bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of antidiabetic agents on lipid metabolism of skeletal muscle: A narrative review
Authors: Xu Ming , Lv Dongqing , Wei Hongxia , Li Zhe , Jin Shuqing , Liu Qinhao , Zhang Yi , Liu Yunfeng 
Published: January 2025

AbstractMetabolic syndrome‐related diseases frequently involve disturbances in skeletal muscle lipid metabolism. The accumulation of lipid metabolites, lipid‐induced mitochondrial stress in skeletal muscle cells, as well as the inflammation of adjacent adipose tissue, are associated with the development of insulin resistance and metabolic dysfunction. Consequently, when antidiabetic medications are used to treat various chronic conditions related to hyperglycaemia, the impact on skeletal muscle lipid metabolism should not be overlooked. However, current research has predominantly focused on muscle mass rather than skeletal muscle lipid metabolism and its interplay with glucose metabolism. In this review, we summarised the latest research on the effects of antidiabetic drugs and certain natural compounds with antidiabetic activity on skeletal muscle lipid metabolism, focusing on data from preclinical to clinical studies. Given the widespread use of antidiabetic drugs, a better understanding of their effects on skeletal muscle lipid metabolism merits further attention in future research.
Unexpected cardiovascular risks of glucagon‐like peptide‐1 receptor agonist and aspirin co‐administration in individuals with obesity, with and without type 2 diabetes: A propensity score matched cohort study
Authors: Lin Chia‐Ming , Chen Jo‐Ching , Meyerowitz‐Katz Gideon , Huang Yu‐Nan , Su Pen‐Hua 
Published: January 2025

AbstractAimsTo examine the cardiovascular safety of combining glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) with aspirin in individuals with obesity, both with and without type 2 diabetes (T2D).Materials and MethodsThis propensity score matched cohort study analysed data from 2 946 579 individuals with obesity, with and without T2D, using the TriNetX US and Global dataset. Participants were categorized into four matched groups: those receiving GLP‐1 RA plus aspirin versus those receiving GLP‐1 RA alone, for both diabetic and non‐diabetic individuals. Cardiovascular outcomes and adverse events were evaluated over 5 years using Cox proportional hazards models.ResultsIndividuals with obesity treated with GLP‐1 RAs plus aspirin showed significantly higher risks of various cardiovascular events compared to those on GLP‐1 RAs alone. In non‐diabetic obese individuals, the combination therapy increased risks of hypertensive heart diseases (HR 1.40, 95% CI 1.15–1.60), ischaemic heart disease (HR 2.39, 95% CI 1.92–2.97) and heart failure (HR 1.97, 95% CI 1.54–2.53). Similar patterns were observed in individuals with T2D. Atrial fibrillation and cardiac arrhythmias showed increasing hazard ratios over time. The combination therapy also led to more frequent adverse events, including gastrointestinal bleeding.ConclusionsThe combination of GLP‐1 RAs with aspirin in individuals with obesity, both with and without T2D, was associated with increased cardiovascular risks compared to GLP‐1 RA monotherapy. These findings suggest that there may be risks associated with the combined use of these treatments and highlight the need for further research into this possible complication with regard to treatment.
Predicting Reliable Improvements in Primary Care Youth Mental Health
Authors: Moore Jeff , Doyle Elizabeth , Carey Eleanor , Blix Anna , Booth Ailbhe , Rossouw Joe , O'Reilly Aileen , O'Brien Siobhan , Duffy Joseph 
Published: January 2025

ABSTRACTBackgroundAmid a youth mental health crisis, community‐based early intervention services have shown promising outcomes. Understanding the specific factors that predict clinical outcomes is crucial for enhancing intervention efficacy, yet these factors remain insufficiently understood.AimThis study examined the individual and service‐related factors associated with reliable improvement for young people (n = 4565) aged 12–25 years attending a brief primary care youth talk therapy mental health service across 14 sites.MethodsReliable improvement was measured using the clinical outcomes in routine evaluation (YP‐CORE and CORE‐10) measure at baseline and follow up. Poisson regression was used to identify individual and service‐related factors associated with reliable improvement.ResultsHigher initial distress levels predicted increased levels of reliable improvement (adjusted risk ratios ranged from 235.7 to 415.1, p < 0.001), indicating that this intervention is particularly effective for individuals with higher initial distress levels. Conversely, extended wait times negatively affected therapeutic outcomes for young people aged 12–16, with waiting times exceeding 60 days associated with lower likelihoods of improvement (adjusted risk ratio = 89.2 for > 60 days, p < 0.01). Waiting times did not significantly impact individuals aged 17–25. Attending nine or more sessions was associated with a lower likelihood of reliable improvement.ConclusionThis study underscores the critical importance of minimising wait times for young people and the importance of tailored approaches to early intervention services. Addressing these factors can enhance the efficacy of early intervention services and better support the mental well‐being of young people.
Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010–2021
Authors: Ohira Masayuki , Takano Ai , Yoshi Kentaro , Arai Akira , Aso Yashuhiro , Furutani Rikiya , Hamano Tadanori , Takahashi‐Iwata Ikuko , Kaneko Chikako , Matsuura Tohru , Maeda Norihisa , Nakajima Hideto , Shindo Katsuro , Suenaga Toshihiko , Sugie Kazuma , Suzuki Yasuhiro , Yamashita Toru , Angulo Frederick J. , Edwards Juanita , Bender Cody Matthew , Harper Lisa R. , Nakayama Yoshikazu , Ito Shuhei , Pilz Andreas , Stark James H. , Moïsi Jennifer C. , Mizusawa Hidehiro , Takao Masaki 
Published: January 2025

AbstractBackground and PurposeClinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance‐reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under‐diagnosed in Japan since diagnostic tests are not readily available. We sought to determine if LNB could be a cause of previously undiagnosed encephalitis or meningitis in Japan.MethodsInvestigators at 15 hospitals in 10 prefectures throughout Japan retrieved serum and/or cerebrospinal fluid (CSF) samples collected in 2010–2021 from 517 patients hospitalized with encephalitis or meningitis which had an etiology that had not been determined. Samples were tested for Bbsl‐specific antibodies using ELISA and Western blot tests. In alignment with the European Union LNB case definition, a confirmed LNB case had CSF pleocytosis and intrathecal production of Bbsl‐specific antibodies and a probable LNB case had a CSF sample with pleocytosis and Bbsl‐specific antibodies.ResultsLNB was identified in three hospitalized patients with meningitis of previously undetermined etiology: a male resident of Aomori Prefecture was a confirmed LNB case, and two female residents of Oita Prefecture were probable LNB cases. None of the patients with confirmed or probable LNB had traveled in the month prior to symptom onset and none had samples previously tested for LB.ConclusionThe identification of previously undiagnosed LNB cases indicates a need for enhanced disease awareness in Japan, particularly beyond Hokkaido Island, and more readily available LB diagnostic testing.
HIF1α Plays a Crucial Role in the Development of TFE3–Rearranged Renal Cell Carcinoma by Orchestrating a Metabolic Shift Toward Fatty Acid Synthesis
Authors: Nishizawa Hidekazu , Funasaki Shintaro , Ma Wenjuan , Kubota Yoshiaki , Watanabe Kazuhide , Arima Yuichiro , Kuroda Shoichiro , Ito Takaaki , Furuya Mitsuko , Motoshima Takanobu , Nishiyama Akira , Mehanna Sally , Satou Yorifumi , Hasumi Hisashi , Jikuya Ryosuke , Makiyama Kazuhide , Tamura Tomohiko , Oike Yuichi , Tanaka Yasuhito , Suda Toshio , Schmidt Laura S. , Linehan W. Marston , Baba Masaya , Kamba Tomomi 
Published: January 2025

ABSTRACTTumor development often requires cellular adaptation to a unique, high metabolic state; however, the molecular mechanisms that drive such metabolic changes in TFE3–rearranged renal cell carcinoma (TFE3‐RCC) remain poorly understood. TFE3‐RCC, a rare subtype of RCC, is defined by the formation of chimeric proteins involving the transcription factor TFE3. In this study, we analyzed cell lines and genetically engineered mice, demonstrating that the expression of the chimeric protein PRCC‐TFE3 induced a hypoxia‐related signature by transcriptionally upregulating HIF1α and HIF2α. The upregulation of HIF1α by PRCC‐TFE3 led to increased cellular ATP production by enhancing glycolysis, which also supplied substrates for the TCA cycle while maintaining mitochondrial oxidative phosphorylation. We crossed TFE3‐RCC mouse models with Hif1α and/or Hif2α knockout mice and found that Hif1α, rather than Hif2α, is essential for tumor development in vivo. RNA‐seq and metabolomic analyses of the kidney tissues from these mice revealed that ketone body production is inversely correlated with tumor development, whereas de novo lipid synthesis is upregulated through the HIF1α/SREBP1‐dependent mechanism in TFE3‐RCC. Our data suggest that the coordinated metabolic shift via the PRCC‐TFE3/HIF1α/SREBP1 axis is a key mechanism by which PRCC‐TFE3 enhances cancer cell metabolism, promoting tumor development in TFE3‐RCC.
Effects of Feed Supplementation With Fulvic Acid on the Systemic and Mucosal Protective Mechanisms of Juvenile Rainbow Trout (Oncorhynchus mykiss)
Authors: Zavvar Fatemeh , Mazandarani Mohammad , Hoseinifar Seyed Hossein , Jafari Valiollah , Lieke Thora 
Published: January 2025

ABSTRACTRainbow trout (Oncorhynchus mykiss) is an important fish species raised in aquaculture, but it is susceptible to stress, infections diseases. The present study aimed to determine the effects of fulvic acid feed addition on the systemic and mucosal protective mechanisms of juvenile rainbow trout and to elucidate the underlying molecular mechanisms of changes in the gut. Rainbow trout (4.30 ± 0.6 g) diet was supplemented with different levels of fulvic acid: 0% (Control), 0.5%, 1% and 2%. At the end of 8‐week feeding trial, growth parameters such as final weight gained weight (%), SGR (F1%) increased, and FCR (all levels) decreased significantly compared to the control group. We found that the activity of lysozyme, glutathione peroxidase, and catalase in the serum were significantly improved, especially after the addition of 0.5% and 1% of fulvic acid. At the same time, the immunoglobulin concentration in the skin mucus was increased with 0.5% supplementation. However, the expression of tnf‐α, il‐6 and gpx in the intestine was strongly upregulated after supplementation with 2%, indicating oxidative stress and inflammation with this level of fulvic acid inclusion. Furthermore, the mucus lysozyme activity was reduced at this concentration, which can increase the susceptibility to pathogen invasion. The results suggest that adding 0.5%−1% of fulvic acid to the feed of juvenile rainbow trout can help to improve their immune and antioxidative defenses and thereby support the wellbeing of fish.
Automatic determination of 3D particle morphology from multiview images using uncertainty‐evaluated deep learning
Authors: Liu Hongchen , Su Huaizhi , Sheil Brian 
Published: January 2025

AbstractParticle morphology is a crucial factor influencing the mechanical properties of granular materials particularly in infrastructure construction processes where accurate shape descriptors are essential. Accurately measuring three‐dimensional (3D) morphology has significant theoretical and practical value for exploring the multiscale mechanical properties of civil engineering materials. This study proposes a novel approach using multiview (two‐dimensional [2D]) particle images to efficiently predict 3D morphology, making real‐time aggregate quality analysis feasible. A 3D convolutional neural network (CNN) model is developed, which combines Monte Carlo dropout and attention mechanisms to achieve uncertainty‐evaluated predictions of 3D morphology. The model incorporates a convolutional block attention module, involving a two‐stage attention mechanism with channel attention and spatial attention, to further optimize feature representation and enhance the effectiveness of the attention mechanism. A new dataset comprising 18,000 images of 300 natural gravel and 300 blasted rock fragment particles is used for model training. The prediction accuracy and uncertainty of the proposed model are benchmarked against a range of alternative models including 2D CNN, 3D CNN, and 2D CNN with attention, in particular, to the influence of the number of input multiview particle images on the performance of the models for predicting various morphological parameters is explored. The results indicate that the proposed 3D CNN model with the attention mechanism achieves high prediction accuracy with an error of less than 10%. Whilst it exhibits initially greater uncertainty compared to other models due to its increased complexity, the model shows significant improvement in both accuracy and uncertainty as the number of training images is increased. Finally, residual challenges associated with the prediction of more complex particle angles and irregular shapes are also discussed.
The aerial epidermis is a major site of quinolizidine alkaloid biosynthesis in narrow‐leafed lupin
Authors: Frick Karen Michiko , Lorensen Marcus Daniel Brandbjerg Bohn , Micic Nikola , Esteban Eddi , Pasha Asher , Schulz Alexander , Provart Nicholas James , Nour‐Eldin Hussam Hassan , Bjarnholt Nanna , Janfelt Christian , Geu‐Flores Fernando 
Published: January 2025

Summary
Lupins are promising protein crops that accumulate toxic quinolizidine alkaloids (QAs) in the seeds, complicating their end‐use. QAs are synthesized in green organs (leaves, stems, and pods) and a subset of them is transported to the seeds during fruit development. The exact sites of biosynthesis and accumulation remain unknown; however, mesophyll cells have been proposed as sources, and epidermal cells as sinks.
We investigated the exact sites of QA biosynthesis and accumulation in biosynthetic organs of narrow‐leafed lupin (Lupinus angustifolius) using mass spectrometry‐based imaging (MSI), laser‐capture microdissection coupled to RNA‐Seq, and precursor feeding studies coupled to LC‐MS and MSI.
We found that the QAs that accumulate in seeds (‘core’ QAs) were evenly distributed across tissues; however, their esterified versions accumulated primarily in the epidermis. Surprisingly, RNA‐Seq revealed strong biosynthetic gene expression in the epidermis, which was confirmed in leaves by quantitative real‐time polymerase chain reaction. Finally, feeding studies using a stably labeled precursor showed that the lower leaf epidermis is highly biosynthetic.
Our results indicate that the epidermis is a major site of QA biosynthesis in narrow‐leafed lupin, challenging the current assumptions. Our work has direct implications for the elucidation of the QA biosynthesis pathway and the long‐distance transport network from source to seed.
The effect of size on mate selection, fecundity and survival in Culex pipiens mosquitoes
Authors: Villarreal Susan , Senior Amelia , Price Matthew 
Published: January 2025

AbstractCulex pipiens L. is a medically important mosquito due to its abundance and ability to transmit West Nile virus. Despite being the focus of many mosquito control strategies, very little is known about its mating behaviour. Several control strategies rely on knowing female mate preferences to ensure their efficacy. Therefore, the purpose of this study was to characterize mate selection based on mate quality. Because larger individuals should have more resources available to be used towards mating behaviour, it was hypothesized that larger mates (males or females) would be of higher value and preferentially mated with compared to smaller ones. By manipulating food availability, males and females were reared to be either large or small adults and were mated with either a large or small mate. Through a series of experiments, the effect of size on mate success and post‐mating responses was assessed via insemination rates, blood feeding, egg laying, fertility and survival. Despite larger females living longer and being more fecund, males did not preferentially mate with larger females, nor did male size influence female survival or fecundity. Because larval rearing environment had an influence on adult morphology and fitness, it should be taken into consideration in mosquito control programmes.
The implications and challenges of the IMO 2020 regulation: Exploring options for compliance
Authors: Pereira Eduardo G. 
Published: January 2025

AbstractThe International Maritime Organisation (IMO), as a part of its continuing efforts to regulate sulphur oxide emissions, adopted the IMO 2020 Regulation. The regulation established a new worldwide cap on the sulphur content of shipping fuel. This article critically analyses the key provisions of the IMO's latest regulation by examining the economic consequences of the regulation and its impact on the shipping industry, petroleum markets and refineries. This article highlights the challenges that State parties face in enforcing the regulation and the repercussions for non‐compliance. The key findings of this article reveal that since the enforcement of the IMO 2020 Regulation, sulphur emissions have decreased by approximately 8.5 to 8.9 million metric tons. By 2025, this reduction is expected to reach around 77% of pre‐regulation levels. Coastal settlements, particularly highly populated areas, are expected to benefit from the reduction in sulphur concentration levels.
Exploring the Relationship Between Humoral and Cellular T Cell Responses Against SARS‐CoV‐2 in Exposed Individuals From Emilia Romagna Region and COVID‐19 Severity
Authors: Mazzotti Lucia , Borges de Souza Patricia , Azzali Irene , Angeli Davide , Nanni Oriana , Sambri Vittorio , Semprini Simona , Bravaccini Sara , Cerchione Claudio , Gaimari Anna , Nicolini Fabio , Ancarani Valentina , Martinelli Giovanni , Pasetto Anna , Calderon Hugo , Juan Manel , Mazza Massimiliano 
Published: January 2025

ABSTRACTCOVID‐19 remains a significant global health problem with uncertain long‐term consequences for convalescents. We investigated the relationships between anti‐N protein antibody levels, severe acute respiratory syndrome (SARS)‐CoV‐2‐associated TCR repertoire parameters, HLA type and epidemiological information from three cohorts of 524 SARS‐CoV‐2‐infected subjects subgrouped in acute phase, seronegative and seropositive convalescents from the Emilia Romagna region. Epidemiological information and anti‐N antibody index were associated with TCR repertoire data. HLA type was inferred from TCR repertoire using the HLA3 tool and its association with clonal breadth (CB) and clonal depth (CD) was assessed. Age above 58 years, male and COVID‐19 hospitalisation were significantly and independently associated with seropositivity (p = 0.004; p = 0.004; p = 0.04), suggesting an association between high antibody titres and symptoms' severity. As for the TCR repertoire analysis, we found no difference in CB among the cohorts, while CD was higher in seronegative than acute (p = 0.04). However, clustering analysis supported that seronegative patients are endowed with broader CB and deeper CD indicating a compensatory mechanism without effective seroconversion. The CD calculated on the TCRs associated with the single SARS‐CoV‐2 ORFs in convalescents is higher when compared to the acute. Lastly, we identified and reported on novel HLAs significantly associated with increased risk of hospitalisation such as HLA‐C*07:02 carriers (OR = 3.9, CI = 1.1–13.4, p = 0.03) and on HLAs that associate significantly with lower or higher TCR repertoire parameters in a population exposed for the first time to SARS‐CoV‐2.
The Novel HLA‐DPB1*1498:01 Allele, Identified by Sanger Dideoxy Nucleotide Sequencing in a Chinese Individual
Authors: Lou Can , Xie Zhi‐cong , Ma Li , Hu Xiao‐zhuang , Lei Hang 
Published: January 2025

ABSTRACTThe HLA‐DPB1*1498:01 allele differs from HLA‐DPB1*02:02:01:01 by a single non‐synonymous nucleotide change in exon 4.
Independently engaging protein tethers of different length enhance synaptic vesicle trafficking to the plasma membrane
Authors: Berns Manon M. M. , Yildiz Mirza , Winkelmann Stefanie , Walter Alexander M. 
Published: January 2025

AbstractSynaptic vesicle (SV) trafficking toward the plasma membrane (PM) and subsequent SV maturation are essential for neurotransmitter release. These processes, including SV docking and priming, are co‐ordinated by various proteins, such as SNAREs, Munc13 and synaptotagmin (Syt), which connect (tether) the SV to the PM. Here, we investigated how tethers of varying lengths mediate SV docking using a simplified mathematical model. The heights of the three tether types, as estimated from the structures of the SNARE complex, Munc13 and Syt, defined the SV–PM distance ranges for tether formation. Geometric considerations linked SV–PM distances to the probability and rate of tether formation. We assumed that SV tethering constrains SV motility and that multiple tethers are associated by independent interactions. The model predicted that forming multiple tethers favours shorter SV–PM distances. Although tethers acted independently in the model, their geometrical properties often caused their sequential assembly, from longer ones (Munc13/Syt), which accelerated SV movement towards the PM, to shorter ones (SNAREs), which stabilized PM‐proximal SVs. Modifying tether lengths or numbers affected SV trafficking. The independent implementation of tethering proteins enabled their selective removal to mimic gene knockout (KO) situations. This showed that simulated SV–PM distance distributions qualitatively aligned with published electron microscopy studies upon removal of SNARE and Syt tethers, whereas Munc13 KO data were best approximated when assuming additional disruption of SNARE tethers. Thus, although salient features of SV docking can be accounted for by independent tethering alone, our results suggest that functional tether interactions not yet featured in our model are crucial for biological function.
imageKey points
A mathematical model describing the role of synaptic protein tethers to localize transmitter‐containing vesicles is developed based on geometrical considerations and structural information of synaptotagmin, Munc13 and SNARE proteins.
Vesicle movement, along with tether association and dissociation, are modelled as stochastic processes, with tethers functioning independently of each other.
Multiple tethers cooperate to recruit vesicles to the plasma membrane and keep them there: Munc13 and Syt as the longer tethers accelerate the movement towards the membrane, whereas short SNARE tethers stabilize them there.
Model predictions for situations in which individual tethers are removed agree with the results from experimental studies upon gene knockout.
Changing tether length or copy numbers affects vesicle trafficking and steady‐state distributions.