bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Neuroplasticity Effects of Continuous Theta Burst Stimulation with Biomarkers from the Motor Evoked Potential TMS Input-Output Curve
Authors: Parchure Shreya , Xu Zihang , Shah-Basak Priyanka , Erickson Brian , Harvey Denise , Wurzman Rachel , McAfee Darrian , Sacchetti Daniela , Faseyitan Olufunsho , Hamilton Roy H. 
Published: February 2025

ABSTRACTThe field of neuromodulation lacks predictors of individual differences in plasticity that influence responses to repetitive transcranial magnetic stimulation (rTMS). Continuous theta burst stimulation (cTBS), a form of rTMS known for its inhibitory effects, shows variable responses between individuals, potentially due to differences in neuroplasticity. Predicting individual cTBS effects could vastly enhance its clinical and experimental utility. This study explores whether motor evoked potential (MEP) input-output (IO) parameters measured prior to neuromodulation can predict motor cortex responses to cTBS. IO curves were sampled from healthy adults by recording MEPs over a range of single pulse TMS intensities to obtain parameters including MEPmaxand S50(midpoint intensity). Subjects later received cTBS over the same location of motor cortex and their MEPs before and after stimulation were compared. Both MEPmaxand S50predicted responses, significantly correlating (p<0.05, R2>0.25) with individuals’ MEP changes at 10, 20, and 30 minutes after cTBS. Further, we introduced and validated an easily implementable biomarker that does not require the time-consuming sampling of full IO curve: MEP130RMT(median of 10 MEPs at 130% RMT). MEP130RMTwas also a strong predictor of cTBS response (p<0.005, R2>0.3). Head-to-head comparison against a previously studied genetic biomarker of rTMS responses (BDNF polymorphism) showed that IO based predictors had a superior performance in explaining more response variability. Thus, IO curves derived prior to cTBS administration can reliably predict cTBS-induced changes in cortical excitability. This work points toward an accessible strategy for tailoring stimulation procedures in both diagnostic and therapeutic applications of rTMS, and potentially boosting response rate to other brain stimulation approaches.HIGHLIGHTSBaseline TMS-MEP Input-Output (IO) Curve parameters significantly predict MEP responses to M1 cTBS.Higher MEPmaxat baseline predicts more robust inhibitory response to cTBS, while higher midpoint intensity (S50) is associated with less response.D We developed and validated a new biomarker MEP130RMT, which predicts cTBS response using just 10 baseline MEPs from single TMS pulses of 130% RMT intensity.Head to head comparison against BDNF genotyping shows superior performance of IO biomarkers.
In vitro reconstitution of minimal human centrosomes
Authors: Rios Manolo U. , Stachera Weronika E. , Familiari Nicole E. , Brito Claudia , Surrey Thomas , Woodruff Jeffrey B. 
Published: February 2025

ABSTRACTCDK5RAP2/CEP215 is a key pericentriolar material (PCM) protein that recruits microtubule-nucleating factors at human centrosomes. Using anin vitroreconstitution system, we show that CDK5RAP2 is sufficient to form micron-scale scaffolds around a nanometer-scale nucleator in a PLK-1-regulated manner. CDK5RAP2 assemblies recruited and activated gamma tubulin ring complexes (γ-TuRCs) which, in the presence of α/β tubulin, generated microtubule asters. We found that F75 in CDK5RAP2 is partially needed to recruit γ-TuRC yet is indispensable for γ-TuRC activation. Furthermore, our system recapitulated key features of centrosome-amplified cancer cells. CDK5RAP2 scaffolds selectively recruited the molecular motor KifC1/HSET, which enhanced concentration of α/β tubulin, microtubule polymerization, and clustering of the assemblies. Our results highlight the specificity and selectivity ofin vitrogenerated CDK5RAP2 scaffolds and identify a minimal set of components required for human centrosome assembly and function. This minimal centrosome model offers a powerful tool for studying centrosome biology and dysfunction in human health and disease.
CRISPR-CISH: Anin situchromogenic DNA repeat detection system for research and life science education
Authors: Potlapalli Bhanu Prakash , Dassau Fabian , Fuchs Jörg , Sushmoy Deboprio Roy , Houben Andreas 
Published: February 2025

AbstractIn situhybridization is a technique to visualize specific DNA sequences within nuclei and chromosomes. Various DNAin situfluorescent labeling methods have been developed, which typically involve global DNA denaturation prior to the probe hybridization and often require fluorescence microscopes for visualization. Here, we report the development of a CRISPR/dCas9-mediated chromogenicin situDNA detection (CRISPR-CISH) method that combines chromogenic signal detection with CRISPR imaging. This non-fluorescent approach uses 3’ biotin-labeled tracrRNA and target-specific crRNA to form mature gRNA, which activates dCas9 to bind to target sequences. The subsequent application of streptavidin alkaline phosphatase or horseradish peroxidase generates chromogenic, target-specific signals that can be analyzed using conventional bright-field microscopes. Additionally, chromatin counterstains were identified to aid in the interpretation of CRISPR-CISH-generated target signals. This advancement makesin situDNA detection techniques more accessible to researchers, diagnostic applications, and educational institutions in resource-limited settings.
Metalation calculator forE. colistrain BW25113 grown in M9 minimal media
Authors: Clough Sophie E. , Glasfeld Arthur , Robinson Nigel J. 
Published: February 2025

AbstractHere we provide the background data supporting an additional web-based calculator to predict in-cell metalation of proteins withinE. coliBW25113 grown in M9 media. Intracellular metal availabilities have been estimated from the calibrated responses of DNA-binding, metal-sensing, transcriptional regulators. We have previously tested and validated metalation calculator predictions. They confirm that when proteins are expressed heterologously inE. coliin LB medium, they can become mismatched to metal availability and be mismetalated. Mg2+GTP-CobW fromRhodobacteris predicted to be correctly metalated with cobalt inE. coligrown in M9 media, although mismetalated with zinc in LB-grown heterologous cells. Similarly, MncA fromSynechocystisPCC 6803 is predicted to be correctly metalated with manganese inE. coligrown in M9 media, although mismetalated with iron in LB-grown heterologous cells. The M9 metalation calculator is available online and as a spreadsheet for use in optimising metalation in engineering biology. An MncA-refined metalation calculator for idealised cells, reflecting the midpoint of intracellular metal availabilities, is also included and available online.
N153-linked glycans on envelope protein protect orthoflaviviruses from antibody-mediated clearance
Authors: Ting Donald Heng Rong , Marzinek Jan Kazimierz , Wan Corrine , Palur Raghuvamsi V. , Idris Fakhriedzwan , Xin Tan Eunice Tze , Clara Koh Wei Teng , Lim Xin Ni , Thein Tun-Linn , Lim Cheer Vee , Ng Chin Huan , Buckley Theresa S. C. , Walsh Ian , MacAry Paul A. , Leo Yee-Sin , Anand Ganesh S. , Chan Kuan Rong , Nguyen-Khuong Terry , Bond Peter John , Alonso Sylvie 
Published: February 2025

AbstractThe envelope (E) protein of dengue virus (DENV) is glycosylated at two highly conserved asparagine (N) sites (N67 and N153). The role and importance of these N-linked glycans in DENV pathogenesis has been elusive. Here, we report the critical role of N153-linked glycans on E protein in preventing antibody-mediated viral clearance. A DENV2 mutant lacking N153-linked glycans (N153Q mutant) was engineered and found to be mildly impairedin vitrobut drastically attenuated in a symptomatic mouse model of severe dengue, as evidenced by accelerated viral clearance. In B cell-deficient mouse models, N153Q mutant displayed parental virulence and viremia profile. Homologous and heterologous passive transfers of purified IgM from infected B cell-proficient mice into B cell-deficient mice demonstrated the role of N153Q-specific IgM in N153Q attenuation and accelerated clearance, while WT DENV was unaffected by IgM from both WT- and N153Q-infected mice. Furthermore,in vitroneutralization assay supported that the accelerated clearance of N153Q mutant in mice was mediated by non-neutralizing IgM. Furthermore, using plasma samples from convalescent dengue patients and monoclonal antibodies,in vitroneutralization assays showed that N153Q virus was more susceptible than WT to IgG-mediated neutralization. Glycoproteomics combined with molecular dynamics (MD) simulations revealed that glycan composition on E protein influenced IgG binding. Our findings were extended to all DENV serotypes and ZIKV, hence supporting that the N153 glycans-mediated immune evasion strategy is conserved across orthoflaviviruses.
Automating Imaging Biomarker Analysis for Knee Osteoarthritis Using an Open-Source MRI-Based Deep Learning Pipeline
Authors: Goyal Ananya , Belibi Francesca , Sahani Vyoma , Pedersen Rune , Vainberg Yael , Williams Ashley , Chu Constance , Haddock Bryan , Gold Garry , Chaudhari Akshay , Kogan Feliks , Gatti Anthony 
Published: February 2025

AbstractOsteoarthritis (OA) is a leading cause of chronic disability worldwide, with knee OA being the most prevalent form. Quantitative assessment of knee joint tissues using Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET) has the potential to enhance OA diagnosis and progression tracking. However, current methodologies for segmenting and extracting quantitative metrics from knee joint images are time-consuming, require extensive expertise, and suffer from inter- and intra-reader variability, limiting their clinical translation.In this study, we present and validate a fully automated AI-based pipeline for comprehensive segmentation and quantitative analysis of knee joint tissues from MRI and PET images. Our pipeline segments key joint tissues, including femoral, tibial, and patellar bones, femoral, patellar, and tibial cartilage, and medial and lateral menisci, using a deep learning-based segmentation model. Furthermore, the pipeline enables automated extraction of critical quantitative OA biomarkers, including regional cartilage thickness and T2 relaxation times, meniscus volume, a neural shape model-derived OA bone shape score, and [18F]NaF PET-based measures of subchondral bone metabolism.To evaluate the segmentation performance, we validated automated segmentations against manual segmentations from two annotators and compared derived quantitative metrics. Results demonstrated high segmentation accuracy, with DSC values ranging from 0.84 to 0.98 across different tissues. Automated quantitative measurements exhibited good to excellent agreement with manual-derived values for most metrics, with ICC values exceeding 0.89. Our findings suggest that the proposed AI-based pipeline provides a robust, open-source tool for efficient and reproducible quantitative analysis for knee OA studies, accelerating research and clinical adoption of whole-joint quantitative imaging.
A Cluster-Randomized Trial to Compare Effectiveness and Cost-effectiveness of Cash Plus Interventions in Preventing Child Wasting in Somalia: An Evidence-Based Methodology
Authors: Walton Shelley , Alier Kemish Kenneth , Garretson Sydney , Grounds Samantha , Khattak Qundeel , Tripaldi Marina , Loddo Fabrizio , Mohamoud Said Aden , Nur Mohamud Ali , Abdiqadir Sadiq , Mitchell Emily , Mahat Mohamed Billow , Gure Maimun , Jibril Dahir I. , Gedi Dahir , Ocircan Michael , Omer Meftuh , Arays Abdullahi , Mohamed Abdifitah Ahmed , Mohamed Adam Abdulkadir , Akseer Nadia 
Published: February 2025

AbstractBackgroundSomalia is a conflict, flood, and drought prone country with high rates of food insecurity and child wasting. Save the Children partnered with Johns Hopkins University to study the most effective and cost-effective combinations of assistance to prevent acute malnutrition among PLW and CU5 in a six-month humanitarian program.ObjectivesThis study implemented an cluster-randomized controlled trial using adaptive design methodology to: (A) Estimate and compare wasting incidence and prevalence of CU5 and their mothers receiving on a monthly basis either cash (Arm 1), cash + social and behavior change communication (Arm 2), or cash+ top-up cash (Arm 3); after 3 months and 6 months; (B) Calculate the costs and cost-effectiveness of the different intervention arms; (C) Understand perspectives and experiences of mothers and fathers of CU5 beneficiaries; (D) Monitor the functionality of markets and availability and prices of foods. This paper presents the approach that was designed and implemented to study these objectives.MethodologyThis study employed a mixed-methods approach with a quantitative component conducted at three timepoints to collect anthropometric measurements and household survey data. Primary outcomes, such as child and maternal wasting, were assessed using standardized WHO criteria. Additional data on food security, maternal and child health, and household conditions were collected to evaluate immediate, underlying, and basic causes of malnutrition. Cost analyses evaluated programmatic and societal costs of the intervention. An adaptive trial design was implemented, allowing the methodology to evolve as new challenges emerged.ConclusionThis trial applied an adaptive mixed methods design to evaluate the effectiveness and cost-effectiveness of cash assistance interventions in Somalia, overcoming complex humanitarian operational challenges. Strong partnerships and flexible trial design allowed us to adjust to unpredictable events and maintain research rigor. These findings highlight the value of adaptive designs and mixed methods for improving child nutrition outcomes in complex settings.RegistrationThe cluster-RCT is registered at ClinicalTrials.gov, ID:NCT06642012.
Cardiovascular-kidney-metabolic disease burden in children and adults following heart transplantation
Authors: Huang Shi , Farber-Eger Eric , Tamaroff Jaclyn , Chow Nelson , Siddiqi Hasan K. , Brinkley D. Marshall , Menachem Jonathan N. , Rali Aniket S. , Lindenfeld JoAnn , Ooi Henry , Punnoose Lynn , Tsai Stacy , Pedrotty Dawn , Zalawadiya Sandip , Sacks Suzanne , Wigger Mark , Williams Aaron M. , Bommareddi Swaroop , Lima Brian , Nguyen Duc , Shah Ashish S. , Trahanas John M. , Bearl David W. , Wells Quinn S. , Schlendorf Kelly H. , Amancherla Kaushik 
Published: February 2025

ABSTRACTBackgroundHeart transplantation (HT) is the definitive therapy for end-stage heart failure. However, with improving post-HT survival in the modern era, recipients are increasingly cumulatively exposed to unique risk factors for cardiovascular-kidney-metabolic (CKM) dysfunction. An expanded understanding of the incidence and prevalence of CKM dysfunction post-HT may inform screening and therapeutic strategies to mitigate adverse events.ObjectivesThe aim of this study was to characterize the incidence and prevalence of CKM risk factors in adult and pediatric HT recipients at a high-volume heart transplant center.MethodsWe conducted a single-center retrospective observational study in adults and children who underwent HT between 1/1/2015 and 6/30/2024. Longitudinal clinical and laboratory data were extracted from the electronic health record. Incidence rates (IRs) of type 2 diabetes mellitus (DM2), overweight or obesity, hypertension, chronic kidney disease (CKD), and dyslipidemia were calculated. We constructed longitudinal predictive models of CKM dysfunction and evaluated the impact of SGLT2 inhibitors (SGLT2i) and GLP1 receptor agonists (GLP1ra) on CKD and body mass index (BMI), respectively.ResultsDuring the study period, 860 adults and 84 children underwent HT. Among adults, the IR (reported as cases per 100 person-years) of DM2, overweight or obesity, dyslipidemia, and CKD were 28.6, 77.3, 139.1, and 69.7 respectively. Among children, the IR of DM2, overweight or obesity, dyslipidemia, and CKD were 2.8, 26.9, 5.5, and 3.6, respectively. Within 12 months post-HT, 99% of adults developed stage 1 or 2 hypertension and 22.1% of all adults developed HbA1c ≥6.5%, regardless of pre-existing diagnosis of DM2. Similarly, 37.5% of adults developed moderate-severe hypertriglyceridemia and 31.1% manifested worsened LDL-C control. Among adults with an eGFR ≥45 mL/min/1.73 m2pre-HT, 86.2% demonstrated worsening renal function (eGFR <45 mL/min/1.73 m2) within 12-months post-HT. In adults initiated on SGLT2i post-HT (N = 242), there was a non-linear improvement in eGFR during the ensuing 12 months while for individuals initiated on GLP1ra (N = 168), there was a predominantly linear reduction in BMI.ConclusionsA significant proportion of HT recipients experience new-onset or worsening CKM dysfunction following HT. Our results indicate that SGLT2i and GLP1ra may mitigate the burden of CKM disease.
Involvement of RNase J in CRISPR RNA maturation and degradosome formation in cyanobacteria
Authors: Bilger Raphael , Drepper Friedel , Knapp Bettina , Berndt Tanja , Landerer Helena , Putzer Harald , Huesgen Pitter , Hess Wolfgang R. 
Published: February 2025

AbstractMany bacteria and archaea use CRISPR-Cas systems, which provide RNA-based, adaptive, and inheritable immune defenses against invading viruses and other foreign genetic elements. The proper processing of CRISPR guide RNAs (crRNAs) is a crucial step in the maturation of the defense complexes and is frequently performed by specialized ribonucleases encoded bycasgenes. However, some systems employ enzymes associated with degradosome or housekeeping functions, such as RNase III or the endoribonuclease RNase E. Here, the endo- and 5′-exoribonuclease RNase J was identified as additional enzyme involved in crRNA maturation, acting jointly with RNase E in the crRNA maturation of a type III-Bv CRISPR-Cas system, and possibly together with a further RNase. Co-IP experiments revealed a small set of proteins that were co-enriched with RNase J, among them PNPase. Despite a measured, strong 3’ exonucleolytic activity of the recombinant enzyme, PNPase was not confirmed to contribute to crRNA maturation. However, the co-IP results indicate that PNPase is a component of the cyanobacterial degradosome that can recruit either RNase E or RNase J, together with additional enriched proteins.
Sequence-based chromatin activity modeling and regulatory impact prediction of genetic variants in farmed animals using deep learning
Authors: Nguyen Dat Thanh , Knutsen Tim Martin , Sandve Simen R. , Lien Sigbjørn , Grønvold Lars 
Published: February 2025

AbstractNon-coding genomic variations are crucial for the genetic regulation of traits; how-ever, their functional impact in farmed animals remains underexplored due to lim-ited genomic resources and the absence of tailored computational tools. Here, we present a deep learning-based framework that utilizes functional genomics data to generate genome-wide predictions of the regulatory impact of non-coding vari-ants in cattle, chicken, pig, and Atlantic salmon. By leveraging chromatin profiles such as ATAC, DHS, and ChIP-seq data, we train and optimize separate deep networks for each species, achieving robust sequence modeling accuracy specific to each. Motif analysis confirms that the models capture regulatory grammar, while in silico saturation mutagenesis experiments provide meaningful interpretations of the functional impact of putative causal variants. Furthermore, functional scores derived from these models predict eQTL causal variants and enhance genomic prediction performance. Our findings highlight the transformative potential of se-quence to function models in prioritizing causal variants and improving genomic prediction for livestock and aquaculture.
Receptor tyrosine kinase AXL regulates Golgi organization and function through an adhesion-Arf1 signaling axis in breast and lung cancers
Authors: Joshi Prachi , Saha Arnav , Malaviya Radhika , Panda Debiprasad , Mehta Grishma , Pattanayak Manojeet , Singh Vibha , Balasubramanian Nagaraj 
Published: February 2025

AbstractCell-matrix adhesion regulates membrane trafficking, Golgi organisation and function. Differential Golgi organisation in cancer cells could drive changes in trafficking and processing of cargoes. A simple screen evaluating Golgi organisation identifies breast (MDAMB231 vs MCF7) and lung cancer (A549 vs CaLu1) cell line pairs with differently organised Golgi, regulated differentially by loss of adhesion. In silico analysis of differentially expressed genes in the CCLE database, evaluated for their association with the Golgi in interaction networks and literature, identified AXL as a putative regulator of Golgi in these cancers. AXL prominently localized at the Golgi, undergoes displacement from the Golgi when inhibited by R428 and knocked down using siRNA, causing the Golgi to disorganize. AXL-dependent regulation of Golgi organisation is also dependent on cell-matrix adhesion. AXL binds active Arf1, whose recruitment to the Golgi is vital for its organisation. On loss of adhesion, loss of AXL and active Arf1 from the Golgi, drives its disorganization to affect Golgi-dependent microtubule acetylation and cell surface glycosylation in MDAMB231 and A549 cells respectively. Together, this validates our screen to identify novel regulators of the Golgi, and identifies AXL-Arf1 crosstalk as a vital mediator of its organisation and function in cancer cells.
Neural circuit mechanisms to transform cerebellar population dynamics for motor control in monkeys
Authors: Herzfeld David J. , Lisberger Stephen G. 
Published: February 2025

AbstractWe exploit identification of neuron types during extracellular recording to demonstrate how the cerebellar cortex’s well-established architecture transforms inputs into outputs. During smooth pursuit eye movements, the floccular complex performs distinct input-output transformations of temporal dynamics and directional response properties. The responses of different interneuron types localize the circuit mechanisms of each transformation. Mossy fibers and unipolar brush cells emphasize eye position dynamics uniformly across the cardinal axes; Purkinje cells and molecular layer interneurons code eye velocity along directionally biased axes; Golgi cells show unmodulated firing. Differential directional response properties of different neuron types localize the directional input-output transformation to the last-order inputs to Purkinje cells. Differential temporal dynamics pinpoint the site of the temporal input-output transformation to granule cells. Specific granule cell population dynamics allow the temporal transformations required in the area we study and generalize to many temporal transformations, providing a complete framework to understand cerebellar circuit computation.Impact statementWe dissect the circuit computations performed by the floccular complex of the cerebellum during an exemplar sensory-motor behavior, taking advantage of knowledge of the circuit architecture, existence of discrete neuron types, and a newfound ability to identify neuron types from extracellular recordings. Our results describe the contributions of the major neuron types to the cerebellar input-output computations, identify the population dynamics needed in granule cells to support those computations, and to create a basis set to enable temporally-specific motor behavior and motor learning.