bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic burden and economic impact associated with non-communicable diseases among countries of the World Health Organization South-East Asia Region: a systematic review protocol
Authors: Menon Geetha R. , Misra Sheuli , Deo Vishal , Yadav Jeetendra , Joshi Pradeep , Varghese Cherian , John Denny 
Published: November 2024

Objective:
The objective of this systematic review is to synthesize studies on the economic burden and economic impact of non-communicable diseases in the World Health Organization South-East Asia Region (WHO SEAR) countries.

Introduction:
WHO SEAR countries represent 8.6% of the world’s population, and 75% of all deaths in this region are attributable to non-communicable diseases. In addition, there is a pattern of low government spending on health in SEAR countries, leading to a high proportion of health financing by patients, risking impoverishment for households.

Inclusion criteria:
We will consider observational (cross-sectional, cohort, and case-control) and interventional (either single arm or comparative) studies that report the economic burden (direct and indirect costs, out-of-pocket expenditure) and economic impact (catastrophic health expenditure, hardship financing, impoverishment, and gross domestic product impact) at the individual, household, and/or country levels. This includes government surveys, surveillance, and secondary data analyses for one or more non-communicable diseases prevalent in the WHO SEAR.

Methods:
We will conduct a comprehensive search for relevant studies in databases, including MEDLINE (PubMed), Embase (Ovid), Scopus, Web of Science, Google Scholar, and gray literature, with no date limits. Two reviewers will independently screen titles and abstracts, followed by full-text screening. Included studies will be critically appraised for quality. Data will be extracted accordingly and, if possible, random effects meta-analyses will be conducted on the pooled data for resource utilization and costs (including burden and impact), presenting the degree of variation between studies. The characteristics and results of the included studies will be narratively summarized with accompanying tables.

Review registration:
PROSPERO CRD42023421302
Respiratory system responses to a maximal apnoea
Authors: Hubbard Colin D. , Cross Troy J. , Merdich Garrett Z. , Vrdoljak Dario , Foretic Nikola , Dujić Željko , Duke Joseph W. 
Published: November 2024

AbstractA maximal apnoea provides significant challenges to one's physiological systems, including significantly altered arterial blood gases, and requires a highly integrative response from multiple systems, that is, changes in blood pressure, maintenance of cerebral blood flow, etc. Previous work and reviews have focused on the cardiovascular responses to a maximal apnoea, but very little work has focused upon the responses of the respiratory muscles and respiratory mechanics. This is important because of the changes to arterial blood gases leading to an increased drive to breath and the appearance of involuntary respiratory muscle contractions. This review outlines what is known about how the respiratory system responds to a maximal apnoea. We put forth the hypothesis that the respiratory muscles may become fatigued following a maximal apnoea and that the respiratory muscles of elite divers may be more fatigue‐resistant, which could be an important feature of these individuals which allows them to be successful in this sport. Finally, we provide direction for future work to explore the long‐term health of apnoea diving.
Imaging the large‐scale and cellular response to focal traumatic brain injury in mouse neocortex
Authors: Bibineyshvili Yelena , Vajtay Thomas J. , Salsabilian Shiva , Fliss Nicholas , Suvarnakar Aastha , Fang Jennifer , Teng Shavonne , Alder Janet , Najafizadeh Laleh , Margolis David J. 
Published: November 2024

AbstractTraumatic brain injury (TBI) affects neural function at the local injury site and also at distant, connected brain areas. However, the real‐time neural dynamics in response to injury and subsequent effects on sensory processing and behaviour are not fully resolved, especially across a range of spatial scales. We used in vivo calcium imaging in awake, head‐restrained male and female mice to measure large‐scale and cellular resolution neuronal activation, respectively, in response to a mild/moderate TBI induced by focal controlled cortical impact (CCI) injury of the motor cortex (M1). Widefield imaging revealed an immediate CCI‐induced activation at the injury site, followed by a massive slow wave of calcium signal activation that travelled across the majority of the dorsal cortex within approximately 30 s. Correspondingly, two‐photon calcium imaging in the primary somatosensory cortex (S1) found strong activation of neuropil and neuronal populations during the CCI‐induced travelling wave. A depression of calcium signals followed the wave, during which we observed the atypical activity of a sparse population of S1 neurons. Longitudinal imaging in the hours and days after CCI revealed increases in the area of whisker‐evoked sensory maps at early time points, in parallel to decreases in cortical functional connectivity and behavioural measures. Neural and behavioural changes mostly recovered over hours to days in our M1‐TBI model, with a more lasting decrease in the number of active S1 neurons. Our results in unanaesthetized mice describe novel spatial and temporal neural adaptations that occur at cortical sites remote to a focal brain injury.
Calmodulin regulates TRPV5 intracellular trafficking and plasma membrane abundance
Authors: Zuidscherwoude Malou , Grigore Teodora , van de Langenberg Brenda , Witte Guusje , van der Wijst Jenny , Hoenderop Joost G. 
Published: November 2024

AbstractAs a member of the transient receptor potential (TRP) superfamily of ion channels, TRPV5 is a unique Ca2+‐selective channel important for active reabsorption of Ca2+ in the kidney. TRPV5‐mediated Ca2+ entry into the cell is controlled by a negative feedback mechanism, in which calmodulin (CaM) blocks the TRPV5 pore upon Ca2+ binding. Combining microscopy techniques and biochemical assays, the present study uncovered an auxiliary role for CaM in the regulation of human (h)TRPV5 intracellular trafficking. Overexpressed hTRPV5 was mainly localised to the endoplasmic reticulum (ER) and associated with peripheral ER tubules. Limiting expression using the HEK293 TET‐off system revealed that hTRPV5 trafficked through the endocytic recycling pathway. CaM co‐localised with hTRPV5 at intracellular sites and overexpression of CaM slowed hTRPV5 exit from the ER. In accordance, CaM binding‐disrupting truncations of the TRPV5 C‐terminus (698X) or knockdown of endogenous CaM by small interfering RNA resulted in an increased fraction of TRPV5 that localised to the plasma membrane. hTRPV5 expressing cells had an increased intracellular Ca2+ concentration upon knockdown of CaM. The protein abundance of the Ca2+ impermeable hTRPV5‐D542 mutant is also regulated by CaM, which suggests that the mode of action is independent of disrupted intracellular calcium concentrations. In conclusion, our study reveals a novel role for CaM in Ca2+‐dependent TRPV5 regulation, modulating TRPV5 intracellular trafficking.
imageKey points
The renal Ca2+ channel TRPV5 is a crucial player in maintenance of the body's Ca2+ homeostasis.
Ca2+ transport through TRPV5 is controlled by single channel activity, as well as TRPV5 plasma membrane abundance.
Calmodulin (CaM) co‐localised with TRPV5 at intracellular sites and retained TRPV5 in the endoplasmic reticulum.
Disrupted CaM–TRPV5 binding or knockdown of endogenous CaM by small interfering RNA (siRNA) resulted in an increased TRPV5 plasma membrane abundance.
Knockdown of endogenous CaM by siRNA resulted in increased intracellular Ca2+ concentrations. The regulation of TRPV5 trafficking by CaM is independent of the effect of CaM on intracellular Ca2+ concentrations.
This study reveals a novel role for CaM in Ca2+‐dependent TRPV5 regulation, next to its ability to directly block the TRPV5 channel pore, by modulating TRPV5 trafficking in the secretory pathway.
Influence of Sport Specialization on Quality of Life, Physical Literacy, and Injury History in Hockey Players
Authors: Marshall Kendall , Chimera Nicole J. , Valovich McLeod Tamara 
Published: November 2024

Sport specialization and its effect on health-related quality of life, physical literacy, and injury among ice hockey players is poorly understood. We examined specialization patterns, quality of life, physical literacy, and injury history in a sample of 63 high school-aged hockey players. Thirty-eight percent of participants reported moderate specialization; over half of the sample reported high specialization. Highly specialized players spent a greater amount of weekly time per week in hockey activities (21.14 hr, 95% confidence interval [17.4, 24.88]) and reported a greater number of injuries when compared with moderate and low specializers (χ2 = 0.026). Acute injuries were more prevalent than chronic or overuse injuries across all groups. No differences were observed on physical literacy or quality of life scores. Despite their increased participation and greater frequency of injuries, specialization did not significantly impact health-related quality of life.
The Magnitude of the Blood Acid–Base Response, but Not Time to Peak, Is Reliable Following the Ingestion of Acute, Individualized Sodium Citrate
Authors: Tinnion Daniel J. , Dobson Ben , Hilton Nathan , McNaughton Lars R. , Sparks S. Andy 
Published: November 2024

Enhanced buffering capacity following sodium citrate (SC) ingestion may be optimized when subsequent exercise commences at individual time-to-peak (TTP) alkalosis (blood pH or bicarbonate concentration [HCO3−]). While accounting for considerable interindividual variation in TTP (188–300 min), a reliable blood alkalotic response is required for practical use. This study evaluated the reliability of blood pH, HCO3−, and sodium (Na+) following acute SC ingestion. Fourteen recreationally active males ingested 0.4 or 0.5 g/kg body mass (BM) of SC on two occasions each and 0.07 g/kg BM of sodium chloride (control) once. Blood pH and HCO3− were measured for 4 hr postingestion. Blood pH and HCO3− displayed good reliability following 0.5 g/kg BM SC (r = .819, p = .002, standardized technical error [sTE] = 0.67 and r = .840, p < .001, sTE = 0.63, respectively). Following 0.4 g/kg BM SC, blood HCO3− retained good reliability (r = .771, p = .006, sTE = 0.78) versus moderate for blood pH (r = .520, p = .099, sTE = 1.36). TTP pH was moderately reliable following 0.5 (r = .676, p = .026, sTE = 1.05) and 0.4 g/kg BM SC (r = .679, p = .025, sTE = 0.91) versus poor for HCO3− following 0.5 (r = .183, p = .361, sTE = 5.38) and 0.4 g/kg BM SC (r = .290, p = .273, sTE = 2.50). Although the magnitude of (and displacement in) blood alkalosis, particularly HCO3−, appears reliable following potentially ergogenic doses of SC, strategies based on individual TTP cannot be recommended.
Movement Mediates the Relationship Between Socioeconomic Position and Socioemotional Outcomes in Youth
Authors: Wilhite Katrina , Noetel Michael , del Pozo Cruz Borja , Lonsdale Chris , Sanders Taren 
Published: November 2024

Background: Youth from lower socioeconomic positions tend to have poorer socioemotional outcomes, be less physically active, have poorer sleep, and engage in more screen time than their peers from higher socioeconomic positions. The objective of this study was to test the hypothesis that movement behaviors (ie, physical activity, sedentary behavior, and sleep) and changes in combinations of movement behaviors over time (movement trajectories) mediate the relationship between socioeconomic position and socioemotional outcomes in youth. Methods: This study used socioeconomic position data, scores from Strengths and Difficulties Questionnaires, and time-use diaries from 980 females and 1014 males (2% Australian Indigenous) aged 10–14 from the Longitudinal Study of Australian Children from 2014 to 2018. Results: Movement trajectories did not mediate the relationship between socioeconomic position and socioemotional outcomes. Least absolute shrinkage and selection operator-based mediation analyses found males from lower socioeconomic positions participated in less moderate- to vigorous-intensity physical activity than their peers from high socioeconomic positions, partially explaining (7%) more peer problems. Youth from lower socioeconomic positions participated in more recreational screen activities than their peers from higher socioeconomic positions, partially explaining (1%–3%) worse total socioemotional outcomes and conduct (females) and emotional problems (males). Conclusions: Future qualitative research should be considered to identify the best ways for youth from lower socioeconomic positions to decrease screen time and increase opportunities to participate in moderate- to vigorous-intensity physical activity in the community, at school, and at home. Other mediators explaining differences in socioemotional outcomes should be explored.
Chicken GSDME, a major pore-forming molecule responsible for RNA virus-induced pyroptosis in chicken
Authors: Chen Zhi , Chang He , Zhang Shujun , Gao Hui , Gao Li , Cao Hong , Li Xiaoqi , Wang Yongqiang , Zheng Shijun J. 
Published: November 2024

ABSTRACT

Pyroptosis is an inflammatory type of programmed cell death that mainly depends on the formation of plasma membrane pores by Gasdermin D (GSDMD) in mammals. However, the genetic deficiency of GSDMD in chicken renders avian pyroptosis elusive. Here, we show that infection of DF-1 cells (a chicken cell line) with infectious bursal disease virus (IBDV) induced cell death associated with chicken GSDME (chGSDME) cleavage, and so did cells with other RNA virus (VSV, AIV, or NDV) infections, indicating a broad role of chGSDME in RNA virus-induced pyroptosis in chicken. Furthermore, infection of DF-1 cells by IBDV or treatment of cells with Poly(I:C) initiated MDA5-mediated signaling pathway, followed by the activation of chCaspase-3/7 cleaving chGSDME at a specific site
270
DAVD
273
. Moreover, knockdown or knockout of chGSDME expression in cells markedly reduced IBDV-induced pyroptosis and viral release. These results unravel the mechanisms of pyroptosis in chickens with RNA virus infection, providing important clues to uncover the role of GSDM proteins of different species in host response against pathogenic infection.

IMPORTANCE
Pyroptosis is an inflammatory type of programmed cell death that mainly depends on the function of GSDMD in mammals and plays a crucial role in the pathogenesis of viral infection, whereas the mechanism of pyroptosis in chicken remains elusive. Herein, we show that IBDV and other RNA virus induced pyroptosis through the chMDA5-CASP8/9-CASP3/7-chGSDME pathway. The finding advances our understanding of GSDM proteins of different species in host response against pathogenic infection.
Colibactin-induced damage in bacteria is cell contact independent
Authors: Lowry Emily , Mitchell Amir 
Published: November 2024

ABSTRACT

The bacterial toxin colibactin, produced primarily by the B2 phylogroup of
Escherichia coli
, underlies some cases of colorectal cancers. Colibactin crosslinks DNA and induces genotoxic damage in both mammalian and bacterial cells. While the mechanisms facilitating colibactin delivery remain unclear, results from multiple studies supported a delivery model that necessitates cell-cell contact. We directly tested this requirement in bacterial cultures by monitoring the spatiotemporal dynamics of the DNA damage response using a fluorescent transcriptional reporter. We found that in mixed-cell populations, DNA damage saturated within 12 hours and was detectable even in reporter cells separated from colibactin producers by hundreds of microns. Experiments with distinctly separated producer and reporter colonies revealed that the intensity of DNA damage decays similarly with distance regardless of colony contact. Our work reveals that cell contact is inconsequential for colibactin delivery in bacteria and suggests that contact dependence needs to be reexamined in mammalian cells as well.

IMPORTANCE

Colibactin is a bacteria-produced toxin that binds and damages DNA. It has been widely studied in mammalian cells due to its potential role in tumorigenesis. However, fundamental questions about its impact in bacteria remain underexplored. We used
Escherichia coli
as a model system to study colibactin toxicity in neighboring bacteria and directly tested if cell-cell contact is required for toxicity, as has previously been proposed. We found that colibactin can induce DNA damage in bacteria hundreds of microns away, and the intensity of DNA damage presents similarly regardless of cell-cell contact. Our work further suggests that the requirement for cell-cell contact for colibactin-induced toxicity also needs to be reevaluated in mammalian cells.
Structural basis of a microbial trimethylamine transporter
Authors: Gao Chao , Ding Hai-Tao , Li Kang , Cao Hai-Yan , Wang Ning , Gu Zeng-Tian , Wang Qing , Sun Mei-Ling , Chen Xiu-Lan , Chen Yin , Zhang Yu-Zhong , Fu Hui-Hui , Li Chun-Yang 
Published: November 2024

ABSTRACT

Trimethylamine (TMA), a simple trace biogenic amine resulting from the decomposition of proteins and other macromolecules, is ubiquitous in nature. It is found in the human gut as well as in various terrestrial and marine ecosystems. While the role of TMA in promoting cardiovascular diseases and depolarizing olfactory sensory neurons in humans has only recently been explored, many microbes are well known for their ability to utilize TMA as a carbon, nitrogen, and energy source. Here, we report the first structure of a TMA transporter, TmaT, originally identified from a marine bacterium. TmaT is a member of the betaine-choline-carnitine transporter family, and we show that TmaT is an Na
+
/TMA symporter, which possessed high specificity and binding affinity toward TMA. Furthermore, the structures of TmaT and two TmaT-TMA complexes were solved by cryo-EM. TmaT forms a homotrimer structure in solution. Each TmaT monomer has 12 transmembrane helices, and the TMA transport channel is formed by a four-helix bundle. TMA can move between different aromatic boxes, which provides the structural basis of TmaT importing TMA. When TMA is bound in location I, residues Trp146, Trp151, Tyr154, and Trp326 form an aromatic box to accommodate TMA. Moreover, Met105 also plays an important role in the binding of TMA. When TMA is transferred to location II, it is bound in the aromatic box formed by Trp325, Trp326, and Trp329. Based on our results, we proposed the TMA transport mechanism by TmaT. This study provides novel insights into TMA transport across biological membranes.

IMPORTANCE
The volatile trimethylamine (TMA) plays an important role in promoting cardiovascular diseases and depolarizing olfactory sensory neurons in humans and serves as a key nutrient source for a variety of ubiquitous marine microbes. While the TMA transporter TmaT has been identified from a marine bacterium, the structure of TmaT and the molecular mechanism involved in TMA transport remain unclear. In this study, we elucidated the high-resolution cryo-EM structures of TmaT and TmaT-TMA complexes and revealed the TMA binding and transport mechanisms by structural and biochemical analyses. The results advance our understanding of the TMA transport processes across biological membranes.
Klebsiella pneumoniae
induces dose-dependent shock, organ dysfunction, and coagulopathy in a nonhuman primate critical care model
Authors: Strich Jeffrey R. , Ramos-Benitez Marcos J. , Warner Seth , Kendall Heather , Stein Sydney , Platt Andrew P. , Ramelli Sabrina C. , Curran Shelly J. , Lach Izabella , Allen Kiana , Babyak Ashley , Perez-Valencia Luis J. , Minai Mahnaz , Sun Junfeng , Vannella Kevin M. , Alves Derron , Herbert Richard , Chertow Daniel S. 
Published: November 2024

ABSTRACT

Nonhuman primate models that closely emulate the disease course, pathogenesis, and supportive care provided to human patients in the modern intensive care unit with bacterial sepsis are urgently needed to study pathogenesis and assess novel therapies. We therefore developed a non-human primate model of septic shock that includes supportive care akin to a modern intensive care unit. In this study, we characterized pathogen kinetics and evaluated the physiologic, immunologic, and pathologic responses in this model of septic shock induced by the clinically relevant pathogen
Klebsiella pneumoniae
across a three-log dose range. We observed dose-dependent bacteremia and circulating levels of
Klebsiella pneumoniae
DNA and endotoxin. Tachycardia and hypotension occurred in all animals and the study endpoint occurred in 8 of 12 animals that were euthanized. The infused bacterial dose was significantly associated with the severity of renal insufficiency and coagulopathy. Neutrophil activation evidenced by increased CD11b expression, decreased CD62L expression, and increased circulating levels of myeloperoxidase, lactoferrin, and neutrophil extracellular traps; monocyte activation evidenced by increased circulating levels of interleukin-6, tumor necrosis factor-alpha, granulocyte-macrophage colony-stimulating factor, and monocyte chemotactic protein-1; and endothelial activation evidenced by increased circulating levels of syndecan-1 and angiopoietin-II were all consistent with human sepsis. Our model provides an opportunity to study pathogenesis and investigate novel therapeutics for the treatment of bacterial sepsis in the setting of modern supportive care.

IMPORTANCE

There is currently a disconnect between the efficacy of sepsis therapies in pre-clinical animal models and human clinical trials. Therefore, developing nonhuman primate models that closely mimic human sepsis pathogenesis to study novel host-targeted therapeutics is a priority. In this study, we developed a model of septic shock with a clinically relevant bacteria (
Klebsiella pneumoniae
) that provides standard supportive care including mechanical ventilation, invasive hemodynamic monitoring, volume resuscitation, vasopressors, antibiotics, and steroids. In a dose-dependent manner, we observed that this model closely emulates the hemodynamic, end-organ dysfunction, and cellular and soluble responses associated with human sepsis. This validated model provides a unique opportunity to study the pathogenesis of acute septic shock and evaluate host-directed therapeutics in a large animal model that closely emulates the modern-day intensive care unit and supportive critical care.