Miracle-dz/UniFAR-FTUs huggingface dataset:
A Phase 3, Open-Label Study of Lumacaftor/Ivacaftor in Children 1 to Less Than 2 Years of Age with Cystic Fibrosis Homozygous for F508del-CFTR

Rationale Previous phase 3 trials showed that treatment with lumacaftor/ivacaftor was safe and efficacious in people aged ⩾2 years with cystic fibrosis (CF) homozygous for the F508del mutation in CFTR (CF transmembrane conductance regulator) (F/F genotype). Objectives To assess the safety, pharmacokinetics, and pharmacodynamics of lumacaftor/ivacaftor in children aged 1 to <2 years with the F/F genotype. Methods This open-label, phase 3 study consisted of two parts (part A [n = 14] and part B [n = 46]) in which two cohorts were enrolled on the basis of age (cohort 1, 18 to <24 mo; cohort 2, 12 to <18 mo). For the 15-day treatment period in part A, the lumacaftor/ivacaftor dose was based on weight at screening. Pharmacokinetic data from part A were used to determine dose-based weight boundaries for part B (24-wk treatment period). Measurements and Main Results The primary endpoint of part A was pharmacokinetics, and the primary endpoint for part B was safety and tolerability. Secondary endpoints for part B were absolute change in sweat chloride concentration from baseline at Week 24 and pharmacokinetics. Analysis of pharmacokinetic data from part A confirmed the appropriateness of part B dosing. In part B, 44 children (95.7%) had adverse events, which for most were either mild (52.2% of children) or moderate (39.1% of children) in severity. The most common adverse events were cough, infective pulmonary exacerbation of CF, pyrexia, and vomiting. At Week 24, mean absolute change from baseline in sweat chloride concentration was −29.1 mmol/L (95% confidence interval, −34.8 to −23.4 mmol/L). Growth parameters (body mass index, weight, length, and associated z-scores) were normal at baseline and remained normal during the 24-week treatment period. Improving trends in some biomarkers of pancreatic function and intestinal inflammation, such as fecal elastase-1, serum immunoreactive trypsinogen, and fecal calprotectin, were observed. Conclusions Lumacaftor/ivacaftor was generally safe and well tolerated in children aged 1 to <2 years with the F/F genotype, with a pharmacokinetic profile consistent with studies in older children. Efficacy results, including robust reductions in sweat chloride concentration, suggest the potential for CF disease modification with lumacaftor/ivacaftor treatment. These results support the use of lumacaftor/ivacaftor in this population. Clinical trial registered with www.clinicaltrials. gov (NCT 03601637).
Clinical features of hepatitis E infections in patients with hematologic disorders

Hepatitis E virus is increasingly being reported to cause chronic infection in immunocompromised patients. However, less is known about patients with an underlying hematologic disease. In particular, the impact of hepatitis E infection on oncological therapy has been poorly described. In this retrospective single-center study, we analyzed 35 hematologic patients with hepatitis E, including 20 patients under active oncological treatment and 15 patients who were in the post-treatment follow-up or under active surveillance. The primary aim was to describe the clinical courses with particular focus on any hepatitis E-related therapy modifications of cancer-directed therapy. In the majority (60%) of patients who were under active oncological treatment, hepatitis E-related therapy modifications were made, and 25% of deaths were due to progression of the hematologic disease. In patients receiving concomitant oncological treatment, no hepatitis E-related deaths occurred. In contrast, two patients in the follow-up group died from hepatitis E-associated acute-on-chronic liver failure. Chronic hepatitis E was observed in 34% of all cases and 43% received ribavirin therapy; of those, 27% achieved a sustained virological response. CD20-directed therapy was the only independent risk factor for developing chronic hepatitis E. We conclude that CD20-directed treatment at any time point is a risk factor for developing chronic hepatitis E. Nevertheless, since mortality from the progression of hematologic disease was higher than hepatitis E-related mortality, we suggest careful case-by-case decisions on modifications of cancer treatment. Patients in the post-treatment follow-up phase may also suffer from severe courses and hepatitis E chronicity occurs as frequently as in patients undergoing active therapy.
Infusing sustainability in higher education in Ireland: the green curriculum model (GCM) and the dispositions, abilities and behaviours (DAB) competency framework

There are numerous sustainability challenges facing the world today, including: climate change, pollution, consumerism and poverty. To make the world a more sustainable and better place to live in, humanity needs to be able to generate solutions to increasingly complex, and ever growing global sustainability challenges. Education is an important vehicle in this respect, in that it can be used to re-orient perspectives and attitudes of learners towards sustainability, motivating learners to seek to transform themselves and society, and thus promote actions for sustainability. In Ireland, despite various initiatives from the turn of the 21st century, the integration of sustainability in academic programmes within higher education has remained largely unchanged. Educators within higher education in Ireland and elsewhere need specific guidance on how best to integrate and/ or infuse sustainability in their programmes and courses of study. This research set out to do this – thus, it explored how sustainability might be integrated/ infused in higher education, with a particular focus on identifying the key sustainability themes, principles, pedagogic practices and specific competencies that should underpin a model for infusing sustainability in higher education, while also investigating how the effectiveness or otherwise of particular competencies (developed within a sustainability-infusion curriculum process) might be evaluated at a meta-level. This mixed methods research study focused on the Irish context, primarily researching and analysing developments within Dublin City University, which was engaged in the reorientation of its curricula towards sustainability in the EU Tempus RUCAS project from 2010-2013. The outcomes of this study have resulted in the design and development of the Green Curriculum Model, a conceptual-design framework for educators to re-orient curricula towards sustainability. The research also resulted in the design, development and evaluation of a sustainability competencies assessment tool called the Dispositions, Abilities and Behaviours (DAB) Framework for profiling learners’ sustainability competencies across higher education faculties, programmes and courses.
Correlation analysis of the triglyceride glucose index and heart failure with preserved ejection fraction in essential hypertensive patients

Triglyceride glucose index (TyG index) is a novel marker of insulin resistance. Studies have shown that TyG index is closely associated with the occurrence of hypertension and cardiovascular disease. However, little is known about the correlation between TyG index and the occurrence of heart failure with preserved ejection fraction (HFpEF) in hypertensive patients.
Economic evaluation of day hospital versus intensive outpatient mentalization-based treatment alongside a randomized controlled trial with 36-month follow-up.

Mentalization-based treatment (MBT) has demonstrated robust effectiveness in the treatment of borderline personality disorder (BPD) in both day-hospital (MBT-DH) and intensive outpatient MBT (MBT-IOP) programs. Given the large differences in intensity and associated treatment costs, there is a need for studies comparing their cost-effectiveness. A health economic evaluation of MBT-DH versus MBT-IOP was performed alongside a multicenter randomized controlled trial with a 36-month follow-up. In three mental health-care institutions in the Netherlands, 114 patients were randomly allocated to MBT-DH (n = 70) or MBT-IOP (n = 44) and assessed every 6 months. Societal costs were compared with quality-adjusted life years (QALYs) gained and the number of months in remission over 36 months. The QALY gains over 36 months were 1.96 (SD = .58) for MBT-DH and 1.83 (SD = .56) for MBT-IOP; the respective number of months in remission were 16.0 (SD = 11.5) and 11.1 (SD = 10.7). Societal costs were €106,038 for MBT-DH and €91,368 for MBT-IOP. The incremental cost for one additional QALY with MBT-DH compared with MBT-IOP was €107,000. The incremental cost for 1 month in remission was almost €3000. Assuming a willingness-to-pay threshold of €50,000 for a QALY, there was a 33% likelihood that MBT-DH is more cost-effective than MBT-IOP in terms of costs per QALY. Although MBT-DH leads to slightly more QALYs and remission months, it is probably not cost-effective when compared with MBT-IOP for BPD patients, as the small additional health benefits in MBT-DH did not outweigh the substantially higher societal costs. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
Ageing meets kidney disease.

Chronic kidney disease (CKD) is defined as abnormalities of kidney structure or function, present for longer than 3 months, with implications for health. The most used diagnostic criteria are a urinary albumin:creatinine ratio ≧30 mg/g or an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. Either of these diagnostic thresholds are associated to adverse health outcomes. GFR decreases with age and the prevalence of CKD is highest in older adults; moreover, the presence of CKD is associated with an increased risk of all-cause and cardiovascular death related to accelerated ageing in all age ranges, and the absolute increase in risk is highest for those aged over 75 years. Indeed, premature death is a more common outcome than CKD progression to kidney failure requiring kidney replacement therapy. The progressive ageing of the world population contributes to the projection that CKD will become the second commonest cause of death before the end of the century in countries with long life expectancy. The current collection of selected studies on kidney disease and ageing published in Age&Ageing, NDT, and CKJ provides an overview of key topics, including cognitive decline, sarcopenia, wasting and cardiovascular and non-cardiovascular morbidity and mortality, the management of kidney failure and gender differences in CKD progression.
Prevalence of probable depression and factors associated with mean Hopkins Symptom Checklist (HSCL) depression score among young women at high risk aged 15–24 years in Kampala, Uganda

Background In populations at high risk of HIV infection, rates of depression can be elevated with far-reaching effects on overall well-being. There is limited research on depression among young women engaged in high-risk sexual behaviour in low and middle-income settings. We investigated the prevalence, correlates and factors associated with mean HSCL depression score among young women at high risk (aged 15–24 years old) in Kampala, Uganda. Methods We conducted a baseline analysis of a randomized controlled trial. Probable depression was measured using the 15-item Hopkins Symptoms Checklist for depression (HSCL). This checklist has been validated in Ugandan populations, and our reliability test gave a Cronbach alpha coefficient of 0.89. The test was administered to all the participants. Participants whose HSCL mean score was greater than 1.75 were categorized as having probable depression. Socio-demographics and behaviour data were collected and factors associated with mean HSCL depression score were analysed using multiple linear regression. Results Data was available for 600 participants, mean age 20.4 (SD±2.44) years. The prevalence of probable depression was 56% (95% CI, 52%-60%). Probable depression symptoms were most prevalent among those who reported ever-experiencing violence from a sexual partner (64.7%), those aged between 20–24 years (58.2%) and those who reported more than 10 sexual exposures in the month prior to the interview (56.8%). At the adjusted analysis level, condom use during their last sexual intercourse prior to the survey decreased probable depression symptoms by 0.147 units compared to those who never used condoms (β = -0.147, 95% CI -0.266–0.027). Having experienced physical violence by a sexual partners increased mean HSCL depression score by 0.183 units compared to those who have never experienced violence (β = 0.183, 95% CI 0.068–0.300). Participants who reported ever using drugs of addiction had their mean HSCL depression scoreincrease by 0.20 units compared to those who have never used (β = 0.20,95% CI 0.083–0.317). Conclusions Probable depression is high in this population and increased mean HSCL depression score is related to violence. Periodic screening for depression and interventions targeting depression, partner violence and risky sexual behaviours are recommended.
Seasonal variation in semen quality is not associated with fecundity in the Utah Population Database

We determine whether a suspected seasonal variability in semen quality affect subsequent live birth rates. This is a retrospective, cohort analysis of men who provided semen analyses as part of fertility workup through a large andrology lab between 1996 and 2013 and corresponding birth rates using the Utah Population Database (UPDB). Semen parameters were analysed including total motile count (TMC), total sperm count, sperm concentration and progressive motility. Corresponding live births reflect those born in the state of Utah and were derived from birth certificate data available in the UPDB. Descriptive statistics were reported along with linear regression analysis with mixed effected models to test for an interaction between seasonal variation in semen quality and birth rates, accounting for age at the time of the semen analysis and abstinence time. A total of 11,929 patients and 14,765 semen samples were included. Only 3597 men (39% of men) had one or more values outside the World Health Organization reference range for their semen parameters. Linear regression demonstrated a consistent U‐shaped relationship between TMC, total sperm count, and sperm concentration and season, with spring and winter yielding the highest values with a decline in the summer and fall. 7319 of these males had recorded live births for a total of 13,502 live births during the study period after a median follow‐up of 7.2 years (IQR: 3.9–11.0). We did not find a significant interaction between specific semen parameters for a specific season and subsequent live births. Semen quality was the highest in the spring and winter, however there was no interaction between seasonal variability in semen quality and subsequent births. This is one of the largest studies describing seasonal variation in semen quality in humans.
International Consensus Classification of Myeloid Neoplasms and Acute Leukemia: Integrating Morphological, Clinical, and Genomic Data.

The classification of myeloid neoplasms and acute leukemias was last updated in 2016 within a collaboration between the World Health Organization (WHO), the Society for Hematopathology, and the European Association for Haematopathology. This collaboration was primarily based on input from a clinical advisory committees (CAC) composed of pathologists, hematologists, oncologists, geneticists, and bioinformaticians from around the world. The recent advances in our understanding of the biology of hematologic malignancies, the experience with the use of the 2016 WHO classification in clinical practice, and the results of clinical trials have indicated the need for further revising and updating the classification. As a continuation of this CAC-based process, the authors, a group with expertise in the clinical, pathologic and genetic aspects of these disorders, developed the International Consensus Classification (ICC) of myeloid neoplasms and acute leukemias. Using a multiparameter approach, the main objective of the consensus process was the definition of real disease entities, including the introduction of new entities and refined criteria for existing diagnostic categories, based on accumulated data. The ICC is aimed at facilitating diagnosis and prognostication of these neoplasms, improving treatment of affected patients, and allowing the design of innovative clinical trials.
Surgical importance of the tympanic bone: multidetector computed tomography findings

Objectives To measure tympanic bone thickness (anterior-superior, anterior-inferior, and inferior wall), external ear canal length, and tympanomandibular distance that can be useful in cases that undergo tympanic bone resection. Materials and Methods The temporal computed tomography (CT) images of 349 patients were retrospectively evaluated. The anterior-inferior, anterior-superior, and inferior wall thicknesses; tympanomandibular distance; and external auditory canal (EAC) bone canal length were measured from the narrowest part of the canal. The shapes of the EAC in the coronal and sagittal planes were also examined. Results The numbers of female and male patients were similar, and the mean age was 49.45±13.95 years. The anterior-superior, anterior-inferior, and inferior wall thicknesses were 1.92±0.60, 2.54±0.74, and 9.16±2.20 mm, respectively. The anterior-superior and anterior-inferior wall thicknesses and canal lengths were greater on the right side (P<0.001). All measurement values were higher in males, except right tympanomandibular distance (P<0.05). A non-significant negative correlation was found between the age of the participants and the left anterior-inferior wall and tympanomandibular distance on both sides. Intra-observer agreement was high for all measurements. We observed four main shapes in the external ear canal in the coronal plane Type 3, Type 2, Type 1, and Type 4 in order of frequency on the right, and Type 2, Type 3, Type 1, and Type 4 on the left. In the sagittal plane, we detected three shapes oval (74.4%), triangular (16.3%), and round (9.4%). Conclusion The anterior wall thicknesses and tympanomandibular distance should be measured on preoperative temporal bone CT to safely perform tympanic bone anterior resection, which is required in some otological procedures, and also to prevent temporomandibular joint damage.
Identification of cranial nerve ganglia using sectioned images and three-dimensional models of a cadaver

Background Cranial nerve ganglia, which are prone to viral infections and tumors, are located deep in the head, so their detailed anatomy is difficult to understand using conventional cadaver dissection. For locating the small ganglia in medical images, their sectional anatomy should be learned by medical students and doctors. The purpose of this study is to elucidate cranial ganglia anatomy using sectioned images and three-dimensional (3D) models of a cadaver. Methods One thousand two hundred and forty-six sectioned images of a male cadaver were examined to identify the cranial nerve ganglia. Using the real color sectioned images, real color volume model having a voxel size of 0.4 × 0.4 × 0.4 mm was produced. Results The sectioned images and 3D models can be downloaded for free from a webpage, anatomy.dongguk. ac.kr/ganglia. On the images and model, all the cranial nerve ganglia and their whole course were identified. In case of the facial nerve, the geniculate, pterygopalatine, and submandibular ganglia were clearly identified. In case of the glossopharyngeal nerve, the superior, inferior, and otic ganglia were found. Thanks to the high resolution and real color of the sectioned images and volume models, detailed observation of the ganglia was possible. Since the volume models can be cut both in orthogonal planes and oblique planes, advanced sectional anatomy of the ganglia can be explained concretely. Conclusions The sectioned images and 3D models will be helpful resources for understanding cranial nerve ganglia anatomy, for performing related surgical procedures.
Metabolic and epigenetic dysfunctions underlie the arrest of in vitro fertilized human embryos in a senescent-like state

Around 60% of in vitro fertilized (IVF) human embryos irreversibly arrest before compaction between the 3- to 8-cell stage, posing a significant clinical problem. The mechanisms behind this arrest are unclear. Here, we show that the arrested embryos enter a senescent-like state, marked by cell cycle arrest, the down-regulation of ribosomes and histones and down-regulation of MYC and p53 activity. The arrested embryos can be divided into 3 types. Type I embryos fail to complete the maternal-zygotic transition, and Type II/III embryos have low levels of glycolysis and either high (Type II) or low (Type III) levels of oxidative phosphorylation. Treatment with the SIRT agonist resveratrol or nicotinamide riboside (NR) can partially rescue the arrested phenotype, which is accompanied by changes in metabolic activity. Overall, our data suggests metabolic and epigenetic dysfunctions underlie the arrest of human embryos.
Grower decision-making factors in adoption of specialty cultivars: A case study of potatoes in the San Luis Valley

Potatoes are the most consumed vegetable worldwide and play an important role in the U.S. economy. Growers make critical decisions each year in choosing which cultivar to grow, based on factors such as yield, resilience to the growing environment, and utility in the food industry. Current research supports the finding that less-common specialty cultivars (SCs) have benefits for human health. However, growers have been slow to adopt SCs into mainstream operations. Here, we identify major factors in the decision-making process that determine whether a population of growers in the San Luis Valley, Colorado, a major potato-growing region, adopt SC potatoes. We used a combination of ethnographic techniques and quantitative methods to examine drivers of adoption. The data demonstrate grower perceptions within potato farming and the complexity of interacting factors in decision-making. An integration of the Theory of Planned Behavior, Rational Expectation Hypothesis, and Diffusion of Innovation models identifies economic and social factors that influence grower decision-making. Growers that were more aware of specialty cultivar innovation and associated consumer demand were more open to SCs adoption. Other influencing factors include a grower’s experience selling a SC in the previous year and access to diverse markets. Based on these data, we developed a new model to explain grower decision-making processes in adopting SCs. The model demonstrates that one current barrier to adoption is access to buyers, including warehouses, retailers, and households. Taken together, this research demonstrates how rational expectations stem from economic outcomes, knowledge, and experience in the potato industry. These results are important in helping to consider opportunities for growers to access new, higher value markets, while also improving consumer access to nutritious cultivars.