Miracle-dz/UniFAR-FTUs huggingface dataset:
Isoform‐specific effects of transforming growth factor β on endothelial‐to‐mesenchymal transition

Endothelial‐to‐mesenchymal transition (EndMT) was first reported in the embryogenesis. Recent studies show that EndMT also occurs in the disease progression of atherosclerosis, cardiac and pulmonary fibrosis, pulmonary hypertension, diabetic nephropathy, and cancer. Although transforming growth factor β (TGFβ) is crucial for EndMT, it is not clear which isoform elicits a predominant effect. The current study aims to directly compare the dose‐dependent effects of TGFβ1, TGFβ2, and TGFβ3 on EndMT and characterize the underlying mechanisms. In our results, all three TGFβ isoforms induced EndMT in human microvascular endothelial cells after 72 hr, as evidenced by the increased expression of mesenchymal markers N‐cadherin and α‐smooth muscle actin as well as the decreased expression of endothelial nitric oxide synthase. Interestingly, the effect of TGFβ2 was the most pronounced. At 1 ng/ml, only TGFβ2 treatment resulted in significantly increased phosphorylation (activation) of Smad2/3 and p38‐MAPK and increased expression of mesenchymal transcription factors Snail and FoxC2. Intriguingly, we observed that treatment with 1 ng/ml TGFβ1 and TGFβ3, but not TGFβ2, resulted in an increased expression of TGFβ2, thus indicating that EndMT with TGFβ1 and TGFβ3 treatments was due to the secondary effects through TGFβ2 secretion. Furthermore, silencing TGFβ2 using small interfering RNA blunted the expression of EndMT markers in TGFβ1‐ and TGFβ3‐treated cells. Together, our results indicate that TGFβ2 is the most potent inducer of EndMT and that TGFβ1‐ and TGFβ3‐induced EndMT necessitates a paracrine loop involving TGFβ2.
DIACYLGLYCEROL ACYLTRANSFERASE and DIACYLGLYCEROL KINASE Modulate Triacylglycerol and Phosphatidic Acid Production in the Plant Response to Freezing Stress1

DGAT1 and DGK2/3/5 modulate the conversion of DAG to TAG and PA, respectively, and determine cold stress tolerance in Arabidopsis. Plants accumulate the lipids phosphatidic acid (PA), diacylglycerol (DAG), and triacylglycerol (TAG) during cold stress, but how plants balance the levels of these lipids to mediate cold responses remains unknown. The enzymes ACYL-COENZYME A:DIACYLGLYCEROL ACYLTRANSFERASE (DGAT) and DIACYLGLYCEROL KINASE (DGK) catalyze the conversion of DAG to TAG and PA, respectively. Here, we show that DGAT1, DGK2, DGK3, and DGK5 contribute to the response to cold in Arabidopsis (Arabidopsis thaliana). With or without cold acclimation, the dgat1 mutants exhibited higher sensitivity upon freezing exposure compared with the wild type. Under cold conditions, the dgat1 mutants showed reduced expression of C-REPEAT/DRE BINDING FACTOR2 and its regulons, which are essential for the acquisition of cold tolerance. Lipid profiling revealed that freezing significantly increased the levels of PA and DAG while decreasing TAG in the rosettes of dgat1 mutant plants. During freezing stress, the accumulation of PA in dgat1 plants stimulated NADPH oxidase activity and enhanced RbohD-dependent hydrogen peroxide production compared with the wild type. Moreover, the cold-inducible transcripts of DGK2, DGK3, and DGK5 were significantly more up-regulated in the dgat1 mutants than in the wild type during cold stress. Consistent with this observation, dgk2, dgk3, and dgk5 knockout mutants showed improved tolerance and attenuated PA production in response to freezing temperatures. Our findings demonstrate that the conversion of DAG to TAG by DGAT1 is critical for plant freezing tolerance, acting by balancing TAG and PA production in Arabidopsis.
Effect of feeding higher concentrations of limiting amino acids on performance, slaughter variables and nitrogen retention in broiler chicken fed graded levels of toasted guar (Cyamopsis tetragonoloba) meal

ABSTRACT 1. An experiment was conducted to study the effect of supplementing higher concentrations (100% vs. 110%) of critical amino acids (CAA) on performance (body weight gain – BWG, feed efficiency – FE), slaughter variables and nitrogen retention in broiler chicken (1–6 weeks of age) fed graded levels of toasted guar meal (TGM) as a protein source in diets. 2. The TGM was included at five graded concentrations (0, 50, 100, 150 and 200 g/kg) in iso-caloric and iso-protein diets with either the recommended concentration (100%) of CAA (lysine, total sulphur amino acids, threonine, tryptophan and valine) or at 10% higher (110%) concentration. A metabolism trial of 3-day duration was conducted during 6th week of age to study nitrogen retention. 3. The TGM levels and CAA concentration at 21 or 42 d of age did not influence BWG, FI and FE. BWG was not affected with inclusion of TGM up to 100 g/kg in starter and overall production (1–42 d of age) phases. The FE improved with TGM supplementation during starter phase, while at the end of experiment (42 d), FE was depressed by inclusion of TGM in dose dependant manner. All performance variables improved with increase in concentration of CAA from 100% to 110%. 4. Breast meat weight improved and abdominal fat weight reduced with higher levels of CAA in diet. Retention of nitrogen reduced with increase in level of TGM in broiler diet. Increasing concentrations of CAA in diet improved nitrogen retention. 5. It was concluded that TGM could be incorporated up to 100 g/kg with 100% CAA and up to 150 g/kg with 110% CAA without affecting performance. Increasing CAA concentration (110%) in diets significantly improved BWG and FE (21 and 42 d), breast meat weight and nitrogen retention in broiler chicken.
Enhancing the Therapeutic Potential of Olfactory Ensheathing Cells in Spinal Cord Repair Using Neurotrophins

Autologous olfactory ensheathing cell (OEC) transplantation is a promising therapy for spinal cord injury; however, the efficacy varies between trials in both animals and humans. The main reason for this variability is that the purity and phenotype of the transplanted cells differs between studies. OECs are susceptible to modulation with neurotrophic factors, and thus, neurotrophins can be used to manipulate the transplanted cells into an optimal, consistent phenotype. OEC transplantation can be divided into 3 phases: (1) cell preparation, (2) cell administration, and (3) continuous support to the transplanted cells in situ. The ideal behaviour of OECs differs between these 3 phases; in the cell preparation phase, rapid cell expansion is desirable to decrease the time between damage and transplantation. In the cell administration phase, OEC survival and integration at the injury site, in particular migration into the glial scar, are the most critical factors, along with OEC-mediated phagocytosis of cellular debris. Finally, continuous support needs to be provided to the transplantation site to promote survival of both transplanted cells and endogenous cells within injury site and to promote long-term integration of the transplanted cells and angiogenesis. In this review, we define the 3 phases of OEC transplantation into the injured spinal cord and the optimal cell behaviors required for each phase. Optimising functional outcomes of OEC transplantation can be achieved by modulation of cell behaviours with neurotrophins. We identify the key growth factors that exhibit the strongest potential for optimizing the OEC phenotype required for each phase.
Death by Suicide in the First Year After Irregular Discharge From Inpatient Hospitalization.

OBJECTIVE Single-site studies indicate irregular hospital discharges are associated with elevated suicide risk. As part of ongoing analytics in the Veterans Affairs (VA) health system, the authors evaluated associations between irregular discharge and suicide over a 15-year period. METHODS All inpatient discharges and discharge types from 2001 through 2014 were identified using VA administrative data. Mortality and cause-of-death data were drawn from comprehensive VA searches of the Centers for Disease Control and Prevention National Death Index. Suicide risk following regular versus irregular discharge was compared by using survival analysis and adjusting for age, gender, and VA facility. RESULTS Among 5,051,051 discharges, 2.1% (103,995) were irregular. Adjusted suicide risk was higher following irregular discharge compared with regular discharge (hazard ratio [HR]=2.02, 95% confidence interval [CI]=1.78-2.29). Stratified analyses by unit type showed that the association was nonsignificant for psychiatric discharges but significant for general medical discharges (HR=3.01, CI=2.54-3.57). CONCLUSIONS Patients were at increased suicide risk after irregular hospital discharges.
Exercise gas exchange in continuous-flow left ventricular assist device recipients

Exercise ventilation/perfusion matching in continuous-flow left ventricular assist device recipients (LVAD) has not been studied systematically. Twenty-five LVAD and two groups of 15 reduced ejection fraction chronic heart failure (HFrEF) patients with peak VO2 matched to that of LVAD (HFrEF-matched) and ≥14 ml/kg/min (HFrEF≥14), respectively, underwent cardiopulmonary exercise testing with arterial blood gas analysis, echocardiogram and venous blood sampling for renal function evaluation. Arterial-end-tidal PCO2 difference (P(a-ET)CO2) and physiological dead space-tidal volume ratio (VD/VT) were used as descriptors of alveolar and total wasted ventilation, respectively. Tricuspid annular plane systolic excursion/pulmonary artery systolic pressure ratio (TAPSE/PASP) and blood urea nitrogen/creatinine ratio were calculated in all patients and used as surrogates of right ventriculo-arterial coupling and circulating effective volume, respectively. LVAD and HFrEF-matched showed no rest-to-peak change of P(a-ET)CO2 (4.5±2.4 vs. 4.3±2.2 mm Hg and 4.1±1.4 vs. 3.8±2.5 mm Hg, respectively, both p >0.40), whereas a decrease was observed in HFrEF≥14 (6.5±3.6 vs. 2.8±2.0 mm Hg, p <0.0001). Rest-to-peak changes of P(a-ET)CO2 correlated to those of VD/VT (r = 0.70, p <0.0001). Multiple regression indicated TAPSE/PASP and blood urea nitrogen/creatinine ratio as independent predictors of peak P(a-ET)CO2. LVAD exercise gas exchange is characterized by alveolar wasted ventilation, i.e. hypoperfusion of ventilated alveoli, similar to that of advanced HFrEF patients and related to surrogates of right ventriculo-arterial coupling and circulating effective volume.
Evaluation of keratoconus progression

Aim To define variables for the evaluation of keratoconus progression and to determine cut-off values. Methods In this retrospective cohort study (2010–2016), 265 eyes of 165 patients diagnosed with keratoconus underwent two Scheimpflug measurements (Pentacam) that took place 1 year apart ±3 months. Variables used for keratoconus detection were evaluated for progression and a correlation analysis was performed. By logistic regression analysis, a keratoconus progression index (KPI) was defined. Receiver-operating characteristic curve (ROC) analysis was performed and Youden Index calculated to determine cut-off values. Results Variables used for keratoconus detection showed a weak correlation with each other (eg, correlation r=0.245 between RPImin and Kmax, p<0.001). Therefore, we used parameters that took several variables into consideration (eg, D-index, index of surface variance, index for height asymmetry, KPI). KPI was defined by logistic regression and consisted of a Pachymin coefficient of −0.78 (p=0.001), a maximum elevation of back surface coefficient of 0.27 and coefficient of corneal curvature at the zone 3 mm away from the thinnest point on the posterior corneal surface of −12.44 (both p<0.001). The two variables with the highest Youden Index in the ROC analysis were D-index and KPI: D-index had a cut-off of 0.4175 (70.6% sensitivity) and Youden Index of 0.606. Cut-off for KPI was −0.78196 (84.7% sensitivity) and a Youden Index of 0.747; both 90% specificity. Conclusions Keratoconus progression should be defined by evaluating parameters that consider several corneal changes; we suggest D-index and KPI to detect progression.
The Genetic Architecture Underlying the Evolution of a Rare Piscivorous Life History Form in Brown Trout after Secondary Contact and Strong Introgression

Identifying the genetic basis underlying phenotypic divergence and reproductive isolation is a longstanding problem in evolutionary biology. Genetic signals of adaptation and reproductive isolation are often confounded by a wide range of factors, such as variation in demographic history or genomic features. Brown trout (Salmo trutta) in the Loch Maree catchment, Scotland, exhibit reproductively isolated divergent life history morphs, including a rare piscivorous (ferox) life history form displaying larger body size, greater longevity and delayed maturation compared to sympatric benthivorous brown trout. Using a dataset of 16,066 SNPs, we analyzed the evolutionary history and genetic architecture underlying this divergence. We found that ferox trout and benthivorous brown trout most likely evolved after recent secondary contact of two distinct glacial lineages, and identified 33 genomic outlier windows across the genome, of which several have most likely formed through selection. We further identified twelve candidate genes and biological pathways related to growth, development and immune response potentially underpinning the observed phenotypic differences. The identification of clear genomic signals divergent between life history phenotypes and potentially linked to reproductive isolation, through size assortative mating, as well as the identification of the underlying demographic history, highlights the power of genomic studies of young species pairs for understanding the factors shaping genetic differentiation.
Influence of Context on Item Parameters in Forced-Choice Personality Assessments

A fundamental assumption in computerized adaptive testing is that item parameters are invariant with respect to context—items surrounding the administered item. This assumption, however, may not hold in forced-choice (FC) assessments, where explicit comparisons are made between items included in the same block. We empirically examined the influence of context on item parameters by comparing parameter estimates from two FC instruments. The first instrument was composed of blocks of three items, whereas in the second, the context was manipulated by adding one item to each block, resulting in blocks of four. The item parameter estimates were highly similar. However, a small number of significant deviations were observed, confirming the importance of context when designing adaptive FC assessments. Two patterns of such deviations were identified, and methods to reduce their occurrences in an FC computerized adaptive testing setting were proposed. It was shown that with a small proportion of violations of the parameter invariance assumption, score estimation remained stable.
Polycystic ovary syndrome and risk factors for gestational diabetes

Objective To study the roles of self-reported symptoms and/or prior diagnosis of polycystic ovary syndrome (PCOS) and other potential risk factors for gestational diabetes mellitus (GDM) and to clarify whether the screening of GDM in early pregnancy is beneficial for all women with PCOS. Design The FinnGeDi multicentre case-control study including 1146 women with singleton pregnancies diagnosed with GDM and 1066 non-diabetic pregnant women. There were 174 women with PCOS (symptoms and/or diagnosis self-reported by a questionnaire) and 1767 women without PCOS (data missing for 271). Methods The study population (N = 1941) was divided into four subgroups: GDM + PCOS (N = 105), GDM + non-PCOS (N = 909), non-GDM + PCOS (N = 69), and controls (N = 858). The participants’ characteristics and their parents’ medical histories were compared. Results The prevalence of PCOS was 10.4% among GDM women and 7.4% among non-diabetics (odds ratios (OR) 1.44, 95% CI: 1.05–1.97), but PCOS was not an independent risk for GDM after adjustments for participants’ age and pre-pregnancy BMI (OR 1.07, 95% CI: 0.74–1.54). In a multivariate logistic regression analysis, the most significant parameters associated with GDM were overweight, obesity, age ≥35 years, participant’s mother’s history of GDM, either parent’s history of type 2 diabetes (T2D) and participant’s own preterm birth. Conclusions The increased risk of GDM in women with PCOS was related to obesity and increased maternal age rather than to PCOS itself, suggesting that routine early screening of GDM in PCOS women without other risk factors should be reconsidered. Instead, family history of GDM/T2D and own preterm birth were independent risk factors for GDM.
Multiple Chemical Sensitivity: Review of the State of the Art in Epidemiology, Diagnosis, and Future Perspectives.

S abrina Rossi and Alessio Pitidis performed an extensive literature survey on nearly 100 publications and combined the latest knowledge on multiple chemical sensitivity (MCS). However, their paper is highly contradictory, and it seems that the authors do not believe themselves what they have written. First, the authors described the natural course of the disease going in stages from the zero which means tolerance to various environmental factors. The tolerance may be lost by increasing sensitization to multiple chemical substances. This is called toxicant induced loss of tolerance. The end stage of the disease is the Stage three which is a devastating condition called deterioration with chronic inflammation that involves almost all organs. Secondly, the authors cited many papers pointing to the fact of oxidative stress reaction and a misbalance in detoxification system. The authors cited the papers showing neurogenic inflammation and hyperreactivity to stimuli detected by accurate modern imaging techniques. The authors made a very fair conclusion that in case of occupational nature of MCS, avoidance of the inflicting substances should be pursued. The authors even proposed the use of an electronic Nose, a portable device to
Mesenchymal stromal cells from human umbilical cord prevent the development of lung fibrosis in immunocompetent mice

Lung fibrosis is a severe condition resulting from several interstial lung diseases (ILD) with different etiologies. Current therapy of ILD, especially those associated with connective tissue diseases, is rather limited and new anti-fibrotic strategies are needed. In this study, we investigated the anti-fibrotic activity in vivo of human mesenchymal stromal cells obtained from whole umbilical cord (hUC-MSC). Adult immunocompetent C57BL/6 mice (n. = 8 for each experimental condition) were injected intravenously with hUC-MSC (n. = 2.5 × 105) twice, 24 hours and 7 days after endotracheal injection of bleomycin. Upon sacrifice at days 8, 14, 21, collagen content, inflammatory cytokine profile, and hUC-MSC presence in explanted lung tissue were analyzed. Systemic administration of a double dose of hUC-MSC significantly reduced bleomycin-induced lung injury (inflammation and fibrosis) in mice through a selective inhibition of the IL6-IL10-TGFβ axis involving lung M2 macrophages. Only few hUC-MSC were detected from explanted lungs, suggesting a “hit and run” mechanism of action of this cellular therapy. Our data indicate that hUC-MSC possess strong in vivo anti-fibrotic activity in a mouse model resembling an immunocompetent human subject affected by inflammatory ILD, providing proof of concept for ad-hoc clinical trials.
Survival and Success Rates of Different Shoulder Designs: A Systematic Review of the Literature

Objectives To identify whether there is a relationship between different implant shoulder positions/orientations/designs and prosthetic and/or implant failures, biological or mechanical complications, radiographic marginal bone loss (MBL), peri-implant buccal recession (RC), aesthetic scores (Papilla Index, PES, and WES), and patient satisfaction after a minimum of 1 year function in the aesthetic zone, compared to the two-piece, conventional implant neck architecture. Materials and Methods The systematic review was written according to the PRISMA guidelines. The search strategy encompassed the English literature from 1967 to September 2016 and was performed online (in the PubMed database of the U.S. National Library of Medicine, Embase, and the Cochrane Library) to identify relevant studies that met the inclusion criteria. The assessment of quality and risk of bias of the selected manuscripts was performed according to the guidelines provided by CONSORT and STROBE statements. Results A total of 16 articles (7 randomized controlled trials, 4 observational comparative studies, and 5 systematic reviews) were selected to fulfill the inclusion criteria. A trend of higher implant failure and prosthetic complications were experienced in the one-piece group compared to the two-piece group, although no statistically significant differences were found. Higher marginal bone loss was found in the test group (one-piece, scalloped implants) compared to the control group (two-piece, flat implants). No comparative studies reporting data on sloped implants were found that fulfilled the inclusion and exclusion criteria of this systematic review. No differences were experienced between groups regarding aesthetic outcomes and patient satisfaction. Conclusions There was sufficient evidence that different implant shoulder positions/orientations/designs (scalloped, sloped, and one piece) offer no benefit when compared to two-piece, conventional flat implants. Current evidence is limited due to the quality of available studies.
Three Insights from a Bayesian Interpretation of the One-Sided P Value

P values have been critiqued on several grounds but remain entrenched as the dominant inferential method in the empirical sciences. In this article, we elaborate on the fact that in many statistical models, the one-sided P value has a direct Bayesian interpretation as the approximate posterior mass for values lower than zero. The connection between the one-sided P value and posterior probability mass reveals three insights: (1) P values can be interpreted as Bayesian tests of direction, to be used only when the null hypothesis is known from the outset to be false; (2) as a measure of evidence, P values are biased against a point null hypothesis; and (3) with N fixed and effect size variable, there is an approximately linear relation between P values and Bayesian point null hypothesis tests.
Women’s empowerment in agriculture and agricultural productivity: Evidence from rural maize farmer households in western Kenya

This paper documents a positive relationship between maize productivity in western Kenya and women’s empowerment in agriculture, measured using indicators derived from the abbreviated version of the Women’s Empowerment in Agriculture Index. Applying a cross-sectional instrumental-variable regression method to a data set of 707 maize farm households from western Kenya, we find that women’s empowerment in agriculture significantly increases maize productivity. Although all indicators of women’s empowerment significantly increase productivity, there is no significant association between the women’s workload (amount of time spent working) and maize productivity. Furthermore, the results show heterogenous effects with respect to women’s empowerment on maize productivity for farm plots managed jointly by a male and female and plots managed individually by only a male or female. More specifically, the results suggest that female- and male-managed plots experience significant improvements in productivity when the women who tend them are empowered. These findings provide evidence that women’s empowerment contributes not only to reducing the gender gap in agricultural productivity, but also to improving, specifically, productivity from farms managed by women. Thus, rural development interventions in Kenya that aim to increase agricultural productivity—and, by extension, improve food security and reduce poverty—could achieve greater impact by integrating women’s empowerment into existing and future projects.