Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-therapeutic strategy targeting parasite and inflammation-related alterations to improve prognosis of chronic Chagas cardiomyopathy: a hypothesis-based approach*

Chagas disease (CD), caused by infection by the protozoan parasite Trypanosoma cruzi, presents as main clinical manifestation the chronic chagasic cardiomyopathy (CCC). CCC afflicts millions of people, mostly in Latin America, and vaccine and effective therapy are still lacking. Comprehension of the host/parasite interplay in the chronic phase of T. cruzi infection may unveil targets for rational trait-based therapies to improve CCC prognosis. In the present viewpoint, I critically summarise a collection of data, obtained by our network of collaborators and other groups on CCC and preclinical studies on pathogenesis, targeting identification for intervention and the use of drugs with immunomodulatory properties to improve CCC. In the last two decades, models combining mouse lineages and T. cruzi strains allowed replication of crucial clinical, histopathological, and immunological traits of CCC. This condition includes conduction changes (heart rate changes, arrhythmias, atrioventricular blocks, prolongation of the QRS complex and PR and corrected QT intervals), ventricular dysfunction and heart failure, CD8-enriched myocarditis, tissue remodeling and progressive fibrosis, and systemic inflammatory profile, resembling “cytokine storm”. Studies on Chagas’ heart disease pathogenesis begins to unveil the molecular mechanisms underpinning the inflammation-related cardiac tissue damage, placing IFNγ, TNF and NFκB signaling as upstream regulators of miRNAs and mRNAs associated with critical biological pathways as cell migration, inflammation, tissue remodeling and fibrosis, and mitochondrial dysfunction. Further, data on preclinical trials using hypothesis-based tools, targeting parasite and inflammation-related alterations, opened paths for multi-therapeutic approaches in CCC. Despite the long path taken using experimental CD models replicating relevant aspects of CCC and testing new therapies and therapeutic schemes, these findings may get lost in translation, as conceptual and economical challenges, underpinning the valley of death across preclinical and clinical trials. It is hoped that such difficulties will be overcome in the near future.
High Resolution MR Imaging of the Testis Using a Small Radiofrequency Coil

We have developed a new device, consisting of a 3-cm RF coil and an immobilizer, to acquire high-resolution MR images of the testis. With the approval of our institutional review board, we conducted an MRI study on a cohort of healthy volunteers to test this device. With the participants in the supine position, we placed the dedicated immobilizer and RF coil on the scrotum for typically no more than 3 min. Subsequently, T2-weighted images were acquired with an in-plane resolution of 117 µm using a 3-T MR scanner and the periodically rotated overlapping parallel lines with enhanced reconstruction (PROPELLER) sequence. The total scan time ranged from 12 to 30 min (average 20 min). High-resolution MR images of the testis were acquired without deterioration by motion artifacts. Our results showed that the combined use of a small RF coil and an immobilizer is a feasible option for acquiring high-resolution MR images of the testis.
Menstrual Product Insecurity Resulting From COVID-19‒Related Income Loss, United States, 2020.

Objectives. To identify key effects of the pandemic and its economic consequences on menstrual product insecurity with implications for public health practice and policy. Methods. Study participants (n = 1496) were a subset of individuals enrolled in a national (US) prospective cohort study. Three survey waves were included (March‒October 2020). Menstrual product insecurity outcomes were explored with bivariate associations and logistic regression models to examine the associations between outcomes and income loss. Results. Income loss was associated with most aspects of menstrual product insecurity (adjusted odds ratios from 1.34 to 3.64). The odds of not being able to afford products for those who experienced income loss was 3.64 times (95% confidence interval [CI] = 2.14, 6.19) that of those who had no income loss and 3.95 times (95% CI = 1.78, 8.79) the odds for lower-income participants compared with higher-income participants. Conclusions. Pandemic-related income loss was a strong predictor of menstrual product insecurity, particularly for populations with lower income and educational attainment. Public Health Implications. Provision of free or subsidized menstrual products is needed by vulnerable populations and those most impacted by pandemic-related income loss. (Am J Public Health. 2022;112(4):675-684. (https://doi.org/10.2105/AJPH.2021.306674).
Longitudinal Examination of an Ethnic Paradox of Stress and Mental Health in Older Black and Latinx Adults

ABSTRACT Objectives To explain the ethnic paradox of mental health in aging, we evaluated whether Black and Latinx older adults experience (1) fewer depressive symptoms (DepSx), but more physical problems, and (2) greater psychological resilience as a result of life stressors than White older adults. Methods DepSx, physical health, and recent stress were obtained biennially from 25,893 older adults (77% White, 15% Black, 9% Latinx) in the U.S. Health and Retirement Study, across 16 years. Psychological resilience, lifetime stress, and discrimination experiences were available for 13,655 individuals. We conducted mixed-effects and linear regression analyses. Results For Blacks and Latinxs, experiencing more-than-usual stress events was associated with less increase in DepSx compared to Whites, although on average Blacks and Latinxs experience more DepSx. Black adults showed worse physical health than White adults and weaker effects of stress on psychological resilience despite experiencing more stress of all types. Findings were mixed for Latinxs. Conclusions Studying effects of time-varying stress on changes in health and multiple stressors on psychological resilience by race/ethnicity elucidates mechanisms for later-age health disparities. Clinical Implications Cross-sectional evaluations of stress and psychological health in a clinical setting may provide incomplete appraisals of health risks for Black and Latinx older Americans.
Targeted systemic therapies for psoriatic arthritis: a systematic review and comparative synthesis of short-term articular, dermatological, enthesitis and dactylitis outcomes

Introduction Randomised controlled trials (RCTs) have compared biological and targeted systemic disease-modifying antirheumatic drugs (DMARDS) against placebo in psoriatic arthritis (PsA); few have compared them head to head. Objectives To compare the efficacy and safety of all evaluated DMARDs for active PsA, with a special focus on biological DMARDs (bDMARDs) licensed for PsA or psoriasis. Methods A systematic review identified RCTs and Bayesian network meta-analysis (NMA) compared treatments on efficacy (American College of Rheumatology (ACR) response, Psoriasis Area and Severity Index (PASI) response, resolution of enthesitis and dactylitis) and safety (patients discontinuing due to adverse events (DAE)) outcomes. Subgroup analyses explored ACR response among patients with and without prior biological therapy exposure. Results The NMA included 46 studies. Results indicate that some tumour necrosis factor inhibitors (anti-TNFs) may perform numerically, but not significantly, better than interleukin (IL) inhibitors on ACR response but perform worse on PASI response. Few significant differences between bDMARDs on ACR response were observed after subgrouping for prior bDMARD exposure. Guselkumab and IL-17A or IL-17RA inhibitors—brodalumab, ixekizumab, secukinumab—were best on PASI response. These IL-inhibitors and adalimumab were similarly efficacious on resolution of enthesitis and dactylitis. Infliximab with and without methotrexate, certolizumab 400 mg every 4 weeks and tildrakizumab showed the highest rates of DAE; abatacept, golimumab and the IL-inhibitors, the lowest. Conclusions Despite similar efficacy for ACR response, IL-17A and IL-17RA inhibitors and guselkumab offered preferential efficacy to anti-TNFs in skin manifestations, and for enthesitis and dactylitis, thereby supporting drug selection based on predominant clinical phenotype.
Quality of energy intake in Malaysian adolescents: prevalence, characteristics, determinants and impact of implausible reporters

Abstract Objective: Misreporting of energy intake (EI) in nutritional epidemiology is common and even severe among adolescents. Thus, the current study aims to examine the presence, bias and impact introduced by implausible reporters. Design: Cross-sectional. Setting: Central and eastern regions of Peninsular Malaysia. Participants: A stratified random sampling was employed to select 917 secondary school-going adolescents (aged 15–17 years). Results: The prevalence of under-reporters was 17·4 %, while no over-reporters were identified. Under-reporters had higher body composition and lower dietary intakes (except for vitamin C, Cr and Fl) compared with plausible reporters (P < 0·05). Adolescents with overweight and obesity had a higher odds of under-reporting compared with under-/normal weight adolescents (P < 0·001). In model 3, the highest regression coefficient (R 2 = 0·404, P < 0·001) was obtained after adjusting for reporting status. Conclusions: Overweight and obese adolescents were more likely to under-report their food intake and consequently affect nutrient intakes estimates. Future analyses that include nutrient intake data should adjust for reporting status so that the impact of misreporting on study outcomes can be conceded and consequently improve the accuracy of dietary-related results.
Deoxycholic Acid and Coronary Artery Calcification in the Chronic Renal Insufficiency Cohort

Background Deoxycholic acid (DCA) is a secondary bile acid that may promote vascular calcification in experimental settings. Higher DCA levels were associated with prevalent coronary artery calcification (CAC) in a small group of individuals with advanced chronic kidney disease. Whether DCA levels are associated with CAC prevalence, incidence, and progression in a large and diverse population of individuals with chronic kidney disease stages 2 to 4 is unknown. Methods and Results In the CRIC (Chronic Renal Insufficiency Cohort) study, we evaluated cross‐sectional (n=1057) and longitudinal (n=672) associations between fasting serum DCA levels and computed tomographic CAC using multivariable‐adjusted regression models. The mean age was 57±12 years, 47% were women, and 41% were Black. At baseline, 64% had CAC (CAC score >0 Agatston units). In cross‐sectional analyses, models adjusted for demographics and clinical factors showed no association between DCA levels and CAC >0 compared with no CAC (prevalence ratio per 1‐SD higher log DCA, 1.08 [95% CI, 0.91–1.26). DCA was not associated with incident CAC (incidence per 1‐SD greater log DCA, 1.08 [95% CI, 0.85–1.39]) or CAC progression (risk for increase in ≥100 and ≥200 Agatston units per year per 1‐SD greater log DCA, 1.05 [95% CI, 0.84–1.31] and 1.26 [95% CI, 0.77–2.06], respectively). Conclusions Among CRIC study participants, DCA was not associated with prevalent, incident, or progression of CAC.
Rapid processing of threatening faces in the amygdala of nonhuman primates: subcortical inputs and dual roles

Abstract A subcortical pathway through the superior colliculus and pulvinar has been proposed to provide the amygdala with rapid but coarse visual information about emotional faces. However, evidence for short-latency, facial expression-discriminating responses from individual amygdala neurons is lacking; even if such a response exists, how it might contribute to stimulus detection is unclear. Also, no definitive anatomical evidence is available for the assumed pathway. Here we showed that ensemble responses of amygdala neurons in monkeys carried robust information about open-mouthed, presumably threatening, faces within 50 ms after stimulus onset. This short-latency signal was not found in the visual cortex, suggesting a subcortical origin. Temporal analysis revealed that the early response contained excitatory and suppressive components. The excitatory component may be useful for sending rapid signals downstream, while the sharpening of the rising phase of later-arriving inputs (presumably from the cortex) by the suppressive component might improve the processing of facial expressions over time. Injection of a retrograde trans-synaptic tracer into the amygdala revealed presumed monosynaptic labeling in the pulvinar and disynaptic labeling in the superior colliculus, including the retinorecipient layers. We suggest that the early amygdala responses originating from the colliculo–pulvino–amygdalar pathway play dual roles in threat detection.
Youtube videos for the most commonly applied radionuclide treatments: sufficient for patients as an information source?

Objectives YouTube is one of the most popular online sources of information for patients. The purpose of the study is to analyze the quality of YouTube videos about the most commonly applied radionuclide treatments. Method Related radionuclide therapy videos were searched on YouTube in October 2021. The quality of the videos was assessed by using the Journal of the American Medical Association (JAMA) benchmark criteria, the DISCERN Scale and the Global Quality Scale (GQS). Results A total of 473 videos were assessed and 270 were included in the study according to inclusion and exclusion criteria. According to the GQS score, videos were categorized as high-quality (n:63, 23.33%), intermediate quality (n:118, 43.70%) and low-quality (n:89, 32.96 %) groups. The findings of our study showed that the highest number of video views and comments were in the low-quality group. In addition; the number of video likes, views and comments were the lowest in the high-quality video group. The most viewed and commented as well as most liked videos and the videos of highest video power index scores were nonphysician sourced videos. The most quality videos were the physician-sourced videos in terms of JAMA, DISCERN and GQS scores. Conclusion Although high-quality videos about radionuclide treatments on YouTube may enlighten and motivate patients positively; it should be kept in mind that improper information may also be uploaded to this platform. Under the guidance of the European Association of Nuclear Medicine, it is necessary to generate an official video in English with multilingual subtitles.
Ovarian cancer today and tomorrow: A global assessment by world region and Human Development Index using GLOBOCAN 2020

Ovarian cancer remains to have relatively poor prognosis particularly in low‐resourced settings. It is therefore important to continually examine the burden of ovarian cancer to identify areas of disparities. Our study aims to provide an overview of the global burden of ovarian cancer using the GLOBOCAN 2020 estimates by country, world region, and Human Development Index (HDI) levels, as well as the predicted future burden by the year 2040 by HDI. Age‐standardized incidence and mortality rates for ovarian cancer in 185 countries were calculated by country, world region, and for the four‐tier HDI. The number of new cases and deaths were projected for the year 2040 based on demographic projections by HDI category. Approximately 314 000 new ovarian cancer cases and 207 000 deaths occurred in 2020. There were marked geographic variations in incidence rates, with the highest rates observed in European countries with very high HDI and low rates were found in African countries within the lowest HDI group. Comparable mortality rates were observed across the four‐tier HDI. Relative to 2020 estimates, our projection for 2040 indicates approximately 96% and 100% increase in new ovarian cancer cases and deaths, respectively, among low HDI countries compared to 19% and 28% in very high HDI countries. Our study highlights the disproportionate current and future burden of ovarian cancer in countries with lower HDI levels, calling for global action to reduce the burden and inequality of ovarian cancer in access to quality cancer care and treatment.
Single-Dose Liposomal Amphotericin B Treatment for Cryptococcal Meningitis

Background Cryptococcal meningitis is a leading cause of HIV-related mortality in sub-Saharan Africa. Based on phase-II data, we performed a phase-III randomized controlled non-inferiority trial to determine the efficacy of a single high-dose liposomal amphotericin B based treatment regimen. Methods HIV-positive adults with cryptococcal meningitis in Botswana, Malawi, South Africa, Uganda and Zimbabwe were randomized 1:1 to induction therapy of either (i) single, high-dose liposomal amphotericin B 10mg/kg given with 14 days of flucytosine 100mg/kg/day and fluconazole 1200mg/day (AmBisome group), or (ii) the current WHO recommended treatment of 7 daily doses of amphotericin B deoxycholate (1mg/kg/day) plus flucytosine (100mg/kg/day), followed by 7 days of fluconazole 1200mg/day (control group). The primary endpoint was all-cause mortality at 10 weeks with the trial powered to show non-inferiority at a 10% margin. Results We randomized 844 participants. None were lost-to-follow-up. In intention-to-treat analysis, 10-week mortality was 24.8% (101 of 407; 95% confidence interval [CI] 20.7-29.3%) in the AmBisome group and 28.7% (117 of 407; 95% CI 24.4-33.4%) in controls. The absolute difference in mortality was -3.9%, with an upper 1-sided 95% confidence interval of 1.2%. Fungal clearance from cerebrospinal fluid was -0.40 log10 CFU/ml/day in the AmBisome group and -0.42 log10 CFU/ml/day in the control group. Fewer participants experienced grade 3 or 4 adverse events in the AmBisome group than the control group (50.0% vs. 62.3%). Conclusions Single dose liposomal amphotericin B (10mg/kg) on a backbone of flucytosine and fluconazole was non-inferior to the current WHO recommended standard of care for HIV-associated cryptococcal meningitis and associated with fewer adverse events. (Trial registration number: ISRCTN72509687.)
Toxicological aspect of bioinsecticide pyrethrum extract and expressions of apoptotic gene levels in human hepotacellular carcinoma HepG2 cells

Abstract Pyrethrum extract (PE), an important natural bioinsecticide, is extensively used across the world to control pest insects in homes and farms. The aim of this study was to evaluate the potential cytotoxic effect of PE using MTT assay and genotoxic effect using micronucleus (MN) assay. The changes in the expressions of the apoptosis genes in mRNA levels were also investigated using Real-Time qPCR analysis as well as the ratio of apoptotic/necrotic cells with AnnexinV-FITC/Propidium iodide (PI) assay in HepG2 cells. PE markedly suppressed the cell proliferation on HepG2 cells. It significantly increased the frequency of micronucleus (MN) at 500 and 1000 µg/mL. PE also induced the percentage of the cell population of late apoptotic/necrotic cells (FITC + PI+) and necrotic cells (FITC- PI+), especially at 4000 μg/mL analyzed by flow cytometry. PE caused significant fold changes in the expression of several apoptotic genes including APAF1, BIK, BAX, BAD, BİD, MCL-1, CASP3, CASP1, CASP2, FAS, FADD and TNFRSF1A. In particular, the pro-apoptotic gene Hrk (Harakiri) remarkably and dose-dependently was overexpressed of the mRNA level. As a result, PE may exhibit cyto-genotoxic effects, especially at higher concentrations and lead to significant changes in the expression of mRNA levels in several apoptotic genes. Highlights Natural bioinsecticide PE exhibited a cytotoxic effect in HepG2 cells. PE significantly induced the micronucleus (MN) frequency at 500 and 1000 µg/mL. This bioinsecticide induced cell death and it lead to significant fold changes in the expression of mRNA levels in several apoptotic genes in HepG2 cells. The highest increase of the expression of mRNA levels was determined in Hrk (Harakiri) at 4000 µg/mL.
Fitness consequences of host colonization in two generalist fleas: Context‐dependency and the effect of spatial co‐occurrence

We studied the fitness consequences of colonizing a novel host by experimental lines of fleas (Synosternus cleopatrae and Xenopsylla ramesis) maintained for 18–22 generations on the principal or novel (sympatric or allopatric) hosts via number, developmental success and size of the offspring of the fleas exploiting these hosts. We asked whether (a) fitness on non‐principal hosts increases after prolonged maintenance; (b) the colonization success depends on the spatial co‐occurrence of a flea and a host and (c) colonization of a novel host is accompanied by a decreased ability to exploit an original host. The ability of fleas to colonize novel hosts differed between species, with S. cleopatrae, but not X. ramesis, increasing its offspring production on novel hosts. Spatial co‐occurrence did not affect colonization success. Maintenance on an alternative host was not accompanied by decreased adaptation to the original host. When fleas returned to the original host, their reproductive output was higher than that of their ancestors. We conclude that the success of colonizing a novel host is (a) context‐dependent and varies between flea and host species and (b) not accompanied by the loss of ability to exploit an ancestral host but may lead to an increase in this ability.
Cross-Sectional Associations of Sedentary Behavior and Sitting with Serum Lipid Biomarkers in Midlife

ABSTRACT Introduction Physical inactivity, excessive total time spent in sedentary behavior (SB) and prolonged sedentary bouts have been proposed to be risk factors for chronic disease morbidity and mortality worldwide. However, which patterns and postures of SB have the most negative impacts on health outcomes is still unclear. This population-based study aimed to investigate the independent associations of the patterns of accelerometer-based overall SB and sitting with serum lipid biomarkers at different moderate- to vigorous-intensity physical activity (MVPA) levels. Methods Physical activity and SB were measured in a birth cohort sample (N = 3272) at 46 yr using a triaxial hip-worn accelerometer in free-living conditions for 14 d. Raw acceleration data were classified into SB and PA using a machine learning–based model, and the bouts of overall SB and sitting were identified from the classified data. The participants also answered health-related questionnaires and participated in clinical examinations. Associations of overall SB (lying and sitting) and sitting patterns with serum lipid biomarkers were investigated using linear regression. Results The overall SB patterns were more consistently associated with serum lipid biomarkers than the sitting patterns after adjustments. Among the participants with the least and the most MVPA, high total time spent in SB and SB bouts of 15–29.99 and ≥30 min were associated with impaired lipid metabolism. Among those with moderate amount of MVPA, higher time spent in SB and SB bouts of 15–29.99 min was unfavorably associated with serum lipid biomarkers. Conclusions The associations between SB patterns and serum lipid biomarkers were dependent on MVPA level, which should be considered when planning evidence-based interventions to decrease SB in midlife.