bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Transcranial Direct Current and Magnetic Stimulation on Fear Extinction and Return of Fear: A meta-analysis and Systematic Review
Authors: Lei Grace L.T. , Lai Cora S.W. , Lee Tatia M.C. , Lam Charlene L.M. 
Published: September 2023

AbstractAnxiety and fear-related disorders are among the most prevalent mental illnesses. Non-invasive brain stimulation methods such as transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) have been employed to modulate anxiety and fear-related symptoms, but their therapeutic effects remain inconclusive. Pavlovian conditioning and extinction are experimental analogues of exposure therapy that investigate the neural mechanisms of fear extinction and return of fear. We conducted a meta-analysis and qualitative review on the effects of tDCS and TMS on fear extinction and return of fear in non-primate animals and humans. Results show that both anodal and cathodal tDCS over the prefrontal cortex inhibit short-term contextual and cued fear retrieval in animal models. In human studies, anodal tDCS over the medial/ventromedial prefrontal cortex enhances fear extinction, whereas TMS over the dorsolateral/ventromedial prefrontal cortex inhibits return of fear. Our findings suggest the optimal non-invasive brain stimulation protocols for threat extinction in humans.
ATP burst is the dominant driver of antibiotic lethality inMycobacterium smegmatis
Authors: Lodhiya Tejan , Palande Aseem , Veeram Anjali , Larrouy-Maumus Gerald , Beste Dany J V , Mukherjee Raju 
Published: September 2023

AbstractAntibiotic-tolerant bacteria, due to their unique physiology, are refractory to antimicrobial killing and pose challenges for infection control. Incomplete knowledge of how bactericidal antibiotics work, limits our understanding of partial resistance due to phenotypic tolerance in mycobacteria, a driver for developing genetic resistance. Using proteomics,13C isotopomer analysis, genetic and biochemical assays, we investigated the physiological response ofM. smegmatischallenged with aminoglycoside and fluoroquinolone antibiotics. Two distinct classes of antibiotics elicited remarkably similar responses and increased flux through the TCA cycle, causing enhanced respiration, ROS generation, and ATP burst. We observed that excessive ATP levels and not ROS, dominantly contributes to cidality, which may in part be, conferred by sequestration of divalent metal ions by ATP. Consequently,13C isotope tracing indicated TCA cycle flux deviation from its oxidative arm as a bacterial adaptive mechanism, which also included activated intrinsic resistance and a higher propensity to develop antibiotic resistance. Our study provides a new understanding of the intricate mechanisms of antibiotic-induced cell death and expands the current paradigm for antibiotic action.
Charting Aging Trajectories of Knee Cartilage Thickness for Early Osteoarthritis Risk Prediction: An MRI Study from the Osteoarthritis Initiative Cohort
Authors: Li Tengfei , Luo Tianyou , Chen Boqi , Huang Chao , Shen Zhengyang , Xu Zhenlin , Nissman Daniel , Golightly Yvonne M. , Nelson Amanda E. , Niethammer Marc , Zhu Hongtu 
Published: September 2023

AbstractKnee osteoarthritis (OA), a prevalent joint disease in the U.S., poses challenges in terms of predicting of its early progression. Although high-resolution knee magnetic resonance imaging (MRI) facilitates more precise OA diagnosis, the heterogeneous and multifactorial aspects of OA pathology remain significant obstacles for prognosis. MRI-based scoring systems, while standardizing OA assessment, are both time-consuming and labor-intensive. Current AI technologies facilitate knee OA risk scoring and progression prediction, but these often focus on the symptomatic phase of OA, bypassing initial-stage OA prediction. Moreover, their reliance on complex algorithms can hinder clinical interpretation. To this end, we make this effort to construct a computationally efficient, easily-interpretable, and state-of-the-art approach aiding in the radiographic OA (rOA) auto-classification and prediction of the incidence and progression, by contrasting an individual’s cartilage thickness with a similar demographic in the rOA-free cohort. To better visualize, we have developed the toolset for both prediction and local visualization. A movie demonstrating different subtypes of dynamic changes in local centile scores during rOA progression is available athttps://tli3.github.io/KneeOA/. Specifically, we constructed age-BMI-dependent reference charts for knee OA cartilage thickness, based on MRI scans from 957 radiographic OA (rOA)-free individuals from the Osteoarthritis Initiative cohort. Then we extracted local and global centiles by contrasting an individual’s cartilage thickness to the rOA-free cohort with a similar age and BMI. Using traditional boosting approaches with our centile-based features, we obtain rOA classification of KLG ≤ 1 versus KLG = 2 (AUC =0.95, F1 =0.89), KLG ≤ 1 versus KLG ≥ 2 (AUC =0.90, F1 =0.82) and prediction of KLG2 progression (AUC =0.98, F1 =0.94), rOA incidence (KLG increasing from <2to ≥2; AUC =0.81, F1 =0.69) and rOA initial transition (KLG from 0 to 1; AUC =0.64, F1 =0.65) within a future 48-month period. Such performance in classifying KLG ≥ 2 matches that of deep learning methods in recent literature. Furthermore, its clinical interpretation suggests that cartilage changes, such as thickening in lateral femoral and anterior femoral regions and thinning in lateral tibial regions, may serve as indicators for prediction of rOA incidence and early progression. Meanwhile, cartilage thickening in the posterior medial and posterior lateral femoral regions, coupled with a reduction in the central medial femoral region, may signify initial phases of rOA transition.
Excess risk of Covid-19 infection and mental distress in healthcare workers during successive pandemic waves. Analysis of matched cohorts of healthcare workers and community referents in Alberta, Canada
Authors: Galarneau Jean-Michel , Labrèche France , Durand-Moreau Quentin , Ruzycki Shannon , Adisesh Anil , Burstyn Igor , Zadunayski Tanis , Cherry Nicola 
Published: September 2023

AbstractObjectivesTo investigate changes in risk of infection and mental distress in healthcare workers (HCWs) relative to the community as the Covid-19 pandemic progressed.MethodsHCWs in Alberta, Canada, recruited to an interprovincial cohort, were asked consent to link to Alberta’s administrative health database (AHDB) and to information on Covid-19 immunization and polymerase chain reaction (PCR) testing. Those consenting were matched to records of up to 5 community referents (CRs). Physician diagnoses of Covid-19 were identified in the AHDB from the start of the pandemic to 31 March 2022. Physician consultations for mental health (MH) conditions (anxiety, stress/adjustment reaction, depressive) were identified from 1 April 2017 to 31 March 2022. Relative risk for HCWs was estimated for each condition, overall and for successive infection waves.Results80% (3050/3812) of HCWs consented to be linked to the AHDB: 97% (2959/3050) were matched to 14546 CRs. HCWs were at greater risk of Covid-19 overall, with first infection defined either from PCR tests or physician records They were also at increased risk for each of the three MH diagnoses. In analyses adjusted for confounding, risk of Covid-19 infection was higher than CRs early in the pandemic and during the fifth (Omicron) wave. The excess risk of stress/adjustment reactions and depressive conditions increased with successive waves during the epidemic, peaking in the 4thwave.ConclusionAdministrative health data, although not a complete reflection of infection or MH, contributed to an understanding of changing risk over time, with excess risk continuing late in the pandemic
Transcriptional Signatures of Hippocampal Tau Pathology in Primary Age-Related Tauopathy and Alzheimer’s Disease
Authors: Stein-O’Brien Genevieve L , Palaganas Ryan , Meyer Ernest M. , Redding-Ochoa Javier , Pletnikova Olga , Guo Haidan , Bell William R , Troncoso Juan C , Huganir Richard L , Morris Meaghan 
Published: September 2023

AbstractBackgroundTau pathology is common in age-related neurodegenerative diseases. Tau pathology in primary age-related tauopathy (PART) and in Alzheimer’s disease (AD) has a similar biochemical structure and anatomic distribution, which is distinct from tau pathology in other diseases. However, the molecular changes associated with intraneuronal tau pathology in PART and AD, and whether these changes are similar in the two diseases, is largely unexplored.MethodsUsing GeoMx spatial transcriptomics, mRNA was quantified in CA1 pyramidal neurons with tau pathology and adjacent neurons without tau pathology in 6 cases of PART and 6 cases of AD, and compared to 4 control cases without pathology. Transcriptional changes were analyzed for differential gene expression and for coordinated patterns of gene expression associated with both disease state and intraneuronal tau pathology.ResultsSynaptic gene changes and two novel gene expression signatures associated with intraneuronal tau were identified in PART and AD. Overall, gene expression changes associated with intraneuronal tau pathology were similar in PART and AD. Synaptic gene expression was decreased overall in neurons in AD and PART compared to control cases. However, this decrease was largely driven by neurons lacking tau pathology. Synaptic gene expression was increased in tau-positive neurons compared to tau-negative neurons in disease. Two novel gene expression signatures associated with intraneuronal tau were identified by examining coordinated patterns of gene expression. Genes in the up-regulated expression pattern were enriched in calcium regulation and synaptic function pathways, specifically in synaptic exocytosis. These synaptic gene changes and intraneuronal tau expression signatures were confirmed in a published transcriptional dataset of cortical neurons with tau pathology in AD.ConclusionsPART and AD show similar transcriptional changes associated with intraneuronal tau pathology in CA1 pyramidal neurons, raising the possibility of a mechanistic relationship between the tau pathology in the two diseases. Intraneuronal tau pathology was also associated with increased expression of genes associated with synaptic function and calcium regulation compared to tau-negative disease neurons. The findings highlight the power of molecular analysis stratified by pathology in neurodegenerative disease and provide novel insight into common molecular pathways associated with intraneuronal tau in PART and AD.Graphical AbstractCreated withBioRender.com(License GLSO).
Long- versus short-duration systemic corticosteroid regimens for acute exacerbations of COPD: A systematic review and meta-analysis of randomized trials and cohort studies
Authors: Zhao Zhen , Lou Owen , Wang Yiyang , Yin Raymond , Gong Carrie , Deng Florence , Wu Ethan C , Xie Jing Yi , Wu Jerry , Ma Avery , Guo Yongzhi , Xiong Wei Ting 
Published: September 2023

AbstractWhile systemic corticosteroids quicken patient recovery during acute exacerbations of COPD, they also have many adverse effects. The optimal duration of corticosteroid administration remains uncertain. We performed a systematic review and meta-analysis to compare patient outcomes between short-(≤7 day) and long- (>7 day) corticosteroid regimens in adults with acute exacerbations of COPD.MEDLINE, EMBASE, CENTRAL, and hand searches were used to identify eight eligible RCTs and three retrospective cohort studies. Risk of bias was assessed using the Cochrane RoB 2.0 tool and ROBINS-I. Data were summarized as odds ratios (ORs) or mean differences (MDs) whenever possible and qualitatively described otherwise.A total of 11532 participants were included, with 1296 eligible for meta-analyses. Heterogeneity was present in the methodology and settings of the studies. The OR for mortality was 0.76 (95% CI=0.40–1.44, n=1055). The MD for hospital length-of-stay was -0.91 days (95% CI=-1.81–-0.02 days, n=421). The OR for re-exacerbations was 1.31 (95% CI=0.90–1.90, n=552). The OR for hyperglycemia was 0.90 (95% CI=0.60–1.33, n=423). The OR for infection incidence was 0.96 (95% CI=0.59–1.156, n=389). The MD for one-second forced expiratory volume change was -18.40 mL (95% CI=-111.80–75.01 mL, n=161).The RCTs generally had low or unclear risks of bias, while the cohort studies had serious or moderate risks of bias. Our meta-analyses were affected by imprecision due to insufficient data. Some heterogeneity was present in the results, suggesting population, setting, and treatment details are potential prognostic factors. Our evidence suggests that short-duration treatments are not worse than long-duration treatments in moderate/severe exacerbations and may lead to considerably better outcomes in milder exacerbations. This supports the current GOLD guidelines for corticosteroid administration.No funding was given for this review. Our protocol is registered in PROSPERO: CRD42023374410.
A novelkitmutant rat enables hematopoietic stem cell engraftment without irradiation
Authors: Iida Ryuya , Ishida Saeko , Wang Jinxi , Hattori Kosuke , Yoshimi Kazuto , Yamazaki Satoshi , Mashimo Tomoji 
Published: September 2023

SummaryHematopoietic stem cell (HSC) transplantation is extensively studied in mouse models, but their limited scale presents challenges for effective engraftment and comprehensive evaluations. Rats, due to their larger size and anatomical similarity to humans, offer a promising alternative. In this study, we establish a rat model with theKitV834Mmutation, mirroringKitW41mice often used in KIT signaling and HSC research.KitV834Mrats are viable and fertile, displaying anemia and mast cell depletion similar toKitW41mice. The mutation affects myeloid cell proliferation and differentiation, as seen in the colony-forming unit granulocyte-macrophage assay. Importantly,KitV834Mrats support donor rat-HSC engraftment without irradiation. Competitive transplantation assays reveal reduced reconstruction capacity inKitV834MHSCs. Leveraging the larger scale of this rat model enhances our understanding of HSC biology and transplantation dynamics, potentially advancing our knowledge in this field.
Cep290 is cooperatively maintained at basal body by Cep131-Cep162 and Cby-Fam92 modules
Authors: Wu Zhimao , Chen Huicheng , Zhang Yingying , Wang Yaru , Wang Qiaoling , Augière Céline , Hou Yanan , Fu Yuejun , Peng Ying , Durand Bénédicte , Wei Qing 
Published: September 2023

AbstractCilia play critical roles in cell signal transduction and organ development. Defects in cilia function result in a variety of genetic disorders. Cep290 is an evolutionarily conserved ciliopathy protein that bridges the ciliary membrane and axoneme at the basal body and plays critical roles in the initiation of ciliogenesis and TZ assembly. How Cep290 is maintained at basal body and whether axonemal and ciliary membrane localized cues converge to determine the localization of Cep290 remain unknown. Here, we report that the Cep131-Cep162 module near the axoneme and the Cby-Fam92 module close to the membrane synergistically control the basal body localization of Cep290 and the subsequent initiation of ciliogenesis. Concurrent deletion of any protein of the Cep131-Cep162 module and of the Cby-Fam92 module leads to a complete loss of Cep290 from basal body and blocks ciliogenesis at its initiation stage. Our results reveal that the first step of ciliogenesis strictly depend on cooperative and retroactive interactions between Cep131-Cep162, Cby-Fam92 and Cep290, which may contribute to the complex pathogenesis of Cep290-related ciliopathies.
m6a methylation orchestrates IMP1 regulation of microtubules during human neuronal differentiation
Authors: Klein Pierre , Harley Jasmine , Crook Harry , Serna Sofia Esteban , Howe Marija Petrić , Roumeliotis Theodoros I. , Choudhary Jyoti S. , Chakrabarti Anob M , Luisier Raphaëlle , Patani Rickie , Ramos Andres 
Published: September 2023

AbstractNeuronal differentiation requires building a complex intracellular architecture, and therefore the coordinated regulation of defined sets of genes. RNA-binding proteins (RBPs) play a key role in this regulation. However, while their action on individual mRNAs has been explored in depth, the mechanisms used to coordinate expression of the gene programs shaping neuronal morphology are poorly understood. To address this, we analysed how the paradigmatic RBP IMP1 (IGF2BP1), an essential developmental factor, selects and regulates its RNA targets during the differentiation of human neurons. We performed a combination of system-wide and molecular analyses, revealing that IMP1 developmentally transitions to and directly regulates the expression of mRNAs encoding essential regulators of the microtubule network, a key component of neuronal morphology. Furthermore, we showed that m6A methylation drives the selection of specific IMP1 mRNA targets and their protein expression during the developmental transition from neural precursors to neurons, providing a molecular principle for the onset of target selectivity.
Hyperpolarization-Activated Currents Drive Neuronal Activation Sequences in Sleep
Authors: Mehrotra Dhruv , Levenstein Daniel , Duszkiewicz Adrian J , Carrasco Sofia Skromne , Booker Sam A , Kwiatkowska Angelika , Peyrache Adrien 
Published: September 2023

AbstractSequential neuronal patterns are believed to support information processing in the cortex, yet their origin is still a matter of debate. We report that neuronal activity in the mouse head-direction cortex (HDC, i.e., the post-subiculum) was sequentially activated along the dorso-ventral axis during sleep at the transition from hyperpolarized “DOWN” to activated “UP” states, while representing a stable direction. Computational modelling suggested that these dynamics could be attributed to a spatial gradient of hyperpolarization-activated current (Ih), which we confirmed inex vivoslice experiments and corroborated in other cortical structures. These findings open up the possibility that varying amounts of Ihacross cortical neurons could result in sequential neuronal patterns, and that travelling activity upstream of the entorhinal-hippocampal circuit organises large-scale neuronal activity supporting learning and memory during sleep.HighlightsNeuronal Activation Sequence in HDC: neuronal activity was sequentially reinstated along the dorsoventral axis of the HDC at UP state but not DOWN state onset.Role of Ihin Sequence Generation: Incorporating the hyperpolarization-activated current (Ih) into computational models, we identified its pivotal role in UP/DOWN dynamics and neuronal activity sequences.Ex VivoVerification: slice physiology revealed a dorsoventral gradient of Ih in the HDC.Implications Beyond HDC: the gradient of Ihcould account for the sequential organization of neuronal activity across various cortical areas.
Characteristics of spontaneous anterior-posterior oscillation-frequency convergences in the alpha band
Authors: Suzuki Satoru , Grabowecky Marcia , Menceloglu Melisa 
Published: September 2023

AbstractAlpha oscillation frequencies vary along the anterior-posterior axis, but they also dynamically converge. We investigated spontaneous anterior-posterior oscillation-frequency convergences while participants rested with their eyes open or closed, by tracking their oscillatory EEG activity in an extended alpha range (5-15 Hz) with appropriate temporal (∽370 ms) and spectral (∽1 Hz) resolutions. Oscillation-frequency convergences were prominent in the alpha band (8-12 Hz) and our analyses revealed three primary characteristics. First, the probability of an additional site joining a frequency convergence increased as more sites frequency-converged, suggesting that synergistic interactions drive anterior-posterior frequency convergences. Second, the oscillatory power at participating sites increased as more sites frequency-converged, suggesting that the synergistic interactions are mediated by regional synchronizations, being boosted by inter-regional frequency matching, facilitating the entrainment of additional regions. Third, frequency convergences generated two opposing phase gradients, posterior-behind and posterior-ahead, potentially mediating directional information flows to and from posterior regions. These gradients became steeper as more sites frequency-converged (while maintaining relatively constant levels of phase consistency), suggesting that frequency convergences increase the directionality of anterior-posterior information flows. Interestingly, when participants closed their eyes, the opposing phase gradients spatially organized, forming posterior-ahead gradients along the midline and posterior-behind gradients within each hemisphere, suggesting that closing eyes streamlines the opposing information flows. Taken together, these results suggest that synergistic interactions drive spontaneous anterior-posterior oscillation-frequency convergences in the alpha band, which may contribute to directional flows of information to and from posterior regions.
A robust measure of metacognitive sensitivity and confidence criteria
Authors: Arnold Derek H. , Clendinen Mitchell , Johnston Alan , Lee Alan L.F. , Yarrow Kielan 
Published: September 2023

Humans experience feelings of confidence in their decisions. In perception, these feelings are typically accurate – we tend to feel more confident about correct decisions. The degree of insight people have into the accuracy of their decisions is known as metacognitive sensitivity. Currently popular methods of estimating metacognitive sensitivity are subject to interpretive ambiguities because they assume that humans experience normally-shaped distributions of different experiences when they are repeatedly exposed to a single input. If, however, people have skewed distributions of experiences, or distributions with excess kurtosis (i.e. a distribution containing greater numbers of extreme experiences than is predicted by a normal distribution), calculations can erroneously underestimate metacognitive sensitivity. Here, we describe a means of estimating metacognitive sensitivity that is more robust against violations of the normality assumption. This improved method relies on estimating the precision with which people transition between making categorical decisions with relatively low to high confidence, and on comparing this with the precision with which they transition between making different types of perceptual category decision. The new method can easily be added to standard behavioral experiments. We provide free Matlab code to help researchers implement these analyses and procedures in their own experiments.Public Significance StatementSignal-detection theory is one of the most popular frameworks for analysing data from experiments of human behaviour – including investigations of confidence. The authors demonstrate that if a key assumption of this framework is inadvertently violated, analyses of confidence can lead to unwarranted conclusions. They develop a new and more robust measure of confidence.