Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of the “universal test and treat” policy on the characteristics of persons registering for HIV care and initiating antiretroviral therapy in Uganda

We examined the effect of the Universal Test and Treat (UTT) policy on the characteristics of people living with HIV (PLHIV) at enrolment in HIV care and initiation of antiretroviral therapy (ART) in Uganda using data from 11 nationally representative clinics of The AIDS Support Organisation (TASO). We created two retrospective PLHIV cohorts: pre-UTT (2004–2016), where ART initiation was conditional on CD4 cell count and UTT (2017–2022), where ART was initiated regardless of World Health Organisation (WHO) clinical stage or CD4 cell count. We used a two-sample test of proportions and Wilcoxon rank-sum test to compare proportions and medians, respectively, between the cohorts. A total of 244,693 PLHIV were enrolled at the clinics [pre-UTT, 210,251 (85.9%); UTT, 34,442 (14.1%)]. Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV that were male (p < 0.001), aged 18–29 years (p < 0.001), aged >69 years, never married (p < 0.001), and educated to primary (p < 0.001) and post-primary (p < 0.001) school level at enrolment in HIV care and ART initiation. Overall, 97.9% of UTT PLHIV initiated ART compared to 45.2% under pre-UTT. The median time from enrolment in HIV care to ART initiation decreased from 301 [interquartile range (IQR): 58–878] pre-UTT to 0 (IQR: 0–0) under UTT. The median CD4 count at ART initiation increased from 254 cells/μL pre-UTT to 482 cells/μL under UTT (p < 0.001). Compared to the pre-UTT cohort, the UTT cohort had higher proportions of PLHIV with a CD4 count >500 cells/μL (47.3% vs. 13.2%, p < 0.001) and WHO stage 1 (31.7% vs. 4.5%, p < 0.001) at ART initiation. Adoption of the UTT policy in Uganda was successful in enrolling previously unreached individuals, such as men and younger and older adults, as well as those with less advanced HIV disease. Future research will investigate the effect of UTT on long-term outcomes such as retention in care, HIV viral suppression, morbidity, and mortality.
The mediating role of emotions in offline and online political participation: A post-social outbreak study in Ecuador and Chile

Introduction In 2019, there was a period of social outbreaks in several Latin American countries, which share a background of social inequality, distrust in authorities, a crisis of representativeness, and discontent towards social and economic policies. In October 2019, in Ecuador and Chile, participation in these protests was characterized by street protests and broad political participation in social networks and alternative media, which were followed or interrupted by the COVID-19 pandemic. These facts have been deeply researched, addressing causal and structural factors of the phenomenon, the alternatives of political participation, and the role of emotions as determinants of action in these contexts. The objective of this study is to explore offline and online political participation (Facebook) after the social outbreak of 2019 in both countries, based on political interest, and how emotions intervene, especially negative ones, in a context of high demobilization. Methods A descriptive, correlational ex post facto and cross-sectional methodology was used, with the participation of 367 people, 210 from Ecuador (57.2%) and 157 from Chile (42.8%), aged between 17 and 48 years (M = 22.13, SD = 3.73). The measurement was carried out from 2020 to 2021. Results A mediation analysis showed that people who are more interested in politics are more likely to experience anger and anxiety with the political and economic situation, which motivates conventional political participation (Model 1). In Model 2 people who showed greater concern about the political and economic impacts of the COVID-19 pandemic and together with anger, favor online political participation, especially local support. Discussion These results suggest the influence of emotions on political participation, which occurs when there is an increase in social discontent due to government policies adopted during the pandemic and which represents a continuity of the discontent that was expressed in the October 2019 social outbreak.
Assessing agricultural gene editing regulation in Latin America: an analysis of how policy windows and policy entrepreneurs shape agricultural gene editing regulatory regimes

This article explores the new developments and challenges of agricultural Gene Editing (GED) regulation in primarily nine countries of Latin America and the Caribbean (LAC) Region: Argentina, Bolivia, Brazil, Colombia, Guatemala, Honduras, Mexico, Paraguay and Peru. As Gene Editing technology develops, Latin America and the Caribbean regulatory regimes struggle to keep pace. Developers and regulators face challenges such as consumer perceptions, intellectual property, R&D funding (private and public), training, environmental and social impact, and access to domestic and international markets. Some Latin America and the Caribbean countries (e.g., Argentina) interpret existing legislation to promulgate regulations for biotechnology and Genetically Modified Organisms (GMOs), while others (e.g., Brazil and Honduras) have specific legislation for Genetically Modified Organisms. In both those cases, often a case-by-case approach is chosen to determine whether a Gene Editing organism is subject to Genetically Modified Organisms regulations or not. Other countries such as Peru have opted to ban the technology due to its perceived resemblance to transgenic Genetically Modified Organisms. After presenting the regulatory landscape for agricultural Gene Editing in Latin America and the Caribbean, this article addresses some of the differences and similarities across the region. Some countries have had more foresight and have dedicated resources to increase capacity and develop regulations (e.g., Brazil, Argentina, Colombia, Guatemala, Honduras, Mexico before 2018) while others struggle with bureaucratic limitations and partisanship of policymaking (e.g., Paraguay, Bolivia, Peru, Mexico after 2018). We propose that the differences and similarities between these regulatory regimes have emerged in part as a result of policy entrepreneurs (influential individuals actively involved in policy making) taking advantage of policy windows (opportunities for shaping policy and regulation). The third and remaining sections of this study discuss our main findings. Based on 41 semi structured interviews with regulators, scientists, product developers, NGOs and activists, we arrived at three main findings. First, there seems to be a consensus among most regulators interviewed that having harmonized regimes is a positive step to facilitate product development and deployment, leading to commercialization. Second, reducing bureaucracy (e.g., paper work) and increasing flexibility in regulation go hand in hand to expedite the acquisition of key lab materials required by developers in countries with less robust regimes such as Peru and Bolivia. Finally, developing public and private partnerships, fostering transparency, and increasing the involvement of marginalized groups may increase the legitimacy of Gene Editing regulation.
Clustering single-cell multimodal omics data with jrSiCKLSNMF

Introduction: The development of multimodal single-cell omics methods has enabled the collection of data across different omics modalities from the same set of single cells. Each omics modality provides unique information about cell type and function, so the ability to integrate data from different modalities can provide deeper insights into cellular functions. Often, single-cell omics data can prove challenging to model because of high dimensionality, sparsity, and technical noise. Methods: We propose a novel multimodal data analysis method called joint graph-regularized Single-Cell Kullback-Leibler Sparse Non-negative Matrix Factorization (jrSiCKLSNMF, pronounced “junior sickles NMF”) that extracts latent factors shared across omics modalities within the same set of single cells. Results: We compare our clustering algorithm to several existing methods on four sets of data simulated from third party software. We also apply our algorithm to a real set of cell line data. Discussion: We show overwhelmingly better clustering performance than several existing methods on the simulated data. On a real multimodal omics dataset, we also find our method to produce scientifically accurate clustering results.
Science for art: multi-years' evaluations of biocidal efficacy in support of artwork conservation

In recent decades, the relationship between Science and Art has been gradually strengthened through the use of diagnostic, conservation, and valorization technologies. New technologies can also be used to support the creation and durability of bio-artworks. Within such a context, starting from the Spring of 2014, we performed in situ experimentations to eventually increase the durability of the graphical artwork of William Kentridge on the Lungotevere embankments, whose creation was scheduled in the following years. We applied various combinations and concentrations of three different biocides (Algophase, Biotin R, and Preventol R80) and two water repellents (Hydrophase surfaces and Silo 111) on 34 test areas. However, the artist preferred to leave his artwork to a natural fading. Right before the realization of the graphical artwork “Triumph and Laments of Rome” in 2016, just the black biological colonizations mainly composed of cyanobacteria were removed through pressurized water. We monitored the artist's work through analyses of images and colorimetric variations and such drawings showed a duration of 4 years in the natural conditions of recolonization. Here we show how the recolonization of treated and control areas, analyzed with the same methods, showed an increased duration, 3 years longer than under natural conditions in the case of Preventol R80® and Biotin R® plus Silo 111®. The tested solutions showed differential effectiveness and multiple possibilities of use to support the maintenance of the artwork if the artist wanted to preserve his artwork for a longer period.
The “Let’s Talk about Children” intervention in a Finnish school context: fidelity, parents’ experiences, and perceived benefits

The Let’s Talk about Children intervention is a tool for parents and professionals to work together to promote children’s positive development, resilience, and psychosocial well-being in social and healthcare services, at school, and in day care. The aim of this study was to evaluate the fidelity, parents’ experiences, and perceived benefits of using the Let’s Talk about Children intervention in a school context. Participants (N = 65 first-grader parents) completed an online questionnaire after the intervention. The results show that the intervention was delivered as designed and conducted with high fidelity. Parents’ experiences of the Let’s Talk about Children discussions were positive, parents felt that the atmosphere was good during the discussion, and the participants reported benefits from the intervention. Clinical trial registration:ClinicalTrials.gov, identifier NCT05038280.
Protective effect of the novel calcineurin inhibitor voclosporin in experimental colitis

Background and aims Acute severe steroid-refractory ulcerative colitis remains a medically challenging condition with frequent need of surgery. It can be treated with the calcineurin inhibitor cyclosporine A with the need for therapeutic drug monitoring and significant toxicity. Recently, a novel calcineurin inhibitor, voclosporin, has been approved for the treatment of lupus nephritis with no need for therapeutic drug monitoring and an improved long-term safety profile. However, the therapeutic effect of voclosporin in acute severe steroid-refractory ulcerative colitis is still uncertain. We aimed to assess the therapeutic potential of voclosporin to ameliorate inflammation in an experimental model of colitis. Methods We used the dextran sodium sulfate-induced model of colitis in C57BL/6 J wildtype mice treated with either cyclosporine A, voclosporin or solvent control. We employed endoscopy, histochemistry, immunofluorescence, bead-based multiplex immunoassays and flow cytometry to study the therapeutic effect of calcineurin inhibitors in a preventive setting. Results Acute colitis was induced by dextran sodium sulfate characterized by weight loss, diarrhea, mucosal erosions and rectal bleeding. Both cyclosporine A and voclosporin strongly ameliorated the course of disease and reduced colitis severity in a similar manner. Conclusion Voclosporin was identified as biologically effective in a preclinical model of colitis and may be a potential therapeutic option in treating acute severe steroid-refractory ulcerative colitis.
Survival benefit of active surveillance for papillary thyroid carcinoma: a propensity score matching analysis based on SEER database

Background Over-treatment of papillary thyroid microcarcinoma (PTMC) has become a common issue. Although active surveillance (AS) has been proposed as an alternative treatment to immediate surgery for PTMC, its inclusion criteria and mortality risk have not been clearly defined. The purpose of this study was to investigate whether surgery can achieve significant survival benefits in patients with larger tumor diameter of papillary thyroid carcinoma (PTC), in order to evaluate the feasibility of expanding the threshold for active surveillance. Methods This study retrospectively collected data of patients with papillary thyroid carcinoma from the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2019. The propensity score matching (PSM) method was used to minimize confounding factors and selection bias between the surgery and non-surgery groups, and to compare the clinical and pathological characteristics between the two groups based on the SEER cohort. Meanwhile, the impact of surgery on prognosis was compared using Kaplan-Meier estimates and Cox proportional hazard models. Results A total of 175,195 patients were extracted from the database, including 686 patients who received non-surgical treatment, and were matched 1:1 with patients who received surgical treatment using propensity score matching. The Cox proportional hazard forest plot showed that age was the most important factor affecting overall survival (OS) of patients, while tumor size was the most important factor affecting disease-specific survival (DSS) of patients. In terms of tumor size, there was no significant difference in DSS between PTC patients with tumor size of 0-1.0cm who underwent surgical treatment and those who underwent non-surgical treatment, and the relative survival risk began to increase after the tumor size exceeded 2.0cm. Additionally, the Cox proportional hazard forest plot showed that chemotherapy, radioactive iodine, and multifocality were negative factors affecting DSS. Moreover, the risk of death increased over time, and no plateau phase was observed. Conclusion For patients with papillary thyroid carcinoma (PTC) staged as T1N0M0, AS is a feasible management strategy. As the tumor diameter increases, the risk of death without surgical treatment gradually increases, but there may be a threshold. Within this range, a non-surgical approach may be a potentially viable management strategy. However, beyond this range, surgery may be more beneficial for patient survival. Therefore, it is necessary to conduct more large-scale prospective randomized controlled trials to further confirm these findings.
Sex steroid hormone levels associated with dopamine D2/3 receptor availability in people who smoke cigarettes

Introduction Sex differences exist in tobacco smoking. Women have greater difficulty quitting smoking than men. Tobacco smoking is driven by the reinforcing effects of nicotine, the primary addictive component in cigarettes. Nicotine binds to nicotinic acetylcholine receptors, facilitating dopamine release in striatal and cortical brain regions. Dysregulated dopamine D2/3 receptor signaling in the dorsolateral prefrontal cortex (dlPFC) is associated with cognitive deficits such as impairments in attention, learning, and inhibitory control that impede quit attempts. Sex steroid hormones, such as estradiol and progesterone, influence drug-taking behaviors, through dopaminergic actions, suggesting that their influence may explain sex differences in tobacco smoking. The goal of this study was to relate dlPFC dopamine metrics to sex steroid hormone levels in people who smoke and healthy controls. Methods Twenty-four (12 women) people who smoke cigarettes and 25 sex- and age-matched controls participated in two same-day [11C]FLB457 positron emission tomography scans, one before and one after amphetamine administration. D2R availability (BPND) at baseline and after amphetamine administration was calculated. On the same day, plasma samples were collected for the analysis of sex steroid hormone levels: estradiol, progesterone, and free testosterone. Results Women who smoke had trending lower levels of estradiol than their sex-matched counterparts. Men who smoke had higher levels of estradiol and trending higher levels of free testosterone than their sex-matched counterparts. Among women only, lower estradiol levels were significantly associated with lower pre-amphetamine dlPFC BPND. Discussion/conclusion This study demonstrated that lower estradiol levels are associated with lower dlPFC D2R availability in women which may underlie difficulty resisting smoking.
Citrus flavonoid extracts alter the profiling of rumen antibiotic resistance genes and virulence factors of dairy cows

Citrus flavonoid extracts (CFE) have the potential to reduce rumen inflammation, improve ruminal function, and enhance production performance in ruminants. Our previous studies have investigated the effects of CFE on the structure and function of rumen microbiota in dairy cows. However, it remains unclear whether CFE affects the prevalence of antibiotic resistance genes (ARG) and virulence factors genes (VFG) in the rumen. Therefore, metagenomics was used to identify the rumen ARG and VFG in lactating dairy cows fed with CFE diets. The results showed that CFE significantly reduced the levels of Multidrug and Antiphagocytosis in the rumen (p < 0.05) and increased the levels of Tetracycline, Iron uptake system, and Magnesium uptake system (p < 0.05). Furthermore, the changes were found to have associations with the phylum Lentisphaerae. It was concluded that CFE could be utilized as a natural plant product to regulate virulence factors and antibiotic resistance of rumen microbiota, thereby improving rumen homeostasis and the health of dairy cows.
Association of bevacizumab and stroke in ovarian cancer: a systematic review and meta-analysis

Background The prognosis for patients with ovarian cancer is bleak. Clinical trials have shown the efficacy of bevacizumab in ovarian cancer treatment. However, life-threatening strokes may limit the usage of bevacizumab and require specific follow-up strategies. This study aims to systematically evaluate the risk of stroke of bevacizumab treatment in ovarian cancer. Methods We retrieved all relevant articles published up to December 4th, 2022, from Embase, PubMed, Web of Science, and the Cochrane Library. The risk of stroke in patients with ovarian cancer treated with bevacizumab combined with chemotherapy was analyzed. Meta-analysis was performed using the Stata 17 software and R 4.2. 1 program. Results Six randomized controlled trials (RCTs) of bevacizumab combined with chemotherapy or chemotherapy for ovarian cancer and six single-experimental-arm trials were included in this study. The meta-analysis showed a pooled risk ratio (RR) of 2.14 [95% confidence interval (CI): 0.88–7.99] for patients with ovarian cancer treated with bevacizumab combined with chemotherapy. Subgroup analyses showed that the incidence of stroke-related adverse events in the carboplatin + paclitaxel + bevacizumab group was 0.01% (95% CI: 0.00–0.01, p < 0.01). The incidence of stroke-related adverse events was 0.01% (95% CI: 0.00–0.01, p < 0.01) in patients aged ≥60. The incidence of stroke caused by cerebral ischemia and cerebral hemorrhage was 0.01% (95% CI: 0.01–0.02, p = 0.27) and 0.01% (95% CI: 0.00–0.01, p < 0.01), respectively. Conclusions This meta-analysis indicates that chemotherapy combined with bevacizumab may not increase the incidence of stroke in patients with ovarian cancer. However, stroke-related adverse events may be higher in older patients. Cerebral hemorrhage might cause the incidence of stroke more than cerebral ischemia. Systematic review registration PROSPERO (CRD42022381003).
Serum cytokine analysis in a cohort of advanced non-small cell lung cancer treated with PD-1 inhibitors reveals predictive markers of CXCL12

Background The circulating predictive factors for the outcomes of advanced non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs) remain elusive. We aimed to assess the predictive value of circulating cytokines for outcomes. Methods Serum samples of 102 advanced-stage NSCLC patients who underwent immunotherapy were collected at baseline. The relative levels of 37 cytokines were detected. PD-L1 expression was also analyzed. Results Higher serum CXCL12 levels (top 33%) were a poor predictive biomarker for durable clinical benefit (DCB) (23.5% vs. 72.1%, p<0.001), progression-free survival (PFS) (3.76 vs. 14.40 months; p<0.001) and overall survival (OS) (12.20 vs. 44.84 months; p=0.008). Compared with PD-L1-negative patients, PD-L1-positive patients had a significantly higher objective response rate (ORR) (70.0% vs. 28.8%, p<0.001) and a prolonged mPFS (25.35 vs. 4.64 months, p=0.003) and tended to have an increased mOS (44.84 vs. 20.42 months, p=0.087). A signature comprising PD-L1<1% and the top 33% CXCL12 level was associated with the lowest ORR (27.3% vs. 73.7%, p<0.001) and DCB (27.3% vs. 73.7%, p<0.001) and the worst mPFS (2.44 vs. 25.35 months, p<0.001) and mOS (11.97 vs. 44.84 months, p=0.007). Area under the curve (AUC) analyses of PD-L1 expression, CXCL12 level and PD-L1 expression plus CXCL12 level to predict DCB or no durable benefit (NDB) showed AUC values of 0.680, 0.719 and 0.794, respectively. Conclusion Our findings suggest that serum cytokine CXCL12 levels can predict the outcomes of patients with NSCLC receiving ICI. Moreover, the combination of CXCL12 levels and PD-L1 status can predict outcomes with a significantly improved discriminatory power.