bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fasting C-peptide in Gestational Diabetes Mellitus
Authors: Hasan Md. Rakibul , Sultana Nusrat , Hasan Mashfiqul , Jahan Sharmin , Hasanat Muhammad Abul 
Published: August 2024

IntroductionInsulin secretion and sensitivity are thought to vary in gestational diabetes mellitus (GDM) as well as in different trimesters within the same individual.ObjectivesTo see the fasting serum C-peptide in subjects with GDM as an indicator of basal insulin secretion and to compare it to the normal glucose tolerance (NGT) control.MethodThis case-control study investigated and compared fasting serum C-peptide in 35 GDM subjects with 37, age, BMI, and trimester-matched control. GDM was diagnosed by WHO 2013 criteria. Plasma glucose was measured by the glucose oxidase method and C-peptide by a chemiluminescent immunometric assay.ResultFasting serum C-peptides were significantly higher in the GDM group than that of the NGT (NGT vs. GDM: 1.45±0.76 vs. 1.99±1.28, mean±SD, p=0.032), but no difference was observed between GDM and NGT with a BMI <25kg/m2(NGT vs. GDM: 1.25±0.44 vs. 1.37±0.77, mean±SD, p=0.597). Within the NGT group, fasting C-peptide was similar with a BMI cut-off 25kg/m2(<25 vs. ≥ 25: 1.25±0.44 vs. 1.61±0.94, p=0.159); however, within the GDM group, the fasting C-peptide was significantly higher with a BMI ≥25 kg/m2(<25 vs. ≥ 25: 1.37±0.77 vs. 2.45±1.41, mean ±SD, p=0.011). We did not observe any trimester-specific difference in fasting C-peptide between the NGT and the GDM (NGT vs. GDM: 1.55±0.45 vs. 1.67±0.57, p=0.736; 1.43±0.95 vs. 2.13±1.10, p=0.085; 1.43±0.71 vs. 1.97±1.60, p= 0.204; ng/dl, mean ± SD, for 1st, 2nd, and 3rdtrimester, respectively). Pearson correlation revealed BMI (r=0.389, p=0.001), Systolic BP (r=0.531, p<0.001), Diastolic BP (r=0.355, p=0.002), FPG (r=0.32, p=0.006) and 1hr PG on OGTT (r=0.423, p<0.001) had significant positive correlation with fasting C-peptide.ConclusionFasting C-peptide increased significantly in GDM with BMI ≥25kg/m2, but not with <25kg/m2
Gait Adaptations to Walking Speeds in Individuals with Myotonic Dystrophy Type 1
Authors: Hoerter Barthélémy , Ballaz Laurent , Cherni Yosra 
Published: August 2024

AbstractBackgroundMyotonic dystrophy type 1 (DM1) is a prevalent inherited muscular dystrophy in adults, affecting distal muscles such as the gastrocnemius, soleus, and tibialis anterior. This leads to significant gait deviations and reduced walking speed, impacting overall well-being and increasing fall risk.ObjectiveThis study aimed to assess how walking speed affects gait kinematics in individuals with DM1.MethodEighteen individuals with genetically confirmed DM1 (4 women, age: 41.0 [35.5; 47.8] years, mass: 76.8 [67.1; 94.6] kg, height: 166.0 [156.7; 173.3] cm) participated in this study. Each participant walked barefoot along a 13-meter walkway at comfortable and fast speeds. Subsequently, spatiotemporal parameters and joint kinematics were assessed.ResultsThe step length (p < 0.001), cycle speed (p < 0.001), and cadence (p < 0.001) increased significantly, leading to a higher walking speed. Moreover, the vertical amplitude of the center of mass (CoM) increased significantly (p = 0.015), while the mediolateral amplitude decreased (p = 0.001) at fast walking condition. In addition, significant kinematic changes included increased trunk tilt (p < 0.001), greater anterior pelvic tilt (p < 0.001), increased hip flexion at initial contact, and enhanced knee flexion during both stance and swing phases. Ankle dorsiflexion showed a trend towards increase during stance phase (p = 0.055) at fast walking condition.ConclusionsFast walking speed in individuals with DM1 lead to significant gait adaptations. These adaptations reflect compensatory mechanisms to manage muscle weakness. The present study revealed significant changes in spatiotemporal parameters related to walking speed. Fast walking also highlighted kinematic adaptations in trunk, pelvis and lower limb joints. These findings enhance our understanding of gait deviation in individuals with DM1 and suggest the potential benefits of targeted fast walking training in this population.
A 10 Years Update of Effects of Exercise on Depression Disorders – in otherwise healthy adults: A Systematic Review of Meta-Analyses and Neurobiological Mechanisms
Authors: Budde Henning , Dolz Nina , Mueller-Alcazar Anett , Velasques Bruna , Ribeiro Pedro , Machado Sergio , Wegner Mirko 
Published: August 2024

AbstractBackgroundDepression is one of the most common mental illnesses worldwide and is a major burden for those affected. As conventional therapies do not always work and are also associated with side effects, alternative treatment methods are urgently indicated. In the past, exercise has established itself as a seemingly good alternative treatment method. The aim of this work is to provide a state of the art review and to check whether there are new findings since the publication of the article by Wegner et al. [1].MethodsA systematic literature search was conducted in which relevant literature was searched in databases such as PsycINFO, PsychARTICLES, PubMed, CI-NAHL Complete, SocINDEX, SPORTDiscus and Psyndex. The effect sizes were calculated and the methodological quality was assessed using the AMSTAR-2 criteria. Finally, the neurobiological explanations for the effect of exercise on depression are discussed.ResultsEleven meta-analyses met the inclusion criteria, with the total sample consisting of 16.255 participants and 229 individual studies. The most frequently implemented intervention was aerobic exercise, while the intervention in the control groups was usually no treatment, waiting list, or attention/activity placebo. The pooled results indicate a moderate clinical effect, suggesting the positive effect of exercise and physical activity in reducing depressive symptoms (SMD = -0.61, 95% CI [− 0.78; -0.43],p= <0.01).ConlcusionThe consistently positive, moderate effects observed in the present study make exercise and physical activity a promising and supportive alternative for adults with depression. The positive effect of exercise and physical activity could potentially be explained by neurological changes. However, the exact mechanisms underlying the antidepressant effects are still unclear.
Monkeypox in Europe: Epidemiology and Risk Factors – A Scoping Review Study
Authors: Ravichandran Nandakumar , Jalili Parnian 
Published: August 2024

AbstractBackgroundMonkeypox (mpox) is a zoonotic disease originating from the Congo Basin (Clade I) and West Africa (Clade II). In 2022, mpox spread to non-endemic European countries, predominantly through human transmission associated with sexual contact. The outbreak in Europe was primarily with the Clade IIb lineage, which is less virulent. The World Health Organization (WHO) declared this outbreak a Public Health Emergency of International Concern (PHEIC) in 2022, which ended in May 2023 after a decline in cases. However, in July 2024, a resurgence of the more virulent Clade I occurred in the Democratic Republic of Congo (DRC), leading WHO to declare mpox a PHEIC again, due to the risk of global spread. Understanding epidemiology and risk factors of mpox is vital for effective public health measures.Methodology and principal findingsA search conducted from 2014 to 2024 across PubMed, Scopus and Embase identified 38 studies on mpox in Europe, which were included for qualitative analysis. The key themes identified were epidemiology and risk factors/ behaviors. High-risk behaviors include sexual contact among men who have sex with men (MSM) with multiple partners, living with HIV, and frequent travel to endemic regions.Conclusions and significanceWith no definitive cure for mpox, public health measures such as surveillance, monitoring, and contact tracing are essential. Additionally, encouraging case-control studies is crucial for exploring other potential risk behaviors and design behavioral interventions, vaccination campaigns and awareness programs aimed at reducing high-risk behaviors among these populations. Although the number of cases in Europe did not surge in August 2024, proactive measures are necessary to prevent further spread.
Synaptic connectome of a neurosecretory network in theDrosophilabrain
Authors: McKim Theresa H. , Gera Jayati , Gayban Ariana J. , Reinhard Nils , Manoli Giulia , Hilpert Selina , Helfrich-Förster Charlotte , Zandawala Meet 
Published: August 2024

AbstractHormones mediate inter-organ signaling which is crucial in orchestrating diverse behaviors and physiological processes including sleep and activity, feeding, growth, metabolism and reproduction. The pars intercerebralis and pars lateralis in insects represent major hubs which contain neurosecretory cells (NSC) that produce various hormones. To obtain insight into how hormonal signaling is regulated, we have characterized the synaptic connectome of NSC in the adultDrosophilabrain. Identification of neurons providing inputs to multiple NSC subtypes implicates diuretic hormone 44-expressing NSC as a major coordinator of physiology and behavior. Surprisingly, despite most NSC having dendrites in the subesophageal zone (primary taste processing center), gustatory inputs to NSC are largely indirect. We also deciphered pathways via which diverse olfactory inputs are relayed to NSC. Further, our analyses revealed substantial inputs from descending neurons to NSC, suggesting that descending neurons regulate both endocrine and motor output to synchronize physiological changes with appropriate behaviors. In contrast to NSC inputs, synaptic output from NSC is sparse and mostly mediated by corazonin NSC. Therefore, we additionally determine putative paracrine interconnectivity between NSC subtypes and hormonal pathways from NSC to peripheral tissues by analyzing single-cell transcriptomic datasets. Our comprehensive characterization of theDrosophilaneurosecretory network connectome provides a platform to understand complex hormonal networks and how they orchestrate animal behaviors and physiology.
Behavioral pharmacology of mescaline - the role of serotonin 5-HT2A, 5-HT2B, 5-HT2C and 5-HT1A receptors
Authors: Olejníková-Ladislavová Lucie , Fujáková-Lipski Michaela , Šíchová Klára , Danda Hynek , Syrová Kateřina , Horáček Jiří , Páleníček Tomáš 
Published: August 2024

ABSTRACTRationaleMescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is not fully understood.ObjectivesIn this study, we aimed to investigate how selective antagonists of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors affect the behavioral changes induced by subcutaneous administration of mescaline (at doses of 10, 20, and 100 mg/kg) in rats.MethodsWe used adult male Wistar rats in all our experiments. We evaluated locomotor activity using the open field test, and assessed sensorimotor gating deficits by measuring prepulse inhibition (PPI) of acoustic startle reaction (ASR).ResultsWhile the highest dose of mescaline induced hyperlocomotion, which almost all the other antagonists reversed, the PPI deficits were selectively normalized by the 5-HT2A antagonist. The 5-HT2C antagonist partially reversed the small decrease in locomotor activity induced by lower doses of mescaline.ConclusionOur findings suggest that mescaline-induced changes in behavior are primarily mediated by the 5-HT2A receptor subtype, with less pronounced contributions from the 5-HT2C receptor. The other antagonists had limited effects.
CDKL5’s role in microtubule-based transport and cognitive function
Authors: Lopes André T. , Janiv Ondine , Claxton Suzanne , Ultanir Sila K. 
Published: August 2024

AbstractCyclin-dependent kinase like 5 (CDKL5) is a serine-threonine kinase highly enriched in mammalian neurons. CDKL5 is located on the X-chromosome and its loss-of-function leads to a severe neurodevelopmental disorder called CDKL5 deficiency disorder (CDD). CDKL5 phosphorylates microtubule-associated protein MAP1S and regulates its binding to microtubules. How MAP1S phosphorylation affects microtubule function is not well understood. To address this question, we generated MAP1S phosphomutant mice, in which the CDKL5 phosphorylation sites S786 and S812 are mutated to Alanine (MAP1S S786/812A or MAP1S SA). Using a microtubule co-sedimentation assay, we showed that dynein binding to microtubules is severely reduced in CDKL5 knockout (KO) and MAP1S SA brains. Time-lapse imaging in primary neurons showed impaired dynein motility in both Cdkl5 KO and MAP1S SA. Dynein-driven cargo transport was affected in mutant neuron dendrites, including the delivery of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. We next studied tubulin tyrosination in Cdkl5 KO and MAP1S SA neurons and found that both mutants had a reduced tubulin tyrosination when compared to WT neurons. Since dynein-dynactin has a higher affinity for tyrosinated microtubules, we hypothesized that reduced tyrosination in MAP1S phosphomutant mice could be the mechanistic cause of impaired dynein motility. In support of this, we show that upon expression of tubulin tyrosine kinase TTL, we rescued dynein motility defects in MAP1S phosphomutant neurons. Hippocampal neurons derived from MAP1S SA mice revealed a significant reduction in spine density and synapses, and altered spine morphology. Finally, behavioral phenotyping of MAP1S phosphomutant mice showed increased anxiety, impaired motor performance, social and memory deficits, mirroring to some extent the clinical manifestations present in CDD patients. Our results reveal MAP1S phosphorylation to be an important contributor to dynein-mediated transport and synapse formation.Graphical abstract
Is this scenery worth exploring? Insight into the visual encoding of navigating ants
Authors: Clement Leo , Schwarz Sebastian , Mahot-Castaing Blandine , Wystrach Antoine 
Published: August 2024

AbstractSolitary foraging insects like desert ants rely heavily on vision for navigation. While ants can learn visual scenes, it is unclear what cues they use to decide if a scene is worth exploring at the first place. To investigate this, we recorded the motor behavior ofCataglyphis veloxants navigating in a virtual reality set-up and measured their lateral oscillations in response to various unfamiliar visual scenes under both closed-loop and open-loop conditions. In naturalistic-looking panorama, ants display regular oscillations as observed outdoors, allowing them to efficiently scan the scenery. Manipulations of the virtual environment revealed distinct functions served by dynamic and static cues. Dynamic cues, mainly rotational optic flow, regulated the amplitude of oscillations but not their regularity. Conversely, static cues had little impact on the amplitude but were essential for producing regular oscillations. Regularity of oscillations decreased in scenes with only horizontal, only vertical or no edges but was restored in scenes with both edge types together. The actual number of edges, the visual pattern heterogeneity across azimuths, the light intensity or the relative elevation of brighter regions did not affect oscillations. We conclude that ants use a simple but functional heuristic to determine if the visual world is worth exploring, relying on the presence of at least two different edge orientations in the scene.Summary statementUsing a virtual reality setup, we reveal that ants rely on a heuristic to trigger visual exploration in an unfamiliar scene. The simultaneous presence of vertical and horizontal edges is necessary and sufficient for the ants to produce lateral oscillations and scan the scene.
Columnar cholinergic neurotransmission onto T5 cells ofDrosophila
Authors: Samara Eleni , Schilling Tabea , Ribeiro Inês M. A. , Haag Juergen , Leonte Maria-Bianca , Borst Alexander 
Published: August 2024

SummarySeveral nicotinic and muscarinic acetylcholine receptors (AChRs) are expressed in the brain ofDrosophila melanogaster. However, the contribution of different AChRs to visual information processing remains poorly understood. T5 cells are the primary motion-sensing neurons in the OFF pathway and receive input from four different columnar cholinergic neurons, Tm1, Tm2, Tm4 and Tm9. We reasoned that different AChRs in T5 postsynaptic sites might contribute to direction selectivity, a central feature of motion detection. We show that the nicotinic nAChRα1, nAChRα4, nAChRα5 and nAChRα7 subunits localize on T5 dendrites. By targeting synaptic markers specifically to each cholinergic input neuron, we find a prevalence of the nAChRα5 in Tm1-, Tm2- and Tm4-to-T5 synapses and of nAChRα7 in Tm9-to-T5 synapses. Knock-down of nAChRα4, nAChRα5, nAChRα7, or mAChR-B individually in T5 cells alters the optomotor response and reduces T5 directional selectivity. Our findings indicate a differential contribution of postsynaptic receptors to input visual processing and, thus, to the computation of motion direction in T5 cells.
Does slow oscillation-spindle coupling contribute to sleep-dependent memory consolidation? A Bayesian meta-analysis
Authors: Ng Thea , Noh Eunsol , Spencer Rebecca M. C. 
Published: August 2024

AbstractThe active system consolidation theory suggests that information transfer between the hippocampus and cortex during sleep underlies memory consolidation. Neural oscillations during sleep, including the temporal coupling between slow oscillations (SO) and sleep spindles (SP), may play a mechanistic role in memory consolidation. However, differences in analytical approaches and the presence of physiological and behavioral moderators have led to inconsistent conclusions. This meta-analysis, comprising 23 studies and 297 effect sizes, focused on four standard phase-amplitude coupling measures including coupling phase, strength, percentage, and SP amplitude, and their relationship with memory retention. We developed a standardized approach to incorporate non-normal circular-linear correlations. We found strong evidence supporting that precise and strong SO-fast SP coupling in the frontal lobe predicts memory consolidation. The strength of this association is mediated by memory type, aging, and dynamic spatio-temporal features, including SP frequency and cortical topography. In conclusion, SO-SP coupling should be considered as a general physiological mechanism for memory consolidation.
In silicoExploration Natural Compounds for the Discovery of Novel DNMT3A Inhibitors as Potential Therapeutic Agents for Acute Myeloid Leukemia
Authors: Das Uddalak , Uttarkar Akshay , Kumar Jitendra , Niranjan Vidya 
Published: August 2024

ABSTRACTAberrant DNA methylation, a hallmark of acute myeloid leukemia (AML), is catalyzed by DNA methyltransferase 3A (DNMT3A). Approximately 20-30% of AML patients harbor DNMT3A mutations, leading to disrupted DNA methylation patterns and leukemogenesis. To identify potential therapeutic interventions, this study employed computational drug discovery. A pharmacophore model was constructed and utilized to screen a natural product database, yielding a set of promising compounds. Subsequent molecular docking, MM-GBSA calculations, and ADMET profiling identified two compounds, CNP0375130 and CNP0256178, as potential DNMT3A inhibitors. These compounds exhibited favorable binding affinities and demonstrated desirable drug-like properties. Molecular dynamics simulations confirmed stable protein-ligand interactions. These findings suggest that CNP0375130 and CNP0256178 may serve as promising lead compounds for the development of novel anti-leukemic therapies targeting DNMT3A, and contribute to the ongoing efforts to develop targeted therapies for leukemia.
Multi-camera Simultaneous Total Internal Reflection and Interference Reflection Microscopy
Authors: Spector Jeffrey O. , Chen Jiayi , Roll-Mecak Antonina 
Published: August 2024

AbstractInterference Reflection Microscopy (IRM) is an optical technique that relies on the interference between the reflected light from an incident beam as it passes through materials of different refractive indices. This technique has been successfully used to image microtubules, biologically important biofilaments with a diameter of 25 nm. However, it is often desirable to image both the microtubule and microtubule interacting proteins simultaneously. Here we present a simple modification to a standard multi-color total internal reflection fluorescence (TIRF) microscope that enables simultaneous high-speed IRM and single molecule TIRF imaging. Our design utilizes a camera for each channel (IRM and TIRF) allowing independent optimization of camera parameters for the two different modalities. We illustrate its application by imaging unlabeled microtubules and GFP-labeled end-binding protein EB1 which forms comets on the tips of polymerizing microtubules. Our design is easily implemented, and with minimal cost, making it accessible to any laboratory with an existing fluorescence microscope.
HLA-A*02:01allele is associated with decreased risk and a longer survival in pancreatic cancer: Results from an exhaustive analysis of theHLAvariation in PDAC
Authors: Langtry Alberto , Rabadan Raul , Alonso Lola , van Eijck Casper , Macarulla Teresa , Lawlor Rita T , Carrato Alfredo , Alvarez-Gallego Rafael , Iglesias Mar , Molero Xavier , Löhr J Matthias , Michalski Christopher W , Perea José , O’Rorke Michael , Barberà Víctor M , Tardón Adonina , Farré Antoni , Muñoz-Bellvís Luís , Crnogorac-Jurcevic Tatjana , Domínguez-Muñoz Enrique , Gress Thomas , Greenhalf William , Sharp Linda , Sabroso-Lasa Sergio , Filip Ioan , Strijk Gaby , Castet Florian , Balsells Joaquim , Costello Eithne , Kleeff Jörg , Kong Bo , Mora Josefina , O’Driscoll Damian , Scarpa Aldo , Ye Weimin , Real Francisco X. , Malats Núria , López de Maturana Evangelina 
Published: August 2024

ABSTRACTGenetic susceptibility loci are associated with PDAC risk and survival, but the impact of germline HLA region variation remains largely unexplored. This study examinedHLAI-II alleles within the PanGenEU study and validated our findings using external datasets (UK Biobank, TCGA, PAN-NGS trial, and Caris trial).HLA-A*02:01and HLA-B*49alleles were linked to a decreased risk of PDAC, whereasHLA-B*39,HLA-DPB1*04,andHLA-A*26:01were directly associated with increased risk. PDAC patients carrying theHLA-A*02:01allele also showed lower mortality rates, with the effect being more pronounced in those withKRASG12Vmutations, pointing to a host*tumor genetic interaction. This research highlightsHLA-A*02:01, found in 20% of Europeans, as a marker for reduced PDAC risk and mortality, especially inKRASG12Vmutated tumors. Results from this study could enhance personalized medicine for PDAC by identifying patients who may benefit from regular screenings through tailored risk assessments. Importantly, our findings are crucial for stratifying PDAC patients based on their genetic background and tumor mutational profile, which can guide treatment strategies.