Miracle-dz/UniFAR-FTUs huggingface dataset:
Impact of tenofovir on SARS-CoV-2 infection and severe outcomes among people living with HIV: a propensity score-matched study

Abstract Background Reports on the impact of some antiretrovirals against SARS-CoV-2 infection and disease severity are conflicting. Objectives We evaluated the effect of tenofovir as either tenofovir alafenamide/emtricitabine (TAF/FTC) or tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) against SARS-CoV-2 infection and associated clinical outcomes among people living with HIV (PLWH). Methods We conducted a propensity score-matched analysis in the prospective PISCIS cohort of PLWH (n = 14 978) in Catalonia, Spain. We used adjusted Cox regression models to assess the association between tenofovir and SARS-CoV-2 outcomes. Results After propensity score-matching, SARS-CoV-2 diagnosis rates were similar in TAF/FTC versus ABC/3TC recipients (11.6% versus 12.5%, P = 0.256); lower among TDF/FTC versus ABC/3TC recipients (9.6% versus 12.8%, P = 0.021); and lower among TDF/FTC versus TAF/FTC recipients (9.6% versus 12.1%, P = 0.012). In well-adjusted logistic regression models, TAF/FTC was no longer associated with reduced SARS-CoV-2 diagnosis [adjusted odds ratio (aOR) 0.90; 95% confidence interval (CI), 0.78–1.04] or hospitalization (aOR 0.93; 95% CI, 0.60–1.43). When compared with ABC/3TC, TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60–1.04) or hospitalization (aOR 0.51; 95% CI, 0.15–1.70). TDF/FTC was not associated with reduced SARS-CoV-2 diagnosis (aOR 0.79; 95% CI, 0.60–1.04) or associated hospitalization (aOR 0.33; 95% CI, 0.10–1.07) compared with TAF/FTC. Conclusions TAF/FTC or TDF/FTC were not associated with reduced SARS-CoV-2 diagnosis rates or associated hospitalizations among PLWH. TDF/FTC users had baseline characteristics intrinsically associated with more benign SARS-CoV-2 infection outcomes. Tenofovir exposure should not modify any preventive or therapeutic SARS-CoV-2 infection management.
Solid cancer patients achieve adequate immunogenicity and low rate of severe adverse events after SARS-CoV-2 vaccination

Background: SARS-CoV-2 vaccination in cancer patients is crucial to prevent severe COVID-19 disease course. Methods: This study assessed immunogenicity of cancer patients on active treatment receiving mRNA-based SARS-CoV-2 vaccine by detection of anti-SARS-CoV-2 S1 IgG antibodies in serum, before, after the first and second doses and 3 months after a complete primary course of vaccination. Results were compared with healthy controls. Results: Of 112 patients, the seroconversion rate was 96%. A significant reduction in antibody levels was observed 3 months after vaccination in patients receiving immune checkpoint inhibitors versus control participants (p < 0.001). Adverse events were mostly mild. Conclusion: Immunogenicity after mRNA-based vaccine in cancer patients is adequate but influenced by the type of anticancer therapy. Antibody levels decline after 3 months, and thus a third vaccination is warranted.
Causality of anthropometric markers associated with polycystic ovarian syndrome: Findings of a Mendelian randomization study

Introduction Using body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed. Objectives To investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers. Methods Summary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables–weight and height), from the IEU Open GWAS Project. As the outcome, we acquired summary data from a large-sample GWAS (118870 samples; 642 cases and 118228 controls) within the FinnGen cohort. Total causal effects were assessed via univariable two-sample Mendelian randomization (2SMR). Genetic architectures underlying causal associations were explored. Direct causal effects were analyzed by multivariable MR modelling. Results Instrumental variables demonstrated no weak instrument bias (F > 10). Four anthropometric exposures, namely, weight (2.69–77.05), BMI (OR: 2.90–4.06), WC (OR: 6.22–20.27), and HC (OR: 6.22–20.27) demonstrated total causal effects as per univariable 2SMR models. We uncovered shared and non-shared genetic architectures underlying causal associations. Direct causal effects of WC and HC on PCOS were revealed by two multivariable MR models containing exclusively the anthropometric markers of central obesity. Other multivariable MR models containing anthropometric markers of both central- and general obesity showed no direct causal effects on PCOS. Conclusions Both and general- and central obesity yield total causal effects on PCOS. Findings also indicated potential direct causal effects of normal weight-central obesity and more complex causal mechanisms when both central- and general obesity are present. Results underscore the importance of addressing both central- and general obesity for optimizing PCOS care.
The role of the Big Two in socially responsible behavior during the COVID-19 pandemic: Agency and communion in adolescents’ personal norm and behavioral adherence to instituted measures

The outbreak of the COVID-19 virus urged all members of the society to adopt COVID-responsible behavioral patterns and practice them in everyday life. Given the variability in its adoption, it is critical to understand psychological factors associated with socially responsible behavior during the pandemic. This might be even more important among adolescents, who are less endangered by the virus but contribute to its spread. In this article, we focus on adolescent boys’ and girls’ agency and communion orientations to explain the level of importance they attribute to the instituted measures to contain the spread of the COVID-19 virus (personal norm), as well as their behavioral adherence to those measures. In total, 12,552 adolescents (67.6% girls, Mage = 15.06, SDage = 2.44, age range 10–21) answered inventory assessing adolescents’ agentic and communal orientation (GRI-JUG) and items related to personal norm regarding the instituted measures and behavioral adherence to the measures. The results showed a small positive role of communion in both boys’ and girls’ personal norm and behavioral adherence, whereas agency played a very small negative role in boys’ and girls’ personal norm and boys’ behavioral adherence to measures. Nevertheless, these findings could indicate the importance of enhancing communal traits and behaviors in both genders in order to assure socially responsible behavior during the pandemic.
Development and Optimization of Osimertinib-loaded Biodegradable Polymeric Nanoparticles Enhance In-vitro Cytotoxicity in Mutant EGFR NSCLC Cell Models and In-vivo Tumor Reduction in H1975 Xenograft Mice Models

Osimertinib (OMB), a third-generation EGFR inhibitor, specifically and irreversibly inhibits EGFRT790M mutant form. Nevertheless, its clinical use is limited due to poor solubility, low absorption, and oral bioavailability. To overcome the low therapeutic capabilities of the free drug, we developed OMB-loaded PCL or CHS nanoparticles and characterized them. Among fifteen devised nanoparticle formulations (Npfs), OMB-PCL-f3, f9, and OMB-CHS-f3 showed great characteristics such as particle size (ranges from 101.3 ± 8.2 to 119.7 ± 10.4 nm), zeta potential (−36.4 ± 3.2 to −31.7 ± 3.9 mV), and polydispersity index (0.227 ± 0.037 to 0.261 ± 0.025). The % entrapment (91.25 ± 5.84 to 95.25 ± 5.88) and drug loading (29.64 ± 2.38 to 33.59 ± 2.36) indicated the formulation optimization. OMB-CHS-f3 demonstrated long-term in-vitro release, with a % cumulative OMB release of 99.99 ± 2.67 within 24 h, and the cytotoxicity of OMB-CHS-f3 showed 2.6- and 2.4-fold superior activity in mutant EGFR harboring H1975 and PC-9 cells, respectively, compared to plain OMB. Quantitative assessment of OMB cellular uptake from OMB-CHS-f3 showed superior drug accumulation of 81.59 ± 5.8% and 77.31 ± 4.6% in H1975 and PC-9 cells which was more than OMB-CHS-f9 and plain OMB. Flow cytometric cell cycle analysis revealed that OMB-CHS-f3 triggered G2/M phase arrest greater than OMB-PCL-f9 and plain OMB. In vivo, OMB-CHS-f3 Npf treatment reduced tumor size and body weight gain compared to Tagrisso treatment (p < 0.05). These findings showed that chitosan-coated OMB Npfs might improve outcomes by overcoming complications, including resistance and disease recurrence in NSCLC patients.
Self-Perceived and Self-Tested Endurance: Associations with Objective Measures

Use of self-report (questionnaires) is often the most realistic means of screening physical fitness in large participant samples because this method is quicker and cheaper than objective testing. Yet, previous studies have reported equivocal validity to reports of self-perceived fitness. A hybrid self-report variant is the use of self-administered/reported objective measurement. I sought to investigate the relative validity of this variant method compared to self-perception reports. In total 26,452 young Norwegian men and women participated in this study. I collected data during obligatory selection for military conscript service. Approximately half of the participants were asked to rate their endurance level on a five-point Likert scale in an online questionnaire. The other half performed a self-administered 3000 m run and reported the result online. Within 18 months, all participants completed an objective maximal treadmill test at a conscript selection center. I used Spearman correlations (rs) and analyses of variance (ANOVAs) to investigate the relationships between these two self-report methods and the observed objective treadmill performance. Self-perceived and self-tested endurance were both identically correlated with the other-observed treadmill run for men (r s = 0.59; p < .001) and for women (rs = 0.50, p < .001); and ANOVAs revealed significant effects of self-perceived and self-tested endurance on treadmill run time, with higher self-reported endurance related to higher treadmill run time. In conclusion, self-perceived and self-tested endurance produced the same correlation coefficients with objectively measured treadmill run time. While there was a moderate relationship between self-reported and objectively measured endurance at the group level, there was substantial individual measurement error that should be considered for individual reports.
Dialysis modality utilization patterns and mortality in older persons initiating dialysis in Australia and New Zealand

The benefits of dialysis in the older population remain highly debated, particularly for certain dialysis modalities. This study aimed to explore the dialysis modality utilization patterns between in‐centre haemodialysis (ICHD), peritoneal dialysis (PD) and home haemodialysis (HHD) and their association with outcomes in older persons.
Identifying new drugs associated with pulmonary arterial hypertension: A WHO pharmacovigilance database disproportionality analysis

Since the 1960s, several drugs have been linked to the onset or aggravation of pulmonary arterial hypertension (PAH): dasatinib, some amphetamine‐like appetite suppressants (aminorex, fenfluramine, dexfenfluramine, benfluorex) and recreational drugs (methamphetamine). Moreover, in numerous cases, the implication of other drugs with PAH have been suggested, but the precise identification of iatrogenic aetiologies of PAH is challenging given the scarcity of this disease and the potential long latency period between drug intake and PAH onset. In this context, we used the World Health Organization's pharmacovigilance database, VigiBase, to generate new hypotheses about drug associated PAH.
Favorable effect of rivaroxaban against vascular dysfunction in diabetic mice by inhibiting NLRP3 inflammasome activation

Cardiovascular disease (CVD) is the leading cause of death in various complications of type 2 diabetes mellitus (T2DM). Rivaroxaban (Xarelto; Bayer), an oral direct factor Xa (FXa) inhibitor, prevents the activation of the coagulation cascade in CVD. Considering its anticoagulant and anti‐inflammatory effects, we assessed the hypothesis that rivaroxaban treatment may attenuate the vascular lesion and dysfunction in T2DM mice. C57BL/6, BKS‐db/db, BKS‐db/+, wild‐type (WT), and NLRP3−/− mice were fed with standard chow or high‐fat diet (HFD). Biochemical indexes, vascular lesions, and protein expression were evaluated using Western blot analysis, immunofluorescent staining, and RNA interference. Rivaroxaban presented favorable protection of vascular dysfunction in T2DM mice with significantly relieved vascular tension, intima‐media thickness, and collagen deposition. Similar improvements in NLR family pyrin domain containing 3 (NLRP3) knockout groups and rivaroxaban pointed to the positive role of rivaroxaban against vascular dysfunction in diabetic mice by ameliorating NLRP3 inflammasome activation. Furthermore, the augmentation of inflammation and cell dysfunction in mice aortic endothelial cells (MAECs) and smooth muscle cells (MOVASs) induced by soluble FXa may be blocked by rivaroxaban via protease‐activated receptors (PAR‐1, PAR‐2), mitogen‐activated protein kinase (MAPK), and nuclear factor κ‐B (NF‐κB) pathway. The data indicate that the development of vascular dysfunction and inflammation in T2DM mice may be blocked by rivaroxaban in vivo and in vitro. Rivaroxaban treatment may also attenuate NLRP3 inflammasome activation via PARs, MAPK, and NF‐κB pathway. This study provides mechanistic evidence of rivaroxaban therapies for vascular complications of T2DM.
1,3,4‐oxadiazole derivatives as potential antimicrobial agents

Due to the emergence of drug‐resistant microbial strains, different research groups are continuously developing novel drug molecules against already exploited and unexploited targets. 1,3,4‐Oxadiazole derivatives exhibited noteworthy antimicrobial activities. The presence of 1,3,4‐oxadiazole moiety in antimicrobial agents can modify their polarity and flexibility, which significantly improves biological activities due to various bonded and non‐bonded interactions viz. hydrogen bond, steric, electrostatic, and hydrophobic with target sites. The present review elaborates the therapeutic targets and mode of interaction of 1,3,4‐oxadiazoles as antimicrobial agents. 1,3,4‐oxadiazole derivatives target enoyl reductase (InhA), 14α‐demethylase in the mycobacterial cell; GlcN‐6‐P synthase, thymidylate synthase, peptide deformylase, RNA polymerase, dehydrosqualene synthase in bacterial strains; ergosterol biosynthesis pathway, P450‐14α demethylase, protein‐N‐myristoyltransferase in fungal strains; FtsZ protein, interfere with purine and functional protein synthesis in plant bacteria. The present review also summarizes the effect of different moieties and functional groups on the antimicrobial activity of 1,3,4‐oxadiazole derivatives.
Regular structures of lines in complex spaces

We study the properties of regular structures of lines, such as equiangular sets of lines and mutually unbiased bases (MUBs) in a general setting that includes real, complex and quaternionic spaces. We formulate a common generalization of several results in real and complex spaces that also hold in the quaternionic space. A set of lines is called equiangular if the angle between each pair is the same. A set of MUBs is a collection of orthonormal bases such that the angle between vectors from different bases is constant. Regular structures of lines have been studied in several fields such as digital communication, quantum computing, discrete mathematics and analysis. Our new concept of a multipartite equiangular set of lines is a common generalization of equiangular lines and MUBs. We prove a bound on the size of such set of lines, which generalizes the well-known absolute upper bounds. The existence of d + 1 MUBs in Cd is only known for prime power dimensions. We study sets of d + 1 MUBs that are the union of a standard basis and an orbit of the Weyl-Heisenberg group. As an example, we construct such MUBs in prime power dimensions. We also show connections between spherical 2-designs and other structures of lines. Fiducial vectors have been widely used to construct large sets of equiangular lines. A complex vector is fiducial if its orbit under a Weyl-Heisenberg group is an equiangular set of d2 lines. We give a new characterization of fiducial vectors, one that simplifies and significantly reduces the number of equations that must be solved to find a fiducial vector. We consider some possible classes of fiducial vectors and prove several nonexistence results. For example, using our new characterization we prove that the construction of fiducial vectors in small prime dimensions by Appleby (2005) essentially does not generalize. Finally, we give some methods for constructing equiangular sets of lines in complex and quaternionic spaces. We also find numerical fiducial vectors with high precision in Cd , d ≤ 21.
Childhood executive control and adolescent substance use initiation: the mediating roles of physical and relational aggression and prosocial behavior

ABSTRACT Although predictive associations between childhood executive control (EC) and adolescent substance use have been established in prior research, the developmental pathways involved in these long-term links have not been well understood. The goal of the current study was to investigate the degree to which aggressive behaviors, including both physical and relational aggression, and prosocial behaviors in elementary school operate as developmental pathways between preschool EC and adolescent substance use, while accounting for participants’ age, sex, family history of substance use, and family socioeconomic status. Participants were 329 youth (49% male; 63.6% European American) who were recruited to participate in a study between 2006 and 2012 while youth were in preschool and elementary school and followed into adolescence. The sample was recruited from a small Midwestern city in the United States. EC was assessed with performance-based tasks when children were 5 years 3 months. Youth behaviors with peers were reported by teachers when participants were in elementary school. Self-reports of the substance use initiation (e-cigarettes, cigarettes, alcohol, and marijuana) were obtained in adolescence via phone surveys. Mediation analyses revealed a statistically significant indirect effect from preschool EC to adolescent substance use through youth’s engagement in relational aggression in elementary school (b = > −0.22 [−0.51; −0.08]; β = > −0.18). Our results suggest that developmental pathways to adolescent substance use may begin in preschool, setting the stage for susceptibility to engagement in relational aggression, which increases, in turn, youth’s likelihood for substance use initiation in adolescence.
GEOGRAPHIC SPREAD OF CANINE DISTEMPER IN WILD CARNIVORES IN MICHIGAN, USA: PATHOLOGY AND EPIDEMIOLOGY, 2008–18

Abstract: Canine distemper is a widespread disease affecting both domestic and wild carnivores. This investigation of the geographic distribution, wildlife species infected, and relative prevalence rates was conducted over an 11-yr period and helps to document the disease spread, most highly infected wildlife species, and histologic lesions. Animals were collected as found dead, hunter and trapper harvested, and euthanized for displaying signs of abnormal behavior or neurologic disease. This disease appeared to spread from the Lower Peninsula of Michigan into the Upper Peninsula, was most frequently documented in raccoons (Procyon lotor), striped skunks (Mephitis mephitis), and gray fox (Urocyon cinereoargenteus), but also involved additional wildlife species. Three unique wildlife virus strains were identified. Two of these grouped within a separate subclade of the America 2 lineage. A third strain appeared to be a unique sequence type that is not associated with any existing subclade of America 2. We recommend the combined use of routine histology and immunohistochemical staining to confirm the diagnosis, and further recommend that both the lungs and spleen be collected as the optimal tissues to utilize for surveillance purposes.
Changes in the components of visual attention following traumatic brain injury: A systematic review and meta-analysis

Purpose We conducted a systematic review and meta-analysis to understand the impact of traumatic brain injury (TBI) on visual attention and whether different components and processes of visual attention (such as selective, sustained, divided, and covert orientation of visual attention) are affected following brain injury. Methods A literature search between January 1980 to May 2021 was conducted using Medline, Scopus, PubMed, and Google Scholar databases was undertaken for studies that assessed visual attention using different tasks that target specific or multiple components of visual attention. Three hundred twenty-nine potentially relevant articles were identified, and 20 studies met our inclusion criteria. Results A total of 123 effect sizes (ES) were estimated from 20 studies that included 519 patients with TBI and 530 normal participants. The overall combined ES was statistically significant and large (ES = 0.92), but with high heterogeneity (Q = 614.83, p < 0.0001, I2 = 80.32%). Subgroup analysis showed that the impact of TBI severity, with the ES for moderate-severe TBI significantly higher than mild TBI (t (112) = 3.11, p = 0.002). Additionally, the component of visual attention was differentially affected by TBI (F (2, 120) = 10.25, p<0.0001); the ES for selective attention (ES = 1.13) and covert orientation of visual attention (ES = 1.14) were large, whilst for sustained attention, the ES was medium at 0.43. A subgroup analysis comparing outcome measures showed that reaction time (ES = 1.12) was significantly more affected compared to performance accuracy (ES = 0.43), F (1, 96) = 25.98, p<0.0001). Conclusion Large and significant deficits in visual attention was found following TBI which can last for years after the initial injury. However, different components of visual attention were not affected to the same extent, with selective visual attention and orientation of visual attention most affected following TBI.
-Tubulin Is Required for Proper Recruitment and Assembly of Kar9–Bim1 Complexes in Budding Yeast□V

Microtubule plus-end–interacting proteins ( TIPs) promote the dynamic interactions between the plus ends ( ends) of astral microtubules and cortical actin that are required for preanaphase spindle positioning. Paradoxically, TIPs such as the EB1 orthologue Bim1 and Kar9 also associate with spindle pole bodies (SPBs), the centrosome equivalent in budding yeast. Here, we show that deletion of four C-terminal residues of the budding yeast -tubulin Tub4 (tub4dsyl) perturbs Bim1 and Kar9 localization to SPBs and Kar9-dependant spindle positioning. Surprisingly, we find Kar9 localizes to microtubule ends in tub4dsyl cells, but these microtubules fail to position the spindle when targeted to the bud. Using cofluorescence and coaffinity purification, we show Kar9 complexes in tub4dsyl cells contain reduced levels of Bim1. Astral microtubule dynamics is suppressed in tub4dsyl cells, but it are restored by deletion of Kar9. Moreover, Myo2and F-actin–dependent dwelling of Kar9 in the bud is observed in tub4dsyl cells, suggesting defective Kar9 complexes tether microtubule ends to the cortex. Overproduction of Bim1, but not Kar9, restores Kar9-dependent spindle positioning in the tub4dsyl mutant, reduces cortical dwelling, and promotes Bim1–Kar9 interactions. We propose that SPBs, via the tail of Tub4, promote the assembly of functional TIP complexes before their deployment to microtubule ends.