Miracle-dz/UniFAR-FTUs huggingface dataset:
Meet and eat, an interdisciplinary group intervention for patients with myotonic dystrophy about healthy nutrition, meal preparation, and consumption: a feasibility study

Abstract Purpose: To develop and evaluate an interdisciplinary group intervention for patients with myotonic dystrophy regarding healthy nutrition, meal preparation, and consumption, called Meet and Eat. Materials and methods: A design-based approach was used, exploring experiences and needs of patients with myotonic dystrophy and their next of kin. This resulted in a 4-week interdisciplinary outpatient group intervention to increase awareness and change behavior. In a mixed-method feasibility study this intervention was evaluated with participants and facilitators. Results: Participants reported on social impact of difficulties with eating and drinking (speaking, swallowing, and social embarrassment) and a variety of complaints affecting meal preparation and consumption. Patients and family members expressed the wish to learn from others. After delivery of the intervention, self-reported outcome measures demonstrated improvement on eating and drinking issues in daily life. The qualitative evaluation showed increased awareness and appreciation of the following design principles: peer support, multidisciplinary approach, active involvement of patient with myotonic dystrophy and their next of kin by using personal goals and motivational interviewing. Conclusion: Participation in Meet and Eat seemed to increase insight in patients’ condition and ways of management. However, a longer self-management life style program is recommended to change behavior. Implications for rehabilitation Patients with myotonic dystrophy experience physical, cognitive and psychosocial problems to manage healthy nutrition, meal preparation, and consumption; This multidisciplinary group intervention Meet and Eat in patients with myotonic dystrophy appears to be feasible and seems to result in increased insight and management strategies; Peer support, multidisciplinary approach, personal goals, and involvement of family were key factors; To change eating and drinking behavior, a 4-week intervention is too short.
Temporal pattern of neuronal insulin release during Caenorhabditis elegans aging: Role of redox homeostasis

The insulin‐IGF‐1/DAF‐2 pathway has a central role in the determination of aging and longevity in Caenorhabditis elegans and other organisms. In this paper, we measured neuronal insulin secretion (using INS‐22::Venus) during C. elegans lifespan and monitored how this secretion is modified by redox homeostasis. We showed that INS‐22::Venus secretion fluctuates during the organism lifetime reaching maximum levels in the active reproductive stage. We also demonstrate that long‐lived daf‐2 insulin receptor mutants show remarkable low levels of INS‐22::Venus secretion. In contrast, we found that short‐lived mutant worms that lack the oxidation repair enzyme MSRA‐1 show increased levels of INS‐22::Venus secretion, specifically during the reproductive stage. MSRA‐1 is a target of the insulin‐IGF‐1/DAF‐2 pathway, and the expression of this antioxidant enzyme exclusively in the nervous system rescues the mutant insulin release phenotype and longevity. The msra‐1 mutant phenotype can also be reverted by antioxidant treatment during the active reproductive stage. We showed for the first time that there is a pattern of neuronal insulin release with a noticeable increment during the peak of reproduction. Our results suggest that redox homeostasis can modulate longevity through the regulation of insulin secretion, and that the insulin‐IGF‐1/DAF‐2 pathway could be regulated, at least in part, by a feedback loop. These findings highlight the importance of timing for therapeutic interventions aimed at improving health span.
Generation of transgene-free porcine intermediate type induced pluripotent stem cells

ABSTRACT Physiologically and anatomically, humans and pigs share many similarities, which make porcine induced pluripotent stem cells (piPSCs) very attractive for modeling human cell therapy as well as for testing safety of iPSC based cell replacement therapies. To date, several integrative and non-integrative strategies have been reported to successfully generate piPSCs, but all resulting piPSCs had integration of transgenes. The use of integrative methods has the disadvantage of potential lack of silencing or inappropriate re-activation of these genes during differentiation, as well as uncertainty regarding disruption of important genomic regions caused by integration. In our study, we performed a non-integrative vector based reprogramming approach using porcine fetal fibroblasts. The resulting four piPSC lines were positive for pluripotency marker and when subjected to in vitro and in vivo differentiation assays, all four lines formed embryoid bodies, capable to differentiate into all three germ layers, and three out of the four cell lines formed teratomas. PCR analysis on genomic and plasmid DNA revealed that the episomal vectors were undetectable in six out of eight subclones derived from one of the piPSC lines (piPSC1) above passage 20. These piPSCs could potentially be ideal cell lines for the generation of porcine in vitro and in vivo models. Furthermore, subsequent analyses of our new transgene independent piPSCs could provide novel insights on the genetic and epigenetic necessities to achieve and maintain piPSCs.
Estimating Returns to College Attainment: Comparing Survey and State Administrative Data–Based Estimates

Background: The increasing availability of massive administrative data sets linking postsecondary enrollees with postcollege earnings records has stimulated a wealth of new research on the returns to college and has accelerated state and federal efforts to hold institutions accountable for students’ labor market outcomes. Many of these new research and policy efforts rely on state databases limited to postsecondary enrollees who work in the same state postcollege, with limited information regarding family background and precollege ability. Objectives: In this article, we use recent waves of data from the National Longitudinal Survey of Youth 1997 to provide new, nationally representative, nonexperimental estimates of the returns to degrees, as well as to assess the possible limitations of single-state, administrative data–based estimates. Research design: To do this, we explore the sensitivity of estimated returns to college, by testing different sample restrictions, inclusion of different sets of covariates, and alternative ways of treating out-of-state earnings to approximate the real-world limitations of state administrative databases. Results: We find that failure to control for measures of student ability leads to upward bias, while limiting the sample to college enrollees only leads to an understatement of degree returns. On net, these two biases roughly balance out, suggesting that administrative data–based estimates may reasonably approximate true returns. Conclusions: We conclude with a discussion of the relative advantages and disadvantages of survey versus administrative data for estimating returns to college as well as implications for research and policy efforts based upon single-state administrative databases.
The Pseudomonas aeruginosa T6SS-VgrG1b spike is topped by a PAAR protein eliciting DNA damage to bacterial competitors

Significance The type VI secretion system (T6SS) is a molecular weapon used for interbacterial competition. It acts like a crossbow bolt to deliver toxic effectors into target cells. Here we characterize a T6SS toxin which we call Tse7. We show that it is a DNase and that its two-domain PAAR-nuclease structure allows coupling to the T6SS VgrG tip via the PAAR domain. Disruption of this interface abrogates toxin delivery and results in the loss of interbacterial killing ability. We identify the corresponding immunity protein, Tsi7, and show it directly interacts with the Tse7 toxin. Finally, as Tse7–Tsi7 sequences vary significantly between Pseudomonas aeruginosa strains, and as Tsi7 protection is strain specific, we show that this toxin/immunity pair contributes to self- nonself-recognition. The type VI secretion system (T6SS) is a supramolecular complex involved in the delivery of potent toxins during bacterial competition. Pseudomonas aeruginosa possesses three T6SS gene clusters and several hcp and vgrG gene islands, the latter encoding the spike at the T6SS tip. The vgrG1b cluster encompasses seven genes whose organization and sequences are highly conserved in P. aeruginosa genomes, except for two genes that we called tse7 and tsi7. We show that Tse7 is a Tox-GHH2 domain nuclease which is distinct from other T6SS nucleases identified thus far. Expression of this toxin induces the SOS response, causes growth arrest and ultimately results in DNA degradation. The cytotoxic domain of Tse7 lies at its C terminus, while the N terminus is a predicted PAAR domain. We find that Tse7 sits on the tip of the VgrG1b spike and that specific residues at the PAAR–VgrG1b interface are essential for VgrG1b-dependent delivery of Tse7 into bacterial prey. We also show that the delivery of Tse7 is dependent on the H1-T6SS cluster, and injection of the nuclease into bacterial competitors is deployed for interbacterial competition. Tsi7, the cognate immunity protein, protects the producer from the deleterious effect of Tse7 through a direct protein–protein interaction so specific that toxin/immunity pairs are effective only if they originate from the same P. aeruginosa isolate. Overall, our study highlights the diversity of T6SS effectors, the exquisite fitting of toxins on the tip of the T6SS, and the specificity in Tsi7-dependent protection, suggesting a role in interstrain competition.
Adipose Tissue Insulin Resistance in Youth on the Spectrum From Normal Weight to Obese and From Normal Glucose Tolerance to Impaired Glucose Tolerance to Type 2 Diabetes

OBJECTIVE Adipose tissue insulin resistance is one of the pathophysiological components of type 2 diabetes. Herein we investigated: 1) adipose insulin resistance index (Adipose-IR) (calculated as fasting insulin × free fatty acids [FFAs]) in youth across the spectrum of adiposity from normal weight to obese and the spectrum from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes, 2) the relationship of Adipose-IR with physical and metabolic characteristics, and 3) the predictive power of Adipose-IR for determining dysglycemia in youth. RESEARCH DESIGN AND METHODS A total of 205 youth had fasting glucose, insulin, FFA, Adipose-IR, body composition, visceral adipose tissue (VAT), leptin, and adiponectin evaluated. RESULTS Adipose-IR was 2.2-fold higher in obese NGT, 4.3-fold higher in IGT, and 4.6-fold higher in type 2 diabetes compared with that in normal-weight peers (all P < 0.05). Females with dysglycemia (IGT and type 2 diabetes) had higher Adipose-IR than their male counterparts (P < 0.001). Adipose-IR correlated positively with total body and visceral adiposity, fasting glucose, HOMA-IR, and leptin and negatively with adiponectin. Receiver operating characteristic curve analysis yielded an optimal cutoff for Adipose-IR of 9.3 μU/mL × mmol/L for determining dysglycemia with 80% predictive power. CONCLUSIONS Adipose-IR is a simple surrogate estimate that reflects pathophysiological alterations in adipose tissue insulin sensitivity in youth, with progressive deterioration from normal weight to obese and from NGT to IGT to type 2 diabetes. Adipose-IR can be applied in large-scale epidemiological/observational studies of the natural history of youth-onset type 2 diabetes and its progression or reversal with intervention strategies.
Pyrite-Type CoS2 Nanoparticles Supported on Nitrogen-Doped Graphene for Enhanced Water Splitting

It is extremely meaningful to develop cheap, highly efficient, and stable bifunctional electrocatalysts for both hydrogen and oxygen evolution reactions (HER and OER) to promote large-scale application of water splitting technology. Herein, we reported the preparation of CoS2 nanoparticles supported on nitrogen-doped graphene (CoS2@N-GN) by one-step hydrothermal method and the enhanced electrochemical efficacy for catalyzing hydrogen and oxygen in water electrolysis. The CoS2@N-GN composites are composed of nitrogen-doped graphene and CoS2 nanocrystals with the average size of 73.5 nm. Benefitting from the improved electronic transfer and synergistic effect, the as-prepared CoS2@N-GN exhibits remarkable OER and HER performance in 1.0 M KOH, with overpotentials of 243 mV for OER and 204 mV for HER at 10 mA cm−2, and the corresponding Tafel slopes of 51.8 and 108 mV dec−1, respectively. Otherwise, the CoS2@N-GN hybrid also presents superior long-term catalytic durability. Moreover, an alkaline water splitting device assembled by CoS2@N-GN as both anode and cathode can achieve a low cell voltage of 1.53 V at 60 °C with a high faraday efficiency of 100% for overall water splitting. The tremendously enhanced electrochemical behaviors arise from favorable factors including small sized, homogenously dispersed novel CoS2 nanocrystals and coupling interaction with the underlying conductive nitrogen-doped graphene, which would provide insight into the rational design of transition metal chalcogenides for highly efficient and durable hydrogen and oxygen-involved electrocatalysis.
Speeding up Lazy-Grounding Answer Set Solving

The grounding bottleneck is an important open issue in Answer Set Programming. Lazy grounding addresses it by interleaving grounding and search. The performance of current lazy-grounding solvers is not yet comparable to that of ground-and-solve systems, however. The aim of this thesis is to extend prior work on lazy grounding by novel heuristics and other techniques like non-ground conflict learning in order to speed up solving. Parts of expected results will be beneficial for ground-and-solve systems as well.
Bridging the intention-behavior gap for cardiac rehabilitation participation: the role of perceived barriers*

Abstract Purpose: Patients referred to cardiac rehabilitation after an acute coronary syndrome event commonly report strong intention to attend, but at least one-third do not participate. This study explored whether well-documented cardiac rehabilitation barriers (e.g., comorbidities, logistical/time constraints, and low social support) moderate the association between intention to participate and actual program enrollment and attendance. Method: Following referral but prior to commencing a 12-week outpatient cardiac rehabilitation program, 100 patients with acute coronary syndrome completed measures of intention to attend cardiac rehabilitation, perceived cardiac rehabilitation barriers, and social support. Program enrollment and attendance were determined by chart review. Results: Despite high reported intention to attend (M = 6.08/7.00, SD = 1.80), nearly one-in-five did not enroll. Weaker intention to attend (b = 0.46, SE = 0.16, p = 0.004) and greater cardiac rehabilitation barriers (b= −1.67, SE = 0.70, p = 0.017) corresponded to lower program enrollment. Similarly, weaker intention (b = 2.29, SE = 0.50, p < 0.001) and greater barriers (b =−6.19, SE = 1.55, p < 0.001) predicted poorer attendance. Barriers moderated the association between intention to participate and cardiac rehabilitation enrollment (b=−0.60, SE = 0.29, p = 0.037) and attendance (b = −3.12, SE = 1.02, p = 0.003). Conclusions: Perceived cardiac rehabilitation barriers influence whether patients successfully translate their intention to attend into actual program participation. Enhancing self-efficacy to overcome barriers may represent an important intervention target among prospective cardiac rehabilitation patients. Implications for Rehabilitation Patients with acute coronary syndrome report strong intention to attend cardiac rehabilitation upon referral, yet cardiac rehabilitation programs remain underutilized. Assessing and addressing perceived barriers during the transition to cardiac rehabilitation, even when patients present as highly motivated to attend, may be critical to promoting program uptake. Rehabilitation professionals should ask patients about specific barriers to attending cardiac rehabilitation (e.g., financial constraints, transportation problems) and provide individualized solutions (e.g., fee subsidization, home- or web-based programs) to increase participation.
Rat Hepatitis E Virus as Cause of Persistent Hepatitis after Liver Transplant

All hepatitis E virus (HEV) variants reported to infect humans belong to the species Orthohepevirus A (HEV-A). The zoonotic potential of the species Orthohepevirus C (HEV-C), which circulates in rats and is highly divergent from HEV-A, is unknown. We report a liver transplant recipient with hepatitis caused by HEV-C infection. We detected HEV-C RNA in multiple clinical samples and HEV-C antigen in the liver. The complete genome of the HEV-C isolate had 93.7% nt similarity to an HEV-C strain from Vietnam. The patient had preexisting HEV antibodies, which were not protective against HEV-C infection. Ribavirin was an effective treatment, resulting in resolution of hepatitis and clearance of HEV-C viremia. Testing for this zoonotic virus should be performed for immunocompromised and immunocompetent patients with unexplained hepatitis because routine hepatitis E diagnostic tests may miss HEV-C infection. HEV-C is also a potential threat to the blood product supply.
Early versus late anticoagulation for ischaemic stroke associated with atrial fibrillation: multicentre cohort study

Background and purpose The optimal time to start oral anticoagulant (OAC) in patients with ischaemic stroke due to non-valvular atrial fibrillation (AF) is unknown. We reviewed OAC timing in relation to 90-day clinical outcomes as a post hoc analysis from a prospective multicentre observational study. Methods We included patients with data on time to initiation of OAC from CROMIS-2 (Clinical Relevence Of Microbleeds In Stroke-2), a prospective observational inception cohort study of 1490 patients with ischaemic stroke or transient ischaemic attack (TIA) and AF treated with OAC. The primary outcome was the composite outcome of TIA, stroke (ischaemic stroke or intracranial haemorrhage) or death within 90 days of the qualifying stroke or TIA. We performed adjusted logistic regression analyses to compare early (0–4 days) and later (≥5 days or never started) OAC initiation. Results We included 1355 patients, mean age 76 (SD 10), 580 (43%) women. OAC was started early in 358 (26%) patients and later (or not at all) in 997 (74%) patients. The event rate within 90 days was 48/997 (5%) in the late-OAC group (2 intracranial haemorrhages, 18 ischaemic strokes or TIAs and 31 deaths (three deaths were as a result of new ischaemic strokes)) versus 7/358 (2%) in the early-OAC group (5 ischaemic strokes or TIAs and 2 deaths). In adjusted analyses, late OAC was not associated with the composite outcome (adjusted OR 1.17, 95% CI 0.48 to 2.84, p=0.736). Conclusion In adjusted analyses, early OAC after acute ischaemic stroke or TIA associated with AF was not associated with a difference in the rate of the composite outcome of stroke, TIA or death at 90 days, compared with late OAC. However, despite adjustment for important baseline factors, patients selected for early OAC and late OAC might still have differed in important respects; evaluation of OAC timing in adequately powered randomised trials is required. Clinical trial registration NCT02513316.
Development of machine learning algorithms for prediction of discharge disposition after elective inpatient surgery for lumbar degenerative disc disorders.

OBJECTIVEIf not anticipated and prearranged, hospital stay can be prolonged while the patient awaits placement in a rehabilitation unit or skilled nursing facility following elective spine surgery. Preoperative prediction of the likelihood of postoperative discharge to any setting other than home (i.e., nonroutine discharge) after elective inpatient spine surgery would be helpful in terms of decreasing hospital length of stay. The purpose of this study was to use machine learning algorithms to develop an open-access web application for preoperative prediction of nonroutine discharges in surgery for elective inpatient lumbar degenerative disc disorders.METHODSThe American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients who underwent elective inpatient spine surgery for lumbar disc herniation or lumbar disc degeneration between 2011 and 2016. Four machine learning algorithms were developed to predict nonroutine discharge and the best algorithm was incorporated into an open-access web application.RESULTSThe rate of nonroutine discharge for 26,364 patients who underwent elective inpatient surgery for lumbar degenerative disc disorders was 9.28%. Predictive factors selected by random forest algorithms were age, sex, body mass index, fusion, level, functional status, extent and severity of comorbid disease (American Society of Anesthesiologists classification), diabetes, and preoperative hematocrit level. On evaluation in the testing set (n = 5273), the neural network had a c-statistic of 0.823, calibration slope of 0.935, calibration intercept of 0.026, and Brier score of 0.0713. On decision curve analysis, the algorithm showed greater net benefit for changing management over all threshold probabilities than changing management on the basis of the American Society of Anesthesiologists classification alone or for all patients or for no patients. The model can be found here: https://sorg-apps.shinyapps. io/discdisposition/. CONCLUSIONSMachine learning algorithms show promising results on internal validation for preoperative prediction of nonroutine discharges. If found to be externally valid, widespread use of these algorithms via the open-access web application by healthcare professionals may help preoperative risk stratification of patients undergoing elective surgery for lumbar degenerative disc disorders.
Particle-Attached and Free-Living Archaeal Communities in the Benthic Boundary Layer of the Mariana Trench

The benthic boundary layer (BBL) is the part of the water column that is situated near to the sediment surface, where active oceanic biogeochemical cycling occurs. Archaea play an important role in mediating this cycling, however, their composition and diversity in the BBL remain largely unknown. We investigated the community composition and abundance of both particle-attached (PA) and free-living (FL) archaea in the BBL on the slopes of the Mariana Trench using Illumina sequencing and quantitative PCR (qPCR), at both the DNA and RNA levels. Our results showed that Thaumarchaeota (>90%) and Woesearchaeota (1–10%) dominated in all the BBL samples, and that the former was composed mainly of Marine Group I (MGI). A clear separation of PA and FL samples was observed, and they showed a high level of similarity to the subsurface sediments and the water column, respectively. No significant differences were detected in the archaeal communities located in the southern and northern slopes of the Mariana Trench, or between the levels of DNA and RNA. However, lower RNA/DNA ratios (estimated by qPCR) were found in the PA samples than in the FL samples, indicating higher transcriptional activities in the FL fractions. A distinct archaeal community structure was found in the middle of the trench when compared with samples collected at the same depth at other stations along the trench slopes. This indicates that a dynamic deep current might affect the distribution of organic matter on the slopes. Our study provides direct information regarding the archaeal communities in the BBL of the Mariana Trench. We suggest that this might promote further exploration of the ecological roles and microbial processes of such communities located in deep-sea ecosystems.