bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired 26S proteasome causes learning and memory deficiency and induces neuroinflammation mediated by NF-κB in mice
Authors: Huber Christa C. , Callegari Eduardo , Paez Maria , Li Xiaoping , Dwamena Abena , Wang Hongmin 
Published: February 2024

AbstractA reduction in proteasome activity, loss of synapses, and increased neuroinflammation in the brain are hallmarks of aging and many neurodegenerative disorders, including Alzheimer’s disease (AD); however, whether proteasome dysfunction is causative to neuroinflammation remains less understood. In this study, we investigated the impact of 26S proteasome deficiency on neuroinflammation in thePsmc1knockout (KO) mice deficient in a 19S proteasome subunit limited to the forebrain region. Our results revealed that impaired 26S proteasome causes reduced learning and memory capability and overt neuroinflammation in thePsmc1KO brain at eight weeks of age. Pronounced neuroinflammation was confirmed by increased levels of several key immune response-related proteins, including Stat1, Trem2, and NF-κB, and by activation of astrocytes and microglia in the KO brain. To validate NF-κB mediating neuroinflammation, we administered a selective NF-κB inhibitor to the KO animals, and following the treatment, the KO mice exhibited improved learning and memory behaviors and reduced neuroinflammation compared to the control animals. These data indicate that impaired 26S proteasome causes AD-like cognitive deficiency and induces neuroinflammation mediated largely by NF-κB. These results may aid the development of effective therapeutics for AD and other neurodegenerative disorders where impaired proteasome activity is consistently coupled with neuroinflammation.
Psilocybin induces dose-dependent changes in functional network organization in rat cortex
Authors: Silverstein Brian H. , Kolbman Nicholas , Nelson Amanda , Liu Tiecheng , Guzzo Peter , Gilligan Jim , Lee UnCheol , Mashour George A. , Vanini Giancarlo , Pal Dinesh 
Published: February 2024

AbstractPsilocybin produces an altered state of consciousness in humans and is associated with complex spatiotemporal changes in brain networks. Given the emphasis on rodent models for mechanistic studies, there is a need for characterization of the effect of psilocybin on brain-wide network dynamics. Previous rodent studies of psychedelics, using electroencephalogram, have primarily been done with sparse electrode arrays that offered limited spatial resolution precluding network level analysis, and have been restricted to lower gamma frequencies. Therefore, in the study, we used electroencephalographic recordings from 27 sites (electrodes) across rat cortex (n=6 male, 6 female) to characterize the effect of psilocybin (0.1 mg/kg, 1 mg/kg, and 10 mg/kg delivered over an hour) on network organization as inferred through changes in node degree (index of network density) and connection strength (weighted phase-lag index). The removal of aperiodic component from the electroencephalogram localized the primary oscillatory changes to theta (4-10 Hz), medium gamma (70-110 Hz), and high gamma (110-150 Hz) bands, which were used for the network analysis. Additionally, we determined the concurrent changes in theta-gamma phase-amplitude coupling. We report that psilocybin, in a dose-dependent manner, 1) disrupted theta-gamma coupling [p<0.05], 2) increased frontal high gamma connectivity [p<0.05] and posterior theta connectivity [p≤0.049], and 3) increased frontal high gamma [p<0.05] and posterior theta [p≤0.046] network density. The medium gamma frontoparietal connectivity showed a nonlinear relationship with psilocybin dose. Our results suggest that high-frequency network organization, decoupled from local theta-phase, may be an important signature of psilocybin-induced non-ordinary state of consciousness.
Bacterial Bloodstream Infections in Cameroon: A Systematic Review and Meta-Analysis of Prevalence and Antibiotic Resistance
Authors: Matakone Moise , Koudoum Patrice Landry , Zemtsa Ravalona Jessica , Ngomtcho Sen Claudine Henriette , Dah Isaac , Noubom Michel 
Published: February 2024

AbstractBackgroundThe paucity of data on the epidemiology of bloodstream infection (BSI) in low and middle-income countries (LMICs) limits its effective prevention and management. This review sought to determine the prevalence, bacteriological and antimicrobial resistance profiles of bacteria implicated in BSI in Cameroon.MethodsPubMed and Google Scholar databases were searched to identify relevant articles, which were screened according to the PRISMA guidelines. The data were analysed using comprehensive meta-analysis software. The I2was used to evaluate heterogeneity between studies, Begg’s and Egger’s regression tests were used to evaluate publication bias, and random effects analysis was used to calculate the pooled prevalence.ResultsA total of 4223 blood cultures were obtained from the 10 included studies. The overall pooled prevalence of bacterial BSI was 26.31% (95% CI= 17.01%–38.35%).Escherichia coli(23.09%; 95% CI= 9.21%–47.05%),Klebsiellaspp. (22.95%; 95% CI= 13.09%–37.07%), andStaphylococcus aureus(16.09%; 95% CI= 8.11%–29.43%) were the most common bacteria species.E. coliandKlebsiellaspp. displayed the highest resistance to amoxicillin (82.65%; 95% CI= 63.25%–92.95% vs 86.42%; 95% CI= 55.90%–96.97%), amoxicillin + clavulanic acid (71.74%; 43.96–89.15% vs 73.06%; 95% CI= 38.70%–92.09%) and cotrimoxazole (76.22%; 95% CI= 51.33%–90.79% vs 65.81%; 95% CI= 45.08–81.86%). However, meropenem (26.73%; 95% CI= 20.76%–33.68%) and fosfomycin (14.85%; 95% CI= 9.07%–23.37%) were the least resistant inE. coliandKlebsiellaspp., respectively.Staphylococcus aureusstrains exhibited highest resistance to penicillin (84.37%; 95% CI= 68.13%–93.16%), erythromycin (44.80%; 95% CI= 33.37%–56.79%) and oxacillin (37.35%; 95% CI= 8.76%–78.74%) and lowest resistance to rifampicin (2.94%; 95% CI= 0.59%–13.39%), fusidic acid (6.73%; 95% CI= 2.55%–16.62%) and vancomycin (13.18%; 95% CI= 2.26%–49.86%).ConclusionThis study reports a high prevalence of bacterial BSIs in Cameroon and the high resistance of these bacteria to common antibiotics. There is a pressing need to conduct BSI surveillance studies in all regions of Cameroon to generate data for evidence-based measures regarding BSI prevention and management.Prospero registration numberCRD42023482760
Physicians’ experiences with telemedicine during the COVID-19 pandemic in India
Authors: Nagaraja Vikranth H. , Ghosh Dastidar Biswanath , Suri Shailesh , Jani Anant R. 
Published: February 2024

AbstractPurposeDigital health is an important factor in India’s healthcare system. Inclusive policy measures, a fertile technological landscape, and relevant infrastructural development with unprecedented levels of telemedicine adoption catalysed by the recent COVID-19 pandemic have thrown open new possibilities and opportunities for clinicians, end-users, and other stakeholders. Nevertheless, there are still several challenges to properly integrating and scaling telemedicine use in India. This study’s objective was to understand the views of practising physicians in India on the use of telemedicine and the challenges experienced during the accelerated rollout during the first wave of the COVID-19 pandemic.MethodsWe acquired data through an anonymous, cross-sectional, internet-based survey of physicians (n=444) across India on the COVID-19 frontline. These responses were subjected to qualitative data analysis (via inductive coding and thematic analyses) and descriptive statistics, as appropriate.ResultsMost responses (n=51) were categorised under a code indicating that telemedicine-led healthcare delivery compromised treatment quality. The second largest proportion of responses (n=22) suggested that ‘Accessibility, quality and maturity of software and hardware infrastructure’ was a considerable challenge.ConclusionsDespite the considerable uptake, perceived benefits, and the foreseen positive role of telemedicine in India, several challenges of telemedicine use (viz., technical, user experience-based integration, and non-user-based integration challenges) have been identified. These must be addressed through suggested relevant opportunities to realise telemedicine’s potential and help inform the future design of effective telemedicine policy and practice in India.FundingNo funding to report.DeclarationsNone
Metabolomic Age (MileAge) predicts health and lifespan: a comparison of multiple machine learning algorithms
Authors: Mutz Julian , Iniesta Raquel , Lewis Cathryn M 
Published: February 2024

AbstractBackgroundMolecular ageing clocks estimate an individual’s biological age. Our aim was to compare multiple machine learning algorithms for developing ageing clocks from nuclear magnetic resonance (NMR) spectroscopy metabolomics data. To validate how well each ageing clock predicted age-related morbidity and lifespan, we assessed their associations with multiple health indicators (e.g., telomere length and frailty) and all-cause mortality.MethodsThe UK Biobank is a multicentre observational health study of middle-aged and older adults. The Nightingale Health platform was used to quantify 168 circulating plasma metabolites at the baseline assessment from 2006 to 2010. We trained and internally validated 17 machine learning algorithms including regularised regression, kernel-based methods and ensembles. Metabolomic age (MileAge) delta was defined as the difference between predicted and chronological age.ResultsThe sample included 101,359 participants (mean age = 56.53 years, SD = 8.10). Most metabolite levels varied by chronological age. The nested cross-validation mean absolute error (MAE) ranged from 5.31 to 6.36 years. 31.76% of participants had an age-bias adjusted MileAge more than one standard deviation (3.75 years) above or below the mean. A Cubist rule-based regression model overall performed best at predicting health outcomes. The all-cause mortality hazard ratio (HR) comparing individuals with a MileAge delta more than one standard deviation above and below the mean was HR = 1.52 (95% CI 1.41-1.64,p< 0.001) over a median follow-up of 13.87 years. Individuals with an older MileAge were frailer, had shorter telomeres, were more likely to have a chronic illness and rated their health worse.ConclusionsMetabolomic ageing clocks derived from multiple machine learning algorithms were robustly associated with health indicators and mortality. Our metabolomic ageing clock (MileAge) derived from a Cubist rule-based regression model can be incorporated in research, and may find applications in health assessments, risk stratification and proactive health tracking.
Incidence of Mortality and Predictors Among Patients with Shock Managed in the Emergency Room of a Large Tertiary Referral Hospital in Ethiopia
Authors: Asfaw Kalsidagn Girma , Adugna Abel Getachew , Mekonen Nahom Mesfin , Leulseged Tigist Workneh , Merahi Merahi Kefyalew , Kejela Segni , Moges Fekadesilassie Henok 
Published: February 2024

ABSTRACTBackgroundShock is a common emergency condition which can lead to organ failure and death if not diagnosed and managed timely. Despite its huge global impact, data is scarce in resource-limited settings, such as Ethiopia, which hinders the provision of quality care for improved patient outcomes. Hence, the aim of the study was to determine the incidence of death and predictors among adult patients with shock managed at the Emergency Department of St. Paul’s Hospital Millennium Medical College in Ethiopia.MethodsA retrospective chart review study was conducted between July to September 2022 among 178 eligible adult patients who were managed at hospital between October 2021 and May 2022. The characteristics of the participants were summarized using frequency and median with interquartile range. The incidence of mortality was estimated using incidence density using person hour (PH) of observation. To identify predictors of mortality, a generalized linear model using poisson regression model with robust standard errors was run at 5% level of significance, where adjusted relative risk (ARR) with its 95% CI was used to interpret significant resultsResultThe incidence of death was 6.87 deaths per 1000 PH (95% CI= 5.44 to 8.69). Significant predictors of death were being triaged orange (ARR=0.46, 95% CI=0.24-0.88, p=0.020), having a high shock index (ARR=1.59, 95% CI=1.07-2.36, p=0.021), being diagnosed with septic shock (ARR=3.66, 95% CI=1.20-11.17, p=0.023), taking vasopressors (ARR=3.18, 95% CI=1.09, 9.27, p=0.034), and developing organ failure (ARR=1.79, 95% CI=1.04-3.07, p=0.035).ConclusionThe incidence of mortality among shock patients was found to be considerable but relatively lower than previous studies. To optimize patient care and improve outcomes, it is important to remain vigilant in the proper triage and early diagnosis of shock using more sensitive tools for prompt identification of high-risk cases, as well as to provide timely, prioritized and effective interventions.
In mice, discrete odors can selectively promote the neurogenesis of sensory neuron subtypes that they stimulate
Authors: Hossain Kawsar , Smith Madeline , Santoro Stephen W. 
Published: February 2024

AbstractIn mammals, olfactory sensory neurons (OSNs) are born throughout life, presumably solely to replace neurons lostviaturnover or injury. This assumption follows from the hypothesis that olfactory neurogenesis is strictly stochastic with respect to neuron subtype, as defined by the single odorant receptor allele that each neural precursor stochastically chooses out of hundreds of possibilities. This hypothesis is challenged by recent findings that the birthrates of a fraction of subtypes are selectively diminished by olfactory deprivation. These findings raise questions about how, and why, olfactory stimuli are required to promote the neurogenesis of some OSN subtypes, including whether the stimuli are generic (e.g., broadly activating odors or mechanical stimuli) or specific (e.g., discrete odorants). Based on RNA-seq and scRNA-seq analyses, we hypothesized that the neurogenic stimuli are specific odorants that selectively activate the same OSN subtypes whose birthrates are accelerated. In support of this, we have found, using subtype-specific OSN birthdating, that exposure to male and musk odors can accelerate the birthrates of responsive OSNs. Collectively, our findings reveal that certain odor experiences can selectively “amplify” specific OSN subtypes, and that persistent OSN neurogenesis may serve, in part, an adaptive function.
Simpler protein domain identification using spectral clustering
Authors: Cazals Frédéric , Herrmann Jules , Sarti Edoardo 
Published: February 2024

AbstractThe decomposition of a biomolecular complex into domains is an important step to investigate biological functions and ease structure determination. A successful approach to do so is theSPECTRUSalgorithm, which provides a segmentation based on spectral clustering applied to a graph coding interatomic fluctuations derived from an elastic network model.We presentSPECTRALDOM, which makes three straightforward and useful additions toSPECTRUS. For single structures, we show that high quality partitionings can be obtained from a graph Laplacian derived from pairwise interactions–without normal modes. For sets of homologous structures, we introduce a Multiple Sequence Alignment mode, exploiting both the sequence based information (MSA) and the geometric information embodied in experimental structures. Finally, we propose to analyse the clusters/- domains delivered using the so-calledD-family-matching algorithm, which establishes a correspondence between domains yielded by two decompositions, and can be used to handle fragmentation issues.Our domains compare favorably to those of the originalSPECTRUS, and those of the deep learning based methodChainsaw. Using two complex cases, we show in particular thatSPECTRALDOMis the only method handling complex conformational changes involving several sub-domains. Finally, a comparison ofSPECTRALDOMandChainsawon the manually curated domain classificationECODas a reference shows that high quality domains are obtained without using any evolutionary related piece of information.SPECTRALDOMis provided in the Structural Bioinformatics Library, seehttp://sbl.inria.frandhttps://sbl.inria.fr/doc/Spectral_domain_explorer-user-manual.html.
Far-red chemigenetic biosensors for multi-dimensional and super-resolved kinase activity imaging
Authors: Frei Michelle S. , Sanchez Samantha A. , Liu Longwei , Schneider Falk , Wang Zichen , Hakozaki Hiroyuki , Li Yajuan , Lyons Anne C. , Rohm Theresa V. , Olefsky Jerrold M. , Shi Lingyan , Schöneberg Johannes , Fraser Scott E. , Mehta Sohum , Wang Yingxiao , Zhang Jin 
Published: February 2024

AbstractFluorescent biosensors revolutionized biomedical science by enabling the direct measurement of signaling activities in living cells, yet the current technology is limited in resolution and dimensionality. Here, we introduce highly sensitive chemigenetic kinase activity biosensors that combine the genetically encodable self-labeling protein tag HaloTag7 with bright far-red-emitting synthetic fluorophores. This technology enables five-color biosensor multiplexing, 4D activity imaging, and functional super-resolution imaging via stimulated emission depletion (STED) microscopy.
Identification of a motif in TPX2 that regulates spindle architecture inXenopusegg extracts
Authors: Pena Guadalupe E. , Zhou Xiao , Slevin Lauren , Brownlee Christopher , Heald Rebecca 
Published: February 2024

AbstractA bipolar spindle composed of microtubules and many associated proteins functions to segregate chromosomes during cell division in all eukaryotes, yet spindle size and architecture varies dramatically across different species and cell types. Targeting protein for Xklp2 (TPX2) is one candidate factor for modulating spindle microtubule organization through its roles in branching microtubule nucleation, activation of the mitotic kinase Aurora A, and association with the kinesin-5 (Eg5) motor. Here we identify a conserved nuclear localization sequence (NLS) motif,123KKLK126inX. laevisTPX2, which regulates astral microtubule formation and spindle pole morphology inXenopusegg extracts. Addition of recombinant TPX2 with this sequence mutated to AALA dramatically increased spontaneous formation of microtubule asters and recruitment of phosphorylated Aurora A, pericentrin, and Eg5 to meiotic spindle poles. We propose that TPX2 is a linchpin spindle assembly factor whose regulation contributes to the recruitment and activation of multiple microtubule polymerizing and organizing proteins, generating distinct spindle architectures.
A proteome-wide quantitative platform for nanoscale spatially resolved extraction of membrane proteins into native nanodiscs
Authors: Brown Caroline , Ghosh Snehasish , McAllister Rachel , Kumar Mukesh , Walker Gerard , Sun Eric , Aman Talat , Panda Aniruddha , Kumar Shailesh , Li Wenxue , Coleman Jeff , Liu Yansheng , Rothman James E , Bhattacharyya Moitrayee , Gupta Kallol 
Published: February 2024

AbstractThe intricate molecular environment of the native membrane profoundly influences every aspect of membrane protein (MP) biology. Despite this, the most prevalent method of studying MPs uses detergent-like molecules that disrupt and remove this vital local membrane context. This severely impedes our ability to quantitatively decipher the local molecular context and comprehend its regulatory role in the structure, function, and biogenesis of MPs. Using a library of membrane-active polymers we have developed a platform for the high-throughput analysis of the membrane proteome. The platform enables near-complete spatially resolved extraction of target MPs directly from their endogenous membranes into native nanodiscs that maintain the local membrane context. We accompany this advancement with an open-access database that quantifies the polymer-specific extraction variability for 2065 unique mammalian MPs and provides the most optimized condition for each of them. Our method enables rapid and near-complete extraction and purification of target MPs directly from their endogenous organellar membranes at physiological expression levels while maintaining the nanoscale local membrane environment. Going beyond the plasma membrane proteome, our platform enables extraction from any target organellar membrane including the endoplasmic reticulum, mitochondria, lysosome, Golgi, and even transient organelles such as the autophagosome. To further validate this platform, we took several independent MPs and demonstrated how our resource can enable rapid extraction and purification of target MPs from different organellar membranes with high efficiency and purity. Further, taking two synaptic vesicle MPs, we show how the database can be extended to capture multiprotein complexes between overexpressed MPs. We expect these publicly available resources to empower researchers across disciplines to efficiently capture membrane ‘nano-scoops’ containing a target MP and interface with structural, functional, and other bioanalytical approaches. We demonstrate an example of this by combining our extraction platform with single-molecule TIRF imaging to demonstrate how it can enable rapid determination of homo-oligomeric states of target MPs in native cell membranes.
Enhancing Bone Regeneration and Osseointegration using rhPTH(1-34) and DimericR25CPTH(1-34) in an Osteoporotic Beagle Model
Authors: Shin Jeong-Oh , Lee Jong-Bin , Lee Sihoon , Kim Jin-Woo 
Published: February 2024

AbstractIntroductionDespite continuous parathyroid hormone (PTH) exposure potentially accelerating bone resorption, intermittent PTH administration has shown anabolic effects on bone microarchitecture. This study investigates the therapeutic impacts of two PTH analogs, rhPTH(1-34) and dimericR25CPTH(1-34) on bone regeneration and osseointegration in a postmenopausal osteoporosis animal model.MethodsTwelve female beagles, osteoporotic post-ovariectomy, underwent implant surgeries. Animals were divided into three groups: control, daily rhPTH(1-34) injection, and daily dimericR25CPTH(1-34) injection. After 10 weeks, bone regeneration and implant osseointegration were evaluated using micro-CT, histological/histomorphometric analyses, and serum biochemical analysis.ResultsWhile the rhPTH(1-34) group demonstrated improved microarchitectural characteristics, such as BMD, BV, trabecular metrics, and osseointegration degree, the dimericR25CPTH(1-34) group showed similarly enhanced anabolic effects around the titanium implants, albeit these were less pronounced than the rhPTH(1-34), yet significantly better than the control group. Histologic and TRAP assays revealed that both PTH analogs significantly promoted bone regeneration and remodeling, especially in artificially created bone defects.ConclusionThis study demonstrated the therapeutic effects of rhPTH(1-34) and dimericR25CPTH(1-34) on bone regeneration and titanium osseointegration in a beagle model with osteoporosis.