Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparing and Contrasting the Effects of Drosophila Condensin II Subunit dCAP-D3 Overexpression and Depletion in Vivo

The Condensin II complex plays important, conserved roles in genome organization throughout the cell cycle and in the regulation of gene expression. Previous studies have linked decreased Condensin II subunit expression with a variety of diseases. Here, we show that elevated levels of Condensin II subunits are detected in somatic cancers. To evaluate potential biological effects of elevated Condensin II levels, we overexpressed the Condensin II subunit, dCAP-D3 in Drosophila melanogaster larval tissues and examined the effects on the mitotic- and interphase-specific functions of Condensin II. Interestingly, while ubiquitous overexpression resulted in pupal lethality, tissue specific overexpression of dCAP-D3 caused formation of nucleoplasmic protein aggregates which slowed mitotic prophase progression, mimicking results observed when dCAP-D3 levels are depleted. Surprisingly, dCAP-D3 aggregate formation resulted in faster transitions from metaphase to anaphase. Overexpressed dCAP-D3 protein failed to precipitate other Condensin II subunits in nondividing tissues, but did cause changes to gene expression which occurred in a manner opposite of what was observed when dCAP-D3 levels were depleted in both dividing and nondividing tissues. Our findings show that altering dCAP-D3 levels in either direction has detrimental effects on mitotic timing, the regulation of gene expression, and organism development. Taken together, these data suggest that the different roles for Condensin II throughout the cell cycle may be independent of each other and/or that dCAP-D3 may possess functions that are separate from those involving its association with the Condensin II complex. If conserved, these findings could have implications for tumors harboring elevated CAP-D3 levels.
Peroral endoscopic myotomy for the treatment of achalasia patients with Roux-en-Y gastric bypass anatomy

Abstract Background The outcome of peroral endoscopic myotomy (POEM) in patients with prior Roux-en-Y gastric bypass (RYGB) is not known and some experts have recommended against its performance in this patient population because of the risk of postoperative regurgitation. The aim of this study was to report on the outcomes of POEM in patients with RYGB anatomy. Methods Patients with RYGB anatomy who underwent POEM for the treatment of achalasia at three tertiary centers were included. POEM was performed in standard fashion using the anterior or posterior approach. Clinical response was defined by a decrease in Eckardt score to ≤ 3. Results of esophageal acid exposure testing/pH-impedance and manometric testing after POEM were reported when available. Results A total of 10 achalasia patients with prior RYGB surgery underwent POEM. All procedures were technically successful with anterior myotomy performed in seven patients. The mean submucosal tunnel length and myotomy length were 12.9 cm and 11.1 cm, respectively. The mean procedure time was 72 minutes and mean length of hospital stay was 1.5 days. Clinical success was achieved in all 10 patients with a significant decrease in Eckardt score from 6.5 to 1 (P < 0.001). None of the patients experienced post-procedural regurgitation. Post-procedural pH testing was obtained in six patients and was normal in all of them. Conclusions This study suggests the feasibility, safety, and efficacy of POEM in patients with prior RYGB surgery. The risk of gastroesophageal reflux disease in these patients seems to be minimal after POEM.
The impact of patient‐centered medical homes on medication adherence?

Accreditation of providers helps resolve the pervasive information asymmetries in health care markets. However, meeting accreditation standards typically involves flexibility in implementation, leading to heterogeneity in performance. For example, the patient-centered medical home (PCMH) is a leading model for recognizing high-performing primary care practices. Flexibility in PCMH implementation allows for varying degrees of emphasis on processes designed to enhance medication adherence. To assess the impact of the PCMH on adherence, we combine 6 years of detailed patient claims data with a novel dataset containing detailed practice-level PCMH attributes. We study the effects of the number and configuration of adherence-relevant capabilities, using variation in the timing of PCMH adoption to estimate its impact. While PCMH adoption improved overall medication adherence, when combining claims data with the unique recognition data detailing what PCMH capabilities were adopted, we find that these gains are concentrated among patients in practices that adopted more adherence-relevant capabilities. Despite mixed evidence in the literature concerning costs and utilization, our results indicate that PCMH recognition improves medication adherence.
Safety and Efficacy of Ledipasvir–Sofosbuvir With or Without Ribavirin for Chronic Hepatitis C in Children Ages 6‐11

Currently, there are no interferon‐free treatments available for hepatitis C virus (HCV)–infected patients younger than 12 years. We evaluated the safety and effectiveness of the all‐oral regimen ledipasvir–sofosbuvir ± ribavirin in HCV‐infected children aged 6 to <12 years. In an open‐label study, patients aged 6 to <12 years received ledipasvir 45 mg–sofosbuvir 200 mg as two fixed‐dose combination tablets 22.5/100 mg once daily, with or without ribavirin, for 12 or 24 weeks, depending on HCV genotype and cirrhosis status. The primary efficacy endpoint was sustained virologic response 12 weeks after therapy (SVR12). Twelve patients underwent intensive pharmacokinetic sampling to confirm the appropriateness of the ledipasvir and sofosbuvir dosages. Ninety‐two patients were enrolled (88 genotype 1, 2 genotype 3, and 2 genotype 4), with a median age of 9 years (range, 6‐11). Most were perinatally infected (97%) and treatment‐naive (78%). Two were confirmed to have cirrhosis, while the degree of fibrosis was unknown in 55 patients. The overall SVR12 rate was 99% (91/92; 95% confidence interval, 94%‐100%). The single patient not reaching SVR relapsed 4 weeks after completing 12 weeks of treatment. The most common adverse events were headache and pyrexia. One patient had three serious adverse events, which were considered to be not related to study treatment: tooth abscess, abdominal pain, and gastroenteritis. The area under the concentration–time curve and maximum concentration values for sofosbuvir, its primary metabolite GS‐331007, and ledipasvir were within predefined pharmacokinetic equivalence boundaries (50%‐200%) compared to values in adults in phase 2/3 of the ledipasvir and sofosbuvir studies. Conclusion: Ledipasvir–sofosbuvir was well tolerated and highly effective in children 6 to <12 years old with chronic HCV.
Can a teacher-led RCT improve adolescent girls’ physical self-perception and perceived motor competence?

ABSTRACT Perceived and actual motor competence (MC) influence physical activity (PA) behaviour. Notably, both are lower in girls than in boys. This study aimed to investigate (i) whether a 12-week, teacher-led intervention that improves actual MC (Lander, N., Morgan, P. J., Salmon, J., & Barnett, L. M. (2017). Improving early-adolescent girls’ motor skill: A cluster randomized controlled trial. Medicine and Science in Sports and Exercise. 49(12), 2498–2505) could also improve adolescent girls’ physical self-perception and perceived MC, and (ii) whether change in actual MC is associated with post-intervention perceptions A randomized controlled trial with 171 girls (mean age 12.48 ± 0.34 years), measured perception (i.e., physical self-perception profile (PSPP) and pictorial scale of perceived movement skill competence (PMSC)) and actual MC (i.e., Victorian FMS Teachers’ Assessment Manual). Mixed models with post-intervention perception as the outcome, adjusting for baseline perception, group, and change in actual MC, as well as clustering, were performed. An interaction term between change in MC and intervention status was included to test the secondary aim. There were significant intervention effects on girls’ physical self-perception as well as their perceived MC. However, there was no association between change in actual MC across the intervention and post intervention perception. While the intervention improved both actual MC and perceived MC, they were not associated.
Meningococcal B Vaccine Immunogenicity in Children With Defects in Complement and Splenic Function

Children with complement deficiency respond less well to immunization with 4CMenB than healthy children in the control category; surveillance for vaccine failures is required to determine the significance of this. BACKGROUND: The capsular group B meningococcal vaccine (4CMenB) is recommended for children with complement deficiencies, asplenia, and splenic dysfunction; however, data on the immunogenicity of 4CMenB in these “at-risk” children are missing. METHODS: Participants aged 2 to 17 years in Italy, Spain, Poland, the United Kingdom, and Russia with complement deficiencies, asplenia, or splenic dysfunction received 2 doses of 4CMenB 2 months apart, as did healthy children in the control group. Exogenous and endogenous human complement serum bactericidal activity (SBA) was determined at baseline and 1 month after the second immunization against 4 test strains: H44/76 (assessing vaccine antigen factor H binding protein), 5/99 (Neisserial adhesion A), NZ98/254 (Porin A), and M10713 (Neisserial heparin binding antigen). RESULTS: Of 239 participants (mean age 10.3 years, 45% female), 40 children were complement deficient (9 eculizumab therapy, 4 terminal-chain deficiencies, 27 “other”), 112 children had asplenia or splenic dysfunction (8 congenital asplenia, 8 functional asplenia, 96 splenectomy), and 87 children were in the control group. After immunization, the proportions of complement-deficient participants with exogenous complement SBA titers ≥1:5 were 87% (H44/76), 95% (5/99), 68% (NZ98/254), and 73% (M10713), compared with 97%, 100%, 86%, and 94%, respectively, for asplenic children and 98%, 99%, 83%, and 99% for children in the control group. When testing with endogenous complement, strain-specific bactericidal activity was evident in only 1 eculizumab-treated participant and 1 terminal chain complement-deficient participant. CONCLUSIONS: 4CMenB administration is similarly immunogenic in healthy children and those with asplenia or splenic dysfunction. The significance of the trend to lower responses of SBA titers in complement-deficient children (especially those with terminal chain complement deficiency or those on eculizumab therapy) must be determined by ongoing surveillance for vaccine failures.
Beneficial Effect of Intradialytic Electrical Muscle Stimulation in Hemodialysis Patients: A Randomized Controlled Trial

Many hemodialysis (HD) patients cannot perform self-administered exercise training for their muscle wasting, weakness, and sarcopenia. Electrical muscle stimulation (EMS) has the advantages of easy application, and minimal risks for these patients. This study aimed to evaluate the effects of intradialytic EMS. This was a prospective, open-label, randomized controlled trial. Twenty-nine HD patients were randomly assigned to either the EMS group or the control (no training) group, and 13 patients in each group were eventually analyzed. The EMS group received intradialytic EMS over an 8-week period. Measurement of isometric knee extensor strength using a handheld dynamometer, evaluation of the quadriceps cross-sectional area (CSA) using magnetic resonance imaging (MRI), the Timed Up & Go Test (TUG) for physical function assessment, the Japanese version of the Short Form-8 Health Survey (SF-8), and blood tests were performed before and after the intervention period. The primary and secondary outcomes were improvement of quadriceps muscle strength and size, respectively. The EMS group demonstrated significant improvement compared with the control group in terms of knee extensor strength (right: 22.3 ± 12.8 vs. -10.8 ± 22.3 N, P < 0.001; left: 26.1 ± 29.7 vs. -8.3 ± 18.7 N, P < 0.001), quadriceps CSA at three positions, 25, 50, and 75% of the segment length from the greater trochanter to the inferior border of the lateral epicondyle of the femur (25% right: EMS group 1.7 ± 2.0 vs. Control group -0.4 ± 1.8cm2 , P = 0.05; 25% left: EMS group 1.3 ± 1.1 vs. Control group -0.6 ± 1.8cm2 , P = 0.01; 50% right: EMS group 2.0 ± 2.2 vs. Control group -0.7 ± 1.9cm2 , P = 0.004; 50% left: EMS group 2.7 ± 2.1 vs. Control group -0.7 ± 1.6cm2 , P = 0.001; 75% right: EMS group 1.8 ± 2.2 vs. Control group -0.7 ± 1.5cm2 , P = 0.003; 75% left: EMS group 2.1 ± 1.9 vs. Control group -0.4 ± 1.5cm2 , P = 0.003); and TUG time (-0.8 ± 0.6 vs. 0.2 ± 0.5s, P < 0.001). The EMS group showed improvement after intervention in all components of SF-8, but these were not statistically significant. EMS could be an effective exercise training tool for HD patients with either muscle wasting, weakness, or sarcopenia.
Minimal residual disease assessed with deep sequencing of NPM1 mutations predicts relapse after allogeneic stem cell transplant in AML

Abstract Mutations in NPM1 can be used for minimal residual disease (MRD) analysis in acute myeloid leukemia (AML). We here applied a newly introduced method, deep sequencing, allowing for simultaneous analysis of all recurrent NPM1 insertions and thus constituting an attractive alternative to multiple PCRs for the clinical laboratory. We retrospectively used deep sequencing for measurement of MRD pre- and post-allogeneic hematopoietic stem cell transplantation (alloHCT). For 29 patients in morphological remission at the time of alloHCT, the effect of deep sequencing MRD on outcome was assessed. MRD positivity was defined as variant allele frequency ≥0.02%. Post-transplant MRD status was significantly and independently associated with clinical outcome; 3-year relapse-free survival 20% vs 85% (p < .001), HR 45 (95% CI 2–1260), and overall survival 20% vs 89% (p < .001), HR 49 (95% CI 2–1253). Thus, the new methodology deep sequencing is an applicable and predictive tool for MRD assessment in AML.
Medications for Alcohol and Opioid Use Disorders and Risk of Suicidal Behavior, Accidental Overdoses, and Crime.

OBJECTIVE: The authors examined associations between medications for alcohol and opioid use disorders (acamprosate, naltrexone, methadone, and buprenorphine) and suicidal behavior, accidental overdoses, and crime. METHOD: In this total population cohort study, 21,281 individuals who received treatment with at least one of the four medications between 2005 and 2013 were identified. Data on medication use and outcomes were collected from Swedish population-based registers. A within-individual design (using stratified Cox proportional hazards regression models) was used to compare rates of suicidal behavior, accidental overdoses, and crime for the same individuals during the period when they were receiving the medication compared with the period when they were not. RESULTS: No significant associations with any of the primary outcomes were found for acamprosate. For naltrexone, there was a reduction in the hazard ratio for accidental overdoses during periods when individuals received treatment compared with periods when they did not (hazard ratio=0.82, 95% CI=0.70, 0.96). Buprenorphine was associated with reduced arrest rates for all crime categories (i.e., violent, nonviolent, and substance-related) as well as reduction in accidental overdoses (hazard ratio=0.75, 95% CI=0.60, 0.93). For methadone, there were significant reductions in the rate of suicidal behaviors (hazard ratio=0.60, 95% CI=0.40-0.88) as well as reductions in all crime categories. However, there was an increased risk for accidental overdoses among individuals taking methadone (hazard ratio=1.25, 95% CI=1.13, 1.38). CONCLUSIONS: Medications currently used to treat alcohol and opioid use disorders also appear to reduce suicidality and crime during treatment.
Epidemiology of anophthalmia and microphthalmia: Prevalence and patterns in Texas, 1999–2009

Anophthalmia and microphthalmia are a set of rare, yet severe, birth defects considered to be part of a spectrum of developmental ocular malformations ranging from smaller than average to completely absent eyes. Despite their clinical significance, little is known about the etiologies of these conditions. The goal of this study was to expand our understanding of the epidemiology of anophthalmia and microphthalmia. Data for this population‐based assessment were obtained from the Texas Birth Defects Registry (TBDR) and Center for Health Statistics for the period 1999–2009. Descriptive analyses and estimates of birth prevalence and prevalence ratios (PR) were determined for this defect. There were 1,262 definite anophthalmia and microphthalmia patients identified in the TBDR, with an overall combined prevalence of 3.0 per 10,000 live births. More than half (55.7%) of the patients had at least one chromosome abnormality or syndrome. In addition, 92.4% of nonsyndromic patients (i.e., have no recorded chromosome abnormalities or syndromes) had at least one additional birth defect. After adjustment for multiple factors, the prevalence of nonsyndromic anophthalmia and microphthalmia was higher among mothers who had ≥2 previous fetal deaths (PR = 1.43, 95% confidence interval [CI]: 1.03–1.97) and among mothers with any reported diabetes (PR = 2.08, 95% CI: 1.49–2.90). Our results confirm that children with anophthalmia and microphthalmia frequently have genetic syndromes or are born with other major birth defects. Our findings add to the limited body of literature on anophthalmia and microphthalmia as well as help define subgroups of women who are more likely to have children with this malformation.
Antibiotic Resistance in Syria: A Local Problem Turns Into a Global Threat

Pharmaceutical sector of Syrian Arab Republic before the war was characterized by bold and successful development since the late 1980s. With the beginning of war in the country back in March 2011, momentum has changed significantly. Traumatism, communicable diseases related to morbidity and mortality as well as wound infections became particularly hot public health concern. This relates not only to the direct victims of military conflict but also to the displaced civilians, refugees, and ordinary citizens alike. Evolving legislative framework in Syria since 1980s tolerated dispensing of antibiotics without appropriate prescription. Such practice led to spreading of antibiotic resistance among the local bacteria frequently causing both community-acquired and nosocomial infections. Laboratory findings of resistant bacteria strains among the Syrian refugees in some European countries serve as evidence of concern spreading far beyond Middle East. Practice of self-diagnosis and self-medication with antibiotics by patients themselves and restraint to pharmacist advice is widespread. A number of recommendations is presented to stakeholders to compact antibiotic resistance after the peace is established in the country. The successful implementation of such recommendations is the way to preserve shrinking golden reserve of highly potent antibiotics as it is the last defense line against resistant bacterial strains causing severe life—threatening infections.
Unmasking the Hypovolemic Shock Continuum: The Compensatory Reserve

Hypovolemic shock exists as a spectrum, with its early stages characterized by subtle pathophysiologic tissue insults and its late stages defined by multi-system organ dysfunction. The importance of timely detection of shock is well known, as early interventions improve mortality, while delays render these same interventions ineffective. However, detection is limited by the monitors, parameters, and vital signs that are traditionally used in the intensive care unit (ICU). Many parameters change minimally during the early stages, and when they finally become abnormal, hypovolemic shock has already occurred. The compensatory reserve (CR) is a parameter that represents a new paradigm for assessing physiologic status, as it comprises the sum total of compensatory mechanisms that maintain adequate perfusion to vital organs during hypovolemia. When these mechanisms are overwhelmed, hemodynamic instability and circulatory collapse will follow. Previous studies involving CR measurements demonstrated their utility in detecting central blood volume loss before hemodynamic parameters and vital signs changed. Measurements of the CR have also been used in clinical studies involving patients with traumatic injuries or bleeding, and the results from these studies have been promising. Moreover, these measurements can be made at the bedside, and they provide a real-time assessment of hemodynamic stability. Given the need for rapid diagnostics when treating critically ill patients, CR measurements would complement parameters that are currently being used. Consequently, the purpose of this article is to introduce a conceptual framework where the CR represents a new approach to monitoring critically ill patients. Within this framework, we present evidence to support the notion that the use of the CR could potentially improve the outcomes of ICU patients by alerting intensivists to impending hypovolemic shock before its onset.
Statistical analyses for studying replication: Meta-analytic perspectives.

Formal empirical assessments of replication have recently become more prominent in several areas of science, including psychology. These assessments have used different statistical approaches to determine if a finding has been replicated. The purpose of this article is to provide several alternative conceptual frameworks that lead to different statistical analyses to test hypotheses about replication. All of these analyses are based on statistical methods used in meta-analysis. The differences among the methods described involve whether the burden of proof is placed on replication or nonreplication, whether replication is exact or allows for a small amount of "negligible heterogeneity," and whether the studies observed are assumed to be fixed (constituting the entire body of relevant evidence) or are a sample from a universe of possibly relevant studies. The statistical power of each of these tests is computed and shown to be low in many cases, raising issues of the interpretability of tests for replication. (PsycINFO Database Record
Engaging Older Men in Physical Activity: Implications for Health Promotion Practice

According to Health Canada (2016), only about 11% of older men meet recommended guidelines for physical activity, and participation decreases as men age. This places men at considerable risk of poor health, including an array of chronic diseases. A demographic shift toward a greater population of less healthy older men would substantially challenge an already beleaguered health-care system. One strategy to alter this trajectory might be gender-sensitized community-based physical activity. Therefore, a qualitative study was conducted to enhance understanding of community-dwelling older men’s day-to-day experiences with physical activity. Four men over age 65 participated in a semistructured interview, three walk-along interviews, and a photovoice project. An interpretive descriptive approach to data analysis was used to identify three key themes related to men’s experiences with physical activity: (a) “The things I’ve always done,” (b) “Out and About,” and (c) “You do need the group atmosphere at times. ” This research extends the knowledge base around intersections among older men, physical activity, and masculinities. The findings provide a glimpse of the diversity of older men and the need for physical activity programs that are unique to individual preferences and capacities. The findings are not generalized to all men but the learnings from this research may be of value to those who design programs for older men in similar contexts. Future studies might address implementation with a larger sample of older men who reside in a broad range of geographic locations and of different ethnicities.