bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of thoracic outlet syndrome to alleviate chronic migraine headache
Authors: Randall L , Ahn S. , Weber J. , Cha Y.H. 
Published: September 2023

ABSTRACTBackgroundPrior case reports have indicated that treating thoracic outlet syndrome (TOS) may relieve intractable migraine headaches, but the reported experience has been limited. We report in a large case series how a strategy of treating concurrent TOS can help relieve intractable migraine headaches in patients with these dual diagnoses.MethodsRetrospective chart review for diagnostic and interventional data on patients with migraine and TOS followed by a questionnaire to investigate specific migraine features and changes in headache burden before and after treatment of TOS.Results50 patients (48 women, 2 men, age = 43.9+/12.7years) with dual diagnoses of chronic migraine and TOS were included (20 migraine with aura, 28 migraine without aura, two hemiplegic migraines). Based on review of available data, headaches had become chronic within one year of onset in 21 patients (42%) and included these characteristics: side-locked or greater severity ipsilateral to limb paresthesia (38/50 patients), presence of limb swelling (32/48 patients), and worsened by recumbency (32/38 patients). Interventions included physical therapy, percutaneous transluminal venoplasty, 1st rib removal, scalenectomy, pectoralis minor tenotomy, and vein patching. Thirty-two patients needed surgery. Mean patient-reported improvement of headaches on the treated side was 72+/-26.7%; 12 patients experienced complete resolution of headaches after surgical treatment of TOS (follow-up 7.2+/-5.2 months). Questionnaire responders reported significant reductions in headache days (18.3+/-8.6 to 11.1+/-10.8 days/month, p<0.0016), severity (7.8+/2.5 to 5.4+/-2.9, p<0.00079), and need for emergency care (3.6+/-4.0 to 0.71+/-1.3 visits/year, p<0.0029) after having had their TOS treated with surgery. Questionnaire responders and non-responders were not significantly different in underlying clinical features.ConclusionChronic migraines can be important manifestations of TOS. Early transition to a chronic state, headaches worsened by recumbency, and headaches with lateralized myofascial pain are clues to a contribution by TOS pathology. The TOS contribution to migraine has been under-recognized. Addressing it can significantly improve migraine headache burden.
Deep multiple-instance learning accurately predicts gene haploinsufficiency and deletion pathogenicity
Authors: Liu Zhihan , Huang Yi-Fei 
Published: September 2023

AbstractCopy number losses (deletions) are a major contributor to the etiology of severe genetic disorders. Although haploinsufficient genes play a critical role in deletion pathogenicity, current methods for deletion pathogenicity prediction fail to integrate multiple lines of evidence for haploinsufficiency at the gene level, limiting their power to pinpoint deleterious deletions associated with genetic disorders. Here we introduce DosaCNV, a deep multiple-instance learning framework that, for the first time, models deletion pathogenicity jointly with gene haploinsufficiency. By integrating over 30 gene-level features potentially predictive of haploinsufficiency, DosaCNV shows unmatched performance in prioritizing pathogenic deletions associated with a broad spectrum of genetic disorders. Furthermore, DosaCNV outperforms existing methods in predicting gene haploinsufficiency even though it is not trained on known haploinsufficient genes. Finally, DosaCNV leverages a state-of-the-art technique to quantify the contributions of individual gene-level features to haploinsufficiency, allowing for human-understandable explanations of model predictions. Altogether, DosaCNV is a powerful computational tool for both fundamental and translational research.
PFAS assessment in fish – samples from Illinois waters
Authors: Sands Mia , Zhang Xing , Jensen Tor , Frano Michael La , Lin Mindy , Irudayaraj Joseph 
Published: September 2023

AbstractPer- and Polyfluoroalkyl substances (PFAS) have been widely used in various industries, including pesticide production, electroplating, packaging, paper making, and the manufacturing of water-resistant clothes. This study investigates the levels of PFAS in fish tissues collected from four target waterways (15 sampling points) in the northwestern part of Illinois during 2021-2022. To assess accumulation, concentrations of 17 PFAS compounds were evaluated in nine fish species to potentially inform on exposure risks to local sport fishing population via fish consumption. At least four PFAS (PFHxA, PFHxS, PFOS, and PFBS) were detected at each sampling site. The highest concentrations of PFAS were consistently found in samples from the Rock River, particularly in areas near urban and industrial activities. PFHxA emerged as the most accumulated PFAS in the year 2022, while PFBS and PFOS dominated in 2021. Channel Catfish exhibited the highest PFAS content across different fish species, indicating its bioaccumulation potential across the food chain. Elevated levels of PFOS were observed in nearly all fish, indicating the need for careful consideration of fish consumption. Additional bioaccumulation data in the future years is needed to shed light on the sources and PFAS accumulation potential in aquatic wildlife in relation to exposures for potential health risk assessment.
Rapamycin mitigates Valproic Acid-induced teratogenicity in human and animal models by suppressing AP-1-mediated senescence
Authors: Pietrogrande Giovanni , Shaker Mohammed R. , Stednitz Sarah J. , Soheilmoghaddam Farhad , Aguado Julio , Morrison Sean , Zambrano Samuel , Tabassum Tahmina , Javed Ibrahim , Cooper-White Justin , Davis Thomas P. , O’Brien Terence J , Scott Ethan K. , Wolvetang Ernst J. 
Published: September 2023

AbstractValproic acid (VPA) is an effective and widely used anti-seizure medication but is teratogenic when used during pregnancy, affecting brain and spinal cord development for reasons that remain largely unclear. Here we designed a genetic recombinase-basedSOX10reporter system in human pluripotent stem cells that enables tracking and lineage tracing of Neural Crest cells (NCCs) in a human organoid model of the developing neural tube. We found that VPA induces extensive cellular senescence and promotes mesenchymal differentiation of human NCCs at the expense of neural lineages. We next show that the clinically-approved drug, Rapamycin, inhibits AP1-mediated senescence and restores aberrant NCC differentiation trajectory in human organoids exposed to VPA. Notably,in vivovalidation in developing zebrafish highlighted the therapeutic promise of this approach. Collectively our data identifies a novel mechanism for VPA-associated neurodevelopmental teratogenicity and a potential pharmacological preventative strategy. The results exemplify the power of genetically modified human stem cell-derived organoid models for drug discovery and safety testing.
Loss of finger control complexity and intrusion of flexor biases are dissociable in finger individuation impairment after stroke
Authors: Xu Jing , Ma Timothy , Kumar Sapna , Olds Kevin , Brown Jeremy , Carducci Jacob , Forrence Alex , Krakauer John 
Published: September 2023

AbstractThe ability to control each finger independently is an essential component of human hand dexterity. A common observation of hand function impairment after stroke is the loss of this finger individuation ability, often referred to as enslavement, i.e., the unwanted coactivation of non-intended fingers in individuated finger movements. In the previous literature, this impairment has been attributed to several factors, such as the loss of corticospinal drive, an intrusion of flexor synergy due to upregulations of the subcortical pathways, and/or biomechanical constraints. These factors may or may not be mutually exclusive and are often difficult to tease apart. It has also been suggested, based on a prevailing impression, that the intrusion of flexor synergy appears to be an exaggerated pattern of the involuntary coactivations of task-irrelevant fingers seen in a healthy hand, often referred to as a flexor bias. Most previous studies, however, were based on assessments of enslavement in a single dimension (i.e., finger flexion/extension) that coincide with the flexor bias, making it difficult to tease apart the other aforementioned factors. Here, we set out to closely examine the nature of individuated finger control and finger coactivation patterns in all dimensions. Using a novel measurement device and a 3D finger-individuation paradigm, we aim to tease apart the contributions of lower biomechanical, subcortical constraints, and top-down cortical control to these patterns in both healthy and stroke hands. For the first time, we assessed all five fingers’ full capacity for individuation. Our results show that these patterns in the healthy and paretic hands present distinctly different shapes and magnitudes that are not influenced by biomechanical constraints. Those in the healthy hand presented larger angular distances that were dependent on top-down task goals, whereas those in the paretic hand presented larger Euclidean distances that arise from two dissociable factors: a loss of complexity in finger control and the dominance of an intrusion of flexor bias. These results suggest that finger individuation impairment after stroke is due to two dissociable factors: the loss of finger control complexity present in the healthy hand reflecting a top-down neural control strategy and an intrusion of flexor bias likely due to an upregulation of subcortical pathways. Our device and paradigm are demonstrated to be a promising tool to assess all aspects of the dexterous capacity of the hand.
OptoDyCE-plate as an affordable high throughput imager for all optical cardiac electrophysiology
Authors: Heinson Yuli W. , Han Julie L. , Entcheva Emilia 
Published: September 2023

AbstractWe present a simple low-cost system for comprehensive functional characterization of cardiac function under spontaneous and paced conditions, in standard 96 and 384-well plates. This full-plate actuator/imager, OptoDyCE-plate, uses optogenetic stimulation and optical readouts of voltage and calcium from all wells in parallel. The system is validated with syncytia of human induced pluripotent stem cell derived cardiomyocytes, iPSC-CMs, grown as monolayers, or in quasi-3D isotropic and anisotropic constructs using electrospun matrices, in 96 and 394-well format. Genetic modifications, e.g. interference CRISPR (CRISPRi), and nine compounds of acute and chronic action were tested, including five histone deacetylase inhibitors (HDACis). Their effects on voltage and calcium were compared across growth conditions and pacing rates. We also demonstrated deployment of optogenetic cell spheroids for point pacing to study conduction in 96-well format, and the use of temporal multiplexing to register voltage and calcium simultaneously on a single camera in this stand-alone platform. Opto-DyCE-plate showed excellent performance even in the small samples in 384-well plates, in the various configurations. Anisotropic structured constructs may provide some benefits in drug testing, although drug responses were consistent across tested configurations. Differential voltage vs. calcium responses were seen for some drugs, especially for non-traditional modulators of cardiac function, e.g. HDACi, and pacing rate was a powerful modulator of drug response, highlighting the need for comprehensive multiparametric assessment, as offered by OptoDyCE-plate. Increasing throughput and speed and reducing cost of screening can help stratify potential compounds early in the drug development process and accelerate the development of safer drugs.
Three-year outcomes with fractional flow reserve- or angiography-guided multivessel percutaneous coronary intervention for myocardial infarction
Authors: Puymirat Etienne , Cayla Guillaume , Simon Tabassome , Steg Philippe Gabriel , Montalescot Gilles , Durand-Zaleski Isabelle , Siaha Fabiola Ngaleu , Gallet Romain , Khalife Khalife , Morelle Jean-François , Motreff Pascal , Lemesle Gilles , Dillinger Jean-Guillaume , Lhermusier Thibault , Silvain Johanne , Roule Vincent , Labèque Jean-Noel , Rangé Grégoire , Ducrocq Grégory , Cottin Yves , Blanchard Didier , Nelson Anaïs Charles , Djadi-Prat Juliette , Chatellier Gilles , Danchin Nicolas ,   the FLOWER-MI study investigators
Published: September 2023

ABSTRACTBackgroundIn multivessel disease (MVD) patients with successful primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI), the Flow Evaluation to Guide Revascularization in Multivessel ST-Elevation Myocardial Infarction (FLOWER-MI) trial showed that a fractional flow reserve (FFR)-guided strategy was not superior to an angiography-guided strategy for treatment of non-infarct-related artery lesions regarding the one-year risk of death from any cause, MI, or unplanned hospitalization leading to urgent revascularization. The extension phase of the trial was planned using the same primary outcome to determine whether a difference in outcomes would be observed with a longer follow-up.MethodsIn this multicenter trial, we randomly assigned patients with STEMI and MVD with successful PCI of the infarct-related artery to receive complete revascularization guided by either FFR (n=586) or angiography (n=577).ResultsAfter 3 years, a primary outcome event occurred in 52 of 498 patients in the FFR-guided group and in 44 of 502 patients in the angiography-guided group (hazard ratio[HR], 1.19; 95% confidence interval [CI], 0.79-1.77;P=0.4). Death occurred in 22 patients in the FFR-guided group and in 23 in the angiography-guided group (HR, 0.96; 95% CI 0.53-1.71); nonfatal MI in 23 and 14), respectively (HR, 1.63; 95% CI 0.84-3.16); and unplanned hospitalization leading to urgent revascularization in 21 and 18 (HR, 1.15; 95% CI 0.61-2.16), respectively.ConclusionsAlthough event rates in the trial were lower than expected, in patients with STEMI undergoing complete revascularization, an FFR-guided strategy had not a significant benefit over an angiography-guided strategy with respect to the risk of death, MI, or urgent revascularization up to 3 years. (Funded by the French Ministry of Health and Abbott; FLOWER-MIClinicalTrials.govnumber,NCT02943954.)CLINICAL PERSPECTIVEWhat Is New?In STEMI patients with MVD, an FFR-guided strategy is not superior to an angiography-guided strategy for treatment of non-infarct-related artery lesions regarding the risk of death from any cause, MI, or unplanned hospitalization leading to urgent revascularization at 3 years.What Are the Clinical Implications?In patients with STEMI undergoing complete revascularization, an FFR-guided strategy had no significant benefit over an angiography-guided strategy with respect to the risk of death, MI, or urgent revascularization up to 3 years.
The Link Between Atrial Fibrillation And Cognitive Impairment: A Systematic Review And Meta-Analysis
Authors: Agarwal Abhimanyu , Mostafa Mohamed A. , Ahmad Muhammad Imtiaz , Soliman Elsayed Z. 
Published: September 2023

AbstractAtrial fibrillation (AF) affects a substantial population of individuals aged ≥55 years globally and has been associated with an increased risk of cognitive impairment (CImp) due to the shared risk factors such as aging, obesity, and diabetes. It is essential to comprehend their unique relationship to manage them effectively to reduce its impact on public health systems. We performed a PubMed search of English language papers published till 31 May 2023. Data was extracted and effect measures were calculated. Meta-analysis of 33 studies revealed a significant association between AF and CImp after adjusting for comorbidities, with considerable between-study heterogeneity (pooled OR: 1.62; 95% CI: 1.43, 1.81, I2= 94.143). Prospective and cross-sectional studies revealed substantial associations. CImp in AF may be mediated through silent brain infarctions, microemboli, brain atrophy, and inflammation. Future research should prioritize investigating the mechanisms and etiology of this association, as well as potential treatment options.
Ultrasound-guided bleomycin sclerotherapy for Warthin’s tumor: preliminary results of a prospective study
Authors: Castren Eeva , Sirviö Minna , Aro Katri , Lappalainen Kimmo , Lindén Riikka , Kurdo Goran , Tarkkanen Jussi , Mäkitie Antti , Atula Timo 
Published: September 2023

AbstractBackgroundWarthin’s tumor (WT) is the second most common parotid gland neoplasm with rising incidence. As some WT patients are not suitable for surgery, non-surgical treatment options are needed. This is the first study to evaluate the feasibility of ultrasound-guided bleomycin sclerotherapy (UGBS) for WT.Patients and methodsWT patients with concordant clinical, imaging, and cytology data were included. UGBS was proposed for patients who desired non-surgical intervention and fulfilled the inclusion criteria. Tumor volume and tumor-related symptoms were registered before UGBS and six months after.ResultsNine patients underwent UGBS between September 2021 and September 2022. In seven of the nine patients (78%), the tumor volume had diminished on average by 34% at six-month follow-up. Also, tumor-related pain, and cosmetic and functional discomfort decreased during the follow-up. One patient was later referred to partial parotidectomy.ConclusionUGBS could be an alternative non-surgical treatment for WT, especially for patients with risk factors for surgery.
Characterizing the Extended Language Network in Individuals with Multiple Sclerosis
Authors: Ratzan Alexander S. , Simani Leila , Dworkin Jordan D. , Buyukturkoglu Korhan , Riley Claire S. , Leavitt Victoria M. 
Published: September 2023

AbstractBackgroundCognitive impairment is a pervasive, functionally limiting symptom of multiple sclerosis (MS), a disease of the central nervous system that is the most common non-traumatic cause of neurologic disability in young adults. Recently, language dysfunction has received increased attention as a prevalent and early affected cognitive domain in individuals with MS.ObjectivesTo establish a network-level model of language dysfunction in MS.MethodsCognitive data and 3T structural and functional brain magnetic resonance imaging (MRI) scans were acquired from 54 MS patients and 54 healthy controls (HCs). Summary measures of the extended language network (ELN) and structural imaging metrics were calculated. Group differences in ELN summary measures were evaluated. Associations between ELN summary measures and language performance were assessed in both groups; in the MS group, a two-step regression analysis was applied to assess relationships between additional language-specific imaging measures and language performance.ResultsIn comparison to the HC group, the MS group performed significantly worse on the semantic fluency and rapid automized naming tests (p< 0.005). Concerning the ELN summary measures, the MS group exhibited higher within-ELN connectivity than the HCs (0.11 ± 0.02 vs. 0.10 ± 0.01,p< 0.05, respectively). While no significant relationships between ELN summary measures and language function were observed in either group, the regression analysis identified a set of 17 imaging features that predicted performance on the rapid automized naming test (p< 0.05) and identified key white matter tracts predicting language function in individuals with MS.ConclusionThe derived functional network-level measures, combined with the identified structural neuroimaging metrics, constitute a comprehensive set of imaging features to characterize language dysfunction in MS. Further studies leveraging these features may uncover underlying mechanisms and clinically relevant predictors of language dysfunction, potentially leading to improved precision treatment strategies for cognitively impaired patients with multiple sclerosis.
The pivotal role of the X-chromosome in the genetic architecture of the human brain
Authors: Jiang Zhiwen , Sullivan Patrick F. , Li Tengfei , Zhao Bingxin , Wang Xifeng , Luo Tianyou , Huang Shuai , Guan Peter Y. , Chen Jie , Yang Yue , Stein Jason L. , Li Yun , Liu Dajiang , Sun Lei , Zhu Hongtu 
Published: September 2023

AbstractGenes on the X-chromosome are extensively expressed in the human brain. However, little is known for the X-chromosome’s impact on the brain anatomy, microstructure, and functional network. We examined 1,045 complex brain imaging traits from 38,529 participants in the UK Biobank. We unveiled potential autosome-X-chromosome interactions, while proposing an atlas outlining dosage compensation (DC) for brain imaging traits. Through extensive association studies, we identified 72 genome-wide significant trait-locus pairs (including 29 new associations) that share genetic architectures with brain-related disorders, notably schizophrenia. Furthermore, we discovered unique sex-specific associations and assessed variations in genetic effects between sexes. Our research offers critical insights into the X-chromosome’s role in the human brain, underscoring its contribution to the differences observed in brain structure and functionality between sexes.One-sentence SummaryWe investigated the genetic impact of the X-chromosome and the sex differences in the human brain.
Risk factors and cognitive correlates of white matter hyperintensities in ethnically diverse populations without dementia: the COSMIC consortium
Authors: Lin Keshuo , Wen Wei , Lipnicki Darren M. , Mewton Louise , Chen Rory , Du Jing , Wang Dadong , Skoog Ingmar , Sterner Therese Rydberg , Najar Jenna , Kim Ki Woong , Han Ji Won , Kim Jun Sung , Ng Tze Pin , Ho Roger , Chua Denise Qian Ling , Anstey Kaarin J. , Cherbuin Nicolas , Mortby Moyra E. , Brodaty Henry , Kochan Nicole , Sachdev Perminder S. , Jiang Jiyang ,   Cohort Studies of Memory in an International Consortium (COSMIC)
Published: September 2023

AbstractINTRODUCTIONWhite matter hyperintensities (WMH) are an important imaging marker for cerebral small vessel diseases, but their risk factors and cognitive associations have not been well-documented in populations of different ethnicities and/or from different geographical regions.METHODMagnetic resonance imaging data of five population-based cohorts of non-demented older individuals from Australia, Singapore, South Korea, and Sweden (N = 1,946) were examined for WMH and their associations with vascular risk factors and cognition.RESULTFactors associated with larger whole brain WMH volumes included diabetes, hypertension, stroke, current smoking, body mass index, higher alcohol intake and insufficient physical activity. Participants with moderate or higher physical activity had less WMH than those who never exercised, but the former two groups did not differ. Hypertension and stroke had stronger associations with WMH volumes in the White, compared to Asian subsample.DISCUSSIONThe current study highlighted the ethnic differences in the contributions of vascular risk factors to WMH.