bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polygenic risk scores for disease risk prediction in Africa: current challenges and future directions
Authors: Fatumo Segun , Sathan Dassen , Samtal Chaimae , Isewon Itunuoluwa , Tamuhla Tsaone , Soremekun Chisom , Jafali James , Panji Sumir , Tiffin Nicki , Fakim Yasmina Jaufeerally 
Published: October 2023

AbstractEarly identification of genetic risk factors for complex diseases can enable timely interventions and prevent serious outcomes, including mortality. While the genetics underlying many Mendelian diseases have been elucidated, it is harder to predict risk for complex diseases arising from the combined effects of many genetic variants with smaller individual effects on disease aetiology. Polygenic risk scores (PRS), which combine multiple contributing variants to predict disease risk, have the potential to influence the implementation for precision medicine. However, the majority of existing PRS were developed from European data with limited transferability to African populations. Notably, African populations have diverse genetic backgrounds, and a genomic architecture with smaller haplotype blocks compared to European genomes. Subsequently, growing evidence shows that using large-scale African ancestry cohorts as discovery for PRS development may generate more generalizable findings. Here, we (1) discuss the factors contributing to the poor transferability of PRS in African populations, (2) showcase the novel Africa genomic datasets for PRS development, (3) explore the potential clinical utility of PRS in African populations, and (4) provide insight into the future of PRS in Africa.
Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats
Authors: Yu Fuyao , Xing Chuan , Fan Yiping , Liu Yanping , Su Peng , Yang Qiuhua , Dong Yanbin , Hou Yang , Pan Shinong 
Published: October 2023

Abstract
Background
Physical exercise is the first-line intervention for prediabetes, and metformin is the most widely used oral insulin-sensitizing agent. Moreover, intermuscular adipose tissue (IMAT) directly affects insulin resistance by helping maintain glucose homeostasis. Here, we evaluated the effects of moderate aerobic exercise and/or metformin on histological IMAT parameters in non-streptozotocin-induced prediabetes.

Methods
Male Wistar rats with prediabetes fed a high-fat diet and high-sugar drinks were randomly assigned to high-fat diet (PRE), metformin (MET), moderate aerobic exercise (EXE), combined therapy (EMC), or EMC + compound-c (EMA) groups for 4 weeks. Multimodal magnetic resonance imaging (MRI) was then performed, and tissue-specific inflammation and energy and lipid metabolism were evaluated in IMAT.

Results
The EXE group had lower inflammatory factor levels, lipid metabolism, and mitochondrial oxidative stress, and shorter IMAT adipocyte diameters than the MET group. The MET group exhibited lower IL-1β and Plin5 expression than the PRE group. Furthermore, the IMAT of the EMC group had lower TNF-α and phosphorylated NF-κB levels and higher GLUT1 and GLUT4 expression than the PRE group. Multimodal MRI revealed significant changes in transverse-relaxation time 2, apparent diffusion coefficient, and fractional anisotropy values in the IMAT and muscles, as well as lower IMAT% values in the EXE and EMC groups than in the MET and PRE groups.

Conclusion
Moderate aerobic exercise training can effectively improve IMAT function and structure via the AMP-activated protein kinase pathway in prediabetes. Combining metformin with moderate aerobic exercise might elicit modest synergy, and metformin does not counterbalance the beneficial effects of exercise.
The immune-adjunctive potential of recombinant LAB vector expressing murine IFNλ3 (MuIFNλ3) against Type A Influenza Virus (IAV) infection
Authors: Yadav Sandeep , Varma Aparna , Muralidharan Aparna Odayil , Bhowmick Sucharita , Mondal Samiran , Mallick Amirul Islam 
Published: October 2023

Abstract
Background
The conventional means of controlling the recurring pandemics of Type A Influenza Virus (IAV) infections remain challenging primarily because of its high mutability and increasing drug resistance. As an alternative to control IAV infections, the prophylactic use of cytokines to drive immune activation of multiple antiviral host factors has been progressively recognized. Among them, Type III Interferons (IFNs) exhibit a pivotal role in inducing potent antiviral host responses by upregulating the expression of several antiviral genes, including the Interferon-Stimulated Genes (ISGs) that specifically target the virus replication machinery. To harness the immuno-adjunctive potential, we examined whether pre-treatment of IFNλ3, a Type III IFN, can activate antiviral host responses against IAV infections.

Methods
In the present study, we bioengineered a food-grade lactic acid-producing bacteria (LAB), Lactococcus lactis (L. lactis), to express and secrete functional murine IFNλ3 (MuIFNλ3) protein in the extracellular milieu. To test the immune-protective potential of MuIFNλ3 secreted by recombinant L. lactis (rL. lactis), we used murine B16F10 cells as an in vitro model while mice (BALB/c) were used for in vivo studies.

Results
Our study demonstrated that priming with MuIFNλ3 secreted by rL. lactis could upregulate the expression of several antiviral genes, including Interferon Regulatory Factors (IRFs) and ISGs, without exacerbated pulmonary or intestinal inflammatory responses. Moreover, we also showed that pre-treatment of B16F10 cells with MuIFNλ3 can confer marked immune protection against mice-adapted influenza virus, A/PR/8/1934 (H1N1) infection.

Conclusion
Since the primary target for IAV infections is the upper respiratory and gastrointestinal tract, immune activation without affecting the tissue homeostasis suggests the immune-adjunctive potential of IFNλ3 against IAV infections.
Training items for trainee residents in community medicine in rural areas
Authors: Kumabe Ayako , Kenzaka Tsuneaki , Mizutani Naoya , Goda Ken , Yahata Shinsuke 
Published: October 2023

Abstract
Objective
To examine the significant events experienced by initial trainees during community medicine training, evaluate their impact on community medicine practice, and support improvements in rural community medicine training.

Results
Three faculty teachers independently evaluated the reports of 25 residents who had completed a four-week community medicine training in a rural area to analyze major events. The reports were analyzed using topics from the Model Core Curriculum for Medical Education that relate to rural medicine. The most frequently reported items were identified as follows: Primary care: 9 (36.0%); integrated community care systems: 8 (32.0%); medical care in the local community: 7 (28.0%); home health care and systems, patient-physician relationship, and end-of-life medical treatment and care: 6 each (24.0%). Reports from residents describing events related to home health care and systems and end-of-life medical treatment and care were related to more than one item.
Blockade of adenosine A2A receptors reverses early spatial memory defects in the APP/PS1 mouse model of Alzheimer’s disease by promoting synaptic plasticity of adult-born granule cells
Authors: Ji Qi , Yang Yang , Xiong Yun , Zhang Ying-Jie , Jiang Jun , Zhou Li-Ping , Du Xiao-Hui , Wang Chun-Xiang , Zhu Zhi-Ru 
Published: October 2023

Abstract
Background
The over-activation of adenosine A2A receptors (A2AR) is closely implicated in cognitive impairments of Alzheimer's disease (AD). Growing evidence shows that A2AR blockade possesses neuroprotective effects on AD. Spatial navigation impairment is an early manifestation of cognitive deficits in AD. However, whether A2AR blockade can prevent early impairments in spatial cognitive function and the underlying mechanism is still unclear.

Methods
A transgenic APP/PS1 mouse model of AD amyloidosis was used in this study. Behavioral tests were conducted to observe the protective effects of A2AR blockade on early spatial memory deficits in 4-month old APP/PS1 mice. To investigate the underlying synaptic mechanism of the protective effects of A2AR blockade, we further examined long-term potentiation (LTP) and network excitation/inhibition balance of dentate gyrus (DG) region, which is relevant to unique synaptic functions of immature adult-born granule cells (abGCs). Subsequently, the protective effects of A2AR blockade on dendritic morphology and synaptic plasticity of 6-week-old abGCs was investigated using retrovirus infection and electrophysiological recordings. The molecular mechanisms underlying neuroprotective properties of A2AR blockade on the synaptic plasticity of abGCs were further explored using molecular biology methods.

Results
APP/PS1 mice displayed DG-dependent spatial memory deficits at an early stage. Additionally, impaired LTP and an imbalance in network excitation/inhibition were observed in the DG region of APP/PS1 mice, indicating synaptic structural and functional abnormalities of abGCs. A2AR was found to be upregulated in the hippocampus of the APP/PS1 mouse model of AD. Treatment with the selective A2AR antagonist SCH58261 for three weeks significantly ameliorated spatial memory deficits in APP/PS1 mice and markedly restored LTP and network excitation/inhibition balance in the DG region. Moreover, SCH58261 treatment restored dendritic morphology complexity and enhanced synaptic plasticity of abGCs in APP/PS1 mice. Furthermore, SCH58261 treatment alleviated the impairment of synaptic plasticity in abGCs. It achieved this by remodeling the subunit composition of NMDA receptors and increasing the proportion of NR2B receptors in abGCs of APP/PS1 mice.

Conclusions
Blockade of A2AR improves early spatial memory deficits in APP/PS1 mice, possibly by reversing synaptic defects of abGCs. This finding suggests that A2AR blockade could be a potential therapy for AD.
The remodeling of metabolic brain pattern in patients with extracranial diffuse large B-cell lymphoma
Authors: Liu Junyi , Tang Ming , Zhu Dongling , Ruan Ge , Zou Sijuan , Cheng Zhaoting , Zhu Xiaohua , Zhu Yuankai 
Published: October 2023

Abstract
Background
Owing to the advances in diagnosis and therapy, survival or remission rates for lymphoma have improved prominently. Apart from the lymphoma- and chemotherapy-related somatic symptom burden, increasing attention has been drawn to the health-related quality of life. The application of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET/CT) has been routinely recommended for the staging and response assessment of FDG-avid lymphoma. However, up till now, only a few researches have investigated the brain metabolic impairments in patients with pre-treatment lymphoma. The determination of the lymphoma-related metabolic brain pattern would facilitate exploring the tailored therapeutic regimen to alleviate not only the physiological, but also the psychological symptoms. In this retrospective study, we aimed to establish the diffuse large B-cell lymphoma-related pattern (DLBCLRP) of metabolic brain network and investigate the correlations between DLBCLRP and several indexes of the staging and response assessment.

Results
The established DLBCLRP was characterized by the increased metabolic activity in bilateral cerebellum, brainstem, thalamus, striatum, hippocampus, amygdala, parahippocampal gyrus and right middle temporal gyrus and by the decreased metabolic activity in bilateral occipital lobe, parietal lobe, anterior cingulate gyrus, midcingulate cortex and medial frontal gyrus. Significant difference in the baseline expression of DLBCLRP was found among complete metabolic response (CMR), partial metabolic response (PMR) and progressive metabolic disease (PMD) groups (P < 0.01). DLBCLRP expressions were also significantly or tended to be positively correlated with international prognostic index (IPI) (rs = 0.306, P < 0.05), lg(total metabolic tumor volume, TMTV) (r = 0.298, P < 0.05) and lg(total lesion glycolysis, TLG) (r = 0.233, P = 0.064). Though no significant correlation of DLBCLRP expression was found with Ann Arbor staging or tumor SUVmax (P > 0.05), the post-treatment declines of DLBCLRP expression were significantly positively correlated with Ann Arbor staging (rs = 0.284, P < 0.05) and IPI (rs = 0.297, P < 0.05).

Conclusions
The proposed DLBCLRP would lay the foundation for further investigating the cerebral dysfunction related to DLBCL itself and/or treatments. Besides, the expression of DLBCLRP was associated with the tumor burden of lymphoma, implying a potential biomarker for prognosis.
Effects of novel androgen receptor signaling inhibitors on PSMA PET signal intensity in patients with castrate-resistant prostate cancer: a prospective exploratory serial imaging study
Authors: Sonni Ida , Gafita Andrei , Unterrainer Lena M. , Alano Rejah M. , Lira Stephanie , Shen John , Drakaki Alexandra , Grogan Tristan , Rettig Matthew B. , Czernin Johannes , Calais Jeremie 
Published: October 2023

Abstract
Background
PSMA expression is influenced by hormonal status. We evaluated changes in PSA and whole-body 68Ga-PSMA-11 PET/CT (WB-PSMA PET) after initiation of androgen receptor signaling inhibitors (ARSi).

Methods
Prospectively enrolled patients with metastatic castration-resistant prostate cancer (mCRPC) initiating ARSi underwent serial PSA measurements and WB-PSMA PET at baseline, 1-week, and 3-months post-ARSi. We correlated WB-PSMA PET metrics and PSA kinetics after ARSi to 1-year clinical outcome.

Results
Due to low enrollment rate, the study was closed before reaching the recruitment goal of 30 patients. Nine patients were enrolled. At 1-year, unfavorable outcome was documented in 6/9 (66%) patients. Nine/9 patients completed PSMA PET at 1-week, 5/9 at 3-months. Changes in PSA, PSMA-VOL, SUVmean and SUVmax were − 12%, + 5%, + 3%, and + 10% at 1-week, − 42%, − 16%, − 15% and − 17% at 3-months, respectively.

Conclusions
Our prospective trial involving 9 mCRPC patients initiating ARSi did not show significant modulation of PSMA expression measured on WB-PSMA PET at 1-week. This study was registered on clinicaltrials.gov (NCT04279561).
Mortality, incidence, and microbiological documentation of ventilated acquired pneumonia (VAP) in critically ill patients with COVID-19 or influenza
Authors: Laurichesse Guillaume , Schwebel Carole , Buetti Niccolò , Neuville Mathilde , Siami Shidasp , Cohen Yves , Laurent Virginie , Mourvillier Bruno , Reignier Jean , Goldgran‐Toledano Dany , Ruckly Stéphane , de Montmollin Etienne , Souweine Bertrand , Timsit Jean‐François , Dupuis Claire ,   for the OUTCOME R. E. A. network
Published: October 2023

Abstract
Background
Data on ventilator associated pneumonia (VAP) in COVID-19 and influenza patients admitted to intensive care units (ICU) are scarce. This study aimed to estimate day-60 mortality related to VAP in ICU patients ventilated for at least 48 h, either for COVID-19 or for influenza, and to describe the epidemiological characteristics in each group of VAP.

Design
Multicentre retrospective observational study.

Setting
Eleven ICUs of the French OutcomeRea™ network.

Patients
Patients treated with invasive mechanical ventilation (IMV) for at least 48 h for either COVID-19 or for flu.

Results
Of the 585 patients included, 503 had COVID-19 and 82 had influenza between January 2008 and June 2021. A total of 232 patients, 209 (41.6%) with COVID-19 and 23 (28%) with influenza, developed 375 VAP episodes. Among the COVID-19 and flu patients, VAP incidences for the first VAP episode were, respectively, 99.2 and 56.4 per 1000 IMV days (p < 0.01), and incidences for all VAP episodes were 32.8 and 17.8 per 1000 IMV days (p < 0.01). Microorganisms of VAP were Gram-positive cocci in 29.6% and 23.5% of episodes of VAP (p < 0.01), respectively, including Staphylococcus aureus in 19.9% and 11.8% (p = 0.25), and Gram-negative bacilli in 84.2% and 79.4% (p = 0.47). In the overall cohort, VAP was associated with an increased risk of day-60 mortality (aHR = 1.77 [1.36; 2.30], p < 0.01), and COVID-19 had a higher mortality risk than influenza (aHR = 2.22 [CI 95%, 1.34; 3.66], p < 0.01). VAP was associated with increased day-60 mortality among COVID-19 patients (aHR = 1.75 [CI 95%, 1.32; 2.33], p < 0.01), but not among influenza patients (aHR = 1.75 [CI 95%, 0.48; 6.33], p = 0.35).

Conclusion
The incidence of VAP was higher in patients ventilated for at least 48 h for COVID-19 than for influenza. In both groups, Gram-negative bacilli were the most frequently detected microorganisms. In patients ventilated for either COVID-19 or influenza VAP and COVID-19 were associated with a higher risk of mortality.
Unraveling the South Asian enigma: concurrent manifestations of child anthropometric failures and their determinants in selected South Asian countries
Authors: Saif Sabeen , Anwar Sofia 
Published: October 2023

AbstractMalnutrition among children is pervasive in South Asia and there are also reports of overnutrition. To better understand this phenomenon, we need a composite measure. However, the existing measures such as CIAF (Composite Index of Anthropometric Failure) and its revised version have ignored the overnutrition aspect of the phenomenon. This study proposes an extended version of CIAF which also considers overnutrition. This new measure was compared with the existing measures by using data from 1990 to 2018 for three selected South Asian countries including Pakistan, India and Bangladesh. We also examined the effects of socioeconomic and environmental variables on the outcome variable. The results reveal that the new measure (ECIAF) is better at measuring the phenomena. The burden of overall malnutrition has been decreased in the region. However, an increase in the concomitant prevalence of wasting and underweight is observed in both Pakistan and India and stunting and overweight is observed only in India. Besides, political stability, prevalence of undernourishment, anemia in children, mother’s education, household size, dependency ratio, air pollution and unimproved sanitation are significantly correlated with childhood malnutrition. The findings also testified to long-run cointegrating relationship among the variables.
Genoprotective potential of Macaranga species phytochemical compounds on HT-29 human colorectal adenocarcinoma cell line
Authors: Siew Ee Ling , Pearanpan Lishantini , Zamkhuri Zhafri , Nordin Fariza Juliana , Ooi Theng Choon , Chan Kok Meng , Kamarozaman Aisyah Salihah , Ahmat Norizan , Rajab Nor Fadilah 
Published: October 2023

Abstract
Background
The species of genus Macaranga are widely found in Malaysian secondary forests and has been used as an alternative for treating varieties of illness. Studies have shown that the medicinal properties of this genus contain anti-inflammatory, antioxidant, and anti-cancer effects. This study aimed to determine the cytotoxicity of six isolated phytochemicals from Macaranga heynei (M. heynei), Macaranga lowii and Shorea leprosula on HT-29 human colorectal adenocarcinoma cell lines.

Results
One out of six isolated phytochemical compounds, identified as “Laevifolin A”, showed a cytotoxicity with an IC50 value of 21.2 µM following 48 h treatment as detected using Sulforhodamine B (SRB) assay. Additionally, no induction of apoptosis and oxidative stress were observed on Laevifolin A treated HT-29 cells as determined using Annexin V-FITC/PI assay and dihydroethidine (HE) staining, respectively. Additionally, no damage to the DNA were observed as measured using the Alkaline Comet assay. Further investigation on menadione-induced oxidative DNA damage showed the genoprotective potential of Laevifolin A on HT-29 cells.

Conclusions
In conclusion, this study indicated that only one compound (Laevifolin A) that extracted from M. heynei has the cytotoxicity potential to be developed as an anticancer agent in human colorectal adenocarcinoma. However, besides exhibiting cytotoxic effect, the compound also exhibits genoprotective capability that warrant further investigation.
Breakfast patterns in relation to physical activity among school adolescents in Karachi, Pakistan
Authors: Ashfaq Mehak Muhammad , Jawed Nida , Safdar Nilofer Fatimi , Bhutto Adnan Ahmed 
Published: October 2023

Abstract
Background
Unhealthy habits and poor diet patterns are significant concerns among adolescents, impacting their overall quality of life. This study aimed to assess and improve these habits in adolescents.

Methods
This is a cross-sectional study conducted in 2017–2018 in Karachi. The research participants, aged 11–17 years, were drawn from lower-middle-income secondary schools using multistage random selection. Sociodemographics, the Physical Activity Questionnaire for Adolescents (PAQ-A), and breakfast consumption were determined through questionnaire and a food frequency survey.

Results
A study of 334 school-going adolescents in Karachi, Pakistan, found that 82% consumed breakfast daily, with chapatti being the preferred choice (72.2%). Physical activity levels varied, but 56.6% engaged in regular activity. No significant differences were found in breakfast consumption by age or parental education.

Conclusions
Understanding South Asian adolescents’ breakfast habits is crucial. Promoting healthier breakfast options and increased physical activity are recommended for long-term well-being, with further research needed for targeted interventions.
The effects of short video app-guided loving-kindness meditation on college students’ mindfulness, self-compassion, positive psychological capital, and suicide ideation
Authors: Liu Chao , Chen Hao , Zhang Ayuan , Gong XiaoGang , Wu Kan , Liu Chia-Yih , Chiou Wen-Ko 
Published: October 2023

Abstract
Objective
The study investigated the effects of a short video app guided loving-kindness meditation (LKM) on college students’ mindfulness, self-compassion, positive psychological capital, and suicide ideation. The purpose of the study is to investigate the intervention effect of LKM training on suicidal ideation among college students with the help of the short video application and to provide an empirical basis for the exploration of early suicide intervention strategies for college students.

Methods
We recruited 80 college students from a university in China. The final 74 eligible participants were divided into two groups: app use group (n = 37) and the control group (n = 37). The app group accepted an 8-week app use interference, while the control group underwent no interference. We measured four major variable factors (mindfulness, self-compassion, positive psychological capital, and suicide ideation) before and after the app use intervention.

Results
In the app group, self-compassion and positive psychological capital were significantly higher, and suicide ideation was significantly lower than the control group. In the control group, there were no noticeable differences in any of the four variables between the pre-test and post-test.

Conclusions
Our findings demonstrate that the short video app guided LKM may help to improve self-compassion, and positive psychological capital, and reduce suicide ideation. The finding of the short video app-guided LKM’s effect extends our understanding of the integrative effects of positive psychology and digital media on the reduction of suicide ideation.