bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contraction and expansion dynamics: deciphering genomic underpinnings of growth rate and pathogenicity in Mycobacterium
Authors: Zhu Xiaoying , Lu Qunfeng , Li Yulei , Long Qinqin , Zhang Xinyu , Long Xidai , Cao Demin 
Published: November 2023

BackgroundMycobacterium bacteria, encompassing both slow growth (SGM) and rapid growth mycobacteria (RGM), along with true pathogenic (TP), opportunistic pathogenic (OP), and non-pathogenic (NP) types, exhibit diverse phenotypes. Yet, the genetic underpinnings of these variations remain elusive.MethodsHere, We conducted a comprehensive comparative genomics study involving 53 Mycobacterium species to unveil the genomic drivers behind growth rate and pathogenicity disparities.ResultsOur core/pan-genome analysis highlighted 1,307 shared gene families, revealing an open pan-genome structure. A phylogenetic tree highlighted clear boundaries between SGM and RGM, as well as TP and other species. Gene family contraction emerged as the primary alteration associated with growth and pathogenicity transitions. Specifically, ABC transporters for amino acids and inorganic ions, along with quorum sensing genes, exhibited significant contractions in SGM species, potentially influencing their distinct traits. Conversely, TP strains displayed contraction in lipid and secondary metabolite biosynthesis and metabolism-related genes. Across the 53 species, we identified 26 core and 64 accessory virulence factors. Remarkably, TP and OP strains stood out for their expanded mycobactin biosynthesis and type VII secretion system gene families, pivotal for their pathogenicity.ConclusionOur findings underscore the importance of gene family contraction in nucleic acids, ions, and substance metabolism for host adaptation, while emphasizing the significance of virulence gene family expansion, including type VII secretion systems and mycobactin biosynthesis, in driving mycobacterial pathogenicity.
Mutation of self-binding sites in the promoter of the MrpC transcriptional regulator leads to asynchronous Myxococcus xanthus development
Authors: McLaughlin Maeve , Higgs Penelope I. 
Published: November 2023

IntroductionMrpC, a member of the CRP/Fnr transcription factor superfamily, is necessary to induce and control the multicellular developmental program of the bacterium, Myxococcus xanthus. During development, certain cells in the population first swarm into haystack-shaped aggregates and then differentiate into environmentally resistant spores to form mature fruiting bodies (a specialized biofilm). mrpC transcriptional regulation is controlled by negative autoregulation (NAR).MethodsWild type and mutant mrpC promoter regions were fused to a fluorescent reporter to examine effects on mrpC expression in the population and in single cells in situ. Phenotypic consequences of the mutant mrpC promoter were assayed by deep convolution neural network analysis of developmental movies, sporulation efficiency assays, and anti-MrpC immunoblot. In situ analysis of single cell MrpC levels in distinct populations were assayed with an MrpC-mNeonGreen reporter.ResultsDisruption of MrpC binding sites within the mrpC promoter region led to increased and broadened distribution of mrpC expression levels between individual cells in the population. Expression of mrpC from the mutant promoter led to a striking phenotype in which cells lose synchronized transition from aggregation to sporulation. Instead, some cells abruptly exit aggregation centers and remain locked in a cohesive swarming state we termed developmental swarms, while the remaining cells transition to spores inside residual fruiting bodies. In situ examination of a fluorescent reporter for MrpC levels in developmental subpopulations demonstrated cells locked in the developmental swarms contained MrpC levels that do not reach the levels observed in fruiting bodies.DiscussionIncreased cell-to-cell variation in mrpC expression upon disruption of MrpC binding sites within its promoter is consistent with NAR motifs functioning to reducing noise. Noise reduction may be key to synchronized transition of cells in the aggregation state to the sporulation state. We hypothesize a novel subpopulation of cells trapped as developmental swarms arise from intermediate levels of MrpC that are sufficient to promote aggregation but insufficient to trigger sporulation. Failure to transition to higher levels of MrpC necessary to induce sporulation may indicate cells in developmental swarms lack an additional positive feedback signal required to boost MrpC levels.
Development and preliminary validation of a virtual reality memory test for assessing visuospatial memory
Authors: Kim Ko Woon , Choi Jong Doo , Chin Juhee , Lee Byung Hwa , Choi Jee Hyun , Na Duk L. 
Published: November 2023

BackgroundVisuospatial memory impairment is a common symptom of Alzheimer’s disease; however, conventional visuospatial memory tests are insufficient to fully reflect visuospatial memory impairment in daily life.MethodsTo address patients’ difficulties in locating and recalling misplaced objects, we introduced a novel visuospatial memory test, the Hidden Objects Test (HOT), conducted in a virtual environment. We categorized HOT scores into prospective memory, item free-recall, place free-recall, item recognition, and place-item matching scores. To validate the VR memory test, we compared HOT scores among individuals with Alzheimer’s disease (AD), amnestic mild cognitive impairment (aMCI), and normal controls (NC), and also compared these scores with those of conventional neuropsychological tests. We tracked the participants’ movement paths in the virtual environment and assessed basic features, such as total distance, duration, and speed. Additionally, we performed walking trajectory pattern mining such as outlier and stay-point detection.ResultsWe designed and implemented the HOT to simulate a house’s living room and assess participants’ ability to locate hidden objects. Our preliminary results showed that the total HOT score differed among 17 patients with AD, 14 with aMCI, and 15 NC (p &lt; 0.001). The total HOT score correlated positively with conventional memory test scores (p &lt; 0.001). Walking trajectories showed that patients with AD and aMCI wandered rather than going straight to the hidden objects. In terms of basic features, the total duration was significantly greater in AD than in NC (p = 0.008). In terms of trajectory pattern mining, the number of outliers, which were over 95% of the estimated trajectory, was significantly higher in AD than in NC (p = 0.002). The number of stay points, an index in which participants stayed in the same position for more than 2 s, was significantly higher in patients with AD and aMCI compared with NC (AD vs. NC: p = 0.003, aMCI vs. NC: p = 0.019).ConclusionThe HOT simulating real life showed potential as an ecologically valid test for assessing visuospatial memory function in daily life. Walking trajectory analysis suggested that patients with AD and aMCI wandered rather than going straight toward the hidden objects.
Integrating serum pharmacochemistry and network pharmacology to reveal the active constituents and mechanism of Corydalis Rhizoma in treating Alzheimer’s disease
Authors: Lyu Yan , Wang Yu , Guo Jianyou , Wang Yuqing , Lu Yifan , Hao Zhuangzhuang , Jiang Tingyue , Fan Wenxin , Li Yihua , Shi Jinli 
Published: November 2023

BackgroundAlzheimer’s disease (AD) is a multifactorial neurodegenerative condition. The search for multi-target traditional Chinese medicines or ingredients for treating AD has attracted much attention. Corydalis rhizome (CR) is a traditional Chinese medicine. Its main components are alkaloids, which have therapeutic effects that can potentially be used for treating AD. However, no systematic study has been conducted to explore the anti-AD efficacy of CR, as well as its active compounds and mechanisms of action.ObjectiveThe present study aimed to clarify CR’s active constituents and its pharmacological mechanisms in treating AD.MethodsA D-galactose &amp; scopolamine hydrobromide-induced AD mouse model was used and CR was administered orally. The prototypical alkaloid components were identified in the serum. The core components, key targets, and possible mechanisms of action of these alkaloids were revealed through network pharmacology. Molecular docking of the key target was performed. Finally, the mechanism was validated by lipopolysaccharide (LPS)-induced activation of BV2 microglia.ResultsThe results showed that CR improved anxiety-like behavior, spatial and non-spatial recognition, and memory capacity in AD mice. It also achieved synergistic AD treatment by modulating neurotransmitter levels, anti-neuroinflammation, and anti-oxidative stress. The core components that enhance CR’s efficacy in treating AD are protoberberine-type alkaloids. The CR may induce the polarization of LPS-activated BV2 microglia from phenotype M1 to M2. This is partially achieved by modulating the IL-6/JAK2/STAT3 signaling pathway, which could be the mechanism by which CR treats AD through anti-inflammation.ConclusionThe present study provided a theoretical and experimental basis for the clinical application of CR in treating AD. It also provides information that aids the secondary development, and precise clinical use of CR.
Electrophysiological neuromuscular alterations and severe fatigue predict long-term muscle weakness in survivors of COVID-19 acute respiratory distress syndrome
Authors: Benedini Marco , Cogliati Marta , Lulic-Kuryllo Tea , Peli Elena , Mombelli Stefano , Calza Stefano , Guarneri Bruno , Cudicio Alessandro , Rizzardi Andrea , Bertoni Michele , Gazzina Stefano , Renzi Stefania , Gitti Nicola , Rasulo Frank A. , Goffi Alberto , Pozzi Matteo , Orizio Claudio , Negro Francesco , Latronico Nicola , Piva Simone 
Published: November 2023

IntroductionLong-term weakness is common in survivors of COVID-19-associated acute respiratory distress syndrome (CARDS). We longitudinally assessed the predictors of muscle weakness in patients evaluated 6 and 12 months after intensive care unit discharge with in-person visits.MethodsMuscle strength was measured by isometric maximal voluntary contraction (MVC) of the tibialis anterior muscle. Candidate predictors of muscle weakness were follow-up time, sex, age, mechanical ventilation duration, use of steroids in the intensive care unit, the compound muscle action potential of the tibialis anterior muscle (CMAP-TA-S100), a 6-min walk test, severe fatigue, depression and anxiety, post-traumatic stress disorder, cognitive assessment, and body mass index. We also compared the clinical tools currently available for the evaluation of muscle strength (handgrip strength and Medical Research Council sum score) and electrical neuromuscular function (simplified peroneal nerve test [PENT]) with more objective and robust measures of force (MVC) and electrophysiological evaluation of the neuromuscular function of the tibialis anterior muscle (CMAP-TA-S100) for their essential role in ankle control.ResultsMVC improved at 12 months compared with 6 months. CMAP-TA-S100 (P = 0.016) and the presence of severe fatigue (P = 0.036) were independent predictors of MVC. MVC was strongly associated with handgrip strength, whereas CMAP-TA-S100 was strongly associated with PENT.DiscussionElectrical neuromuscular abnormalities and severe fatigue are independently associated with reduced MVC and can be used to predict the risk of long-term muscle weakness in CARDS survivors.
MRI-based radiomics features uncover the micro-change of dorsal root ganglia lesion for patients with post-herpetic neuralgia
Authors: Cao Xueqin , Wen Donglin , Yu Shangchen , Zheng Hua , Wu Gang , Zhang Xianwei 
Published: November 2023

ObjectiveTo create and authenticate MRI-based radiomic signatures to identify dorsal root ganglia (DRG) lesions in post-herpetic neuralgia (PHN) patients generalizable and interpretable.MethodThis prospective diagnostic study was conducted between January 2021 and February 2022. Lesioned DRG in patients with PHN and normal DRG in age-, sex-, height-, and weight-matched healthy controls were selected for assessment and divided into two groups (8:2) randomly: training and testing sets. The least absolute shrinkage and selection operator algorithm was employed to generate feature signatures and construct a model, followed by the assessment of model efficacy using the area under the curve (AUC) of the receiver operating characteristic (ROC), as well as sensitivity and specificity metrics.ResultsThe present investigation involved 30 patients diagnosed with postherpetic neuralgia (PHN), consisting of 18 males and 12 females (mean age 60.70 ± 10.18 years), as well as 30 healthy controls, comprising 18 males and 12 females (mean age 58.13 ± 10.54 years). A total of 98 DRG were randomly divided into two groups (8:2), namely a training set (n = 78) and a testing set (n = 20). Five radiomic features were chosen to construct the models. In the training dataset, the area under the curve (AUC) was 0.847, while the sensitivity and specificity were 71.79 and 97.44%, respectively. In the test dataset, the AUC was 0.87, and the sensitivity and specificity were 80.00 and 100.00%, respectively.ConclusionAn MRI-based radiomic signatures model has the capacity to uncover the micro-change of damaged DRG in individuals afflicted with postherpetic neuralgia.
The influence of environmental risk factors in the development of ALS in the Mediterranean Island of Cyprus
Authors: Mitsi Ellie , Christodoulou Christiana C. , Nicolaou Paschalis , Christodoulou Kyproula , Zamba-Papanicolaou Eleni 
Published: November 2023

IntroductionAmyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disease of motor neurons, presenting with relentlessly progressive muscle atrophy and weakness. The etiology of ALS remains unexplained for over 85% of all cases, suggesting that besides the genetic basis of the disease, various environmental factors are implicated in the pathogenesis of ALS. This study aimed to investigate the contribution of known environmental risk factors of ALS in the Cypriot population.MethodsWe conducted a case–control study with a total of 56 ALS cases and 56 healthy gender/age-matched controls of Cypriot nationality. Demographic, lifestyle characteristics, medical conditions, and environmental exposures were collected through the use of a detailed questionnaire. Statistical analyses using the R programming language examined the association between the above environmental factors and ALS.ResultsA chi-square test analysis revealed a statistically significant (p = 0.000461) difference in smoking status between the two groups. In addition, univariate logistic regression analysis showed a statistically significant association between ALS cases for head trauma/injury (p = 0.0398) and exposure to chemicals (p = 0.00128), compared to controls.ConclusionThis case–control investigation has shed some light on the epidemiological data of ALS in Cyprus, by identifying environmental determinants of ALS, such as smoking, head trauma, and chemical exposure, in the Cypriot population.
Neck stabilization through sensory integration of vestibular and visual motion cues
Authors: Happee Riender , Kotian Varun , De Winkel Ksander N. 
Published: November 2023

BackgroundTo counteract gravity, trunk motion, and other perturbations, the human head–neck system requires continuous muscular stabilization. In this study, we combine a musculoskeletal neck model with models of sensory integration (SI) to unravel the role of vestibular, visual, and muscle sensory cues in head–neck stabilization and relate SI conflicts and postural instability to motion sickness.MethodA 3D multisegment neck model with 258 Hill-type muscle elements was extended with postural stabilization using SI of vestibular (semicircular and otolith) and visual (rotation rate, verticality, and yaw) cues using the multisensory observer model (MSOM) and the subjective vertical conflict model (SVC). Dynamic head–neck stabilization was studied using empirical datasets, including 6D trunk perturbations and a 4 m/s2 slalom drive inducing motion sickness.ResultsRecorded head translation and rotation are well matched when using all feedback loops with MSOM or SVC or assuming perfect perception. A basic version of the model, including muscle, but omitting vestibular and visual perception, shows that muscular feedback can stabilize the neck in all conditions. However, this model predicts excessive head rotations in conditions with trunk rotation and in the slalom. Adding feedback of head rotational velocity sensed by the semicircular canals effectively reduces head rotations at mid-frequencies. Realistic head rotations at low frequencies are obtained by adding vestibular and visual feedback of head rotation based on the MSOM or SVC model or assuming perfect perception. The MSOM with full vision well captures all conditions, whereas the MSOM excluding vision well captures all conditions without vision. The SVC provides two estimates of verticality, with a vestibular estimate SVCvest, which is highly effective in controlling head verticality, and an integrated vestibular/visual estimate SVCint which can complement SVCvest in conditions with vision. As expected, in the sickening drive, SI models imprecisely estimate verticality, resulting in sensory conflict and postural instability.ConclusionThe results support the validity of SI models in postural stabilization, where both MSOM and SVC provide credible results. The results in the sickening drive show imprecise sensory integration to enlarge head motion. This uniquely links the sensory conflict theory and the postural instability theory in motion sickness causation.
Case report and literature review: exploration of molecular therapeutic targets in recurrent malignant meningioma through comprehensive genetic analysis with Todai OncoPanel
Authors: Ohara Kenta , Miyawaki Satoru , Nakatomi Hirofumi , Okano Atsushi , Teranishi Yu , Shinya Yuki , Ishigami Daiichiro , Hongo Hiroki , Takayanagi Shunsaku , Tanaka Shota , Shinozaki-Ushiku Aya , Kohsaka Shinji , Kage Hidenori , Oda Katsutoshi , Miyagawa Kiyoshi , Aburatani Hiroyuki , Mano Hiroyuki , Tatsuno Kenji , Saito Nobuhito 
Published: November 2023

BackgroundDespite accumulating research on the molecular characteristics of meningiomas, no definitive molecularly targeted therapy for these tumors has been established to date. Molecular mechanisms underlying meningioma progression also remain unclear. Comprehensive genetic testing approaches can reveal actionable gene aberrations in meningiomas. However, there is still limited information on whether profiling the molecular status of subsequent recurrent meningiomas could influence the choice of molecular-targeted therapies.Case presentationWe report a case of meningioma with malignant progression and multiple recurrences. We performed matched tumor pair analysis using the Todai OncoPanel to investigate the possibility of additional standard treatments. The loss of several chromosomal regions, including NF2 and CDKN2A, which is associated with aggressive meningiomas, was considered a significant driver event for malignant progression. Using additional matched tumor pair analysis, mutations in TRAF7, ARID1A, and ERBB3 were identified as subclonal driver events at the time of recurrence. No genetic aberrations were found for which evidence-based targeted therapy was applicable. We also reviewed previous reports of molecular therapies in meningioma to discuss issues with the current molecular testing approach.ConclusionGene panel testing platforms such as the Todai OncoPanel represent a powerful approach to elucidate actionable genetic alterations in various types of tumors, although their use is still limited to the diagnosis and prediction of prognosis in meningiomas. To enable targeted molecular therapy informed by gene-panel testing, further studies including matched tumor pair analyses are required to understand the molecular characteristics of meningiomas and develop treatments based on genetic abnormalities.
Adaptive yoga versus low-impact exercise for adults with chronic acquired brain injury: a pilot randomized control trial protocol
Authors: Stephens Jaclyn A. , Hernandez-Sarabia Jesus A. , Sharp Julia L. , Leach Heather J. , Bell Christopher , Thomas Michael L. , Burzynska Agnieszka , Weaver Jennifer A. , Schmid Arlene A. 
Published: November 2023

BackgroundEach year, millions of Americans sustain acquired brain injuries (ABI) which result in functional impairments, such as poor balance and autonomic nervous system (ANS) dysfunction. Although significant time and energy are dedicated to reducing functional impairment in acute phase of ABI, many individuals with chronic ABI have residual impairments that increase fall risk, decrease quality of life, and increase mortality. In previous work, we have found that yoga can improve balance in adults with chronic (i.e., ≥6 months post-injury) ABI. Moreover, yoga has been shown to improve ANS and brain function in healthy adults. Thus, adults with chronic ABI may show similar outcomes. This protocol details the methods used to examine the effects of a group yoga program, as compared to a group low-impact exercise, on primary and secondary outcomes in adults with chronic ABI.MethodsThis study is a single-blind randomized controlled trial comparing group yoga to group low-impact exercise. Participants must be ≥18 years old with chronic ABI and moderate balance impairments. Group yoga and group exercise sessions occur twice a week for 1 h for 8 weeks. Sessions are led by trained adaptive exercise specialists. Primary outcomes are balance and ANS function. Secondary outcomes are brain function and structure, cognition, quality of life, and qualitative experiences. Data analysis for primary and most secondary outcomes will be completed with mixed effect statistical methods to evaluate the within-subject factor of time (i.e., pre vs. post intervention), the between-subject factor of group (yoga vs. low-impact exercise), and interaction effects. Deductive and inductive techniques will be used to analyze qualitative data.DiscussionDue to its accessibility and holistic nature, yoga has significant potential for improving balance and ANS function, along with other capacities, in adults with chronic ABI. Because there are also known benefits of exercise and group interaction, this study compares yoga to a similar, group exercise intervention to explore if yoga has a unique benefit for adults with chronic ABI.Clinical trial registration:ClinicalTrials.gov, NCT05793827. Registered on March 31, 2023.