bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disentangling the effects of intermittent faecal shedding and imperfect test sensitivity on the microscopy-based detection of gut parasites in stool samples
Authors: Ferreira-Sá Lana C. E. , Machado Eleuza R. , Gurgel-Gonçalves Rodrigo , Abad-Franch Fernando 
Published: December 2024

Background
Gut-parasite transmission often involves faecal shedding, and detecting parasites in stool samples remains the cornerstone of diagnosis. However, not all samples drawn from infected hosts contain parasites (because of intermittent shedding), and no test can detect the target parasites in 100% of parasite-bearing samples (because of imperfect sensitivity). Disentangling the effects of intermittent shedding and imperfect sensitivity on pathogen detection would help us better understand transmission dynamics, disease epidemiology, and diagnostic-test performance. Using paediatric Giardia infections as a case-study, here we illustrate a hierarchical-modelling approach to separately estimating the probabilities of host-level infection (Ψ); stool-sample–level shedding, given infection (θ); and test-level detection, given infection and shedding (p).

Methods/Findings
We collected 1–3 stool samples, in consecutive weeks, from 276 children. Samples (413 overall) were independently examined, via standard sedimentation/optical microscopy, by a senior parasitologist and a junior, trained student (826 tests overall). Using replicate test results and multilevel hierarchical models, we estimated per-sample Giardia shedding probability at θ^≈0.440±0.116SE and observer-specific test sensitivities at p^Senior≈0.639±0.080SE and p^Junior≈0.460±0.071SE. Gender-specific infection-frequency estimates were Ψ^Girls≈0.540±0.137SE and Ψ^Boys≈0.337±0.098SE. Had we used a (hypothetical) Perfect Test with 100% narrow-sense sensitivity (pPT_≡1.0), the average probability of detecting Giardia in a sample drawn from an infected child (Ψ≡1.0) would have been Pr(d|i,PT_)=Ψ×θ×pPT_≈1.0×0.44×1.0≈0.44. Because no test can be >100% sensitive, Pr(d|i) (which measures clinical sensitivity) can only be brought above ~ 0.44 by tinkering with the availability of Giardia in stool samples (i.e., θ); for example, drawing-and-pooling 3 replicate samples would yield θ^3s≈1−(1−0.44)3≈0.82.

Conclusions
By allowing separate estimation (and modelling) of pathogen-shedding probabilities, the approach we illustrate provides a means to study pathogen transmission cycles and dynamics in unprecedented detail. Separate estimation (and modelling) of true test sensitivity, moreover, may cast new light on the performance of diagnostic tests and procedures, whether novel or routine-practice.
Generation Healthy Kids: Protocol for a cluster-randomized controlled trial of a multi-component and multi-setting intervention to promote healthy weight and wellbeing in 6–11-year-old children in Denmark
Authors: Thomsen Louise T. , Schmidt-Persson Jesper , Damsgaard Camilla Trab , Krustrup Peter , Grøntved Anders , Krølner Rikke Fredenslund , Nielsen Glen , Lundbye-Jensen Jesper , Skovgaard Thomas , Mølgaard Christian , Hansen Anders Blædel Gottlieb , Hoeeg Didde , Larsen Malte Nejst , Lund Line , Melby Paulina Sander , Pedersen Natascha Holbæk , Troelsen Jens , Nordsborg Nikolai Baastrup , Toft Ulla 
Published: December 2024

Background
Childhood obesity can have significant negative consequences for children’s wellbeing and long-term health. Prior school-based interventions to prevent child overweight and obesity have shown limited effects, highlighting the necessity for comprehensive approaches addressing complex drivers of childhood obesity. “Generation Healthy Kids” (GHK) is a multi-setting, multi-component intervention to promote healthy weight development, health and wellbeing in Danish children aged 6–11 years. This protocol describes the GHK main trial, which is a cluster-randomized trial evaluating effectiveness and implementation of the GHK intervention.

Methods
Twenty-four schools from the Capital, Zealand and Southern Denmark Regions are randomly allocated 1:1 to intervention or control. The intervention will run for two school years (18–20 months) from October 2023 to June 2025 and will include children in 1st–3rd grade (approx. n = 1,600). The intervention targets multiple settings, including families, schools, after-school clubs, and local communities. Within four focus areas–diet, physical activity, screen media use, and sleep habits–the intervention incorporates several fixed elements, including a school lunch program and three weekly sessions of physical activity at school. Furthermore, building on whole-systems thinking, the intervention encompasses co-created elements developed in collaboration with local stakeholders, e.g. municipalities, sports clubs and supermarkets. This part of the intervention emphasizes building local capacity and engagement to promote child health. Effectiveness data will be collected from participating children and families at baseline, and at the end of school year one (after 6–8 months) and school year two (after 18–20 months). The primary outcome is the change in fat mass, measured by air-displacement plethysmography, from baseline to end-of-study in the intervention group compared to the control group. This is supplemented with numerous secondary outcomes and other prespecified outcomes related to child health and wellbeing. Furthermore, thorough process evaluation will be performed.

Discussion
GHK combines evidence-based intervention elements targeting multiple settings with a whole-systems approach focusing on capacity building and stakeholder involvement. This novel approach holds promise as an innovative way to promote child health and wellbeing and prevent childhood obesity.

Trial registration
ClinicalTrials.gov: NCT05940675 (registered on 4 July 2023).
Measuring the rate of NADPH consumption by glutathione reductase in the cytosol and mitochondria
Authors: Ting Kenneth K. Y. , Floro Eric , Dow Riley , Jongstra-Bilen Jenny , Cybulsky Myron I. , Rocheleau Jonathan V. 
Published: December 2024

Background
NADPH is an essential co-factor supporting the function of enzymes that participate in both inflammatory and anti-inflammatory pathways in myeloid cells, particularly macrophages. Although individual NADPH-dependent pathways are well characterized, how these opposing pathways are co-regulated to orchestrate an optimized inflammatory response is not well understood. To investigate this, techniques to track the consumption of NADPH need to be applied. Deuterium tracing of NADPH remains the gold standard in the field, yet this setup of mass-spectrometry is technically challenging and not readily available to most research groups. Furthermore, NADPH pools are compartmentalized in various organelles with no known membrane transporters, suggesting that NADPH-dependent pathways are regulated in an organelle-specific manner. Conventional methods such as commercial kits are limited to quantifying NADPH in whole cells and not at the resolution of specific organelles. These limitations reflect the need for a novel assay that can readily measure the consumption rate of NADPH in different organelles.

Methods
We devised an assay that measures the consumption rate of NADPH by glutathione-disulfide reductase (GSR) in the mitochondria and the cytosol of RAW264.7 macrophage cell lines. RAW264.7 cells were transfected with Apollo-NADP+ sensors targeted to the mitochondria or the cytosol, followed by the treatment of 2-deoxyglucose and diamide. Intravital imaging over time then determined GSR-dependent NADPH consumption in an organelle-specific manner.

Discussion
In lipopolysaccharide (LPS)-stimulated RAW264.7 cells, cytosolic and mitochondrial NADPH was consumed by GSR in a time-dependent manner. This finding was cross validated with a commercially available NADPH kit that detects NADPH in whole cells. Loading of RAW264.7 cells with oxidized low-density lipoprotein followed by LPS stimulation elevated GSR expression, and this correlated with a more rapid drop in cytosolic and mitochondrial NADPH in our assay. The current limitation of our assay is applicability to transfectable cell lines, and higher expression of plasmid-encoded sensors relative to endogenous glucose-6-phosphate dehydrogenase.
Effects of three types of resistance training on knee osteoarthritis: A systematic review and network meta-analysis
Authors: Jiang Yutao , Tan Yajun , Cheng Liang , Wang Jintao 
Published: December 2024

Background
Resistance training (RT) is recognized in clinical guidelines as a beneficial treatment for knee osteoarthritis (KOA), but the efficacy of different RT types is not well-established.

Objective
This network meta-analysis (NMA) aimed to compare the effects of different types of RT, namely, isometric muscle strengthening (IMMS), isokinetic muscle strengthening (IKMS) and isotonic muscle strengthening (ITMS), on pain, function and quadriceps muscle strength of patients with KOA.

Methods
A systematic search was conducted up to September 2023 on databases, including PubMed, Cochrane Library, EMbase, Web of Science and China National Knowledge Infrastructure. The included studies comprised randomised controlled trials (RCTs) comparing RT with conventional rehabilitation and physiotherapy or other types of RT.

Results
Compared with the control group (CG) that received conventional physiotherapy, IKMS was optimal in terms of pain relief (MD = -1.33, 95% CI: -1.83 to -0.83), function (MD = -12.24, 95% CI: -17.29 to -7.19) and knee extension torque (SMD = -0.44, 95% CI: -0.74 to -0.14).

Conclusions
Compared with conventional rehabilitation therapy, all three types of RT can improve pain and knee-joint function in KOA patients. IKMS demonstrated the best results among the different RT modalities.

PROSPERO registration
PROSPERO registration number: CRD42023448579.
Digital boundaries: A study on WeChat parent-child relationships among Chinese college students and their association with family factors
Authors: Feng Zhao , Hu Chun-Mei , He Ling-Ling 
Published: December 2024

Objective
This study aims to investigate the current state of WeChat parent-child relationships among college students and their association with family factors.

Methods
Using convenient sampling, 6159 students,age from 18 to 25,the participants were selected from colleges of Chengdu to complete a questionnaire survey on response and attitudes towards parents’ WeChat friend requests, Family APGAR Index,Parental Management Scale,Family Conflict Scale,were used as measurement tools.

Results
Responses to parental WeChat friend requests showed significant positive correlations with higher levels of family function satisfaction (r = 0.10, P<0.01) and parental management (r = 0.11, P<0.01), and a significant negative correlation with family conflict (r = -0.03, P<0.05).

Conclusion
This study reveals that Chinese college students generally accept their parents’ WeChat friend requests, influenced by family dynamics and traditional values. Positive parental management, family harmony, and good marital relationships enhance students’ willingness to connect with their parents on WeChat, indicating the complex interplay between digital interactions and traditional family concepts.This underscores the importance for parents to adopt modern and scientific parenting approaches, fostering a harmonious and nurturing family atmosphere rooted in trust and mutual respect for their children.
Health care providers’ decision-making and early adoption of tenofovir alafenamide for HIV preexposure prophylaxis: An inductive qualitative study
Authors: Merchant Elisabeth , Solleveld Patricia , Gibas Kevin , Krakower Douglas 
Published: December 2024

Background
Over the past several years, there have been several changes affecting the available options for oral HIV preexposure prophylaxis, including approvals for tenofovir alafenamide with emtricitabine in 2019 and a generic formulation of tenofovir disoproxil fumarate with emtricitabine in 2020.

Methods
In order to better understand providers’ decision-making processes when deciding between these two drugs for pre-exposure prophylaxis, we conducted semi-structured in-depth interviews with resident, fellow and attending physicians in internal medicine and infectious diseases between May 2020 and March 2021. These interviews were analyzed to identify emergent codes, which were utilized in an inductive thematic analysis to identify major themes pertinent to pre-exposure prophylaxis decision-making.

Results
Of 21 participants, 18 expressed a general preference for prescribing tenofovir disoproxil fumarate with emtricitabine, 2 preferred tenofovir alafenamide with emtricitabine and 1 had no specific preference. Providers perceived similar efficacy of the two formulations, and their clinical decisions were influenced primarily by whether HIV pre-exposure prophylaxis users belonged to a population with an indication for each of the two drugs (e.g. gender-related restrictions for tenofovir alafenamide), the medications’ differing side effect profiles, cost and insurance considerations, prior personal and collective experience with each of these medications, and personal preferences. Respondents also noted that both providers and HIV pre-exposure prophylaxis users were influenced by external factors, including institutional prescribing guidance, advertising, and social influences, including from peers and colleagues.

Conclusions
Our findings suggest that unbiased educational campaigns for both prescribers and users of HIV pre-exposure prophylaxis will be important to support evidence-based prescribing practices and cost-effective decisions among oral pre-exposure prophylaxis options.
Pharmacokinetic evaluation of single-dose migalastat in non-Fabry disease subjects with ESRD receiving dialysis treatment, and use of modeling to select dose regimens in Fabry disease subjects with ESRD receiving dialysis treatment
Authors: Johnson Franklin K. , Wu Shirley , Schmith Ginny , Williams Hadis , Rutecki Jasmine , Halabi Atef , Feldkamp Thorsten , Sileno Anthony 
Published: December 2024

Background
Fabry disease (FD) is an X-linked lysosomal disorder leading to multiorgan dysfunction, including renal impairment and the risk of significant accumulation for renally excreted drugs. Migalastat, an approved therapy in FD patients with amenable variants, is primarily eliminated in urine; however, its use had not been studied in patients with end-stage renal disease (ESRD) receiving dialysis therapy. This study investigated the pharmacokinetics (PK), dialyzability, and tolerability of 123 mg migalastat in non-FD subjects with ESRD on stable hemodialysis/hemodiafiltration (EudraCT 2018-003684-57). Results were analyzed by population PK and physiologically based PK (PBPK) modeling and intended to propose dose regimens resulting in negligible migalastat trough levels in plasma and comparable concentrations above the threshold in target tissues in FD patients with ESRD.

Methods
Subjects with ESRD received 123 mg migalastat 24 hours before dialysis and, following an 8-day washout, immediately before dialysis. Matched controls with normal renal function (NRF) received migalastat 123 mg. Migalastat concentrations were measured in plasma, urine, and dialysate, and modeled to select regimens providing similar disposition to NRF.

Results
Migalastat was extracted by hemodialysis/hemodiafiltration (74%/72%). PBPK modeling predicted that 123 mg every other week (QOW) with regular dialysis 2–3 times weekly in ESRD subjects produced: a fraction of time above EC50 similar to FD patients with NRF; adequate Cmax for intracellular trafficking of mutant α-galactosidase A to the lysosome; and Ctrough levels near the lower limit of quantification (LLOQ) similar to NRF subjects receiving 123 mg every other day. Migalastat 82 mg weekly produced a greater fraction of time above EC50 and longer duration of concentrations above the LLOQ, potentially resulting in accumulation in tissues.

Conclusion
Migalastat was well extracted by hemodialysis/hemodiafiltration. Migalastat 123 mg QOW is the proposed dose regimen for further evaluation in FD patients with ESRD, which could inform expansion of treatment options.

Trial registration
Trial registration: EU Clinical Trials Register, EudraCT number 2018-003684-57.
Exploring the strategies and components of interventions to build adolescent awareness about stunting prevention in West Java: A qualitative study
Authors: Nurhaeni Nani , Huda Mega Hasanul , Chodidjah Siti , Agustini Nur , Tri Waluyanti Fajar , Nadi Hartin I. K. , Armini Ni Ketut Sri , Sari Maya , Jackson Debra 
Published: December 2024

Aim
This study aimed to explore the strategies and important components that can be implemented to build adolescent awareness about stunting prevention.

Methods
This study used descriptive qualitative design. The data were collected through focus group discussions (FGDs) and semi-structured interviews. Purposive sampling method was employed to select the participants. The FGDs involved adolescents (n = 6) and high school counselling teachers (n = 5), while the semi-structured interviews were conducted with experts frequently involved in overcoming stunting problems in Indonesia (n = 7). The interview results were transcribed in verbatim transcription and analysed by using thematic analysis.

Results
Five themes were identified from the results: 1) Adolescent identity development with three sub-themes: online identity exploration, rebellious stage, and peer influence; 2) Creative and visually appealing website with six sub-themes: interesting appearance, short time span, serial content, story pattern, scenario using adolescent idol’s name, and attractive website menu; 3) Nutritional needs for adolescents with three sub-themes: iron and calcium intake, less sugar consumption, and nutritional status; 4) Engaging content for adolescents with seven sub-themes: stunting, reproductive health, anaemia, diet, wellness, early marriage, and physical activity; and 5) Effective communication strategy with two sub-themes: consistency of activities and communicative.

Implications
In designing adolescent stunting prevention interventions, multidisciplinary programs utilizing engaging digital health modules and grassroots partnerships should be developed and tested. These programs aim to enhance knowledge retention among youth through appealing online content and interactive community activities. Rigorous evaluation of biopsychosocial approaches can establish integrated best practices across individual, social and policy dimensions for reducing stunting.
Epidemiology of canine ehrlichiosis and molecular characterization of Erhlichia canis in Bangladeshi pet dogs
Authors: Kabir Ajran , Chouhan Chandra Shaker , Habib Tasmia , Hossain Md. Zawad , Raihan Abu , Yeasmin Farzana , Siddique Mahbubul Pratik , Rahman A. K. M. Anisur , Nahar Azimun , Rahman Md. Siddiqur , Ehsan Md. Amimul 
Published: December 2024

Background
Ehrlichia canis, a rickettsial organism, is responsible for causing ehrlichiosis, a tick-borne disease affecting dogs.

Objectives
This study aimed to estimate ehrlichiosis prevalence and identify associated risk factors in pet dogs.

Methods
A total of 246 peripheral blood samples were purposively collected from pet dogs in Dhaka, Mymensingh, and Rajshahi districts between December 2018 and December 2020. Risk factor data were obtained through face-to-face interviews with dog owners using a pre-structured questionnaire. Multivariable logistic regression analysis identified risk factors. Polymerase chain reaction targeting the 16S rRNA gene confirmed Ehrlichia spp. PCR results were further validated by sequencing.

Results
The prevalence and case fatality of ehrlichiosis were 6.9% and 47.1%, respectively. Dogs in rural areas had 5.8 times higher odds of ehrlichiosis (odd ratio, OR: 5.84; 95% CI: 1.72–19.89) compared to urban areas. Dogs with access to other dogs had 5.14 times higher odds of ehrlichiosis (OR: 5.14; 95% CI: 1.63–16.27) than those without such access. Similarly, irregularly treated dogs with ectoparasitic drugs had 4.01 times higher odds of ehrlichiosis (OR: 4.01; 95% CI: 1.17–14.14) compared to regularly treated dogs. The presence of ticks on dogs increased ehrlichiosis odds nearly by 3 times (OR: 3.02; 95% CI: 1.02–8.97). Phylogenetic analysis, based on 17 commercially sequenced isolates, showed different clusters of aggregation, however, BAUMAH-13 (PP321265) perfectly settled with a China isolate (OK667945), similarly, BAUMAH-05 (PP321257) with Greece isolate (MN922610), BAUMAH-16 (PP321268) with Italian isolate (KX180945), and BAUMAH-07 (PP321259) with Thailand isolate (OP164610).

Conclusions
Pet owners and veterinarians in rural areas should be vigilant in monitoring dogs for ticks and ensuring proper preventive care. Limiting access to other dogs in high-risk areas can help mitigate disease spread. Tick prevention measures and regular treatment with ectoparasitic drugs will reduce the risk of ehrlichiosis in dogs. The observed genetic similarity of the Bangladeshi Ehrlichia canis strain highlights the need for ongoing surveillance and research to develop effective control and prevention strategies, both within Bangladesh and globally.
Mechanism of exacerbation of traumatic brain injury under warfarin anticoagulation in male mice
Authors: Tatara Yuki , Nakao Ken-ichiro , Shimada Ryo , Kibayashi Kazuhiko 
Published: December 2024

Introduction
Traumatic brain injury (TBI) is exacerbated in patients on antithrombotic medications, with warfarin leading to increased bleeding in some cases. However, the extent to which this bleeding increases lethality and its long-term effects remain unclear. This study aimed to investigate the exacerbation of TBI by warfarin treatment and comprehensively evaluate the impact of TBI on the anticoagulant effects of warfarin.

Methods
We induced TBI in mice after pre-treatment with warfarin and analyzed TBI exacerbation based on the prothrombin time-international normalized ratio (PT-INR) value, brain hemorrhage volume, blood warfarin and 7-hydroxywarfarin levels, and cytochrome P450 2C9 (CYP2C9) protein expression. C57BL/6J mice fed with a vitamin K-deficient diet received oral warfarin (low dose, 0.35 mg/kg/24 h; high dose, 0.70 mg/kg/24 h), and focal brain damage was induced in the cerebral cortices using a brain contusion device. Warfarin-treated injured mice were compared with sham-treated mice (scalp incision alone or scalp incision + bone window formation).

Results
When warfarin was administered, the PT-INR value and brain hemorrhage volume associated with cerebral contusion increased on the first day post-injury. High blood warfarin and 7-hydroxywarfarin levels were observed. However, no significant differences in CYP2C9 expression were observed between the groups.

Discussion
Elevated warfarin levels post-injury can increase cerebral hemorrhage risk, possibly worsening TBI. TBI might also elevate warfarin levels, heightening its anticoagulant effects. Therefore, assessing injury severity levels and PT-INR values in patients with TBI on warfarin is crucial to anticipate delayed bleeding risks.