bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reflex Responses in Muscles of the Lower Extremities Elicited by Transcutaneous Stimulation of Cauda Equina: Part 1. Methodology and Normative Data
Authors: Rimac Julija , Jančuljak Davor , Kovač Biserka , Jovičić Miloš , Forjan Josipa 
Published: June 2024

Introduction:
Transcutaneous electrical stimulation is used to stimulate the dorsal roots of the cauda equina. Multiple elicited responses recorded in the lower extremity muscles are called posterior root muscle reflexes (PRMRs). Normal PRMR values in the muscles of healthy lower extremities have yet to be determined.

Methods:
Thirty subjects without known lumbosacral spinal root illness were included in this study. Subsequently, they were subjected to transcutaneous electrical stimulation of the cauda equina. Posterior root muscle reflex was recorded in the four muscle groups of both lower extremities. We elicited multiple PRMR and examined their characteristics in order to establish normal electrophysiological parameter values.

Results:
Posterior root muscle reflex was successfully elicited in the tibialis anterior (96.7%), gastrocnemius (100%), quadriceps femoris (93.3%), and hamstring (96.7%). No statistically significant differences were found in the intensity of stimulation, latencies, or area under the PRMR between the right and left leg muscles. The area under PRMR varied significantly among the participants. Higher body weight and abdominal girth showed a significant positive correlation with stimulation intensity for eliciting PRMR, and a significant negative correlation with the area under PRMR. Older age showed a significant negative correlation with the success of eliciting PRMR and the area under the PRMR.

Conclusions:
Posterior root muscle reflex is a noninvasive and successful method for eliciting selective reflex responses of cauda equina posterior roots. Obtained values could be used in future studies to evaluate the utility of this methodology in clinical practice. This methodology could improve testing of the proximal lumbosacral nervous system functional integrity.
Contributions of site- and sex-specific LTPs to everyday memory
Authors: Gall Christine M. , Le Aliza A. , Lynch Gary 
Published: June 2024

Commentaries about long-term potentiation (LTP) generally proceed with an implicit assumption that largely the same physiological effect is sampled across different experiments. However, this is clearly not the case. We illustrate the point by comparing LTP in the CA3 projections to CA1 with the different forms of potentiation in the dentate gyrus. These studies lead to the hypothesis that specialized properties of CA1-LTP are adaptations for encoding unsupervised learning and episodic memory, whereas the dentate gyrus variants subserve learning that requires multiple trials and separation of overlapping bodies of information. Recent work has added sex as a second and somewhat surprising dimension along which LTP is also differentiated. Triggering events for CA1-LTP differ between the sexes and the adult induction threshold is significantly higher in females; these findings help explain why males have an advantage in spatial learning. Remarkably, the converse is true before puberty: Females have the lower LTP threshold and are better at spatial memory problems. A mechanism has been identified for the loss-of-function in females but not for the gain-of-function in males. We propose that the many and disparate demands of natural environments, with different processing requirements across ages and between sexes, led to the emergence of multiple LTPs.
This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Synapse-specific structural plasticity that protects and refines local circuits during LTP and LTD
Authors: Harris Kristen M. , Kuwajima Masaaki , Flores Juan C. , Zito Karen 
Published: June 2024

Synapses form trillions of connections in the brain. Long-term potentiation (LTP) and long-term depression (LTD) are cellular mechanisms vital for learning that modify the strength and structure of synapses. Three-dimensional reconstruction from serial section electron microscopy reveals three distinct pre- to post-synaptic arrangements: strong active zones (AZs) with tightly docked vesicles, weak AZs with loose or non-docked vesicles, and nascent zones (NZs) with a postsynaptic density but no presynaptic vesicles. Importantly, LTP can be temporarily saturated preventing further increases in synaptic strength. At the onset of LTP, vesicles are recruited to NZs, converting them to AZs. During recovery of LTP from saturation (1–4 h), new NZs form, especially on spines where AZs are most enlarged by LTP. Sentinel spines contain smooth endoplasmic reticulum (SER), have the largest synapses and form clusters with smaller spines lacking SER after LTP recovers. We propose a model whereby NZ plasticity provides synapse-specific AZ expansion during LTP and loss of weak AZs that drive synapse shrinkage during LTD. Spine clusters become functionally engaged during LTP or disassembled during LTD. Saturation of LTP or LTD probably acts to protect recently formed memories from ongoing plasticity and may account for the advantage of spaced over massed learning.
This article is part of a discussion meeting issue ‘Long-term potentiation: 50 years on’.
Tocilizumab Reduces Hypercoagulation in COVID-19 – Perspectives from The Coagulation and Immunomodulation Covid Assessment (Coag- ImmCovA) Clinical Trial
Authors: Almskog Lou M. , Sjöström Anna , Sundén-Cullberg Jonas , Taxiarchis Apostolos , Ågren Anna , Freyland Sara , Börjesson Madeleine , Wikman Agneta , Wahlgren Carl Magnus , Wanecek Michael , van der Linden Jan , Antovic Jovan , Lampa Jon , Magnusson Maria 
Published: June 2024

AbstractBackgroundDespite medical interventions, COVID-19 continues to persist at pandemic proportions. A hypercoagulation state was rapidly observed in the severely ill, and the incidence of thromboembolic events remains elevated. Interleukin inhibitors have demonstrated positive effects on the hyperactivation of the immune system in COVID-19, with the interleukin-6 inhibitor tocilizumab showing promising results in reducing mortality. Nevertheless, the impact of interleukin inhibitors on the coagulation system remains incompletely understood.MethodsIn this clinical trial conducted in Stockholm, Sweden, interleukin inhibitors, namely anakinra (ANA) or tocilizumab (TOCI), were randomly administered in addition to standard care (SC) to hospitalized patients with COVID-19. A control group received only SC. The primary outcome sought to measure effects on global hemostasis, as indicated by changes in functional coagulation tests, specifically Rotational Thromboelastometry (ROTEM) or Overall Hemostatic Potential (OHP), visualized through scanning electron microscopy images. Secondary outcomes included effects on conventional coagulation laboratory tests.ResultsThe study enrolled 74 patients who were randomized to receive either ANA or TOCI in addition to SC, or SC alone. In the TOCI group, ROTEM variables exhibited less hypercoagulation after 29 days compared with ANA or SC treatment groups, characterized by prolonged clot formation time and decreased clot firmness. OHP decreased, but there were no significant differences among the three treatment groups. Plasma fibrinogen levels, initially elevated, decreased significantly in TOCI recipients over time.ConclusionTocilizumab treatment demonstrated a significant reduction of hypercoagulation in hospitalized COVID-19 patients, by improvements in both global coagulation tests and conventional laboratory tests, in comparison with anakinra or SC alone. This finding underscores the significance of tocilizumab as a viable treatment option in severe COVID-19 cases, with the potential to decrease thrombosis incidence.
Neurophysiology of Resilience in Juvenile Fibromyalgia
Authors: Suñol Maria , Pascual-Diaz Saül , Dudley Jon , Payne Michael , Jackson Catherine , Tong Han , Ting Tracy , Kashikar-Zuck Susmita , Coghill Robert , López-Solà Marina 
Published: June 2024

AbstractObjectiveJuvenile fibromyalgia (JFM) is a chronic pain syndrome predominantly affecting adolescent girls. Resilience may be a protective factor in coping with pain, reducing affective burden, and promoting positive outlooks. Brain regions affected in JFM overlap with those linked to resilience, particularly in the default-mode network (DMN). We investigate the role of resilience on core somatic and affective symptoms in JFM and assess the neurophysiological substrates for the first time.MethodsForty-one girls with JFM and 40 pain-free adolescents completed a resting-state fMRI assessment and self-report questionnaires. We used clustering analyses to group JFM participants based on resilience, and principal component analyses to summarize core somatic and affective symptoms. We estimated whole-brain and within-DMN connectivity and assessed differences between higher and lower resilience JFM groups and compared their connectivity patterns to pain-free participants.ResultsThe higher resilience JFM group had less affective (T=4.03; p<.001) but similar core somatic symptoms (T=1.05; p=.302) than the lower resilience JFM group. They had increased whole-brain (T’s>3.90, pFDR’s<.03) and within-DMN (T=2.20, p=.03) connectivity strength, and higher connectivity between DMN nodes and self-referential, regulatory, and reward-processing regions. Conversely, higher DMN-premotor connectivity was observed in the lower resilience group.ConclusionJFM participants with higher resilience were protected affectively but not in core somatic symptoms. Greater resilience was accompanied by higher signal integration within the DMN, a network central to internally oriented attention and flexible attention shifting. Crucially, the connectivity pattern in highly resilient patients resembled that of pain-free adolescents, which was not the case for the lower resilience group.
Restriction Spectrum Imaging as a quantitative biomarker for prostate cancer with reliable positive predictive value
Authors: Rojo Domingo Mariluz , Do Deondre D , Conlin Christopher C , Bagrodia Aditya , Barrett Tristan , Baxter Madison T , Cooperberg Matthew , Feng Felix , Hahn Michael E , Harisinghani Mukesh , Hollenberg Gary , Javier-Desloges Juan , Kallis Karoline , Kamran Sophia , Kane Christopher J , Kessler Dimitri , Kuperman Joshua , Lee Kang-Lung , Levine Jonathan , Liss Michael A , Margolis Daniel JA , Matthews Ian , Murphy Paul M , Nakrour Nabih , Ohliger Michael , Ollison Courtney , Osinski Thomas , Pamatmat Anthony James , Pompa Isabella R , Rakow-Penner Rebecca , Roberts Jacob L , Santhosh Karan , Shabaik Ahmed S , Song Yuze , Song David , Tempany Clare M. , Wehrli Natasha , Weinberg Eric P. , Woolen Sean , Xu George , Zhong Allison Y , Dale Anders M , Seibert Tyler M 
Published: June 2024

AbstractBackground and ObjectivePositive predictive value of PI-RADS for clinically significant prostate cancer (csPCa, grade group [GG]≥2) varies widely between institutions and radiologists. The Restriction Spectrum Imaging restriction score (RSIrs) is a metric derived from diffusion MRI that could be an objectively interpretable biomarker for csPCa.MethodsIn patients scanned for suspected or known csPCa at 7 centers, we calculated patient-level csPCa probability based on maximum RSIrs in the prostate, without relying on subjectively defined lesions. We used area under the ROC curve (AUC) to compare patient-level csPCa detection for RSIrs, ADC, and PI-RADS. Finally, we combined RSIrs with clinical risk factors via multivariable regression, training in a single-center cohort and testing in an independent, multi-center dataset.Key Findings and LimitationsAmong all patients (n=1892), probability of csPCa increased with higher RSIrs . GG≥4 csPCa was most common in patients with very high RSIrs. Among biopsy-naïve patients (n=877), AUCs for GG≥2 vs. non-csPCa were 0.73 (0.69-0.76), 0.54 (0.50-0.57), and 0.75 (0.71-0.78) for RSIrs, ADC, and PI-RADS, respectively. RSIrs significantly outperformed ADC (p<0.01) and was comparable to PI-RADS (p=0.31). The combination of RSIrs and PI-RADS outperformed either alone. Combining RSIrs with PI-RADS, age, and PSA density in a multivariable model achieved the best discrimination of csPCa.Conclusions and Clinical ImplicationsRSIrs is an accurate and reliable quantitative biomarker that performs better than conventional ADC and comparably to expert-defined PI-RADS for patient-level detection of csPCa. RSIrs provides objective estimates of probability of csPCa that do not require radiology expertise.
KAN-EEG: Towards Replacing Backbone-MLP for an Effective Seizure Detection System
Authors: Herbozo Contreras Luis Fernando , Cui Jiashuo , Yu Leping , Huang Zhaojing , Nikpour Armin , Kavehei Omid 
Published: June 2024

AbstractThe landscape of artificial intelligence (AI) research is witnessing a transformative shift with the emergence of the Kolmogorov-Arnold Network (KAN), presenting a novel architectural paradigm aimed to redefine the structural foundations of AI models, which are based on Multilayer Perceptron (MLP). Through rigorous experimentation and meticulous evaluation, we introduce the KAN-EEG model, a tailored design for efficient seizure detection. Our proposed network is tested and successfully generalized on three different datasets, one from the USA, one from Europe, and one from Oceania, recorded with different front-end hardware. All datasets are scalp Electroencephalogram (EEG) in adults and are from patients living with epilepsy. Our empirical findings reveal that while both architectures demonstrate commendable performance in seizure detection, the KAN model exhibits high-level out-of-sample generalization across datasets from diverse geographical regions, underscoring its inherent adaptability and efficacy at the backbone level. Furthermore, we demonstrate the resilience of the KAN architecture to model size reduction and shallow network configurations, highlighting its versatility and efficiency by preventing over-fitting insample datasets. This study advances our understanding of innovative neural network architectures and underscores the pioneering potential of KANs in critical domains such as medical diagnostics.
Al-Powered classification of Ovarian cancers Based on Histopathological lmages
Authors: Kussaibi Haitham , Alibrahim Elaf , Alamer Eman , Alhaji Ghada , Alshehab Shrooq , Shabib Zahraa , Alsafwani Noor , Meneses Ritesh G. 
Published: June 2024

1AbstractBackgroundOvarian cancer is the leading cause of gynecological cancer deaths due to late diagnosis and high recurrence rates. While histopathological analysis is the gold standard for diagnosis, artificial intelligence (AI) models have shown promise in accurately classifying ovarian cancer subtypes from his-topathology images. Herein, we developed an AI pipeline for automated identification of epithelial ovar-ian cancer (EOC) subtypes based on histopathology images and evaluated its performance compared to the pathologists’ diagnosis.MethodsA dataset of over 2 million image tiles from 82 whole slide images (WSIs) of the major EOC subtypes (clear cell, endometrioid, mucinous, serous) was curated from public and institutional sources. A convolutional neural network (ResNet50) was used to extract features which were then input to 2 classifiers (CNN, and LightGBM) to predict the cancer subtype.ResultsBoth AI classifiers achieved patch-level accuracy (97-98%) on the test set. Furthermore, adding a class-weighted cross-entropy loss function to the pipeline showed better discriminative performance between the subtypes.ConclusionAI models trained on histopathology image data can accurately classify EOC subtypes, potentially assisting pathologists and reducing subjectivity in ovarian cancer diagnosis.
Rapidly deployable mobile BSL-3 laboratory: A response to nipah virus outbreak in Kozhikode, Kerala, India 2023
Authors: Sahay Rima R. , Patil Deepak Y. , Shete Anita M. , Mohandas Sreelekshmy , Gupta Nivedita , Mourya Devendra T. , Yadav Pragya D. 
Published: June 2024

AbstractThe Nipah virus (NiV) outbreak was declared in Kozhikode district, Kerala state, India on September 12, 2023. The local, state, and national authorities worked in an integrated way to tackle and control the outbreak. Indian Council of Medical Research (ICMR) deployed a team from ICMR-National Institute of Virology (NIV), Pune, India along with an indigenously developed and validated Mobile BSL-3 (MBSL-3) laboratory for providing onsite NiV diagnosis. The Kozhikode district of Kerala state has been an epicenter of three NiV outbreaks in May 2018, August 2021, and recently in September 2023. The Ernakulam district, Kerala also reported NiV outbreak in June 2019. In the 2023 outbreak, six confirmed NiV cases were detected with two deaths. During previous outbreaks in 2019 and 2021, the team from ICMR-NIV, Pune had successfully established the field laboratory utilizing the BSL-2 facility for NiV onsite diagnosis. The BSL-3 personnel protective equipment and standard operative procedures were used to handle the clinical specimens. Post COVID-19 pandemic, under the pioneering initiative of the Government of India, ICMR and Klenzaids Contamination Control Pvt Ltd, Mumbai developed a rapidly deployable, pragmatic, access control and containment laboratory on bus chassis. This MBSL-3 laboratory was utilized for the NiV onsite diagnosis for early containment of outbreak reducing the turnaround time to diagnosis to just 4 hours. MBSL-3 laboratory played a significant role in NiV outbreak response and could be utilized in the future also reaching the remotest areas of the country.
Fluoroquinolone-Specific Resistance Trajectories inE. coliand their Dependence on the SOS-Response
Authors: Teichmann Lisa , Luitwieler Sam , Bengtsson-Palme Johan , ter Kuile Benno 
Published: June 2024

AbstractFluoroquinolones are essential for treating bacterial infections in both human and veterinary medicine. This study investigates the mechanisms behind acquired resistance to fluoroquinolones with a specific focus on the SOS response - a critical cellular pathway activated by DNA damage. Utilizing an experimental evolution approach, we exposedEscherichia colito four fluoroquinolones and monitored the adaptation process. ArecAknock-out mutant deficient in the SOS response was used as biological control. The emergence of resistance was accompanied by numerous DNA mutations, consisting of some observed often and others that infrequently appeared. Our findings indicate that the development of resistance depends in varying degrees on the SOS response among the tested fluoroquinolones, with notable dissimilarities in clinical resistance development. Resistance developed slowest to ciprofloxacin, then levofloxacin, followed by enrofloxacin, and fastest to moxifloxacin. Genomic analysis revealed distinct mutation profiles in cultures exposed to the tested antimicrobials, emphasizing the unique adaptation strategies of bacteria. This research underscores the importance of recognizing the differences among fluoroquinolones in scientific research and clinical practice.
Policy perspectives on the sustainable introduction of pneumococcal conjugate vaccines in middle-income countries
Authors: Weeks Rose , Dhaliwal Baldeep K. , Huber Jasmine , Nabia Sarah , Al-Shaikh Ala’a F. , Chokephaibulkit Kulkanya , Fernando LaKKumar , Baghagho Ehssan , Shet Anita 
Published: June 2024

AbstractDespite the well-documented life-saving potential of pneumococcal conjugate vaccines (PCV) and global efforts to widen vaccine availability, access to PCV in middle-income countries (MICs) has remained suboptimal due, in part, to vaccine pricing and limited external funding opportunities. To understand gaps and opportunities for improving vaccine equality, this qualitative study engaged government policymakers and program leaders from MICs that do not currently have PCV in their national immunization programs to explore their perspectives on decision-making contexts and constraints related to PCV introduction. In-depth interviews with 17 participants from Egypt, Jordan, Sri Lanka, and Thailand in 2023 documented that, despite high routine immunization coverage and commitment toward building equitable health systems, implementing new vaccines such as PCV has remained challenging. Among the six thematic areas that emerged, two were strong enablers to vaccine implementation: 1) the existence of strong primary healthcare systems; and 2) established policy processes for vaccine decision-making. Three themes that emerged have historically hindered PCV introduction, including; 1) limited information on disease burden and available vaccine products; 2) competing country health priorities; and 3) financing challenges. The interplay of these thematic areas has documented a paradox unique to MICs, further contributing to inequalities in vaccine access. While a subset of MICs recently became eligible for support from Gavi, the Vaccine Alliance for introducing new vaccines, the marketplace has historically lacked tiered vaccine pricing that MICs could sustain for the long term. This is despite the great need with existing inequities and a substantial proportion of the world’s low-income and displaced populations. Finally, participants pointed to opportunities to address barriers through support from global and regional actors providing technical capacity-strengthening, advocacy, and strategic financial support. These findings are informative for strengthening equality in access to vaccines and developing sustainable strategies to introduce and sustain life-saving childhood vaccines, including PCV.
Characterizing Genetic Pathways Unique to Autism Spectrum Disorder at Multiple Levels of Biological Analysis
Authors: Schaffer Lukas S. , Breunig Sophie , Lawrence Jeremy M. , Foote Isabelle F. , Grotzinger Andrew D. 
Published: June 2024

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by atypical patterns of social functioning and repetitive/restricted behaviors. ASD commonly co-occurs with ADHD and, despite their clinical distinctiveness, the two share considerable genetic overlap. Given their shared genetic liability, it is unclear which genetic pathways confer unique risk for ASD independent of ADHD. We applied Genomic Structural Equation Modeling (SEM) to GWAS summary statistics for ASD and ADHD, decomposing the genetic signal for ASD into that which is unique to ASD (uASD)and that which is shared with ADHD. We computed genetic correlations betweenuASDand 75 external traits to estimate genetic overlap betweenuASDand other clinically relevant phenotypes. We went on to apply Stratified Genomic SEM to identify classes of genes enriched foruASD. Finally, we implemented Transcriptome-Wide SEM (T-SEM) to explore patterns of gene-expression associated withuASD. We observed positive genetic correlations betweenuASDand several external traits, most notably those relating to cognitive/educational outcomes and internalizing psychiatric traits. Stratified Genomic SEM showed that heritability foruASDwas significantly enriched in genes involved in evolutionarily conserved processes, as well as for a histone mark in the germinal matrix. T-SEM revealed 83 unique genes with expression associated withuASD,many of which were novel. These findings delineate the unique biological underpinnings of ASD which exist independent of ADHD and demonstrate the utility of Genomic SEM and its extensions for disambiguating shared and unique risk pathways for genetically overlapping traits.