bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histone demethylase inhibitor KDM5-C70 regulates metabolomic and lipidomic programming during an astrocyte differentiation of rat neural stem cell
Authors: Shim Minki , San Thin Thin , Shin Bohyun , Lee Hyojeong , Han Sang Beom , Lee Dong-Kyu , Kim Hyun-Jung 
Published: February 2025

Abstract
Lysine-specific histone demethylase (KDM) 5 inhibition by KDM5-C70 induces astrocytogenesis and highlights the importance of modulation of histone methylation in cell fate specification. This study investigated the role of the histone demethylase inhibitor KDM5-C70 in modulating the metabolic and lipidomic landscape during astrocyte differentiation of rat neural stem cells (NSCs). Using chemical derivatisation combined with gas chromatography-mass spectrometry, 42 metabolites were detected, indicating potential regulation of phospholipid metabolism. Subsequent lipidomic analysis, employing reverse-phase liquid chromatography with high-resolution quadrupole time-of-flight mass spectrometry, identified 180 lipid species and 9 lipid subclasses. Integrative analysis revealed that KDM5-C70 promoted astrocytogenesis through epigenetic changes linked to the attenuation of phosphatidylethanolamine (PE) biosynthesis pathways. The reduced expression of transcripts related to PE highlighted the significance of the PE pathway in influencing cell fate decisions. These quantitative metabolomic and lipidomic analyses not only advance our understanding of NSC differentiation but also lay the groundwork for potential therapeutic strategies targeting metabolic pathways in neurodegenerative diseases and neural injuries.
Functionally characterizing obesity-susceptibility genes using CRISPR/Cas9, in vivo imaging and deep learning
Authors: Mazzaferro Eugenia , Mujica Endrina , Zhang Hanqing , Emmanouilidou Anastasia , Jenseit Anne , Evcimen Bade , Metzendorf Christoph , Dethlefsen Olga , Loos Ruth JF , Vienberg Sara Gry , Larsson Anders , Allalou Amin , den Hoed Marcel 
Published: February 2025

Abstract
Hundreds of loci have been robustly associated with obesity-related traits, but functional characterization of candidate genes remains a bottleneck. Aiming to systematically characterize candidate genes for a role in accumulation of lipids in adipocytes and other cardiometabolic traits, we developed a pipeline using CRISPR/Cas9, non-invasive, semi-automated fluorescence imaging and deep learning-based image analysis in live zebrafish larvae. Results from a dietary intervention show that 5 days of overfeeding is sufficient to increase the odds of lipid accumulation in adipocytes by 10 days post-fertilization (dpf, n = 275). However, subsequent experiments show that across 12 to 16 established obesity genes, 10 dpf is too early to detect an effect of CRISPR/Cas9-induced mutations on lipid accumulation in adipocytes (n = 1014), and effects on food intake at 8 dpf (n = 1127) are inconsistent with earlier results from mammals. Despite this, we observe effects of CRISPR/Cas9-induced mutations on ectopic accumulation of lipids in the vasculature (sh2b1 and sim1b) and liver (bdnf); as well as on body size (pcsk1, pomca, irs1); whole-body LDLc and/or total cholesterol content (irs2b and sh2b1); and pancreatic beta cell traits and/or glucose content (pcsk1, pomca, and sim1a). Taken together, our results illustrate that CRISPR/Cas9- and image-based experiments in zebrafish larvae can highlight direct effects of obesity genes on cardiometabolic traits, unconfounded by their – not yet apparent – effect on excess adiposity.
Modulation of tumor inflammatory signaling and drug sensitivity by CMTM4
Authors: Xu Yitian , Kang Kyeongah , Coakley Brian A , Eisenstein Samuel , Parveen Arshiya , Mai Sunny , Wang Yuan Shuo , Zheng Junjun , Boral Debasish , Mai Junhua , Pan William , Zhang Licheng , Aaronson Stuart A , Fang Bingliang , Divino Celia , Zhang Bin , Song Won-Min , Hung Mien-Chie , Pan Ping-Ying , Chen Shu-Hsia 
Published: February 2025

Abstract
Although inflammation has been widely associated with cancer development, how it affects the outcomes of immunotherapy and chemotherapy remains incompletely understood. Here, we show that CKLF-like MARVEL transmembrane domain-containing member 4 (CMTM4) is highly expressed in multiple human and murine cancer types including Lewis lung carcinoma, triple-negative mammary cancer and melanoma. In lung carcinoma, loss of CMTM4 significantly reduces tumor growth and impairs NF-κB, mTOR, and PI3K/Akt pathway activation. Furthermore, we demonstrate that CMTM4 can regulate epidermal growth factor (EGF) signaling post-translationally by promoting EGFR recycling and preventing its Rab-dependent degradation. Consequently, CMTM4 knockout sensitizes human lung tumor cells to EGFR inhibitors. In addition, CMTM4 knockout tumors stimulated with EGF show a decreased ability to produce inflammatory cytokines including granulocyte colony-stimulating factor (G-CSF), leading to decreased recruitment of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and therefore establishing a less suppressive tumor immune environment in both lung and mammary cancers. We also present evidence indicating that CMTM4-targeting siRNA-loaded liposomes reduce lung tumor growth in vivo and prolong animal survival. Knockout of CMTM4 enhances immune checkpoint blockade or chemotherapy to further reduce lung tumor growth. These data suggest that CMTM4 represents a novel target for the inhibition of tumor inflammation, and improvement of the immune response and tumor drug sensitivity.
The tempo and presence of university students’ learning across schoolscapes
Authors: Peltoniemi Aaron Joshua , Szabó Tamás Péter , Hämäläinen Raija 
Published: February 2025

Abstract
Although the term schoolscapes often alludes to physical spaces, contemporary schoolscapes not
only exist physically but also virtually, requiring students to navigate through different spatialities and temporalities. In this
study, we interviewed six Information and Software Engineering university students to explore how tempo and presence converge with
learning experiences within physical and virtual schoolscapes. Using thematic analysis, two themes were identified: I) synchronous
learning in designated learning spaces, and II) asynchronous learning in non-designated learning spaces. Presence was the
principal concept, which was divided into social presence, co-presence, cognitive presence, emotional presence, teaching presence,
and place presence, and captured students’ learning experiences across schoolscapes. Results showed that the tempo of Information
and Software Engineering university students’ learning was based on how each category of presence and learning mode
(synchronous/asynchronous) related to their learning needs or preferences.
The use of D-D reactions to diagnose the lifetime of spin polarized fuel
Authors: Garcia Alvin , Heidbrink William W , Sandorfi Andrew M J 
Published: February 2025

Abstract
If the nuclei remain polarized, spin polarized fuel can increase the fusion power produced in a reactor while using less fuel. This study assesses whether reactions between an unpolarized deuterium (D) beam and polarized deuterium nuclei can in principle experimentally ascertain the persistence of nuclear polarization in a magnetic fusion experiment. The differential cross section for D-D reactions between unpolarized and polarized nuclei depends upon polarization, so the polarization state can be inferred from measurements of the D-D fusion products. An evaluation is performed for 3-MeV proton detection in the DIII-D tokamak using 81 keV neutral beams and polarized target fuel injected as a pellet. Measurement of the escaping proton pitch v
3,‖/v
3 is insensitive to the degree of polarization but energy-resolved measurements are sensitive. The sensitivity is comparable for different angles of beam injection. Because the D-D reaction rate is large for this scenario, uncertainties associated with counting statistics are small, making inference of the polarization feasible with current technology.
When should the nephrologist think about genetics in patients with glomerular diseases?
Authors: Torra Roser , Barros Xoana , Díaz-Encarnación Montserrat , Fayos Leonor , Furlano Mónica , Pilco Melissa , Pybus Marc , Shabaka Amir , Viera Elizabeth , Ars Elisabet 
Published: February 2025

Abstract
This review discusses the significance of genetics in diagnosing glomerular diseases. Advances in genetic testing, particularly next-generation sequencing, have improved the accessibility and accuracy of diagnosing monogenic diseases, allowing for targeted gene panels and whole-exome/genome sequencing to identify genetic variants associated with glomerular diseases.
Key indicators for considering a genetic cause include the age of onset, extrarenal features, family history, and inconclusive kidney biopsy results. Early-onset diseases, for instance, have a higher likelihood of being genetically caused, while extrarenal manifestations can also suggest an underlying genetic conditions. A thorough family history can reveal patterns of inheritance that point to monogenic causes, although complexities like incomplete penetrance, skewed X inactivation and mosaicism can complicate the assessment. Also, autosomal recessive conditions imply asymptomatic parents, making genetic suspicion less likely, while de novo mutations can occur without any family history, further obscuring genetic assessment.
Focal Segmental Glomerulosclerosis (FSGS) is characterized by podocyte injury and depletion, presenting in various forms including primary, genetic, and secondary FSGS. Accurate classification of FSGS patients based on clinical and histological features is essential for guiding treatment decisions, optimizing therapeutic plans, avoiding unnecessary immunosuppression, and predicting relapse risk after kidney transplantation.
Overall, a clinicopathological approach, enriched by genetic testing, offers a precise framework for diagnosis and management in glomerular diseases. Future directions for research and clinical practice include potential advancements in genetic testing and personalized medicine, which could further improve diagnostic precision and individualized treatment strategies.
May Measurement Month 2022: an analysis of blood pressure screening results from Venezuela
Authors: Guzmán-Franolic Monica L , Duin-Balza Amanda , Beaney Thomas , Kerr Gabriela , Rawik-Dagher Yuly , Poulter Neil R , Armas-Hernandez María J , Octavio-Seijas José A , Armas-Padilla María C , Silva Eglé , Sosa-Canache Beatriz , Morr Igor , Hernández-Hernandez Rafael 
Published: February 2025

Abstract
Cardiovascular diseases continue to be the main cause of death in Venezuela, and hypertension is the primary risk factor. The May Measurement Month (MMM) campaign has been conducted annually in Venezuela since 2017. In 2022 (MMM22), the campaign included 46 239 participants with a mean age of 57.3 (SD 14.9) years and 57.2% were female. The percentage of participants with hypertension was 59.0% (females: 56.1%; males: 62.9%), of those 80.6% were aware of their condition and 78.9% were on antihypertensive medication. Among those receiving drug treatment, 58.8% were controlled to &lt;140/90 mmHg, and of the overall hypertensive population, 46.4% were controlled. Of those taking antihypertensive medication, 58.5% received one antihypertensive drug, 31.7% two drugs and 9.8% were on three or more drugs. When results were age-sex standardised, the prevalence of hypertension was lower at 39.9%. Other CV risk factors were also identified: 8.3% reported having diabetes, 21.0% were obese (BMI ≥ 30 kgm2), 36.3% were overweight (BMI ≥ 25 & &lt;30 kgm2), 8.5% were current smokers, and 53.9% reported inadequate physical activity. Additionally, 53.1% of females and 25.4% of males had an abnormal abdominal circumference classified as abdominal obesity. Furthermore, a previous myocardial infarction, stroke, or heart failure was reported by 2.7%, 1.7% and 2.4%, respectively. In conclusion, this study confirms the suitability of opportunistic screening in detecting large numbers with previously unknown hypertension, although the population prevalence of hypertension may be overestimated. It also identified overall poor control rates, highlighting the need for improved initiatives for BP screening and management.
May Measurement Month 2022: an analysis of blood pressure screening results from Uganda
Authors: Mondo Charles Kiiza , Poulter Neil R , Baluku Joseph Baruch , Anthony Ocanit , Jane Okutiru , Beaney Thomas , Kerr Gabriele , Wanzhu Zhang 
Published: February 2025

Abstract
The May Measurement Month (MMM) campaign was carried out in Uganda in 2022 with the aim of raising awareness of raised blood pressure (BP). Here, we report on the findings of the campaign.
Adults aged ≥ 18 years were recruited opportunistically at St Francis Hospital, Nsambya and Kiruddu National Referral Hospital in Kampala. Three seated BP readings were taken for each participant, along with completion of a questionnaire on demographics, lifestyle factors, and comorbidities. Hypertension was defined as a systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg or being on antihypertensive medication. Controlled BP was defined as being on antihypertensive medication with a BP &lt;140/90 mmHg. Multiple imputation was used to estimate any missing BP readings. In total, 2414 were screened, with a mean age of 44.4 years and 58.0% were female. Of all participants, 1086 (45.0%) had hypertension, of whom 725 (66.8%) were aware, and 691 (63.6%) were on antihypertensive medication. Of those on antihypertensive medication, 244 (35.3%) had controlled BP, and of all participants with hypertension, 22.5% had controlled BP.
Conclusion The MMM campaign in Uganda identified significant numbers of participants with either untreated or inadequately treated hypertension, highlighting the potential impact of this campaign on hypertension awareness and BP control.
Bioprospecting Endophytic Fungi of Forest Plants for their Monoamine Oxidase A and Cholinesterases Inhibitors, and Peroxisome Proliferator-Activated Receptor Gamma Agonists
Authors: El-Sayed El-Sayed R , Grzelczyk Joanna , Strzała Tomasz , Gałązka-Czarnecka Ilona , Budryn Grażyna , Boratyński Filip 
Published: February 2025

Abstract

Aims
The urgent search for new natural bioactive compounds is crucial to address growing clinical demands. With this perspective, this paper focuses on isolating and bioprospecting fungal endophytes from some plant species in a local forest in Wroclaw, Poland.

Methods and Results
Forty-three fungal endophytes were isolated and their extracts were tested for inhibitory potential against monoamine oxidase A (MAO-A), acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and peroxisome proliferator-activated receptor gamma (PPAR-γ) agonists. Six promising strains after screening were identified to possess all these activities. These strains and their respective plant hosts were Sphaeropsis sapinea BUK-L2 (Fagus sylvatica), Coniochaeta velutina SW-B (Picea abies), Epicoccum nigrum COR-B (Corylus avellana), Paraphaeosphaeria verruculosa JAR-B (Sorbus aucuparia), Umbelopsis isabellina COR-L1 (Corylus avellana), and Epicoccum mezzettii QR-B (Quercus robur). Moreover, gamma irradiation at several doses (Gy) was separately applied to the fungal cultures to study their enhancement effects on the recorded activities. Finally, compounds of active bands from preparative TLC of the two promising strains (Coniochaeta velutina SW-B and Epicoccum nigrum COR-B), were identified by GC-MS.

Conclusions
The present study is the first report on bioprospecting endophytic fungi of forest plants for aforementioned activities.
Altruism or Selfishness: Floral behavior based on genetic relatedness with neighboring plants
Authors: Tomizuka Haruto , Yamawo Akira , Tachiki Yuuya 
Published: February 2025

Abstract
Kin recognition in plants may lead to plastic changes in their behavior, such as altering their floral display size. In this study, we conducted evolutionary simulations of the two floral tactics utilized by plants depending on the genetic relatedness of their neighboring plants. We found that the evolutionary consequences of the floral display size in plants can be classified into four types, based on whether the floral display size increased or decreased in comparison with the case plants disable of kin recognition. As a typical result, the plants that grew with kin behaved altruistically by increasing their floral display size, whereas those that coexisted with strangers behaved selfishly by reducing their floral display size, as is observed in the field. The kin recognition and resultant evolution of the floral display size had the spillover effect on the population scale. Kin recognition generally increased the intraspecific variation in the floral display size and seed production, and decreased the genetic diversity of plant populations.
Investigating ungulate site use as a driver of Culicoides (Diptera: Ceratopogonidae) emergence from larval habitats
Authors: McGregor Bethany L , Markwardt Chip F , Davis Travis M 
Published: February 2025

Abstract
Culicoides (Diptera: Ceratopogonidae) Latreille biting midges are the vectors of several viruses of veterinary significance. The larvae of some biting midge species develop in semiaquatic habitats that are affected by the activity of vertebrates. However, the importance of vertebrate animal activity in biting midge density has not been satisfactorily quantified. The goal of this study was to investigate the impact that three different hooved animals representing agricultural (cattle), wild (cervids), and intermediate (bison) animal populations have on the density and emergence of Culicoides from larval habitats. Trail cameras recorded vertebrate activity at eight sites at the Konza Prairie Biological Station with cattle, cervids, and/or bison, which was paired with larval substrate sampling to investigate midge density. The total time spent by all 3 target animals over the previous month and the average time spent by bison were significantly positively correlated with overall biting midge emergence. Species-specific analyses revealed significant positive associations of C. crepuscularis Malloch with several cattle variables including number of cattle days and events and average number of cattle, while more bison variables were found to be significant for C. haematopotus Malloch (bison days and bison events, negative associations) and C. variipennis Coquillett (negative associations for bison days and average number of bison; positive relationship with average bison time). Significant results for cervids included negative associations of C. crepuscularis with average cervid time and C. variipennis with cervid days. These results show that different ungulates impact midge abundance and emergence in different ways, improving our understanding of midge population drivers.
The role of electric dominance for particle injection in relativistic reconnection
Authors: Gupta Sanya , Sridhar Navin , Sironi Lorenzo 
Published: February 2025

Abstract
Magnetic reconnection in relativistic plasmas—where the magnetization σ ≫ 1—is regarded as an efficient particle accelerator, capable of explaining the most dramatic astrophysical flares. We employ two-dimensional (2D) particle-in-cell simulations of relativistic pair-plasma reconnection with vanishing guide field and outflow boundaries to quantify the impact of the energy gain occurring in regions of electric dominance (E &gt; B) for the early stages of particle acceleration (i.e., the “injection” stage). Given an injection threshold energy ε* = σ/4 for the particles that eventually attain energy εT by time T, we calculate the mean fractional contribution ζ(ε*, εT) by E &gt; B fields to particle energization at the time when the threshold ε* is reached. We find that ζ monotonically increases with σ and εT; for σ ≳ 50 and εT/σ ≳ 8, we find that ≳ 80 % of the energy gain obtained before reaching ε* = σ/4 occurs in E &gt; B regions. We find that ζ is independent of simulation box size Lx, as long as εT is normalized to the maximum particle energy, which scales as $\epsilon _{\rm max}\propto L_{\rm x}^{1/2}$ in 2D. The distribution of energy gains εχ acquired in E &gt; B regions can be modeled as $dN/d\epsilon _{\chi }\propto \epsilon _{\chi }^{-0.35}\exp [-(\epsilon _{\chi }/0.06\, \sigma )^{0.5}]$. Our results help assess the role of electric dominance in relativistic reconnection with vanishing guide fields, which is realized in the magnetospheres of black holes and neutron stars.
An update on the pathogenesis of idiopathic inflammatory myopathies
Authors: Tiniakou Eleni 
Published: February 2025

Purpose of review
As the question of the pathogenesis of inflammatory myopathies remains unanswered, there has been a significant effort in recent years to investigate various components of the innate and adaptive immune systems, with evidence pointing that they work together to initiate and propagate the autoimmune response. This review aims to explore recent advancements in understanding the mechanisms underlying myopathies.

Recent findings
Recent research has concentrated on uncovering potential triggers, examining the role of immune cells, both lymphocytes and myeloids, and investigating the contribution of inflammatory mediators to the autoimmune response in inflammatory myopathies. Unsuccessful clinical trials helped reshape established hypotheses about pathogenesis, while genetic mutations offered clues to the disease's root causes. The pathogenic role of autoantibodies is being reconsidered based on transcriptional data. Repurposing existing medications to combat muscle fiber dysfunction is also emerging as a potential therapeutic approach.

Summary
Our understanding of inflammatory myopathies has evolved significantly as our understanding of the disease has grown. Even though breakthroughs have been documented on the underlying mechanisms of myopathies, important questions remain unanswered.
Influence of the Surgeon’s First Operation of the Day on Patient Outcomes
Authors: Dagnino Filippo , Polazzi tephanie , Lifante Jean-Christophe , Dey Tanujit , Duclos Antoine ,   TopSurgeons Study Group
Published: February 2025

Objective:
To investigate whether the cumulative operative time spent by a surgeon operating on patients on the same day prior to starting a new procedure was associated with surgical outcomes.

Background:
The impact of daily operating room workload on a surgeon’s performance and patient outcomes is uncertain.

Methods:
All elective patients, operated by attending surgeons across seven specialties in four French hospitals between 11/01/2020-12/31/2021, were included. Surgeons’ operative workload the same day before each operation was measured in minutes by cumulating incision-to-closure times for all their patients as the primary operator. Composite of adverse events within 30 days post-surgery, encompassed major surgical complications, unplanned reoperation, extended ICU stay, and patient death. Generalized linear mixed models estimated the association between each outcome and operative workload, considering the clustering of operations by surgeons, and adjusting for patient comorbidities, procedure complexity, and surgeon characteristics.

Results:
The cohort included 7,979 elective surgeries performed by 44 surgeons. Composite adverse events rates were higher in the 0-minute group compared to those with a higher duration (20.7% vs. 12.5%, P<0.001), as were rates of major complications (19.3% vs. 11.7%, P<0.001), reoperations (6.5% vs. 3.4%, P=0.005), and ICU stay (3.7% vs. 1.2%, P=0.016). When the surgeon had already spent time operating on patients prior to the procedure, adjusted relative risks were lower for composite adverse events (aRR 0.85 [95%CI 0.76–0.95]), major complications (0.86 [0.76–0.97]), reoperation (0.78 [0.63–0.97]), and ICU stay (0.69 [0.49–0.98]).

Conclusions:
First patient of the day may experience worse outcomes, prompting surgeons to warm up before starting surgery. Further research is needed to replicate these findings, as many surgeons may prioritize starting with the most complex and challenging cases, which inherently carry greater risks.