bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulation of inhibitory synaptic plasticity for restoration of basal ganglia dynamics in Parkinson’s disease
Authors: Spencer KA , Boogers A , Sumarac S , Crompton DJ , Steiner LA , Zivkovic L , Buren Y , Lozano AM , Kalia SK , Hutchison WD , Fasano A , Milosevic L 
Published: August 2024

AbstractIntroductionParkinson’s disease is characterized, in part, by hypoactivity of both direct pathway inhibitory projections from striatum to the globus pallidus internus (GPi) and indirect pathway inhibitory projections from globus pallidus externus (GPe) to the subthalamic nucleus (STN), giving rise to disrupted basal ganglia circuit activity. In this study, we explored the use of intracranial stimulation for eliciting long-term potentiation (LTP) of each of these pathologically underactive inhibitory projections for the restoration of basal ganglia circuit dynamics and amelioration of motor symptoms.MethodsData were collected from a total of 31 people with Parkinson’s disease (42 hemispheres). During deep brain stimulation (DBS) surgery, we assessed microelectrode stimulation-induced changes to inhibitory evoked field potentials (fEP) and hand kinematics before versus after a 40-second train of high-frequency stimulation (HFS) in the GPi (n = 7, 11 sites at 100 Hz) and STN (n = 10, 14 sites at 100 Hz; n = 4, 7 sites at 180 Hz). Additionally, we assessed changes to beta oscillations and hand kinematics in people with chronic DBS implants in the GPi (n = 6 at 125 Hz) and STN (n = 4 at 180 Hz).ResultsIntraoperatively, increases in fEP amplitude (p = 0.002) and improved motor performance (p = 0.003) were observed after 100 Hz HFS in the GPi; while in STN, HFS did not potentiate fEPs (p = 0.589) or improve motor performance (p = 0.460) (similar results yielded for 180 Hz in STN). Similarly, extraoperative GPi-DBS produced suppression of beta power (p=0.096) and motor improvement (p = 0.077) before versus after HFS at 125 Hz; while STN-DBS at 180 Hz did not significantly affect beta power (p = 0.267) or motor performance (p=0.850).InterpretationOur findings support that LTP-like effects in GPi may produce motor improvements that extend beyond stimulation cessation, aligning with optogenetic studies showing long-lasting motor recovery through periodic D1-striatal activation in rodents. The lack of effects in STN suggests that stimulation paradigms may require optimization for effective LTP induction. These findings nevertheless highlight the potential of LTP-based strategies for sustained therapeutic benefits in Parkinson’s disease, warranting further investigation into periodic stimulation paradigms for optimizing DBS efficacy and side effect profiles.
Whole genome sequencing improves tissue of origin diagnosis and treatment options for cancer of unknown primary
Authors: Rebello Richard J. , Posner Atara , Dong Ruining , Prall Owen W.J. , Sivakumaran Tharani , Mitchell Camilla B. , Flynn Aidan , Caneborg Alex , Mitchell Catherine , Kanwal Sehrish , Fedele Clare , Webb Samantha , Fisher Krista , Wong Hui-Li , Balachander Shiva , Zhu Wenying , Nicolson Shannon , Dimitriadis Voula , Wilcken Nicholas , DeFazio Anna , Gao Bo , Singh Madhu , Collins Ian , Steer Christopher , Warren Mark , Karanth Narayan , Xu Huiling , Fellowes Andrew , Hicks Rodney J. , Stewart Kym Pham , Shale Charles , Priestley Peter , Dawson Sarah-Jane , Vissers Joseph H.A. , Fox Stephen B. , Schofield Penelope , Bowtell David , Hofmann Oliver , Grimmond Sean M. , Mileshkin Linda , Tothill Richard W. 
Published: August 2024

AbstractGenomics holds promise for precision treatment and identifying the primary tissue of origin (TOO) in cases of cancer of unknown primary (CUP). We evaluated the feasibility and diagnostic superiority of whole genome and transcriptome sequencing (WGTS) over conventional panel testing in 72 patients using routine pathology samples. WGTS not only detected all reportable mutations identified by panel testing but also uncovered additional clinically relevant features in 76% of cases. Utilizing a CUP prediction algorithm (CUPPA) trained on WGTS data of known primary cancers, WGTS informed TOO in 77% of cases. Importantly, WGTS suggested potential treatment options for 79% of patients, a significant improvement over the 62% informed by panel testing. Additionally, WGTS and CUPPA applied to 22 cell-free DNA samples yielded high-likelihood TOO predictions in 41% of cases. These findings demonstrate that WGTS is diagnostically superior to panel testing, broadens treatment options, and is feasible using archived tissues and cell-free DNA.
Genome-Wide Association Study Meta-Analysis Uncovers Novel Genetic Variants Associated with Olfactory Dysfunction
Authors: Imtiaz Mohammed Aslam , Melas Konstantinos , Tin Adrienne , Talevi Valentina , Chen Honglei , Fornage Myriam , Shrestha Srishti , Gögele Martin , Emmert David , Pattaro Cristian , Pramstaller Peter , Förster Franz , Horn Katrin , Mosley Thomas H. , Fuchsberger Christian , Scholz Markus , Breteler Monique M.B. , Aziz N. Ahmad 
Published: August 2024

AbstractIMPORTANCEOlfactory dysfunction is among the earliest signs of many age-related neurodegenerative diseases and has been associated with increased mortality in older adults; however, its genetic basis remains largely unknown.OBJECTIVETo identify the genetic loci associated with olfactory dysfunction in the general population.DESIGN, SETTING AND PARTIICIPANTSThis genome-wide association study meta-analysis (GWMA) included participants of European ancestry (N = 22,730) enrolled in four different large population-based studies, followed by a multi-ancestry GWMA including participants of African ancestry (N = 1,030). The data analysis was performed from March 2023 through June 2024.EXPOSURESGenome-wide single nucleotide polymorphisms.MAIN OUTCOMES AND MEASURESOlfactory dysfunction was the outcome and assessed using a 12-item smell identification test.RESULTSGWMA revealed a novel genome-wide significant locus (tagged by rs11228623 at 11q12) associated with olfactory dysfunction. Gene-based analysis revealed a high enrichment for olfactory receptor genes in this region. Phenome-wide association studies demonstrated associations between genetic variants related to olfactory dysfunction and blood cell counts, kidney function, skeletal muscle mass, cholesterol levels and cardiovascular disease. Using individual-level data, we also confirmed and quantified the strength of these associations on a phenotypic level. Moreover, employing two-sample Mendelian Randomization analyses, we found evidence for causal associations between olfactory dysfunction and these phenotypes.CONCLUSIONSThese findings provide novel insights into the genetic architecture of the sense of smell and highlight its importance for many aspects of human health.Key PointsQuestionWhat is the genetic basis of olfactory dysfunction, and is it causally related to adverse health outcomes?FindingsThis genome-wide association study meta-analysis (GWMA) of 22,730 European and 1,030 African participants identified a novel genomic locus, enriched for olfactory receptor genes, robustly associated with olfactory dysfunction. Two-sample Mendelian Randomization analyses provided evidence for causal associations of olfactory dysfunction with biochemical, anthropometric and cardiovascular health outcomes.MeaningThese findings provide new insights into the genetic architecture of olfaction and implicate olfactory dysfunction as a causal risk factor for many aspects of human health.
Empowering Refugee Voices: Using Nominal Group Technique with a Diverse Refugee Patient Advisory Committee (PAC) to Identify Health and Research Priorities
Authors: Altahsh Deyana , Holdbrook Linda , Norrie Eric , Sahilie Adanech , Essar Mohammad Yasir , Grewal Rabina , Horbach Olha , Abdaly Fawzia , Santana Maria , Talavlikar Rachel , Aucoin Michael , Coakley Annalee , Fabreau Gabriel E. 
Published: August 2024

AbstractBackgroundDespite rising forced displacement globally, refugees’ health and research priorities are largely unknown. We investigated whether a diverse refugee committee could utilize participatory methods to identify health priorities and a research agenda to address them.MethodsWe conducted a qualitative study with focus groups of current and former refugees, asylum claimants and evacuees from a specialized refugee clinic over a year. We collected sociodemographic data using standardized instruments, then utilized a four-step nominal group technique process (idea generation, recording, discussion, and voting) to identify and rank participants’ health and research priorities. Participants ranked their top five priorities across three time periods: Pre-migration/early arrival (0–3 months), post-migration (3 months–2 years), and long-term health (>2 years). Participants created overarching priorities and corroborated findings via a member checking step.FindingsTwenty-three participants (median age 35 years) attended one or more of five focus groups. Twenty-one completed sociodemographic surveys: 16/21 (76%) were women, representing 8 countries of origin. Participants identified “more family physicians” and “improving health system navigation” (11/60 votes each) as top health and research priorities respectively across all resettlement periods. Participants also prioritized pre-departure healthcare system orientation and improved post-arrival and long-term mental health services. Twelve participants completed the member checking process, affirming the results with minor clarifications.InterpretationThis proof-of-concept study illustrates how refugees can use a rigorous consensus process without external influence to prioritize their healthcare needs, direct a health research agenda to address those needs, and co-produce research. These low-cost participatory methods should be replicated elsewhere.FundingFunded by the O’Brien Institute for Public Health at the University of Calgary.
Factors Associated with the Ability of Adolescent Girls and Young Women (AGYW) in Sexual Unions to Negotiate for Safer Sex. An Analysis of Data from the 2018 Zambia Demographic and Health Survey (ZDHS)
Authors: Zulu Teebeny , Musukuma Mwiche , Jacobs Choolwe , Musonda Patrick 
Published: August 2024

AbstractThe ability of AGYW to negotiate for safer sex is key in the fight against the Human Immunodeficiency Virus (HIV). We determined the prevalence of safer sex negotiation among AGYW in sexual unions aged 15–24 and its associated factors in Zambia. Of 1879 respondents, 78.0% (1466) had the ability to negotiate for safer sex (ANSS). While adjusting for other variables in the model, condom use at last sex with the most recent partner (AOR 4.08, 95% CI 1.74-9.60, p=0.001), experiencing any sexual violence by husband or partner (AOR 1.74, 95% CI 1.17-2.59, p=0.006), listening to the radio at least once a week (AOR 2.03, 95% CI 1.32-3.13, p=0.001), secondary or higher education (AOR1.77, 95% CI 1.04-2.99, p=0.034), being in the richest wealth quintile (AOR 2.70, 95% CI 1.30-5.60, p=0.008), and living in Eastern Province (AOR 2.75, 95% CI 1.53-4.93 p=0.001), Northwestern (AOR 2.31, 95% CI 1.15-4.65, p=0.019) and Southern (AOR 3.11, 95% CI 1.58-6.09, p=0.001) was associated with a significant increase in the odds of ANSS among AGYW aged 15-24 years in sexual unions. On the other hand, being in Muchinga province (AOR 0.48, 95% CI 0.28–0.81, p = 0.006) decreased the odds of ANSS. In conclusion, safer sex negotiation is crucial in combating HIV; hence, tailor-made interventions that promote condom use, frequency of listening to health programmes on the radio, education, and wealth acquisition should be implemented to build and sustain safer sex negotiation, particularly among AGYW in sexual unions.
What is the relationship between viral prospecting in animals and medical countermeasure development?
Authors: Aatresh Aishani V. , Lipsitch Marc 
Published: August 2024

AbstractIn recent decades, surveillance in nonhuman animals has aimed to detect novel viruses before they “spill over” to humans. However, the extent to which these viral prospecting efforts have enhanced preparedness for disease outbreaks remains poorly characterized, especially in terms of whether they are necessary, sufficient, or feasible ways to spur medical countermeasure development. We find that several viruses which pose known threats to human health lack approved vaccines and that known viruses discovered in human patients prior to 2000 have caused most major 21st-century outbreaks. WithFiloviridaeas a case study, we show there is little evidence to suggest that viral prospecting has accelerated countermeasure development or that systematically discovering novel zoonotic viruses in animal hosts before they cause human outbreaks has been feasible. These results suggest that prospecting for novel viral targets does not accelerate a rate-limiting step in countermeasure development and underscore questions about the importance of zoonotic viral discovery for outbreak preparedness. We consider limitations to these conclusions and alternative but related approaches to preparedness and response.
Changes in prediction modelling in biomedicine – do systematic reviews indicate whether there is any trend towards larger data sets and machine learning methods?
Authors: Lusa Lara , Kappenberg Franziska , Collins Gary S. , Schmid Matthias , Sauerbrei Willi , Rahnenführer Jörg 
Published: August 2024

AbstractThe number of prediction models proposed in the biomedical literature has been growing year on year. In the last few years there has been an increasing attention to the changes occurring in the prediction modeling landscape. It is suggested that machine learning techniques are becoming more popular to develop prediction models to exploit complex data structures, higher-dimensional predictor spaces, very large number of participants, heterogeneous subgroups, with the ability to capture higher-order interactions.We examine these changes in modelling practices by investigating a selection of systematic reviews on prediction models published in the biomedical literature. We selected systematic reviews published since 2020 which included at least 50 prediction models. Information was extracted guided by the CHARMS checklist. Time trends were explored using the models published since 2005.We identified 8 reviews, which included 1448 prediction models published in 887 papers. The average number of study participants and outcome events increased considerably between 2015 and 2019, but remained stable afterwards. The number of candidate and final predictors did not noticeably increase over the study period, with a few recent studies using very large numbers of predictors. Internal validation and reporting of discrimination measures became more common, but assessing calibration and carrying out external validation were less common. Information about missing values was not reported in about half of the papers, however the use of imputation methods increased. There was no sign of an increase in using of machine learning methods. Overall, most of the findings were heterogeneous across reviews.Our findings indicate that changes in the prediction modeling landscape in biomedicine are less dramatic than expected and that poor reporting is still common; adherence to well established best practice recommendations from the traditional biostatistics literature is still needed. For machine learning best practice recommendations are still missing, whereas such recommendations are available in the traditional biostatistics literature, but adherence is still inadequate.
Leveraging Pretrained Models for Multimodal Medical Image Interpretation: An Exhaustive Experimental Analysis
Authors: Fagbola Temitayo Matthew , Success Igwebuike 
Published: August 2024

AbstractArtificial intelligence (AI) in radiology, particularly pretrained machine learning models, holds promise for overcoming image interpretation complexities and improving diagnostic accuracy. Although extensive research highlights their potential, challenges remain in adapting these models for generalizability across diverse medical image modalities, such as Magnetic Resonance Imaging (MRI), Computed Tomography (CT), and X-rays. Most importantly, limited generalizability across image modalities hinders their real-world application in diverse medical settings. This study addresses this gap by investigating the effectiveness of pretrained models in interpreting diverse medical images. We evaluated ten state-of-the-art convolutional neural network (CNN) models, including ConvNeXtBase, EfficientNetB7, VGG architectures (VGG16, VGG19), and InceptionResNetV2, for their ability to classify multimodal medical images from brain MRI, kidney CT, and chest X-ray (CXR) scans. Our evaluation reveals VGG16’s superior generalizability across diverse modalities, achieving accuracies of 96% for brain MRI, 100% for kidney CT, and 95% for CXR. Conversely, EfficientNetB7 excelled in brain MRI with 96% accuracy but showed limited generalizability to kidney CT (56% accuracy) and CXR (33% accuracy), suggesting its potential specialization for MRI tasks. Future research should enhance the generalizability of pretrained models across diverse medical image modalities. This includes exploring hybrid models, advanced training techniques, and utilizing larger, more diverse datasets. Integrating multimodal information, such as combining imaging data with patient history, can further improve diagnostic accuracy. These efforts are crucial for deploying robust AI systems in real-world medical settings, ultimately improving patient outcomes.
Safety and Efficacy of Cardiac Sympathetic Denervation for Ventricular Arrhythmias: An Updated Review and Meta-Analysis
Authors: Hanna Daniel B. , Karimianpour Ahmadreza , Mamprejew Nicole , Fiechter Chris , Verghese Dhiran , Sierra Juan , Navas Viviana , Sharma Dinesh 
Published: August 2024

AbstractIntroductionThe role of sympathetic nervous system in the initiation and continuation of ventricular tachyarrhythmias (VTA) is well established. However, whether CSD reduces implantable cardioverter defibrillator (ICD) shocks and recurrent VTA is still uncertain.ObjectiveTo explore long-term arrhythmic outcomes, safety, and efficacy of CSD by measuring event rates of recurrent VTA and ICD shocks after CSD.MethodsA comprehensive literature search was performed at Medline and Embase until March 2023. Our primary outcome was event rate of ICD shocks and VTA. Analyses were conducted using Comprehensive Meta-Analysis software.ResultsInitial search yielded 1,324 scientific studies with a total of 15 studies fitting our inclusion criteria. ICD shocks at 1 year post CSD revealed an event rate of 69.8% (95% CI, 56.4% – 80.4% with 50% heterogeneity) (I2statistic)). ICD shocks at 6 months had an event rate of 59.1% (95% CI 46.9% - 70.4%, 47 I2). Freedom of VTA 1 year post CSD revealed an event rate of 64.3% (95% CI, 42.3% - 81.5%, 26% I2). Freedom from VTA at 6 months revealed an event rate of of 62.3% (95% CI, 51.2% - 72.2%, 40% I2). Reported mortality due to VTA was subdivided into short-term (0-30 days), intermediate-term (31-364 days) and long-term (32-364 days). The event rate for the short-term tertile was 8.9% (95% CI, 5.0% - 15.4%, 0% I2), medium-term was 5.3% (95% CI, 2.4% - 11.3%, 0% I2) and long-term 5.2% (95% CI, 2.4% - 10.9%, 0% I2).ConclusionCSD seems to be promising as an acceptable treatment strategy for recurrent VTA refractory to traditional pharmacological or ablation therapy.
Mechanism of recurrent outbreak of the scarlet fever epidemics in mainland China
Authors: Sun Meirong , Li Meijia , Haihambo Naem , Zhang Huiwen , Zhang Zhizhen , Zhao Xixi , Wang Bin , Guo Mingrou , Han Chuanliang 
Published: August 2024

AbstractIn mainland China, most infectious diseases occur once a year, except for scarlet fever, which has been steadily breaking out twice a year in recent years. Over the years, the recurrence of scarlet fever, a contagious disease characterized by a distinctive red rash, has been a focus of attention. However, the oscillatory mechanism of scarlet fever remains unclear. This study aimed to uncover how meteorological factors contribute to the recrudescence of scarlet fever in mainland China. The study used a longitudinal public dataset covering 31 provinces in mainland China, containing 14 years of monthly scarlet fever infections, along with available local meteorological data. Power spectrum analysis was conducted on time series data, and correlation analyses were performed to assess the relationship between the oscillatory nature of epidemics and meteorological factors. We found that the scarlet fever epidemics generally occur twice a year in various provinces of China, and the timing of these outbreaks’ peaks progressively from southern to northern regions. Furthermore, we established an atlas that shows the relationship between scarlet fever oscillation and meteorological factors. Our findings indicated a significant correlation between the oscillation characteristics of scarlet fever in 50% of provinces and each natural meteorological factor. Our study presents a detailed description of the temporal and spatial changes in the oscillatory characteristics of scarlet fever for the first time and explores the oscillatory characteristics of natural meteorological conditions and their correlation with the number of scarlet fever infections. These findings could serve as a valuable guide for government prevention and control measures for the scarlet fever epidemic.
Ultrastructure of immature synaptic inputs in the lateral superior olive of rodent brainstem
Authors: Ma Siyi , Watanabe Shigeki , Gillespie Deda C. 
Published: August 2024

AbstractNeurons of the lateral superior olive (LSO), which compute intensity differences between the two ears, receive two primary inputs, an ipsilaterally arising excitatory input and a contralaterally arising inhibitory input, that are precisely matched for stimulus frequency. Circuit refinement to establish this precise match takes place within the first few postnatal weeks through elimination of single-fiber inputs and concomitant strengthening of the remaining inputs. However, little is known about the ultrastructure of these young synapses and about how changes in physical features of these synapses could contribute to refinement. To characterize pre-hearing postnatal development of somatic synapses in the LSO, we performed transmission electron microscopy and examined synapses in the rodent LSO from birth to hearing onset at postnatal day 13. Synaptic vesicles and mitochondria in putative synaptic boutons were surprisingly scarce at birth. During the second week, bouton enlargement was accompanied by an increase in the number of vesicles and mitochondria. The size of mitochondria also increased, pointing to changes in functional and metabolic needs of synapses. Our results reveal extensive remodeling at individual presynaptic terminals that could strengthen single-fiber inputs and contribute to the development of robust synaptic transmission.