bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antimicrobial resistance of bacteria isolates among patients with chronic wound infections in Tanga Regional Referral Hospital, Tanzania
Authors: Dawer Aleena , Msengi Victor , Mtui Theresia B. , Sarakikya Sarah , Suleiman Rashid , Lusingu John P. A. 
Published: December 2024

AbstractBackgroundBacterial wound infections are the second leading cause of mortality globally, with approximately 50% of contaminated wounds evolving into chronic infections. In Tanzania, this challenge is exacerbated by the over prescription of antibiotics and the emergence of drug-resistant bacteria, compounded by inadequate hospital hygiene and sanitation practices. This study investigated chronic wound infections in Tanga, Tanzania, focusing on antibiotic susceptibility patterns.MethodsA cross-sectional, mixed-methods study was conducted at the Tanga Regional Referral Hospital (TRRH) from July 2023 to December 2023. Pus and Culture Sensitivity tests were performed on samples from 89 chronic wound patients to identify bacterial isolates and assess antibiotic susceptibility. Data was analyzed using STATA, Excel, and Python.ResultsOf 89 patients, 82 (92.1%) had positive bacterial isolates in wound cultures, predominantly withStaphylococcus aureus,24 (29.3%). Surgical-site infections (SSI) were the most prevalent diagnosis, followed by diabetic foot ulcers and septic wounds. Antibiotic resistance analysis revealed a marked trend in multi-drug resistance (MDR), notably against amoxicillin, while meropenem was identified as the most effective antibiotic.ConclusionThe elevated rate of MDR at TRRH, particularly against commonly used antibiotics, emphasizes the need for improved antibiotic stewardship and healthcare worker education. It necessitates increased health awareness about effective wound management and the development of robust healthcare strategies to combat the escalating challenge of MDR.
NuMA mechanically reinforces the spindle independently of its partner dynein
Authors: Cho Nathan H. , Aslan Merve , Yildiz Ahmet , Dumont Sophie 
Published: December 2024

ABSTRACTBoth motor and non-motor proteins organize microtubules to build the spindle and maintain it against opposing forces. NuMA, a long microtubule binding protein, is essential to spindle structure and function. NuMA recruits the motor dynein to spindle microtubule minus-ends to actively cluster them, but whether NuMA performs other spindle roles remains unknown. Here, we show that NuMA acts independently of dynein to passively reinforce the mammalian spindle. NuMA that cannot bind dynein is sufficient to protect spindle poles against fracture under external force. In contrast, NuMA with a shorter coiled-coil or disrupted self-interactions cannot protect spindle poles, and NuMA turnover differences cannot explain mechanical differences.In vitro, NuMA’s C-terminus self-interacts and bundles microtubules without dynein, dependent on residues essential to pole protectionin vivo. Together, this suggests that NuMA reinforces spindle poles by crosslinking microtubules, using its long coiled-coiled and self-interactions to reach multiple, far-reaching pole microtubules. We propose that NuMA acts as a mechanical “multitasker” targeting contractile motor activity and separately crosslinking microtubules, both functions synergizing to drive spindle mechanical robustness.
Unveiling miR-451a and miR-142-3p as Prognostic Markers in NSCLC via sEV Liquid Biopsy
Authors: Burdiel Miranda , Arauzo Ana , Jiménez Julia , Moreno-Velasco Rocío , Antolín Carlos Rodríguez- , Pernía Olga , Higuera Oliver , Gutiérrez-Sainz Laura , Yubero Paloma , Sanchez Julia Villamayor , Losantos-García Itsaso , Sagalés Nadina Erill , Rumayor Víctor González , de Castro Javier , de Cáceres Inmaculada Ibáñez , Vera Olga 
Published: December 2024

ABSTRACTDespite advancements in personalized cancer therapies, platinum-based chemotherapy remains the cornerstone for treating solid tumors, including Non-Small Cell Lung Cancer (NSCLC). The integration of novel immunotherapies with platinum compounds has shown promising outcomes for the treatment of advanced disease. However, a significant proportion of patients experience therapeutic failure due to innate or acquired resistance. Thus, identifying molecular profiles and biomarkers to monitor patient progress and treatment response is crucial for tailoring therapeutic strategies. Small extracellular vesicle (sEV)-based liquid biopsy emerges as a promising non-invasive method for cancer management. sEVs play a critical role in cell communication and provide molecular insights into the tumor environment. In this study, we characterized the microRNome content of sEVs from cisplatin-resistant and -sensitive cancer cells using small-RNA sequencing. We identified and validated three miRNAs in two cohorts of 78 and 49 patients treated with either chemotherapy alone or chemo-immunotherapy, respectively, analyzed via liquid biopsy, differentiating NSCLC patients based on progression and overall survival. Notably, miR-451a emerged as a prognostic marker for chemo and chemo-immunotherapy, while miR-142-3p was identified for the first time as a potential prognostic marker specifically for stage IV patients, irrespective of the treatment. The combination of miR-451, miR-142-3p, and miR-55745, a novel miRNA identified from our miRNome screening, serves as a valuable biomarker for both cisplatin and chemo-immunotherapy treatment responses. This study underscores the role of sEVs in acquired cisplatin resistance and introduces novel miRNA-sEV biomarkers for managing NSCLC progression.
Positron emission tomography (PET) tracer enables imaging of high CD73 expression in cancer
Authors: Dobelmann Clemens , Schmies Constanze C. , Rolshoven Georg Wilhelm , Scortichini Mirko , Wagner Stefan , Isaak Andreas , Idris Riham M. , Dabel Jennifer , Grey Lucie , Losenkova Karolina , Moschütz Susanne , Keim Antje , Höppner Sandra , Sandholm Jouko , Boström Pia , Hollmén Maija , Sträter Norbert , Hermann Sven , Yegutkin Gennady G. , Jacobson Kenneth A. , Schelhaas Sonja , Müller Christa E. , Junker Anna 
Published: December 2024

AbstractEcto-5’-nucleotidase (CD73) is a potential new drug target for cancer immunotherapy. Its overexpression is associated with various aggressive cancers, including triple-negative breast cancer (TNBC) and pancreatic cancer, making it a promising target for diagnostic imaging. Besides antibodies, small molecule CD73 inhibitors have been developed and are currently in clinical trials. This study aimed to develop and evaluate fluorine-18 labeled high-affinity CD73 inhibitors as tracers for the non-invasive positron emission tomography (PET) imaging of CD73 expression in cancer. Two CD73 inhibitors were selected for radiolabeling based on their high potency (Kivalues of ca. 1 nM), and favorable pharmacokinetic properties providing [18F]PSB-19427 ([18F]1) and [18F]MRS-4648 ([18F]2). Ex vivo imaging studies on human breast cancer tissues indicated specific binding of both radiotracers. Subsequent in vivo studies proved [18F]1to be superior due to its long elimination half-life and its accumulation in TNBC and pancreatic cancer tissues, suggesting its potential as a versatile PET tracer for imaging various solid tumors. [18F]1significantly outperformed [18F]FDG in visualizing triple-negative breast cancer, offering potential advantages over [18F]FDG in terms of specificity and diagnostic accuracy. Thus, [18F]1is a PET tracer with outstanding properties suitable for broad application in cancer diagnosis and potentially in therapy control. Based on these results, further clinical development of PET tracers targeting CD73 is warranted.One Sentence SummaryA PET tracer for imaging CD73 expression was developed, enabling cancer diagnosis.
Coordinated organic and inorganic nitrogen transformations fuel soil microbial blooms and increase nitrogen retention during snowmelt
Authors: Sorensen Patrick O. , Karaoz Ulas , Beller Harry R. , Bill Markus , Bouskill Nicholas J. , Banfied Jillian F. , Chu Rosalie K. , Hoyt David W. , Eder Elizabeth , Eloe-Fadrosh Emiley , Sharrar Allison , Tfaily Malak M. , Toyoda Jason , Tolic Nikola , Wang Shi , Wong Allison , Williams Kenneth H. , Zhong Yangquanwei , Brodie Eoin L. 
Published: December 2024

AbstractSnowmelt in high-elevation watersheds triggers a microbial bloom and crash that affects nitrogen (N) export. Predicting watershed N dynamics as snowpack declines is a challenge because the mechanisms that underlie this microbial bloom and crash are uncertain. Using a multi-omic approach, we show that the dynamic molecular properties of dissolved organic N, plus high gene expression for peptidases that recycle microbial biomass, suggested that microbial turnover provided N for biosynthesis during the microbial bloom. Amino acid fermentation byBradyrhizobiaproduced organic acids that also fueled denitrification and dissimilatory nitrate reduction to ammonia (DNRA) during snowmelt. Nitrification in spring was driven by Spring-AdaptedNitrososphaerales, which utilized ammonium derived from osmolyte degradation by Winter-AdaptedSolirubrobacteraceae. High DNRA gene expression after snowmelt suggested significant nitrate retention, increasing watershed N retention potential. However, declining snowfall may compromise microbial regulation of soil N retention, with implications for watershed N export.
Healthy lifestyles, plasma proteomic profile and long-term risk of dementia
Authors: Shen Jie , Wu Minyu , Huang Yuhui , Yan Minqin , Yang Yang , Xu Xin , Zong Geng , Yang Jie , Li Xue , Chen Hui , Yuan Changzheng 
Published: December 2024

AbstractConsidering the irreversible nature of dementia, lifestyle modification has been recognized as potentially effective preventive strategies. However, whether proteomic signatures of individuals mediate or modifiy the associations between healthy lifestyles and cognitive health remain unclear. Herein, we conducted proteome-wide association analyses and identified 12 plasma proteomic markers that were associated with both overall healthy lifestyle score and incident dementia (Bonferroni correctedP-values <0.05) among 53,014 individuals aged 55 years and older in the UK Biobank. Aggregately, they mediated 17.6% (95% CI, 10.0%, 29.6%) of the lifestyle-dementia association. The associations between overall healthy lifestyle score and two key proteinomic markers (GDF15 and IGFBP3) were further replicated in the Framingham Heart Study Offspring cohort. In the proteome-wide interaction analysis, the lifestyle-dementia association significanly differed by certain proteomic features. Using a machine-learning approach, we developed and tested 8 lifestyle protein stratification scores (LPSSs) to identify pariticipants showing stronger associations between overall or individual healthy lifestyles and dementia. In particular, the LPSS for overall healthy lifestyle (consisting of 25 proteins) identified a population with a substantially stronger lifestyle-dementia association (Harzard Ratio: 0.38, 95%CI: 0.32-0.45) compared with overall population (0.67, 0.60-0.75). Individuals with higher LPSS thus may exibit stronger responses to healthy lifestyle interventions, leading to substantially improved proportions of potentially preventable dementia cases. For example, the population attributable fraction of unhealthy diet increased from 1.63% in the overall population to 29.15% in the targeted population with higher LPSS for healthy diet. Our findings highlighted the key proteomic biomarkers that may serve as intervention intermediate outcomes and inform targeted lifestyle interventions for primary prevention of dementia.
Use of routine health data to monitor malaria intervention effectiveness: a scoping review
Authors: Reithinger Richard , Bisanzio Donal , Cushnie Anya , Craig Jessica 
Published: December 2024

ABSTRACTThe expansive scale-up of malaria interventions has contributed to substantial reductions in malaria morbidity and mortality in the past 15–20 years. The effectiveness of these interventions has traditionally been estimated through research studies and trials, nationally representative surveys, and mathematical modelling. Because of their sheer volume across space and time, programmatic data collected and reported routinely through health management information systems (HMIS) can complement and even offer an alternative to nationally representative and other ad hoc surveys to assess health intervention effectiveness, and ultimately impact on health outcomes. The objective of this scoping review was to describe the different analytical approaches for estimating the impact and effectiveness of malaria interventions using routine HMIS and surveillance data.We examined PubMed using combination searches of the following terms: “malaria” AND “intervention” AND “effect*” OR “impact” AND “system” OR “surveillance”. We limited inclusion to studies and analyses that were conducted in the past decade. We purposefully chose this time cut-off, as that is when countries’ routine HMIS began to substantially mature, with data reported by these systems progressively becoming more robust. Out of 957 records generated from the PubMed search, following title and abstract screening, 93 were included for full-text review, with 49 records ultimately meeting the inclusion criteria and being included in the scoping review.We summarize included studies by publication year, geography, outcome variables, target populations, interventions assessed, HMIS data platform used—we show that analytical approaches used a range of modelling and non-modelling approaches to assess intervention effectiveness.This scoping review shows that routine HMIS data can also be used to regularly assess the effectiveness of various malaria interventions—an important exercise to ensure that implemented malaria interventions continue to be effective, have the desired effect, and ultimately help countries progress towards their national strategic goals and targets.Strengths and Limitations of this Study► This scoping review describes the different analytical approaches for estimating the impact and effectiveness of malaria interventions using routine health management information system (HMIS) and surveillance data.► A range of analytical approaches to assess malaria intervention effectiveness using routine HMIS and surveillance data were identified in the records (studies) reviewed, which broadly can be categorized into modelling and non-modelling approaches.► Limitations lie in the inclusion criteria and main literature database used for the review: some papers and grey literature may not have been included, as well as papers in languages other than English may have been missed.Article Summary LineMonitoring malaria intervention effectiveness
General assessment of genetically-encoded reporters inYarrowia lipolytica
Authors: Zhang Hanqing , Khoury Luai R. , Xu Peng 
Published: December 2024

AbstractThe development of genetically-encoded reporters is important to characterize gene expression dynamics and investigate cellular-level events. Unlike Baker’s yeast, the thick cell wall and the high oil content in oleaginous yeast have restricted our ability to establish efficient fluorescence or enzyme-based reporters. In this book chapter, we detailed the protocol for how to clone and construct fluorescence reporters including hrGFP, TurboGFP, and mScarlet-I3, and the Nanoluc luciferase reporters. We quantified the fluorescence/luciferase reporter efficiency with 96-well microplate readers, flow cytometry, and confocal microscopy. Our results indicate that TurboGFP and hrGFP have a relatively low signal/noise ratio, and mScarlet-I3 yields a very high signal/noise ratio. Compared to fluorescence, luciferase Nanoluc exhibits the highest signal/noise ratio. The downside of using luciferase is the relatively laborious procedure and the related high cost. This chapter may guide us to establish an efficient and reliable reporter system to study gene expression or protein-labeling in nonconventional yeast.
Discovery of diverse chimeric peptides in a eukaryotic proteome sets the stage for the experimental proof of the mosaic translation hypothesis
Authors: Çakır Umut , Gabed Noujoud , Köroğlu Yunus Emre , Kaya Selen , Sinharoy Senjuti , Benedito Vagner A. , Brunet Marie , Roucou Xavier , Kryvoruchko Igor S. 
Published: December 2024

AbstractThe high complexity of eukaryotic organisms enabled their evolutionary success, which became possible due to the diversification of eukaryotic proteomes. Various mechanisms contributed to this process. Alternative splicing had the largest known impact among these mechanisms: tens or hundreds of protein isoforms produced from a single genetic locus. Earlier, we hypothesized that along with alternative splicing, a different but conceptually similar mechanism creates novel versions of existing proteins in all eukaryotes. However, this mechanism acts at the level of translation, where the novelty of an amino acid sequence is achieved via multiple programmed ribosomal frameshifting. This mechanism, which is termed mosaic translation, is very difficult to demonstrate even with the most up-to-date molecular tools. Thus, it remained unnoticed so far. Using only a portion of all mass spectrometry proteomic data generated from various organs of the model plantMedicago truncatula, we attempted the first step toward the experimental proof of this hypothesis. Our originalin silicoapproach resulted in the discovery of two candidates for mosaic proteins (homologs of EF1α and RuBisCo) and 154 candidates for chimeric peptides. Chimeric peptides and polypeptides are produced in the course of one ribosomal frameshifting event and may correspond to parts of mosaic proteins. In addition, our analysis reveals the possibility of translation of chimeric peptides from five ribosomal RNA transcripts, ten long non-coding RNA transcripts, and one transfer RNA transcript. These findings are very novel and will be the basis for experimental validation in future studies. In this work, we present multiple lines of indirect evidence that support the validity of ourin silicodata.
The GluA1 cytoplasmic tail regulates intracellular AMPA receptor trafficking and synaptic transmission onto dentate gyrus GABAergic interneurons, gating response to novelty
Authors: Leana-Sandoval Gerardo , Kolli Ananth V. , Chinn Carlene A. , Madrid Alexis , Lo Iris , Sandoval Matthew A. , Vera Vanessa Alizo , Simms Jeffrey , Wood Marcelo A. , Diaz-Alonso Javier 
Published: December 2024

AbstractThe GluA1 subunit, encoded by the putative schizophrenia-associated gene GRIA1, is required for activity-regulated AMPA receptor (AMPAR) trafficking, and plays a key role in cognitive and affective function. The cytoplasmic, carboxy-terminal domain (CTD) is the most divergent region across AMPAR subunits. The GluA1 CTD has received considerable attention for its role during long-term potentiation (LTP) at CA1 pyramidal neuron synapses. However, its function at other synapses and, more broadly, its contribution to different GluA1-dependent processes, is poorly understood. Here, we used mice with a constitutive truncation of the GluA1 CTD to dissect its role regulating AMPAR localization and function as well as its contribution to cognitive and affective processes. We found that GluA1 CTD truncation affected AMPAR subunit levels and intracellular trafficking. ΔCTD GluA1 mice exhibited no memory deficits, but presented exacerbated novelty-induced hyperlocomotion and dentate gyrus granule cell (DG GC) hyperactivity, among other behavioral alterations. Mechanistically, we found that AMPAR EPSCs onto DG GABAergic interneurons were significantly reduced, presumably underlying, at least in part, the observed changes in neuronal activity and behavior. In summary, this study dissociates CTD-dependent from CTD-independent GluA1 functions, unveiling the GluA1 CTD as a crucial hub regulating AMPAR function in a cell type-specific manner.
DietaryPhyllanthus emblica L.(Indian gooseberry, Amla) improves fecundity and resistance to oxidative stress in aDrosophila melanogastermodel of early-life malnutrition
Authors: Padmaraj Pallavi , Megha  
Published: December 2024

AbstractAmla is a celebrated ethnobotanical fruit whose consumption is associated with several beneficial claims. Many studies have demonstrated Amla’s positive impact on molecular and systemic readouts in diseased conditions. Studies on Amla’s potential as a nutraceutical however are limited. To test if daily dietary supplementation with Amla improves select systemic readouts associated with wellbeing, and alleviate phenotypes associated with early life malnutrition, we deployed the fly animal model system. Benefits were compared between adult flies that were subject to larval starvation (ELS) and controls, and between genders. The most dramatic effect was observed in resistance to oxidative stress: prophylactic feeding of 1% Amla Juice (AJ) increased median survival by ∼75% (control) and 200% (ELS) in males, and ∼167% (control) and ∼150% (ELS) in females, respectively. Interestingly, survival also increased in both genders when AJ was fed only during stress or, before and during stress. For other assays, impacts were seen only in ELS flies: AJ feeding decreased lifespan in female ELS flies, increased egg numbers by ∼25% and improved survival uponP. entomophilainfection by ∼80%. Together, these suggest that prophylactic AJ dietary intake has selective biological effects and in the context of malnutrition, it can be explored further as a nutraceutical.Abstract Figure
Exploring genetic confounding of the associations between excessive screen time and depressive symptoms in adolescence and early adulthood
Authors: Xu Jiayao , Baldwin Jessie , Hughes Amanda , Herbert Annie , Munafo Marcus R , Howe Laura D 
Published: December 2024

AbstractBackgroundDigital devices have become a major aspect of children’s life. Associations between screen time and mental health have been observed, but the causality remains unclear. This study aimed to investigate the associations between excessive screen time and later depressive symptoms, and to test the robustness of these associations when accounting for genetic confounding.MethodsThis study used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective cohort of children born between 1991 and 1992 in the UK. Different forms of screen time and depressive symptoms at ages 16, 22 and 26 were assessed through self-completion questionnaires. Screen time > 2 hours per day was defined as excessive. Depressive symptoms at age 26 were measured using the Short Mood and Feelings Questionnaire (SMFQ). Polygenic scores for mental health problems were calculated. Linear regression models were used to examine the associations between screen time at ages 16, 22 and 26 and depressive symptoms at age 26, adjusting for sociodemographic confounders and polygenic scores. Genetic sensitivity analysis (Gsens) was used to test for genetic confounding in these associations.ResultsA total of 3,005 participants were included in analysis. Some, but not all, forms of excessive screen time were associated with higher SMFQ scores, e.g. more than 2 hours of television time per day at age 16 (β: 0.07 [95%CI 0.04, 0.11] for weekdays; β: 0.06 [0.02, 0.09] for weekends) and more than 2 hours of gaming time at age 22 (β: 0.07 [95%CI 0.03, 0.10] for weekdays; β: 0.07 [0.04, 0.11] for weekends). These associations persisted after adjusting for sociodemographic confounders and polygenic scores but were attenuated to the null in the genetic sensitivity analysis (β=0.02 [-0.02, 0.06] for the association with >2 hours of television time at age 16 on weekdays; β=-0.01 [-0.05, 0.03]) for >2 hours of gaming time at age 22 on weekdays).ConclusionsFor most measures of screen time, there were no associations with depressive symptoms. Where associations were seen, they were completely attenuated in genetic sensitivity analysis, implying genetic confounding is present in the relationship between excessive screen time and depressive symptoms in adolescents and young adults.