Miracle-dz/UniFAR-FTUs huggingface dataset:
Interictal amylin levels in chronic migraine patients: A case-control study

Background Recently, amylin and its receptors were found in different structures involved in migraine pathophysiology. Here, we evaluate interictal concentrations of amylin and calcitonin gene-related peptide in peripheral blood as biomarkers for chronic migraine. Methods We prospectively recruited patients with episodic migraine, chronic migraine and healthy controls. Interictal amylin and calcitonin gene-related peptide levels were assessed in blood samples using enzyme linked immunosorbent assay. Results We assessed plasma samples from 58 patients with episodic migraine (mean age 37.71 ± 10.47, 87.9% female), 191 with chronic migraine (mean age 46.03 ± 11.93, 95% female), and on 68 healthy controls (mean age 43.58 ± 11.08 years, 86% female). Body mass index was 25.94 ± 4.53 kg/m2 for migraine patients and 25.13 ± 4.92 kg/m2 for healthy controls (p = 0.0683). Interictal plasma amylin levels were higher in chronic migraine patients (47.1 pg/mL) than in the episodic migraine patients (28.84 pg/mL, p < 0.0001) and healthy controls (24.74 pg/mL, p < 0.0001). Plasma calcitonin gene-related peptide levels were increased (20.01 pg/mL) in chronic migraine patients when compared to healthy controls (11.37 pg/mL, p = 0.0016), but not to episodic migraine patients (18.89 pg/mL, p = 0.4369). Applying a cut-off concentration of 39.68 pg/mL plasma amylin, the sensitivity to differentiate chronic migraine from healthy controls was 57.6% and the specificity was 88.2%. Variables such as age, analgesic overuse, depression, allodynia, use of preventive medication or a history of aura did not influence the plasma concentrations of amylin or calcitonin gene-related peptide. Conclusion Interictal plasma amylin levels are higher in patients with chronic migraine and may serve as a diagnostic biomarker for chronic migraine.
Modeling the epidemiological impact and cost-effectiveness of a combined schoolgirl HPV vaccination and cervical cancer screening program among Chinese women

ABSTRACT Human papillomavirus (HPV) infection is common in women and also the main cause of cervical cancer. Based on a dynamic compartmental model, we aimed to evaluate the population impact and cost-effectiveness of strategies that combined cervical cancer screening and HPV schoolgirl vaccination for Chinese women. The effectiveness of interventions was assessed by comparing modeled scenarios to the status quo, where a 3-y cervical cancer screening program remained at a 20% coverage and without a universal HPV vaccination program. Our study demonstrated that increasing screening coverage from 20% to 50% would reduce the high-risk HPV (HR-HPV) prevalence to 5.4%, whereas a universal schoolgirl vaccination program using the quadrivalent vaccine (qHPV) with a coverage of 50% would reduce the prevalence to 2.9% by 2069. Scaling-up the cervical screening coverage to 50% will prevent 16,012 (95% CI: 8,791 to 25,913) Disability-Adjusted Life-Years (DALYs) per year, with an incremental cost-effectiveness ratio (ICER) of US$ 10,958 (95% CI: $169 to $26,973)/DALY prevented. At the current qHPV price, vaccinating 50% of school girls will prevent 13,854 (95% CI: 8,355 to 20,776) DALYs/year, but the corresponding incremental cost-effectiveness ratio (ICER, US$ 83,043, 95% CI: $52,234 to $138,025) exceeds cost-effectiveness threshold (i.e., 3 times GDP per-capita of China: $30,792). The qHPV vaccine requires at least a 50% price reduction to be cost-effective. Vaccinating schoolgirls will result in a large population health benefit in the long term, but such a universal HPV vaccination program can only be cost-effective with a substantial price reduction.
SARS-CoV-2 Inhibition by Sulfonated Compounds

Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) depends on angiotensin converting enzyme 2 (ACE2) for cellular entry, but it might also rely on attachment receptors such as heparan sulfates. Several groups have recently demonstrated an affinity of the SARS-CoV2 spike protein for heparan sulfates and a reduced binding to cells in the presence of heparin or heparinase treatment. Here, we investigated the inhibitory activity of several sulfated and sulfonated molecules, which prevent interaction with heparan sulfates, against vesicular stomatitis virus (VSV)-pseudotyped-SARS-CoV-2 and the authentic SARS-CoV-2. Sulfonated cyclodextrins and nanoparticles that have recently shown broad-spectrum non-toxic virucidal activity against many heparan sulfates binding viruses showed inhibitory activity in the micromolar and nanomolar ranges, respectively. In stark contrast with the mechanisms that these compounds present for these other viruses, the inhibition against SARS-CoV-2 was found to be simply reversible.
Mesenchymal Characteristics and Predictive Biomarkers on Circulating Tumor Cells for Therapeutic Strategy

Simple Summary Circulating tumor cells (CTCs) are the seeds that spread through the circulatory system and generate the metastatic sites. Among the various phenotypes exhibited by CTCs, epithelial-to-mesenchymal transition (EMT) has extensively gained attention because of its contribution to the acquisition of invasiveness and motility of CTCs, which is critical for the successful metastasis process. So far, many clinical studies have demonstrated that expressions of mesenchymal features in CTCs are associated with poor clinical outcomes in many types of solid cancer. In this review, the clinical significance of CTCs as a liquid biopsy is described in terms of the mesenchymal characteristics, expression of predictive biomarkers, and their correlations. Detailed analysis of these multivariate targets in CTCs could improve therapeutic decision-making. Abstract Metastasis-related events are the primary cause of cancer-related deaths, and circulating tumor cells (CTCs) have a pivotal role in metastatic relapse. CTCs include a variety of subtypes with different functional characteristics. Interestingly, the epithelial–mesenchymal transition (EMT) markers expressed in CTCs are strongly associated with poor clinical outcome and related to the acquisition of circulating tumor stem cell (CTSC) features. Recent studies have revealed the existence of CTC clusters, also called circulating tumor microemboli (CTM), which have a high metastatic potential. In this review, we present current opinions regarding the clinical significance of CTCs and CTM with a mesenchymal phenotype as clinical surrogate markers, and we summarize the therapeutic strategy according to phenotype characterization of CTCs in various types of cancers for future precision medicine.
Aggregating Long-Term Context for Learning Laparoscopic and Robot-Assisted Surgical Workflows

Analyzing surgical workflow is crucial for surgical assistance robots to understand surgeries. With the understanding of the complete surgical workflow, the robots are able to assist the surgeons in intra-operative events, such as by giving a warning when the surgeon is entering specific keys or high-risk phases. Deep learning techniques have recently been widely applied to recognizing surgical workflows. Many of the existing temporal neural network models are limited in their capability to handle long-term dependencies in the data, instead, relying upon the strong performance of the underlying per-frame visual models. We propose a new temporal network structure that leverages task-specific network representation to collect long-term sufficient statistics that are propagated by a sufficient statistics model (SSM). We implement our approach within an LSTM backbone for the task of surgical phase recognition and explore several choices for propagated statistics. We demonstrate superior results over existing and novel state-of-the-art segmentation techniques on two laparoscopic cholecystectomy datasets: the publicly available Cholec80 dataset and MGH100, a novel dataset with more challenging and clinically meaningful segment labels.
Measuring Welfare and Inequality with Incomplete Price Information

We propose and implement a new approach that allows us to estimate income-specific changes in household welfare in contexts where well-measured prices are not available for important subsets of consumption. Using rich but widely available expenditure survey microdata, we show that we can recover income-specific equivalent and compensating variations from horizontal shifts in what we term “relative Engel curves”—as long as preferences fall within the broad quasi-separable class (Gorman 1970; 1976). Our approach is flexible enough to allow for nonparametric estimation at each point of the income distribution. We apply the methodology to estimate inflation and welfare changes in rural India between 1987 and 2000. Our estimates reveal that lower rates of inflation for the rich erased the real income convergence found in the existing literature that uses the subset of consumption with well-measured prices to calculate inflation.
Fertilidade do solo, crescimento e qualidade de frutos do mamoeiro Tainung sob fertirrigação com potássio

The objective of this study was to evaluate the effects of soil fertility, plant growth, mineral composition in leaves and petioles, productivity and fruit quality of papaya Formosa, Cv. 'Tainung No.1' in terms of levels of potassium fertilization on soil applied by fertigation. The experiment was carried during the growing seasons of 2008/2009 and 2010/2011 in a randomized blocks, with five replications, installed in an area of commercial cultivation in the of Russas city in Ceara state, Brazil. The treatments were: four doses of KCl (60; 120; 180 and 240 g plant month-1), applied as KCl in irrigation water along with conventional fertilizers used in cultivation of papaya in a Typic Quartzipisamment of farm. Treatment doses influence soil fertility by increasing the concentrations of N, P, K, organic matter and leached the soil base maximized the growth and yield of papaya. The absorption of N, P and K in the papaya tree was greater during the highest productivity. P showed the greates accumulation in the fruit. The levels of K influenced fruit quality. The dose 180 g plant per montn-1 favors the production of best quality fruits for table consumption and processing of pulp.
A model for the influence of defect interactions during heating on thermoluminescence in LiF:Mg,Ti (TLD-100)

Thermoluminescence in LiF:Mg,Ti is frequently described with the Randall-Wilkins model which assumes first-order kinetics. This model fits a measured single glow curve (light output as a function of temperature during heating up the sample) very well. If this model describes the thermoluminescence phenomenon correctly, one expects that the model parameters are not dependent on the experimental conditions. However, the model parameters show a strong dependence on read-out heating rate and annealing procedure. To explain this dependence it is assumed that the defects involved in the thermoluminescence process are also involved in reactions with other defects. In this article, defect reactions are incorporated into the rate equations for thermoluminescence. Glow curves are simulated at different read-out heating rates for the simple case in which one defect reaction occurs simultaneously with a trap emptying process. It appears that the simulated glow curves can be very well fitted by the Randall-Wilkins model and that the dependence of the parameters of these simulated curves on the heating rate during read-out is comparable with measured data of LiF:Mg,Ti. Moreover, the occurrence of defect reactions during read-out also gives an explanation for (i) the dependence of the Randall-Wilkins parameters on the annealing procedure and impurity concentration, (ii) the too low values of the fading rates predicted by the Randall-Wilkins parameters and (iii) the unexpected high E and s values of peak 5 of LiF:Mg,Ti.
Effect of low-energy laser irradiation on cytokine secretion from skeletal muscle cells: involvement of calcium in the process

Low energy laser irradiation has an effect on Nerve Growth Factor and anti mitotic factors release from rat and mouse skeletal muscle cultures. It was found that there is a transient elevation of intracellular calcium in the myotubes immediately after irradiation. Calcium changes were detected by dynamic video imaging systems and with a photometric system. Pre incubation of the myotubes with photosensitizers enhance the elevation of both cytosolic calcium and cytokines release from the cells after Helium/Neon irradiation with energy of 3-10 J/cm2. These findings can lead to an hypothesis that transient changes in calcium can accelerate cytokines release from the myotubes.
Temporal Lobe Activation Predicts Episodic Memory Following Traumatic Brain Injury

The temporal lobes are critical for episodic memories and are preferentially affected following a traumatic brain injury (TBI). As such, episodic memory difficulties are common following TBI; however, the underlying neural changes that precipitate or maintain these difficulties in the early phase of recovery remains poorly understood. Here, we use functional magnetic resonance imaging (fMRI) to interrogate the relationship of temporal lobe activation in response to face, scene, and animal stimuli. Twenty-five patients with moderate to severe TBI were recruited an average of 2 months’ post-injury and compared with 21 demographically similar healthy controls. Findings indicate that memory for faces was preferentially impaired, compared to scene and animal stimuli. Decreased activity in temporal lobe structures was present for both face (right transverse temporal gyrus) and scene stimuli (right fusiform gyrus), but not for animals. Greater activation in these structures was associated with better long-term recognition. These findings provide evidence to suggest that TBI: a) preferentially affects memory for complex stimuli such as faces and scenes, and b) causes aberrant neuronal processes despite lack of evidence of significant impairment in behavioural performance. The mechanisms underpinning these findings are discussed in terms of differences in strategy use and reduced neural efficiency.
Celecoxib Colorectal Bioavailability and Chemopreventive Response in Familial Adenomatous Polyposis Patients

The chemopreventive activity of celecoxib against colorectal cancer is limited to a proportion of familial adenomatous polyposis (FAP) patients who experience a response. The cause of this response variability and the potential mechanisms underlying these responses remain poorly understood. Preclinical studies showed that celecoxib increases the production of main oxidative metabolism product of linoleic acid, 13-S-hydroxyoctadecadienoic acid (13-S-HODE), to suppress colorectal tumorigenesis. We conducted a phase II clinical study to determine whether celecoxib increases 13-S-HODE production in colonic adenomas from FAP patients. Twenty seven FAP patients completed a 6-month oral course of 400 mg of celecoxib twice a day and had colonoscopies before and after celecoxib treatment to assess colorectal polyp tumor burden and obtain colorectal normal and polyp biopsies to measure celecoxib, 13-HODE, 15-HETE, 12-HETE, and LTB4 levels by LC/MS. Celecoxib levels in sera from those patients were also measured before treatment and 2, 4, and 6 months of treatment. Seventeen of the 27 patients experienced a response to celecoxib, with a more than 30% reduction of colonic polyp burden on the basis of a reproducible quantitative assessment of colonoscopy results. Celecoxib levels were significantly lower in polyp tissues than in normal colorectal tissues. Celecoxib levels in sera and normal colorectal tissues were correlated in patients who experienced a response to celecoxib but not in those who did not. Among the measured lipoxygenase products, only 13-HODE levels were significantly lower in polyp tissues than in normal tissues. Our findings demonstrate the differential bioavailability of celecoxib between normal and polyp tissues and its potential effects on clinical response in FAP patients.
Post-infectious inflammatory disease in MIS-C features elevated cytotoxicity signatures and autoreactivity that correlates with severity

Multisystem inflammatory syndrome in children (MIS-C) is a life-threatening post-infectious complication occurring unpredictably weeks after mild or asymptomatic SARS-CoV2 infection in otherwise healthy children. Here, we define immune abnormalities in MIS-C compared to adult COVID-19 and pediatric/adult healthy controls using single-cell RNA sequencing, antigen receptor repertoire analysis, unbiased serum proteomics, and in vitro assays. Despite no evidence of active infection, we uncover elevated S100A-family alarmins in myeloid cells and marked enrichment of serum proteins that map to myeloid cells and pathways including cytokines, complement/coagulation, and fluid shear stress in MIS-C patients. Moreover, NK and CD8 T cell cytotoxicity genes are elevated, and plasmablasts harboring IgG1 and IgG3 are expanded. Consistently, we detect elevated binding of serum IgG from severe MIS-C patients to activated human cardiac microvascular endothelial cells in culture. Thus, we define immunopathology features of MIS-C with implications for predicting and managing this SARS-CoV2-induced critical illness in children.
The epidemiology and direct medical costs of diseases associated with human papillomavirus infection among men in Manitoba, Canada

Background: There is little information on the economic burden of human papillomavirus-related diseases (HPV-RDs) among men. We used province-wide clinical, administrative and accounting databases to measure the direct medical costs of HPV infections in men in Manitoba (Canada). Methods: We included all males aged 9 years and older with health insurance coverage in Manitoba between January 1997 and December 2016. We identified HPV-RD patient cohorts and matched each patient to HPV-RD-free men. We estimated the net direct medical cost (excess cost of hospitalizations, outpatient visits, and prescription drugs) of patients compared to their matches for anogenital warts (AGWs) and HPV-caused cancers. We adjusted costs to 2017 Canadian dollars. For each condition, we attributed costs to HPV based on the etiological fraction caused by HPV infection. Results: We found that the median net direct medical cost was about $250 for AGW patients and $16,000 for invasive cancer patients. The total cost was about $49 million or $2.6 million per year. Overall, 54%-67% ($26-$33 million) was attributable to HPV infection according different estimates of the attributable fraction. The net annual attributable cost was $2.37-$2.95 per male resident and $161-$200 per male newborn. The estimated potential savings was 30% for the bivalent vaccine and 56%-60% for the quadrivalent and nonavalent vaccines. Conclusions: Overall, HPV's economic burden on males remains significant, the average cost of treating all conditions attributable to HPV was about $180 per male newborn. Invasive cancer accounted for the majority of these costs.
Clinical Evaluation of a COVID-19 Antibody Lateral Flow Assay using Point of Care Samples

Introduction: The ongoing SARS-CoV-2 pandemic has spurred the development of numerous point of care (PoC) immunoassays. Assessments of performance of available kits are necessary to determine their clinical utility. Previous studies have mostly performed these assessments in a laboratory setting, which raises concerns of translating findings for PoC use. The aim of this study was to assess the performance of a lateral flow immunoassay for the detection of SARS-CoV-2 antibodies using samples collected at PoC. Method: One lateral flow immunoassay (Humasis(R) COVID-19 IgG/IgM) was tested. In total, 50 PCR RT-PCR positive and 52 RT-PCR negative samples were collected at PoC. Fifty serum specimens from Dec 2018 to Feb 2019 were used as controls for specificity. Serum samples collected between Dec 2019 to Feb 2020 were used as additional comparators. Clinical data including symptom onset date was collected from patient history and the medical record. Results: The overall sensitivity for the kit was 74% (95% CI: 59.7% - 85.4%). The sensitivity for IgM and IgG detection >14 days after date of onset was 88% (95% CI: 68.8% - 97.5%) and 84% (95% CI: 63.9% - 95.5%), with a negative predictive value (NPV) of 94% for IgM (95% CI: 83.5% - 98.8%) and 93% for IgG (95% CI: 81.8% - 97.9%). The overall specificity was 94% (95% CI: 83.5% - 98.8%). The Immunoglobulin specific specificity was 94% for IgM (95% CI: 83.5% - 98.8%) and 98% for IgG (95% CI: 89.4% - 100.0%), with a positive predictive value (PPV) of 88% for IgM (95% CI: 68.8% - 97.5%) and 95% for IgG (95% CI: 77.2% - 99.9%) respectively for samples collected from patients >14 days after date of onset. Specimen collected during early phase of COVID-19 pandemic (Dec 2019 to Feb 2020) showed 11.8% antibody positivity, and 11.3% of PCR-negative patients demonstrated antibody positivity. Discussion: Humasis(R) COVID-19 IgG/IgM LFA demonstrates greater than 90% PPV and NPV for samples collected 14 days after the onset of symptoms using samples collected at PoC. While not practical for the diagnosis of acute infection, the use of the lateral flow assays with high specificity may have utility for determining seroprevalence or seroconversion in longitudinal studies.
Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Suicide is a leading cause of death worldwide and non-fatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both are known to have a substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium and conditioned the results on psychiatric disorders using GWAS summary statistics, to investigate their shared and divergent genetic architectures. Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, which remained associated after conditioning and has previously been implicated in risk-taking, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, lower socioeconomic status, pain, lower educational attainment, reproductive traits, risk-taking, sleep disturbances, and poorer overall general health. After conditioning, the genetic correlations between SA and psychiatric disorders decreased, whereas those with non-psychiatric traits remained largely unchanged. Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest the existence of a shared genetic etiology between SA and known risk factors that is not mediated by psychiatric disorders.