bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visuospatial Learning Selectively Enhanced by Personalized Transcranial Magnetic Stimulation over Parieto-Hippocampal Network among Patients at Clinical High-Risk for Psychosis
Authors: Tang Yingying , Xu Lihua , Zhu Tianyuan , Cui Huiru , Qian Zhenying , Kong Gai , Tang Xiaochen , Wei Yanyan , Zhang Tianhong , Hu Yegang , Sheng Jianhua , Wang Jijun 
Published: February 2023

AbstractBackground and HypothesisCognitive deficits in visuospatial learning (VSL) are highly associated with an increased risk of developing psychosis among populations with clinical high risk (CHR) for psychosis. Early interventions targeting VSL enhancement are warranted in CHR but remain rudimentary. We investigated whether personalized transcranial magnetic stimulation (TMS) over the left parieto-hippocampal network could improve VSL performance in CHR patients and if it could reduce the risk of psychosis conversion within 1 year.Study DesignSixty-five CHR patients were randomized to receive active or sham TMS treatments using an accelerated TMS protocol, consisting of 10 sessions of 20 Hz TMS treatments within 2 days. TMS target was defined by individual parieto-hippocampal functional connectivity and precisely localized by individual structural magnetic resonance imaging. VSL performance was measured using Brief Visuospatial Memory Test-Revised included in measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery (MCCB). Fifty-eight CHR patients completed the TMS treatments and MCCB assessments and were included in the data analysis.Study ResultsWe observed significant VSL improvements in the active TMS subgroup (Cohen’s d = 0.71, P &lt; .001) but not in the sham TMS subgroup (Cohen’s d = 0.07, P = .70). In addition, active TMS improved the precision of VSL performance. At a 1-year follow-up, CHR patients who received active TMS showed a lower psychosis conversion rate than those who received sham TMS (6.7% vs 28.0%, χ2 = 4.45, P = .03).ConclusionsOur findings demonstrate that personalized TMS in the left parieto-hippocampal network may be a promising preventive intervention that improves VSL in CHR patients and reduces the risk of psychosis conversion at follow-up.
Validation and clinical discovery demonstration of a real-world data extraction platform
Authors: Nottke Amanda , Alan Sophia , Brimble Elise , Cardillo Anthony B. , Henderson Lura , Littleford Hana E. , Rojahn Susan , Sage Heather , Taylor Jessica , West-Odell Lisandra , Berk Alexandra 
Published: February 2023

ABSTRACTObjectiveTo validate and demonstrate the clinical discovery utility of a novel patient-mediated, medical record collection and data extraction platform developed to improve access and utilization of real-world clinical data.MethodsClinical variables were extracted from the medical records of consented patients with metastatic breast cancer. To validate the extracted data, case report forms completed using the structured data output of the platform were compared to manual chart review for 50 patients. To demonstrate the platform’s clinical discovery utility, we assessed associations between time to distant metastasis (TDM) and tumor histology, molecular type, and germlineBRCAstatus in the platform-extracted data of 194 patients.ResultsThe platform-extracted data had 97.6% precision (91.98%–100% by variable type) and 81.48% recall (58.15%–95.00% by variable type) compared to manual chart review. In our discovery cohort, the shortest TDM was significantly associated with metaplastic (739.0 days) and inflammatory histologies (1,005.8 days), HR-/HER2- molecular types (1,187.4 days), and positiveBRCAstatus (1,042.5 days) as compared to other histologies, molecular types, and negativeBRCAstatus, respectively. Multivariable analyses did not produce statistically significant results, but the average TDMs are reported.DiscussionThe platform-extracted clinical data are precise and comprehensive. The data can generate clinically-relevant insights.ConclusionThe structured real-world data produced by a patient-mediated, medical record-extraction platform are reliable and can power clinical discovery.
Initial Experience with Intercostal Insertion of an Extravascular ICD Lead Compatible with Existing Pulse Generators
Authors: Burke Martin C. , Knops Reinoud E. , Reddy Vivek , Aasbo Johan , Husby Michael , Marcovecchio Alan , O’Connor Mark , Sanghera Rick , Scheck Don , Pepplinkhuizen Shari , Ebner Adrian 
Published: February 2023

Structured AbstractObjectivesThis study assessed safety and feasibility of a novel extravascular (EV) implantable cardioverter-defibrillator (ICD) lead when inserted anteriorly through a rib space and connected to various commercially available ICD pulse generators (PGs) placed in either a left mid-axillary or left pectoral pocket.BackgroundCurrently available or investigational, EV-ICDs include a subcutaneous or subxiphoid lead connected to customized EV-ICD PGs. This novel EV-ICD (AtaCor Medical, Inc, San Clemente, CA) employs a unique intercostal implant technique and is designed to function with commercial DF-4 ICD PGs.MethodsIn this non-randomized, single-center, acute study, 36 de novo or replacement transvenous (TV) ICD patients enrolled to receive a concomitant EV-ICD lead inserted through an intercostal space along the left parasternal margin. EV-ICD leads were connected to DF-4 compatible ICD PGs positioned in either a left mid-axillary or pectoral pocket for acute sensing and defibrillation testing. Defibrillation testing started at 30 Joules (J) and stepped down in 10 J increments following conversion success and stepped up in 5 J increments following conversion failure.ResultsSuccessful acute defibrillation using ≤ 35 J was noted in 100% of left mid-axillary PG subjects (n=27, mean 16.3 ± 8.6 J) and 83% of left pectoral PG subjects (n=6, mean 21.0 ± 8.4 J). All evaluable episodes (n=93) were automatically sensed, detected, and shocked. No serious device-related intraoperative adverse events were observed.ConclusionsThis first-in-human study documented safe and reliable placement of a novel extravascular ICD lead with effective sensing and defibrillation of induced ventricular fibrillation using commercial DF-4 ICD pulse generators.Condensed AbstractThis study assessed feasibility of intercostal implantation of a novel extravascular implantable cardioverter-defibrillator (ICD) lead designed to function with commercial DF-4 pulse generators (PGs). Lead placement was successful in 33 of 36 attempts (94%). Acute defibrillation with ≤35 J was successful in 27 of 27 left mid-axillary PG subjects (100%) and 5 of 6 left pectoral PG subjects (83%). All evaluable episodes (n=93) were automatically detected. No serious device-related intraoperative adverse events were observed. This study demonstrates feasibility of a novel extravascular ICD lead with effective sensing and defibrillating of induced ventricular fibrillation using commercial DF-4 PGs.
Hypertensive adults exhibit lower myelin content: A multicomponent relaxometry and diffusion MRI study
Authors: Laporte John P. , Faulkner Mary E. , Gong Zhaoyuan , Akhonda Mohammad A.B.S. , Ferrucci Luigi , Egan Josephine M. , Bouhrara Mustapha 
Published: February 2023

AbstractIt is unknown whether hypertension plays any role in cerebral myelination. To fill this knowledge gap, we studied ninety cognitively unimpaired adults, age range 40 to 94 years, that are participants in the Baltimore Longitudinal Study of Aging (BLSA) and the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) to look for potential associations between hypertension and cerebral myelin content across fourteen white matter brain regions. Myelin content was probed using our advanced multicomponent magnetic resonance (MR) relaxometry method of myelin water fraction (MWF), a direct and specific MR imaging (MRI) measure of myelin content, and longitudinal and transverse relaxation rates (R1andR2), two highly sensitive MRI metrics of myelin content. We also applied diffusion tensor imaging (DTI) MRI to measure fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AxD) values, which are metrics of cerebral microstructural tissue integrity, to provide contact with previous MRI findings. After adjustment of age, sex, systolic blood pressure, smoking status, diabetes status and cholesterol level, our results indicated that participants with hypertension exhibited lower MWF, FA,R1andR2values and higher MD, RD and AxD values, indicating lower myelin content and higher impairment to the brain microstructure. These associations were significant across several white matter regions, particularly in the corpus callosum, fronto-occipital fasciculus, temporal lobes, internal capsules, and corona radiata. These original findings suggest a direct association between myelin content and hypertension, and form the basis for further investigations including longitudinal assessments of this relationship.
A Snapshot of COVID-19 Incidence, Hospitalizations, and Mortality from Indirect Survey Data in China in January 2023
Authors: Ramírez Juan M. , Díaz-Aranda Sergio , Aguilar Jose , Ojo Oluwasegun , Lillo Rosa Elvira , Anta Antonio Fernández 
Published: February 2023

AbstractIn this work we estimate the incidence of COVID-19 in China using online indirect surveys (which preserve the privacy of the participants). The indirect surveys deployed collect data on the incidence of COVID-19, asking the participants about the number of cases, deaths, vaccinated, and hospitalized that they know. The incidence of COVID-19 (cases, deaths, etc.) is then estimated using a modified Network Scale-up Method (NSUM). Survey responses (100, 200 and 1,000, respectively) were collected from Australia, the UK, and China in January 2023. The estimates in Australia and the UK are compared with official data, showing that they are in the confidence intervals or rather close. Cronbach’s alpha values also indicate good confidence in the estimates. The estimates obtained in China are, among others, that 91% of the population is vaccinated, almost 80% had been infected in the last month, and almost 3% in the last 24 hours.
Disability evaluation in patients with Guillain-Barre syndrome and SARS-CoV-2 infection from a neurological reference center in Peru
Authors: Sanchez Boluarte Sofia Stefanie , Quispe Wilfor Aguirre , Sanchez Boluarte Arantxa Noelia , Cuellar Jhon Tacunan , Segura Chávez Darwin Alberto 
Published: February 2023

ABSTRACTIntroductionseveral cases of Guillain-Barre Syndrome (GBS) associated with SARS-CoV-2 infection have been described. This study illustrated the demographic, clinical, and neurophysiological characteristics of patients with GBS and COVID-19, as well as associated factors with disability at discharge.MethodsA retrospective analytical observational study was conducted. It included patients diagnosed with GBS admitted in a national reference center in Peru between 2019 and 2021. Epidemiological, clinical, neurophysiological and cerebrospinal fluid data were analyzed. A multivariate analysis, using the generalized linear model, was performed, considering the presence of disability at discharge as the dependent variable.Results81 subjects diagnosed with GBS were included. The mean age was 46.8 years (SD: 15.2), with a predominance of males (61.73%). The most frequent clinical presentation was the classic sensory-motor form in 74 cases (91.36%) with AIDP (82.35%) as the most frequent neurophysiological pattern in the group with COVID-19, while AMAN pattern predominated (59.26%) in those without COVID-19 (p=<0.000). The disability prevalence ratio at discharge between subjects with COVID-19 and those without COVID-19 was 1.89 (CI 1.06–3.34), p=0.030, adjusted for age, sex, and neurophysiological subtype.ConclusionsThe neurophysiologic subtype AIDP, and a higher disability were associated with the presence of COVID-19.
Systematic review and meta-analysis of the accuracy of McIsaac and Centor score in patients presenting to secondary care with Pharyngitis
Authors: Kanagasabai Atchchuthan , Evans Callum , Jones Hayley E , Hay Alastair D , Dawson Sarah , Savović Jelena , Elwenspoek Martha M C 
Published: February 2023

AbstractBackgroundCentor and modified Centor (McIsaac) scores are clinical prediction rules used to diagnose group A streptococcus infection in patients with pharyngitis. They aim to identify the patients most likely to benefit from antibiotic treatment and reduce unnecessary antibiotic prescribing.ObjectivesTo systematically review the literature on the diagnostic accuracy of McIsaac and Centor, and produce pooled estimates of accuracy at each score threshold, in patients presenting with acute pharyngitis to secondary care.Data sourcesMEDLINE, Embase and Web of science were searched from inception to June 2021.Eligibility criteriaStudies that included patients who presented with acute pharyngitis to hospital emergency departments and outpatient clinics, reported McIsaac or Centor scores, and used throat cultures and/or rapid antigen detection tests as the reference standard.Review methodsThe review protocol was registered on PROSPERO (CRD42021267413). Study selection was performed by two reviewers independently and risk of bias was assessed using the QUADAS-2 tool. Sensitivities and specificities of McIsaac and Centor scores were pooled at each threshold using bivariate random effects meta-analysis.ResultsThe McIsaac score had higher estimated sensitivity and lower specificity relative to Centor scores at equivalent thresholds, but with wide and overlapping confidence regions. Using either score as a triage to rapid antigen detection tests (RADT) to decide antibiotic treatment would reduce antibiotic prescription to non-GAS pharyngitis patients relative to RADT test for everyone, but also reduce antibiotic prescription to GAS patients.ConclusionOur findings suggest that high thresholds of either score excludes a proportion of true positive patients from potentially beneficial treatment. The use of a low threshold before a RADT test would reduce antibiotic prescription relative to prescribing based on score only but the economics and clinical effectiveness of this combination strategy needs assessment. We recommend continued use of existing antibiotic prescribing guidelines and patient safety netting.
Deep learning predicts HRD and platinum response from histology slides in breast and ovarian cancer
Authors: Bergstrom Erik N. , Abbasi Ammal , Díaz-Gay Marcos , Galland Loïck , Lippman Scott M. , Ladoire Sylvain , Alexandrov Ludmil B. 
Published: February 2023

ABSTRACTBreast and ovarian cancers harboring homologous recombination deficiencies (HRD) can benefit from platinum-based chemotherapies and PARP inhibitors. Standard diagnostic tests for detecting HRD utilize molecular profiling, which is not universally available especially for medically underserved populations. Here, we trained a deep learning approach for predicting genomically derived HRD scores from routinely sampled hematoxylin and eosin (H&E)-stained histopathological slides. For breast cancer, the approach was externally validated on three independent cohorts and allowed predicting patients’ response to platinum treatment. Using transfer learning, we demonstrated the method’s clinical applicability to H&E-images from high-grade ovarian tumors. Importantly, our deep learning approach outperformed existing genomic HRD biomarkers in predicting response to platinum-based therapies across multiple cohorts, providing a complementary approach for detecting HRD in patients across diverse socioeconomic groups.One-Sentence SummaryA deep learning approach outperforms molecular tests in predicting platinum response of HRD cancers from histological slides.
Dynamic functional connectivity MEG features of Alzheimer’s disease
Authors: Jin Huaqing , Ranasinghe Kamalini G , Prabhu Pooja , Dale Corby , Gao Yijing , Kudo Kiwamu , Vossel Keith , Raj Ashish , Nagarajan Srikantan S , Jiang Fei 
Published: February 2023

AbstractDynamic resting state functional connectivity (RSFC) characterizes time-varying fluctuations of functional brain network activity. While many studies have investigated static functional connectivity, it has been unclear whether features of dynamic functional connectivity are associated with neurodegenerative diseases. Popular sliding-window and clustering methods for extracting dynamic RSFC have various limitations that prevent extracting reliable features to address this question. Here, we use a novel and robust time-varying dynamic network (TVDN) approach to extract the dynamic RSFC features from high resolution magnetoencephalography (MEG) data of participants with Alzheimer’s disease (AD) and matched controls. The TVDN algorithm automatically and adaptively learns the low-dimensional spatiotemporal manifold of dynamic RSFC and detects dynamic state transitions in data. We show that amongst all the functional features we investigated, the dynamic manifold features are the most predictive of AD. These include: the temporal complexity of the brain network, given by the number of state transitions and their dwell times, and the spatial complexity of the brain network, given by the number of eigenmodes. These dynamic features have high sensitivity and specificity in distinguishing AD from healthy subjects. Intriguingly, we found that AD patients generally have higher spatial complexity but lower temporal complexity compared with healthy controls. We also show that graph theoretic metrics of dynamic component of TVDN are significantly different in AD versus controls, while static graph metrics are not statistically different. These results indicate that dynamic RSFC features are impacted in neurodegenerative disease like Alzheimer’s disease, and may be crucial to understanding the pathophysiological trajectory of these diseases.
Identifying the role of household immunity in driving individual dengue virus infection risk
Authors: Hamins-Puértolas Marco , Buddhari Darunee , Salje Henrik , Cummings Derek A.T. , Fernandez Stefan , Farmer Aaron , Kaewhiran Surachai , Khampaen Direk , Iamsirithaworn Sopon , Thomas Stephen J. , Endy Timothy , Srikiatkhachorn Anon , Rothman Alan L. , Rodriguez-Barraquer Isabel , Anderson Kathryn B. 
Published: February 2023

AbstractDengue virus (DENV) infection risk is known to vary substantially, even across small communities, with infections in and around the home driving transmission. However, It remains unclear how the immune status of an individual or household dictate this risk in part due to transmission being dominated by subclinical infections. In this study, we used demographic, household characteristic, and serological data from a multigenerational cohort study of 2860 individuals from 470 households in Kamphaeng Phet, Thailand, to determine the incidence and risk factors for DENV infections. We used hemagglutination inhibition (HAI) antibody titers measured in sequential serum samples to identify subclinical infections through a gradient boosted regression model. This approach identified ∼10% more cases than commonly used methods with approximately 90% of all infections being subclinical. As expected, we found that having higher DENV antibody titers was protective against infection. Individuals were additionally protected if other household members had higher titers suggesting that there are indirect effects of household immunity on the individuals found within a household. Our study provides a framework for inferring subclinical infections and characterizing the epidemiology of DENV infection in households.
Efficient and scalablede novoprotein design using a relaxed sequence space
Authors: Frank Christopher , Khoshouei Ali , de Stigter Yosta , Schiewitz Dominik , Feng Shihao , Ovchinnikov Sergey , Dietz Hendrik 
Published: February 2023

AbstractDeep learning techniques are being used to design new proteins by creating target backbone geometries and finding sequences that can fold into those shapes. While methods like ProteinMPNN provide an efficient algorithm for generating sequences for a given protein backbone, there is still room for improving the scope and computational efficiency of backbone generation. Here, we report a backbone hallucination protocol that uses a relaxed sequence representation. Our method enables protein backbone generation using a gradient descent driven hallucination approach and offers orders-of-magnitude efficiency enhancements over previous hallucination approaches. We designed and experimentally produced over 50 proteins, most of which expressed well in E. Coli, were soluble and adopted the desired oligomeric state along with the correct composition of secondary structure as measured by CD. Exemplarily,wedetermined 3D electron density maps using single-particle cryo EM analysis for three single-chainde-novoproteins comprising 600 AA which closely matched with the designed shape. These have no structural analogues in the protein data bank (PDB), representing potentially novel folds or arrangement of domains. Our approach broadens the scope of de novo protein design and contributes to accessibility to a wider community.
Chromosome-specific maturation of the epigenome in the Drosophila male germline
Authors: Anderson James , Henikoff Steven , Ahmad Kami 
Published: February 2023

AbstractSpermatogenesis in the Drosophila male germline proceeds through a unique transcriptional program controlled both by germline-specific transcription factors and by testis-specific versions of core transcriptional machinery. This program includes the activation of genes on the heterochromaticYchromosome, and reduced transcription from theXchromosome, but how expression from these sex chromosomes is regulated has not been defined. To resolve this, we profiled active chromatin features in the testes from wildtype and meiotic arrest mutants and integrate this with single-cell gene expression data from the Fly Cell Atlas. These data assign the timing of promoter activation for genes with germline-enriched expression throughout spermatogenesis, and general alterations of promoter regulation in germline cells. By profiling both active RNA polymerase II and histone modifications in isolated spermatocytes, we detail widespread patterns associated with regulation of the sex chromosomes. Our results demonstrate that theXchromosome is not enriched for silencing histone modifications, implying that sex chromosome inactivation does not occur in the Drosophila male germline. Instead, a lack of dosage compensation in spermatocytes accounts for the reduced expression from this chromosome. Finally, profiling uncovers dramatic ubiquitinylation of histone H2A and lysine-16 acetylation of histone H4 across theYchromosome in spermatocytes that may contribute to the activation of this heterochromatic chromosome.