Miracle-dz/UniFAR-FTUs huggingface dataset:
The ratio of preoperative alpha-fetoprotein level to total tumor volume as a prognostic factor of hepatocellular carcinoma after liver transplantation

Abstract To evaluate the effect of preoperative serum alpha-fetoprotein(AFP) level to total tumor volume (TTV) ratio as a prognostic marker on predicting the tumor recurrence and overall survival time of patients with hepatocellular carcinoma (HCC) after liver transplantation. One-hundred eight patients with HCC who underwent liver transplantation in Beijing Chaoyang Hospital from April 2013 to October 2017 were studied. Divided into AFP/TTV≤2 group and AFP/TTV>2 group by the best cut-off score calculated by receiver operation characteristic curve, the clinical and pathological data of the patients in two groups were compared to explore the relationship between AFP/TTV and tumor recurrence together with the prognosis of HCC patients after liver transplantation. Risk factors of early tumor recurrence and poor prognosis of HCC in patients after liver transplantation were studied by multivariate regression analysis. Kaplan-Meier survival analysis was used to compare the tumor-free survival and overall survival between the two groups of patients. In 108 patients, 47 patients have AFP/TTV≤2 while 61 patients have AFP/TTV>2. Patients in AFP/TTV≤2 group have longer tumor-free survival time and overall survival time compared with patients in AFP/TTV>2 group. The age, total bilirubin level, serum AFP level, TTV, portal vein tumor thrombus and AFP/TTV (all P < .05) of patient with HCC are closely related to poor prognosis after liver transplantation. Multivariate regression analysis showed that have portal vein tumor thrombus (hazard ratio [HR] = 2.345, P < .05), TTV≥65.5 cm3 (HR = 2.701, P < .05) and AFP/TTV > 2 (HR = 4.624, P < .05) are independent risk factors for poor prognosis of patients with HCC after liver transplantation while TTV≥65.5 cm3 (HR = 2.451, P < .05) and AFP/TTV > 2 (HR = 4.257, P < 0.05) were independent risk factors for tumor recurrence at the same time. The tumor recurrence and the prognosis of patients with HCC after liver transplantation is affected by many factors. AFP/TTV ratio has important predictive value for the tumor recurrence and the prognosis of patients with HCC after liver transplantation. AFP/TTV>2 is an independent risk factor for both early tumor recurrence and poor prognosis of patients with HCC after liver transplantation.
A phase Ib/IIa clinical trial of dantrolene sodium in patients with Wolfram syndrome

BACKGROUND Wolfram syndrome is a rare ER disorder characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, and progressive neurodegeneration. Although there is no treatment for Wolfram syndrome, preclinical studies in cell and rodent models suggest that therapeutic strategies targeting ER calcium homeostasis, including dantrolene sodium, may be beneficial. METHODS Based on results from preclinical studies on dantrolene sodium and ongoing longitudinal studies, we assembled what we believe is the first-ever clinical trial in pediatric and adult Wolfram syndrome patients with an open-label phase Ib/IIa trial design. The primary objective was to assess the safety and tolerability of dantrolene sodium in adult and pediatric Wolfram syndrome patients. Secondary objectives were to evaluate the efficacy of dantrolene sodium on residual pancreatic β cell functions, visual acuity, quality-of-life measures related to vision, and neurological functions. RESULTS Dantrolene sodium was well tolerated by Wolfram syndrome patients. Overall, β cell functions were not significantly improved, but there was a significant correlation between baseline β cell functions and change in β cell responsiveness (R2, P = 0.004) after 6-month dantrolene therapy. Visual acuity and neurological functions were not improved by 6-month dantrolene sodium. Markers of inflammatory cytokines and oxidative stress, such as IFN-γ, IL-1β, TNF-α, and isoprostane, were elevated in subjects. CONCLUSION This study justifies further investigation into using dantrolene sodium and other small molecules targeting the ER for treatment of Wolfram syndrome. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT02829268 FUNDING NIH/National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (DK112921, DK113487, DK020579), NIH/National Center for Advancing Translational Sciences (NCATS) (TR002065, TR000448), NIH training grant (F30DK111070), Silberman Fund, Ellie White Foundation, Snow Foundation, Unravel Wolfram Syndrome Fund, Stowe Fund, Eye Hope Foundation, Feiock Fund, Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from NIH/NCATS, Bursky Center for Human Immunology & Immunotherapy Programs.
Making the Call: College Students’ Legal Consciousness and Hypothetical Activation of Police for Sexual Assaults

Research has identified the necessity of sexual assault victims to label their experience as criminal to initiate reporting. However, barriers exist in labeling uninvited sexual contact as criminal. This study examined college students’ assessments of whether eight nonconsensual behaviors met the legal definition of sexual assault, and whether such behaviors should be reported to police. Results indicated students acknowledged the nonconsensual behaviors as criminal; however, gaps were identified between awareness that the acts were criminal and willingness to report to police. Findings demonstrate a need for continued efforts for sexual assault prevention among college students.
Activation of the hypothalamic–pituitary–adrenal axis by exogenous and endogenous GDF15

Significance GDF15, a hormone produced by a wide variety of cells undergoing different types of stress, acts on a receptor in the brain where it transmits signals that are perceived by the organism as aversive. We now report an action of GDF15, whereby it activates the endocrine stress response and increases circulating levels of the principal glucocorticoid (a “stress” steroid). By studying mice genetically deficient in GDF15, we also demonstrate that GDF15 is a key signal through which damage due to toxic chemicals activates the steroid stress response. GDF15 is currently being explored as an antiobesity drug and examination of the degree and duration of the steroid effect will need to be incorporated into any human trials. An acute increase in the circulating concentration of glucocorticoid hormones is essential for the survival of severe somatic stresses. Circulating concentrations of GDF15, a hormone that acts in the brain to reduce food intake, are frequently elevated in stressful states. We now report that GDF15 potently activates the hypothalamic–pituitary–adrenal (HPA) axis in mice and rats. A blocking antibody to the GDNF-family receptor α-like receptor completely prevented the corticosterone response to GDF15 administration. In wild-type mice exposed to a range of stressful stimuli, circulating levels of both corticosterone and GDF15 rose acutely. In the case of Escherichia coli or lipopolysaccharide injections, the vigorous proinflammatory cytokine response elicited was sufficient to produce a near-maximal HPA response, regardless of the presence or absence of GDF15. In contrast, the activation of the HPA axis seen in wild-type mice in response to the administration of genotoxic or endoplasmic reticulum toxins, which do not provoke a marked rise in cytokines, was absent in Gdf15−/− mice. In conclusion, consistent with its proposed role as a sentinel hormone, endogenous GDF15 is required for the activation of the protective HPA response to toxins that do not induce a substantial cytokine response. In the context of efforts to develop GDF15 as an antiobesity therapeutic, these findings identify a biomarker of target engagement and a previously unrecognized pharmacodynamic effect, which will require monitoring in human studies.
Youth-friendly HIV self-testing: Acceptability of campus-based oral HIV self-testing among young adult students in Zimbabwe

Background Targeted HIV testing strategies are needed to reach remaining undiagnosed people living with HIV and achieve the UNAIDS’ 95-95-95 goals for 2030. HIV self-testing (HIVST) can increase uptake of HIV testing among young people, but user perspectives on novel distribution methods are uncertain. We assess the acceptability, perceived challenges, and recommendations of young adult lay counselor-led campus-based HIVST delivery among tertiary school students aged 18–24 years in Zimbabwe. Methods We purposively sampled participants from an intervention involving campus-based HIVST using lay workers for distribution. We conducted in-depth interviews (IDIs) and focus group discussions (FGDs) among young adults from 10 universities and colleges in Zimbabwe who: (1) self-tested on campus; (2) self-tested off campus; and (3) opted not to self-test. We audio recorded and transcribed all interviews. Using applied thematic analysis, two investigators identified emergent themes and independently coded transcripts, achieving high inter-coder agreement. Results Of the 52 young adults (53.8% male, 46.1% female) interviewed through 26 IDIs and four FGDs, most IDI participants (19/26, 73%) favored campus-based HIVST, describing it as a more autonomous, convenient, and socially acceptable experience than other facility or community-based HIV testing services. Despite general acceptability, participants identified challenges with this delivery model, including: perceived social coercion, insufficient privacy and access to post-test counseling. These challenges influenced some participants to opt against self-testing (6/52, 11.5%). Recommendations for improved implementation included integrating secondary distribution of test kits and increased HIV counseling options into campus-based programs. Conclusions Barriers to HIV testing among young people are numerous and complex. As the number of new HIV infections among youth continue to grow worldwide, targeted strategies and youth friendly approaches that increase access to testing are needed to close the diagnostic coverage gap. This is the first study to describe young adult acceptance of campus-based delivery of HIVST by lay counselors in Zimbabwe.
Large-scale quantification of human osteocyte lacunar morphological biomarkers as assessed by ultra-high-resolution desktop micro-computed tomography

Ultra-high-resolution imaging of the osteocyte lacuno-canalicular network (LCN) three-dimensionally (3D) in a high-throughput fashion has greatly improved the morphological knowledge about the constituent structures – positioning them as potential biomarkers. Technologies such as serial focused ion beam/scanning electron microscopy (FIB/SEM) and confocal scanning laser microscopy (CLSM) can image in extremely high resolution, yet only capture a small number of lacunae. Synchrotron radiation computed tomography (SR-CT) can image with both high resolution and high throughput but has a limited availability. Desktop micro-computed tomography (micro-CT) provides an attractive balance: high-throughput imaging on the micron level without the restrictions of SR-CT availability. Over the past decade, desktop micro-CT has been used to image osteocyte lacunae in a variety of animals, yet few studies have employed it to image human lacunae using clinical biopsies. In this study, accuracy, reproducibility, and sensitivity of large-scale quantification of human osteocyte lacunar morphometries were assessed by ultra-high-resolution desktop micro-computed tomography. For this purpose, thirty-one transiliac human bone biopsies containing trabecular and cortical regions were imaged using ultra-high-resolution desktop micro-CT at a nominal isotropic voxel resolution of 1. 2μm. The resulting 3D images were segmented, component labeled, and the following morphometric parameters of 7.71 million lacunae were measured: Lacunar number (Lc.N), density (Lc.N/BV), porosity (Lc.TV/BV), volume (Lc.V), surface area (Lc.S), surface area to volume ratio (Lc.S/Lc.V), stretch (Lc.St), oblateness (Lc.Ob), sphericity (Lc.Sr), equancy (Lc.Eq), and angle (Lc.θ). Accuracy was quantified by comparing automated lacunar identification to manual identification. Mean true positive rate (TPR), false positive rate (FPR), and false negative rate (FNR) were 89.0%, 3.4%, and 11.0%, respectively. Regarding the reproducibility of lacunar morphometry from repeated measurements, precision errors were low (0.2 – 3.0%) and intraclass correlation coefficients were high (0.960 – 0.999). Significant differences between cortical and trabecular regions (p<0.001) existed for Lc.N/BV, Lc.TV/BV, local lacunar surface area (), and local lacunar volume (), all of which demonstrate the sensitivity of the method and are possible biomarker candidates. This study provides the foundation required for future large-scale morphometric studies using ultra-high-resolution desktop micro-CT and high-throughput analysis of millions of osteocyte lacunae in human bone samples. Furthermore, the validation of this technology for imaging of human lacunar properties establishes the quality and reliability required for the accurate, precise, and sensitive assessment of osteocyte morphometry in clinical bone biopsies.
Wild meat trade over the last 45 years in the Peruvian Amazon

The trade in wild meat is an important economic component of rural people's livelihoods, but it has been perceived to be among the main causes of the decline of wildlife species. Recently, the COVID‐19 pandemic has brought to light an additional concern of wildlife markets as a major human‐health challenge. We analyzed data from the largest longitudinal monitoring (1973–2018) of the most important urban wild‐meat markets in Iquitos, Peru, to examine the trends in and impacts of these markets on people's livelihoods. Over the last 45 years, wild meat sales increased at a rate of 6.4 t/year (SD 2.17), paralleling urban population growth. Wild meat sales were highest in 2018 (442 t), contributing US$2.6 million (0.76%) to the regional gross domestic product. Five species of ungulates and rodents accounted for 88.5% of the amount of biomass traded. Vulnerable and Endangered species represented 7.0% and 0.4% of individuals sold, respectively. Despite growth in sales, the contribution of wild meat to overall urban diet was constant: 1–2%/year of total meat consumed. This result was due to greater availability and higher consumption of cheaper meats (e.g., in 2018, poultry was 45.8% cheaper and was the most consumed meat) coupled with the lack of economic incentives to harvest wild meat species in rural areas. Most wild meat was sold salted or smoked, reducing the likelihood of foodborne diseases. Community‐based wildlife management plans and the continued trade bans on primates and threatened taxa may avoid biodiversity loss. Considering the recent COVID‐19 pandemic, future management plans should include potential viral hosts and regulation and enforcement of hygiene practices in wild‐meat markets.
Deletion of adipose triglyceride lipase abolishes blood flow increase after β3-adrenergic stimulation in visceral adipose tissue of mice

Dynamic changes in adipose tissue blood flow (ATBF) with nutritional status play a role in the regulation of metabolic and endocrine functions. Activation of the sympathetic nervous system via β-adrenergic receptors (β-AR) contributes to the control of postprandial enhancement of ATBF. Herein, we sought to identify the role of each β-AR subtype in the regulation of ATBF in mice. We monitored the changes in visceral epididymal ATBF (VAT BF), induced by local infusion of dobutamine, salbutamol, and CL316,243 (a selective β1-, β2-, and β3-AR agonist, respectively) into VAT of lean CD-1 mice and global adipose triglyceride lipase (ATGL) knockout (KO) mice, using laser Doppler flowmetry. Administration of CL316,243, known to promote lipolysis in adipocytes, significantly increased VAT BF of CD-1 mice to a greater extent compared to that of the vehicle, whereas administration of dobutamine or salbutamol did not produce significant differences in VAT BF. The increase in VAT BF induced by β3-AR stimulation disappeared in ATGL KO mice as opposed to their wild-type (WT) littermates, implying a role of ATGL-mediated lipolysis in the regulation of VAT BF. Different vascular reactivities occurred despite no significant differences in vessel density and adiposity between the groups. Additionally, the expression levels of the angiogenesis-related genes were significantly higher in VAT of ATGL KO mice than in that of WT, implicating an association of ATBF responsiveness with angiogenic activity in VAT. Our findings suggest a potential role of β3-AR signaling in the regulation of VAT BF via ATGL-mediated lipolysis in mice.
Emotion regulation and peripheral psychophysiological correlates in the management of induced pain: A systematic review

Cognitive reappraisal and acceptance strategies have been shown to be effective in reducing pain experience and increasing pain tolerance. However, no systematic reviews have focused on the relationship between the use of these two strategies and peripheral physiological correlates when pain is experimentally induced. This systematic review aims to summarize the existing literature that explores the relationship between emotion regulation strategies (i.e., cognitive reappraisal and acceptance) and peripheral correlates of the autonomic nervous system and facial electromyography, such as affect-modulated responses and corrugator activity, on laboratory tasks where pain is induced. The systematic review identifies nine experimental studies that meet our inclusion criteria, none of which compare these strategies. Although cognitive reappraisal and acceptance strategies appear to be associated with decreased psychological responses, mixed results were found for the effects of the use of both strategies on all the physiological correlates. These inconsistencies between the studies might be explained by the high methodological heterogeneity in the task designs, as well as a lack of consistency between the instructions used in the different studies for cognitive reappraisal, acceptance, and the control conditions.
Warning system improve the clinical outcomes in transfer patients with ST-segment elevation myocardial infarction

Abstract A warning system included directly faxing electrocardiography information to the mobile phone immediately after an ST-segment elevation myocardial infarction (STEMI) diagnosis was made at a non-percutaneous coronary intervention (PCI) capable hospital. This study aimed to explore the outcomes after using a warning system in transfer STEMI patients. From October 2013 to December 2016, 667 patients experienced a STEMI event and received primary PCI at our institution. 274 patients who were divided into transfer group were transferred from non-PCI capable hospitals and connected to a first-line cardiovascular doctor by the warning system. Other 393 patients were divided into the non-transfer group. The transfer group still had a longer pain-to-reperfusion time and presented higher troponin-I level when compared with non-transfer group. There was no significant difference in the use of drug-eluting stent and procedural devices between non-transfer and transfer groups. The prevalence of different anti-platelet agents loading did not differ between non-transfer and transfer groups. Non-significant trend about higher prevalence of statin use was noted in transfer group (78.9% vs 86.1%, P = .058). The transfer group presented similar clinical short-term results regarding both cardiovascular and all-cause mortality when comparing with non-transfer group. The transfer group provided non-significant trend about lower one-year cardiovascular mortality (10.7% vs 6.2%, P = .052) and lower all-cause mortality (12.2% vs 6.9%, P = .026) when compared with non-transfer group. There was a significant difference in the Kaplan–Meier curve of 1-year cardiovascular mortality between the transfer group and the non-transfer group (P = .049). After using the warning system, the inter-facility transfer group had comparable outcomes even though a longer pain-to-reperfusion time and a higher peak troponin-I level when comparing with non-transfer group.
New species and records of Caulleriella (Annelida, Cirratulidae) from shelf and slope depths of the Western North Atlantic Ocean.

Six species of Caulleriella (Cirratulidae), four new to science, are reported from continental shelf and slope depths of the western North Atlantic. The majority of new material was collected as part of deep-water reconnaissance and monitoring surveys along the U.S. Atlantic coast from New England to the Carolinas that were intended to understand the potential impacts of oil and gas exploration in poorly known offshore environments. Additional materials from shallow water and shelf habitats off New England and New York as part of other projects are also included. New species include: Caulleriella filiformia n. sp. , C. nobska n. sp. , C. pintada n. sp. , and C. rodmani n. sp. In addition, new records and comments are provided for C. venefica Doner Blake, 2016 a widespread shelf species and C. sp. , a potential new species represented by a few specimens from rocky nearshore New England habitats. The latter may be related to the enigmatic C. fragilis (Leidy, 1855). A review of known deep-water species of Caulleriella is provided.
Efficacy of B12 Fortified Nutrient Bar and Yogurt in Improving Plasma B12 Concentrations—Results From 2 Double-Blind Randomized Placebo Controlled Trials

Background: Dietary vitamin B12 (B12) deficiency is common in Indians. Long-term compliance to tablet supplementation is poor in asymptomatic individuals. Objective: To study efficacy of B12 fortified nutrient bar and yogurt in improving plasma B12 concentrations in children and adults. Methods: Two double-blind, placebo-controlled directly observed therapy randomized controlled trials were conducted for 120 days: (1) Healthy children (10-13 years) were fed nutrient bar fortified with B12 (2 μg), multiple micronutrients B12 (1.8 μg) or placebo. (2) Healthy adults (18-50 years) were fed yogurt fortified with B12 (2 μg) or Propionibacterium (1 × 108 cfu/g) or placebo. B12, folate, homocysteine, and hemoglobin concentrations were measured before and post intervention. Results: We randomized 164 children and 118 adults; adherence was 96% and 82%, respectively. In children, B12 fortified bars increased B12 concentrations significantly above baseline (B12 alone +91 pmol/L, B12+ multiple micronutrients +82 pmol/L) compared to placebo. In adults, B12 fortified yogurt increased B12 significantly (+38 pmol/L) but Propionibacterium and placebo did not. In both trials, homocysteine fell significantly with B12 supplementation. Rise of B12 and fall of homocysteine were influenced by dose of B12 and folic acid. There was no significant difference in change of anthropometry and hemoglobin between groups. Conclusions: B12 fortified foods are effective in improving B12 status in Indian children and adults. They could be used to improve B12 status in the national programs for children, adolescents, and women of reproductive age. They could also be used as over-the-counter products.