bluuebunny/crossref_metadata_2025_split huggingface dataset:
EFFECTS OF MODIFIED PROGRESSIVE MUSCLE RELAXATION COMBINED WITH SLOW STROKE BACK MASSAGE ON BLOOD PRESSURE REDUCTION, STRESS ALLEVIATION, AND ENHANCED SLEEP QUALITY IN OLDER ADULTS: A LITERATUR REVIEW
Authors: Asriadi  , Pandin Moses Glorino Rumambo , Nursalam  
Published: January 2025

AbstractBackgroundProgressive muscle relaxation is a systematic technique used to achieve deep states of relaxation and has been proven to improve the quality of life related to both medical and non-medical conditions. The goal is to consciously experience the difference between tension and relaxation, just like applying pressure to the muscles, where all the muscles in the body from the tip of the head to the tip of the toes, which were initially tense, become relaxed after receiving progressive pressure. Therefore, an explanation is needed that discusses the influence of modified slow stroke back massage progressive muscle relaxation on reducing blood pressure, stress, and sleep quality in the elderly.Objectiveto identify the effects of progressive muscle relaxation and slow stroke back massage on the reduction of blood pressure, stress, and sleep quality in the elderly.Methoda scope review of this research by searching for articles related to the effects of progressive muscle relaxation and slow stroke back massage on the reduction of blood pressure, stress, and sleep quality in the elderly. Using several databases such as Scopus, Proquest, PubMed, and Google Scholar. Then, the found articles were checked for duplication using Mendeley, resulting in 327 articles. After the title screening process, 129 articles remained. Then 25 articles were included and 15 articles were excluded because they did not meet the study quality.ResultsFrom the review of 10 journals, two main topics were identified, including the effect of progressive muscle relaxation on lowering blood pressure, reducing stress and anxiety, stabilizing vital signs, and improving sleep quality, and the effect of slow stroke back massage therapy on lowering blood pressure, reducing stress and anxiety, and improving sleep quality.ConclusionProgressive muscle relaxation and slow stroke back massage therapy have a significant impact on lowering blood pressure, reducing stress, and improving the sleep quality of the elderly.
RNA-triggered CRISPR-Cas12a2 Preferentially and Cooperatively Cleaves Collateral DNA
Authors: Hallmark Thomson , Kunwar Sobita , Manna Sudeshna , Keiser Dylan , Naegle Bronson , Thomas Aaron , Beisel Chase L. , Jackson Ryan N. 
Published: January 2025

AbstractCRISPR-Cas systems often rely on collateral cleavage activities against nucleic-acid substrates to combat recognized mobile genetic elements. Of the associated RNA-guided Cas effector nucleases, Cas12a2 stands out as the only known example exhibiting RNA-triggered collateral cleavage of three distinct substrates: single-stranded (ss)RNA, ssDNA, and double-stranded (ds)DNA. However, little is known about the underlying mechanisms of collateral cleavage, including which of these activities dominates during the Cas12a2-mediated immune response. Here, we show that Cas12a2 cleaves collateral DNA substrates over RNA substrates, even when RNA substrates are more abundant. This preference relies on a positive cooperativity mechanism that requires the four “aromatic clamp” residues that stabilize unwound and distorted dsDNA in the RuvC nuclease active site. Leveraging the cleavage preference for collateral DNA, we demonstrate that RNA-activated Cas12a2 can cleave a ssDNA probe in the presence of high concentrations of non-target RNA, while the RNA-targeting Cas13a cannot. This work thus reveals how Cas12a2 decides amongst different collateral cleavage substrates, with immediate implications for understanding Cas12a2-based immunity, improving molecular diagnostics, and laying a mechnastic foundation for future Cas12a2-based technologies.
Transcriptional stochasticity reveals multiple mechanisms of long non-coding RNA regulation at the Xist – Tsix locus
Authors: Kesler Benjamin K. , Adams John , Neuert Gregor 
Published: January 2025

ABSTRACTLong noncoding RNAs (LncRNAs) are increasingly recognized as being involved in human physiology and diseases, but there is a lack of mechanistic understanding for the majority of lncRNAs. We comparatively tested proposed mechanisms of antisense lncRNA regulation at the X-chromosome Inactivation (XCI) locus. We find that due to stochasticity in transcription, different mechanisms based on the act of transcription regulate Xist and Tsix at different levels of nascent transcription. At medium levels, RNA polymerases transcribe Xist and Tsix on each strand at the same transcription site and deposit significant amounts of the histone mark H3K36me3, which inhibits Xist. At high levels of nascent transcription, many RNA polymerases transcribe Xist or Tsix resulting in transcriptional interference. Therefore, lncRNA expression variability is not just a quirk of transcription but an important aspect of regulation that allows multiple mechanisms to be employed by the same gene locus within the same cell population.
Nutrient availability dictates cancer metabolism-based therapeutic responses of non-oncology drugs
Authors: Pyun Woo Yang , Park Jae Hyung , Roh Jae Won , Jeon Dongkyu , Kim Jongwan , Paik Ji Eun , Cho Seok Chan , Park So Yeon , Lim Hocheol , Kim Hyungwoo , Jang Young Jin , Lee Jaehoon , Kim Soo-Youl , Guan Kun-Liang , Gee Heon Yung , Lee Han-Woong , No Kyoung Tai , Jeong Han-Sol , Namkung Wan , Nam Joo Hyun , Park Hyun Woo 
Published: January 2025

AbstractMetabolic deregulation is a major hallmark of cancer, therefore, interventions that modify tumor nutrient availability are considered attractive adjuvants for improving clinical outcomes for cancer patients. Much work remains, however, in clarifying how the nutritional status of each patient can affect the metabolic vulnerability of drugs and inform individual medication guidelines. Working toward the goal of oncometabolic precision medicine, we introduce CM-SLP (cancer metabolism-based synthetic lethality platform), a high-throughput screening platform that explores the metabolic vulnerability of non-oncology drugs induced by altered nutrient availability and predicts the potential synthetic lethal interactions with either hyper- or hypo-nutrient conditions. We present promising CM-SLP candidates, such as propafenone and biguanides, as representative non-oncology drugs that cooperatively enhance cytotoxicity via dysregulated metabolic pathways. Furthermore, identifying mTOR and Hippo pathways as mediators of combined propafenone/hypoglycemia or biguanides/hypoglycemia treatments, respectively, we were able to circumvent the need for dietary interventions by administering the mTOR or TEAD inhibitors to induce energy stress and cancer cell death. Together, CM-SLP represents a critical step toward integrating metabolic profiling into precision oncology, offering novel therapeutic avenues tailored to individual patient needs.
Combining seasonal malaria chemoprevention with novel therapeutics for malaria prevention: a mathematical modelling study
Authors: Braunack-Mayer Lydia , Malinga Josephine , Nekkab Narimane , Kelly Sherrie L , Möhrle Jörg J , Penny Melissa A 
Published: January 2025

AbstractBackgroundVaccines, monoclonal antibodies, and long-acting injectables are being developed to preventPlasmodium falciparummalaria. These therapeutics may target multiple stages of the parasite life cycle, and evidence is needed to articulate their benefits with chemoprevention and prioritise candidates for clinical development.MethodsWe used an individual-based malaria transmission model to estimate the health impact of combining new therapeutics with seasonal malaria chemoprevention (SMC). Our modelling framework used emulator-based methods with models of pre-liver and blood stage therapeutic dynamics. We evaluated the benefit of combining therapeutics with SMC in children under five by estimating reductions in the cumulative incidence of uncomplicated and severe malaria, relative to SMC or the new therapeutic alone, during and five years after deployment.ResultsNew therapeutics may require extended pre-liver stage duration or multi-stage activity to combine with SMC. For three SMC cycles in a high transmission setting, a pre-liver stage therapeutic with partial initial efficacy (>50%) required a protection half-life >230 days to reduce cumulative severe cases by >5% five years after deployment stopped (>23% during interventions). Longer protection was needed when combined with four or five SMC cycles. Combining SMC with a multi-stage therapeutic increased public health impact both during and after deployment.ConclusionsCombining SMC with malaria therapeutics active against multiple stages of the parasite life cycle can improve the effectiveness of SMC, highlighting the need to prioritise the clinical development of these therapeutics for combination with malaria chemoprevention.
Race and ethnic disparities in rehabilitation services and functional recovery post-stroke
Authors: Bishop Lauri , Gardener Hannah , Brown Scott C. , Veledar Emir , Johnson Karlon H. , Marulanda-Londono Erika T , Gutierrez Carolina M. , Kirk-Sanchez Neva , Romano Jose , Rundek Tatjana 
Published: January 2025

AbstractObjectiveTo identify race/ethnic disparities in rehabilitation services after stroke and characterize the independent associations of each of race/ethnicity and rehabilitation to functional recovery post-stroke.MethodsThe Transitions of Care Stroke Disparities Study (TCSD-S) is a prospective cohort study designed to reduce disparities and to optimize the transitions of care for stroke survivors throughout the state of Florida. Participant characteristics were extracted from the American Heart Association’s Get-With-The-Guidelines-Stroke dataset. Rehabilitation services, and modified Rankin Scale were recorded via follow up phone calls at 30- and 90-days after hospital discharge. Logistic regression models adjusted for potential confounders were used to determine: 1) race/ethnic differences in rehabilitation services received; 2) race/ethnic differences in functional change from discharge to 30- and 90-days, respectively; and 3) the influence of rehabilitation on functional change from discharge to 30- and 90-days.ResultsOf 1,083 individuals, 43% were female, 52% were Non-Hispanic White (NHW), 22% were Non-Hispanic Black (NHB), and were 22% Hispanic. Individuals who engaged in rehabilitation were more likely to show improvements [aOR=1.820, 95%CI (1.301,2.545)] at 90-days from hospital discharge. Irrespective of rehabilitation services, there were no differences in functional change between NHW and NHB individuals, yet Hispanic individuals were less likely to improve [aOR=0.647, 95%CI (0.425,0.983)] compared to NHW. Additionally, Hispanic individuals were significantly less likely to receive any rehabilitation services [aOR=0.626, 95%CI (0.442,0.886)] and were half as likely to receive outpatient services [aOR=0.543, 95%CI (0.368,0.800)] as compared to NHW.ConclusionsRehabilitation is key to functional improvement after stroke. We are making strides in health equity between NHW and NHB individuals, yet there remain disparities in functional outcomes and in rehabilitation services particularly for Hispanic individuals after stroke.
Aging-related Changes in Bimanual Coordination As a Screening Tool for Healthy Aging
Authors: Shizuka Yusuke , Murata Shin , Goda Akio , Sawai Shun , Fujikawa Shoya , Yamamoto Ryosuke , Maru Takayuki , Nakagawa Kotaro , Nakano Hideki 
Published: January 2025

AbstractThe steady increase in the global older adult population highlights critical challenges, including the development of preventive strategies to extend healthy life expectancy and support independence in activities of daily living. Although there is an aging-related reduction in manual dexterity, the difference in bimanual coordination performance between young and older adults remains unclear. We aimed to elucidate the characteristics of bimanual coordination among young, young-old, and old-old adults participants. The participants performed in-phase (tapping the thumb and index finger together as fast as possible) and anti-phase (alternating movement between the left and right fingers) bimanual coordination tasks, and intergroup comparison of the task parameters as performed. The number and frequency of taps significantly decreased sequentially in young, young-old, and old-old adults, whereas the average tap interval significantly increased in this order (p< 0.05). There was no significant difference between the young-old and old-old groups in the average local maximum distance (p> 0.05). These findings indicate that bimanual coordination task performance varies depending on specific parameters. Thus, the number, average interval, and frequency of taps are potential indicators of aging-related changes in bimanual coordination.
Engineering 3D Skeletal Muscle Tissue with Complex Multipennate Myofiber Architectures
Authors: Stang Maria A. , Lee Andrew , Bliley Jacqueline M. , Coffin Brian D. , Yerneni Saigopalakrishna S. , Campbell Phil G. , Feinberg Adam W. 
Published: January 2025

AbstractThe hierarchical architecture of skeletal muscle spans from microscale sarcomeres to macroscale myofibers and is integral to its contractile functionality. Pathologies such as volumetric muscle loss (VML) compromise this structure and destroy the native extracellular matrix (ECM), exceeding the regenerative capacity of endogenous repair mechanisms. Here, we present a novel method for tissue engineering biomimetic three-dimensional (3D) skeletal muscle with complex architectures by leveraging freeform reversible embedding of suspended hydrogels (FRESH) 3D bioprinting of the ECM. Collagen type I scaffolds mimicking diverse muscle architectures— including parallel, unipennate, bipennate, multipennate, and convergent—were designed, FRESH printed, and seeded with C2C12 myoblasts to guide myogenesis. Engineered muscle tissues demonstrated scaffold-mediated alignment and fusion into functional myotubes, exhibiting contractile responses to electrical stimulation with architecture-dependent specific force of ∼1 kN/m2and a positive force-frequency relationship.In vivoimplantation further revealed scaffold-directed cellular and vascular organization, underscoring the translational potential of this approach. In summary, this study demonstrates the capability to use FRESH 3D bioprinting to engineer physiologically relevant muscle architectures, significantly advancing the design of functional muscle tissues for regenerative medicine and in vitro modeling applications.
Light and chloroplast redox state modulate the progression of tobacco leaf infection byPseudomonas syringaepvtabaci
Authors: Arce Rocío C. , Demarchi Mariana , Figueroa Nicolás , Delprato María L. , Hajirezaei Mohammad-Reza , Mayta Martín L. , Lodeyro Anabella F. , Krapp Adriana R. , Carrillo Néstor 
Published: January 2025

AbstractLight significantly influences plant stress responses, with chloroplasts playing a pivotal role as both energy providers and light sensors. They communicate with the nucleus through retrograde signals, including secondary metabolites and reactive oxygen species (ROS). To investigate the contribution of chloroplast redox biochemistry to biotic responses, we studied the interactions of tobacco leaves expressing the alternative electron shuttle flavodoxin with virulent and nonhostPseudomonas syringaepathovars under light and dark conditions. Flavodoxin is reported to limit light-dependent ROS propagation and over-reduction of the photosynthetic electron transport system under stress. Light intensified the hypersensitive response against the nonhost pathovartomato (Pto), but slowed disease progression caused by the virulent pathovartabaci (Pta). Flavodoxin mitigated light responses during both interactions, including decreased ROS levels, reduced stromule occurrence, and lower phytoalexin production, with different signatures depending on the pathovar. Similar leaf metabolic profiles were observed in the dark for both strains, with a general up-regulation of sugars, metabolic intermediates, and amino acids. In the light, instead,Ptaincreased sugars and intermediates, whilePtodecreased them. Our results suggest that HR-like responses are elicited in the light even during virulent interactions, and that light effects are related to signals originating at the photosynthetic machinery.Highlights- Light inhibits disease progression during a tobacco-Pseudomonasvirulent interaction.- Light exacerbates the hypersensitive response (HR) during a nonhost interaction.- HR-like responses are elicited in the light even during virulent interactions.- Plastid-targeted flavodoxin decreases plant damage only in photoperiod.- The chloroplast redox state modulates plant biotic response.
protPheMut: An Interpretable Machine Learning Tool for Classification of Cancer and Neurodevelopmental Disorders in Human Missense Variants
Authors: Wang Jingran , Yang Miao , Zong Chang , Verkhivker Gennady , Fei Xiao , Hu Guang 
Published: January 2025

AbstractMotivationRecent advances in human genomics have revealed that missense mutations in a single protein can lead to distinctly different phenotypes. In particular, some mutations in oncoproteins like Ras, MEK, PI3K, PTEN, and SHP2 are linked various cancers and Neurodevelopmental Disorders (NDDs). While numerous tools exist for predicting the pathogenicity of missense mutations, linking these variants to certain phenotypes remains a major challenge, particularly in the context of personalized medicine.ResultsTo fill this gap, we developed protPheMut (Protein Phenotypic Mutations Analyzer), leveraging multiple interpretable machine learning methods and integrate diverse biophysics and network dynamics-based signatures, for the prediction of mutations of the same protein can promote cancer, or NDDs. We illustrate the utility of protPheMut in phenotypes (cancer/NDDs) prediction by the mutation analysis of two protein cases, that are PI3Kα and PTEN. Compared to seven other predictive tools, protPheMut demonstrated exceptional accuracy in forecasting phenotypic effects, achieving an AUROC of 0.8501 for PI3Kα mutations related to cancer and Cowden syndrome. For multi-phenotypes prediction of PTEN mutations related to cancer, PHTS, and HCPS, protPheMut achieved an AUC of 0.9349 through micro-averaging. Using SHAP model explanations, we gained insights into the mechanisms driving phenotype formation. A userfriendly website deployment is also provided.AvailabilitySource code and data are available athttps://github.com/Spencer-JRWang/protPheMut. We also provide a user-friendly website athttp://netprotlab.com/protPheMut.Supplementary informationSupplementary data are available atBioinformaticsonline.Graphical Abstract
Viral Simulation Reveals Overestimation Bias in Within-Host Phylodynamic Migration Rate Estimates Under Selection
Authors: Ochsner Nicolas , Bouman Judith , Vaughan Timothy , Stadler Tanja , Bonhoeffer Sebastian , Regoes Roland 
Published: January 2025

AbstractPhylodynamic methods are widely used to infer the population dynamics of viruses between and within hosts. For HIV-1, these methods have been used to estimate migration rates between different anatomical compartments within a host. The methods typically assume that there is no selective pressure acting on the virus, even though it is known that viruses often experience strong selection pressures. In this study, we investigate how selection affects phylodynamic migration rate estimates. To this end, we developed a novel agent-based simulation tool, virolution, to simulate the evolution of virus within two anatomical compartments of a host. Using this tool, we generated viral sequences and genealogies assuming both, neutral evolution and purifying selection that is concordant in both compartments. We found that, under the selection regime, migration rates are significantly overestimated with a stochastic mixture model and a structured coalescent model in the Bayesian inference framework BEAST2. Our results reveal that commonly used phylogeographic methods, which assume neutral evolution, can significantly bias migration rate estimates in selective regimes. This study underscores the need for assessing the robustness of phylodynamic analysis with respect to more realistic selection regimes.
Quantifying Metagenomic Strain Associations from Microbiomes with Anpan
Authors: Ghazi Andrew R. , Thompson Kelsey N. , Bhosle Amrisha , Mei Zhendong , Yan Yan , Wang Fenglei , Wang Kai , Franzosa Eric A. , Huttenhower Curtis 
Published: January 2025

AbstractGenetic and genomic variation among microbial strains can dramatically influence their phenotypes and environmental impact, including on human health. However, inferential methods for quantifying these differences have been lacking. Strain-level metagenomic profiling data has several features that make traditional statistical methods challenging to use, including high dimensionality, extreme variation among samples, and complex phylogenetic relatedness. We present Anpan, a set of quantitative methods addressing three key challenges in microbiome strain epidemiology. First, adaptive filtering designed to interrogate microbial strain gene carriage is combined with linear models to identify strain-specific genetic elements associated with host health outcomes and other phenotypes. Second, phylogenetic generalized linear mixed models are used to characterize the association of sub-species lineages with such phenotypes. Finally, random effects models are used to identify pathways more likely to be retained or lost by outcome-associated strains. We validated our methods by simulation, showing that we achieve more accurate effect size estimation and a lower false positive rate compared to alternative methodologies. We then applied our methods to a dataset of 1,262 colorectal cancer patients, identifying functionally adaptive genes and strong phylogenetic effects associated with CRC status, sometimes complementing and sometimes extending known species-level microbiome CRC biomarkers. Anpan’s methods have been implemented as a publicly available R library to support microbial community strain and genetic epidemiology in a variety of contexts, environments, and phenotypes.
Simple controls exceed best deep learning algorithms and reveal foundation model effectiveness for predicting genetic perturbations
Authors: Wong Daniel R. , Hill Abby S. , Moccia Robert 
Published: January 2025

AbstractModeling genetic perturbations and their effect on the transcriptome is a key area of pharmaceutical research. Due to the complexity of the transcriptome, there has been much excitement and development in deep learning (DL) because of its ability to model complex relationships. In particular, the transformer-based foundation model paradigm emerged as the gold-standard of predicting post-perturbation responses. However, understanding these increasingly complex models and evaluating their practical utility is lacking, along with simple but appropriate benchmarks to compare predictive methods. Here, we present a simple baseline method that outperforms both state of the art (SOTA) in DL and other proposed simpler neural architectures, setting a necessary benchmark to evaluate in the field of post-perturbation prediction. We also elucidate the utility of foundation models for the task of post-perturbation prediction via generalizable fine-tuning experiments that can be translated to different applications of transformer-based foundation models to tasks of interest. Furthermore, we provide a corrected version of a popular dataset used for benchmarking perturbation prediction models. Our hope is that this work will properly contextualize further development of DL models in the perturbation space with necessary control procedures.