Miracle-dz/UniFAR-FTUs huggingface dataset:
The diagnostic and prognostic value of copeptin in patients with acute ischemic stroke and transient ischemic attack: A systematic review and meta-analysis

Background Stroke is the second main cause of mortality and the third leading cause of mortality and permanent disability combined. Many potential biomarkers have been described to contribute to the diagnosis, prognosis of outcomes, and risk stratification after stroke. Copeptin is an inactive peptide that is produced in an equimolar ratio to arginine vasopressin in response to the activation of the endogenous stress system. Methods The present study is a systematic review and meta-analysis to assess plasma copeptin concentrations, diagnostic and prognostic values for risk stratification after acute ischemic stroke and transient ischemic attack. Results Mean copeptin level in stroke vs. non-stroke groups varied and amounted to 19.8 ± 17.4 vs. 9.7 ± 6.6 pmol/L, respectively (mean differences [MD]: 12.75; 95% confidence interval [CI]: 5.00 to 20.49; p < 0.001), in good vs. poor outcome 12.0 ± 3.6 vs. 29.4 ± 14.5 (MD: −8.13; 95% CI: −8.37 to −7.88; p < 0.001) and in survive vs. non-survive stroke patients: 13.4 ± 3.2 vs. 33.0 ± 12.3, respectively (MD: −13.43; 95% CI: −17.82 to −9.05; p < 0.001). Conclusions The above systematic review and meta-analysis suggests that monitoring the copeptin levels may help predict the long-term prognosis of ischemic stroke efficiently. Determining the copeptin level may help individualize the management of ischemic stroke patients, keep stroke risk lower, reduce post-stroke complications, including patient death, and minimize healthcare costs.
A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging

Background and Objectives To elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging. Methods Low and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF β-amyloid (Aβ) peptide biomarkers. These Aβ cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients. Results A total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. Discussion The proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
Resilient Optimal Defensive Strategy of Micro-Grids System via Distributed Deep Reinforcement Learning Approach Against FDI Attack

The ever-increasing false data injection (FDI) attack on the demand side brings great challenges to the energy management of interconnected microgrids. To address those aspects, this article proposes a resilient optimal defensive strategy with the distributed deep reinforcement learning (DRL) approach. To evaluate the FDI attack on demand response (DR), an online evaluation approach with the recursive least-square (RLS) method is proposed to evaluate the extent of supply security or voltage stability of the microgrids system is affected by the FDI attack. On the basis of evaluated security confidence, a distributed actor network learning approach is proposed to deduce optimal network weight, which can generate an optimal defensive scheme to ensure the economic and security issue of the microgrids system. From the methodology’s view, it can also enhance the autonomy of each microgrid as well as accelerate DRL efficiency. According to those simulation results, it can reveal that the proposed method can evaluate FDI attack impact well and an improved distributed DRL approach can be a viable and promising way for the optimal defense of microgrids against the FDI attack on the demand side.
Pruning recurrent neural networks replicates adolescent changes in working memory and reinforcement learning

Significance Adolescence is a period during which there are important changes in behavior and the structure of the brain. In this manuscript, we use theoretical modeling to show how improvements in working memory and reinforcement learning that occur during adolescence can be explained by the reduction in synaptic connectivity in prefrontal cortex that occurs during a similar period. We train recurrent neural networks to solve working memory and reinforcement learning tasks and show that when we prune connectivity in these networks, they perform the tasks better. The improvement in task performance, however, can come at the cost of flexibility as the pruned networks are not able to learn some new tasks as well.
Pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects

Abstract Objectives: To explore associations between maternal pre-pregnancy exposure to arsenic in diet and non-cardiac birth defects. Design: This is a population-based, case–control study using maternal responses to a dietary assessment and published arsenic concentration estimates in food items to calculate average daily total and inorganic arsenic exposure during the year before pregnancy. Assigning tertiles of total and inorganic arsenic exposure, logistic regression analysis was used to estimate OR for middle and high tertiles, compared to the low tertile. Setting: US National Birth Defects Prevention Study, 1997–2011. Participants: Mothers of 10 446 children without birth defects and 14 408 children diagnosed with a non-cardiac birth defect. Results: Maternal exposure to total dietary arsenic in the middle and high tertiles was associated with a threefold increase in cloacal exstrophy, with weak positive associations (1·2–1·5) observed either in both tertiles (intercalary limb deficiency) or the high tertile only (encephalocele, glaucoma/anterior chamber defects and bladder exstrophy). Maternal exposure to inorganic arsenic showed mostly weak, positive associations in both tertiles (colonic atresia/stenosis, oesophageal atresia, bilateral renal agenesis/hypoplasia, hypospadias, cloacal exstrophy and gastroschisis), or the high (glaucoma/anterior chamber defects, choanal atresia and intestinal atresia stenosis) or middle (encephalocele, intercalary limb deficiency and transverse limb deficiency) tertiles only. The remaining associations estimated were near the null or inverse. Conclusions: This exploration of arsenic in diet and non-cardiac birth defects produced several positive, but mostly weak associations. Limitations in exposure assessment may have resulted in exposure misclassification. Continued research with improved exposure assessment is recommended to identify if these associations are true signals or chance findings.
Nonsynonymous SNPs within C7H15orf39 and NOS2 are associated with boar semen quality

Abstract Spermatogenesis is the developmental process that produces spermatozoa. The aim of this study was to investigate the single nucleotide polymorphisms (SNPs) within C7H15orf39 and NOS2 genes and to determine the correlations between two SNPs and semen quality in Duroc boars (n = 604). The polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method was used for genotyping the selected two nonsynonymous SNPs. The significant correlation was observed between two SNPs (rs80969873: g.58385473 G > A within C7H15orf39; rs325865291: g.44175445 G > A within NOS2) and semen traits in Duroc boars. This study indicates the SNPs in C7H15orf39 and NOS2 may be the potential molecular marker for improving the semen quality traits in Duroc boars.
Endometritis - Diagnosis,Treatment and its impact on fertility - A Scoping Review

Endometritis is defined as an infection or inflammation of the endometrium. Endometritis is of two types: acute and chronic. Acute endometritis is the symptomatic acute inflammation of the endometrium, which upon examination with a microscope shows micro-abscess and neutrophil invasion in the superficial endometrium. One of its most common manifestations is postpartum endometritis. Chronic endometritis is a silent disease usually diagnosed on the workup of secondary amenorrhoea and infertility. An important cause of chronic endometritis is tuberculosis, especially in developing nations. Chronic and acute endometritis have been associated with poor reproductive outcomes. Worse outcomes have been reported for individuals with chronic endometritis. This is a scoping review of endometritis and its impact on fertility.
A novel bioassay to detect Nociceptin/Orphanin FQ release from single human polymorphonuclear cells

Nociceptin/Orphanin FQ (N/OFQ) is the endogenous opioid agonist for the N/OFQ receptor or NOP. This receptor system is involved in pain processing but also has a role in immune regulation. Indeed, polymorphonuclear cells (PMNs) express mRNA for N/OFQ precursor and are a potential source for circulating N/OFQ. Current measurements are based on ELISA and RIA techniques. In this study we have designed a bioassay to measure N/OFQ release from single PMNs. Chinese Hamster Ovary (CHO) cells transfected with the human (h) NOP receptor and Gαiq5 chimera force receptor coupling in biosensor cells to increase intracellular Ca2+; this can be measured with FLUO-4 dye. If isolated PMNs from healthy human volunteers are layered next to CHOhNOPGαiq5 biosensor cells then stimulated with the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (fMLP) we hypothesise that released N/OFQ will activate the biosensor. PMNs also release ATP and CHO cells express purinergic receptors coupled to elevated Ca2+. In a system where these receptors (P2Y1, P2Y2 and P2X7) are blocked with high concentrations of PPADS and oATP, PMN stimulation with fMLP increases Ca2+ in PMNs then shortly afterwards the biosensor cells. Our data therfore reports detection of single cell N/OFQ release from immune cells. This was absent when cells were preincubated with the selective NOP antagonist; SB-612111. Collectively this is the first description of single cell N/OFQ release. We will deploy this assay with further purified individual cell types and use this to further study the role of the N/OFQ-NOP system in disease; in particular sepsis where there is strong evidence for increased levels of N/OFQ worsening outcome.
Morphological and molecular study of Didymodiclinus marginati n. sp. (Trematoda: Didymozoidae) gill parasite of Epinephelus marginatus from the central and western Mediterranean Sea

Abstract Abstract The current study provides a morphological and molecular characterization of a new species of Didymodiclinus (Trematoda: Didymozoidae) infecting the dusky grouper, Epinephelus marginatus (Teleostei: Serranidae) from the Mediterranean Sea. A total of 279 dusky grouper specimens were examined for didymozoid gill parasites from the Mediterranean Sea between 1998 and 2020. New species differs from the most similar congeneric species by the rudiments of female reproductive organs in functional male specimens, and the seminal receptacle, Mehlis gland and accessory gland cells in functional female specimens, not observed in Didymodiclinus branchialis (Yamaguti, 1970), Didymodiclinus epinepheli (Abdul-Salam, Sreelatha and Farah, 1990) and Didymodiclinus pacificus (Yamaguti, 1938), respectively. These species are also characterized by their different hosts and location within the host tissues, being from other geographical localities. Moreover, this is the first species reported in E. marginatus from the central and western Mediterranean Sea. Genetic analyses were performed on partial 28S and partial internal transcribed spacer-2 ribosomal RNA regions and the mitochondrial cytochrome oxidase 1 (cox1) gene by polymerase chain reaction. Comparison of genetic sequences of Didymodiclinus marginati n. sp. with the available deposited sequences of 28S revealed that the new isolates cluster with several unidentified didymozoids and groups as a sister clade of the Nematobothrinae subfamily. Moreover, 28S and cox1 phylogenetic trees evidenced that Didymodiclinae is well separated from Didymozoinae and other gonochoric didymozoids. Following both morphological and genetic results, a key of identification for the genus Didymodiclinus is proposed.
Sectioning and Counting of Motor Neurons in the L3 to L6 Region of the Adult Mouse Spinal Cord

Histology is the study of the microscopic structure of tissues. This protocol permits the generation of frozen transverse sections of lumbar spinal cord regions L3 to L6. It enables counting of murine ventral horn lumbar motor neurons in a reproducible manner. Methods include spinal column dissection, hydraulic extrusion, and histological processing. The preparation for cryo‐sectioning includes embedding lumbar spinal cord in optimal cutting temperature (OCT) medium. The correct orientation of the tissue is critical as calculating the amount of tissue to discard saved time overall. Specific details regarding section thickness and mounting are described. These requirements not only allow optimum coverage of specific regions but also ensure that no individual motor neuron was counted twice. The Nissl bodies of the motor neurons were stained using gallocyanin. The sections obtained are all of a comparable area and quality assurance is consistent. The specificity of the staining enables the scientist to identify and reliably quantify lumbar motor neurons. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC.
Network pharmacology and experimental validation identify the potential mechanism of sophocarpine for COVID-19.

Introduction. Coronavirus disease 2019 (COVID-19) has caused a serious threat to public health worldwide, and there is currently no effective therapeutic strategy for treating COVID-19.Hypothesis/Gap Statement. We propose that sophocarpine (SOP) might have potential therapeutic effects on COVID-19 through inhibiting the cytokine storm and the nuclear factor NF-κB signalling pathway.Aim. The objective was to elucidate the potential mechanism of SOP against COVID-19 through a network pharmacology analysis and its experimental validation.Methodology. The BATMAN-TCM database was used to identify the therapeutic targets of SOP, while the GeneCards and DisGeNET databases were used to identify the targets related to COVID-19. A protein-protein interaction (PPI) network was constructed from the STRING and analysed using Cytoscape software. Gene ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) and disease ontology (DO) enrichment analyses of the co-targets were performed using Metascape. Autodock 4.2. 6 and Pymol software were applied for molecular docking. Levels of the proinflammatory cytokines IL-6, TNFα and IL-1β were measured by ELISA, while mRNA expression levels of intercellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor A (VEGFA) and IFN gamma (IFNG) were detected by real-time quantitative reverse transcription PCR. The protein levels of the molecules involved in the NF-κB signalling pathway were validated by western blot analysis.Results. A total of 65 co-targets of SOP and COVID-19 were determined. GO and KEGG enrichment analyses suggested that SOP affected COVID-19 by regulating the IL-17 signalling pathway, TNF signalling pathway and other signalling pathways. The PPI network and molecular docking showed that p65, ICAM-1 and VEGFA were key targets of SOP against COVID-19 and the underlying mechanism was validated in A549 cells in vitro. SOP attenuated the LPS-induced production of TNF-α and IL-6 and downregulated the LPS-induced mRNA expression of ICAM-1, VEGFA and IFNG. Mechanistically, SOP pretreatment inhibited the phosphorylation of p65 and facilitated the activation of Nrf2.Conclusions. SOP has a potential therapeutic effect on COVID-19 through multiple pathways and targets, and inhibits the production of pro-inflammatory cytokines and molecules involved in the NF-κB signalling pathway.
Risk of Cerebro-Cardiovascular Diseases among Police Officers and Firefighters: A Nationwide Retrospective Cohort Study

Purpose Police officers and firefighters are exposed to risk factors for cerebro-cardiovascular diseases, and the actual risk is expected to increase compared with other occupational groups. The present study aimed to estimate the risks of cerebro-cardiovascular diseases in police officers and firefighters compared to other occupational groups. Materials and Methods Using the National Health Insurance Service data, we constructed a retrospective cohort of public officers. Three-year consecutive health insurance registration data were used to identify police officers and firefighters. Cerebro-cardiovascular diseases consisted of acute myocardial infarction, other ischemic heart disease, cardiac arrhythmia, and stroke. We compared the incidences of cerebro-cardiovascular diseases between each of the two occupational groups (police officers and firefighters) and other public officers by calculating standardized incidence ratios (SIRs). Results SIRs and 95% confidence intervals of all cerebro-cardiovascular diseases for police officers and firefighters were 1.71 (1.66–1.76) and 1.22 (1.12–1.31), respectively, as compared with all public officers. The incidence ratios remained significantly higher compared to general and education officers. Subgroup analyses for myocardial infarction, stroke, and cardiac arrhythmia exhibited significant increases in incidence ratios among police officers and firefighters. Conclusion This study suggests that both police officers and firefighters are at high risk of cerebro-cardiovascular diseases. Therefore, medical protection measures for these occupational groups should be improved.
Measuring user interactions with websites: A comparison of two industry standard analytics approaches using data of 86 websites

This research compares four standard analytics metrics from Google Analytics with SimilarWeb using one year’s average monthly data for 86 websites from 26 countries and 19 industry verticals. The results show statistically significant differences between the two services for total visits, unique visitors, bounce rates, and average session duration. Using Google Analytics as the baseline, SimilarWeb average values were 19.4% lower for total visits, 38.7% lower for unique visitors, 25.2% higher for bounce rate, and 56.2% higher for session duration. The website rankings between SimilarWeb and Google Analytics for all metrics are significantly correlated, especially for total visits and unique visitors. The accuracy/inaccuracy of the metrics from both services is discussed from the vantage of the data collection methods employed. In the absence of a gold standard, combining the two services is a reasonable approach, with Google Analytics for onsite and SimilarWeb for network metrics. Finally, the differences between SimilarWeb and Google Analytics measures are systematic, so with Google Analytics metrics from a known site, one can reasonably generate the Google Analytics metrics for related sites based on the SimilarWeb values. The implications are that SimilarWeb provides conservative analytics in terms of visits and visitors relative to those of Google Analytics, and both tools can be utilized in a complementary fashion in situations where site analytics is not available for competitive intelligence and benchmarking analysis.
Effective Treatment of Human Breast Carcinoma Xenografts with Single-Dose 211At-Labeled Anti-HER2 Single-Domain Antibody Fragment

Visual Abstract Single-domain antibody fragments (sdAbs) are attractive for targeted α-particle therapy, particularly with 211At, because of their rapid accumulation in tumor and clearance from normal tissues. Here, we evaluate the therapeutic potential of this strategy with 5F7 and VHH_1028—2 sdAbs that bind with high affinity to domain IV of human epidermal growth factor receptor type 2 (HER2). Methods: The HER2-specific sdAbs and HER2-irrelevant VHH_2001 were labeled using N-succinimidyl-3-211At-astato-5-guanidinomethyl benzoate (iso-211At-SAGMB). The cytotoxicity of iso-211At-SAGMB-5F7 and iso-211At-SAGMB-VHH_2001 were compared on HER2-expressing BT474 breast carcinoma cells. Three experiments in mice with subcutaneous BT474 xenografts were performed to evaluate the therapeutic effectiveness of single doses of iso-211At-SAGMB-5F7 (0.7–3.0 MBq), iso-211At-SAGMB-VHH_1028 (1.0–3.0 MBq), and iso-211At-SAGMB-VHH_1028 and iso-211At-SAGMB-VHH_2001 (∼1.0 MBq). Results: Clonogenic survival of BT474 cells was reduced after exposure to iso-211At-SAGMB-5F7 (D0 = 1.313 kBq/mL) whereas iso-211At-SAGMB-VHH_2001 was ineffective. Dose-dependent tumor growth inhibition was observed with 211At-labeled HER2-specific 5F7 and VHH_1028 but not with HER2-irrelevant VHH_2001. At the 3.0-MBq dose, complete tumor regression was seen in 3 of 4 mice treated with iso-211At-SAGMB-5F7 and 8 of 11 mice treated with iso-211At-SAGMB-VHH_1028; prolongation in median survival was 495% and 414%, respectively. Conclusion: Combining rapidly internalizing, high-affinity HER2-targeted sdAbs with the iso-211At-SAGMB residualizing prosthetic agent is a promising strategy for targeted α-particle therapy of HER2-expressing cancers.
Visuo-spatial working memory for objects and configurations in natural scenes in university students with ADHD

ABSTRACT Adults with ADHD typically show reduced performance in visuo-spatial working memory (VSWM) tasks. These limitations have been observed mainly in tasks probing VSWM for low-level visual information. The current study investigated whether these limitations extended to memory for real-world objects, and memory for the spatial context in which they were presented. Sixty-four university students with and without ADHD memorised the form of real-world objects embedded in natural scenes. Following a short delay, participants were probed on a single object in the scene that could change in token or orientation, and that could appear within the original scene or in isolation. Consistent with previous studies, memory for the individual objects was impaired in the ADHD group relative to the control group, demonstrating that this deficit extends to complex real-world objects. Nevertheless, participants in the ADHD group benefited from the reinstatement of the scene during retrieval to the same extent as participants in the control group. This finding suggests that participants in the ADHD group formed and maintained a representation of the spatial context of the scene that aided memory retrieval. Overall, the results support an emerging view that VSWM operates on multiple, possibly independent, representations at different hierarchal levels.