Miracle-dz/UniFAR-FTUs huggingface dataset:
Cys34 Adductomics Links Colorectal Cancer with the Gut Microbiota and Redox Biology.

Chronic inflammation is an established risk factor for colorectal cancer (CRC). To study reactive products of gut inflammation and redox signaling on CRC development we used untargeted adductomics to detect adduct features in pre-diagnostic serum from the EPIC-Italy cohort. We focused on modifications to Cys34 in human serum albumin (HSA), which is responsible for scavenging small reactive electrophiles that might initiate cancers. Employing a combination of statistical methods, we selected seven Cys34 adducts associated with CRC, as well as BMI (a well-known risk factor). Five adducts were more abundant in CRC cases than controls and clustered with each other, suggesting a common pathway. Since two of these adducts were Cys34 modifications by methanethiol, a microbial-human co-metabolite, and crotonaldehyde, a product of lipid peroxidation, these findings further implicate infiltration of gut microbes into the intestinal mucosa and the corresponding inflammatory response as causes of CRC. The other two associated adducts were Cys34 disulfides of homocysteine that were less abundant in CRC cases than controls and may implicate homocysteine metabolism as another causal pathway. The selected adducts and BMI ranked higher as potentially causal factors than variables previously associated with CRC (smoking, alcohol consumption, physical activity and total meat consumption). Regressions of case-control differences in adduct levels on days to diagnosis showed no statistical evidence that disease progression, rather than causal factors at recruitment, contributed to the observed differences. These findings support the hypothesis that infiltration of gut microbes into the intestinal mucosa and the resulting inflammation are causal factors for CRC.
Tibiotalocalcaneal Arthrodesis Using a Novel Retrograde Intramedullary Nail

Background. Tibiotalocalcaneal (TTC) arthrodesis is a common treatment option for complex hindfoot pathology. Overall union rates range from 50% to 86% but can be even lower in certain populations. A novel retrograde intramedullary nail has recently been developed. The purpose of this study was to report fusion rates, time to weight-bearing, and complications with the use of the A3 Fusion Nail. Methods. All patients 18 years or older who underwent TTC arthrodesis with an A3 Fusion Nail at a single institution from 2010 to 2015 with a minimum 3-month follow-up were included in this study. Rates of successful fusion, time to union, time to weight-bearing, and complications were evaluated. A total of 20 patients with an average age of 58.1 years and an average follow-up of 12.5 months met inclusion criteria. Results. Successful TTC arthrodesis was achieved in 14 of 20 patients (70%) overall. Average time to union was 8.1 months, and average time to weight-bearing was 6.8 weeks. Of 20 patients, 17 (85%) required femoral head allograft for bulk bone defects, and the union rate in this subset of patients was 76.5%. The rates of revision surgery (10%) and complications were low. Conclusion. The A3 Fusion Nail demonstrated a favorable safety profile and achieved TTC arthrodesis at a rate consistent with historical data despite being used in a patient population at high risk for nonunion. In patients with bulk bone defects at high risk for nonunion, the A3 Fusion Nail demonstrated superior rates of fusion (76.5%) to those reported in the literature (50%). Level of Evidence: Level III: Retrospective cohort study
Water Extract of Curcuma longa L. Ameliorates Non-Alcoholic Fatty Liver Disease

Our aim was to investigate whether hot water extract (CLW) of Curcuma longa L. could prevent non-alcoholic fatty liver disease (NAFLD). HepG2 cells were treated with free fatty acid (FFA) mixture (oleic acid: palmitic acid, 2:1) for 24 h to stimulate in vitro fatty liver. In addition, C57BL/6 mice were fed 60 kcal% high-fat (HF) diet for eight weeks to induce fatty liver in vivo. Intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) productions were increased by FFA and HF-diet, but supplementation with CLW significantly decreased these levels. CLW treatment ameliorated antioxidant activities that were suppressed by exposure to the FFA and HF-diet. Cluster of differentiation 36 (CD36) and fatty acid transport proteins (FATP2 and FATP5) were increased in HF-diet groups, while CLW suppressed their expression levels. Moreover, sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) expression levels were down-regulated in the CLW groups compared to HF-diet groups. On the other hand, 5′ adenosine monophosphate-activated protein kinase (AMPK), Peroxisome proliferator-activated receptor alpha (PPAR-α), and carnitine palmitoyltransferase 1 (CPT-1) expressions were up-regulated in the CLW groups. HF-diet fed mice showed high hepatic triglycerides (TG) content compared to the normal diet mice. However, the administration of CLW restored the hepatic TG level, indicating an inhibitory effect against lipid accumulation by CLW. These results suggest that CLW could be a potentially useful agent for the prevention of NAFLD through modulating fatty acid uptake.
GABA‐A receptor and mitochondrial TSPO signaling act in parallel to regulate melanocyte stem cell quiescence in larval zebrafish

Tissue regeneration and homeostasis often require recruitment of undifferentiated precursors (adult stem cells; ASCs). While many ASCs continuously proliferate throughout the lifetime of an organism, others are recruited from a quiescent state to replenish their target tissue. A long‐standing question in stem cell biology concerns how long‐lived, non‐dividing ASCs regulate the transition between quiescence and proliferation. We study the melanocyte stem cell (MSC) to investigate the molecular pathways that regulate ASC quiescence. Our prior work indicated that GABA‐A receptor activation promotes MSC quiescence in larval zebrafish. Here, through pharmacological and genetic approaches we show that GABA‐A acts through calcium signaling to maintain MSC quiescence. Unexpectedly, we identified translocator protein (TSPO), a mitochondrial membrane‐associated protein that regulates mitochondrial function and metabolic homeostasis, as a parallel regulator of MSC quiescence. We found that both TSPO‐specific ligands and induction of gluconeogenesis likely act in the same pathway to promote MSC activation and melanocyte production in larval zebrafish. In contrast, TSPO and gluconeogenesis appear to act in parallel to GABA‐A receptor signaling to regulate MSC quiescence and vertebrate pigment patterning.
Double burden of maternal and child malnutrition and socioeconomic status in urban Sri Lanka

Child malnutrition and maternal obesity are serious public health issues in Sri Lanka. This study explores the associations between socioeconomic status and the double burden of malnutrition among school-aged children and within their household. A total of 543 primary school children aged 5–10 years (204 boys and 339 girls) in Gampaha District, Sri Lanka, were included in the analysis. The nutritional statuses of thinness, normal, overweight, and obesity for children and mothers were defined according to WHO growth references and body mass index. Maternal education, household equivalent income, and maternal employment were used as socioeconomic status indicators. The proportion of child thinness and overweight was 19.3% and 13.4%, respectively, and that of maternal overweight (body mass index ≥ 25 kg/m2) was 36.5%. A positive correlation was found between maternal body mass index and the child’s body mass index for age z-score in older boys and younger girls. A multivariate stepwise logistic regression analysis showed that lower education of mothers posed a higher association with child thinness (adjusted odds ratio = 2.33, 95% confidence interval: 1.08–5.00). Mothers with overweight and obesity were less likely to have a child with thinness (adjusted odds ratio = 0.30, 95% confidence interval: 0.16–0.58). Maternal employment status and household equivalent income were not significantly, but marginally, associated with child overweight and obesity. Socioeconomic inequality combined with maternal nutritional status affected child malnutrition. These findings suggest that the underlying circumstances within households should be considered to improve child malnutrition.
Autophagy in Kidney Disease.

Autophagy is a cellular homeostatic program for the turnover of cellular organelles and proteins, in which double-membraned vesicles (autophagosomes) sequester cytoplasmic cargos, which are subsequently delivered to the lysosome for degradation. Emerging evidence implicates autophagy as an important modulator of human disease. Macroautophagy and selective autophagy (e.g., mitophagy, aggrephagy) can influence cellular processes, including cell death, inflammation, and immune responses, and thereby exert both adaptive and maladaptive roles in disease pathogenesis. Autophagy has been implicated in acute kidney injury, which can arise in response to nephrotoxins, sepsis, and ischemia/reperfusion, and in chronic kidney diseases. The latter includes comorbidities of diabetes and recent evidence for chronic obstructive pulmonary disease-associated kidney injury. Roles of autophagy in polycystic kidney disease and kidney cancer have also been described. Targeting the autophagy pathway may have therapeutic benefit in the treatment of kidney disorders. Expected final online publication date for the Annual Review of Physiology, Volume 82 is February 10, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Direct replication of task‐dependent neural activation patterns during sadness introspection in two independent adolescent samples

Functional neuroimaging results need to replicate to inform sound models of human social cognition and its neural correlates. Introspection, the capacity to reflect on one's thoughts and feelings, is one process required for normative social cognition and emotional functioning. Engaging in introspection draws on a network of brain regions including medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), middle temporal gyri (MTG), and temporoparietal junction (TPJ). Maturation of these regions during adolescence mirrors the behavioral advances seen in adolescent social cognition, but the neural correlates of introspection in adolescence need to replicate to confirm their generalizability and role as a possible mechanism. The current study investigated whether reflecting upon one's own feelings of sadness would activate and replicate similar brain regions in two independent samples of adolescents. Participants included 156 adolescents (50% female) from the California Families Project and 119 adolescent girls from the Pittsburgh Girls Study of Emotion. All participants completed the Emotion Regulation Questionnaire (ERQ) and underwent a functional magnetic resonance imaging scan while completing the same facial emotion‐processing task at age 16–17 years. Both samples showed similar whole‐brain activation patterns when engaged in sadness introspection and when judging a nonemotional facial feature. Whole‐brain activation was unrelated to ERQ scores in both samples. Neural responsivity to task manipulations replicated in regions recruited for socio‐emotional (mPFC, PCC, MTG, TPJ) and attention (dorsolateral PFC, precentral gyri, superior occipital gyrus, superior parietal lobule) processing. These findings demonstrate robust replication of neural engagement during sadness introspection in two independent adolescent samples.
Strategic science communication as planned behavior: Understanding scientists’ willingness to choose specific tactics

Strategic science communicators need to select tactics that can help them achieve both their short-term communication objectives and long-term behavioral goals. However, little previous research has sought to develop theory aimed at understanding what makes it more likely that a communicator will prioritize specific communication tactics. The current study aims to advance the development of a theory of strategic science communication as planned behavior based on the Integrated Behavioral Model. It does so in the context of exploring Canadian scientists’ self-reported willingness to prioritize six different tactics as a function of attitudinal, normative, and efficacy beliefs. The results suggest that scientists’ beliefs about ethicality, norms, response efficacy, and self-efficacy, are all meaningful predictors of willingness to prioritize specific tactics. Differences between scientists in terms of demographics and related variables provide only limited benefit in predicting such willingness.
EEG Electrode-induced Skin Injury among Adult Patients Undergoing Ambulatory EEG Monitoring

ABSTRACT Introduction: Ambulatory electroencephalography technology has improved in the last 40 years. Many clinicians believe that some skin injury is an unavoidable complication of prolonged EEG monitoring. In this study, we examined potential risk factors associated with electrode-induced skin injury in adult patients with AEEG monitoring. Methods: A cross-sectional observational study was conducted from December 2017 to October 2018, in the outpatient clinic at a teaching hospital in Sydney, Australia. Patients were included if they were older than 16 years of age and had been referred for AEEG monitoring of two to five days duration. Trained neurophysiology nurses completed a pre-application skin assessment before they applied the EEG electrodes. Daily assessments of the skin condition were conducted. The patients completed a questionnaire to assess comfort levels at the completion of the testing. Results: A total of 251 patients participated in this study. Two groups were established – those who were monitored for 2–3 days (Group 1; n = 92) and those who were monitored for 4–5 days (Group 2; n = 159). There was a significant acceleration in inflammation which occurred between day 2 and day 4/5. Cross-sectional analyses of patient characteristics showed that increasing age, fair skin color, dry skin texture and fine hair texture were the prevailing risk factors for greater inflammation scores. Conclusion: The patient discomfort and inflammatory burden associated with this procedure were high. Inflammation was shown to increase with the duration of electrode application.
Maternal Characteristics Affect Fetal Growth Response in the Women First Preconception Nutrition Trial

The objective of this secondary analysis was to identify maternal characteristics that modified the effect of maternal supplements on newborn size. Participants included 1465 maternal–newborn dyads in Guatemala, India, and Pakistan. Supplementation commenced before conception (Arm 1) or late 1st trimester (Arm 2); Arm 3 received usual care. Characteristics included body mass index (BMI), stature, anemia, age, education, socio-economic status (SES), parity, and newborn sex. Newborn outcomes were z-scores for length (LAZ), weight (WAZ), and weight to length ratio-for-age (WLRAZ). Mixed-effect regression models included treatment arm, effect modifier, and arm * effect modifier interaction as predictors, controlling for site, characteristics, and sex. Parity (para-0 vs. para ≥1), anemia (anemia/no anemia), and sex were significant effect modifiers. Effect size (95% CI) for Arm 1 vs. 3 was larger for para-0 vs. ≥1 for all outcomes (LAZ 0.56 (0.28, 0.84, p < 0.001); WAZ 0.45 (0.20, 0.07, p < 0.001); WLRAZ 0.52 (0.17, 0.88, p < 0.01) but only length for Arm 2 vs. 3. Corresponding effects for para ≥1 were >0.02. Arm 3 z-scores were all very low for para-0, but not para ≥1. Para-0 and anemia effect sizes for Arm 1 were > Arm 2 for WAZ and WLRAZ, but not LAZ. Arm 1 and 2 had higher WAZ for newborn boys vs. girls. Maternal nulliparity and anemia were associated with impaired fetal growth that was substantially improved by nutrition intervention, especially when commenced prior to conception.
Using AST-platelet ratio index and fibrosis 4 index for detecting chronic hepatitis C in a large-scale community screening

Background Aspartate transaminase-platelet ratio index (APRI) and fibrosis 4 (FIB-4) are two non-invasive indexes to predict liver fibrosis in liver disease. This study was to use APRI and FIB-4 to detect chronic virus hepatitis in community screenings. Methods From 2004 to 2013, a series of community-based health screenings for residents aged 40 and older were held in Tainan city. APRI and FIB-4 of each participant were calculated and their association further analyzed with hepatitis status. Results We enrolled 180359 participants including 18726 (10.4%) hepatitis B virus (HBV), 13428 (7.4%) hepatitis C virus (HCV), 1337 (0.7%) HBV plus HCV and 146868 (81.5%) Non-HBV Non-HCV. The prevalence of chronic HCV increased with the elevation of APRI cut-offs or FIB-4 cut-offs (13.9%, 28.1%, 38.8%, 45.2%, to 49.9% in APRI≥0.3, 0.5, 0.7, 0.9,1.1, p<0.001 for the linear trend; or 15.8%, 26.4%, 34.4% to 39.7% in FIB-4≥1.75, 2.75, 3.5, 4.25, p<0.001). At the township level, APRI≥ 0.7 and FIB-4≥ 3.5 were highly correlated with HCV infection (r = 0.95, p<0.001 in APRI and r = 0.809, p<0.001 in FIB-4) and hepatocellular carcinoma (HCC) development (r = 0.894, p<0.001 in APRI and r = 0.804, p<0.001 in FIB-4), but not correlated with HBV infection. Conclusions Community screenings derived APRI or FIB-4 can identify patient subsets with increased of underlying HCV infection and risk of incident HCC.
How information about perpetrators’ nature and nurture influences assessments of their character, mental states, and deserved punishment

Evidence of perpetrators’ biological or situational circumstances has been increasingly brought to bear in courtrooms. Yet, research findings are mixed as to whether this information influences folk evaluations of perpetrators’ dispositions, and subsequently, evaluations of their deserved punishments. Previous research has not clearly dissociated the effects of information about perpetrators’ genetic endowment versus their environmental circumstances. Additionally, most research has focused exclusively on violations involving extreme physical harm, often using mock capital sentences cases as examples. To address these gaps in the literature, we employed a “switched-at-birth” paradigm to investigate whether positive or negative information about perpetrators’ genetic or environmental backgrounds influence evaluations of a perpetrator’s mental states, character, and deserved punishment. Across three studies, we varied whether the transgression involved direct harm, an impure act that caused no harm, or a case of moral luck. The results indicate that negative genetic and environmental backgrounds influenced participants’ evaluations of perpetrators’ intentions, free will, and character, but did not influence participants’ punishment decisions. Overall, these results replicate and extend existing findings suggesting that perpetrators’ supposed extenuating circumstances may not mitigate the punishment that others assign to them.
Analysis of determinants for in vitro resistance to the small molecule deubiquitinase inhibitor b-AP15

Background b-AP15/VLX1570 are small molecule inhibitors of the ubiquitin specific peptidase 14 (USP14) and ubiquitin carboxyl-terminal hydrolase 5 (UCHL5) deubiquitinases (DUBs) of the 19S proteasome. b-AP15/VLX1570 have been shown to be cytotoxic to cells resistant to bortezomib, raising the possibility that this class of drugs can be used as a second-line therapy for treatment-resistant multiple myeloma. Limited information is available with regard to potential resistance mechanisms to b-AP15/VLX1570. Results We found that b-AP15-induced cell death is cell-cycle dependent and that non-cycling tumor cells may evade b-AP15-induced cell death. Such non-cycling cells may re-enter the proliferative state to form colonies of drug-sensitive cells. Long-term selection of cells with b-AP15 resulted in limited drug resistance (~2-fold) that could be reversed by buthionine sulphoximine, implying altered glutathione (GSH) metabolism as a resistance mechanism. In contrast, drug uptake and overexpression of drug efflux transporters were found not to be associated with b-AP15 resistance. Conclusions The proteasome DUB inhibitors b-AP15/VLX1570 are cell cycle-active. The slow and incomplete development of resistance towards these compounds is an attractive feature in view of future clinical use.
Anticancer effect of zinc oxide nanoparticles prepared by varying entry time of ion carriers against A431 skin cancer cells in vitro

Although, zinc oxide nanoparticles (ZRTs) as an anti-cancer agent have been the subject of numerous studies, none of the reports has investigated the impact of the reaction entry time of ion-carriers on the preparation of ZRTs. Therefore, we synthesized variants of ZRTs by extending the entry time of NaOH (that acts as a carrier of hydroxyl ions) in the reaction mixture. The anti-proliferative action, morphological changes, reactive oxygen species (ROS) production, and nuclear apoptosis of ZRTs on human A431 skin carcinoma cells were observed. The samples revealed crystallinity and purity by X-ray diffraction (XRD). Scanning electron microscopy (SEM) images of ZRT-1 (5 min ion carrier entry) and ZRT-2 (10 min ion carrier entry) revealed microtubule like morphology. On prolonging the entry time for ion carrier (NaOH) introduction in the reaction mixture, a relative ascent in the aspect ratio was seen. The typical ZnO band with a slight shift in the absorption maxima was evident with UV-visible spectroscopy. Both ZRT-1 and ZRT-2 exhibited non-toxic behavior as evident by RBC lysis assay. Additionally, ZRT-2 showed better anti-cancer potential against A431 cells as seen by MTT assay, ROS generation and chromatin condensation analyses. At 25 μM of ZRT-2, 5.56% cells were viable in MTT test, ROS production was enhanced to 166.71%, while 33.0% of apoptotic cells were observed. The IC50 for ZRT-2 was slightly lower (6 μM) than that for ZRT-1 (8 μM) against A431 cells. In conclusion, this paper presents a modest, economical procedure to generate ZRT nano-structures exhibiting strong cytotoxicity against the A431 cell line, indicating that ZRTs may have application in combating cancer.
Uso y percepciones hacia las tecnologías de información y comunicación en pacientes con diabetes, en un hospital público del Perú

Diabetes is a global health problem with a growing number of individuals with diabetes mellitus in the world. Information and communication technologies (ICT) could play an important role in this group of patients. Objective. To report the use and perceptions regarding ICT in patients with diabetes. Material and methods. During August 2008, previously validated surveys were applied to patients with diabetes attending a national hospital in Peru. Results. Two hundred patients with diabetes were surveyed (median: 60 years old, 78.5% women). Most of them never used a computer (89.5%), E-mail (90%), Internet (92%), or chat (91.5%). Most of the participants (91.5%) never sought health information on the Internet. forty nine percent of participants make and/or receive calls using cell phones at least once a week. However, most of them (84.5% and 67%) never have sent or received text messages, respectively. Almost all of participants would like to receive information about diabetes care. Most of them (70.5% and 61.5%) expressed their interest to participate in a program to support their diabetes using cell phones and the Internet, respectively. Conclusions. Besides use of ICT was relatively low, the perception towards a system or a program using cell phones or the Internet for diabetes support is positive. It is necessary to further explore the reasons why patients do not use cell phones and/or the Internet, and to evaluate the feasibility of ICT interventions for better diabetes care.