Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Antibody Responses to the Live-Attenuated and Recombinant Herpes Zoster Vaccines

These observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity and neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. ABSTRACT Two herpes zoster (HZ) vaccines licensed in the United States are recommended by the Advisory Committee on Immunization Practices (ACIP): (i) live-attenuated vaccine (ZVL) using vOka strain varicella-zoster virus (VZV) and (ii) recombinant adjuvanted vaccine (RZV) containing recombinant varicella-zoster virus (VZV) glycoprotein E (gE). Two phase 3 clinical trials of RZV led the Advisory Committee on Immunization Practices (ACIP) to recommend it with preferred status. VZV T cell-mediated immunity (CMI), but not humoral immunity, is considered essential for protection against HZ. Published studies of humoral immunity focused on VZV-specific IgG concentration. To complement reports comparing the CMI responses to these vaccines, we compared humoral responses in ZVL and RZV recipients, emphasizing functional qualities (avidity and neutralization). Baseline avidities to a VZV glycoprotein mixture (gp) were near the upper limit of detection, but avidity to gE was much lower. Small increases in gp avidity were observed for both RZV and ZVL vaccination (19 and 12 avidity index units [AIU], respectively). RZV boosted both gE avidity and VZV neutralizing antibody significantly more than ZVL (mean gE avidity boost, 47 AIU versus 22 AIU; mean neutralizing antibody boost, 22-fold versus 8-fold). Increases in neutralizing antibodies strongly correlated with gE avidity increases (r = 0.5) and moderately with gp avidity increases (r = 0.23). After 1 year, 81% of RZV recipients and only 18% of ZVL recipients retained >50% of their peak avidity boosts. These results are consistent with the CMI responses to these vaccines: RZV responses are skewed to long-term memory, whereas ZVL preferentially induces transient effector responses. IMPORTANCE These observations further distinguish the immunogenicity and duration of the immune response of the two vaccines. In addition, measurements of functional humoral immunity (IgG avidity and neutralizing antibody) in response to zoster immunization, alone or combined with other immune markers, might contribute to practical in vitro correlates of protection. Combined with previous observations of the cell-mediated response to these vaccines, this study suggests that vaccine development will benefit from more expansive and granular assessments of acquired immunity during early phase 1 immunogenicity trials.
The influence of education on women’s well-being: Evidence from Australia

This study investigates the relationship between women’s education and their level of well-being, using data from the Household, Income and Labor Dynamics in Australia (HILDA). To take into account potential endogeneity, the instrumental variables (IV) approach is employed, with partners’ education as an instrument. The findings show that higher education levels lead to a higher level of eudaimonic well-being, hedonic well-being, positive affect, and reduced psychological distress, highlighting a non-monetary benefit of education. Thus, policymakers should continue to widely promote education, in order for women to achieve higher levels of future well-being. Additionally, the findings show that the connection between education and well-being is mediated by healthy behaviors, such as engaging in physical activity, abstaining from drinking and smoking, social interactivity, and higher income. Therefore, public health campaigns which promote healthy behaviors among women should potentially mitigate gaps in formal education.
Sialylation on O-linked glycans protects von Willebrand factor from macrophage galactose lectin-mediated clearance

Terminal sialylation determines the plasma half-life of von Willebrand factor (VWF). A role for macrophage galactose lectin (MGL) in regulating hyposialylated VWF clearance has recently been proposed. In this study, we showed that MGL influences physiological plasma VWF clearance. MGL inhibition was associated with a significantly extended mean residence time and 3-fold increase in endogenous plasma VWF antigen levels (P<0.05). Using a series of VWF truncations, we further demonstrated that the A1 domain of VWF is predominantly responsible for enabling the MGL interaction. Binding of both full-length and VWF-A1-A2-A3 to MGL was significantly enhanced in the presence of ristocetin (P<0.05), suggesting that the MGL-binding site in A1 is not fully accessible in globular VWF. Additional studies using different VWF glycoforms demonstrated that VWF O-linked glycans, clustered at either end of the A1 domain, play a key role in protecting VWF against MGLmediated clearance. Reduced sialylation has been associated with pathological, increased clearance of VWF in patients with von Willebrand disease. Herein, we demonstrate that specific loss of α2-3 linked sialylation from O-glycans results in markedly increased MGL-binding in vitro, and markedly enhanced MGL-mediated clearance of VWF in vivo. Our data further show that the asialoglycoprotein receptor (ASGPR) does not have a significant role in mediating the increased clearance of VWF following loss of O-sialylation. Conversely however, we observed that loss of N-linked sialylation from VWF drives enhanced circulatory clearance predominantly via the ASGPR. Collectively, our data support the hypothesis that in addition to regulating physiological VWF clearance, the MGL receptor works in tandem with ASGPR to modulate enhanced clearance of aberrantly sialylated VWF in the pathogenesis of von Willebrand disease.
The Regulatory Subunit PPP2R2A of PP2A Enhances Th1 and Th17 Differentiation through Activation of the GEF-H1/RhoA/ROCK Signaling Pathway

Key Points PPP2R2A promotes Th1 and Th17 but not Treg cell differentiation. PPP2R2A deficiency impairs GEF-H1/RhoA/ROCK pathway in Th1 and Th17 cells. PPP2R2A deficiency in T cells mitigates experimental autoimmune encephalomyelitis. Protein phosphatase 2A (PP2A) composed of a scaffold subunit, a catalytic subunit, and multiple regulatory subunits is a ubiquitously expressed serine/threonine phosphatase. We have previously shown that the PP2A catalytic subunit is increased in T cells from patients with systemic lupus erythematosus and promotes IL-17 production by enhancing the activity of Rho-associated kinase (ROCK) in T cells. However, the molecular mechanism whereby PP2A regulates ROCK activity is unknown. In this study, we show that the PP2A regulatory subunit PPP2R2A is increased in T cells from people with systemic lupus erythematosus and binds to, dephosphorylates, and activates the guanine nucleotide exchange factor GEF-H1 at Ser885, which in turn increases the levels of RhoA-GTP and the activity of ROCK in T cells. Genetic PPP2R2A deficiency in murine T cells reduced Th1 and Th17, but not regulatory T cell differentiation and mice with T cell–specific PPP2R2A deficiency displayed less autoimmunity when immunized with myelin oligodendrocyte glycoprotein peptide. Our studies indicate that PPP2R2A is the regulatory subunit that dictates the PP2A-directed enhanced Th1 and Th17 differentiation, and therefore, it represents a therapeutic target for pathologies linked to Th1 and Th17 cell expansion.
First detection of Herpesvirus anguillae (AngHV-1) associated with mortalities in farmed giant mottled eel (Anguilla marmorata) in Vietnam.

Giant mottled eel (Anguilla marmorata) farming in Vietnam is a multistage process starting from wild harvest of glass eels through the so-called "hatcheries" and distribution centres from which individuals are transferred to rearing farms and subsequently sold by one eel farm to another every 3-5 months. The information on viral agents spread and persistence in the Vietnamese eel aquaculture is scarce. Therefore, the mortality of A. marmorata at the Van Xuan Farm was the prerequisite to identify the possible aetiologic agent and additionally to formulate first recommendations for viral disease screening in the Vietnamese eel aquaculture. Juvenile giant mottled eels with haemorrhagic lesions in the skin and liver, and hyperaemia of the gut were tested with qPCR and end-point PCR for AngHV-1 presence. Here, we report the first detection of AngHV-1 associated with mortality in giant mottled eel in winter and spring seasons. On the basis of the obtained results, we recommend to test eel seeds in "hatcheries," since tropical eel farms operate in interconnected scheme and monitoring of AngHV-1 prevalence requires well-implemented measures. Disease screening in the rearing centres and on-growing facilities should be based on everyday health checks, including by-catch fish used as a base of the feeding programmes at eel farms in Vietnam.
Study of enteric pathogens among children in the tropics and effects of prolonged storage of stool samples

The study was performed to compare real‐time PCR after nucleic acid extraction directly from stool samples as well as from samples stored and transported on Whatman papers or flocked swabs at ambient temperature in the tropics. In addition, the possible suitability for a clear determination of likely aetiological relevance of PCR‐based pathogen detections based on cycle threshold (Ct) values was assessed. From 632 Tanzanian children <5 years of age with and without gastrointestinal symptoms, 466 samples were subjected to nucleic acid extraction and real‐time PCR for gastrointestinal viral, bacterial and protozoan pathogens. Equal or even higher frequencies of pathogen detections from Whatman papers or flocked swabs were achieved compared with nucleic acid extraction directly from stool samples. Comparison of the Ct values showed no significant difference according to the nucleic acid extraction strategy. Also, the Ct values did not allow a decision whether a detected pathogen was associated with gastrointestinal symptoms.
Selection and socialization accounts of the relation between fraternity membership and sexual aggression.

OBJECTIVE The current project aims to enhance our understanding of the well-established relation between fraternity membership and sexual aggression on college campuses. Most prior research has been cross-sectional and unable to distinguish selection and socialization accounts of the relation, and only one prior longitudinal study has simultaneously examined selection and socialization effects. METHOD Fraternity membership, sexual aggression, binge drinking, sociosexual attitudes and behaviors, and perceived peer sexual aggression were assessed for 772 male participants (n = 116 fraternity members) in a longitudinal survey study from the summer prior to college through Year 2 of college. RESULTS Longitudinal path analyses revealed three key findings. First, fraternity membership was prospectively correlated with sexual aggression in Years 1 and 2 of college (socialization effect), controlling for selection effects, when the two prospective paths were constrained to be equivalent. Second, more frequent binge drinking and sociosexual attitudes prior to college prospectively correlated with an increased likelihood of joining a fraternity (selection effect), and both selection variables indirectly correlated with future sexual aggression via fraternity membership. Third, fraternity membership was associated with increased binge drinking and perceived peer sexual aggression (socialization effects). CONCLUSIONS These findings identify critical targets for the prevention of sexually aggressive behavior that are linked to fraternity membership: Binge drinking and sociosexual attitudes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
Spectroscopic investigation on molecular aspects and structural and functional effects of tetraethyl pyrophosphate organophosphorus insecticide interaction with adult human hemoglobin

Abstract Organophosphates are extremely toxic compounds that use extensively in agriculture and household as insecticides. However, their binding mechanism to bio-macromolecules especially blood proteins is not clearly understood. In this research, various spectroscopic techniques utilized to analyze the effect of Tetraethyl Pyrophosphate (TEPP), as an organophosphorus insecticide, on the structure, function, stability, and aggregation of adult human hemoglobin and also hemolysis potential of the TEPP on red blood cells (RBCs) examined. Molecular docking was used for TEPP binding to human Hemoglobin (Hb), too. The results demonstrated that the TEPP insecticide has the potential for lysing RBCs. UV-Vis experiment indicated that globin part and heme group influenced by TEPP. Oxygen affinity measurements revealed the formation of deoxy-Hb and met-Hb, also decreased in oxygen affinity of Hb upon interaction with TEPP that is due to heme destruction. Fluorescence spectroscopy confirmed the production of heme degradation species after interaction of Hb with TEPP, which is inconsistent with oxygen affinity measurements. Thermal and aggregation studies indicated that TEPP induced aggregation of Hb in a concentration manner and Tm of protein reduced to lower temperatures. Docking's study also showed that TEPP interacts with Hb through hydrophobic interactions, which confirms UV-Vis results. ATR-FTIR study also revealed that TEPP can induce changes in the alpha helix element of Hb’s secondary structure. Totally, Experimental and theoretical results indicate that tetraethyl pyrophosphate has unfavorable effects on hemoglobin structure and function. Communicated by Ramaswamy H. Sarma
Small mitochondrial RNAs as mediators of nuclear gene regulation, and potential implications for human health

Much research has focused on the effects of pathogenic mitochondrial mutations on health. Notwithstanding, the mechanisms regulating the link between these mutations and their effects remain elusive in several cases. Here, we propose that certain mitochondrial mutations may disrupt function of a set of mitochondrial‐transcribed small RNAs, perturbing communication between mitochondria and nucleus, leading to disease. Our hypothesis synthesises two lines of supporting evidence. First, several mitochondrial mutations cannot be directly linked to effects on energy production or protein synthesis. Second, emerging studies have described the existence of small RNAs encoded by the mitochondria and proposed their involvement in RNA interference. We present a roadmap to testing this hypothesis.
Abrocitinib versus Placebo or Dupilumab for Atopic Dermatitis.

BACKGROUND The oral Janus kinase 1 (JAK1) inhibitor abrocitinib, which reduces interleukin-4 and interleukin-13 signaling, is being investigated for the treatment of atopic dermatitis. Data from trials comparing JAK1 inhibitors with monoclonal antibodies, such as dupilumab, that block interleukin-4 receptors are limited. METHODS In a phase 3, double-blind trial, we randomly assigned patients with atopic dermatitis that was unresponsive to topical agents or that warranted systemic therapy (in a 2:2:2:1 ratio) to receive 200 mg or 100 mg of abrocitinib orally once daily, 300 mg of dupilumab subcutaneously every other week (after a loading dose of 600 mg), or placebo; all the patients received topical therapy. The primary end points were an Investigator's Global Assessment (IGA) response (defined as a score of 0 [clear] or 1 [almost clear] on the IGA [scores range from 0 to 4], with an improvement of ≥2 points from baseline) and an Eczema Area and Severity Index-75 (EASI-75) response (defined as ≥75% improvement from baseline in the score on the EASI [scores range from 0 to 72]) at week 12. The key secondary end points were itch response (defined as an improvement of ≥4 points in the score on the Peak Pruritus Numerical Rating Scale [scores range from 0 to 10]) at week 2 and IGA and EASI-75 responses at week 16. RESULTS A total of 838 patients underwent randomization; 226 patients were assigned to the 200-mg abrocitinib group, 238 to the 100-mg abrocitinib group, 243 to the dupilumab group, and 131 to the placebo group. An IGA response at week 12 was observed in 48.4% of patients in the 200-mg abrocitinib group, 36.6% in the 100-mg abrocitinib group, 36.5% in the dupilumab group, and 14.0% in the placebo group (P<0.001 for both abrocitinib doses vs. placebo); an EASI-75 response at week 12 was observed in 70.3%, 58.7%, 58.1%, and 27.1%, respectively (P<0.001 for both abrocitinib doses vs. placebo). The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. Nausea occurred in 11.1% of the patients in the 200-mg abrocitinib group and 4.2% of those in the 100-mg abrocitinib group, and acne occurred in 6.6% and 2.9%, respectively. CONCLUSIONS In this trial, abrocitinib at a dose of either 200 mg or 100 mg once daily resulted in significantly greater reductions in signs and symptoms of moderate-to-severe atopic dermatitis than placebo at weeks 12 and 16. The 200-mg dose, but not the 100-mg dose, of abrocitinib was superior to dupilumab with respect to itch response at week 2. Neither abrocitinib dose differed significantly from dupilumab with respect to most other key secondary end-point comparisons at week 16. (Funded by Pfizer; JADE COMPARE ClinicalTrials.gov number, NCT03720470.).
Clinicopathological significance of SOX4 and epithelial−mesenchymal transition markers in patients with laryngeal squamous cell carcinoma

Abstract Background and aim: Sex-determining region-Y-related high-mobility-group box 4 (SOX4) is associated with the metastasis and prognosis of many cancer types. However, studies on the role of SOX4 in laryngeal squamous cell carcinoma (LSCC) are few, and hence the mechanism is unclear. Epithelial–mesenchymal transition (EMT) allows neoplastic cells to gain the plasticity and motility required for tumor progression and metastasis. This study aimed to analyze the relationship between SOX4 and EMT, and their relationship with clinicopathological factors and related prognosis. Methods: Immunohistochemical staining was used to detect the positive expression of SOX4 protein, EMT-related transcription factor protein, and related marker protein in 127 LSCC tissue samples. At the same time, data on various parameters of clinical pathology and postoperative survival were collected. Results: The positive expression rate of SOX4 and Slug in LSCC was related to pathological differentiation, lymphatic invasion, and pathological tumor node metastasis (TNM) of a tumor. The expression rates of ZEB1, Twist, E-cadherin, N-cadherin, and β-catenin in LSCC correlated with lymphatic invasion and pathological tumor node metastasis. The expression of SOX4, combined expression of SOX4 and ZEB1, and lymphatic invasion were independent prognostic factors for the total survival time of patients with LSCC. Conclusions: In summary, SOX4 was vital in the LSCC EMT process, which might be mediated by transcription factor ZEB1. SOX4 and ZEB1 might serve as potential biomarkers of metastasis and prognosis, as well as promising therapeutic targets of LSCC.
Frailty in patients undergoing transcatheter aortic valve replacement: prognostic value of the Geriatric Nutritional Risk Index

Malnutrition is a hallmark of frailty, is common among elderly patients, and is a predictor of poor outcomes in patients with severe symptomatic aortic stenosis (AS). The Geriatric Nutritional Risk Index (GNRI) is a simple and well‐established screening tool to predict the risk of morbidity and mortality in elderly patients. In this study, we evaluated whether GNRI may be used in the risk stratification and management of patients undergoing transcatheter aortic valve replacement (TAVR).
Clinical Presentation of Toddlers With New Intracranial Space-Occupying Lesions

Objective Intracranial space occupying lesions (ICSOLs) like tumors and abscesses can be life-threatening conditions. It can be especially difficult to diagnose these conditions in toddlers. We aimed to describe symptoms and signs present in a sample of toddlers with ICSOLs. Methods We performed a retrospective chart review of 15 toddlers with intracranial tumors, abscesses, or infected cysts. We collected data on the presence of various signs and symptoms on presentation to the emergency department. Results Eight toddlers (53%) presented with vomiting. A change in behavior was the second most common symptom (6, 40%). Seven children (47%) had motor weakness, and 5 (33%) had ataxia. Eleven of the 12 children with tumors (92%) had documented abnormal neurologic signs on initial physical examination. Conclusions Vomiting, a change in behavior, and an abnormal neurologic examination were common signs and symptoms in our sample of toddlers with ICSOLs. An accurate history and appropriate neurologic examination can help physicians make this challenging diagnosis in this age group.
Intravitreal Ranibizumab Versus Aflibercept for Diabetic Macular Edema in Vitrectomized Eyes: 12 Month Results

ABSTRACT Purpose To evaluate and compare the effect of intravitreal ranibizumab and aflibercept on the treatment of diabetic macular edema in previously vitrectomized eyes. Materials and Methods A total of fifty-two vitrectomized eyes with diabetic macular edema were retrospectively evaluated. Patients were divided into two groups; Group 1 (n = 30 eyes) received 0.5 mg/0.05 mL intravitreal ranibizumab and Group 2 (n = 22 eyes) received 2 mg/0.05 mL intravitreal aflibercept for 3 monthly injections and thereafter as needed over 12 months. Best-corrected visual acuity (BCVA), central macular thickness (CMT) and injection number of the drugs were the outcomes of the study. Results Fifty-two previously vitrectomized eyes were enrolled in this study. Thirty-eight of them (73.1%) were male and 14 (26.9%) were female. The mean age was 61.54 ± 7.33 year (range: 50–72 year). BCVA increased and CMT decreased significantly in both groups at the end of the follow-up period (p < .05). The change in BCVA and CMT was not statistically different between the groups (p > .05). However, there was a statistically significant difference between the groups in terms of the injection number (p < .05). Conclusion Both ranibizumab and aflibercept were found to be effective on diabetic macular edema in previously vitrectomized eyes. There was no difference between the groups in terms of visual acuity gain and CMT improvement. However, the number of injections was found to be lower in aflibercept group. Therefore, aflibercept may be preferred in the treatment of macular edema in previously vitrectomized eyes.