bluuebunny/crossref_metadata_2025_split huggingface dataset:
Associations of fruit intake with adiposity and cardiometabolic biomarkers in UK Biobank
Authors: Trichia Eirini , MacLean Fiona , Perez-Cornago Aurora , Tong Tammy Y. N. , Emberson Jonathan R. , Key Timothy J. , Lewington Sarah , Carter Jennifer L. 
Published: August 2024

Abstract
Background
Fruit consumption has been associated with a lower cardiovascular disease (CVD) risk but the underlying mechanisms are unclear. We investigated the cross-sectional and prospective associations of fruit consumption with markers of adiposity, blood pressure, lipids, low-grade inflammation, glycaemia, and oxidative stress.

Methods
The main analyses included 365 534 middle-aged adults from the UK Biobank at baseline, of whom 11 510, and 38 988 were included in the first and second follow-up respectively, free from CVD and cancer at baseline. Fruit consumption frequency at baseline was assessed using a questionnaire. We assessed the cross-sectional and prospective associations of fruit with adiposity (body mass index, waist circumference and %body fat), systolic and diastolic blood pressure, lipids (low-density and high-density lipoproteins, triglycerides and apolipoprotein B), glycaemia (haemoglobin A1c), low-grade inflammation (C-reactive protein) and oxidative stress (gamma-glutamyl-transferase) using linear regression models adjusted for socioeconomic and lifestyle factors. Analyses were repeated in a subset with two to five complete 24-h dietary assessments (n = 26 596) allowing for adjustment for total energy intake.

Results
Fruit consumption at baseline generally showed weak inverse associations with adiposity and biomarkers at baseline. Most of these relationships did not persist through follow-up, except for inverse associations with diastolic blood pressure, C-reactive protein, gamma-glutamyl transferase and adiposity. However, for most mechanisms, mean levels varied by less than 0.1 standard deviations (SD) between high and low fruit consumption (> 3 vs < 1 servings/day) in further adjusted models (while the difference was < 0.2 SD for all of them). For example, waist circumference and diastolic blood pressure were 1 cm and 1 mmHg lower in high compared to low fruit intake at the first follow-up (95% confidence interval: -1.8, -0.1 and -1.8, -0.3, respectively). Analyses in the 24-h dietary assessment subset showed overall similar associations.

Conclusions
We observed very small differences in adiposity and cardiometabolic biomarkers between those who reported high fruit consumption vs low, most of which did not persist over follow-up. Future studies on other mechanisms and detailed assessment of confounding might further elucidate the relevance of fruit to cardiovascular disease.
Production and bioprocessing of epothilone B from Aspergillus niger, an endophyte of Latania loddegesii, with a conceivable biosynthetic stability: anticancer, anti-wound healing activities and cell cycle analysis
Authors: Refaat Sara , Fikry Eman , Tawfeek Nora , El-Sayed Ashraf S. A. , El-Domiaty Maher M. , El-Shafae Azza M. 
Published: August 2024

AbstractEpothilones are one of the common prescribed anticancer drugs for solid tumors, for their exceptional binding affinity with β-tubulin microtubule, stabilizing their disassembly, causing an ultimate arrest to the cellular growth. Epothilones were initially isolated from Sornagium cellulosum, however, their extremely slow growth rate and low yield of epothilone is the challenge. So, screening for a novel fungal endophyte dwelling medicinal plants, with higher epothilone productivity and feasibility of growth manipulation was the objective. Aspergillus niger EFBL-SR OR342867, an endophyte of Latania loddegesii, has been recognized as the heady epothilone producer (140.2 μg/L). The chemical structural identity of the TLC-purified putative sample of A. niger was resolved from the HPLC, FTIR and LC–ESI–MS/MS analyses, with an identical molecular structure of the authentic epothilone B. The purified A. niger epothilone B showed a resilient activity against MCF-7 (0.022 μM), HepG-2 (0.037 μM), and HCT-116 (0.12 μM), with selectivity indices 21.8, 12.9 and 4, respectively. The purified epothilone B exhibited a potential anti-wound healing activity to HepG-2 and MCF-7 cells by ~ 54.07 and 60.0%, respectively, after 24 h, compared to the untreated cells. The purified epothilone has a significant antiproliferative effect by arresting the cellular growth of MCF-7 at G2/M phase by ~ 2.1 folds, inducing the total apoptosis by ~ 12.2 folds, normalized to the control cells. The epothilone B productivity by A. niger was optimized by the response surface methodology, with ~ 1.4 fold increments (266.9 μg/L), over the control. The epothilone productivity by A. niger was reduced by ~ 2.4 folds by 6 months storage as a slope culture at 4 °C, however, the epothilone productivity was slightly restored with ethylacetate extracts of L. loddegesii, confirming the plant-derived chemical signals that partially triggers the biosynthetic genes of A. niger epothilones. So, this is the first report emphasizing the metabolic potency of A. niger, an endophyte of L. loddegesii, to produce epothilone B, that could be a new platform for industrial production of this drug.
Application of multivariate binary logistic regression grouped outlier statistics and geospatial logistic model to identify villages having unusual health-seeking habits for childhood malaria in Malawi
Authors: Hamuza Gracious A. , Singogo Emmanuel , Kaombe Tsirizani M. 
Published: August 2024

Abstract
Background
Early diagnosis and prompt treatment of malaria in young children are crucial for preventing the serious stages of the disease. If delayed treatment-seeking habits are observed in certain areas, targeted campaigns and interventions can be implemented to improve the situation.

Methods
This study applied multivariate binary logistic regression model diagnostics and geospatial logistic model to identify traditional authorities in Malawi where caregivers have unusual health-seeking behaviour for childhood malaria. The data from the 2021 Malawi Malaria Indicator Survey were analysed using R software version 4.3.0 for regressions and STATA version 17 for data cleaning.

Results
Both models showed significant variability in treatment-seeking habits of caregivers between villages. The mixed-effects logit model residual identified Vuso Jere, Kampingo Sibande, Ngabu, and Dzoole as outliers in the model. Despite characteristics that promote late reporting of malaria at clinics, most mothers in these traditional authorities sought treatment within twenty-four hours of the onset of malaria symptoms in their children. On the other hand, the geospatial logit model showed that late seeking of malaria treatment was prevalent in most areas of the country, except a few traditional authorities such as Mwakaboko, Mwenemisuku, Mwabulambya, Mmbelwa, Mwadzama, Zulu, Amidu, Kasisi, and Mabuka.

Conclusions
These findings suggest that using a combination of multivariate regression model residuals and geospatial statistics can help in identifying communities with distinct treatment-seeking patterns for childhood malaria within a population. Health policymakers could benefit from consulting traditional authorities who demonstrated early reporting for care in this study. This could help in understanding the best practices followed by mothers in those areas which can be replicated in regions where seeking care is delayed.
The Greenhouse gas Observations of Biospheric and Local Emissions from the Upper sky (GOBLEU): a mission overview, instrument description, and results from the first flight
Authors: Suto Hiroshi , Kuze Akihiko , Matsumoto Ayako , Oda Tomohiro , Mori Shigetaka , Miyashita Yohsuke , Hoshino Chiharu , Shigetoh Mayumi , Kataoka Fumie , Tsubakihara Yasuhiro 
Published: August 2024

Abstract
Background
The Greenhouse gas Observations of Biospheric and Local Emissions from the Upper sky (GOBLEU) is a new joint project by Japan Aerospace Exploration Agency (JAXA) and ANA HOLDING INC. (ANAHD), which operates ANA flights. GOBLEU aims to visualizes our climate mitigation effort progress in support of subnational climate mitigation by collecting greenhouse gas (GHG) data as well as relevant data for emissions (nitrous dioxide, NO2) and removals (Solar-Induced Fluorescence, SIF) from regular passenger flights. We developed a luggage-sized instrument based on the space remote-sensing techniques that JAXA has developed for Japan’s Greenhouse gas Observing SATellite (GOSAT). The instrument can be conveniently installed on a coach-class passenger seat without modifying the seat or the aircraft.

Results
The first GOBLEU observation was made on the flight from the Tokyo Haneda Airport to the Fukuoka Airport, with only the NO2 module activated. The collected high-spatial-resolution NO2 data were compared to that from the TROPOspheric Monitoring Instrument (TROPOMI) satellite and surface NO2 data from ground-based air quality monitoring stations. While GOBLEU and TROPOMI data shared the major concentration patterns largely driven by cities and large point sources, regardless of different observation times, we found fine-scale concentration pattern differences, which might be an indication of potential room for GOBLEU to bring in new emission information and thus is worth further examination. We also characterized the levels of NO2 spatial correlation that change over time. The quickly degrading correlation level of GOBLEU and TROPOMI suggests a potentially significant impact of the time difference between CO2 and NO2 as an emission marker and, thus, the significance of co-located observations planned by future space missions.

Conclusions
GOBLEU proposes aircraft-based, cost-effective, frequent monitoring of greenhouse emissions by GOBLEU instruments carried on regular passenger aircraft. Theoretically, the GOBLEU instrument can be installed and operated in most commercially used passenger aircraft without modifications. JAXA and ANAHD wish to promote the observation technique by expanding the observation coverage and partnership to other countries by enhancing international cooperation under the Paris Agreement.
Musculoskeletal manifestations in childhood-onset systemic lupus erythematosus: an in-depth exploration
Authors: Sukharomana Maynart , Vonginyoo Siritida , Piyaphanee Nuntawan , Charuvanij Sirirat 
Published: August 2024

Abstract
Background
Childhood-onset systemic lupus erythematosus (c-SLE) is a multifaceted autoimmune disorder predominantly affecting the musculoskeletal (MSK) system. This investigation delineated the spectrum and sequelae of MSK involvement in c-SLE patients.

Methods
This retrospective analysis included SLE patients aged ≤ 18 years treated at a tertiary center between 2009 and 2019. Data were extracted from electronic health records.

Results
The cohort comprised 321 SLE patients (mean age 13.2 ± 2.5 years, 91.3% female). MSK manifestations were observed in 134 (41.7%) individuals, with joint pain universally present, followed by joint swelling in 32.1% and morning stiffness in 9.7%. Arthritis was documented in 52 (38.8%) patients, whereas 82 (61.2%) had arthralgia. Symmetrical joint involvement was observed in 96 (71.7%) subjects. The knees, wrists, and fingers were most commonly affected, with incidences of 43.3%, 40.3%, and 33.6%, respectively. Neither erosive arthritis nor Jaccoud’s arthropathy was detected. MSK symptoms were significantly correlated with older age at diagnosis, the presence of non-scarring alopecia, neuropsychiatric manifestations, and elevated SLE disease activity index scores at diagnosis. Over a median follow-up of 53.6 months (IQR 26.1–84.6), five patients developed septic arthritis or osteomyelitis, and avascular necrosis was identified in 16 (4.9%) patients.

Conclusions
Nearly half of c-SLE patients demonstrated MSK manifestations, chiefly characterized by symmetrical involvement of both large and small joints without evidence of erosive arthritis or Jaccoud’s arthropathy. Avascular necrosis is a critical concern and warrants close monitoring.
Non- or minimally displaced distal radius fractures in adult patients < 50 years of age
Authors: van Delft Eva A. K. , van Bruggen Suus G. J. , Sosef Nico L. , Bloemers Frank W. , Schep Niels W. L. , Vermeulen Jefrey 
Published: August 2024

Abstract
Background
Currently, non- or minimally displaced distal radius fractures are treated by 3 to 5 weeks of cast immobilisation. Many patients with a distal radius fracture suffer from long-term functional restrictions, which might be related to stiffness due to cast immobilisation. Current literature indicates that 1 week of immobilisation might be safe; however, no level 1 evidence is available. This trial aims to compare 1 week of brace immobilisation with 3 weeks of cast immobilisation in patients with distal radius fractures that do not need reduction.

Methods
The aim of this trial is to evaluate the non-inferiority of 1 week of brace immobilisation in patients with non- or minimally displaced distal radius fractures. A two-armed single blinded multicentre randomised clinical trial will be conducted in three hospitals. Adult patients, between 18 and 50 years old, independent for activities of daily living, with a non- or minimally displaced distal radius fracture can be included in this study. The intervention group is treated with 1 week of brace immobilisation, and the control group with 3 weeks of cast immobilisation. Primary outcome is the patient-reported outcome measured by the Patient-Related Wrist Evaluation score (PRWE) at 6 months. Secondary outcomes are patient-reported outcome measured by the Quick Disabilities of the Arm, Shoulder and Hand score at 6 weeks and 6 months, PRWE at 6 weeks, range of motion, patient-reported pain score measured by VAS score, radiological outcome (dorsal/volar tilt, radial height, ulnar variance, presence of intra-articular step off), complications and cost-effectiveness measured by the EuroQol 5 Dimension questionnaire, Medical Consumption Questionnaire and Productivity Cost Questionnaire.

Discussion
This study will provide evidence on the optimal period of immobilisation in non-operatively treated displaced and reduced distal radius fractures. Both treatment options are accepted treatment protocols and both treatment options have a low risk of complications. Follow-up will be according to the current treatment protocol. This study will provide level 1 evidence on the optimal period and way of immobilisation for non- or minimally displaced distal radius fractures in adult patients.

Trial registration
ABR 81638 | NL81638.029.22 | www.toetsingonline.nl. 18th of October 2023
Efficacy of personalized repetitive transcranial magnetic stimulation based on functional reserve to enhance ambulatory function in patients with Parkinson’s disease: study protocol for a randomized controlled trial
Authors: Yun Seo Jung , Lee Ho Seok , Kim Dae Hyun , Im Sun , Yoo Yeun Jie , Kim Na Young , Lee Jungsoo , Kim Donghyeon , Park Hae-Yeon , Yoon Mi-Jeong , Kim Young Seok , Chang Won Hyuk , Seo Han Gil 
Published: August 2024

Abstract

Background
Repetitive transcranial magnetic stimulation (rTMS) is one of the non-invasive brain stimulations that modulate cortical excitability through magnetic pulses. However, the effects of rTMS on Parkinson’s disease (PD) have yielded mixed results, influenced by factors including various rTMS stimulation parameters as well as the clinical characteristics of patients with PD. There is no clear evidence regarding which patients should be applied with which parameters of rTMS. The study aims to investigate the efficacy and safety of personalized rTMS in patients with PD, focusing on individual functional reserves to improve ambulatory function.

Methods
This is a prospective, exploratory, multi-center, single-blind, parallel-group, randomized controlled trial. Sixty patients with PD will be recruited for this study. This study comprises two sub-studies, each structured as a two-arm trial. Participants are classified into sub-studies based on their functional reserves for ambulatory function, into either the motor or cognitive priority group. The Timed-Up and Go (TUG) test is employed under both single and cognitive dual-task conditions (serial 3 subtraction). The motor dual-task effect, using stride length, and the cognitive dual-task effect, using the correct response rate of subtraction, are calculated. In the motor priority group, high-frequency rTMS targets the primary motor cortex of the lower limb, whereas the cognitive priority group receives rTMS over the left dorsolateral prefrontal cortex. The active comparator for each sub-study is bilateral rTMS of the primary motor cortex of the upper limb. Over 4 weeks, the participants will undergo 10 rTMS sessions, with evaluations conducted pre-intervention, mid-intervention, immediately post-intervention, and at 2-month follow-up. The primary outcome is a change in TUG time between the pre- and immediate post-intervention evaluations. The secondary outcome variables are the TUG under cognitive dual-task conditions, Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part III, New Freezing of Gait Questionnaire, Digit Span, trail-making test, transcranial magnetic stimulation-induced motor-evoked potentials, diffusion tensor imaging, and resting state functional magnetic resonance imaging.

Discussion
The study will reveal the effect of personalized rTMS based on functional reserve compared to the conventional rTMS approach in PD. Furthermore, the findings of this study may provide empirical evidence for an rTMS protocol tailored to individual functional reserves to enhance ambulatory function in patients with PD.

Trial registration
ClinicalTrials.gov NCT06350617. Registered on 5 April 2024.
Sexually dimorphic DNA methylation and gene expression patterns in human first trimester placenta
Authors: Gonzalez Tania L. , Willson Bryn E. , Wang Erica T. , Taylor Kent D. , Novoa Allynson , Swarna Akhila , Ortiz Juanita C. , Zeno Gianna J. , Jefferies Caroline A. , Lawrenson Kate , Rotter Jerome I. , Chen Yii-Der Ida , Williams John , Cui Jinrui , Goodarzi Mark O. , Pisarska Margareta D. 
Published: August 2024

Abstract
Background
Fetal sex and placental development impact pregnancy outcomes and fetal–maternal health, but the critical timepoint of placenta establishment in first trimester is understudied in human pregnancies.

Methods
Pregnant subjects were recruited in late first trimester (weeks 10–14) at time of chorionic villus sampling, a prenatal diagnostic test. Leftover placenta tissue was collected and stored until birth outcomes were known, then DNA and RNA were isolated from singleton, normal karyotype pregnancies resulting in live births. DNA methylation was measured with the Illumina Infinium MethylationEPIC BeadChip array (n = 56). Differential methylation analysis compared 25 females versus 31 males using a generalized linear model on 743,461 autosomal probes. Gene expression sex differences were analyzed with RNA-sequencing (n = 74). An integrated analysis was performed using linear regression to correlate gene expression and DNA methylation in 51 overlapping placentas.

Results
Methylation analysis identified 151 differentially methylated probes (DMPs) significant at false discovery rate < 0.05, including 89 (59%) hypermethylated in females. Probe cg17612569 (GABPA, ATP5J) was the most significant CpG site, hypermethylated in males. There were 11 differentially methylated regions affected by fetal sex, with transcription factors ZNF300 and ZNF311 most significantly hypermethylated in males and females, respectively. RNA-sequencing identified 152 genes significantly sexually dimorphic at false discovery rate < 0.05. The 151 DMPs were associated with 18 genes with gene downregulation (P < 0.05) in the direction of hypermethylation, including 2 genes significant at false discovery rate < 0.05 (ZNF300 and CUB and Sushi multiple domains 1, CSMD1). Both genes, as well as Family With Sequence Similarity 228 Member A (FAM228A), showed significant correlation between DNA methylation and sexually dimorphic gene expression, though FAM228A DNA methylation was less sexually dimorphic. Comparison with other sex differences studies found that cg17612569 is male-hypermethylated across gestation in placenta and in human blood up to adulthood.

Conclusions
Overall, sex dimorphic differential methylation with associated differential gene expression in the first trimester placenta is small, but there remain significant genes that may be regulated through methylation leading to differences in the first trimester placenta.
Democratizing cheminformatics: interpretable chemical grouping using an automated KNIME workflow
Authors: Moreira-Filho José T. , Ranganath Dhruv , Conway Mike , Schmitt Charles , Kleinstreuer Nicole , Mansouri Kamel 
Published: August 2024

AbstractWith the increased availability of chemical data in public databases, innovative techniques and algorithms have emerged for the analysis, exploration, visualization, and extraction of information from these data. One such technique is chemical grouping, where chemicals with common characteristics are categorized into distinct groups based on physicochemical properties, use, biological activity, or a combination. However, existing tools for chemical grouping often require specialized programming skills or the use of commercial software packages. To address these challenges, we developed a user-friendly chemical grouping workflow implemented in KNIME, a free, open-source, low/no-code, data analytics platform. The workflow serves as an all-encompassing tool, expertly incorporating a range of processes such as molecular descriptor calculation, feature selection, dimensionality reduction, hyperparameter search, and supervised and unsupervised machine learning methods, enabling effective chemical grouping and visualization of results. Furthermore, we implemented tools for interpretation, identifying key molecular descriptors for the chemical groups, and using natural language summaries to clarify the rationale behind these groupings. The workflow was designed to run seamlessly in both the KNIME local desktop version and KNIME Server WebPortal as a web application. It incorporates interactive interfaces and guides to assist users in a step-by-step manner. We demonstrate the utility of this workflow through a case study using an eye irritation and corrosion dataset.Scientific contributionsThis work presents a novel, comprehensive chemical grouping workflow in KNIME, enhancing accessibility by integrating a user-friendly graphical interface that eliminates the need for extensive programming skills. This workflow uniquely combines several features such as automated molecular descriptor calculation, feature selection, dimensionality reduction, and machine learning algorithms (both supervised and unsupervised), with hyperparameter optimization to refine chemical grouping accuracy. Moreover, we have introduced an innovative interpretative step and natural language summaries to elucidate the underlying reasons for chemical groupings, significantly advancing the usability of the tool and interpretability of the results.