bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Anemia of Chronic Disease/Inflammation at a Tertiary Care Hospital in North India
Authors: Bhendekar Sidheshwar Vishnu , Kirtani Jay , Naithani Rahul 
Published: June 2024

AbstractBackgroundThere is lack of data from India on prevalence of anemia of chronic disease or inflammation (ACD).Patients & methodsThis was a prospective observational cross sectional prevalence study. Anemic patients underwent a complete blood count with peripheral smear, serum ferritin level, iron, total iron binding capacity, transferrin saturation, vitamin B12 and folic acid level, reticulocyte count and stool for occult blood. Other investigations were performed as required according to patient’s clinical profile.ResultsThree hundred fifty five patients were enrolled. A total of 109 patients (30.7%) had anemia of chronic disease ACD (30.7%). Sixty three/263 (24%) females had ACD compared to 46/95 (48.4%) males. ACD was four times more common in age group 80 years and above (56.5%) compared to age group 18 to 39 years (13.9%). Seventy two (66%) patients had mild anemia, 19 patients (17%) had moderate anemia and 18 patients (16%) had severe anemia. Diabetes mellitus (44%), hypertension (39%) and chronic kidney disease (25%) were the commonest underlying morbidity. Thirty six patients (33%) had no underlying comorbidity or cause.ConclusionThe prevalence of anemia of chronic disease increases with age. Majority of anemia of chronic disease patients have mild anemia.
Risk factors in the first 1000 days of life associated with childhood obesity: a systematic review and risk factor quality assessment
Authors: Blaauwendraad Sophia M , Kamphuis Arwen SJ , Ruiz-Ojeda Francisco Javier , Brandimonte-Hernández Marco , Flores-Ventura Eduard , Abrahamse-Berkeveld Marieke , Collado Maria Carmen , van Diepen Janna A , Iozzo Patricia , Knipping Karen , van Loo-Bouwman Carolien A , Gil Ángel , Gaillard Romy 
Published: June 2024

ABSTRACTBackgroundAdverse early life exposures might negatively affect foetal and infant development, predisposing children to obesity. We aimed to systematically identify and evaluate risk factors for childhood obesity in preconception, pregnancy, and infancy, and assess their potential as targets for future prediction and prevention strategies.MethodsThis systematic review (PROSPERO, CRD42022355152) included longitudinal studies from selected electronic databases published between inception and August 17th, 2022, identifying maternal, paternal, or infant risk factors from preconception until infancy for childhood obesity between 2 and 18 years. Screening and data extraction was performed through standardized extraction forms. We assessed risk factor quality on modifiability and predictive power using a piloted criteria template from ILSI-Europe-Marker-Validation-Initiative.FindingsWe identified 172 observational and 5 intervention studies involving n=1.879.971 children from 37, predominantly high-income, countries. 59%, 25% and 16% of studies measured childhood obesity between 2- <6 years, 6-10 years, and >10 -18 years respectively. Average reported childhood obesity prevalence was 11·1%. Pregnancy and infancy risk factors were mostly studied. We identified 59 potential risk factors, 24 of which were consistently associated with childhood obesity risk. Higher maternal prepregnancy weight (n=28/31 positive associations from 31 studies, respectively), higher gestational weight gain (n=18/21), maternal smoking during pregnancy (n=23/29), higher birth weight (n=20/28), LGA (n=17/18), no breastfeeding (n=20/31), and higher infant weight gain (n=12/12) were the strongest risk factors, which may aid in prediction or be targets for prevention. Level of evidence was generally moderate due to unreliable exposure measurement, short follow-up/loss-to-follow up, and risk of confounding.InterpretationWe identified 7 early life risk factors, which were strongly associated with a higher risk of childhood obesity, and can contribute to future prediction and prevention strategies. These findings support implementation of prevention strategies targeting these early-life risk factors from a clinical and population perspective, where possible integrated with implementation studies.FundingThis work was conducted by an expert group of the European branch of the International Life Sciences Institute, ILSI Europe.
The yield of tuberculosis contact investigation in São Paulo, Brazil: a community-based cross-sectional study
Authors: Silva José Mário Nunes da , Diaz-Quijano Fredi Alexander 
Published: June 2024

AbstractThe strategy of tuberculosis (TB) contact investigation is essential for enhancing disease detection. We conducted a cross-sectional study to evaluate the yield of contact investigation for new TB cases, estimate the prevalence of TB, and identify characteristics of index cases associated with infection among contacts of new cases notified between 2010 and 2020 in São Paulo, Brazil. Out of 186,466 index TB cases, 131,055 (70.3%) underwent contact investigation. A total of 652,286 contacts were screened, of which 451,704 (69.2%) were examined. Of these, 12,243 were diagnosed with active TB (yield of 2.0%), resulting in a number needed to screen of 51 and a number needed to test of 37 to identify one new TB case. The weighted prevalence for the total contacts screened was 2.8% (95% confidence interval [CI]: 2.7%–2.9%), suggesting underreporting of 6,021 (95% CI: 5,269–6,673) cases. The likelihood of TB diagnosis was higher among contacts of cases with active case-finding, abnormal chest X-ray, pulmonary TB, or drug resistance, as well as among children, adults, women, individuals in socially vulnerable situations, and those with underlying clinical conditions. The study highlights significant TB underreporting among contacts, recommending strengthened contact investigation to promptly identify and treat new cases.
Midline Assembloids Reveal Regulators of Human Axon Guidance
Authors: Onesto Massimo M. , Amin Neal D. , Pan Chenjie , Chen Xiaoyu , Reis Noah , Valencia Alfredo M. , Hudacova Zuzana , McQueen James P. , Tessier-Lavigne Marc , Paşca Sergiu P. 
Published: June 2024

AbstractOrganizers are specialized cell populations that orchestrate cell patterning and axon guidance in the developing nervous system. Although non-human models have led to fundamental discoveries about the organization of the nervous system midline by the floor plate, an experimental model of human floor plate would enable broader insights into regulation of human neurodevelopment and midline connectivity. Here, we have developed stem cell-derived organoids resembling human floor plate (hFpO) and assembled them with spinal cord organoids (hSpO) to generate midline assembloids (hMA). We demonstrate that hFpO promote Sonic hedgehog-dependent ventral patterning of human spinal progenitors and Netrin-dependent guidance of human commissural axons, paralleling non-human models. To investigate evolutionary-divergent midline regulators, we profiled the hFpO secretome and identified 27 evolutionarily divergent genes between human and mouse. Utilizing the hMA platform, we targeted these candidates in an arrayed CRISPR knockout screen and reveal thatGALNT2, a gene involved in O-linked glycosylation, impairs floor plate-mediated guidance of commissural axons in humans. This novel platform extends prior axon guidance discoveries into human-specific neurobiology with implications for mechanisms of nervous system evolution and neurodevelopmental disorders.
CryoEM Structure of the human THIK-1 K2P K+Channel Reveals a Lower ‘Y-gate’ Regulated by Lipids and Anaesthetics
Authors: Rödström Karin EJ , Eymsh Bisher , Proks Peter , Hayre Mehtab S , Madry Christian , Rowland Anna , Newstead Simon , Baukrowitz Thomas , Schewe Marcus , Tucker Stephen J 
Published: June 2024

AbstractTHIK-1 (KCNK13) is a halothane-inhibited and anionic lipid-activated Two-Pore Domain (K2P) K+channel implicated in microglial activation and neuroinflammation, and a current target for the treatment of neurodegenerative disorders such as Alzheimer’s and Amyothropic Lateral Sclerosis (ALS). However, compared to other K2P channels, little is known about the structural and functional properties of THIK-1. Here we present a 3.16 Å resolution cryoEM structure of human THIK-1 that reveals several unique features, in particular, a tyrosine in M4 (Y273) which contributes to a lower ‘Y-gate’ that opens upon activation by physiologically-relevant signalling pathways. We further demonstrate that binding of linoleic acid within a modulatory pocket adjacent to the filter also activates THIK-1, and that halothane inhibition involves a binding site within the inner cavity resulting in changes to the Y-gate. Finally, the extracellular cap domain contains positively-charged residues that line the ion exit pathway and which contribute to the unique biophysical properties of this channel. Overall, our results provide important insights into the structural basis of THIK1 function and identify distinct regulatory sites that expand its potential as a drug target for the modulation of microglial function.
Dietary protein from different sources escapes host digestion and is differentially modified by the microbiota
Authors: Awan Ayesha , Bartlett Alexandria , Blakeley-Ruiz J. Alfredo , Richie Tanner , Theriot Casey M. , Kleiner Manuel 
Published: June 2024

AbstractProtein is an essential macronutrient and variations in its source and quantity have been shown to impact long-term health outcomes. Differential health impacts of dietary proteins from various sources are likely driven by differences in their digestibility by the host and subsequent availability to the intestinal microbiota. However, our current understanding regarding the fate of dietary proteins from different sources in the gut, specifically how component proteins within these sources interact with the host and the gut microbiota, is limited. To determine which dietary proteins are efficiently digested by the host and which proteins escape host digestion and are used by the gut microbiota, we used high-resolution mass spectrometry to quantify the proteins that make up different dietary protein sources before and after digestion in germ-free and conventionally raised mice. Contrary to expectation, we detected proteins from all sources in fecal samples of both germ-free and conventional mice suggesting that even protein sources with a high digestive efficiency make it in part to the colon where they can serve as a substrate for the microbiota. Additionally, we found clear patterns where specific component proteins of the dietary protein sources were used as a preferred substrate by the microbiota or were not as accessible to the microbiota. We found that specific proteins with functions that could impact host health and physiology were differentially enriched in germ-free or conventionally raised mice. These findings reveal large differences in the fate of dietary protein from various sources in the gut that could explain some of their differential health impacts.
A family of lanthipeptides with anti-phage function
Authors: Shomar Helena , Tesson Florian , Guillaume Marie , Ongenae Véronique , Le Bot Margot , Georjon Héloïse , Mordret Ernest , Zhang Le , van Wezel Gilles P. , Rozen Daniel , Briegel Ariane , Zirah Séverine , Claessen Dennis , Li Yanyan , Bernheim Aude 
Published: June 2024

AbstractBacteria synthesize natural products to adapt to their environment, where phage-bacteria interactions play a crucial role in bacterial ecology. Although a few natural products have been shown to protect bacteria from phage infection, the prevalence and diversity of chemical anti-phage defense remain largely unexplored. Here, we uncover a novel family of over 2000 lanthipeptide biosynthetic gene clusters from Actinobacteria that participate in anti-phage defense, which we named lanthiphages. Lanthiphages colocalize with other anti-phage systems in defense islands. We demonstrate that native lanthiphage expression protects the model strainStreptomyces coelicoloragainst diverse phages. Heterologous expression of four additional lanthiphage pathways shows that the anti-phage function is conserved across this family of biosynthetic gene clusters. Finally, we demonstrate that lanthiphage expression leads to the production of a novel compound and alters phage transcription. Our findings highlight that biosynthetic gene clusters with anti-phage functions can be successfully identified through genomic analysis. This work paves the way for the systematic mining of anti-phage natural products, which could constitute a novel reservoir of antiviral drugs.
Energy-based bond graph models of glucose transport with SLC transporters
Authors: Hunter Peter J. , Ai Weiwei , Nickerson David P. 
Published: June 2024

ABSTRACTThe SLC (solutecarrier) superfamily mediates the passive transport of small molecules across apical and basolateral cell membranes in nearly all tissues. In this paper we employ bond graph approaches to develop models of SLC transporters that conserve mass, charge and energy, respectively, and which can be parameterised for a specific cell and tissue type for which the experimental kinetic data is available. We show how analytic expressions that preserve thermodynamic consistency can be derived for a representative four- or six-state model, given reasonable assumptions associated with steady-state flux conditions. We present details on fitting parameters forSLC2A2(a GLUT transporter) andSLC5A1(an SGLT transporter) to experimental data and show how well the steady-state flux expressions match the full kinetic analysis. Since the bond graph approach will not be familiar to many readers, we provide a detailed description of the approach and illustrate its application to a number of familiar biophysical processes.SIGNIFICANCEPhysiological systems typically involve coupled mechanical, electrical and chemical processes, with energy acting as a universal currency across these domains. We propose a new visual representation for all components of these processes using bond graphs. Bringing all physical processes under one consistent framework greatly simplifies the task of understanding multiscale physiological processes. This energy-based framework, which is the 0D version of a more general 3D port-Hamiltonian theory, can be used to model all lumped parameter physiological processes. A small number of bond graph templates can be used to model all members of the large SLC transporter family, and reduced thermodynamically consistent steady-state flux models provide a useful simplification for many situations. Glucose transport is chosen here to illustrate the bond graph approach because it represents the first step in cell metabolic processes, where energy conservation needs to be a fundamental characteristic of quantitative models. Our future work on cell metabolism will build on the foundation established here.
Maternal prenatal psychological distress is associated with aortic intima-media thickness in infants in the FinnBrain Birth Cohort Study
Authors: Aatsinki Anna-Katariina , Snäll Martha , Pahkala Katja , Karlsson Hasse , Perasto Laura , Raitakari Olli T. , Karlsson Linnea , Rovio Suvi P. 
Published: June 2024

AbstractAimsThe origins of cardiovascular health are embedded in early life. It has been suggested that exposure to prenatal stress is linked with markers of cardiovascular structure and functioning. We aimed to explore in the FinnBrain Birth Cohort Study if and how maternal prenatal psychological distress – a potentially modifiable risk factor – associates with infant aortic intima-media thickness (aIMT).MethodsMaternal symptoms were measured 2-3 times during pregnancy using EPDS for depressive symptoms, SCL-90 anxiety subscale for general anxiety and PRAQ-R2 for pregnancy-specific anxiety. Vascular ultrasonography was performed at the age of 2-3 months (n=273) and aIMT was measured.ResultsIn adjusted models, mean PRAQ-R2 across pregnancy was positively associated with aIMT. In boys, mean EPDS across pregnancy was associated with a thicker aIMT.ConclusionsOur results indicate that pregnancy-specific anxiety associates with thicker aIMT in both sexes, whereas maternal depressive symptoms associate with thicker aIMT in boys only.Lay SummaryStress during pregnancy changes maternal physiology, and is related with child development. We studied how mother’s tress, i.e. symptoms of depression and anxiety, during pregnancy links with cardiovascular structure of the infants.Mothers were asked about their symptoms of depression and anxiety 2-3 times during pregnancy. They were also asked about pregnancy-specific anxiety, meaning worries related to labour, future health of the child and pregnancy-related changes. At the age of 2-3 months, infants were imaged with ultrasound, and the thickness of two innermost layers of the wall of abdominal aorta was measured (aIMT). The thickness may relate with cardiovascular disease risk.pregnancy-related anxiety was linked with thicker aIMT. Additionally, boys showed thicker aIMT when their mothers had depressive symptoms during pregnancy.
High-resolution respirometry reveals altered mammalian tissue ketone body oxidation in different cardiometabolic diseases
Authors: Zweck Elric , Piel Sarah , Schmidt Johannes W. , Scheiber Daniel , Schön Martin , Kahl Sabine , Burkart Volker , Dewidar Bedair , Remus Ricarda , Chadt Alexandra , Al-Hasani Hadi , Aubin Hug , Boeken Udo , Lichtenberg Artur , Polzin Amin , Kelm Malte , Westenfeld Ralf , Wagner Robert , Szendroedi Julia , Roden Michael , Granata Cesare 
Published: June 2024

SummaryAbnormal mitochondrial oxidative phosphorylation (OXPHOS) is key to the pathogenesis of several cardiometabolic diseases. The ketone bodies (KBs), β-hydroxybutyrate (HBA) and acetoacetate (ACA), are critical for tissue-specific energy metabolism under various pathophysiological conditions. However, robust methods quantifying their contribution as substrates for OXPHOS are lacking. Here, we first established comprehensive high-resolution respirometry protocols for assessing the differential contributions of HBA, ACA, and related ketolytic enzymes to OXPHOS in translational studies in mice and humans. We then utilized these protocols to demonstrate (i) organ-specific differences in KB-driven mitochondrial respiration in mice, (ii) lower KB-driven mitochondrial respiration in liver of humans with steatosis, skeletal muscle of humans with diabetes and in kidney of diet-induced obese mice, as well as (iii) higher mitochondrial KB utilization capacity in mouse and human failing heart. These results highlight organ-specific roles of KB metabolism in cardiometabolic diseases and shall help to identify novel targets in these pathways.
MAPK Phosphatase-5 is required for TGF-β signaling through a JNK-dependent pathway
Authors: Dorry Sam , Perla Sravan , Bennett Anton M. 
Published: June 2024

AbstractMitogen-activated protein kinase (MAPK) phosphatases (MKPs) constitute members of the dual-specificity family of protein phosphatases that dephosphorylate the MAPKs. MKP-5 dephosphorylates the stress-responsive MAPKs, p38 MAPK and JNK, and has been shown to promote tissue fibrosis. Here, we provide insight into how MKP-5 regulates the transforming growth factor-β (TGF-β) pathway, a well-established driver of fibrosis. We show that MKP-5-deficient fibroblasts in response to TGF-β are impaired in SMAD2 phosphorylation at canonical and non-canonical sites, nuclear translocation, and transcriptional activation of fibrogenic genes. Consistent with this, pharmacological inhibition of MKP-5 is sufficient to block TGF-β signaling, and that this regulation occurs through a JNK-dependent pathway. By utilizing RNA sequencing and transcriptomic analysis, we identify TGF-β signaling activators regulated by MKP-5 in a JNK-dependent manner, providing mechanistic insight into how MKP-5 promotes TGF-β signaling. This study elucidates a novel mechanism whereby MKP-5-mediated JNK inactivation is required for TGF-β signaling and provides insight into the role of MKP-5 in fibrosis.
How does budget participation affect managerial performance in the higher education sector? A mediated-moderated model
Authors: Alhasnawi Mushtaq Yousif , Mohd Said Ridzwana , Alshdaifat Sajead Mowafaq , Elorabi Khaled Ahmed , Al-Hasnawi Maytham Hameed , Khudhair Ali Hussein 
Published: June 2024

PurposeEmployee participation in budgeting enhances motivation and commitment, leading to better performance by enhancing ownership. Within Iraqi higher education institutions (HEIs), the current investigation delves into the influence of participative budgeting on managerial performance. Drawing upon goal-setting theory, this study discerns budget goal commitment as a mediating variable while also examining directive leadership as a moderator in the dynamics of this association.Design/methodology/approachThe current study used partial least squares structural equation modelling (PLS-SEM) using SmartPLS 4.0. 373 questionnaires were collected from managers in Iraqi public universities, with 58.37% responding.FindingsThe findings show that budget goal commitment partially mediates the connection between budget participation and managerial performance. Furthermore, the results showed that directive leadership increases the positive associations between budget goal commitment and managerial performance.Originality/valueThis study expands the existing literature by shedding light on the mediating role of budget goal commitment and the moderating influence of directive leadership. It also enriches the discourse in management accounting by providing a more elucidation of how employee involvement in the budgeting process enhances managerial performance.
Transformational leadership and task performance: the mediating role of leader–member exchange, organizational support and work engagement
Authors: López-Zapata Esteban , Torres-Vargas Yésica , Ortiz-Puentes Marco Aurelio 
Published: June 2024

PurposeThis research analyzes the impact of transformational leadership on task performance in sales team members, considering the mediating role of leader–member exchange (LMX), perceived organizational support and work engagement.Design/methodology/approachA structural equations model was analyzed utilizing the partial least squares (PLS-SEM) method based on data collected from a survey of 142 members and 19 leaders of sales teams in Colombian companies.FindingsThe present study establishes that social exchange variables, including perceived organizational support and LMX, mediate the relationship between transformational leadership and task performance. Nevertheless, work engagement does not demonstrate a statistically significant mediating effect.Originality/valueThe outcomes of this study contribute significant insights into how transformational leadership, directly and indirectly, affects task performance in an emerging economy. It specifically addresses the cultural context of Colombia, marked by a high distance to power and a perceived low aversion to uncertainty – contrary to a desired higher uncertainty avoidance.