bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Acupuncture on Lower Limb Motor Dysfunction Following Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Chen Peng , Jin Xing , Yu Debiao , Chen Xiaotin , Lin Yaoyu , Wu Fuchun , Shao Bin 
Published: October 2024

AbstractBackgroundAcupuncture is widely used for Lower Limb Motor Dysfunction Following Stroke (LLMD) in China but its effect is unclear. We aim to evaluate the effect of acupuncture for LLMD.MethodsWe searched eight databases, including PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang, VIP, and CBM, up to December 2023. Randomized controlled trials on acupuncture therapy for LLMD after stroke were enrolled in this study. Outcome measures comprised motor function, balance function, walking ability, and daily living activities. Two researchers conducted independent literature screening, data extraction, and quality assessment in accordance with Cochrane Collaboration network’s standards. Review Manager 5.3 and Stata 17.0 were used in data analysis. Results were presented as mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (95% CI).ResultsTwelve studies involving 1318 patients, most of which showed low or unclear risk of bias, were included in this review. Meta-analysis results indicate that compared with conventional treatment, acupuncture intervention can improve scores in Fugl–Meyer Assessment for lower scale (SMD=0.41, 95% CI (−0.92, –0.04), Z=2.16, P =.03), Berg Balance Scale (SMD=-0.86, 95%CI (−1.65, –0.07), Z=2.14, P=.03), Functional Ambulation Category scale (SMD=-0.74, 95%CI (−2.33, 0.84), Z=0.92, P=.36), and Modified Barthel Index Scale (SMD=0.27, 95%CI (−0.30, 0.84), Z=0.94, P=.35).ConclusionThe results of this study suggest that acupuncture combined rehabilitation training may be more effective than pure treatment in improving LLMD, balance function, walking ability, and daily living activities after stroke. Despite limitations due to the low quality of the included studies and methodological constraints, acupuncture combined rehabilitation training may serve as an effective approach for the treatment of LLMD poststroke.
The association between medical accessibility and glycemic status in patients with type 2 diabetes mellitus: A retrospective study in Taiwan rural population
Authors: Sun Chong-Fong , Pan Bo-Lin , Wang Pei-Ming , Huang Kun-Siang , Lu Yueh-Chien , Kung Hsin-Yi , Chiang Jui-Chin 
Published: October 2024

AbstractIntroductionType 2 diabetes mellitus represents a significant chronic health concern, with rural populations being particularly vulnerable due to geographic and socio-economic barriers to healthcare access. To date, few studies have focused on the medical accessibility of rural diabetic patients in Taiwan. This study aims to explore the association between the proximity to healthcare facilities and glycohemoglobin levels in the rural Taiwanese population.MethodsWe conducted a retrospective cross-sectional study in rural districts of southern Taiwan. Medical accessibility was calculated from subject’s address to medical units by Google Maps platform. Spearman’s Rank Analysis was performed for the correlation between distance from patient’s address to medical units and glycohemoglobin level. Logistic regression was applied to identify factors associated with glycemic control.ResultsIn total, 117 patients with type 2 diabetes mellitus were enrolled (mean glycohemoglobin: 8.17±1.92%). Glycohemoglobin level was modestly and positively associated with distance to clinic (Rho: 0.252) and hospital (Rho: 0.241) respectively. In logistic regression analysis, good glycemic control (glycohemoglobin less than 7%) was associated with covariates as not-working status, the address district near downtown, fasting plasma glucose equal to or less than 130 mg/dL, and normal high-density lipoprotein cholesterol level.ConclusionOur study reveals that accessibility to healthcare facility is modestly correlated with long-term glycemic status in Taiwan rural diabetic population. Besides, we also identified several protective factors associated with chronic glycemic status. These findings may pave the way for improvement of policy and healthcare strategies in rural diabetic care.
MRI signature of brain age underlying post- traumatic stress disorder in World Trade Center responders
Authors: Invernizzi Azzurra , La Rosa Francesco , Sather Anna , Rechtman Elza , Jalees Maryam , Nabeel Ismail , Pellecchia Alison C. , Santiago-Michels Stephanie , Bromet Evelyn J. , Lucchini Roberto G. , Luft Benjamin J. , Clouston Sean A. , Beck Erin S , Tang Cheuk Y. , Horton Megan K. 
Published: October 2024

AbstractThe men and women involved in rescue and recovery operations at the 9/11 World Trade Center (WTC) site have a greater prevalence (23%) of persistent, clinically significant post- traumatic stress disorder (PTSD). Recent structural and functional magnetic resonance imaging (MRI) studies demonstrate significant neural differences between WTC responders with and without PTSD. Here, we used brain age, a novel MRI-based data-driven biomarker optimized to detect accelerated structural aging, and examined the impact of PTSD on this process. Using BrainAgeNeXt, a novel convolutional neural network trained and validated on 11,574 magnetic resonance imaging (MRI) T1- weighted scans, we predicted brain age in WTC responders with PTSD (WTC-PTSD,n= 47) and age/sex matched responders without PTSD (non-PTSD,n= 52). Predicted Age Difference (PAD) was then calculated for each WTC responder by subtracting chronological age from brain age. A positive PAD indicates that the responder’s brain is aging faster than expected for their chronological age. We found that PAD is significantly greater with WTC-PTSD compared to non-PTSD responders (p< 0.001). Further, we found that WTC exposure duration (months working on site) moderates the association between PTSD and PAD (p=0.0050). Our results suggested that brain age is a valid biomarker to compare aging trajectories in responders with and without PTSD. In particular, PTSD may be a substantial risk factor for accelerated neurodegeneration in this vulnerable and aging population.
Highly adaptive LASSO: Machine learning that provides valid nonparametric inference in realistic models
Authors: Butzin-Dozier Zachary , Qiu Sky , Hubbard Alan E. , Shi Junming (Seraphina) , van der Laan Mark J. 
Published: October 2024

AbstractUnderstanding treatment effects on health-related outcomes using real-world data requires defining a causal parameter and imposing relevant identification assumptions to translate it into a statistical estimand. Semiparametric methods, like the targeted maximum likelihood estimator (TMLE), have been developed to construct asymptotically linear estimators of these parameters. To further establish the asymptotic efficiency of these estimators, two conditions must be met: 1) the relevant components of the data likelihood must fall within a Donsker class, and 2) the estimates of nuisance parameters must converge to their true values at a rate faster thann−1/4. The Highly Adaptive LASSO (HAL) satisfies these criteria by acting as an empirical risk minimizer within a class ofcàdlàgfunctions with a bounded sectional variation norm, which is known to be Donsker. HAL achieves the desired rate of convergence, thereby guaranteeing the estimators’ asymptotic efficiency. The function class over which HAL minimizes its risk is flexible enough to capture realistic functions while maintaining the conditions for establishing efficiency. Additionally, HAL enables robust inference for non-pathwise differentiable parameters, such as the conditional average treatment effect (CATE) and causal dose-response curve, which are important in precision health. While these parameters are often considered in machine learning literature, these applications typically lack proper statistical inference. HAL addresses this gap by providing reliable statistical uncertainty quantification that is essential for informed decision-making in health research.
Circulating cardiovascular proteomic associations with genetics and disease
Authors: McGurk Kathryn A. , Curran Lara , Sau Arunashis , Ng Fu Siong , Halliday Brian , Ware James S. , O’Regan Declan P. 
Published: October 2024

AbstractBackgroundThe analysis of the circulating proteome can identify translational modifiers and biomarkers of disease expressivity and severity at a given time point. Here we explore the relationships between protein measures implicated in cardiovascular disease and whether they mediate causal relationships between cardiovascular risk factors and disease development.MethodsTo understand the relationships between circulating biomarkers and genetic variants, medications, anthropometric traits, lifestyle factors, imaging-derived measures, and diagnoses of cardiovascular disease, we analysed measures of nine plasma proteins witha prioriroles in genetic and structural cardiovascular disease or treatment pathways (ACE2, ACTA2, ACTN4, BAG3, BNP, CDKN1A, NOTCH1, NT-proBNP, and TNNI3) from the Pharma Proteomics Project of the UK Biobank cohort (over 45,000 participants sampled at recruitment).ResultsWe identified significant variability in circulating proteins with age, sex, ancestry, alcohol intake, smoking, and medication intake. Phenome-wide association studies highlighted the range of cardiovascular clinical features with relationships to protein levels. Genome-wide genetic association studies identified variants nearGCKR,APOE, andSERPINA1, that modified multiple circulating protein levels (BAG3, CDKN1A, and/or NOTCH1). NT-proBNP and BNP levels associated with variants inBAG3. ACE2 levels were increased with a diagnosis of hypertension or diabetes and were influenced by variants in genes associated with diabetes (HNF1A, HNF4A). Two-sample Mendelian randomisation identified ACE2 as protective for systolic blood pressure and Type-2 diabetes.ConclusionsFrom a panel of circulating proteins, the results from this observational study provide evidence that ACE2 is causally associated with hypertension and diabetes. This suggests that ACE2 stimulation may provide additional protection from these cardiovascular diseases. This study provides an improved understanding of the circulating pathways depicting cardiovascular disease dynamics.Graphical abstract
Global comparative structural analysis of responses to protein phosphorylation
Authors: Correa Marrero Miguel , Mello Victor Hugo , Sartori Pablo , Beltrao Pedro 
Published: October 2024

AbstractPost-translational modifications (PTMs), particularly protein phosphorylation, are key regulators of cellular processes, impacting numerous aspects of protein activity. Despite widespread phosphorylation of eukaryotic proteomes, the function of most phosphosites remains unknown. Elucidating the structural mechanisms underlying phosphorylation is crucial for understanding its regulatory roles. Here, we conducted a comparative structural analysis of phosphorylated and non-phosphorylated proteins taken from the Protein Data Bank (PDB). Our study systematically evaluates how phosphorylation affects backbone conformation, protein dynamics, and mechanical strain. We found that phosphorylation commonly induces small, stabilizing conformational changes through conformational selection and frequently modulates local residue fluctuations, influencing overall protein motion. Notably, a small but significant subset of phosphosites shows mechanical coupling with functional sites, aligning with the domino model of allosteric signal transduction. This work provides a foundation for studying phosphorylation and other PTMs in their structural context, which will guide the rational design of synthetic phosphosites and enable the engineering of PTM-driven regulatory circuits in synthetic biology.
Measurement and classification of bold-shy behaviours in medaka fish
Authors: Pierotti Saul , Brettell Ian , Fitzgerald Tomas , Herder Cathrin , Aadepu Narendar , Pylatiuk Christian , Wittbrodt Joachim , Birney Ewan , Loosli Felix 
Published: October 2024

AbstractMotivationBoldness-shyness is considered a fundamental axis of behavioural variation in humans and other species, with obvious adaptive causes and evolutionary implications. Besides an individual’s own genetics, this phenotype is also affected by the genetic makeup of peers in the individual’s social environment. To identify genetic determinants of variation along the bold-shy behavioural axis, a reliable experimental and analytical setup able to highlight direct and indirect genetic effects is needed.ResultsWe describe a custom assay designed to detect bold-shy behaviours in medaka fish, combining an open-field and novel-object component. We use this assay to explore direct and social genetic effects on the behaviours of 307 pairs of fish from five inbred medaka strains. Applying a Hidden Markov Model (HMM) to classify behavioural modes, we find that direct genetic effects influence the proportions of time the five strains spent in slow-moving states, explaining up to 29.7% of the variance in time spent in those states. We also found that an individual’s behaviour is influenced by the genetics of its tank partner, explaining up to 8.64% of the variance in the time spent in slow-moving states. Our behavioural assay in combination with the HMM analysis is applicable to follow-up genetic linkage studies of genetic variants involved in direct behavioural effects and indirect social genetic effects. A suitable genetic resource for such studies, the Medaka Inbred Kiyosu-Karlsruhe panel (MIKK) has recently been established.
Phosphorylation-dependent tuning of mRNA deadenylation rates
Authors: Stowell James A.W. , Yu Conny W.H. , Chen Zhuo A. , Lee Giselle , Morgan Tomos , Sinn Ludwig , Agnello Sylvie , O’Reilly Francis J. , Rappsilber Juri , Freund Stefan M.V. , Passmore Lori A. 
Published: October 2024

AbstractmRNA decay is a major determinant of gene regulation that is controlled through shortening of mRNA poly(A) tails by the Ccr4-Not complex. The specificity of deadenylation can be mediated through RNA adaptors – RNA-binding proteins that tether substrate mRNAs to Ccr4-Not in a regulated and context-specific manner. Interaction with Ccr4-Not is mediated by intrinsically disordered regions (IDRs) within the RNA adaptors. Due to the difficulty in studying large IDR-containing complexes, the determinants of specificity and their regulation remain unclear. Here we use structural biology and biochemical reconstitution to show that dispersed segments within IDRs of RNA adaptors bind to several distinct binding sites on Ccr4-Not through multivalent interactions. We further demonstrate that binding can be modulated by phosphorylation, altering the consequent deadenylation rate in a continuously tunable manner. This mechanism is broadly applicable in evolutionarily divergent IDRs from multiple RNA adaptors including fission yeast Puf3, and human Pumilio/PUM1 and Tristetraprolin/TTP. Together, our work suggests that multivalent interactions and phosphorylation represent conserved strategies for regulating gene expression. Thus, in response to cellular cues, mRNA decay can be regulated by a graded mechanism, rather than a bistable on/off switch, rationalizing how post-transcriptional gene expression is fine-tuned.
In vitrobiofilms ofClostridioides difficileundomesticated strains: Morphology and properties according to strain diversity
Authors: Lemaire Anaïs , Bridoux Ludovic , Costache Vlad , Crouzols Aline , Barbut Frédéric , Petry Sandrine , Poquet Isabelle 
Published: October 2024

AbstractClostridioides difficileis a Gram-positive, spore-forming, obligate anaerobe and an entero-pathogen representing a One Health problem.C. difficileinfections are difficult to treat and recurrences frequent.C. difficilebiofilms may play a role in persistence. We studied the biofilms formedin vitroby a collection ofC. difficileundomesticated strains (n=27, 20 toxigenic and 7 non-toxigenic) of 11 PCR-ribotypes (WRT) and isolated from equids. After growth in rich BHIS medium supplemented with glucose for 48h, the biomass of biofilms stained by crystal violet, i. e. adhesive to the surface, was measured, while intact biofilms were observedin situ, by confocal laser scanning microscopy, to determine their total biovolume and 3D morphology. All biofilms were relatively similar, even though adhesive, stained biofilms of non-toxigenic strains of ribotype 009 significantly displayed highest biomass. These results suggested that strains of ribotype 009 were able to form a highly cohesive and polystyrene-adhesive biofilm than any other strains. 8 common, representative ribotypes in equids, including 6 clinically important ribotypes in humans, were then selected and one strain chosen for each of them. Their biofilms and planktonic cultures grown under the same conditions were compared for sporulation, toxin production and susceptibility to vancomycin at a highly inhibitory concentration (8 MIC). In both the biofilm and planktonic culture of all selected strains, sporulation was low and toxin production undetectable. The addition of vancomycin at T0=24h followed by a 24 hours exposure barely reduced the viability of neither planktonic cultures nor biofilms of any strains. On the contrary, for all selected strains, addition of vancomycin at T0=6h followed by a 24 hours exposure significantly and more efficiently reduced the viability of planktonic cultures than that of biofilms, which was not decreased at all in the case of strains of ribotype WRT 005, 009 and 035. The biofilms of these selected strains of eight ribotypes, compared to their planktonic cultures, therefore showed a higher tolerance to vancomycin, suggesting that they could play a role in persistence.
Establishment & Characterization of a Non-Adherent Insect Cell Line for Cultivated Meat
Authors: Letcher Sophia M. , Calkins Olivia P. , Clausi Halla J. , McCreary Aidan , Trimmer Barry A. , Kaplan David L. 
Published: October 2024

AbstractThis study presents a blueprint for developing, scaling, and analyzing novel insect cell lines for food. The large-scale production of cultivated meat requires the development and analysis of cell lines that are simple to grow and easy to scale. Insect cells may be a favorable cell source due to their robust growth properties, adaptability to different culture conditions, and resiliency in culture. Cells were isolated from Tobacco hornworm (Manduca sexta)embryos and subsequently adapted to single-cell suspension culture in animal-free growth media. Cells were able to reach relatively high cell densities of over 20 million cells per mL in shake flasks. Cell growth data is presented in various culture vessels and spent media analysis was performed to better understand cell metabolic processes. Finally, a preliminary nutritional profile consisting of proximate, amino acid, mineral, and fatty acid analysis is reported.Graphical Abstract
Stroke impairs the proactive control of dynamic balance during predictable treadmill accelerations
Authors: Cornwell Tara , Finley James M. 
Published: October 2024

AbstractWe maintain balance during gait using both proactive and reactive control strategies. Damage to the brain from a stroke impairs reactive balance, but little is known about how a stroke impacts proactive control during walking. Identifying stroke-related impairments to proactive control could inform the design of interventions to improve balance and reduce fall risk. Therefore, we determined if people with and without stroke differ in their ability to use proactive strategies during predictable treadmill accelerations. Groups of 14 adults with and without stroke walked with single-belt accelerations at random (every one to five strides) and regular (every three strides) intervals. We quantified the effects of the perturbations as changes to center of mass (COM) speed and used mechanical leg work to quantify the proactive strategies to slow the COM. Participants without stroke reduced peak COM speed better than those with stroke when perturbations were at regular intervals (-0.023 versus -0.001 m/s; p=0.007). They also reduced positive leg work more during the perturbation step than the group post-stroke (-7.7% versus - 1.9%; p=0.004). Together, these results demonstrate that the sensorimotor impairments resulting from a stroke impair the ability to generate effective proactive adjustments to reduce the destabilizing effects of predictable perturbations.
Chromosomal-level reference genome and microRNAs of the ricefield flatsedgeCyperus iria
Authors: Tsang Stacey S.K. , Nong Wenyan , Law Sean T.S. , Bede Jacqueline C. , Chen Shan-Shan , Li Sa , Xie Yichun , Swale Thomas , Zhao Yiqiang , Lau David T.W. , Kai Zhen-peng , Chan Ting Fung , Tobe Stephen S. , Bendena William G. , Hui Jerome H.L. 
Published: October 2024

AbstractBackgroundGrass-like plants in the Cyperaceae family, commonly known as sedges, have a global distribution and include many economically problematic weeds. The ricefield flatsedge,Cyperus iria, is an aggressive weed in rice crops in Asia.ResultHere, we present a chromosomal-level genome assembly forC. iria(461.2 Mb, scaffold N50 = 7.3 Mbp, 99.6% BUSCO score) providing potential targets for the control of this devastating weed. Based on the genome assembly and transcriptomes of vegetative tissues, 52,574 protein-coding genes were predicted to be encoded. A total of 26 conserved and 75 novel microRNAs, including 9 microRNA clusters, were also annotated. Synteny and microRNA cluster analyses further showed thatC. iriahad undergone at least one round of whole genome duplication.ConclusionThe genomic resource established in this study sets up a foundation to further address basic and applied questions in the Cyperaceae.
Highly enhanced transgene integration in human pluripotent stem cells by serine integrase BxbI
Authors: Autio Matias I. , Perrin Arnaud 
Published: October 2024

SummaryGenome engineering and especially integration of large DNA payloads in human pluripotent stem cells (hPSC) remains challenging largely due to the sensitive nature of hPSCs. Site specific recombinases such as the serine integrase Bxb1 have been utilised successfully to target hPSC, however the targeting efficiencies remain low. Here we leveraged codon optimisation, inclusion of a nuclear localisation signal, mRNA modality and co-introduction of p53 dominant negative fragment to increase the transgene payload integration efficiency by up to 20-fold in defined genomic safe harbours in hPSCs.