bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stakeholder-informed pragmatic trial protocol of the TabCAT-BHA for the detection of cognitive impairment in primary care
Authors: Sideman Alissa Bernstein , Nguyen Huong Q. , Langer-Gould Annette , Lee Eric A. , Borson Soo , Shen Ernest , Tsoy Elena , Macias Mayra , Goode Collette , Rankin Katherine , Kramer Joel , Possin Katherine L. 
Published: August 2024

Abstract
Background
Cognitive impairment and dementia are frequently under-recognized. Health system strategies anchored in primary care are essential to address gaps in timely, comprehensive diagnosis. The goal of this paper is to describe the adaptation of a tablet-based brain health assessment (TabCAT-BHA) intervention and the study protocol to test its effectiveness in improving the detection of cognitive impairment, including dementia.

Methods
This mixed-methods, pragmatic, cluster randomized, hybrid effectiveness-implementation trial is being conducted in two 18-month waves with 26 Kaiser Permanente Southern California primary care clinics, with 13 serving as intervention clinics and 13 as usual care clinics. Patients 65 years and older with memory concerns (n ~ 180,000) receiving care at the 26 clinics will be included in the analyses. Primary care clinics are provided the following practice supports as part of the TabCAT-BHA intervention: brief education and training on neurocognitive disorders and study workflows; digital tools to assess cognitive function and support clinician decision making and documentation; and registered nurse support during the work-up and post-diagnosis periods for primary care providers, patients, and families. The intervention was adapted based on engagement with multiple levels of clinical and operational leaders in the healthcare system. Effectiveness outcomes include rates of cognitive impairment diagnosis in primary care and rates of completed standardized cognitive assessments and specialist referrals with incident diagnoses. Implementation outcomes include acceptability-appropriateness-feasibility, adoption, and fidelity.

Results
We identified seven themes organized by system-, provider-, and patient-level domains that were used to adapt the TabCAT-BHA intervention. Accordingly, changes were made to the provider education, diagnostic work-up, and post-diagnostic support. Results will be reported in fall of 2027.

Conclusions
Our engagement with multiple primary and specialty care clinical and operational leaders to adapt the TabCAT-BHA intervention to these primary care clinics has informed the protocol to evaluate the intervention’s effectiveness for improving the detection of cognitive impairment, including dementia, in an integrated healthcare system.

Trial Registation
Clinicaltrials.gov: NCT06090578 (registered 10/24/23).
Do behavioral drivers matter for healthcare decision-making during crises? A study of low-income women in El Salvador during the COVID-19 pandemic
Authors: Lara Pedro Bernal , Daga Giuliana , Kossuth Lajos , Boo Florencia Lopez 
Published: August 2024

Abstract
Understanding health-seeking behaviors and their drivers is key for governments to manage health policies. A growing body of research explores the role of cognitive biases and heuristics in health and care-seeking behaviors, but little is known about how a context of heightened anxiety and uncertainty might influence these behavioral drivers. This study analyzes the association between four behavioral predictors—internal locus of control, impatience, optimism bias, and aspirations—and healthcare decisions among low-income women in El Salvador, controlling for other factors. We find positive associations between internal locus of control and preventive health behaviors during the COVID-19 pandemic. For instance, a one standard deviation increase in locus of control is associated with a 10% increase in an index measuring the use of masks, distancing, hand washing, and vaccination. Locus of control was also associated with women’s use of preventive health services (one standard deviation improves the likelihood of having a hypertension test in the last six months by 5.8 percentage points). In a sub-sample of mothers, we find significant relationships between the four behavioral drivers and the decisions the mothers make for their children. However, we find these associations are less robust compared to the decisions they make for themselves. Some associations were stronger during the pandemic, suggesting that feelings of uncertainty and stress could amplify behavioral drivers’ influence on health-related behaviors. This novel finding is relevant for designing policy responses for future shocks.

JEL Codes
I12, D10, D91, I30.
How women living with HIV in the UK manage infant-feeding decisions and vertical transmission risk – a qualitative study
Authors: Kasadha Bakita , Hinton Lisa , Tariq Shema , Nyatsanza Farai , Namiba Angelina , Freeman-Romilly Nell , Rai Tanvi 
Published: August 2024

Abstract
Background
The World Health Organization (WHO) recommends that women with HIV breastfeed for a minimum of one year. In contrast, across high-income countries, HIV and infant-feeding guidelines recommend exclusive formula feeding if parents want to avoid all risk of postpartum transmission. However, recently these guidelines (including in the United Kingdom (UK)) increasingly state that individuals with HIV should be supported to breast/chest feed if they meet certain criteria; such as an undetectable maternal HIV viral load and consent to additional clinical monitoring. Between 600 and 800 pregnancies are reported annually in women with HIV in the UK, with low rates of vertical transmission (0.22%). Informed infant-feeding decision-making requires clinical support. Currently, little research addresses how individuals with HIV in high-income countries navigate infant-feeding decisions with their clinical teams and familial and social networks, and the resources needed to reach an informed decision.

Methods
Semi-structured remote interviews were conducted between April 2021 – January 2022 with UK-based individuals with a confirmed HIV diagnosis who were pregnant or one-year postpartum. Using purposive sampling, pregnant and postpartum participants were recruited through NHS HIV clinics, community-based organisations and snowballing. Data were analysed thematically and organised using NVivo 12.

Results
Of the 36 cisgender women interviewed, 28 were postpartum. The majority were of Black African descent (n = 22) and born outside the UK. The majority of postpartum women had chosen to formula feed. Women’s decision-making regarding infant-feeding was determined by (1) information and support; (2) practicalities of implementing medical guidance; (3) social implications of infant-feeding decisions.

Conclusion
The evolution of UK HIV and infant-feeding guidelines are not reflected in the experiences of women living with HIV. Clinicians’ emphasis on reducing the risk of vertical transmission, without adequately considering personal, social and financial concerns, prevents women from making fully informed infant-feeding decisions. For some, seeking advice beyond their immediate clinical team was key to feeling empowered in their decision. The significant informational and support need among women with HIV around their infant-feeding options must be addressed. Furthermore, training for and communication by healthcare professionals supporting women with HIV is essential if women are to make fully informed decisions.
MSI2 regulates NLK-mediated EMT and PI3K/AKT/mTOR pathway to promote pancreatic cancer progression
Authors: Huang Longping , Sun Jian , Ma Yuteng , Chen He , Tian Chen , Dong Ming 
Published: August 2024

Abstract
Background
The incidence of pancreatic cancer is increasing by years, and the 5-year survival rate is very low. Our team have revealed that Musashi2 (MSI2) could promote aggressive behaviors in pancreatic cancer by downregulating Numb and p53. MSI2 also facilitates EMT in pancreatic cancer induced by EGF through the ZEB1-ERK/MAPK signaling pathway. This study aims to further explore the molecular mechanisms of MSI2-regulated downstream pathways in pancreatic cancer.

Methods
In vitro and in vivo experiments were conducted to investigate the role and mechanism of MSI2 in promoting malignant behaviors of pancreatic cancer through regulation of NLK.

Results
Genes closely related to MSI2 were screened from the GEPIA and TCGA databases. We found that NLK showed the most significant changes in mRNA levels with consistent changes following MSI2 interference and overexpression. The high correlation between MSI2 and NLK was also observed at the protein level. Multivariate analysis revealed that both MSI2 and NLK were independent adverse indicators of survival in pancreatic cancer patients, as well as join together. In vitro, silencing or overexpressing NLK altered cell invasion and migration, by regulating EMT and the PI3K-AKT-mTOR pathway. Silencing MSI2 reduced protein expression in the EMT and PI3K-AKT-mTOR pathways, leading to decreased cell invasion and migration abilities, while these effects could be reversed by overexpression of NLK. In vivo, MSI2 silencing inhibited liver metastasis, which could be reversed by overexpressing NLK. Mechanistically, MSI2 directly binds to the translation regulatory region of NLK mRNA at positions 79–87 nt, enhancing its transcriptional activity and exerting post-transcriptional regulatory roles. The analysis of molecular docking showed the close relationship between MSI2 and NLK in pancreatic cancer patients.

Conclusions
Our findings elucidate the regulatory mechanisms of the MSI2-NLK axis in modulating aggressive behaviors of pancreatic cancer cells, which providing new evidence for therapeutic strategies in pancreatic cancer.
Investigation of pulmonary inflammatory responses following intratracheal instillation of and inhalation exposure to polypropylene microplastics
Authors: Tomonaga Taisuke , Higashi Hidenori , Izumi Hiroto , Nishida Chinatsu , Kawai Naoki , Sato Kazuma , Morimoto Toshiki , Higashi Yasuyuki , Yatera Kazuhiro , Morimoto Yasuo 
Published: August 2024

Abstract
Background
Microplastics have been detected in the atmosphere as well as in the ocean, and there is concern about their biological effects in the lungs. We conducted a short-term inhalation exposure and intratracheal instillation using rats to evaluate lung disorders related to microplastics. We conducted an inhalation exposure of polypropylene fine powder at a low concentration of 2 mg/m3 and a high concentration of 10 mg/m3 on 8-week-old male Fischer 344 rats for 6 h a day, 5 days a week for 4 weeks. We also conducted an intratracheal instillation of polypropylene at a low dose of 0.2 mg/rat and a high dose of 1.0 mg/rat on 12-week-old male Fischer 344 rats. Rats were dissected from 3 days to 6 months after both exposures, and bronchoalveolar lavage fluid (BALF) and lung tissue were collected to analyze lung inflammation and lung injury.

Results
Both exposures to polypropylene induced a persistent influx of inflammatory cells and expression of CINC-1, CINC-2, and MPO in BALF from 1 month after exposure. Genetic analysis showed a significant increase in inflammation-related factors for up to 6 months. The low concentration in the inhalation exposure of polypropylene also induced mild lung inflammation.

Conclusion
These findings suggest that inhaled polypropylene, which is a microplastic, induces persistent lung inflammation and has the potential for lung disorder. Exposure to 2 mg/m3 induced inflammatory changes and was thought to be the Lowest Observed Adverse Effect Level (LOAEL) for acute effects of polypropylene. However, considering the concentration of microplastics in a real general environment, the risk of environmental hazards to humans may be low.
Utilization of integrated community-based case management of childhood illness and associated factors in Ethiopia: a systematic review and meta-analysis
Authors: Mekie Maru , Belachew Yismaw Yimam , Fenta Setegn Muche , Ferede Wassie Yazie , Yehuala Enyew Dagnew , Taklual Wubet , Mekonen Demewoz Kefale , Addisu Dagne 
Published: August 2024

Abstract
Background
Despite significant progress being made in reducing under-five mortality, three-fourths of under-five deaths are still caused by preventable conditions such as pneumonia, diarrhea, malaria, and newborn issues. Integrated community case management of childhood illnesses (ICCM) could serve as a means to reduce preventable child mortality in Low- and Middle-Income countries. Our aim was to assess the overall level of ICCM utilization and its associated factors in Ethiopia.

Methods
Candidate studies for inclusion in this review were identified through searches across various databases, including PubMed, EMBASE, Google Scholar, and university repositories online databases, spanning from February 1, 2024, to March 18, 2024. The quality assessment of the studies included in this systematic review and meta-analysis was conducted using the Newcastle-Ottawa Quality Assessment Scale (NOS). Data extraction and analysis were carried out using Microsoft Excel and Stata 17 software, respectively. Heterogeneity among the studies was assessed using Cochran’s Q test and I2 statistics, while the presence of publication bias was evaluated through funnel plots and Egger’s regression asymmetry test. Subgroup analysis was performed based on sample size and study site.

Results
In this study, the pooled level of ICCM utilization was found to be 42.73 (95%, CI 27.65%, 57.80%) based on the evidence obtained from ten primary studies. In this review, parents’ awareness about illness (OR = 2.77, 95%, CI 2.06, 3.74), awareness about ICCM service (OR = 3.64, 95%, CI 2.16, 6.14), perceived severity of the disease (OR = 3.14, 95%, CI 2.33, 4.23), secondary/above level of education (OR = 2.57, 95%, CI 1.39, 4.77), and live within 30 min distance to the health post (OR = 3.93, 95%, CI 2.30, 6.74) were variables significantly associated with utilization of ICCM in Ethiopia.

Conclusion
The utilization of ICCM was found to be low in Ethiopia. Factors such as parents’ awareness about the illness, knowledge of ICCM services, perceived severity of the disease, attending a secondary or more level of education, and living within 30 min distance to the health post were significantly associated with the utilization of ICCM. Therefore, it is crucial to focus on creating awareness and improving access to high-quality ICCM services to reduce child morbidity and mortality from preventable causes.
DNA-binding factor footprints and enhancer RNAs identify functional non-coding genetic variants
Authors: Biddie Simon C. , Weykopf Giovanna , Hird Elizabeth F. , Friman Elias T. , Bickmore Wendy A. 
Published: August 2024

Abstract
Background
Genome-wide association studies (GWAS) have revealed a multitude of candidate genetic variants affecting the risk of developing complex traits and diseases. However, the highlighted regions are typically in the non-coding genome, and uncovering the functional causative single nucleotide variants (SNVs) is challenging. Prioritization of variants is commonly based on genomic annotation with markers of active regulatory elements, but current approaches still poorly predict functional variants. To address this, we systematically analyze six markers of active regulatory elements for their ability to identify functional variants.

Results
We benchmark against molecular quantitative trait loci (molQTL) from assays of regulatory element activity that identify allelic effects on DNA-binding factor occupancy, reporter assay expression, and chromatin accessibility. We identify the combination of DNase footprints and divergent enhancer RNA (eRNA) as markers for functional variants. This signature provides high precision, but with a trade-off of low recall, thus substantially reducing candidate variant sets to prioritize variants for functional validation. We present this as a framework called FINDER—Functional SNV IdeNtification using DNase footprints and eRNA.

Conclusions
We demonstrate the utility to prioritize variants using leukocyte count trait and analyze variants in linkage disequilibrium with a lead variant to predict a functional variant in asthma. Our findings have implications for prioritizing variants from GWAS, in development of predictive scoring algorithms, and for functionally informed fine mapping approaches.
Study protocol: perinatal mood treatment study
Authors: Wolitzky-Taylor Kate , Richards Misty C. , Welborn Amelia , McDonald Vanessa , Arnaudova Inna , Fears Scott , O’Mahen Heather , Newby Jill M. , Millard Mike , Metts Allison V. , Stein Alan , Freimer Nelson , Craske Michelle G. 
Published: August 2024

AbstractPerinatal depression (PND) affects up to 20% of women and is associated with significant impairment and disability in affected women. In addition, perinatal depression is associated with broader public health and multigenerational consequences. Innovative approaches are needed to reduce the burden of perinatal depression through identification, tracking, and treatment of depressive symptoms during the perinatal period. This study is a randomized clinical trial comparing the relative efficacy of a multi-tiered system of care, Screening and Treatment of Anxiety and Depression (STAND) to perinatal care delivered by a reproductive psychiatrist in reducing symptoms of depression and anxiety. A sample of 167 individuals was randomized between week 28 of pregnancy and 6 months postpartum. A secondary aim compares the original online therapy intervention used in the first half of the study to a newer online therapy program used in the second half of the study for individuals assigned to the STAND treatment. The study measures, intervention groups, and analysis methods are described, as well as expected implications. The findings from this study may improve the methods for tracking symptom changes over time, monitoring treatment response, and providing personalized care for individuals with PND. As such, this study may improve the lives of patients with PND and their families and lower the related health care costs to society.Trial registration NCT: 9/24/2021NCT direct link: https://www.clinicaltrials.gov/study/NCT05056454?term=NCT05056454&rank=1&a=1.
Clinical trials with mechanism evaluation of intervention(s): mind the power and sample size calculation
Authors: Lee Kim May , Hellier Jennifer , Emsley Richard 
Published: August 2024

Abstract
Background
Mediation analysis, often completed as secondary analysis to estimating the main treatment effect, investigates situations where an exposure may affect an outcome both directly and indirectly through intervening mediator variables. Although there has been much research on power in mediation analyses, most of this has focused on the power to detect indirect effects. Little consideration has been given to the extent to which the strength of the mediation pathways, i.e., the intervention-mediator path and the mediator-outcome path respectively, may affect the power to detect the total effect, which would correspond to the intention-to-treat effect in a randomized trial.

Methods
We conduct a simulation study to evaluate the relation between the mediation pathways and the power of testing the total treatment effect, i.e., the intention-to-treat effect. Consider a sample size that is computed based on the usual formula for testing the total effect in a two-arm trial. We generate data for a continuous mediator and a normal outcome using the conventional mediation models. We estimate the total effect using simple linear regression and evaluate the power of a two-sided test. We explore multiple data generating scenarios by varying the magnitude of the mediation paths whilst keeping the total effect constant.

Results
Simulations show the estimated total effect is unbiased across the considered scenarios as expected, but the mean of its standard error increases with the magnitude of the mediator-outcome path and the variability in the residual error of the mediator, respectively. Consequently, this affects the power of testing the total effect, which is always lower than planned when the mediator-outcome path is non-trivial and a naive sample size was employed. Analytical explanation confirms that the intervention-mediator path does not affect the power of testing the total effect but the mediator-outcome path. The usual effect size consideration can be adjusted to account for the magnitude of the mediator-outcome path and its residual error.

Conclusions
The sample size calculation for studies with efficacy and mechanism evaluation should account for the mediator-outcome association or risk the power to detect the total effect/intention-to-treat effect being lower than planned.
Acute abducens nerve palsy following coronavirus disease 2019 vaccination: a case report
Authors: Wang Chen-Ting , Li Jie-Yuan 
Published: August 2024

Abstract
Background
Abducens nerve palsy is the most common isolated ocular cranial nerve palsy. In adults, nontraumatic etiologies of isolated sixth cranial nerve palsy can include vascular disease, inflammation, tumors, and a prior history of infection.

Case presentation
We present a case of a 52-year-old Asian male who developed acute abducens nerve palsy after vaccination with the AstraZeneca coronavirus disease 2019 vaccine. A complete workup including magnetic resonance imaging of the brain and orbits revealed no abnormalities. The patient experienced a gradual recovery over 10 weeks through alternative eye patching. The abducens nerve palsy is postulated to be correlated with the coronavirus disease 2019 vaccine.

Conclusion
Despite the recognized efficacy and cost benefits of coronavirus disease 2019 vaccines, clinicians should be aware of the possible association between cranial nerve palsies and coronavirus disease 2019 vaccines.
Advancements in biotransformation pathway prediction: enhancements, datasets, and novel functionalities in enviPath
Authors: Hafner Jasmin , Lorsbach Tim , Schmidt Sebastian , Brydon Liam , Dost Katharina , Zhang Kunyang , Fenner Kathrin , Wicker Jörg 
Published: August 2024

Abstract
enviPath is a widely used database and prediction system for microbial biotransformation pathways of primarily xenobiotic compounds. Data and prediction system are freely available both via a web interface and a public REST API. Since its initial release in 2016, we extended the data available in enviPath and improved the performance of the prediction system and usability of the overall system. We now provide three diverse data sets, covering microbial biotransformation in different environments and under different experimental conditions. This also enabled developing a pathway prediction model that is applicable to a more diverse set of chemicals. In the prediction engine, we implemented a new evaluation tailored towards pathway prediction, which returns a more honest and holistic view on the performance. We also implemented a novel applicability domain algorithm, which allows the user to estimate how well the model will perform on their data. Finally, we improved the implementation to speed up the overall system and provide new functionality via a plugin system.

Scientific contribution
The main scientific contributions are the development of a pathway prediction model applicable to diverse chemicals, a specialized evaluation method for holistic performance assessment, and a novel applicability domain algorithm for user-specific performance estimation. The introduction of two new data sets, and the creation of links to EC classes make enviPath a unique resource in microbial biotransformation research.