Miracle-dz/UniFAR-FTUs huggingface dataset:
Bystander T-Cells Support Clonal T-Cell Activation by Controlling the Release of Dendritic Cell-Derived Immune-Stimulatory Extracellular Vesicles

Extracellular vesicles (EV) that are released by immune cells are studied intensively for their functions in immune regulation and are scrutinized for their potential in human immunotherapy, for example against cancer. In our search for signals that stimulate the release of functional EV by dendritic cells we observed that LPS-activated human monocyte-derived dendritic cells (moDC) changed their morphological characteristics upon contact with non-cognate activated bystander T-cells, while non-activated bystander T-cells had no effect. Exposure to activated bystander T-cells also stimulated the release of EV-associated proteins by moDC, particularly CD63, and ICAM-1, although the extent of stimulation varied between individual donors. Stimulation of moDC with activated bystander T-cells also increased the release of EV-associated miR155, which is a known central modulator of T-cell responses. Functionally, we observed that EV from moDC that were licensed by activated bystander T-cells exhibited a capacity for antigen-specific T-cell activation. Taken together, these results suggest that non-cognatei interactions between DC and bystander T-cells modulates third party antigen-specific T-cell responses via EV.
Analysis of the cost-effectiveness of treatment strategies for CML with incorporation of treatment discontinuation.

The cost of tyrosine kinase inhibitors (TKIs) in the treatment of chronic myeloid leukemia (CML) is a substantial economic burden. In Japan, imatinib, dasatinib, and nilotinib are now approved as first-line treatment of CML in chronic phase. Recent "stop TKI" trials have shown that TKIs can be safely discontinued in nearly one-half of patients with sustained deep molecular response (DMR). In this study, we analyzed the cost-effectiveness of a simulated 10 years of CML treatment including stop TKI in both the United States and Japan. We constructed Markov models to compare 4 strategies in which treatment was initiated with imatinib, dasatinib, nilotinib, or any of these TKIs at the physician's discretion. Treatment was switched to another TKI in the case of intolerance or resistance to the initial TKI, and TKIs were discontinued if DMR persisted for 2 years. "Imatinib first" offered 7.34 quality-adjusted life years (QALYs) at the cost of $1 022 148 in the United States (US dollars) and ¥32 526 785 in Japan (Japanese yen). In comparison with imatinib first, the incremental cost-effectiveness ratio per QALY of "dasatinib first" (7.68 QALY, $1 236 052, ¥51 506 254), "nilotinib first" (7.64 QALY, $1 245 667, ¥39 635 598), and "physician's choice" (7.55 QALY, $1 167 818, ¥41 187 740) was $641 324, $696 717, and $666 634 in the United States and ¥54 456 325, ¥23 154 465, and ¥39 635 615 in Japan, respectively. None of the 3 strategies met the willingness-to-pay threshold. The results were robust to univariate and multivariate sensitivity analyses. Imatinib first was shown to be the most cost-effective approach even with the incorporation of stop TKI.
Interventions for Attitudes and Empathy Toward People With Dementia and Positive Aspects of Caregiving: A Systematic Review and Meta-Analysis

Objective: This systematic review and meta-analysis of randomized controlled trials (RCTs) examined the effect of interventions on three outcomes among caregivers of people with dementia and health professionals, including positive aspects of caregiving, attitudes toward people with dementia, and empathy. Methods: Three electronic databases were searched to find RCTs published in peer-reviewed journals until January 7, 2019. A total of 13 studies met the eligibility criteria and were included in meta-analysis. Results: The included studies compared psychoeducational interventions, a combination of education, skill-building, and coping strategies, to control group. Meta-analyses of the included studies found that the overall effects of psychoeducational interventions on three outcomes were not statistically significant compared to control groups. Conclusions: The findings indicate that there is no evidence for the positive effect of psychoeducational interventions on these outcomes, warranting further RCT studies designed to target on these outcomes.
Medium Chain Triglyceride (MCT) Oil Affects the Immunophenotype via Reprogramming of Mitochondrial Respiration in Murine Macrophages

Medium chain triglyceride (MCT) oil has been postulated to modulate inflammatory responses, but the detailed mechanisms have not been fully elucidated. Based on recent studies demonstrating that mitochondrial metabolic reprogramming and immune responses are correlated, the current study sought to determine whether MCT oil controls inflammatory responses through modulation of mitochondria using both in vitro and in vivo models. The mitochondrial metabolic phenotypes of macrophages were assessed according to oxygen consumption rate (OCR). Inflammatory responses were assessed for production of cytokines and expression of activation markers. MCT oil was more rapidly oxidized as observed by increased OCR in macrophages. The production of pro-inflammatory cytokines was down-regulated and anti-inflammatory cytokine was elevated by MCT oil. In addition, classically activated M1 and alternatively activated M2 markers were reciprocally regulated by MCT intervention. Overall, up-regulated β-oxidation by MCT contributes to the anti-inflammatory M2-like status of macrophages, which may aid in the dietary prevention and/or amelioration of inflammation.
Analysis of Graphene Antenna Properties for 5G Applications

The incoming 5G technology requires antennas with a greater capacity, wider wireless spectrum utilisation, high gain, and steer-ability. This is due to the cramped spectrum utilisation in the previous generation. As a matter of fact, conventional antennas are unable to serve the new frequency due to the limitations in fabrication and installation mainly for smaller sizes. The use of graphene material promises antennas with smaller sizes and thinner dimensions, yet capable of emitting higher frequencies. Hence, graphene antennas were studied at a frequency of 15 GHz in both single and array elements. The high-frequency antenna contributed to a large bandwidth and was excited by coplanar waveguide for easy fabrication on one surface via screen printing. The defected ground structure was applied in an array element to improve the radiation and increase the gain. The results showed that the printed, single element graphene antenna produced an impedance bandwidth, gain, and efficiency of 48.64%, 2.87 dBi, and 67.44%, respectively. Meanwhile, the array element produced slightly better efficiency (72.98%), approximately the same impedance bandwidth as the single element (48.98%), but higher gain (8.41 dBi). Moreover, it provided a beam width of 21.2° with scanning beam capability from 0° up to 39.05°. Thus, it was proved that graphene materials can be applied in 5G.
Effects of bile on arterial anastomosis in a rat model

Objective: Liver transplantation has been one of the areas in which microvascular surgery is frequently practiced. With the use of microsurgical techniques in hepatic artery anastomosis, the incidence of hepatic artery thrombosis has been signifi- cantly reduced. Hepatic artery anastomosis is realized after the anastomoses of the hepatic vessel and portal vessel are completed, and clamps are removed; in other words, after hepatic circulation starts. During hepatic artery anastomosis, bile runs towards the hepatic artery anastomosis line. This study aimed to investigate effects of bile on arterial anastomosis. Materials and Methods: Forty male Sprague Dawley rats were randomly divided into 2 groups. Femoral artery anasto- mosis was performed in rats of the control group (n = 20) through heparinized serum (10 U/ml) irrigation. In the rats of the study group (n = 20), however, femoral artery anastomosis was performed through heparinized serum (10 U/ml)+0.5 cc bile irrigation. After the 1st week, anastomosis patency was evaluated with color duplex ultrasonography. A 1 cm segment of the femoral artery involving the anastomosis line was removed for histopathological evaluation. Results: In the control group, no flow to the distal was observed in one anastomosis. All the anastomoses in the study group were patent. Histopathologically, perivascular polymorphonuclear leucocyte infiltration was observed in the study group. No statistically significant differences were observed for endothelial continuity and intimal thickening, and no statisti- cally significant differences were observed for anastomosis patency. Conclusions: In the light of these findings, it was determined that bile contamination did not have any negative or positive effects on artery anastomosis.
Colorectal cancer-associated microbiota contributes to oncogenic epigenetic signatures

Significance This study advances our appreciation and understanding of the role of colon dysbiosis in the pathogenesis of colorectal cancer. In a human pilot study of 266 individuals, greater epigenomic (methylation) DNA alterations correlated with CRC and microbiota composition. Beyond this correlative evidence, when germ-free mice received fresh feces from CRC patients and their healthy controls, the former animals developed colon epithelial renewal, more precancerous lesions, and increased tissue and blood DNA methylation in intestinal tissues. Confirmation was obtained in a larger cohort of 1,000 patients, indicating that CRC-associated dysbiosis may promote colon carcinogenesis via epigenome dysregulation. Gene methylation can therefore serve as a marker for CRC and likely for predicting efficacy of prebiotic supplementation in average-risk individuals. Sporadic colorectal cancer (CRC) is a result of complex interactions between the host and its environment. Environmental stressors act by causing host cell DNA alterations implicated in the onset of cancer. Here we investigate the stressor ability of CRC-associated gut dysbiosis as causal agent of host DNA alterations. The epigenetic nature of these alterations was investigated in humans and in mice. Germ-free mice receiving fecal samples from subjects with normal colonoscopy or from CRC patients were monitored for 7 or 14 wk. Aberrant crypt foci, luminal microbiota, and DNA alterations (colonic exome sequencing and methylation patterns) were monitored following human feces transfer. CRC-associated microbiota induced higher numbers of hypermethylated genes in murine colonic mucosa (vs. healthy controls’ microbiota recipients). Several gene promoters including SFRP1,2,3, PENK, NPY, ALX4, SEPT9, and WIF1 promoters were found hypermethylated in CRC but not in normal tissues or effluents from fecal donors. In a pilot study (n = 266), the blood methylation levels of 3 genes (Wif1, PENK, and NPY) were shown closely associated with CRC dysbiosis. In a validation study (n = 1,000), the cumulative methylation index (CMI) of these genes was significantly higher in CRCs than in controls. Further, CMI appeared as an independent risk factor for CRC diagnosis as shown by multivariate analysis that included fecal immunochemical blood test. Consequently, fecal bacterial species in individuals with higher CMI in blood were identified by whole metagenomic analysis. Thus, CRC-related dysbiosis induces methylation of host genes, and corresponding CMIs together with associated bacteria are potential biomarkers for CRC.
Exposure to low-dose arsenic in early life alters innate immune function in children

Abstract Early-life exposure to arsenic (As) increases risks of respiratory diseases/infections in children. However, data on the ability of the innate immune system to combat bacterial infections in the respiratory tracts of As-exposed children are scarce. To evaluate whether persistent low-dose As exposure alters innate immune function among children younger than 5 years-of-age, mothers and participating children (N = 51) that were members of the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in rural Bangladesh were recruited. Household water As, past and concurrent maternal urinary As (U-As) as well as child U-As were all measured at enrollment. In addition, U-As metabolites were evaluated. Innate immune function was examined via measures of cathelicidin LL-37 in plasma, ex vivo monocyte-derived-macrophage (MDM)-mediated killing of Streptococcus pneumoniae (Spn), and serum bactericidal antibody (SBA) responses against Haemophilus influenzae type b (Hib). Cyto-/chemokines produced by isolated peripheral blood mononuclear cells (PBMC) were assayed using a Multiplex system. Multivariable linear regression analyses revealed that maternal (p < 0.01) and child (p = 0.02) U-As were positively associated with plasma LL-37 levels. Decreased MDM-mediated Spn killing (p = 0.05) and SBA responses (p = 0.02) were seen to be each associated with fractions of mono-methylarsonic acid (MMA; a U-As metabolite) in the children. In addition, U-As levels were seen to be negatively associated with PBMC formation of fractalkine and IL-7, and positively associated with that for IL-13, IL-17 and MIP-1α. These findings suggested that early-life As exposure may disrupt the innate host defense pathway in these children. It is possible that such disruptions may have health consequences later in life.
Gender disparity within academic Canadian urology.

INTRODUCTION Increasing female matriculation into medical school has shown an increase in women training in academic urology, but gender disparity still exists within this male-dominated field. This study aims to evaluate publication productivity and rank differences of Canadian female and male academic urologists. METHODS The Canadian Residency Matching Service (CaRMS) was used to compile a list of 12 Canadian accredited urology programs. Using each institution's website, faculty members' names, genders, academic positions, and leadership ranks were noted. SCOPUS© was consulted to tabulate the number of documents published, citations, and h-index of each faculty member. To account for temporal bias associated with the h-index, the m-quotient was also computed. RESULTS There was a significantly higher number of men (164, 88.17%) among academic faculty than women (22, 11.83%). As academic rank increased, the proportion of female urologists decreased. Overall, male urologists had higher academic ranks, h-index values, number of publications, and citations (p=0.038, p=0.0038, p=0.0011, and p=0.014, respectively). There was an insignificant difference between men and women with respect to their m-quotient medians (p=0.25). CONCLUSIONS There is an increasing number of women completing residency in urology, although there are disproportionally fewer female urologists at senior academic positions. Significant differences were found in the h-index, publication count, and citation number between male and female urologists. When using the m-quotient to adjust for temporal bias, no significant differences were found between the gender in terms of academic output.
A prognostic five long–noncoding RNA signature for patients with rectal cancer

This study aimed to identify prognostic long noncoding RNAs (lncRNAs) signature for predicting the prognosis of patients with rectal cancer. LncRNA‐sequencing data and clinicopathological data of patients with rectal cancer were retrieved from The Cancer Genome Atlas database. Univariate and multivariate Cox proportional hazards regression analysis, the least absolute shrinkage, and selection operator analysis and the Kaplan‐Meier curve method were employed to identify prognostic lncRNAs and construct multi‐lncRNA signature. Finally, five lncRNAs (AC079789.1, AC106900.2, AL121987.1, AP004609.1, and LINC02163) were identified to construct a five‐lncRNA signature. According to the five‐lncRNA signature, patients with rectal cancer were divided into a high‐risk group and low‐risk group. Patients with rectal cancer had significantly poorer overall survival in the high‐risk group than in the low‐risk group. We used a time‐dependent receiver operating characteristic curve to assess the power of the five‐lncRNA signature by calculating the area under the curve (AUC). The AUCs for predicting 3‐year survival and 5‐year survival were 0.742 and 0.935, respectively, which indicated a good performance of the five‐lncRNA signature. The five‐lncRNA signature was independently associated with the prognosis of patients with rectal cancer through using univariate and multivariate Cox regression analysis. The biological function of the five lncRNAs was enriched in some cancer‐related biological processes and pathways by performing functional enrichment analysis of their correlated protein‐coding genes. In conclusion, we developed a five‐lncRNA signature as a potential indicator for rectal cancer.
Adipose tissue NAD+ biosynthesis is required for regulating adaptive thermogenesis and whole-body energy homeostasis in mice

Significance Thermogenesis is a fundamental aspect of energy homeostasis. Here, we present evidence that adipose tissue NAD+ metabolism is essential for thermogenesis. We found cold exposure activates NAD+ biosynthesis mediated by a rate-limiting enzyme, NAMPT, in mouse and human brown adipose tissue (BAT). Loss of NAMPT impairs the gene programs involved in thermogenesis and mitochondrial function in BAT. Mice lacking NAMPT in both BAT and white adipose tissue (WAT) but not in BAT alone have impaired thermogenic responses to cold exposure, fasting, and β-adrenergic stimulation. In WAT, NAMPT deletion decreases adrenergic-mediated lipolysis through inactivation of caveolin-1, which likely impairs whole-body thermogenesis. Nicotinamide mononucleotide administration normalized these metabolic derangements. These findings demonstrate the importance of adipose tissue NAD+ biology in energy metabolism. Nicotinamide adenine dinucleotide (NAD+) is a critical coenzyme for cellular energy metabolism. The aim of the present study was to determine the importance of brown and white adipose tissue (BAT and WAT) NAD+ metabolism in regulating whole-body thermogenesis and energy metabolism. Accordingly, we generated and analyzed adipocyte-specific nicotinamide phosphoribosyltransferase (Nampt) knockout (ANKO) and brown adipocyte-specific Nampt knockout (BANKO) mice because NAMPT is the rate-limiting NAD+ biosynthetic enzyme. We found ANKO mice, which lack NAMPT in both BAT and WAT, had impaired gene programs involved in thermogenesis and mitochondrial function in BAT and a blunted thermogenic (rectal temperature, BAT temperature, and whole-body oxygen consumption) response to acute cold exposure, prolonged fasting, and administration of β-adrenergic agonists (norepinephrine and CL-316243). In addition, the absence of NAMPT in WAT markedly reduced adrenergic-mediated lipolytic activity, likely through inactivation of the NAD+–SIRT1–caveolin-1 axis, which limits an important fuel source fatty acid for BAT thermogenesis. These metabolic abnormalities were rescued by treatment with nicotinamide mononucleotide (NMN), which bypasses the block in NAD+ synthesis induced by NAMPT deficiency. Although BANKO mice, which lack NAMPT in BAT only, had BAT cellular alterations similar to the ANKO mice, BANKO mice had normal thermogenic and lipolytic responses. We also found NAMPT expression in supraclavicular adipose tissue (where human BAT is localized) obtained from human subjects increased during cold exposure, suggesting our finding in rodents could apply to people. These results demonstrate that adipose NAMPT-mediated NAD+ biosynthesis is essential for regulating adaptive thermogenesis, lipolysis, and whole-body energy metabolism.
Response to: "Comments on Somatostatin as Inflow Modulator in Liver-Transplant Recipients With Severe Portal Hypertension: A Randomized Trial" by Shao et al.

Reply: We thank Shao et al for their comments on our trial. Their objections deserve indeed, clarifications. When the study was conceived, the only known hemodynamic properties of somatostatin were those on cirrhotic patients with portal hypertension. No data were available at that time on liver grafts during liver transplantation. Hence, the hemodynamic changes occurring with the native cirrhotic liver (M1) were chosen as endpoint to calculate the study sample size, including possible nonresponder recipients. The main conclu-
Impact of Wartime Stress Exposures and Mental Health on Later-Life Functioning and Disability in Vietnam-Era Women Veterans: Findings from The Health of Vietnam-Era Women's Study (HealthViEWS).

OBJECTIVES The effect of stress exposures and mental health sequelae on health-related outcomes is understudied among older women veterans. We examined (1) the impact of wartime stress exposures on later-life functioning and disability in Vietnam-era women veterans, and (2) the extent to which mental health conditions known to be associated with stress-posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and generalized anxiety disorder (GAD)-are associated with additional later-life functioning and disability. METHODS Data were collected in 2011-2012 using a mail survey and telephone interview of 4,219 women veterans who were active duty during the Vietnam Era. Health functioning was assessed using the Veterans RAND 36-Item Health Survey, and disability was assessed using the World Health Organization Disability Assessment Schedule 2.0. Wartime exposures were assessed using the Women's War-Zone Stressor Scale-revised; the Composite International Diagnostic Interview, version 3.0 was used to assess PTSD, MDD, and GAD. RESULTS Several wartime stress exposures-including job-related pressures, dealing with death, and sexual discrimination and harassment-were associated with worse later-life health (β ranges: -0.04 - -0.26 for functioning, 0.05 - 0.30 for disability). Current PTSD was linked with lower health functioning (physical: β = -0.06; mental: β = -0.15) and greater disability (β = -0.14). Current MDD and GAD were also associated with lower mental health functioning (MDD: β = -0.29; GAD; β = -0.10) and greater disability (MDD: β = 0.16; GAD; β = 0.06). CONCLUSIONS Results underscore the importance of detection and treatment for the potential long-term effects of wartime stressors and mental health conditions among women veterans.
Complications and Explantation Reasons in Intracorneal Ring Segments (ICRS) Implantation: A Systematic Review.

PURPOSE To review the intraoperative and postoperative complications after intracorneal ring segment implantation and to report the explantation rate among the available scientific literature. METHODS Three different databases (PubMed, Web of Science, and Scopus) were assessed from January 1995 to June 2019. The keywords used were: ring, rings, ICRS (intracorneal ring segments), segment, segments or Intacs, complication, explantation, explanted, retired, and removal. RESULTS The selection process of this systematic review study is described in a flow diagram. A total of 39 studies published between 1995 and 2019 were included. Sixteen studies were case reports, 21 were case series studies, and 2 were chart analysis works. This study enrolled 1,946 participants, and 2,590 eyes were included. The postoperative complications described in most studies included migration, ring extrusion, corneal thinning, corneal melting, and some type of infective keratitis. These complications together with glare, halos, fluctuating vision, neovascularization, foreign body sensation, or pain represented most of the causes. The percentage rate of explantation ranged from 0.5% up to 83.3%. If we analyze those articles with a high number of implantations (2,124 eyes), an explantation rate between 0% and 1.4% was obtained. CONCLUSIONS The complication rate and explantation ratio in segments of the intracorneal ring segments analyzed in the available scientific literature are minimal. Therefore, patient selection, surgery planning, and postoperative follow-up are critical to the success of surgery. [J Refract Surg. 2019;35(11):740-747. ].