bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge, Attitudes, and Practices Regarding Urinary Tract Infections Among Women in the United Arab Emirates
Authors: Alhaj Shaikha Salah , Allami Sajad , Mohamadiyeh Amjad , Agha Ammar , Ali Abdul Kareem Abu , Habbal Joudi M Bassam , Saeed Balsam Qubais 
Published: February 2024

AbstractBackgroundUrinary tract infections (UTIs), which are infections of the kidneys, ureters, bladder, or urethra, are a worldwide public health concern. As compared to men, women are more prone to UTIs. There have been several studies that explore the knowledge, attitudes, and practices of women regarding UTIs in different countries, but no such study has been conducted in the UAE; therefore, we conducted this study in the UAE setting.MethodsThis study was conducted using an online survey created on Microsoft Forms. The minimum sample size required for our study was 385. This study was conducted after obtaining ethical approval from the Research Ethics Committee at the University of Sharjah (Reference Number: REC-23-09-19-01-F). A personally designed questionnaire consisting of 21 items, derived from previous research was used to record data. The data was analyzed using SPSS.ResultsA total of 475 females were included in the study. Most respondents were aged 18-30 years (47.4%). Our study found that a majority of the participants (69.7%) correctly identified bacteria as the most common cause of UTIs. With regards to practices undertaken during UTIs, among the participants with a history of UTI episodes, 32.6% waited 24-48 hours before seeking medical attention at a hospital or clinic, while 10% did not visit a hospital at all. Distinct trends were found when comparing demographic factors with knowledge levels. Most notably, the age group of 18-30 years showed the highest percentage of high-knowledge individuals (49%) compared to other age groups (p < 0.05). Education level was significantly (p = 0.003) associated with UTI knowledge. Going to the hospital/clinic was reported by 41% with high knowledge but only by 20% of those with poor knowledge. Moreover, a higher proportion of individuals with high knowledge sought medical attention immediately within 24 hours (47%).ConclusionMost of the participants possessed adequate knowledge regarding UTIs. Higher knowledge levels were associated with more proactive & appropriate health behaviors, such as seeking medical attention promptly & drinking more water.
Early altered directionality of resting brain network state transitions in the TgF344-AD rat model of Alzheimer’s disease
Authors: De Waegenaere Sam , van den Berg Monica , Keliris Georgios A. , Adhikari Mohit H. , Verhoye Marleen 
Published: February 2024

AbstractAlzheimer’s disease (AD) is a progressive neurodegenerative disease resulting in memory loss and cognitive decline. Synaptic dysfunction is an early hallmark of the disease whose effects on whole-brain functional architecture can be identified using resting-state functional MRI (rsfMRI). Insights into mechanisms of early, whole-brain network alterations can help our understanding of the functional impact of AD’s pathophysiology. Here, we obtained rsfMRI data in the TgF344-AD rat model at the pre- and early-plaque stages. This model recapitulates the major pathological and behavioural hallmarks of AD. We used co-activation pattern (CAP) analysis to investigate if and how the dynamic organization of intrinsic brain functional networks states, undetectable by earlier methods, is altered at these early stages. We identified and characterized six intrinsic brain states as CAPs, their spatial and temporal features, and the transitions between the different states. At the pre-plaque stage, the TgF344-AD rats showed reduced co-activation of hub regions in the CAPs corresponding to the default mode-like and lateral cortical network. Default mode-like network activity segregated into two distinct brain states, with one state characterised by high co-activation of the basal forebrain. This basal forebrain co-activation was reduced in TgF344-AD animals mainly at the pre-plaque stage. Brain state transition probabilities were altered at the pre-plaque stage between states involving the default mode-like network, lateral cortical network, and basal forebrain regions. Additionally, while the directionality preference in the network-state transitions observed in the wild-type animals at the pre-plaque stage had diminished at the early-plaque stage, TgF344-AD animals continued to show directionality preference at both stages. Our study enhances the understanding of intrinsic brain state dynamics and how they are impacted at the early stages of AD, providing a nuanced characterization of the early, functional impact of the disease’s neurodegenerative process.
Crebinostat Facilitates Memory Formation
Authors: Dama Deepti , Sharma Shiv K 
Published: February 2024

AbstractObjectivesProtein modifications importantly contribute to memory formation. Protein acetylation is a posttranslational modification of proteins that regulates memory formation. Acetylation level is determined by the relative activities of acetylases and deacetylases. Crebinostat is a histone deacetylase inhibitor. In this study, our aim was to examine whether Crebinostat affects memory formation in object recognition task. Further, we aimed to understand regulation of plasticity-related proteins by Crebinostat.MethodsObject recognition task was used to examine the effect of Crebinostat on memory formation. The effect of Crebinostat on plasticity-related proteins was examined using Western blot experiments.ResultsWe show that Crebinostat facilitates memory formation by a weak training in object recognition task. Further, this compound enhances acetylation of α-tubulin, and reduces the level of histone deacetylase 6, an α-tubulin deacetylase.ConclusionsThe results suggest that enhanced acetylation of α-tubulin by Crebinostat contributes to its facilitatory effect on memory formation.AbstractProtein modifications importantly contribute to memory formation. Protein acetylation is a posttranslational modification of proteins that regulates memory formation. Acetylation level is determined by the relative activities of acetylases and deacetylases. Crebinostat is a histone deacetylase inhibitor. Here we show that in object recognition task, Crebinostat facilitates memory formation by a weak training. Further, this compound enhances acetylation of α-tubulin, and reduces the level of histone deacetylase 6, an α-tubulin deacetylase. The results suggest that enhanced acetylation of α-tubulin by Crebinostat contributes to its facilitatory effect on memory formation.
The MYCN oncoprotein and helicases DDX17 and DDX5 have opposite effects on the production of chimeric transcripts in neuroblastoma cells
Authors: Clerc Valentine , Valat Jessica , Grand Xavier , Fontrodona Nicolas , Bazire Matéo , Rama Nicolas , Auboeuf Didier , Gibert Benjamin , Mortreux Franck , Bourgeois Cyril F. 
Published: February 2024

AbstractDEAD box helicases DDX17 and DDX5 control the termination of transcription and the associated cleavage of the 3’ end of transcripts. Here we show that the transcriptional readthrough induced by their depletion in neuroblastoma cells also results in increased production of chimeric transcripts from tandemly oriented genes. Analysis of neuroblastoma tumours in which chimeric transcripts are abundant revealed that low expression of the DDX17 and DDX5 genes is associated with poor overall patient survival. Low DDX17 expression is also significantly associated with high-risk tumours and is inversely correlated with MYCN oncogene amplification, suggesting a link between these two factors. We demonstrate that changes in MYCN expression do not affect the expression of either helicase, but alter transcription termination leading to the production of chimeric transcripts. We provide evidence that MYCN acts on termination through its direct binding to the 3’ region of genes and that it interacts with DDX17, suggesting that it may inhibit the activity of the helicase. Collectively, our work reveals a novel function of MYCN in transcription termination and suggests that the deregulation of MYCN and DDX17/DDX5 expression in neuroblastoma may lead to the expression of non-canonical and potentially harmful RNA molecules.
Multimodal brain age prediction using machine learning: combining structural MRI and 5-HT2AR PET derived features
Authors: Dörfel Ruben P. , Arenas-Gomez Joan M. , Svarer Claus , Ganz Melanie , Knudsen Gitte M. , Svensson Jonas E. , Plavén-Sigray Pontus 
Published: February 2024

AbstractTo better assess the pathology of neurodegenerative disorders and the efficacy of neuroprotective interventions, it is necessary to develop biomarkers that can accurately capture age-related biological changes in the human brain. Brain serotonin 2A receptors (5-HT2AR) show a particularly profound age-related decline and are also reduced in neurodegenerative disorders, such as Alzheimer’s disease.This study investigates whether the decline in 5-HT2AR binding, measured in vivo using positron emission tomography (PET), can be used as a biomarker for brain aging. Specifically, we aim to 1) predict brain age using 5-HT2AR binding outcomes, 2) compare 5-HT2AR-based predictions of brain age to predictions based on gray matter (GM) volume, as determined with structural magnetic resonance imaging (MRI), and 3) investigate whether combining 5-HT2AR and GM volume data improves prediction.We used PET and MR images from 209 healthy individuals aged between 18 and 85 years (mean=38, std=18), and estimated 5-HT2AR binding and GM volume for 14 cortical and subcortical regions. Different machine learning algorithms were applied to predict chronological age based on 5-HT2AR binding, GM volume, and the combined measures. The mean absolute error (MAE) and a cross-validation approach were used for evaluation and model comparison.We find that both the cerebral 5-HT2AR binding (mean MAE=6.63 years, std=0.74 years) and GM volume (mean MAE=6.95 years, std=0.83 years) predict chronological age accurately. Combining the two measures improves the prediction further (mean MAE=5.54 years, std=0.68). In conclusion, 5-HT2AR binding measured using PET might be useful for improving the quantification of a biomarker for brain aging.
Dysregulation of Neuropilin-2 Expression in Inhibitory Neurons Impairs Hippocampal Circuit Development and Enhances Risk for Autism-Related Behaviors and Seizures
Authors: Subramanian Deepak , Eisenberg Carol , Huang Andrew , Baek Jiyeon , Naveed Haniya , Komatireddy Samiksha , Shiflett Michael W. , Tran Tracy S. , Santhakumar Vijayalakshmi 
Published: February 2024

AbstractDysregulation of development, migration, and function of interneurons, collectively termed interneuronopathies, have been proposed as a shared mechanism for autism spectrum disorders (ASDs) and childhood epilepsy. Neuropilin-2 (Nrp2), a candidate ASD gene, is a critical regulator of interneuron migration from the median ganglionic eminence (MGE) to the pallium, including the hippocampus. While clinical studies have identified Nrp2 polymorphisms in patients with ASD, whether selective dysregulation of Nrp2-dependent interneuron migration contributes to pathogenesis of ASD and enhances the risk for seizures has not been evaluated. We tested the hypothesis that the lack of Nrp2 in MGE-derived interneuron precursors disrupts the excitation/inhibition balance in hippocampal circuits, thus predisposing the network to seizures and behavioral patterns associated with ASD. Embryonic deletion of Nrp2 during the developmental period for migration of MGE derived interneuron precursors (iCKO) significantly reduced parvalbumin, neuropeptide Y, and somatostatin positive neurons in the hippocampal CA1. Consequently, when compared to controls, the frequency of inhibitory synaptic currents in CA1 pyramidal cells was reduced while frequency of excitatory synaptic currents was increased in iCKO mice. Although passive and active membrane properties of CA1 pyramidal cells were unchanged, iCKO mice showed enhanced susceptibility to chemically evoked seizures. Moreover, iCKO mice exhibited selective behavioral deficits in both preference for social novelty and goal-directed learning, which are consistent with ASD-like phenotype. Together, our findings show that disruption of developmental Nrp2 regulation of interneuron circuit establishment, produces ASD-like behaviors and enhanced risk for epilepsy. These results support the developmental interneuronopathy hypothesis of ASD epilepsy comorbidity.
Biochemical fractionation of human α-Synuclein in aDrosophilamodel of synucleinopathies
Authors: Imomnazarov Khondamir , Lopez-Scarim Joshua , Bagheri Ila , Joers Valerie , Tansey Malú Gámez , Martín-Peña Alfonso 
Published: February 2024

ABSTRACTSynucleinopathies are a group of central nervous system pathologies that are characterized by neuronal accumulation of misfolded and aggregated α-synuclein in proteinaceous depositions known as Lewy Bodies (LBs). The transition of α-synuclein from its physiological to pathological form has been associated with several post-translational modifications such as phosphorylation and an increasing degree of insolubility, which also correlate with disease progression in post-mortem specimens from human patients. Neuronal expression of α-synuclein in model organisms, includingDrosophila melanogaster,has been a typical approach employed to study its physiological effects. Biochemical analysis of α-synuclein solubility via high-speed ultracentrifugation with buffers of increasing detergent strength offers a potent method for identification of α-synuclein biochemical properties and the associated pathology stage. Unfortunately, the development of a robust and reproducible method for evaluation of human α-synuclein solubility isolated fromDrosophilatissues has remained elusive. Here, we tested different detergents for their ability to solubilize human α-synuclein carrying the pathological mutation A53T from brains of aged flies. We also assessed the effect of sonication on solubility of human α-synuclein and optimized a protocol to discriminate relative amounts of soluble/insoluble human α-synuclein from dopaminergic neurons of theDrosophilabrain. Our data established that, using a 5% SDS buffer, the 3-step protocol distinguishes between cytosolic soluble proteins in fraction 1, detergent-soluble proteins in fraction 2 and insoluble proteins in fraction 3. This protocol shows that sonication breaks down α-synuclein insoluble complexes from the fly brain, making them soluble in the SDS buffer and enriching fraction 2 of the protocol.
Dynamic phospho-proteogenomic analysis of gastric cancer cells suggests host immunity provides survival benefit
Authors: Kume Kohei , Iida Midori , Iwaya Takeshi , Yashima-Abo Akiko , Koizumi Yuka , Konta Akari , Wade Kaitlin , Hiraki Hayato , Calvert Valerie , Wulfkuhle Julia , Espina Virginia , Siwak Doris R. , Lu Yiling , Takemoto Kazuhiro , Suzuki Yutaka , Sasaki Yasushi , Tokino Takashi , Petricoin Emanuel , Liotta Lance A. , Mills Gordon B. , Nishizuka Satoshi S. 
Published: February 2024

AbstractThe mainstay of advanced gastric cancer (GC) therapy is DNA-damaging drugs. Using proteogenomic analysis of a panel of eight GC cell lines, we identified genetic alterations and signaling pathways, potentially associated with resistance to DNA-damaging drugs. Notably, 5-fluorouracil (5FU) resistance was associated with PD-L1 expression, but not established GC subtypes. In publicly available cohort data, PD-L1 expression was associated with a reduced risk of GC progression. In addition to PD-L1, expression of inflammatory genes induced by lymphocyte cytokines was consistently associated with prolonged survival in GC. In our validation cohort, total lymphocyte count (TLC) predicted a better relapse-free survival rate in GC patients with 5FU-based adjuvant chemotherapy than those with surgery alone. Moreover, TLC+patients who had no survival benefit from adjuvant chemotherapy were discriminated by IκBα expression. Collectively, our results suggest that 5FU resistance observed in cell lines may be overcome by host immunity or by combination therapy with immune checkpoint blockade.
Osirisgene family defines the cuticle nano-patterns ofDrosophila
Authors: Sun Zhengkuan , Inagaki Sachi , Miyoshi Keita , Saito Kuniaki , Hayashi Shigeo 
Published: February 2024

AbstractNanostructures of pores and protrusions in the insect cuticle modify molecular permeability and surface wetting and help insects sense a variety of environmental cues. The cellular mechanism specifying cuticle nanostructures is poorly understood. Here, we show that insect-specificOsirisfamily genes are expressed in various cuticle-secreting cells in theDrosophilahead in the early stage of cuticle secretion and collectively cover nearly the entire surface of the head epidermis. We show that each sense organ cell with various cuticular nanostructures expresses a unique combination ofOsirisgenes.Osirisgene mutations caused various cuticle defects in the corneal nipples of the eye and pores of the chemosensory sensilla.Osirisgenes provide an entry point for investigating cuticle nanopatterning in insects.
Local muscle pressure stimulates the principal receptors for proprioception
Authors: Torell Frida , Dimitriou Michael 
Published: February 2024

SUMMARYProprioception plays a crucial role in motor coordination and self-perception. Muscle spindles are the principal receptors for proprioception. They are believed to encode muscle stretch and signal limb position and velocity. Here, we applied percutaneous pressure to a small area of extensor muscles at the forearm while recording spindle afferent responses, skeletal muscle activity and hand kinematics. Three levels of sustained pressure were applied on the spindle-bearing muscle when the hand was relaxed and immobile (‘isometric’ condition) and when the participant’s hand moved rhythmically at the wrist. As hypothesized to occur due to compression of the spindle capsule, we show that muscle pressure is an ‘adequate’ stimulus for human spindles in isometric conditions, and that pressure enhances spindle responses during stretch. Interestingly, release of sustained pressure in isometric conditions lowered spindle firing below baseline rates. Our findings urge a re-evaluation of muscle proprioception in sensorimotor function and various neuromuscular pathologies.HIGHLIGHTSLocal muscle pressure is an adequate stimulus for spindles in isometric conditionsRelease of pressure in isometric conditions lowers spindle firing below baseline ratesLocal muscle pressure enhances spindle afferent responses during muscle stretch
Gut microbial-mediated polyphenol metabolism is restrained by parasitic whipworm infection and associated with altered immune function in mice
Authors: Andersen-Civil Audrey Inge Schytz , Arora Pankaj , Zhu Ling , Myhill Laura J. , Gökgöz Nilay Büdeyri , Castro-Mejia Josue L. , Leppä Milla M. , Hansen Lars H. , Lessard-Lord Jacob , Salminen Juha-Pekka , Thamsborg Stig M. , Nielsen Dennis Sandris , Desjardins Yves , Williams Andrew R. 
Published: February 2024

AbstractPolyphenols are phytochemicals commonly found in plant-based diets which have demonstrated immunomodulatory and anti-inflammatory properties. However, the interplay between polyphenols and pathogens at mucosal barrier surfaces has not yet been elucidated in detail. Here, we show that proanthocyanidin (PAC) polyphenols interact with gut parasites to influence immune function and gut microbial-derived metabolites in mice. PAC intake inhibited mastocytosis during infection with the small intestinal roundwormHeligmosomoides polygyrus, and induced a type-1, interferon-driven mucosal immune response during infection with the large intestinal whipwormTrichuris muris.PAC also induced alterations in mesenteric lymph node T-cell populations that were dependent on infection model, with a Th2/Treg bias duringH. polygyrusinfection, and a Th1 bias duringT. murisinfection. In the absence of infection, PAC intake promoted the expansion ofTuricibactersp. within the gut microbiota, increased faecal short chain fatty acids, and enriched phenolic metabolites such as phenyl-γ-valerolactones in the caecum. However, these putatively beneficial effects were reduced in PAC-fed mice infected withT. muris,suggesting concomitant parasite infection can attenuate gut microbial-mediated PAC catabolism. Collectively, our results suggest an inter-relationship between a phytonutrient and infection, whereby PAC may augment parasite-induced inflammation (most prominently with the caecum dwellingT. muris), and infection may abrogate the beneficial effects of health-promoting phytochemicals.
DrosophilaHCN mediates gustatory homeostasis by preserving sensillar transepithelial potential in sweet environments
Authors: Lee MinHyuk , Park Se Hoon , Joo Kyeung Min , Kwon Jae Young , Lee Kyung-Hoon , Kang KyeongJin 
Published: February 2024

AbstractEstablishing transepithelial ion disparities is crucial for sensory functions in animals. In insect sensory organs called sensilla, a transepithelial potential, known as the sensillum potential (SP), arises through active ion transport across accessory cells, sensitizing receptor neurons such as mechanoreceptors and chemoreceptors. Because multiple receptor neurons are often co-housed in a sensillum and share SP, niche-prevalent overstimulation of single sensory neurons can compromise neighboring receptors by depleting SP. However, how such potential depletion is prevented to maintain sensory homeostasis remains unknown. Here, we find that theIh-encoded hyperpolarization-activated cyclic nucleotide gated (HCN) channel bolsters the activity of bitter-sensing gustatory receptor neurons (bGRNs), albeit acting in sweet-sensing GRNs (sGRNs). For this task, HCN maintains SP despite prolonged sGRN stimulation induced by the diet mimicking their sweet feeding niche, such as overripe fruit. We present evidence thatIh-dependent demarcation of sGRN excitability is implemented to throttle SP consumption, which may have facilitated adaptation to a sweetness-dominated environment. Thus, HCN expressed in sGRNs serves as a key component of a simple yet versatile peripheral coding that regulates bitterness for optimal food intake in two contrasting ways: sweet-resilient preservation of bitter aversion and the previously reported sweet-dependent suppression of bitter taste.
Distinct Effects of Aducanumab and Lecanemab on Intraneuronal Endogenous Aβ42 and Phosphorylated Tau in Alzheimer’s Disease Treatment
Authors: Liu Ming-Jie , Long Zhu , Li Fuyun , Shi Xiaobang , Shen Yan-Fei , Liu Meng-Lu 
Published: February 2024

AbstractIn the treatment of Alzheimer’s Disease (AD), two FDA-approved monoclonal antibodies, Aducanumab (Adu) and Lecanemab (LCN), exhibit significant differences in clinical benefits. By utilizing human-induced basal forebrain cholinergic neurons (BFCNs) derived from AD patient skin fibroblasts, we successfully recapitulated the natural endogenous neuropathologies of Aβ42 and Tau within just 21 days and revealed distinct intraneuronal effects of Adu and LCN. Both antibodies are internalized into BFCNs and localize with cytosolic Aβ42. However, LCN, selectively targeting Aβ42 oligomers and protofibrils, triggers TRIM21 pathway and significantly enhances autolysosome- and proteasome-mediated Aβ42 clearance, thereby leading to a marked reduction in phosphorylated Tau181 (pTau181) pathology. In contrast, the fibrillized Aβ42-selective Adu shows considerably weaker effects. This study not only reveals the unique intraneuronal actions of Adu and LCN but also provides a reliable and accessible human neuronal model for evaluating potential AD therapeutics, emphasizing the importance of intraneuronal pathology in the treatment of AD.