Miracle-dz/UniFAR-FTUs huggingface dataset:
Mendelian randomization analysis of plasma levels of CD209 and MICB proteins and the risk of varicose veins of lower extremities

Varicose veins of lower extremities (VVs) are a highly prevalent condition, the pathogenesis of which is still not fully elucidated. Mendelian randomization (MR) can provide useful preliminary information on the traits that are potentially causally related to the disease. The aim of the present study is to replicate the effects of the plasma levels of MHC class I polypeptide-related sequence B (MICB) and cluster of differentiation 209 (CD209) proteins reported in a previous hypothesis-free MR study. We conducted MR analysis using a fixed effects inverse-variance weighted meta-analysis of Wald ratios method. For MICB and CD209, we used data from a large-scale genome-wide association study (GWAS) for plasma protein levels (N = 3,301). For VVs, we used GWAS data obtained in the FinnGen project (N = 128,698), the eMERGE network (phase 3, N = 48,429), and the UK Biobank data available in the Gene ATLAS (N = 452,264). The data used in the study were obtained in individuals of European descent. The results for MICB did not pass criteria for statistical significance and replication. The results for CD209 passed all statistical significance thresholds, indicating that the genetically predicted increase in CD209 level is associated with increased risk of VVs (βMR (SE) = 0.07 (0.01), OR (95% CI) = 1.08 (1.05–1.10), P-value = 5.9 ×10−11 in the meta-analysis of three cohorts). Our findings provide further support that CD209 can potentially be involved in VVs. In future studies, independent validation of our results using data from more powerful GWASs for CD209 measured by different methods would be beneficial.
Validation of a HACCP community-based infants’ complementary food safety assurance method in cash crop producing communities in Gedeo zone, Southern Ethiopia

Abstract A method based on a hazard analysis critical control point (HACCP)-based standard operating procedure (SOP) has been developed and implemented in community-based (CB) production of complementary foods (CFs) in agrarian regions in rural Ethiopia. The objective of this study was to validate the method in another setup, more specifically in cash crop (coffee and khat) producing communities in Southern Ethiopia. A quasi-experimental study was employed for the method validation. Two villages in the Gedeo zone, Southern Ethiopia were selected and a total of 40 mother-child pairs, 20 in each village, were involved in the study. Sociodemographic data, knowledge, and complementary feeding practices were collected using pretested questionnaires. The training was given to each mother for 1 h about community-based CFs production and implementation of the method. Then, 30 CF samples were collected and the level of aflatoxins (AFB1, AFB2, AFG1, and AFG2) was determined using a validated method. The majority (77.5%) of the mothers understand the importance of complementary feeding and give it to their infants beyond 6 months. Nearly two-thirds (62.5%) of the mothers had knowledge about the health impacts of aflatoxins, but the remaining 37.5% lacked awareness about the health risks of aflatoxins. Mothers were very well-motivated for the training and they promised to implement the knowledge and skill gained from the training for improving the nutritional status of their children. Overall, 23.3% of the CFs were contaminated by aflatoxins. AFB1 and AFG1 were detected in 6.7 and 16.7% of the CF samples, respectively. In cash crop-producing communities around the country, the HACCP-based SOP is easily validated in CB CFs production. Therefore, a scaleup of the method at the national level and beyond is recommended.
Comparison of conventional ligatures and a vessel sealing device for haemostasis during open ovariohysterectomy in rabbits

ABSTRACT Aims To compare surgical times and rates of intra-operative and post-operative complications for open ovariohysterectomy (OVH) in female rabbits using conventional ligatures or a vessel sealing device (VSD) for haemostasis. Methods Female pet rabbits (n = 23) presented for OVH for either desexing or treatment of reproductive disorders were randomly assigned to a conventional ligatures (CL) group (n = 12) or a LigaSure 5-mm (LS5) group (n = 11). In the CL group, the ovarian pedicles were ligated with a single surgeon’s knot. After transection of the ovarian pedicles, the broad ligament was manually broken down along the uterine horns to their respective cervices. In the LS5 group, both ovarian pedicles and the broad ligaments were sealed with a LigaSure Dolphin Tip VSD with 5-mm forceps. All the rabbits were hospitalised for 24 hours after surgery. Two weeks after discharge, a clinical recheck examination was performed. Incision length, overall surgical time (from initial incision to completion of intradermal suturing), OVH time (from identification of the first ovary to transection of the vaginal vault), and intra- and post-operative complications were recorded and compared between groups, using the Student’s t-test for normally distributed continuous data, the Wilcoxon–Mann–Whitney test for non-normally distributed continuous data and Pearson’s χ 2 test for categorical data. Results The mean overall surgical time was 14.1 (SD 4.4) minutes. The surgery took 15.0 (SD 4.9) minutes in the CL group and 13.1 (SD 3.8) minutes in the LS5 group (p=0.10). The OVH time was shorter in the LS5 group (mean 4.2 (SD 0.9) minutes) than in the CL group (mean 6.3 (SD 1.7) minutes; p = 0.005). No intra-operative complications were encountered in the LS5 group. Haemorrhage occurred in three rabbits in the CL group. One rabbit in the LS5 group developed steatonecrosis post-operatively. There was no evidence of a difference in the proportion of rabbits that experienced intra- and post-operative complications (p = 0.25 and p = 0.94 respectively) between groups. Conclusions The use of a LigaSure 5-mm VSD and conventional ligatures during open OVH were both associated with similar overall surgical times and complication rates. The OVH times were shorter in the LS5 group compared to the CL group. Clinical relevance Use of the LigaSure 5-mm VSD allows efficient haemostasis while performing open OVH in female pet rabbits.
A Dimeric FAP-Targeting Small-Molecule Radioconjugate with High and Prolonged Tumor Uptake

Visual Abstract Imaging procedures based on small-molecule radioconjugates targeting fibroblast activation protein (FAP) have recently emerged as a powerful tool for the diagnosis of a wide variety of tumors. However, the therapeutic potential of radiolabeled FAP-targeting agents is limited by their short residence time in neoplastic lesions. In this work, we present the development and in vivo characterization of BiOncoFAP, a new dimeric FAP-binding motif with an extended tumor residence time and favorable tumor-to-organ ratio. Methods: The binding properties of BiOncoFAP and its monovalent OncoFAP analog were assayed against recombinant human FAP. Preclinical experiments with 177Lu-OncoFAP-DOTAGA (177Lu-OncoFAP) and 177Lu-BiOncoFAP-DOTAGA (177Lu-BiOncoFAP) were performed on mice bearing FAP-positive HT-1080 tumors. Results: OncoFAP and BiOncoFAP displayed comparable subnanomolar dissociation constants toward recombinant human FAP in solution, but the bivalent BiOncoFAP bound more avidly to the target immobilized on solid supports. In a comparative biodistribution study, 177Lu-BiOncoFAP exhibited a more stable and prolonged tumor uptake than 177Lu-OncoFAP (∼20 vs. ∼4 percentage injected dose/g, respectively, at 24 h after injection). Notably, 177Lu-BiOncoFAP showed favorable tumor-to-organ ratios with low kidney uptake. Both 177Lu-OncoFAP and 177Lu-BiOncoFAP displayed potent antitumor efficacy when administered at therapeutic doses to tumor-bearing mice. Conclusion: 177Lu-BiOncoFAP is a promising candidate for radioligand therapy of cancer, with favorable in vivo tumor-to-organ ratios, a long tumor residence time, and potent anticancer efficacy.
Classification of the loosening zones and estimation of the loosening pressures of tunnels in layered jointed rock strata

Due to the complexity of tunnels, accurate prediction of their loosening pressures in layered jointed rock strata is a very difficult engineering task. To recognize loosening patterns and estimate loosening pressures, numerical tests were employed in areas where tunnels were excavated in layered jointed rock strata. A total of 12 influential factors, including joints, tunnel depth, and strata, were considered in each of the numerical models. Three loosening patterns were found in the numerical testing: a ringent trumpet-shaped boundary, an arch-shaped boundary, and a closing-trend trumpet-shaped loosening zone. Empirical expressions for the loosening zone boundaries were further established and, in the form of the 12 influential factors, considered in the simulation. Given the boundary function, the loosening pressures were further deduced, which were categorized according to loosening pattern, i.e., ringent trumpet shape or arch shape, and the excavation condition of whether or not the embedded depth was deeper than the soft layer. Two case studies were used to test this method. The newly-proposed method was found to perform better than existing methods, with loosening pressure values that were slightly larger than, but very close to, actual measured field data.
Elevated serum cholesterol levels are associated with proteinuria over 0.5 g/day in premenopausal women with systemic lupus erythematosus

Background: Systemic lupus erythematosus (SLE) commonly occurs in premenopausal women and is associated with elevated estrogen levels. Patients with SLE may have abnormal serum triglyceride (TG) levels, and lipid reportedly promotes kidney damage in patients with nephrosis. Since estrogen regulates lipid levels, we investigated the serum lipid levels of premenopausal women with SLE and their relationship with proteinuria. Methods: This cross-sectional study included 123 premenopausal women with SLE (SLE group), who were classified into 24-h urine protein exceeding 0.5 g (24 h-UPRO > 0.5 g, n = 22) and 24 h-UPRO ≤ 0.5 g (n = 101) subgroups, and 100 similarly aged healthy women (control group). Clinical characteristics and biomarker levels were compared between these groups. The associated factors of proteinuria over 0.5 g/day were evaluated using multivariate logistic regression. A receiver operating characteristic (ROC) curve was plotted to assess the cholesterol (CH) cut-off associated with increased development of proteinuria over 0.5 g/day. Results: The SLE group had significantly higher serum TG levels than that of control group. 24 h-UPRO were significantly correlated with serum creatinine, CH, TG, and uric acid levels. Serum CH level was the greatest associated factor for proteinuria over 0.5 g/day. The area under the ROC curve was 0.843, with a CH cut-off of 4.58 mmol/L. Patients with serum CH above 4.58 mmol/L had a higher proportion of type IV LN, but with no statistical difference. Conclusions: In premenopausal SLE patients, serum TG levels were higher than in healthy women, and serum CH levels were the primary associated factor for proteinuria over 0.5 g/day. Proteinura over 0.5 g/day may occur in women with SLE with serum CH levels >4.58 mmol/L. CH levels may be useful for predicting proteinuria.
Gambling along the schizotypal spectrum: The associations between schizotypal personality, gambling-related cognitions, luck, and problem gambling

Abstract Objective Schizotypal personality (schizotypy) is a cluster of traits in the general population, including alterations in belief formation that may underpin delusional thinking. The psychological processes described by schizotypy could also fuel cognitive distortions in the context of gambling. This study sought to characterize the relationships between schizotypy, gambling-related cognitive distortions, and levels of problem gambling. Methods Analyses were conducted on three groups, a student sample (n = 104) with minimal self-reported gambling involvement, a crowdsourced sample of regular gamblers (via MTurk; n = 277), and an additional crowdsourced sample with a range of gambling involvement (via MTurk; n = 144). Primary measures included the Schizotypal Personality Questionnaire – Brief (SPQ-B), the Peters et al. Delusions Inventory (PDI-21), the Gambling Related Cognitions Scale (GRCS), and the Problem Gambling Severity Index (PGSI). Luck was measured with either the Belief in Good Luck Scale (BIGLS) or the Beliefs Around Luck Scale (BALS). Results Small-to-moderate associations were detected between the components of schizotypy, including delusion proneness, and the gambling-related variables. Schizotypy was associated with the general belief in luck and bad luck, but not beliefs in good luck. A series of partial correlations demonstrated that when the GRCS was controlled for, the relationship between schizotypy and problem gambling was attenuated. Conclusions This study demonstrates that schizotypy is a small-to-moderate correlate of erroneous gambling beliefs and PG. These data help characterize clinical comorbidities between the schizotypal spectrum and problem gambling, and point to shared biases relating to belief formation and decision-making under chance.
Removing Barriers: Using a PDS Model to Enable Collaborative Community and School Partnerships to Serve At-Risk Students

The purpose of this chapter is to articulate the success of a partnership facilitated by a PDS relationship in serving at-risk students in a collection of schools proximal to a university in the Midwest. The authors begin by describing characteristics of community partnerships, including professional development schools, which both enable and hinder schools and stakeholders when they attempt to build innovative partnerships promoting positive school and community outcomes. They then discuss how they leveraged the resources of the local community, a teacher education program, and the local schools to develop and implement an afterschool academic support program targeting students at-risk for school failure. In addition to explaining the procedural elements that were found to be useful in breaking down traditional barriers to effective partnerships (e.g., space, finance, staff, quality curriculum support), the authors present the results of their study that demonstrate student gains in both math and reading.
Total-Body 18F-FDG PET/CT in Autoimmune Inflammatory Arthritis at Ultra-Low Dose: Initial Observations

Visual Abstract Autoimmune inflammatory arthritides (AIA), such as psoriatic arthritis and rheumatoid arthritis, are chronic systemic conditions that affect multiple joints of the body. Recently, total-body (TB) PET/CT scanners exhibiting superior technical characteristics (total-body coverage, geometric sensitivity) that could benefit AIA evaluation, compared with conventional PET/CT systems, have become available. The objectives of this work were to assess the performance of an ultra-low-dose, 18F-FDG TB PET/CT acquisition protocol for evaluating systemic joint involvement in AIA and to report the association of TB PET/CT measures with joint-by-joint rheumatologic examination and standardized rheumatologic outcome measures. Methods: Thirty participants (24 with AIA and 6 with osteoarthritis) were prospectively enrolled in this single-center, observational study. All participants underwent a TB PET/CT scan for 20 min starting at 40 min after intravenous injection of 78.1 ± 4.7 MBq of 18F-FDG. Qualitative and quantitative evaluation of 18F-FDG uptake and joint involvement were performed from the resulting images and compared with the rheumatologic assessments. Results: TB PET/CT enabled the visualization of 18F-FDG uptake at joints of the entire body, including those of the hands and feet, in a single bed position, and in the same phase of radiotracer uptake. A range of pathologies consistent with AIA (and non-AIA in the osteoarthritis group) were visualized, and the feasibility of extracting PET measures from joints examined by rheumatologic assessments was demonstrated. Of 1,997 evaluable joints, there was concordance between TB PET qualitative assessments and joint-by-joint rheumatologic evaluation in the AIA and non-AIA cohorts for 69.9% and 91.1% joints, respectively, and an additional 20.1% and 8.8% joints, respectively, deemed negative on rheumatologic examination showed PET positivity. On the other hand, 10.0% and 0% joints in the AIA and non-AIA cohorts, respectively, were positive on rheumatologic evaluation but negative on TB PET. Quantitative measures from TB PET in the AIA cohort demonstrated a moderate-to-strong correlation (Spearman ρ = 0.53–0.70, P < 0.05) with the rheumatologic outcome measures. Conclusion: Systemic joint evaluation in AIA (and non-AIA) is feasible with a TB PET/CT system and an ultra-low-dose protocol. Our results provide the foundation for future larger studies to evaluate the possible improvements in AIA joint assessment via the TB PET/CT technology.
Resting heart rate and incident atrial fibrillation: A stratified Mendelian randomization in the AFGen consortium

Background Both elevated and low resting heart rates are associated with atrial fibrillation (AF), suggesting a U-shaped relationship. However, evidence for a U-shaped causal association between genetically-determined resting heart rate and incident AF is limited. We investigated potential directional changes of the causal association between genetically-determined resting heart rate and incident AF. Method and results Seven cohorts of the AFGen consortium contributed data to this meta-analysis. All participants were of European ancestry with known AF status, genotype information, and a heart rate measurement from a baseline electrocardiogram (ECG). Three strata of instrumental variable-free resting heart rate were used to assess possible non-linear associations between genetically-determined resting heart rate and the logarithm of the incident AF hazard rate: <65; 65–75; and >75 beats per minute (bpm). Mendelian randomization analyses using a weighted resting heart rate polygenic risk score were performed for each stratum. We studied 38,981 individuals (mean age 59±10 years, 54% women) with a mean resting heart rate of 67±11 bpm. During a mean follow-up of 13±5 years, 4,779 (12%) individuals developed AF. A U-shaped association between the resting heart rate and the incident AF-hazard ratio was observed. Genetically-determined resting heart rate was inversely associated with incident AF for instrumental variable-free resting heart rates below 65 bpm (hazard ratio for genetically-determined resting heart rate, 0.96; 95% confidence interval, 0.94–0.99; p = 0.01). Genetically-determined resting heart rate was not associated with incident AF in the other two strata. Conclusions For resting heart rates below 65 bpm, our results support an inverse causal association between genetically-determined resting heart rate and incident AF.
Severity and Incidence of Multisystem Inflammatory Syndrome in Children During 3 SARS-CoV-2 Pandemic Waves in Israel.

Severity and Incidence of Multisystem Inflammatory Syndrome in Children During 3 SARS-CoV-2 Pandemic Waves in Israel Multisystem inflammatory syndrome in children (MIS-C) is a serious complication of SARS-CoV-2 infection.1 A previous study that described MIS-C cases in the first 3 waves of the COVID-19 pandemic found that the proportion of individuals with severe illness declined after the first wave.2 In Israel, the Omicron (B.1.1.529) variant started to spread in November 2021.3 We describe outcomes of MIS-C in a multicenter cohort and assessed incidence nationally during the Alpha, Delta, and Omicron variant waves.
Laparoscopic Versus Laparotomy Surgical Interventions for Trauma Patients With Single Upper Left Quadrant Penetrating Injuries: Analysis of the American College of Surgeons Trauma Quality Improvement Program Dataset

Background We aim to identify patient cohorts where laparoscopy can be safely utilized with comparable or better outcomes to laparotomy among patients with single penetrating LUQ injuries with a hypothesis that compared to laparotomy, laparoscopy may be associated with equal or improved outcomes of low injury severity patients. Methods Retrospective review of the ACS-TQP-Participant Use File 2016-2019 dataset. Patients with single LUQ penetrating injuries were included. Primary outcome was risk-adjusted in-hospital mortality. Secondary outcomes included: risk-adjusted complication rates, hospital length-of-stay (H-LOS), and ICU-LOS. Descriptive statistics and multivariable regression with reliability adjustments to account for variations in practice were performed. Results Of 4149 patients analyzed, 3571 (86.1%) underwent laparotomy, 489 (11.8%) underwent laparoscopy, and 89 (2.1%) underwent laparoscopy-to-laparotomy conversion. Adjusted mortality rates were not significantly different among all study cohorts (P > .05). Compared to laparoscopy, adjusted odds of complications were 4.3-fold higher for all patients who underwent laparotomy and 4-fold higher for laparoscopy-to-laparotomy (LtL) patients (P < .05). Diaphragmatic injuries were associated with significantly increased odds of undergoing LtL, whereas sustaining a colonic injury, gastric injury, hepatic injury, or requiring PRBC transfusions were associated with significantly increased odds of undergoing laparotomy (P < .05). H-LOS (days) was significantly longer for patients who underwent laparotomy compared to laparoscopy (3.9 ± 4.0 vs. 10.8 ± 13.4, P < .0001). Conclusions Laparoscopy may be considered a viable alternative to laparotomy for hemodynamically stable adult patients with single penetrating LUQ injuries of low injury burden validating our hypothesis. Laparoscopy may be less safe for patients with associated diaphragmatic, colonic, or hepatic injuries.
Matthew J. Friedman, M.D., Ph.D. and His Legacy of Leadership in the Field of Post-traumatic Stress Disorder

In 2004, Matthew J. Friedman, M.D., Ph.D. co-wrote a paper calling for the establishment of a national brain tissue repository that would serve as a resource for post-traumatic stress disorder (PTSD) research (Friedman & Harris, 2004). It appeared among a set of related papers on this topic (Bonne & Charney, 2004; Deep-Soboslay et al., 2004; Krystal & Duman, 2005; Osuch et al., 2004; Raskind, 2004; Yehuda, 2004) from groups within the Department of Veterans Affairs, NIMH Intramural Research Program, and Department of Defense. Under the leadership of Dr. Friedman (“Matt”), this group had already invested several years in planning and these papers constituted the first public statements from this effort. But it would take over 10 more years until a brain tissue repository for PTSD became a reality. At the time of his retirement, it is opportune to reflect on this paper and its relationship to his unique legacy of leadership in the field of PTSD research. From 1989– 2015, Matt served as Executive Director of the National Center for PTSD (NCPTSD) of the U.S. Department of Veterans Affairs, overseeing its founding, functioning and rapid growth. Over the past seven years, he led the creation of NCPTSD’s National PTSD Brain Bank (Brain Bank). The opportunity to acknowledge Matt’s leadership and to thank him is very important to us. We (JHK, SMS) have known Matt since the founding of NCPTSD over 30 years ago. We have worked particularly closely with Matt in our roles as the Director (JHK) and until recently, Medical Director (SMS) of the NCPTSD Clinical Neuroscience Division (CND), and as the Director of the main intramural laboratory for the Brain Bank (MJG).