month postinjection, a single injection of mRNA-1345 boosted RSV neutralizing antibody titers (geometric mean fold rise: RSV-A, 20.0–23.5; RSV-B, 11.7–16.0) and RSV prefusion binding antibody concentrations (geometric mean fold rise, 16.1–21.8), with no apparent dose response. Antibody levels remained above baseline through 6 months. Sequential doses of 100 µg were well tolerated but did not further boost antibody levels.

Conclusions
A single mRNA-1345 injection demonstrated an acceptable safety profile in younger adults and induced a durable neutralizing antibody response, supporting its continued development.

Clinical Trials Registration
ClinicalTrials.gov NCT04528719.
Minimal Impact on the Resistome of Children in Botswana After Azithromycin Treatment for Acute Severe Diarrheal Disease
Authors: Guitor Allison K , Katyukhina Anna , Mokomane Margaret , Lechiile Kwana , Goldfarb David M , Wright Gerard D , McArthur Andrew G , Pernica Jeffrey M 
Published: February 2024

Abstract

Background
Macrolide antibiotics, including azithromycin, can reduce under 5 years of age mortality rates and treat various infections in children in sub-Saharan Africa. These exposures, however, can select for antibiotic-resistant bacteria in the gut microbiota.

Methods
Our previous randomized controlled trial (RCT) of a rapid-test-and-treat strategy for severe acute diarrheal disease in children in Botswana included an intervention (3-day azithromycin dose) group and a control group that received supportive treatment. In this prospective matched cohort study using stools collected at baseline and 60 days after treatment from RCT participants, the collection of antibiotic resistance genes or resistome was compared between groups.

Results
Certain macrolide resistance genes increased in prevalence by 13%–55% at 60 days, without differences in gene presence between the intervention and control groups. These genes were linked to tetracycline resistance genes and mobile genetic elements.

Conclusions
Azithromycin treatment for bacterial diarrhea for young children in Botswana resulted in similar effects on the gut resistome as the supportive treatment and did not provide additional selective pressure for macrolide resistance gene maintenance. The gut microbiota of these children contains diverse macrolide resistance genes that may be transferred within the gut upon repeated exposures to azithromycin or coselected by other antibiotics.

Clinical Trials Registration
NCT02803827.
Does soil history decline in influencing the structure of bacterial communities of Brassica napus host plants across different growth stages?
Authors: Blakney Andrew J C , St-Arnaud Marc , Hijri Mohamed 
Published: February 2024

Abstract
Soil history has been shown to condition future rhizosphere microbial communities. However, previous experiments have also illustrated that mature, adult plants can “re-write,” or mask, different soil histories through host plant–soil community feedbacks. This leaves a knowledge gap concerning how soil history influences bacterial community structure across different growth stages. Thus, here we tested the hypothesis that previously established soil histories will decrease in influencing the structure of Brassica napus bacterial communities over the growing season. We used an on-going agricultural field experiment to establish three different soil histories, plots of monocrop canola (B. napus), or rotations of wheat-canola, or pea-barley-canola. During the following season, we repeatedly sampled the surrounding bulk soil, rhizosphere, and roots of the B. napus hosts at different growth stages—the initial seeding conditions, seedling, rosette, bolting, and flower—from all three soil history plots. We compared composition and diversity of the B. napus soil bacterial communities, as estimated using 16S rRNA gene metabarcoding, to identify any changes associated with soil history and growth stages. We found that soil history remained significant across each growth stage in structuring the bacterial bulk soil and rhizosphere communities, but not the bacterial root communities. This suggests that the host plant’s capacity to “re-write” different soil histories may be quite limited as key components that constitute the soil history’s identity remain present, such that the previously established soil history continues to impact the bacterial rhizosphere communities, but not the root communities. For agriculture, this highlights how previously established soil histories persist and may have important long-term consequences on future plant–microbe communities, including bacteria.
The Methodological Machinery of Wargaming: A Path toward Discovering Wargaming’s Epistemological Foundations
Authors: Banks David E 
Published: February 2024

Abstract
This paper proposes a comprehensive research program for determining the epistemological foundations of analytic wargaming. Wargaming has been used in military, government, and private sectors for decades, with tens of millions of dollars spent annually on it. In light of the changing strategic circumstances of the twenty-first century, it has only become more popular. However, the epistemological foundations of the method are poorly understood. Many professional wargamers contend that wargaming is an “art” and thus unable to be systemically evaluated. Recent work by a small coterie of international relations scholars has contended that wargaming can be reconciled with social science, typically by evaluating wargaming according to experimental standards. However, this solution strips wargames of most of their unique features and cannot explain why some of the most prominent wargames in history produced meaningful results. In this paper, I argue that in the attempt to better understand wargaming’s epistemology, scholars should begin by recognizing the prominent features of wargames and research each of these to determine if and how wargames produce rigorous knowledge. In making this argument, I identify five distinct “methodological machineries” of wargaming—the recurring processes through which wargames may produce knowledge—that distinguish wargaming from other social science methods: (i) they are representative, (ii) they feature consequential decisions made by human players, (iii) they are adjudicated, (iv) they are immersive, and (v) they are bespoke designs. I show how each of these machineries offers potential opportunities and dangers in the production of knowledge through the method of wargaming. In outlining these distinct features, I offer a clear and viable research program for epistemologists of wargaming.
Accreditation of antimicrobial stewardship programmes: addressing a global need to tackle antimicrobial resistance
Authors: Sneddon Jacqueline , Drummond Felicity , Guise Tracey , Gilchrist Mark , Jenkins David R 
Published: February 2024

Abstract
Accreditation of healthcare services provides quality assurance of hospital practice to support safe and effective care for patients. Accreditation programmes focused on antimicrobial stewardship (AMS) have been developed in high-income countries (HIC) and recently the WHO has developed a toolkit to support AMS practice in low and middle-income (LMIC) countries. BSAC has developed their Global Antimicrobial Stewardship Accreditation Scheme (GAMSAS) for hospitals based on globally applicable standards. GAMSAS aims to support healthcare organizations to build measurable AMS programmes and to support spread of best practice. GAMSAS involves a desktop assessment by BSAC experts followed by a hospital visit to gather further insight into how a hospital’s AMS programme operates. A final report of compliance with the GAMSAS standards and a recommendation about accreditation at one of three levels is formally approved at a GAMSAS panel meeting involving well-established global experts in AMS. The BSAC GAMSAS team reflect on progress during the first year and ambitions for future spread.
The effect of ciprofloxacin prophylaxis during haematopoietic cell transplantation on infection episodes, exposure to treatment antimicrobials and antimicrobial resistance: a single-centre retrospective cohort study
Authors: Baltas Ioannis , Kavallieros Konstantinos , Konstantinou Giannis , Koutoumanou Eirini , Gibani Malick M , Gilchrist Mark , Davies Frances , Pavlu Jiri 
Published: February 2024

Abstract

Objectives
Fluroquinolone prophylaxis during haematopoietic cell transplantation (HCT) remains contentious. We aimed to determine its effectiveness and association with exposure to treatment antimicrobials and antimicrobial resistance.

Methods
All admission episodes for HCT (N = 400 , 372 unique patients) in a tertiary centre between January 2020 and December 2022 were studied. Allogeneic HCT (allo-HCT) recipients received prophylaxis with ciprofloxacin during chemotherapy-induced neutropenia, while autologous HCT (auto-HCT) recipients did not.

Results
Allo-HCT was performed for 43.3% (173/400) of patients, auto-HCT for 56.7% (227/400). Allo-HCT was associated with an average of 1.01 fewer infection episodes per 100 admission days (95% CI 0.62–1.40, P &lt; 0.001) compared with auto-HCT. In allo-HCT, the total exposure to all antimicrobials was higher [+24.8 days of therapy (DOT)/100 admission days, P &lt; 0.001], as was exposure to ciprofloxacin (+40.5 DOT/100 admission days, P &lt; 0.001). By contrast, exposure to meropenem (−4.5 DOT/100 admission days, P = 0.02), piperacillin/tazobactam (−5.2 DOT/100 admission days, P &lt; 0.001), aminoglycosides (−4.5 DOT/100 admission days, P &lt; 0.001) and glycopeptides (−6.4 DOT/100 admission days, P &lt; 0.001) was reduced. Enterobacteriaceae isolated during allo-HCT were more resistant to ciprofloxacin (65.5%, 19/29 versus 6.1%, 2/33, P &lt; 0001), ceftriaxone (65.5%, 19/29 versus 9.1%, 3/33, P &lt; 0.001), other antimicrobial classes. Vancomycin-resistant enterococci were more common in allo-HCT recipients (11%, 19/173 versus 0.9%, 2/227, P &lt; 0.001). Inpatient mortality during allo- and auto-HCT was 9.8% (17/173) and 0.4% (1/227). respectively (P &lt; 0.001).

Conclusions
Ciprofloxacin prophylaxis in allo-HCT was associated with fewer infection episodes and reduced exposure to treatment antimicrobials. Mortality in auto-HCT remained low. A significant burden of antimicrobial resistance was detected in allo-HCT recipients.
Fentanyl as a marker of illicit drug use in morphine-positive urine specimens from workplace drug testing
Authors: Vikingsson Svante , Winecker Ruth E , Kuntz David J , Clark Michael , Jacques Martin , Hart E Dale , Hayes Eugene D , Flegel Ronald R , Davis Lisa S 
Published: February 2024

Abstract
Total morphine is an important urinary marker of heroin use but can also be present from prescriptions or poppy seed ingestion. In specimens with morphine concentrations consistent with poppy seed ingestion (&lt;4,000 ng/mL), 6-acetylmorphine has served as an important marker of illicit drug use. However, as illicit fentanyl has become increasingly prevalent as a contaminant in the drug supply, fentanyl might be an alternative marker of illicit opioid use instead of or in combination with 6-acetylmorphine. The aim of this study was to quantify opiates, 6-acetylmorphine, fentanyl and fentanyl analogs in 504 morphine-positive (immunoassay 2,000 ng/mL cutoff) urine specimens from workplace drug testing. Almost half (43%) of morphine-positive specimens had morphine concentrations below 4,000 ng/mL, illustrating the need for markers to differentiate illicit drug use. In these specimens, fentanyl (22% co-positivity) was more prevalent than 6-acetylmorphine (12%). Co-positivity of 6-acetylmorphine and semi-synthetic opioids increased with morphine concentration, while fentanyl prevalence did not. In 110 fentanyl-positive specimens, the median norfentanyl concentration (1,520 ng/mL) was 9.6× higher than the median fentanyl concentration (159 ng/mL), illustrating the possibility of using norfentanyl as a urinary marker of fentanyl use. The only fentanyl analog identified was para-fluorofentanyl (n = 50), with results from most specimens consistent with para-fluorofentanyl contamination in illicit fentanyl. The results confirm the use of fentanyl by employees subject to workplace drug testing and highlight the potential of fentanyl and/or norfentanyl as important markers of illicit drug use.
Formation of the NLRP3 inflammasome inhibits stress granule assembly by multiple mechanisms
Authors: Yoshioka Daisuke , Nakamura Takanori , Kubota Yuji , Takekawa Mutsuhiro 
Published: February 2024

Abstract
Proper regulation of cellular response to environmental stress is crucial for maintaining biological homeostasis and is achieved by the balance between cell death processes, such as the formation of the pyroptosis-inducing NLRP3 inflammasome, and pro-survival processes, such as stress granule (SG) assembly. However, the functional interplay between these two stress-responsive organelles remains elusive. Here, we identified DHX33, a viral RNA sensor for the NLRP3 inflammasome, as a SG component, and the SG-nucleating protein G3BP as an NLRP3 inflammasome component. We also found that a decrease in intracellular potassium (K+) concentration, a key ‘common’ step in NLRP3 inflammasome activation, markedly inhibited SG assembly. Therefore, when macrophages are exposed to stress stimuli with the potential to induce both SGs and the NLRP3 inflammasome, such as cytoplasmic poly(I:C) stimulation, they preferentially form the NLRP3 inflammasome but avoid SG assembly by sequestering G3BP into the inflammasome and by inducing a reduction in intracellular K+ levels. Thus, under such conditions, DHX33 is primarily utilized as a viral RNA sensor for the inflammasome. Our data reveal the functional crosstalk between NLRP3 inflammasome-mediated pyroptosis and SG-mediated cell survival pathways and delineate a molecular mechanism that regulates cell-fate decisions and anti-viral innate immunity under stress.
Epigenetic regulation of innate immune dynamics during inflammation
Authors: Caldwell Blake A , Li Liwu 
Published: February 2024

Abstract
Innate immune cells play essential roles in modulating both immune defense and inflammation by expressing a diverse array of cytokines and inflammatory mediators, phagocytizing pathogens to promote immune clearance, and assisting with the adaptive immune processes through antigen presentation. Rudimentary innate immune “memory” states such as training, tolerance, and exhaustion develop based on the nature, strength, and duration of immune challenge, thereby enabling dynamic transcriptional reprogramming to alter present and future cell behavior. Underlying transcriptional reprogramming are broad changes to the epigenome, or chromatin alterations above the level of DNA sequence. These changes include direct modification of DNA through cytosine methylation as well as indirect modifications through alterations to histones that comprise the protein core of nucleosomes. In this review, we will discuss recent advances in our understanding of how these epigenetic changes influence the dynamic behavior of the innate immune system during both acute and chronic inflammation, as well as how stable changes to the epigenome result in long-term alterations of innate cell behavior related to pathophysiology.
The story of the R number: How an obscure epidemiological figure took over our lives. Part 1: History
Authors: Freeguard Gavin 
Published: February 2024

Abstract
The R number was the “breakout star” of the early weeks of the Covid-19 lockdowns, swiftly taking up residence in the general public’s consciousness and conversations. In this new six-part series, Gavin Freeguard will delve into the evolution of the R number and how it was modelled, used by the UK government and the media and regarded by the average person during the pandemic. He will also consider its limitations, lessons learned and how such statistical tools should be managed for disease planning and response in the future. In this first instalment, he introduces the history of this statistical concept.
The ascorbate biosynthesis pathway in plants is known, but there is a way to go with understanding control and functions
Authors: Smirnoff Nicholas , Wheeler Glen L 
Published: February 2024

Abstract
Ascorbate (vitamin C) is one of the most abundant primary metabolites in plants. Its complex chemistry enables it to function as an antioxidant, as a free radical scavenger, and as a reductant for iron and copper. Ascorbate biosynthesis occurs via the mannose/l-galactose pathway in green plants, and the evidence for this pathway being the major route is reviewed. Ascorbate accumulation is leaves is responsive to light, reflecting various roles in photoprotection. GDP-l-galactose phosphorylase (GGP) is the first dedicated step in the pathway and is important in controlling ascorbate synthesis. Its expression is determined by a combination of transcription and translation. Translation is controlled by an upstream open reading frame (uORF) which blocks translation of the main GGP-coding sequence, possibly in an ascorbate-dependent manner. GGP associates with a PAS-LOV protein, inhibiting its activity, and dissociation is induced by blue light. While low ascorbate mutants are susceptible to oxidative stress, they grow nearly normally. In contrast, mutants lacking ascorbate do not grow unless rescued by supplementation. Further research should investigate possible basal functions of ascorbate in severely deficient plants involving prevention of iron overoxidation in 2-oxoglutarate-dependent dioxygenases and iron mobilization during seed development and germination.