bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding Bilateral Motor Coordination in Stroke Using the Towel Folding Task: An Exploratory Biomechanical Study
Authors: Wu Jingyi , Kwong Patrick Wai-Hang , Sidarta Ananda , Zhang Jack Jiaqi , Zhuang Jingwen , Li Yining , Fong Kenneth NK 
Published: September 2024

AbstractObjectivesCoordination deficits in bilateral upper limbs make daily activities more difficult for stroke survivors. Previous studies showed worse kinematics during unilateral tasks compared to healthy individuals, but this was unclear for bimanual tasks. We aim to assess the potential of the towel folding task from the Wolf Motor Function Assessment as a measure of bimanual control by examining kinematic differences between stroke survivors and healthy individuals and correlating these differences with clinical parameters in the stroke group.MethodsThis was a cross-sectional design. Seventeen people with stroke and sixteen healthy individuals participated. Vicon motion capture obtained kinematics of bilateral upper limbs during the task, including movement time, initiation delay, velocity, trunk displacement, smoothness, and inter-/intra-limb coordination. Statistical analyses compared groups and correlated kinematic variables with clinical parameters.ResultsStroke survivors had longer movement times (P< .001, Cohen’s d = 1.396), slower initiation (P< .001, Cohen’s d = 0.797), lower max velocity (P= .026, Cohen’s d = −.815;P< .001, Cohen’s d = −2.156; andP= .005, Cohen’s d = −.736; respectively), greater trunk displacement (P< .001, Cohen’s d = 2.173 andP< .001, Cohen’s d = 1.727, respectively), less smoothness (P= .031, Cohen’s d = 0.883 andP< .001, Cohen’s d = .725, respectively), and altered inter-/intra-limb coordination. Regarding bilateral elbow-elbow coordination, stroke group exhibited decreased in-phase patterns (P< .001, partial η² = .368) and increased anti-phase and non-hemiplegic elbow dominancy patterns (P= .001, partial η² = .298 andP= .004, partial η² = .244, respectively). Regarding bilateral shoulder-shoulder coordination, stroke group showed decreased hemiplegic shoulder leading patterns (P= .010, partial η² = .196) and increased anti-phase and non-hemiplegic shoulder dominancy patterns (P= .001, partial η² = .315 andP< .001, partial η² = .463, respectively). For hemiplegic shoulder-elbow coordination, stroke group showed decreased anti-phase patterns (P< .001, partial η² = .382) and increased elbow dominancyPatterns (P< .001, partial η² = .324). Fugl-Meyer Assessment scores positively correlated with smoothness and hemiplegic shoulder-elbow coordination (r = −.500,P= .039 and r = .600,P= .010, respectively), while Action Research Arm Test scores negatively correlated with movement initiation delay (r = −.600,P= .010).ConclusionsThis study enhances understanding of the folding towel task and may provide metrics to quantify bilateral coordination task performance in stroke survivors.
In-cell architecture of the mitochondrial respiratory chain
Authors: Waltz Florent , Righetto Ricardo D. , Kelley Ron , Zhang Xianjun , Obr Martin , Khavnekar Sagar , Kotecha Abhay , Engel Benjamin D. 
Published: September 2024

AbstractMitochondria produce energy through oxidative phosphorylation, carried out by five membrane-bound complexes collectively known as the respiratory chain. These complexes work in concert to transfer electrons and pump protons, leading to ATP regeneration. The precise organization of these complexes in native cells is debated, notably their assembly into higher-order supercomplexes called respirasomes. Here, we usein situcryo-electron tomography to visualize the native structures and organization of several major mitochondrial complexes insideChlamydomonas reinhardtiicells. ATP synthases and respiratory complexes are segregated into curved and flat crista membrane domains, respectively. Respiratory complexes I, III, and IV assemble into a single type of respirasome, from which we determined a native 5 Å-resolution structure showing the binding of electron carrier cytochromec. Combined with single-particle cryo-electron microscopy reconstruction at 2.4 Å resolution, we assemble a detailed model of how the respiratory complexes interact with each other inside native mitochondria.
Integrin-activating Yersinia protein Invasin sustains long-term expansion of primary epithelial cells as 2D organoid sheets
Authors: Wijnakker Joost J.A.P.M. , van Son Gijs J. F. , Krueger Daniel , van de Wetering Willine , Lopez-Iglesias Carmen , Schreurs Robin , van Rijt Fenna , Lim Sangho , Lin Lin , Peters Peter J. , Isberg Ralph R. , Yanda Claudia , de Lau Wim , Clevers Hans 
Published: September 2024

AbstractMatrigel/BME, a basement membrane-like preparation, supports long-term growth of epithelial 3D organoids from adult stem cells (ASC)1,2. Here, we show that interaction between Matrigel’s major component Laminin111 with epithelial α6β1-integrin is crucial for this process. The outer membrane protein Invasin ofYersiniais known to activate multiple integrin-β1 complexes, including integrin-α6β1. A C-terminal integrin-binding fragment of Invasin, coated on culture plates, mediated gut epithelial cell adhesion. Addition of organoid growth factors allowed multi-passage expansion in 2D. Polarization, junction formation and generation of enterocytes, goblet cells, Paneth cells, and enteroendocrine cells was stable over time. Sustained expansion of other human-, mouse-, and even snake epithelia was accomplished under comparable conditions. The 2D ‘organoid sheet’ format holds advantages over the 3D ‘in gel’ format in terms of imaging, accessibility of basal and apical domains and automation for high throughput screening. Invasin represents a fully defined, affordable, versatile, and animal-free complement to Matrigel/BME.
A workflow for practical training in ecological genomics using Oxford Nanopore long-read sequencing
Authors: Foster Robert , Weerd Heleen De , Medd Nathan , Booth Tim , Newman Caitlin , Ritch Helen , Santoyo-Lopez Javier , Trivedi Urmi , Twyford Alex D. 
Published: September 2024

AbstractLong-read single molecule sequencing technologies continue to grow in popularity for genome assembly and provide an effective way to resolve large and complex genomic variants. However, uptake of these technologies for teaching and training is hampered by the complexity of high molecular weight DNA extraction protocols, the time required for library preparation and the costs for sequencing, as well as challenges with downstream data analyses. Here, we present a full long-read workflow optimised for teaching, that covers each stage from DNA extraction, to library preparation and sequencing, to data QC and genome assembly and characterisation, that can be completed in under two weeks. We use a specific case study of plant identification, where students identify an anonymous plant sample by sequencing and assembling the genome and comparing it to other samples and to reference databases. In testing, long-read genome skimming of nine wild-collected plant species extracted with a modified kit-based approach produced an average of 8Gb of Oxford Nanopore data, enabling the complete assembly of plastid genomes, and partial assembly of nuclear genomes. In the classroom, all students were able to complete the protocols, and to correctly identify their plant samples based on BOLD searches of barcoding loci extracted from the plastid genome, coupled with phylogenetic analyses of whole plastid genomes. We supply all the learning material and raw data allowing this to be adapted to a range of teaching settings.
Compensatory role of KatG in defending H2O2stress inmsrdeletion strain ofSalmonellaTyphimurium
Authors: Lalhmangaihzuali Lalhmangaihzuali , Upreti Suchitra , Sahoo Raj , Chauhan Tapan Kumar Singh , Mahawar Manish 
Published: September 2024

AbstractKatG and Msrs are important enzymes associated with ROS homeostasis and bacterial survival under oxidative stress. Consistent to this notion, mutant strains in these enzymes showed hypersensitivity to oxidants and accumulates elevated levels of ROS. In current study we observed that a panmsrdeletion (Δ5msrmutant) strain ofS.Typhimurium accumulates significantly higher levels of ROS. However, unexpectedly, as compared toS.Typhimurium, the Δ5msrmutant strain exhibits more than 2000 folds resistance to H2O2. Transcriptional and mass spectrometry analyses reveal the upregulation of KatG in Δ5msrmutant strain. Further, Δ5msrmutant strain exhibits ∼6 folds higher KatG activity. Supplementation of Δ5msrmutant culture with reduced glutathione resulted in ROS neutralization, decreased KatG activity and abrogation of H2O2resistance. However, Δ5msrmutant strain showed negligible KatE and KatN activities. The findings of current study suggest that theSalmonellahave evolved the mechanism to upregulate one antioxidant gene in absence of others to mitigate oxidative stress.
The Aquaporin-4 expression and localization in the olfactory epithelium modulate the odorant-evoked responses and olfactory driven behavior
Authors: Lobraico Donatella , Abbrescia Pasqua , Fioriello Maria Grazia , Barile Barbara , Palazzo Claudia , Valente Onofrio , Nicchia Grazia Paola , Dibattista Michele , Frigeri Antonio 
Published: September 2024

AbstractAquaporin-4 (AQP4) is a water-selective channel expressed in glial cells throughout the central nervous system. It serves as the main water channel in the neuropil, and is involved in various physiological functions, ranging from regulating water homeostasis by adjusting cell volume to modulating neuronal activity. Different isoforms of AQP4 are expressed in glial-like cells known as sustentacular cells (SUSs) of the olfactory epithelium (OE). Interestingly, mice lacking all AQP4 isoforms exhibit impaired olfactory abilities. Hence, we aim to uncover the physiological role of two AQP4 isoforms, the perivascular AQP4ex isoform and the Orthogonal Array of Particle (OAP)-forming isoform (AQP4M23) in the OE. Primarily, we investigated the impact of AQP4 isoforms on OE protein expression, finding reduced levels of mature olfactory sensory neurons (OSNs) in mice lacking AQP4ex (AQP4ex-KO) or OAPs (OAP-null). Moreover, the reduced number of OSNs, SUSs, and globose basal cells (GBCs) suggests that AQP4 isoforms are involved in maintaining an optimal microenvironment in the OE, preserving the overall cell density. Then, we explored the role of AQP4 in modulating odorant-evoked responses through electro-olfactogram recordings, finding reduced odorant responses in mice lacking AQP4 isoforms. Olfactory ability assessments revealed deficits in odor-guided food-seeking test in AQP4ex-KO and OAP-null mice. Furthermore, AQP4ex-KO mice showed a reduced ability to discriminate between different odorants, while OAP-null mice were unable to recognize them as distinct. Overall, our data highlight the role of AQP4 isoforms in modulating neuronal homeostasis, affecting odorant-evoked responses and cell density in the OE. These results shed light on SUSs involvement in mediating these processes and establish a foundation for further understanding their role in controlling OE physiology.
Pre and Post antibiotic epoch: insights into the historical spread of antimicrobial resistance
Authors: Cazares Adrian , Figueroa Wendy , Cazares Daniel , Lima Leandro , Turnbull Jake D. , McGregor Hannah , Dicks Jo , Alexander Sarah , Iqbal Zamin , Thomson Nicholas R. 
Published: September 2024

AbstractPlasmids are now the primary vectors of antimicrobial resistance, but our understanding of how human industrialisation of antibiotics influenced this is limited by a paucity of data predating the antibiotic era (PAE). By investigating plasmids from clinically relevant bacteria isolated between 1917 and 1954 and comparing them to modern plasmids, we captured over 100 years of evolution. We show that while all PAE plasmids were devoid of resistance genes and most never acquired them, a small minority evolved to drive the global spread of resistance to first-line and last-resort antibiotics in Gram-negative bacteria. They have evolved through complex microevolution and fusion events into a distinct group of highly recombinogenic, multi-replicon, self-transmissible plasmids that now pose the highest risk to resistance dissemination, and therefore human health.One Sentence SummaryPre-antibiotic era bacteria reveal the origin and evolution of drug-resistance vectors.
Sensory context of initiation-cue modulates action goal-relevant neural representations
Authors: Kreter Nicholas , Dundon Neil M. , Smith Jolinda , Marneweck Michelle 
Published: September 2024

AbstractThe ability to produce goal-directed movement relies on the integration of diverse sources of sensory information specific to the task goal. Neural representations of goal-relevant features, such as target location and gaze direction, have been well studied in sensorimotor areas. It remains less clear whether goal-relevant motor representations are influenced by sensory changes to initiation-relevant information, such as a go-cue that provides no information about target location. We used Bayesian pattern component modelling of fMRI data during a delayed reach task with either visual or audiovisual go-cues to explore whether neural representations of goal-related features in sensorimotor areas are modulated by changes to initiation-relevant sensory information. We found that representations of target direction and gaze direction in the primary sensory areas, motor areas, and posterior parietal cortex, were sensitive to whether a reach was cued with a visual or audiovisual go-cue. These findings indicate that the central nervous system flexibly delegates the tasks of ‘where’ to move and ‘when’ to move based on available sensory context, even if initiation-relevant stimuli provide no additional information about target location.
Circadian meal timing is heritable and associated with insulin sensitivity
Authors: Vahlhaus Janna , Peters Beeke , Hornemann Silke , Ost Anne-Cathrin , Kruse Michael , Busjahn Andreas , Pfeiffer Andreas F.H. , Pivovarova-Ramich Olga 
Published: September 2024

AbstractBackgroundAlthough the contribution of the circadian clock to metabolic regulation is widely recognized, the role of meal timing in glucose metabolism and diabetes risk remains insufficiently studied. This study aimed (i) to investigate the link between individual circadian meal timing pattern and glucose homeostasis and (ii) to explore the contribution of genetic and environmental factors to meal timing parameters.MethodsIn the German NUtriGenomic Analysis in Twins (NUGAT) cohort, which includes 92 adult twins, glucose metabolism parameters were assessed using fasting samples and the oral glucose tolerance test (OGTT). Parameters of meal timing pattern (meal timing itself, daily calorie distribution, and meal number) were extracted from five-day food records. Circadian eating timing was determined relative to the individual’s chronotype (MSFsc) assessed by the Munich chronotype questionnaire. The heritability of meal timing components was estimated using the ACE model.ResultsMultiple meal timing components showed associations with glucose metabolism parameters. Most associations were found for the calorie midpoint defined as the time point at which 50% of daily calories were consumed. Indices of insulin sensitivity, ISI Stumvoll (β = 0.334, p = 2.9 x 10-4) and HOMA-IR (β = -0.276, p = 0.007), as well as fasting insulin levels were significantly associated with the circadian caloric midpoint even after the model adjustment for gender, age, energy intake, and sleep duration. BMI and waist circumference also demonstrated robust associations with circadian caloric midpoint. High or moderate heritability was shown for all meal timing components. Meal timing pattern was also strongly related to individual sleep timing and chronotype, both of which also showed a marked genetic impact.ConclusionCircadian meal timing is associated with insulin sensitivity and shows significant genetic influences, sharing a common genetic architecture with sleep behaviour. Shifting the main calorie intake to earlier circadian time might protect against diabetes, although this could be challenging due to the high heritability of meal timing components.Graphical abstractHighlightsCircadian caloric midpoint shows a robust association with insulin sensitivityIt remains significant after the adjustment for energy intake and other cofoundersMeal timing, daily calorie distribution, and meal number show a high or moderate heritabilityMeal timing strongly relates to the sleeping behaviour and chronotype
Effect of maximum voluntary isometric contraction of the triceps surae muscle on a subsequent drop jump
Authors: Ino Taiki , Ogawara Keita , Uchiyama Shuichi , Endo Shinya , Miyazaki Seiji , Yamada Hiroshi 
Published: September 2024

ABSTRACTPurposePre-muscle contraction improves sports performance because post-activation potentiation (PAP), induced by a previous intense voluntary contraction (conditioning contraction), amplifies the subsequent target muscle contraction. This study aims to examine the influence of conditioning contraction on the performance of ballistic motion, particularly on the stretch-shortening cycle (SSC).MethodsFourteen male university students specializing in athletic jumping events performed a drop jump from a height of 0.3 m. Maximal voluntary isometric plantarflexion for 6 seconds was considered a conditioning contraction. We set two conditions: in the PAP condition, participants performed a conditioning contraction 10 s before the drop jump, and in the control condition, they simply performed the drop jump. After 10 minutes of rest from the reference drop jump, both conditions were performed. A 3D motion analysis system, force plates, and surface electromyography were used to record the jump data.ResultsIn the PAP conditions, the jump height and velocity of the center of gravity increased by 4 cm and 14 cm/s, respectively. Lower limb torque increment was observed only in the ankle joint between the PAP and control conditions (0.31 Nm/kg). However, there was no change in the magnitude of muscle activity based on the electromyogram.ConclusionOur study showed that PAP could potentiate the contraction mechanism under excitation-contraction coupling, irrespective of the effect on the central nervous system. Therefore, PAP enhances jump performance by improving SSC.
Deep Learning Model and Multi Modal Late Fusion For Predicting Adverse Events Following Cardiothoracic Surgery in the ICU Using STS Data and Time Series Intraoperative Data
Authors: Korutla Rajashekar , Hicks Anne , Milosevic Marko , Kulkarni Dipti , Mazhude Felistas , Mortazawy Mehdi , Seyed Vahedein Yashar , Kelting Tyler , Rabib Jaime B , Jin Qingchu , Kramer Robert , Sawyer Douglas , Winslow Raimond L , Amal Saeed 
Published: September 2024

AbstractAccurate prediction of post-operative adverse events following cardiothoracic surgery is crucial for timely interventions, potentially improving patient outcomes and reducing healthcare costs. By leveraging advanced deep learning techniques, this study highlights the transformative potential of incorporating intraoperative variables into predictive analytics models to enhance postoperative care for cardiothoracic surgery patients in the ICU. We developed deep learning predictive models for anticipating adverse events in patients following cardiothoracic surgery using a dataset from the Society of Thoracic Surgeons’ database (4) and intraoperative data. Our models perform late fusion by integrating static patient data and intra-operative time-series data, utilizing Fully Connected Neural Networks (FCNN) and long short-term memory (LSTM) networks, respectively. The hybrid model was validated through five-fold cross-validation, demonstrating robust performance with a mean AUC of 0.93, Sensitivity of 0.83 and Specificity of 0.89. This work represents a significant step forward in the proactive management of cardio thoracic surgery patients in the ICU by effectively predicting potential adverse events associated with mortality in the post operative period.
Improving Individualized Rhabdomyosarcoma Prognosis Predictions Using Somatic Molecular Biomarkers
Authors: Zobeck Mark , Khan Javed , Venkatramani Rajkumar , Okcu M. Fatih , Scheurer Michael E. , Lupo Philip J. 
Published: September 2024

AbstractPurposeMolecular markers, such asFOXO1fusion genes andTP53andMYOD1mutations, increasingly influence risk-stratified treatment selection for pediatric rhabdomyosarcoma (RMS). This study aims to integrate molecular and clinical data to produce individualized prognosis predictions that can further improve treatment selection.Patients and MethodsClinical variables and somatic mutation data for 20 genes from 641 RMS patients in the United Kingdom and the United States were used to develop three Cox proportional hazard models for predicting event-free survival (EFS). The ‘Baseline Clinical’ (BC) model included treatment location, age, fusion status, and risk group. The ‘Gene Enhanced 2’ (GE2) model addedTP53andMYOD1mutations to the BC predictors. The ‘Gene Enhanced 6’ (GE6) model further includedNF1,MET,CDKN2A, andMYCNmutations, selected through LASSO regression. Model performance was assessed using likelihood ratio (LR) tests and optimism-adjusted, bootstrapped validation and calibration metrics.ResultsThe GE6 model demonstrated superior predictive performance, offering 39% more predictive information than the BC model (LR p<0.001) and 15% more than the GE2 model (LR p<0.001). The GE6 model achieved the highest discrimination with a C-index of 0.7087, a Nagalkerke R2of 0.205, and appropriate calibration. Mutations inTP53,MYOD1,CDKN2A,MET, andMYCNwere associated with higher hazards, while NF1 mutation correlated with lower hazard. Individual prognosis predictions varied between models in ways that may suggest different treatments for the same patient. For example, the 5-year EFS for a 10-year-old patient with high-risk, fusion-negative,NF1-positive disease was 50.0% (95% confidence interval: 39-64%) from BC but 76% (64-90%) from GE6.ConclusionIncorporating molecular markers into RMS prognosis models improves prognosis predictions. Individualized prognosis predictions may suggest alternative treatment regimens compared to traditional risk-classification schemas. Improved clinical variables and external validation are required prior to implementing these models into clinical practice.
Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls
Authors: Muir Ryan T. , Stukas Sophie , Cooper Jennifer G. , Beaudin Andrew E. , McCreary Cheryl R. , Gee Myrlene , Nelles Krista , Nukala Nikita , Valencia Janina , Kirmess Kristopher M , Black Sandra E. , Hill Michael D. , Camicioli Richard , Wellington Cheryl L. , Smith Eric. E 
Published: September 2024

ABSTRACTINTRODUCTIONCerebral Amyloid Angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ42/40,phosphorylated-tau (p-tau), neurofilament light chain (NfL) and Glial Fibrillary Acidic Protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls.METHODSPlasma Aβ42/40,p-tau-181, NfL and GFAP were quantified using Simoa and Aβ42/40was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS).RESULTS45 participants with CAA and 47 healthy controls had available plasma. Aβ42/40ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ42/40(Simoa), p-tau-181, and NfL resulted in an AUC of 0.90 (95% CI: 0.80, 0.95).DISCUSSIONPlasma Aβ42/40, p-tau-181 and NfL differ in those with CAA and together can discriminate CAA from healthy controls.