Miracle-dz/UniFAR-FTUs huggingface dataset:
Fuchs endothelial corneal dystrophy: current treatment recommendations and experimental surgical options

Fuchs endothelial corneal dystrophy is a common disorder characterized by the progressive thickening of Descemet membrane (DM), manifesting as guttae and leading to a decrease in endothelial cells and corneal clearance. Numerous studies have tried to better characterize the genetics of Fuchs endothelial corneal dystrophy, and suggest that it is a complex heterogenic disorder with an array of variants in severity and disease progression. Currently the most effective treatment for replacing diseased endothelium is endothelial keratoplasty (EK). In the last decade, EK has evolved into selective transplantation of an isolated DM and its endothelium, referred to as Descemet membrane endothelial keratoplasty (DMEK), which enables near normal anatomical and visual outcomes after surgery. Unexpected observations after DMEK, however, may bring new insights on endothelial cell wound healing, potentially allowing novel ‘non-keratoplasty’ surgical approaches like Descemet membrane endothelial transfer, endothelial cell injection techniques or even only a descemetorhexis as alternatives for selected cases.
High rates of sexual violence by both intimate and non-intimate partners experienced by adolescent girls and young women in Kenya and Zambia: Findings around violence and other negative health outcomes

Background While links between intimate-partner violence (IPV) and HIV risk have been established, less is known about violence perpetrated by people other than intimate partners. In addition, much of the research on IPV has been conducted with adults, while relatively little is known about violence experienced by adolescent girls and young women (AGYW). We examined experiences of sexual violence and associated sexual and mental health among AGYW in Kenya and Zambia. Methods Using cross-sectional surveys with women aged 15–24 years, we assessed experience of partner sexual violence among respondents who reported a boyfriend/husband in the last 12 months (Kenya N = 597; Zambia N = 426) and non-partner sexual violence among all respondents (Kenya N = 1778; Zambia N = 1915). We conducted logistic regression analyses to examine experiences of sexual violence and health outcomes. Results Sexual violence from intimate partners over the last year was reported by 19.1 percent of AGYW respondents in Kenya and 22.2 percent in Zambia; sexual violence from non-partners was reported by 21.4 percent in Kenya and 16.9 percent in Zambia. Experience of sexual violence was associated with negative health outcomes. Violence from non-partners was associated with increased odds of STI symptoms and increased levels of anxiety and depression. Results were similar for violence from partners, although only significant in Kenya. While sexual violence from a non-partner was associated with increased HIV risk perception, it was not associated when the violence was experienced from an intimate partner. Conclusions AGYW reported high levels of sexual violence from both intimate partners and non-partners. These experiences were associated with negative health outcomes, though there were some differences by country context. Strengthening sexual violence prevention programs, increasing sexual violence screening, and expanding the provision of post-violence care are needed to reduce intimate and non-partner violence and the effects of violence on AGYW.
Precision Medicine in Type 2 Diabetes: Clinical Markers of Insulin Resistance Are Associated With Altered Short- and Long-term Glycemic Response to DPP-4 Inhibitor Therapy

OBJECTIVE A precision approach to type 2 diabetes therapy would aim to target treatment according to patient characteristics. We examined if measures of insulin resistance and secretion were associated with glycemic response to dipeptidyl peptidase 4 (DPP-4) inhibitor therapy. RESEARCH DESIGN AND METHODS We evaluated whether markers of insulin resistance and insulin secretion were associated with 6-month glycemic response in a prospective study of noninsulin-treated participants starting DPP-4 inhibitor therapy (Predicting Response to Incretin Based Agents [PRIBA] study; n = 254), with replication for routinely available markers in U.K. electronic health care records (Clinical Practice Research Datalink [CPRD]; n = 23,001). In CPRD, we evaluated associations between baseline markers and 3-year durability of response. To test the specificity of findings, we repeated analyses for glucagon-like peptide 1 (GLP-1) receptor agonists (PRIBA, n = 339; CPRD, n = 4,464). RESULTS In PRIBA, markers of higher insulin resistance (higher fasting C-peptide [P = 0.03], HOMA2 insulin resistance [P = 0.01], and triglycerides [P < 0.01]) were associated with reduced 6-month HbA1c response to DPP-4 inhibitors. In CPRD, higher triglycerides and BMI were associated with reduced HbA1c response (both P < 0.01). A subgroup defined by obesity (BMI ≥30 kg/m2) and high triglycerides (≥2.3 mmol/L) had reduced 6-month response in both data sets (PRIBA HbA1c reduction 5.3 [95% CI 1.8, 8.6] mmol/mol [0.5%] [obese and high triglycerides] vs. 11.3 [8.4, 14.1] mmol/mol [1.0%] [nonobese and normal triglycerides]; P = 0.01). In CPRD, the obese, high- triglycerides subgroup also had less durable response (hazard ratio 1.28 [1.16, 1.41]; P < 0.001). There was no association between markers of insulin resistance and response to GLP-1 receptor agonists. CONCLUSIONS Markers of higher insulin resistance are consistently associated with reduced glycemic response to DPP-4 inhibitors. This finding provides a starting point for the application of a precision diabetes approach to DPP-4 inhibitor therapy.
Whose emotion is it? Measuring self-other discrimination in romantic relationships during an emotional evaluation paradigm

In healthy subjects, emotional stimuli, positive stimuli in particular, are processed in a facilitated manner as are stimuli related to the self. These preferential processing biases also seem to hold true for self-related positive stimuli when compared to self-related negative or other-related positive stimuli suggesting a self-positivity bias in affective processing. The present study investigates the stability of this self-positivity bias and its possible extension to the emotional other in a sample of N = 147 participants including single participants (n = 61) and individuals currently in a romantic relationship (n = 86) reporting moderate to high levels of passionate love. Participants were presented a series of emotional and neutral words that could be related to the reader’s self (e.g., “my pleasure”, “my fear”), or to an insignificant third person, unknown to the reader (e.g., “his pleasure”, “his fear”) or devoid of any person reference (e.g., “the pleasure”, “the fear”). The task was to read the words silently and to evaluate the word pairs in reference to one’s own feelings elicited during reading. Results showed a self-positivity bias in emotional judgments in all participants, particularly in men. Moreover, participants in a romantic relationship (women and men) evaluated positive, other-related stimuli more often as valence-congruent with one’s own feelings than single participants. Taken together, these findings support the idea of a self-positivity bias in healthy subjects and an expansion of this bias while being in a romantic relationship.
Global Diabetes Prevention Interventions: A Systematic Review and Network Meta-analysis of the Real-World Impact on Incidence, Weight, and Glucose

OBJECTIVE Understanding the real-world impacts of lifestyle modification (LSM) for diabetes prevention is imperative to inform resource allocation. The purpose of this study was to synthetize global evidence on the impact of LSM strategies on diabetes incidence and risk factors in one parsimonious model. RESEARCH DESIGN AND METHODS PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for studies published between January 1990 and April 2015. Effectiveness/translation studies of any design testing LSM strategies, targeting high-risk populations (with prediabetes or diabetes risk factors), and reporting diabetes incidence, weight, or glucose outcomes were included. We extracted number of diabetes cases/incidence rates and mean changes in weight (kg), fasting blood glucose (FBG, mmol/L), 2-h postload glucose (mmol/L), and hemoglobin A1c (%). Pairwise random-effects and frequentist random-effects network meta-analyses were used to obtain pooled effects. RESULTS Sixty-three studies were pooled in the meta-analysis (n = 17,272, mean age 49.7 years, 28.8% male, 60.8% white/European). In analyses restricted to controlled studies (n = 7), diabetes cumulative incidence was 9% among intervention participants and 12% among control participants (absolute risk reduction 3%; relative risk 0.71 [95% CI 0.58, 0.88]). In analyses combining controlled and uncontrolled studies (n = 14), participants receiving group education by health care professionals had 33% lower diabetes odds than control participants (odds ratio 0.67 [0.49, 0.92]). Intervention participants lost 1.5 kg more weight [−2.2, −0.8] and achieved a 0.09 mmol/L greater FBG decrease [−0.15, −0.03] than control participants. Every additional kilogram lost by participants was associated with 43% lower diabetes odds (β = 0.57 [0.41, 0.78]). CONCLUSIONS Real-world LSM strategies can reduce diabetes risk, even with small weight reductions.
Food cue-induced craving in individuals with bulimia nervosa and binge-eating disorder

Individuals with bulimia nervosa (BN) or binge-eating disorder (BED) experience more frequent and intense food cravings than individuals without binge eating. However, it is currently unclear whether they also show larger food cue-induced increases in craving (i.e., food cue reactivity) than those without binge eating, as suggested by conditioning theories of binge eating. A group of individuals with BN or BED (binge-eating group, n = 27) and a group of individuals with low trait food craving scores and without binge eating (control group, n = 19) reported their current food craving before and after a food cue exposure. Although food craving intensity significantly increased in both groups, this increase was significantly stronger in the binge-eating group than in the control group. This result is in line with conditioning models of binge eating that propose that food cues are conditioned stimuli that elicit a conditioned response (e.g., food craving) and that this association is stronger in individuals with binge eating. As food craving increased in individuals with low trait food craving scores as well—although to a lesser extent—previous null results might be explained by methodological considerations such as not screening control participants for trait food craving.
ATRX loss induces multiple hallmarks of the alternative lengthening of telomeres (ALT) phenotype in human glioma cell lines in a cell line-specific manner

Cancers must maintain their telomeres at lengths sufficient for cell survival. In several cancer subtypes, a recombination-like mechanism termed alternative lengthening of telomeres (ALT), is frequently used for telomere length maintenance. Cancers utilizing ALT often have lost functional ATRX, a chromatin remodeling protein, through mutation or deletion, thereby strongly implicating ATRX as an ALT suppressor. Herein, we have generated functional ATRX knockouts in four telomerase-positive, ALT-negative human glioma cell lines: MOG-G-UVW, SF188, U-251 and UW479. After loss of ATRX, two of the four cell lines (U-251 and UW479) show multiple characteristics of ALT-positive cells, including ultrabright telomeric DNA foci, ALT-associated PML bodies, and c-circles. However, telomerase activity and overall telomere length heterogeneity are unaffected after ATRX loss, regardless of cellular context. The two cell lines that showed ALT hallmarks after complete ATRX loss also did so upon ATRX depletion via shRNA-mediated knockdown. These results suggest that other genomic or epigenetic events, in addition to ATRX loss, are necessary for the induction of ALT in human cancer.
Multi-informant path models of the influence of psychosocial and treatment-related variables on adherence and metabolic control in adolescents with type 1 diabetes mellitus

Background We assessed the associations between metabolic control and adherence and a broad range of adolescent and family characteristics (e.g., gender, family structure), treatment-related variables (e.g., disease duration, treatment modality), and psychosocial factors (e.g., symptoms of depression and anxiety, parental support, self-efficacy) in a nationwide study of Danish adolescents (age 12–17 years) with type 1 diabetes mellitus (T1DM). Methods Sixty-four percent of invited families participated by completing a survey and providing a blood sample. Two path models of associations between generic and diabetes-related family factors, adolescent self-efficacy, emotional difficulties, and metabolic control and adherence were tested, one for adolescents and one for caregivers. Demographic variables were included as covariates. Results Both path models demonstrated a satisfying model fit. In both models, metabolic control was associated with adherence, age, and T1DM duration. In the adolescent model, metabolic control was also related to treatment modality, single-parent household, caregiver non-support, and anxiety, whereas in the caregiver model metabolic control was associated with family conflict and caregiver support. In both models, adherence was related to age, duration, treatment modality, family conflict, caregiver support, family functioning, and emotional difficulties of the adolescent. In the adolescent model, adherence was also related to adolescent self-efficacy, whereas in the caregiver model adherence was associated with adolescent gender and caregiver non-support and support. Adolescent self-efficacy, emotional well-being, and difficulties related to adolescent/caregiver interaction appeared to be particularly important, as indicated by their stronger association with adherence and/or metabolic control. Conclusion The results highlight the value of applying a multi-informant approach to address the psychosocial well-being of adolescents with diabetes in a large national sample. Self-efficacy, emotional, and family-related difficulties are important aspects to address in both clinical care and future research regarding adolescents with T1DM.
Oral probiotic combination of Lactobacillus and Bifidobacterium alters the gastrointestinal microbiota during antibiotic treatment for Clostridium difficile infection

Perturbations in the gastrointestinal microbiome caused by antibiotics are a major risk factor for Clostridium difficile infection (CDI). Probiotics are often recommended to mitigate CDI symptoms; however, there exists only limited evidence showing probiotic efficacy for CDI. Here, we examined changes to the GI microbiota in a study population where probiotic treatment was associated with significantly reduced duration of CDI diarrhea. Subjects being treated with standard of care antibiotics for a primary episode of CDI were randomized to probiotic treatment or placebo for 4 weeks. Probiotic treatment consisted of a daily multi-strain capsule (Lactobacillus acidophilus NCFM, ATCC 700396; Lactobacillus paracasei Lpc-37, ATCC SD5275; Bifidobacterium lactis Bi-07, ATCC SC5220; Bifidobacterium lactis B1-04, ATCC SD5219) containing 1.7 x 1010 CFUs. Stool was collected and analyzed using 16S rRNA sequencing. Microbiome analysis revealed apparent taxonomic differences between treatments and timepoints. Subjects administered probiotics had reduced Verrucomicrobiaceae at week 8 compared to controls. Bacteroides were significantly reduced between weeks 0 to 4 in probiotic treated subjects. Ruminococcus (family Lachnospiraceae), tended to be more abundant at week 8 than week 4 within the placebo group and at week 8 than week 0 within the probiotic group. Similar to these results, previous studies have associated these taxa with probiotic use and with mitigation of CDI symptoms. Compositional prediction of microbial community function revealed that subjects in the placebo group had microbiomes enriched with the iron complex transport system, while probiotic treated subjects had microbiomes enriched with the antibiotic transport system. Results indicate that probiotic use may impact the microbiome function in the face of a CDI; yet, more sensitive methods with higher resolution are warranted to better elucidate the roles associated with these changes. Continuing studies are needed to better understand probiotic effects on microbiome structure and function and the resulting impacts on CDI.
Influence of contextual variables and the pressure to keep category on physical match performance in soccer players

Previous studies have analysed the influence of contextual variables on performance and physical demands in soccer. However, the points needed to remain in the category have been an element that has not been analysed previously. The aim of the present study was to investigate the influence of match location, match period, strength of the opponent and the points required to keep category on physical performance in professional soccer players. Fourteen Spanish second B Division League matches played by a professional football team were analysed during the 2016/17 season using GPS devices. The 10 main players of each match used the GPS throughout the match. The variables of Total Distance (m), High Intensity Distance (m), High intensity Accelerations (n), Sprint Time (s) and Sprint Distance (m) were analysed. The most notable differences are found in Total Distance covered. Away games accumulated significantly more distance than those played at home, but only in the second half (+230.65 m, IC95%: 21.94 to 438.19, ES: 0.46, p = 0.031). There are no differences depending on the strength of the opponent. However, players covered greater distances during the first half in those matches that were played furthest from salvation (+235.86 m, 95% CI: 49.03 to 422.70, ES: 0.51, p = 0.014). Total Distance is the main parameter affected by situational variables. In addition, the pressure of being further away from saving the category increases the distance covered by players in a game.
Psychometric validation of the Serbian version of the Fear Avoidance Component Scale (FACS)

Objective The Fear Avoidance Components Scale (FACS) is a new patient-reported outcome (PRO) questionnaire designed to comprehensively evaluate fear avoidance (FA) beliefs and attitudes in persons with painful medical conditions. The original English version has demonstrated acceptable psychometric properties, including concurrent and predictive validity. Two factors have been identified: 1. general fear avoidance; and 2. types of activities that are avoided. Methods The FACS was first translated into Serbian, and then psychometrically validated. A cohort of 322 chronic musculoskeletal pain subjects completed the FACS-Serb and additional FA-related patient-reported outcome (PRO) measures. Their FACS-Serb scores were then compared to a cohort of 68 acute pain subjects. Results Test-retest reliability (ICC2,1 = 0.928) and internal consistency for both Factors (Cronbach α 0.904 and 0,880 respectively) were very good. An acceptable fit was found with a confirmatory factor analysis of the 2-factor model found with the original English version of the FACS. Strong associations were found among FACS-Serb scores and other PRO measures of pain catastrophizing, depressive/anxiety symptoms, perceived disability, and pain intensity (p<0.001 for all analyses). FACS-Serb total scores, separate Factor scores, and subjective pain ratings were significantly higher in the chronic vs. acute pain cohorts (p<0.001 for all analyses). Conclusions The FACS-Serb demonstrated strong psychometric properties, including strong reliability and internal consistency, criterion validity (through associations with other FA-related PRO measures), and discriminant validity (through comparisons with a separate acute pain cohort). The FACS-Serb appears to be a potentially useful pain-related assessment tool.
Long-term Mortality After Kidney Transplantation in a Nationwide Cohort of Patients With Type 1 Diabetes in Finland

OBJECTIVE To examine time trends in mortality rates and causes of death in patients with type 1 diabetes and end-stage renal disease on dialysis and after kidney transplantation. RESEARCH DESIGN AND METHODS In a nationwide retrospective cohort analysis, all patients with type 1 diabetes in Finland who received a kidney transplant alone were compared with patients who remained on dialysis. The main outcome was patient survival after starting dialysis. The cohort was divided into dialysis, functioning kidney transplant, and dialysis after transplant loss. Causes of death were retrieved and standardized mortality ratios calculated. RESULTS We studied 2,383 patients. Patients survived a median of 15.9 years after a successful transplant, 11.2 years if transplant function was lost, and 2.9 years if they remained on chronic dialysis. Standardized mortality ratio decreased in all subgroups during the past four decades: from 2005 onwards, it was 3.9 in patients receiving a kidney transplant, 11.5 in patients with graft loss, and 32.5 in patients on dialysis. The most common cause of death in all patients was ischemic heart disease (45%) followed by infection (18%), which was more common in patients on dialysis. CONCLUSIONS Kidney transplantation is the treatment of choice for patients with type 1 diabetes and end-stage renal disease because it substantially reduces the excess death risk when compared with dialysis. Even when kidney graft function is lost, the excess death risk is still considerably lower. Although overall mortality has decreased over the years, premature death due to ischemic heart disease remains high.
A stochastic model of myeloid cell lineages in hematopoiesis and pathway mutations in acute myeloid leukemia

A model for hematopoiesis is presented that explicitly includes the erythrocyte, granulocyte, and thrombocyte lineages and their common precursors. A small number of stem cells proliferate and differentiate through different compartments to produce the vast number of blood cells needed every day. Growth factors regulate the proliferation of cells dependent on the current demand. We provide a steady state analysis of the model and rough parameter estimates. Furthermore, we extend the model to include mutations that alter the replicative capacity of cells and introduce differentiation blocks. With these mutations the model develops signs of acute myeloid leukemia.