bluuebunny/crossref_metadata_2025_split huggingface dataset:
A deoxynucleoside triphosphate triphosphohydrolase promotes cell cycle progression inCaulobacter crescentus
Authors: Hellenbrand Chandler N. , Stevenson David M. , Gromek Katarzyna A. , Amador-Noguez Daniel , Hershey David M. 
Published: April 2024

AbstractIntracellular pools of deoxynucleoside triphosphates (dNTPs) are strictly maintained throughout the cell cycle to ensure accurate and efficient DNA replication. DNA synthesis requires an abundance of dNTPs, but elevated dNTP concentrations in nonreplicating cells delay entry into S phase. Enzymes known as deoxyguanosine triphosphate triphosphohydrolases (Dgts) hydrolyze dNTPs into deoxynucleosides and triphosphates, and we propose that Dgts restrict dNTP concentrations to promote the G1 to S phase transition. We characterized a Dgt from the bacteriumCaulobacter crescentustermedflagellar signaling suppressor C(fssC) to clarify the role of Dgts in cell cycle regulation. DeletingfssCincreases dNTP levels and extends the G1 phase of the cell cycle. We determined that the segregation and duplication of the origin of replication (oriC) is delayed in ΔfssC, but the rate of replication elongation is unchanged. We conclude that dNTP hydrolysis by FssC promotes the initiation of DNA replication through a novel nucleotide signaling pathway. This work further establishes Dgts as important regulators of the G1 to S phase transition, and the high conservation of Dgts across all domains of life implies that Dgt-dependent cell cycle control may be widespread in both prokaryotic and eukaryotic organisms.ImportanceCells must faithfully replicate their genetic material in order to proliferate. Studying the regulatory pathways that determine when a cell initiates DNA replication is important for understanding fundamental biological processes, and it can also improve the strategies used to treat diseases that affect the cell cycle. Here, we describe a nucleotide signaling pathway that regulates when cells will begin DNA replication. We show that this pathway promotes the transition from the G1 to the S phase of the cell cycle in the bacteriumCaulobacter crescentusand propose that this pathway is prevalent in all domains of life.
Multiple Omics Find New Cecal Microbial Features Associated with Feed Efficiency in Ducks
Authors: Guo Rongbing , Chang Yuguang , Wang Dandan , Sun Hanxue , Zhao Ayong , Gu Tiantian , Zong Yibo , Zhou Shiheng , Huang Zhizhou , Chen Li , Tian Yong , Xu Wenwu , Lu Lizhi , Zeng Tao 
Published: April 2024

ABSTRACTAs the global population continues to grow exponentially, the competition for resources between livestock and humans has become increasingly intense. Breeding efficient animal breeds, fully utilizing feed resources, and reducing environmental damage are major challenges facing the livestock industry. To address these issues, enhancing the feed utilization efficiency in the poultry industry is crucial. Recent studies have elucidated the pivotal role of gut microbiota in modulating the feeding behavior of their host organisms. Thus, we used metagenomics, transcriptomics, and metabolomics to explore how the intestinal microbiome affects the feed utilization efficiency in ducks. Our metagenomic analysis revealed a significant up-regulation ofElusimicrobiotaat the phylum level within the high residual feed intake (HRFI) group, in comparison to the low residual feed intake (LRFI) group. Additionally, functional analysis using Clusters of Orthologous Groups of proteins (COG) indicated prominent disparities in the category of secondary metabolites biosynthesis, transport, and catabolism between the HRFI and LRFI groups. Furthermore, our metabolomics investigation identified an upregulated expression of the secondary metabolite 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) in the HRFI group compared to the LRFI group. Liver transcriptome analysis identified prostaglandin-endoperoxide synthase 2 (PTGS2) as a key hub gene, exerting significant regulatory influence within the arachidonic acid pathway. Notably, the metabolite 15d-PGJ2 is a terminal product in the metabolic pathway of arachidonic acid. The correlation analysis between the cecal microbiota and differential metabolites revealed a significant negative correlation betweenElusimicrobiotaand the metabolite 15d-PGJ2. In summary, we assumed that the intestinal microbiomeElusimicrobiotaregulates the expression of thePTGS2gene, consequently inducing variations inPTGS2efficiency between the HRFI and LRFI groups, ultimately leading to diverse residual feed intake levels in ducks.IMPORTANCEThis investigation utilizes metabolomics to elucidate the interplay between genes and microbiome communities. We present evidence of disparities in the composition of microbial consortia among ducks RFI, alongside identification of pivotal genes within the liver that potentially modulate RFI. These results provide novel perspectives on the processes through which the cecum and liver influence RFI.
ELUCIDATION OF THE ROLE OF miRNA 4263 IN DYSREGULATED MITOCHONDRIAL ENERGETICS AND CARCINOGENESIS
Authors: Maurya Ashutosh Kumar , Sruthi TV. , Kumar V.B. Sameer 
Published: April 2024

AbstractDysfunctional mitochondria have been reported to be associated with several pathological conditions and in cancer, dysregulated mitochondrial metabolism is considered as an important hallmark of the disease. Cancer cells alter their mitochondrial machinery and activate glycolytic pathway as an alternate source of continuous energy, required for their indefinite growth. This modulation of the mitochondria could be due to the dysrupted expression of important mitochondrial genes involved in the normal functioning of the mitochondria. MicroRNAs are known to regulate the expression pattern of a variety of genes. With our in-silico analysis, we found that miR 4263 has targets on important mitochondrial genes, involved in mitochondrial energetics. Next, we checked the role of miR 4263 in modulating the mitochondrial metabolism and impact of this alteration on carcinogenesis. The results revealed that miR 4263 contributes to carcinogenesis in hepatic cells by altering the mitochondrial energetics.
In-silico analysis of important mitochondrial microRNAs and their differential expression in mitochondria
Authors: Maurya Ashutosh Kumar , Rabina P , Kumar V.B. Sameer 
Published: April 2024

AbstractMitochondria, often called as the power house of cell, serves important role in cellular physiology and survivability. It plays crucial role in the normal functioning of the cell. Dysfunctional mitochondria have been found to be associated with various pathological conditions including cancer. The modulation of mitochondrial machinery could be due to the suppression of the expression pattern of important mitochondrial genes and microRNAs could be considered as the key player in reprograming of the mitochondrial metabolism. Apart from the microRNAs coded by mitochondrial genome, nuclear coded microRNAs gets localized to the mitochondria and they influence the mitochondrial machinery by targeting the important mitochondrial genes. This group of microRNAs are called mitochondrial miRNAs or MitomiRs. In this study we selected 10 important candidate mitochondrial microRNAs and checked their abundance in the cancerous and non cancerous hepatic cell line (HepG2 and WRL68), followed by their differential expression in the mitochondria of the respective cell line. The results shown an inverse relation in the expression pattern of the candidate microRNAs with mitochondrial target genes, suggesting their direct targeting, as predicted by our in-silico data.
Mild Hyperthermia Enhanced Liposomal Doxorubicin Delivery and CD8+T cell Infiltration in Triple Negative Breast Cancer
Authors: Rezazadeh Farzaneh , Saadat Wajfa , Smith Ryan , Pattyn Alexander , Malik Mohammad , Yazdani Fuad , Saliganan Allen-Dexter , Mehrmohammadi Mohammad , Viola Nerissa T. 
Published: April 2024

AbstractMild hyperthermia (MHTh) is often used in combination with chemotherapy and radiotherapy for cancer treatment. In the current study, the effect of MHTh on the enhanced uptake of the FDA-approved chemotherapy drug, liposomal doxorubicin (dox) in syngeneic 4T1 tumors was investigated. Doxorubicin has inherent fluorescence properties having an emission signal at 590 nm upon excitation with a 480 nm laser. A group of mice administered with doxorubicin (dox) were exposed to MHTh (42 °C) for 30 minutes whereas control group given dox did not receive MHTh.Ex vivooptical imaging of harvested tumors confirmed higher uptake of dox in treated versus the control untreated tumors. Confocal microscopy of tumor sections indicates higher fluorescent intensity due to increased accumulation of dox in MHTh-treated compared to untreated tumors. We examined the effect of MHTh to enhance CD8 tumor infiltration, production of interferon-γ (IFN-γ) and expression of programmed death ligand-1 (PD-L1). mRNAin situhybridization was performed to test for transcripts of CD8, IFN-γ and PD-L1. Results showed that higher expression of CD8 mRNA was observed in MHTh-administered tumors versus untreated cohorts. The signal for IFN-γ and PD-L1 in both groups were not significantly different. Taken together, our findings imply that MHTh can improve tumor uptake of dox. Importantly, our data suggests that MHTh can boost CD8+T cell infiltration.
From Web to RheumaLpack: Creating a Linguistic Corpus for Exploitation and Knowledge Discovery in Rheumatology
Authors: Madrid-García Alfredo , Merino-Barbancho Beatriz , Freites-Núñez Dalifer , Rodríguez-Rodríguez Luis , Menasalvas-Ruíz Ernestina , Rodríguez-González Alejandro , Peñas Anselmo 
Published: April 2024

AbstractThis study introducesRheumaLinguisticpack(RheumaLpack), the first specialised linguistic web corpus designed for the field of musculoskeletal disorders. By combining web mining (i.e., web scraping) and natural language processing (NLP) techniques, as well as clinical expertise,RheumaLpacksystematically captures and curates structured and unstructured data across a spectrum of web sources including clinical trials registers (i.e.,ClinicalTrials.gov), bibliographic databases (i.e., PubMed), medical agencies (i.e. EMA), social media (i.e., Reddit), and accredited health websites (i.e., MedlinePlus, Harvard Health Publishing, and Cleveland Clinic). Given the complexity of rheumatic and musculoskeletal diseases (RMDs) and their significant impact on quality of life, this resource can be proposed as a useful tool to train algorithms that could mitigate the diseases’ effects. Therefore, the corpus aims to improve the training of artificial intelligence (AI) algorithms and facilitate knowledge discovery in RMDs. The development ofRheumaLpackinvolved a systematic six-step methodology covering data identification, characterisation, selection, collection, processing, and corpus description. The result is a non-annotated, monolingual, and dynamic corpus, featuring almost 3 million records spanning from 2000 to 2023.RheumaLpackrepresents a pioneering contribution to rheumatology research, providing a useful resource for the development of advanced AI and NLP applications. This corpus highlights the value of web data to address the challenges posed by musculoskeletal diseases, illustrating the corpus’s potential to improve research and treatment paradigms in rheumatology. Finally, the methodology shown can be replicated to obtain data from other medical specialities. The code and details on how to buildRheumaL(inguistic)packare also provided to facilitate the dissemination of such resource.
Vitamin D, acute respiratory infections, and Covid-19: the curse of small-size randomised trials. A critical review with meta-analysis of randomised trials
Authors: Autier Philippe , Doi Giulia , Mullie Patrick , Vankrunkelsven Patrick , D’Ecclesiis Oriana , Gandini Sara 
Published: April 2024

AbstractBackgroundRandomised trials conducted before 2021 indicated that vitamin D supplementation (VDS) was able to prevent severe COVID-19 and acute respiratory infections (ARI). However, these health benefits were not confirmed by larger randomised trials published after 2021.ObjectiveTo examine the characteristics of randomised trials on VDS to COVID-19 patients and admission to intensive care unit (ICU), and on VDS for the prevention of ARI.MethodA systematic search retrieved randomised trials on VDS to COVID-19 patients and admission to ICU. Data on VDS and ARI were extracted from the meta-analysis of Jolliffe et al., 2021. The associations between VDS vs no VDS, and admission to ICU were evaluated using random effect models. Meta-analyses were done for all trials and by groups trial size. Publication bias was assessed using the LFK index (no bias if index between -1 and +1) and the Trim and Fill method.ResultsNine trials on VDS for preventing admission to ICU were identified. The summary odds ratio (SOR) was 0.61 (95%CI: 0.39-0.95) for all trials, 0.34 (0.13-0.93) for trials including 50 to <106 patients and 0.88 (0.62-1.24) for trials including 106 to 548 patients (effect modification: p=0.04). The LFK index was -3.79, and after Trim and Fill, the SOR was 0.80 (0.40-1.61). The SOR for the 37 trials on VDS for ARI prevention was 0.92 (0.86-0.99) for all trials, 0.69 (0.57-0.83) for trials including 25 to <248 patients and 0.98 (0.94-1.03) for trials including 248 to 16,000 patients (effect modification p=0.0001). The LFK index was -3.11, and after Trim and Fill, the SOR was 0.96 (0.88-1.05).ConclusionStrong publication bias affected randomised trials on VDS for the prevention of severe COVID-19 and of ARI. Systematic reviews should beware of small-size randomised trials that generally exaggerate health benefits.
Radiomic analysis of patient and inter-organ heterogeneity in response to immunotherapies and BRAF targeted therapy in metastatic melanoma
Authors: Tompkins Alexandra , Gray Zane N. , Dadey Rebekah E. , Zenkin Serafettin , Batavani Nasim , Newman Sarah , Amouzegar Afsaneh , Ak Murat , Ak Nursima , Pak Taha Yasin , Peddagangireddy Vishal , Mamindla Priyadarshini , Behr Sarah , Goodman Amy , Ploucha Darcy L. , Kirkwood John M. , Zarour Hassane M. , Najjar Yana G. , Davar Diwakar , Colen Rivka , Luke Jason J. , Bao Riyue 
Published: April 2024

AbstractBackgroundVariability in treatment response may be attributable to organ-level heterogeneity in tumor lesions. Radiomic analysis of medical images can elucidate non-invasive biomarkers of clinical outcome. Organ-specific radiomic comparison across immunotherapies and targeted therapies has not been previously reported.MethodsWe queried UPMC Hillman Cancer Center registry for patients with metastatic melanoma (MEL) treated with immune checkpoint inhibitors (ICI) (anti-PD1/CTLA4 [ipilimumab+nivolumab; I+N] or anti-PD1 monotherapy) or BRAF targeted therapy. Best overall response was measured using RECIST v1.1. Lesions were segmented into discrete volume-of-interest with 400 radiomics features extracted. Overall and organ-specific machine-learning models were constructed to predict disease control (DC)versusprogressive disease (PD) using XGBoost.Results291 MEL patients were identified, including 242 ICI (91 I+N, 151 PD1) and 49 BRAF. 667 metastases were analyzed, including 541 ICI (236 I+N, 305 PD1) and 126 BRAF. Across cohorts, baseline demographics included 39-47% female, 24-29% M1C, 24-46% M1D, and 61-80% with elevated LDH. Among patients experiencing DC, the organs with the greatest reduction were liver (−88%±12%, I+N; mean±S.E.M.) and lung (−72%±8%, I+N). For patients with multiple same-organ target lesions, the highest inter-lesion heterogeneity was observed in brain among patients who received ICI while no intra-organ heterogeneity was observed in BRAF. 267 patients were kept for radiomic modeling, including 221 ICI (86 I+N, 135 PD1) and 46 BRAF. Models consisting of optimized radiomic signatures classified DC/PD across I+N (AUC=0.85) and PD1 (0.71) and within individual organ sites (AUC=0.72∼0.94). Integration of clinical variables improved the models’ performance. Comparison of models between treatments and across organ sites suggested mostly non-overlapping DC or PD features. Skewness, kurtosis, and informational measure of correlation (IMC) were among the radiomic features shared between overall response models. Kurtosis and IMC were also utilized by multiple organ-site models.ConclusionsDifferential organ-specific response was observed across BRAF and ICI with within organ heterogeneity observed for ICI but not for BRAF. Radiomic features of organ-specific response demonstrated little overlap. Integrating clinical factors with radiomics improves the prediction of disease course outcome and prediction of tumor heterogeneity.
Patients with Achilles Tendinopathy use compensation strategies to reduce tendon load during rehabilitation exercises
Authors: Deroost Frea , Petrella Davide , Mylle Ine , Vanwanseele Benedicte 
Published: April 2024

AbstractPurposeThis study aimed to determine differences in the Achilles tendon loading during rehabilitation exercises for Achilles tendinopathy (AT), and the ranking of these exercises in patients with AT and controls.MethodsSixteen patients with AT (5F & 11M, 44.1 ± 12.9yr) and sixteen controls (4F & 12M, 39.4 ± 15.6yr) performed rehabilitation exercises while 3D motion and ground reaction forces were measured. Musculoskeletal modeling was used to compute joint kinematics and triceps surae muscle forces. Individual triceps surae muscle forces were summed to estimate Achilles tendon load. Subsequently, peak Achilles tendon loading, loading impulse, loading rate, loading indexes (combining the different loading parameters), and ankle and knee angles at the time of peak loading were determined.ResultsPatients with AT have a significantly reduced peak loading of the Achilles tendon compared to controls during the exercises with the highest peak loading: unilateral heel drop with flexed knee (3.66 ± 0.90BW [AT] vs. 4.65 ± 1.10BW [Control], p=0.003, d=0.979) and walking (3.37 ± 0.49BW [AT] vs. 3.68 ± 0.33BW [Control], p=0.044, d=0.742). Furthermore, ankle dorsiflexion and knee flexion were reduced during unilateral heel drop with a flexed knee for the AT group. The ranking of exercises by peak loading or loading index was similar for people with and without AT. However, the ranking of exercises depends on the parameter used to define Achilles tendon loading.ConclusionDuring the highest load-imposing exercises, patients with AT employ compensatory strategies to reduce the load on their Achilles tendon. Clear instructions and feedback on the patient’s performance are crucial as altered exercise execution influences Achilles tendon loading.
Do Sleep Quality Can Be the Intervening Factors of Personality Data to Occupational Fatigue?
Authors: Izhar Doddy , Kusmawan David , Aswin Budi 
Published: April 2024

AbstractFatigue during work among oil and gas employees can have dangerous effects on wellbeing, economics, safety, and health. This cross-sectional survey was conducted in July and August of 2022 at two national oil and gas companies located in Muara Jambi and Jambi City. A convenience sample of 116 respondents was selected in total. To address the study hypotheses, partial least square-structural equation modeling (PLS-SEM) was employed. This study aims to determine the relationship between the risk of job weariness among Indonesian oil and gas workers in Jambi Province and the direct and indirect impacts of mental workload, sociodemographic characteristics, and sleep quality. Personality data has a significant and negative direct impact on occupational weariness at alpha 5% and with a path value of -0.203 (p-value: 0.047), corroborating the earlier hypothesis. For the second hypothesis, the path coefficient value of 0.462 (p-value: 0.000) clearly shows that sleep quality has an impact on occupational weariness. In order to improve sleep hygiene and address personality factors like age and length of employment, fatigue risk management strategies can be combined with those that are currently being used to control job tiredness.
Day 3 parasitemia andPlasmodium falciparum Kelch 13mutations among uncomplicated malaria patients treated with artemether-lumefantrine in Adjumani district, Uganda
Authors: Angwe Martin Kamilo , Mwebaza Norah , Nsobya Sam Lubwama , Vudriko Patrick , Dralabu Savior , Omali Denis , Tumwebaze Maria Agnes , Ocan Moses 
Published: April 2024

AbstractArtemisinin resistance threatens malaria control and elimination efforts globally. Recent studies have reported the emergence ofPlasmodium falciparumparasites tolerant to artemisinin agents in sub-Saharan Africa, including Uganda. The current study assessed the day 3 parasite clearance and its correlation withP. falciparum K13propeller gene (pfkelch13) mutations inP. falciparumparasites isolated from patients with uncomplicated malaria under artemether-lumefantrine (AL) treatment. This study enrolled 100P. falciparum-positive patients to whom AL was prescribed between 09/September/2022 and 06/November/2022. Blood samples were collected in EDTA tubes before treatment initiation (day 0) and on day 3. Parasitemia was assessed by microscopy from blood smears and quantitative polymerase chain reaction (qPCR) from the DNA extracted. The day 0 parasiteK13gene was sequenced using Sanger sequencing. Sequence data were analysed using MEGAversion11 software. The data were analysed using STATAversion15, and the Mann‒Whitney U test was used to compare PCR parasite clearance on day 3 using the comparative CT value method andpfkelch13mutations.The prevalence of day 3 parasitaemia was 24% (24/100) by microscopy and 63% (63/100) by qPCR from the AL-treated patients.P. falciparum K13-propeller gene polymorphism was detected in 18.8% (15/80) of the day 0 DNA samples. TheK13mutations found were C469Y, 12.5% (10/80); A675V, 2.5% (2/80); A569S, 1.25%, (1/80), A578S, 1.25%, (1/80) and; F491S, 1.25%, (1/80) a new allele not reported anywhere. The C469Y mutation, compared to the wild-type, was associated with delayed parasite clearancep=0.0278, Hodges-Lehmann estimation 3.2108 on the log scale, (95%CI 1.7076, 4.4730).There was a high prevalence of day 3P. falciparumamong malaria patients treated using artemether-lumefantrine. We conclude that theK13mutation associated with artemisinin resistance byP. falciparumis present in Adjumani district, Uganda. This necessitates regular surveillance of the effectiveness and efficacy of artemether-lumefantrine in the country.