Miracle-dz/UniFAR-FTUs huggingface dataset:
Divergent Preferences for HIV Prevention: A Discrete Choice Experiment for Multipurpose HIV Prevention Products in South Africa

Background. The development of antiretroviral (ARV)-based prevention products has the potential to substantially change the HIV prevention landscape; yet, little is known about how appealing these products will be outside of clinical trials, as compared with the existing options. Methods. We conducted a discrete choice experiment (DCE) to measure preferences for 5 new products among 4 important populations in the HIV response: adult men and women in the general population (aged 18 to 49 y), adolescent girls (aged 16 to 17 y), and self-identifying female sex workers (aged 18 to 49 y). We interviewed 661 self-reported HIV-negative participants in peri-urban South Africa, who were asked to choose between 3 unique, hypothetical products over 10 choice sets. Data were analyzed using multinomial, latent class and mixed multinomial logit models. Results. HIV protection was the most important attribute to respondents; however, results indicate significant demand among all groups for multipurpose prevention products that offer protection from HIV infection, other STIs, and unwanted pregnancy. All groups demonstrated a strong preference for long-lasting injectable products. There was substantial heterogeneity in preferences within and across population groups. Limitations. Hypothetical DCE data may not mirror real-world choices, and products will have more attributes in reality than represented in choice tasks. Background data on participants, including sensitive areas of HIV status and condom use, was self-reported. Conclusions. These results suggest that stimulating demand for new HIV prevention products may require a more a nuanced approach than simply developing highly effective products. No single product is likely to be equally attractive or acceptable across different groups. This study strengthens the call for effective and attractive multipurpose prevention products to be deployed as part of a comprehensive combination prevention strategy.
Human catecholamine sulfotransferase (SULT1A3) pharmacogenetics: functional genetic polymorphism

Sulfotransferase (SULT) 1A3 catalyzes the sulfate conjugation of catecholamines and structurally related drugs. As a step toward studies of the possible contribution of inherited variation in SULT1A3 to the pathophysiology of human disease and/or variation in response to drugs related to catecholamines, we have resequenced all seven coding exons, three upstream non‐coding exons, exon–intron splice junctions and the 5′‐flanking region of SULT1A3 using DNA samples from 60 African‐American (AA) and 60 Caucasian‐American (CA) subjects. Eight single nucleotide polymorphisms (SNPs) were observed in AA and five in CA subjects, including one non‐synonymous cSNP (Lys234Asn) that was observed only in AA subjects with an allele frequency of 4.2%. This change in amino acid sequence resulted in only 28 ± 4.5% (mean ± SEM) of the enzyme activity of the wild‐type (WT) sequence after transient expression in COS‐1 cells, with a parallel decrease (54 ± 2.2% of WT) in level of SULT1A3 immunoreactive protein. Substrate kinetic studies failed to show significant differences in apparent Km values of the two allozymes for either dopamine (10.5 versus 10.2 µm for WT and variant, respectively) or the cosubstrate 3′‐phosphoadenosine 5′‐phosphosulfate (0.114 versus 0.122 µm, respectively). The decrease in level of immunoreactive protein in response to this single change in amino acid sequence was due, at least in part, to accelerated SULT1A3 degradation through a proteasome‐mediated process. These observations raise the possibility of ethnic‐specific inherited alterations in catecholamine sulfation in humans.
CREB1 directly activates the transcription of ribonucleotide reductase small subunit M2 and promotes the aggressiveness of human colorectal cancer

As the small subunit of Ribonucleotide reductase (RR), RRM2 displays a very important role in various critical cellular processes such as cell proliferation, DNA repair, and senescence, etc. Importantly, RRM2 functions like a tumor driver in most types of cancer but little is known about the regulatory mechanism of RRM2 in cancer development. In this study, we found that the cAMP responsive element binding protein 1 (CREB1) acted as a transcription factor of RRM2 gene in human colorectal cancer (CRC). CREB1 directly bound to the promoter of RRM2 gene and induced its transcriptional activation. Knockdown of CREB1 decreased the expression of RRM2 at both mRNA and protein levels. Moreover, knockdown of RRM2 attenuated CREB1-induced aggressive phenotypes of CRC cells in vitro and in vivo. Analysis of the data from TCGA database and clinical CRC specimens with immunohistochemical staining also demonstrated a strong correlation between the co-expression of CREB1 and RRM2. Decreased disease survivals were observed in CRC patients with high expression levels of CREB1 or RRM2. Our results indicate CREB1 as a critical transcription factor of RRM2 which promotes tumor aggressiveness, and imply a significant correlation between CREB1 and RRM2 in CRC specimens. These may provide the possibility that CREB1 and RRM2 could be used as biomarkers or targets for CRC diagnosis and treatment.
Rigorous tests of gene–environment interactions in a lab study of the oxytocin receptor gene (OXTR), alcohol exposure, and aggression

Naturalistic studies of gene–environment interactions (G X E) have been plagued by several limitations, including difficulty isolating specific environmental risk factors from other correlated aspects of the environment, gene‐environment correlation (rGE), and the use of a single genetic variant to represent the influence of a gene. We present results from 235 Finnish young men in two lab studies of aggression and alcohol challenge that attempt to redress these limitations of the extant G X E literature. Specifically, we use a latent variable modeling approach in an attempt to more fully account for genetic variation across the oxytocin receptor gene (OXTR) and to robustly test its main effects on aggression and its interaction with alcohol exposure. We also modeled aggression as a latent variable comprising various indices, including the average and maximum levels of aggression, the earliest trial on which aggression was expressed, and the proportion of trials on which the minimum and maximum levels of aggression were expressed. The best fitting model for the genetic variation across OXTR included six factors derived from an exploratory factor analysis, roughly corresponding to six haplotype blocks. Aggression levels were higher on trials in which participants were administered alcohol, won, or were provoked. There was a significant main effect of OXTR on aggression across studies after controlling for covariates. The interaction of OXTR and alcohol was also significant across studies, such that OXTR had stronger effects on aggression in the alcohol administration condition. © 2015 Wiley Periodicals, Inc.
Thalamostriatal and cerebellothalamic pathways in a songbird, the Bengalese finch

The thalamostriatal system is a major network in the mammalian brain, originating principally from the intralaminar nuclei of thalamus. Functions of the thalamostriatal system remain unclear, but a subset of these projections provides a pathway through which the cerebellum communicates with the basal ganglia. Both the cerebellum and basal ganglia play crucial roles in motor control. Although songbirds have yielded key insights into the neural basis of vocal learning, it is unknown whether a thalamostriatal system exists in the songbird brain. Thalamic nucleus DLM is an important part of the song system, the network of nuclei required for learning and producing song. DLM receives output from song system basal ganglia nucleus Area X and sits within dorsal thalamus, the proposed avian homolog of the mammalian intralaminar nuclei that also receives projections from the cerebellar nuclei. Using a viral vector that specifically labels presynaptic axon segments, we show in Bengalese finches that dorsal thalamus projects to Area X, the basal ganglia nucleus of the song system, and to surrounding medial striatum. To identify the sources of thalamic input to Area X, we map DLM and cerebellar-recipient dorsal thalamus (DTCbN). Surprisingly, we find both DLM and immediately-adjacent subregions of DTCbN project to Area X. In contrast, a medial-ventral subregion of DTCbN projects to medial striatum outside Area X. Our results suggest the basal ganglia in the song system, like the mammalian basal ganglia, integrate feedback from the thalamic region to which they project as well as thalamic regions that receive cerebellar output.
A measurement-based generalized source model for Monte Carlo dose simulations of CT scans

The goal of this study is to develop a generalized source model for accurate Monte Carlo dose simulations of CT scans based solely on the measurement data without a priori knowledge of scanner specifications. The proposed generalized source model consists of an extended circular source located at x-ray target level with its energy spectrum, source distribution and fluence distribution derived from a set of measurement data conveniently available in the clinic. Specifically, the central axis percent depth dose (PDD) curves measured in water and the cone output factors measured in air were used to derive the energy spectrum and the source distribution respectively with a Levenberg–Marquardt algorithm. The in-air film measurement of fan-beam dose profiles at fixed gantry was back-projected to generate the fluence distribution of the source model. A benchmarked Monte Carlo user code was used to simulate the dose distributions in water with the developed source model as beam input. The feasibility and accuracy of the proposed source model was tested on a GE LightSpeed and a Philips Brilliance Big Bore multi-detector CT (MDCT) scanners available in our clinic. In general, the Monte Carlo simulations of the PDDs in water and dose profiles along lateral and longitudinal directions agreed with the measurements within 4%/1 mm for both CT scanners. The absolute dose comparison using two CTDI phantoms (16 cm and 32 cm in diameters) indicated a better than 5% agreement between the Monte Carlo-simulated and the ion chamber-measured doses at a variety of locations for the two scanners. Overall, this study demonstrated that a generalized source model can be constructed based only on a set of measurement data and used for accurate Monte Carlo dose simulations of patients’ CT scans, which would facilitate patient-specific CT organ dose estimation and cancer risk management in the diagnostic and therapeutic radiology.
Stapled Trans-Anal Rectal Resection (STARR) for Obstructive Defecation Syndrome—Functional Outcome and Quality of Life after Two Years

Background: Stapled transanal rectal resection (STARR) has been shown to improve patients’ functional and quality of life outcomes in several studies. Although it is a safe and effective treatment for obstructive defecation syndrome, still data on long-term follow-up are missing. Methods: From January 2010 to July 2014, 46 consecutive patients undergoing STARR using the CONTOUR® TRANSTAR™ device, shortly named TRANSTAR (transanal stapler assisted resection), were prospectively followed. Recurrence rate, quality of life (Patient Assessment of Constipation-Quality of Life (PAC-Qol)) and complication were documented at baseline, 12 and 24 months after operation. Two subgroups of patients were compared to assess the impact of resection length on outcome. Results: We included 46 patients (89% female) in the study. The mean age was 65 ± 16 years and the duration of the operation was 48 ± 4 min. Total PAC-QoL score improved from 2.0 (SD 0.3) to 0.9 (1.4) after 12 months, but deteriorated to 1.2 (0.3) after 24 months (p < 0.001 for both comparisons). Complications were noted in 7% of the patients: Urinary retention (2 patients), postoperative bleeding (1 patient). No major complications or mortality were seen. After one year, we had one prolapse recurrence and after 24 month we had another. There was no significant relation between the length of the specimen and the improvement of life quality. Conclusions: The STARR procedure seems to be a safe and fast therapeutic option for patients with ODS and/or rectal prolapse. It is a tailored transanal full-thickness rectal resection improving the patients’ quality of life still two years after the operation.
Predictors of Long-Term Psychosocial Functioning and Health-Related Quality of Life in Children and Adolescents With Prior Concussions

Abstract Objectives: Individual differences in long-term psychosocial functioning after concussions in children and adolescents are poorly understood. The aim of the study was to investigate potential predictors of long-term psychosocial functioning and health-related quality of life in youth after prior concussion. Methods: Participants (N=75; mean age=14.3 years old; 52% girls) with one prior concussion (n=24), multiple prior concussions (n=24), or a prior orthopedic injury and no concussion (n=27) were seen on average 2.7 years after their most recent injury. Psychosocial functioning was assessed using the self-report versions of the Behavior Assessment System for Children (BASC-2; Anxiety and Depression scales only), the Strengths and Difficulties Questionnaire, and the Pediatric Quality of Life Inventory TM 4.0. Pre-existing conditions (attention problems, learning difficulties, mood concerns, anxiety concerns, and migraines) were reported by parents using a checklist and examined as predictors of long-term functioning. Other potential predictors included age at testing, sex, time between most recent injury and testing, and number of prior concussions. Results: The groups did not differ significantly on long-term psychosocial functioning. Moreover, only pre-existing mood concerns or attention problems significantly predicted psychosocial adjustment. Conclusions: Children’s functioning before a concussion is critical to understanding outcome. Pre-injury attention and mood concerns should be assessed in clinical settings to prevent and treat long-term psychosocial problems after concussion. (JINS, 2018, 24, 540–548)
A Pilot Study of Serum MicroRNAs Panel as Potential Biomarkers for Diagnosis of Nonalcoholic Fatty Liver Disease

Background The invasive nature of liver biopsy makes the histopathological diagnosis of non-alcoholic fatty liver disease (NAFLD) difficult and its diagnostic performance unsatisfactory. The present study aimed to identify a serum microRNA (miRNA) expression profile that could serve as a novel diagnostic biomarker for NAFLD. Methods Serum miRNA expression was investigated using three cohorts comprising 465 participants (healthy controls and NAFLD patients) recruited between August 2010 and June 2013. miRNA expression was initially screened by Illumina sequencing using serum samples pooled from 20 patients and 20 controls. Quantitative reverse transcriptase polymerase chain reaction assay was then used to evaluate the expression of selected miRNAs. A logistic regression model was constructed using a training cohort (n = 242) and validated using another cohort (n = 183). The area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. Results We identified an miRNA panel (hsa-miR-122-5p, hsa-miR-1290, hsa-miR-27b-3p, and hsa-miR-192-5p) with a high diagnostic accuracy for NAFLD. The satisfactory diagnostic performance of the miRNA panel remained regardless of the NAFLD activity score (NAS) status. There was significant difference between the AUC values of the miRNA panel and those of ALT (AUC = 0.786, 95% CI = 0.717–0.855; P = 0.142) and FIB-4 (AUC = 0.795, 95% CI = 0.730–0.860; sensitivity = 69.9%, specificity = 83.7%. Conclusion We identified a serum microRNA panel with considerable clinical value in NAFLD diagnosis. The results indicate that the miRNA panel is a more sensitive and specific biomarker for NAFLD than ALT and FIB-4.
Effect of Adiponectin on Kidney Crystal Formation in Metabolic Syndrome Model Mice via Inhibition of Inflammation and Apoptosis

The aims of the present study were to elucidate a possible mechanism of kidney crystal formation by using a metabolic syndrome (MetS) mouse model and to assess the effectiveness of adiponectin treatment for the prevention of kidney crystals. Further, we performed genome-wide expression analyses for investigating novel genetic environmental changes. Wild-type (+/+) mice showed no kidney crystal formation, whereas ob/ob mice showed crystal depositions in their renal tubules. However, this deposition was remarkably reduced by adiponectin. Expression analysis of genes associated with MetS-related kidney crystal formation identified 259 genes that were >2.0-fold up-regulated and 243 genes that were <0.5-fold down-regulated. Gene Ontology (GO) analyses revealed that the up-regulated genes belonged to the categories of immunoreaction, inflammation, and adhesion molecules and that the down-regulated genes belonged to the categories of oxidative stress and lipid metabolism. Expression analysis of adiponectin-induced genes related to crystal prevention revealed that the numbers of up- and down-regulated genes were 154 and 190, respectively. GO analyses indicated that the up-regulated genes belonged to the categories of cellular and mitochondrial repair, whereas the down-regulated genes belonged to the categories of immune and inflammatory reactions and apoptosis. The results of this study provide compelling evidence that the mechanism of kidney crystal formation in the MetS environment involves the progression of an inflammation and immunoresponse, including oxidative stress and adhesion reactions in renal tissues. This is the first report to prove the preventive effect of adiponectin treatment for kidney crystal formation by renoprotective activities and inhibition of inflammation and apoptosis.
MicroRNAs as critical regulators of the endothelial to mesenchymal transition in vascular biology

The endothelial to mesenchymal transition (EndMT) is a newly recognized, fundamental biological process involved in development and tissue regeneration, as well as pathological processes such as the complications of diabetes, fibrosis and pulmonary arterial hypertension. The EndMT process is tightly controlled by diverse signaling networks, similar to the epithelial to mesenchymal transition. Accumulating evidence suggests that microRNAs (miRNAs) are key regulators of this network, with the capacity to target multiple messenger RNAs involved in the EndMT process as well as in the regulation of disease progression. Thus, it is highly important to understand the molecular basis of miRNA control of EndMT. This review highlights the current fund of knowledge regarding the known links between miRNAs and the EndMT process, with a focus on the mechanism that regulates associated signaling pathways and discusses the potential for the EndMT as a therapeutic target to treat many diseases.
Effect of organic solvents on the mechanical properties of graphene/epoxy Nanocomposites

In this research, effects of solutions and in-situ polymerization on mechanical properties were investigated. Graphene at various contents (0.05, 0.1 and 0.25 %wt) was dispersed with mechanical stirring and sonication techniques in epoxy resin. Tetrahydrofuran (THF) and acetone were used in solution method to reduce the suspension viscosity. Scanning electron microscopy (SEM) was used to image the graphene particles. The tension test is performed on fabricated Nanocomposites. In solution method, effects of THF and acetone on epoxy resin were considered and more efficiency for acetone is observed. Also, two methods, vacuum chamber and direct vacuum pump, to achieve low pressure for removing any trapped air were implemented. It is found that behavior of the Nanocomposites via different mentioned methods on mechanical properties is same. Addition of graphene at very low content (0.05 wt %) increases the mechanical properties. However, introducing more filler leads to deterioration of properties. SEM results show that the more filler is added, the more agglomeration can be seen in the specimens. Thus, it is assumed that agglomerations lead to decrease in mechanical properties. Also, results indicate that in-situ polymerization method has better effect on improving the tensile properties rather than the solution method.
Endoscopic Fundoplication

Objective Transoral incisionless fundoplication (TIF) is a completely endoscopic approach to treat gastroesophageal reflux disease (GERD). We previously reported our initial results demonstrating safety and early effectiveness. We now present an updated experience describing outcomes with longer follow-up. Methods For a three-year period, TIF procedures were performed on 80 patients. Preoperative workup routinely consisted of contrast esophagram and manometry. PH testing was reserved for patients with either atypical symptoms or typical symptoms unresponsive to protonpump inhibitors (PPIs). Heartburn severity was longitudinally assessed using the GERD health-related quality of life index. Safety analysis was performed on all 80 patients, and an effectiveness analysis was performed on patients with at least 6-month follow-up. Results Mean procedure time was 75 minutes. There were seven (8.75%) grade 2 complications and one (1.25%) grade 3 complication (aspiration pneumonia). The median length of stay was 1 day (mean, 1.4). Forty-one patients had a minimum of 6-month of follow-up (mean, 24 months; range, 6–68 months). The mean satisfaction scores at follow-up improved significantly from baseline (P < 0.001). Sixty-three percent of patients had completely stopped or reduced their PPI dose. Results were not impacted by impaired motility; however, the presence of a small hiatal hernia or a Hill grade 2/4 valve was associated with reduced GERD health-related quality of life scores postoperatively. Conclusions At a mean follow-up of 24 months, TIF is effective. Although symptoms and satisfaction improved significantly, many patients continued to take PPIs. Future studies should focus on longer-term durability and comparisons with laparoscopic techniques.