Miracle-dz/UniFAR-FTUs huggingface dataset:
Injection Practices and Sexual Behaviors Among Persons with Diagnosed HIV Infection Who Inject Drugs — United States, 2015–2017

During 2016, 6% of persons in the United States who received a diagnosis of human immunodeficiency virus (HIV) infection had their HIV infection attributed to injection drug use (1). Injection practices and sexual behaviors among HIV-positive persons who inject drugs, such as injection equipment sharing and condomless sex, can increase HIV transmission risk; nationally representative estimates of the prevalences of these behaviors are lacking. The Medical Monitoring Project (MMP) is an annual, cross-sectional survey that reports nationally representative estimates of clinical and behavioral characteristics among U.S. adults with diagnosed HIV (2). CDC used MMP data to assess high-risk injection practices and sexual behaviors among HIV-positive persons who injected drugs during the preceding 12 months and compared their HIV transmission risk behaviors with those of HIV-positive persons who did not inject drugs. During 2015-2017, approximately 10% (weighted percentage estimate) of HIV-positive persons who injected drugs engaged in distributive injection equipment sharing (giving used equipment to another person for use); nonsterile syringe acquisition and unsafe disposal methods were common. Overall, among HIV-positive persons who injected drugs, 80% received no treatment, and 57% self-reported needing drug or alcohol treatment. Compared with HIV-positive persons who did not inject drugs, those who injected drugs were more likely to have a detectable viral load (48% versus 35%; p = 0.008) and engage in high-risk sexual behaviors (p<0.001). Focusing on interventions that reduce high-risk injection practices and sexual behaviors and increase rates of viral suppression might decrease HIV transmission risk among HIV-positive persons who inject drugs. Successful substance use treatment could also lower risk for transmission and overdose through reduced injection.
High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis

Objective We examined whether plasma β-amyloid (Aβ)42/Aβ40, as measured by a high-precision assay, accurately diagnosed brain amyloidosis using amyloid PET or CSF p-tau181/Aβ42 as reference standards. Methods Using an immunoprecipitation and liquid chromatography–mass spectrometry assay, we measured Aβ42/Aβ40 in plasma and CSF samples from 158 mostly cognitively normal individuals that were collected within 18 months of an amyloid PET scan. Results Plasma Aβ42/Aβ40 had a high correspondence with amyloid PET status (receiver operating characteristic area under the curve [AUC] 0.88, 95% confidence interval [CI] 0.82–0.93) and CSF p-tau181/Aβ42 (AUC 0.85, 95% CI 0.79–0.92). The combination of plasma Aβ42/Aβ40, age, and APOE ε4 status had a very high correspondence with amyloid PET (AUC 0.94, 95% CI 0.90–0.97). Individuals with a negative amyloid PET scan at baseline and a positive plasma Aβ42/Aβ40 (<0.1218) had a 15-fold greater risk of conversion to amyloid PET-positive compared to individuals with a negative plasma Aβ42/Aβ40 (p = 0.01). Conclusions Plasma Aβ42/Aβ40, especially when combined with age and APOE ε4 status, accurately diagnoses brain amyloidosis and can be used to screen cognitively normal individuals for brain amyloidosis. Individuals with a negative amyloid PET scan and positive plasma Aβ42/Aβ40 are at increased risk for converting to amyloid PET-positive. Plasma Aβ42/Aβ40 could be used in prevention trials to screen for individuals likely to be amyloid PET-positive and at risk for Alzheimer disease dementia. Classification of evidence This study provides Class II evidence that plasma Aβ42/Aβ40 levels accurately determine amyloid PET status in cognitively normal research participants.
PD-L1 Expression and Clinical Outcomes to Cabozantinib, Everolimus, and Sunitinib in Patients with Metastatic Renal Cell Carcinoma: Analysis of the Randomized Clinical Trials METEOR and CABOSUN

Purpose: Programmed death-ligand 1 (PD-L1) status by IHC is prognostic in metastatic renal cell carcinoma (mRCC), and its role as a potential predictive biomarker is under investigation. Using tumor tissue from the METEOR (NCT01865747) and CABOSUN (NCT01835158) clinical trials, we explored whether PD-L1 expression and the extent of the immune cell infiltrate can serve as prognostic and/or predictive biomarkers for cabozantinib and other targeted agents. Experimental Design: IHC double staining for PD-L1 and CD45/CD163 (immune cell markers) was performed on tumor tissue from METEOR (n = 306) and CABOSUN (n = 110) clinical trials. Immune cell density and MET expression levels were also analyzed. Our primary aim was to correlate progression-free survival (PFS) by independent central review with PD-L1 status in patients treated with cabozantinib, everolimus (METEOR), or sunitinib (CABOSUN). Overall survival (OS) was also interrogated. Results: Tumor cell (TC) PD-L1 expression (≥1% cutoff) was detected in 29% and 23% of tumors from patients in the METEOR and CABOSUN trials, respectively. On univariate analysis, patients with PD-L1–positive TC had poorer PFS and OS than patients with PD-L1–negative TC on both trials, independent of therapy. On multivariable analysis and when combining the two trials, the association between TC PD-L1 expression and OS was statistically significant for all patients (P = 0.034) and for patients treated with cabozantinib only (P = 0.038). Cabozantinib was associated with improved PFS (HR < 0.70) and OS (HR < 0.85) compared with everolimus and sunitinib irrespective of PD-L1 expression. Conclusions: Higher PD-L1 expression results in worse clinical outcomes in mRCC treated with targeted therapy. Furthermore, PD-L1 expression is not predictive of response to cabozantinib therapy.
Blunted cardiovascular responses to acute psychological stress predict low behavioral but not self-reported perseverance.

Emerging evidence relates attenuated physiological stress reactions to poor behavioral regulation. However, only a small number of behaviors such as impulsivity and risk taking have been explored. Nevertheless, one opportunistic study suggested that blunted reactivity might relate to poor perseverance. The present study examined the relationship between cardiovascular reactivity to acute active psychological stress and self-reported and behavioral perseverance. Participants (N = 64) completed a self-report perseverance questionnaire before heart rate (HR) and blood pressure (BP) were measured at rest and in response to 4-min active (paced auditory serial addition; PASAT) and passive (cold pressor) stress tests. This was followed by an unsolvable Euler puzzle tracing task, with the time spent and number of attempts endeavoring to solve the puzzle recorded as behavioral perseverance measures. Blunted systolic and diastolic BP reactivity to the PASAT was associated with fewer attempts at the impossible puzzle, and lower diastolic BP PASAT reactivity related to less time persevering at the puzzle. Moreover, attenuated diastolic BP and HR PASAT reactivity predicted poorer perseverance at keeping one's hand in the iced water of the cold pressor task. There was no association between reactivity and self-reported perseverance. These preliminary findings add to the evidence that implicates blunted reactivity as a physiological marker of poor behavioral regulation, and this may indicate why individuals with blunted reactivity are at increased risk of developing negative health outcomes (e.g., obesity and addictions).
Clinical characteristics and survival in non-small cell lung cancer patients by smoking history: a population-based cohort study

Abstract Introduction: Approximately, 10–15% of lung cancer patients have never smoked. Previous epidemiological studies on non-tobacco associated lung cancer have been hampered by selected data from a small number of hospitals or limited numbers of patients. By use of data from large population-based registers with national coverage, this study aims to compare characteristics and survival of patients with non-small cell lung cancer (NSCLC) with different smoking histories. Methods: Swedish national population-based registers were used to retrieve data on patients diagnosed with primary NSCLC between 2002 and 2016. The Kaplan–Meier method and Cox proportional hazard models were used to estimate overall survival and lung cancer-specific survival by smoking history. Results: In total, 41,262 patients with NSCLC were included. Of those, 4624 (11%) had never smoked. Never-smokers were more often women and older compared to ever smokers (current and former). Adenocarcinoma was proportionally more common in never-smokers (77%) compared to current (52%) and former smokers (57%). Stage IV disease was more common in never-smokers (57%) than in current (48%) and former smokers (48%). Epidermal growth factor receptor mutation was observed more in never-smokers (37%) compared to current (5%) and former smokers (9%). Both lung cancer-specific and overall survival were higher for never-smokers compared to current smokers. Conclusions: The observed differences in characteristics between never-smokers and smokers, and the higher survival in never-smokers compared to smokers from this large population-based study provide further evidence that lung cancer in never-smokers is clinically different to tobacco-associated lung cancer. The findings from this study emphasise the need for an improved understanding of genetics, pathogenesis, mechanisms and progression of non-tobacco associated lung cancer that may help prevent lung cancer or identify individually targeted treatments.
Glucocorticoids delay RAF-induced senescence promoted by EGR1

ABSTRACT Expression of hyperactive RAF kinases, such as the oncogenic B-RAF-V600E mutant, in normal human cells triggers a proliferative arrest that blocks tumor formation. We discovered that glucocorticoids delayed the entry into senescence induced by B-RAF-V600E in human fibroblasts, and allowed senescence bypass when the cells were regularly passaged, but that they did not allow proliferation of cells that were already senescent. Transcriptome and siRNA analyses revealed that the EGR1 gene is one target of glucocorticoid action. Transcription of the EGR1 gene is activated by the RAF-MEK-ERK MAPK pathway and acts as a sensor of hyper-mitogenic pathway activity. The EGR1 transcription factor regulates the expression of p15 and p21 (encoded by CDKN2B and CDKN1A, respectively) that are redundantly required for the proliferative arrest of BJ fibroblasts upon expression of B-RAF-V600E. Our results highlight the need to evaluate the action of glucocorticoid on cancer progression in melanoma, thyroid and colon carcinoma in which B-RAF-V600E is a frequent oncogene, and cancers in which evasion from senescence has been shown. Summary: In human fibroblasts, glucocorticoids induce a delay or bypass entry into senescence induced by oncogenic B-RAF-V600E. This senescence is promoted by EGR1 through transcriptional activation of the key cell cycle inhibitors CDKN1A and CDKN2B.
Threefold Increases in Population HIV Viral Load Suppression Among Men and Young Adults — Bukoba Municipal Council, Tanzania, 2014–2017

Reducing HIV-related morbidity and mortality, and effectively eliminating HIV transmission risk, depends on use of antiretroviral therapy (ART) to achieve and maintain viral load suppression (VLS)* (1,2). By 2020, sub-Saharan African countries are working to achieve VLS among 90% of persons using ART and 73% of all persons living with HIV infection (1). In Tanzania, a country with 1.4 million persons with HIV infection, 49.6% of HIV-positive persons aged 15-49 years had achieved VLS in 2017, including only 21.5% of men and 44.6% of women aged 25-29 years (3). To identify interventions that might increase VLS in Tanzania, and reduce VLS-associated sex and age-group disparities, the Bukoba Combination Prevention Evaluation (BCPE) scaled up new HIV testing, linkage to care, and retention on ART interventions throughout Bukoba Municipal Council (Bukoba), Tanzania, during October 2014-March 2017 (4,5). Located on the western shore of Lake Victoria, Bukoba is a mixed urban and rural municipality of 150,000 persons and capital of Kagera Region. Of the 31 regions of Tanzania, Kagera has the fourth highest prevalence of HIV infection (6.8%) among residents aged 15-49 years (3). CDC analyzed data from BCPE preintervention and postintervention surveys and found that VLS prevalence among HIV-positive Bukoba residents aged 18-49 years increased approximately twofold overall (from 28.6% to 64.8%) and among women (33.3% to 67.8%) and approximately threefold among men (20.5% to 59.1%) and young adults aged 18-29 years (15.6% to 56.7%). During 2017, BCPE facility-based testing and linkage interventions were approved as new service delivery models by the Tanzania Ministry of Health, Community Development, Gender, Elderly and Children (4,5). After a successful rollout to 208 facilities in 11 regions in 2018, BCPE interventions are being scaled up in all regions of Tanzania in 2019 with support from the United States President's Emergency Plan for AIDS Relief (PEPFAR). †.
Transcriptome analysis of virulence gene regulation by the ATP-dependent Lon protease in Salmonella Typhimurium.

Aim: Determination of the virulence regulatory network controlled by the ATP-dependent Lon protease in Salmonella enterica serovar Typhimurium. Materials & methods: The effect of Lon on S. Typhimurium virulence genes expression was investigated by RNA sequencing, and virulence-associated phenotypes between the wild-type and lon mutant were compared. Results: SPI-1, SPI-4, SPI-9 and flagellar genes were activated, while SPI-2 genes were repressed in the lon mutant. Accordingly, the lon mutant exhibited increased adhesion to and invasion of epithelial cells, increased motility and decreased replication in macrophages. The activation of SPI-2 genes by Lon partially accounts for the replication defect of the mutant. Conclusion: A wide range of virulence regulatory functions are governed by Lon in S. Typhimurium.
Genetic variants in the nucleotide excision repair genes are associated with the risk of developing endometriosis

Abstract Endometriosis is a major health issue among women of reproductive age. However, its etiology has not yet been completely understood. We investigated 10 single nucleotide polymorphisms from six novel nucleotide excision repair genes and the susceptibility to endometriosis. A total of 153 patients with endometriosis were recruited during 2000–2010 from central Taiwan. Pathological confirmation was necessary for all patients, and exclusion criteria included the presence of leiomyoma, adenomyosis, or cancer of the uterine, cervix, or ovary and a prescription of hormone therapy. Furthermore, a total of 636 age-matched individuals without endometriosis were recruited during the same time period from central Taiwan. The polymerase chain reaction coupled with restriction fragment length polymorphism methodology was applied for genotyping. The multivariate logistic regression analysis showed that subjects carrying the ERCC1 rs11615 TT (OR = 2.04, 95% CI = 1.36–3.41), ERCC2 rs1799793 AA (OR = 1.86, 95% CI = 1.14–3.11), and ERCC6 rs2228528 AA genotypes (OR = 1.79, 95% CI = 1.13–2.83) exhibited significantly increased risks of developing endometriosis compared with their counterparts carrying the wild-type genotypes. This study suggests that certain single nucleotide polymorphisms of nucleotide excision repair genes excision repair cross-complementation group 1 (ERCC1, ERCC2, and ERCC6) predispose women to the development of endometriosis. Summary Sentence Genetic variants in the nucleotide excision repair genes, such as ERCC1, ERCC2, and ERCC6, may contribute to the development of endometriosis.
Experiential Explanation

People often answer why-questions with what we call experiential explanations: narratives or stories with temporal structure and concrete details. In contrast, on most theories of the epistemic function of explanation, explanations should be abstractive: structured by general relationships and lacking extraneous details. We suggest that abstractive and experiential explanations differ not only in level of abstraction, but also in structure, and that each form of explanation contributes to the epistemic goals of individual learners and of science. In particular, experiential explanations support mental simulation and survive transitions across background theories; as a result, they support learning and help us translate between competing frameworks. Experiential explanations play an irreducible role in human cognition-and perhaps in science.
Therapeutic Potential of Lespedeza bicolor to Prevent Methylglyoxal-Induced Glucotoxicity in Familiar Diabetic Nephropathy

Lespedeza bicolor (LB) is often used in traditional medicine to remove toxins, replenish energy stores, and regulate various symptoms of diabetes. This study aimed to explore the use of LB as a therapeutic to prevent diabetic nephropathy in methylglyoxal (MGO)-treated models in vitro and in vivo. Western blotting, immunostaining, and biochemical assays were used to obtain several experimental readouts in renal epithelial cells (LLC-PK1) and BALB/c mice. These include: production of reactive oxygen species (ROS), formation of advanced glycation end-products (AGEs), expression of receptor for advanced glycation end-products (RAGE), apoptotic cell death, glucose levels, fatty acid and triglyceride levels, expression of pro-inflammatory cytokines IL-1β and TNF-α, glyoxalase 1 (Glo1), and nuclear factor erythroid 2-related factor 2 (Nrf2). Pretreatment with LB significantly reduced MGO-induced cellular apoptosis, intracellular production of ROS, and formation of AGEs to ameliorate renal dysfunction in vitro and in vivo. Interestingly, administering LB in MGO-treated cells and mice upregulated the expression of Nrf2 and Glo1, and downregulated the expression of IL-1β and TNF-α. Moreover, LB reduced MGO-induced AGE accumulation and RAGE expression in the kidneys, which subsequently reduced AGE-RAGE interactions. Overall, LB ameliorates renal cell apoptosis and corrects renal dysfunction in MGO-treated mice. These findings extend our understanding of the pathogenic mechanism of MGO-induced nephrotoxicity and regulation of the AGE/RAGE axis by Lespedeza bicolor.
Progress Evaluation for Transnational Restaurant Chains to Reformulate Products and Standardize Portions to Meet Healthy Dietary Guidelines and Reduce Obesity and Non-Communicable Disease Risks, 2000–2018: A Scoping and Systematic Review to Inform Policy

Transnational restaurant chains sell food and beverage products in 75 to 139 countries worldwide linked to obesity and non-communicable diseases (NCDs). This study examined whether transnational restaurant chains reformulated products and standardized portions aligned with healthy dietary guidelines and criteria. Firstly, we describe the transnational restaurant industry structure and eating trends. Secondly, we summarize results from a scoping review of healthy dietary guidelines for restaurants. Thirdly, we describe a systematic review of five electronic databases (2000–2018) to identify studies on nutrient profile and portion size changes made by transnational restaurants over 18 years. We used Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, identified 179 records, and included 50 studies conducted in 30 countries across six regions. The scoping review found a few expert-recommended targets for restaurants to improve offerings, but no internationally accepted standard for portions or serving sizes. The systematic review results showed no standardized assessment methods or metrics to evaluate transnational chain restaurants’ practices to improve menu offerings. There was wide variation within and across countries, regions, firms, and chains to reduce energy, saturated and trans fats, sodium, and standardized portions. These results may inform future research and encourage transnational chain restaurants to offer healthy product profiles and standardized portions to reduce obesity and NCD risks worldwide.
Functional morphology and identity of the thenar pad in the subterranean genus Ctenomys (Rodentia, Caviomorpha)

As in many other fossorial tetrapods, the most obvious adaptations to scratch‐digging in the subterranean tuco‐tuco (Rodentia, Ctenomyidae, Ctenomys) are found in the hands, which among other adaptations, present the mesaxonic condition; i.e. the central digits are more developed, and also their claws, which are curved and elongated. The thumb is atrophied and aligned with the rest of the digits, showing a small and flat claw. This configuration of digits and claws seems to be in accordance with what it is expected for rodents: rudimentary movements when handling food items. However, on the palmar side of the hand, tuco‐tucos have several pads, the thenar (located under the thumb) being the most developed. In this study, we investigated the functional morphology of the thenar pad through different approaches: musculoskeletal anatomy, histology and functionality. The analysis of radiographs and clarified and double‐stained hand samples of Ctenomys talarum and C. australis showed that the thenar pad is supported by a paddle‐shaped bone that articulates with a protrusion in the scapholunate bone. This bone, flat and long, continues in a flat cartilaginous structure, with a shape similar to a claw. Dissections showed that the thenar pad has several associated muscles: the m. palmaris longus, the m. abductor pollicis longus, and a massive muscular complex located between the thumb and the thenar pad. By topology it might be inferred that this complex is formed by the m. abductor pollicis brevis, the m. flexor pollicis brevis and the m. adductor pollicis brevis. Longitudinal histological sections of the thenar pad stained with hematoxylin‐eosin showed a thick layer of keratin at the distal end, external face. The observation of live specimens of C. talarum foraging on two food items of different size and filmed at 300 fps showed that the thenar pad acts as an opposable thumb, with digit‐like movements. Tuco‐tucos are able to perform more precise movements than expected, and to grasp and manipulate the food with one hand. In previous studies, it was suggested that the thenar pad was supported by a ‘palmar ossicle’, or ‘prepollex’ (= radial sesamoid bone). Our results suggest that this sesamoid underwent a radical change on its morphology, making the thenar pad a part of the food handling system in Ctenomys, so the thenar pad might be considered a ‘false thumb’, rather than a palmar pad. It is suggested to advance on the description and functional analysis of the thenar pad, redefining the structure, since the terms used so far to define it would not be accurate.