bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and segmentation of hyperdense middle cerebral artery sign on non-contrast CT using artificial intelligence
Authors: Kim Pyeong Eun , Ha Sue Young , Lee Myungjae , Kim Nakhoon , Kim Dongmin , Sunwoo Leonard , Ryu Wi-Sun , Kim Beom Joon 
Published: July 2024

AbstractBackgroundThe hyperdense artery sign (HAS) in patients with large vessel occlusion (LVO) is associated with outcomes after ischemic stroke. Considering the labor-intensive nature of manual segmentation of HAS, we developed and validated an automated HAS segmentation algorithm on non-contrast brain CT (NCCT) images using a multicenter dataset with independent annotations by two experts.MethodsFor the training dataset, we included patients with ischemic stroke undergoing concurrent NCCT and CT angiography between May 2011 and December 2022 from six stroke centers. The model was externally validated using a dataset from one stroke center. For the clinical validation dataset, a consecutive series of patients admitted within 24 hours of symptom onset were included between December 2020 and April 2023 from six stroke centers. The model was trained using a 2D U-Net algorithm with manual segmentation by two experts. We constructed models trained on datasets annotated individually by each expert, and an ensemble model using shuffled annotations from both experts. The performance of the models was compared using area under the receiver operating characteristics curve (AUROC), sensitivity, and specificity.ResultsA total of 673, 365, and 774 patients were included in the training, external validation, and clinical validation datasets, respectively, with mean (SD) ages of 68.8 (13.2), 67.6 (13.4), and 68.8 (13.6) years and male frequencies of 55.0%, 59.5%, and 57.6%. The ensemble model achieved higher AUROC and sensitivity compared to the models trained on annotations from a single expert in the external validation dataset. In the clinical validation dataset, the ensemble model exhibited an AUROC of 0.846 (95% CI, 0.819–0.871), sensitivity of 76.8% (65.1–86.1%), and specificity of 88.5% (85.9–90.8%). The predicted volume of the clot was significantly correlated with infarct volume on follow-up diffusion-weighted imaging (r=0.42; p<0.001).ConclusionOur algorithm promptly and accurately identifies clot signs, facilitating the screening of potential patients who may require intervention.
Cognitive Enhancement in Bipolar Disorder: A Double-Blind, Randomized Controlled Trial Utilizing a Novel DTI-Guided Multimodal Neuro-stimulation Protocol
Authors: Wang Minmin , Zhang Xiaomei , Zhou Hetong , Chen Qianfeng , Tong Qiqi , Han Qiai , Zhao Xudong , Wang Dandan , Lai Jianbo , He Hongjian , Zhang Shaomin , Hu Shaohua 
Published: July 2024

AbstractBackgroundTraditional neuromodulation strategies for enhancing cognitive abilities in bipolar disorder (BD) patients have shown promise, yet there remains a need for novel intervention modalities to improve therapeutic outcomes.MethodsThis study introduces a novel multi-modal neuro-stimulaton (MNS) protocol using individualized DTI data to identify fiber tracts between the DLPFC and dACC. The highest structural connectivity point is selected as the individualized stimulation target, which is targeted using a combination of optimized tACS and robot-assisted navigated rTMS. A double-blind randomized controlled trial (Trial registration number:NCT05964777) was conducted to investigate the clinical efficacy of this innovative neuromodulation approach on cognitive abilities in BD patients. One hundred BD patients were randomly assigned to four groups: Group A (Active tACS-Active rTMS (MNS Protocol)), Group B (Sham tACS-Active rTMS), Group C (Active tACS-Sham rTMS), and Group D (Sham tACS-Sham rTMS). Participants underwent 15 sessions over three weeks. Cognitive assessments (THINC integrated tool) were conducted at baseline (Week 0), post-treatment (Week 3), and follow-up (Week 8).ResultsSixty-six participants completed all 15 sessions. Group A (MNS Protocol) showed superior improvements in Spotter CRT, TMT, and DSST scores compared to other groups at Week 3, with sustained cognitive enhancement in Spotter CRT at Week 8 (P< 0.01). Only Group A exhibited significant activation in the left frontal region post-MNS intervention. The novel MNS protocol was well tolerated, with no significant side effects observed.ConclusionsDTI-guided multimodal neuro-stimulation mode significantly improves cognitive impairments and is safe for BD patients.HighlightsUsing DTI-derived neural fiber density to determine the target sites for tACS and rTMS in patients with bipolar disorder.Combining sequential tACS and rTMS to significantly improve cognitive function in the bipolar disorder patients.Utilizing individually optimized tACS and robot-assisted navigated rTMS to achieve high-precision transcranial stimulation.
Utility of cellular imaging modality in subcellular spatial transcriptomic profiling of tumor tissues
Authors: Song Xiaofei , Yu Xiaoqing , Moran-Segura Carlos M , Grass G Daniel , Li Roger , Wang Xuefeng 
Published: July 2024

ABSTRACTSpatial transcriptomics (ST) technologies, like GeoMx Digital Spatial Profiler, are increasingly utilized to reveal the role of diverse tumor microenvironment components, particularly in relation to cancer progression, treatment response, and therapeutic resistance. However, in many ST studies, the spatial information obtained from immunofluorescence imaging is primarily used for identifying regions of interest, rather than as an integral part of downstream transcriptomic data interpretation. We developed ROICellTrack, a deep learning-based framework, to better integrate cellular imaging with spatial transcriptomic profiling. By examining 56 ROIs from urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC), ROICellTrack accurately identified cancer-immune mixtures and associated cellular morphological features. This approach also revealed different sets of spatial clustering patterns and receptor-ligand interactions. Our findings underscore the importance of combining imaging and transcriptomics for comprehensive spatial omics analysis, offering potential new insights into within-sample heterogeneity and implications for targeted therapies and personalized medicine.
Disentangling shared genetic etiologies for kidney function and cardiovascular diseases
Authors: Qiao Jun , Yao Kaixin , Yuan Yujuan , Yang Xichen , Zhou Le , Long Yinqi , Chen Miaoran , Xie Wenjia , Yang Yixuan , Cao Yangpo , Pauklin Siim , Xu Jinguo , Yang Yining , Feng Yuliang 
Published: July 2024

AbstractCardiovascular diseases (CVDs) are the leading cause of death worldwide, with chronic kidney disease (CKD) identified as a significant risk factor. CKD is primarily monitored through the estimated glomerular filtration rate (eGFR), calculated using the CKD-EPI equation. Although epidemiological and clinical studies have consistently demonstrated strong associations between eGFR and CVDs, the genetic underpinnings of this relationship remain elusive. Recent genome-wide association studies (GWAS) have highlighted the polygenic nature of these conditions and identified several risk loci correlating with their cross-phenotypes. Nonetheless, the extent and pattern of their pleiotropic effects have yet to be fully elucidated. We analyzed the most comprehensive GWAS summary statistics, involving around 7.5 million individuals, to investigate the shared genetic architectures and the underlying mechanisms between eGFR and CVDs, focusing on single nucleotide polymorphisms (SNPs), genes, biological pathways, and proteins exhibiting pleiotropic effects. Our study identified 508 distinct genomic locations associated with pleiotropic effects across multiple traits, involving 379 unique genes, notablyL3MBTL3(6q23.1),MMP24(20q11.22), andABO(9q34.2). Additionally, pathways such as stem cell population maintenance and the glutathione metabolism pathway were pivotal in mediating the relationships between these traits. From the perspective of vertical pleiotropy, our findings suggest a causal relationship between eGFR and conditions such as atrial fibrillation and venous thromboembolism. These insights significantly enhance our understanding of the genetic links between eGFR and CVDs, potentially guiding the development of novel therapeutic strategies and improving the clinical management of these conditions.
Discussions about Goals of Care in the Emergency Department: a Qualitative Study of Emergency Physicians’ Opinions Using the Normalization Process Theory
Authors: Péloquin Fannie , Marmen Emile , Gélinas Véronique , Plaisance Ariane , Linteau Maude , Nolet Audrey , Germain Nathalie , Archambault Patrick 
Published: July 2024

AbstractPurposeWe explored emergency department (ED) physicians’ opinions about the feasibility of leading goals of care discussions (GCD) in their daily practice.MethodThis qualitative study was based on the Normalization Process Theory (NPT). We conducted semi-structured interviews between April and May 2018 with a convenience sample of ten emergency physicians from one academic ED (Lévis, Canada) and aimed to reach data saturation. Using a mixed deductive and inductive thematic analysis, two authors codified the interviews under the four NPT constructs: coherence, cognitive participation, collective action, and reflexive monitoring. We calculated a kappa statistic to measure inter-rater agreement.ResultsWe interviewed 10 emergency physicians. No new ideas emerged after the ninth interview and the inter-rater agreement was substantial. Fourteen themes were identified as factors influencing the feasibility of implementing GCD: (1) interpersonal communication, (2) efficiency of care, (3) anxiety generated by the discussion, (4) identification of an acute deterioration leading to the GCD, (5) meeting of the clinician, patient, and family, (6) importance of knowing the patient’s goals of care before medical handover, (7) lack of training, (8) availability of protocols, (9) heterogeneous prioritization for leading GCD, (10) need to take action before patients consult in the ED, (11) need to develop education programs, (12) need for legislation, (13) need to improve the ED environment and human resources, and (14) selective systematization of GCD for patients.ConclusionGoals of care discussions are possible and essential with selected ED patients. Physicians identified outstanding needs to normalize GCD in their practice: education for both themselves and patients on the concept of GCD, legislative action for the systematization of GCD for patients, and proactive documentation of patients’ preferences pre-ED. Patient, clinician and system-level policy-making efforts remain necessary to address these needs and ensure the normalization of GCD in emergency physicians’ daily practice as suggested by clinical guidelines.Clinician’s capsuleWhat is known about the topic?Goals of care discussions are important to provide care aligned with patients’ values and medical preferences.What did this study ask?According to emergency physicians, are goals of care discussions feasible in the emergency department?What did this study find?Goals of care discussions are essential and possible if patient, clinician and system-level policymaking structured efforts are deployed.Why does this study matter to clinicians?This study identified action items to improve the implementation and quality of goals of care discussions in the emergency department.
Using the Emergency Care Data Set for the epidemiological surveillance of Children and Young People aged less than 18 years: a case study of COVID-19 in England 2020-2023
Authors: Boateng Jacob , Oeser Clarissa , Seghezzo Giulia , Harman Katie , Dabrera Gavin , Webster Harriet , Hope Russell , Thelwall Simon , Lamagni Theresa 
Published: July 2024

AbstractBackgroundThe Emergency Care Data Set provides insight into emergency care activity in England, and combined with COVID-19 surveillance data, can provide new insights into acute COVID-19 infection.MethodsThis study identified individuals <18 years old who tested positive for SARS-CoV-2 between February 2020 and March 2023 and attended emergency care 1-14 days after a positive test. The study’s main objective was to explore ED attendance outcomes by demographic characteristics.ResultsThere were significant differences (p < 0.05) across most of the characteristics of <18s admitted to hospital from emergency departments, and those who were discharged from ED. <18s in IMD decile 1 (14.9%) made up the highest proportion of admissions, with those in less deprived areas having a greater proportion of individuals discharged from ED. February to August 2020 (1.5%) and September 2022 to March 2023 (2.8%) saw the highest proportion of <18 cases attending ED, though the highest number of cases were seen between September 2021 and February 2022.ConclusionsThere is great value in the use of ECDS. It facilitates quick, regular insights into the health outcomes of key demographics, and provides a window into the health-seeking behaviours of individuals. Furthermore, outcomes of emergency care attendance can potentially inform assessments of infection severity across multiple demographics during outbreaks and pandemics.
A qualitative study of Benzodiazepine/Z-drug and Opioid co-use patterns and overdose risk
Authors: Family Hannah E. , Vojt Gabriele , Poulter Hannah , Bailey Chris P. , Abdala Sheikh Ana Paula , Cavallo Damiana , Karimi Sara , Booth Nick , Silva Peter Da , Aitken Louise , Stewart Samantha , Hickman Matthew , Henderson Graeme , Scott Jenny , Kesten Joanna M. 
Published: July 2024

AbstractBackgroundCo-use of benzodiazepines and/or ‘z-drugs’ along with opioids is linked to the rise in drug related deaths (DRD) in the UK. Understanding patterns of co-use could inform harm reduction strategies for reducing DRDs. This study explored how people co-use, including dosages, timings, methods of administration, use of other substances and desired effects sought.MethodsForty-eight semi-structured interviews across Glasgow in Scotland (n=28), Bristol (n=10) and Teesside (n=10) in England with individuals who co-use illicit and/or prescribed opioids and benzodiazepines/z-drugs were conducted. Eighteen interviews were co-facilitated with qualitatively trained local peer researchers. Interviews were analysed using the Framework method.ResultsSix co-use patterns were generated: (1) co-use to aid sleep or come down, (2) curated co-use, opioid agonist therapy (OAT) only (3) morning and evening benzodiazepine doses with opioids throughout the day (4) co-use binges (5) co-use throughout the day, (6) benzodiazepine use throughout the day plus OAT. Patterns one to three reflected more controlled co-use with a focus on self-medicating to give confidence, manage anxiety, promote sleep and come-down from cocaine/ketamine. Patterns four to six involved greater poly-drug use, and less controlled co-use with a focus on seeking euphoria (“warm glow”, “gouching out”)or oblivion (to escape untreated mental health conditions and trauma). Patterns two, three, five and six involved daily co-use. People switched between patterns depending on available resources (e.g. finances) or changes to prescriptions (opioids or benzodiazepines). Near-fatal overdoses were reported by participants across all co-use patterns.Patterns four to six were conceptualised as presenting greater overdose risk due to less controlled co- use and more extensive polydrug use.ConclusionsThe patterns identified provide opportunities for future harm reduction strategies, tailoring advice to patterns of use, updated prescribing guidance and policies, and the need for better access to mental health care, for people who co-use benzodiazepines and opioids to reduce DRDs.
Do smoking and alcohol behaviours influence risk of type 2 diabetes? A Mendelian randomisation study
Authors: Reed Zoe E. , Sallis Hannah M. , Richmond Rebecca C. , Attwood Angela S. , Lawlor Deborah A. , Munafò Marcus R. 
Published: July 2024

AbstractBackgroundPrevious studies suggest that smoking and higher alcohol consumption are both associated with greater risk of type 2 diabetes (T2D). However, studies examining whether these associations reflect causal relationships are limited and do not consider continuous glycaemic traits. The aim of the study was to determine whether there are causal effects of smoking and alcohol consumption on T2D risk and related glycaemic traits.Methods and FindingsWe conducted both two-sample and one-sample MR to examine the effects of lifetime smoking index (LSI) and alcoholic drinks per week on T2D and continuous traits (fasting glucose, fasting insulin and glycated haemoglobin, HbA1c). For two-sample MR we used results from genome-wide association studies (GWAS) of LSI (N=462,690), alcohol consumption (N=941,280), T2D (N= 148,726 cases and 965,732 controls) and continuous traits (N=149,289 to 209,605). We used inverse variance weighting (IVW) for our main analyses and conducted several sensitivity analyses to explore violation of MR assumptions. We compared two-sample MR to one-sample MR results for alcohol effects on T2D and HbA1c in UK Biobank (N=336,984). Only these analyses were conducted to avoid sample overlap and due to data availability. The main IVW two-sample MR results suggested possible causal effects of higher LSI on T2D risk (OR per 1SD higher LSI=1.42, 95% CI=1.22 to 1.64); however, sensitivity analyses did not consistently support this finding, and there was evidence of potential horizontal pleiotropy. There was no robust evidence that higher drinks per week influenced risk of T2D from our main IVW two-sample MR analyses (OR per 1 SD higher log-transformed drinks per week=1.04, 95% CI=0.40 to 2.65), despite evidence of causal effects on higher fasting glucose (difference in mean fasting glucose in mmol/l per 1SD higher log-transformed drinks per week=0.34, 95% CI=0.09 to 0.59). One-sample MR results suggested a possible causal effect of higher drinks per week on T2D risk (OR per 1 SD higher log-transformed drinks per week=1.71, 95% CI: 1.24 to 2.36), but in contrast, lower HbA1c levels (difference in mean SD of log transformed HbA1c (mol/mol) per 1 SD higher log-transformed drinks per week=-0.07, 95% CI: -0.11 to -0.02). Key limitations include limited generalisability of results due to analyses being conducted in European populations, and potential selection bias in UK Biobank influencing results.ConclusionOur results suggest effective public health interventions to prevent and/or reduce smoking and alcohol consumption are unlikely to reduce the prevalence of T2D.
High-sensitivity detection ofMycobacterium tuberculosisDNA in tongue swab samples
Authors: Olson Alaina M. , Wood Rachel C. , Weigel Kris M. , Yan Alexander J. , Lochner Katherine A. , Dragovich Rane B. , Luabeya Angelique K. , Yager Paul , Hatherill Mark , Cangelosi Gerard A. 
Published: July 2024

AbstractTongue swab (TS) sampling combined with qPCR to detectMycobacterium tuberculosis(MTB) DNA is a promising alternative to sputum testing for tuberculosis (TB) diagnosis. In prior studies, the sensitivity of tongue swabbing has usually been lower than sputum. In this study, we evaluated two strategies to improve sensitivity. In one, centrifugation was used to concentrate tongue dorsum bacteria from 2-mL suspensions eluted from high-capacity foam swab samples. The pellets were resuspended as 500-µL suspensions, and then mechanically lysed prior to dual-target qPCR to detect MTB insertion elements IS6110and IS1081. Fractionation experiments demonstrated that most of the MTB DNA signal in clinical swab samples (99.22% ± 1.46%) was present in the sedimentable fraction. When applied to archived foam swabs collected from 124 South Africans with presumptive TB, this strategy exhibited 83% sensitivity (71/86) and 100% specificity (38/38) relative to sputum MRS (microbiological reference standard; sputum culture and/or Xpert® Ultra). The second strategy used sequence- specific magnetic capture (SSMaC) to concentrate DNA released from MTB cells. This protocol was evaluated on archived Copan FLOQSwabs® flocked swab samples collected from 128 South African participants with presumptive TB. Material eluted into 500 µL buffer was mechanically lysed. The suspensions were digested by proteinase K, hybridized to biotinylated dual-target oligonucleotide probes, and then concentrated ∼20-fold using magnetic separation. Upon dual-target qPCR testing of concentrates, this strategy exhibited 90% sensitivity (83/92) and 97% specificity (35/36) relative to sputum MRS. These results point the way toward automatable, high-sensitivity methods for detecting MTB DNA in TS.ImportanceImproved testing for tuberculosis (TB) is needed. Using a more accessible sample type than sputum may enable the detection of more cases, but it is critical that alternative samples be tested appropriately. Here, we describe two new, highly accurate methods for testing tongue swabs for TB DNA.
A Methodological Evaluation of Meta-Analyses in tDCS - Motor Learning Research
Authors: Alsalti Taym , Hussey Ian , Elson Malte , Krause Robert , Pohl Steffi 
Published: July 2024

AbstractWith transcranial direct-current stimulation’s (tDCS) rising popularity both in motor learning research and as a commercial product, it is becoming increasingly important that the quality of evidence on its effectiveness be evaluated. Special attention should be paid to meta-analyses, as they usually have a large impact on research and clinical practice. The aim of this study was to evaluate the methodological quality of meta-analyses estimating the effect of tDCS on motor learning with respect to reproducibility as the main focus, and reporting quality and publication bias control as secondary aspects. The three meta-analyses we reviewed largely adhered to PRISMA reporting guidelines and reported the primary effect sizes and sampling variances / confidence intervals they calculated, enabling successful reproductions of pooled effect size estimates. However, akin to previous meta-research reviews with similar aims, we found the methods and results sections of the meta-analyses to be severely underreported, which compromises the ability to judge the soundness of the methodological procedure adopted as well as its reproducibility. While publication bias detection methods were applied, the approaches chosen do not allow for well informed decisions about the presence or extent of publication bias. These results reemphasise the need to transparently report methods in meta-analyses and to meticulously evaluate their quality before and after publication.