Miracle-dz/UniFAR-FTUs huggingface dataset:
Classification of thyroid dysfunction in pregnant women differs by analytical method and type of thyroid function test.

CONTEXT Physiological alterations challenge the assessment of maternal thyroid function in pregnancy. It remains uncertain how the reference ranges vary by week of pregnancy, and how the classification of disease varies by analytical method and type of thyroid function test. DESIGN Serum samples from Danish pregnant women (n=6,282) were used for the measurement of thyrotropin (TSH), total and free thyroxine (T4), total and free 3,5,3'-triiodothyronine (T3), and T-uptake using 'Method A' (Cobas 8000, Roche Diagnostics). TSH and free T4 were also measured using 'Method B' (ADVIA Centaur XP, Siemens Healthineers). MAIN OUTCOME MEASURES Pregnancy week- and method-specific reference ranges were established among thyroid antibody-negative women (n=4,612). The reference ranges were used to classify maternal thyroid function, and. RESULTS were compared by analytical method and type of thyroid function test. RESULTS The reference ranges for TSH showed a gradual decrease during pregnancy week 4-14, a gradual increase was observed for total T4, total T3, and T-uptake, whereas free T4 and free T3 showed less variation. When TSH and free T4 were used, Method A classified 935 (14.9%) with abnormal thyroid function, Method B a total of 903 (14.4%), and the methods agreed on 554 individuals. When TSH and total T4 were used, 947 (15.1%) were classified with abnormal thyroid function, and classifications by either total T4 or free T4 agreed on 584 individuals. CONCLUSIONS Even when pregnancy week- and method-specific reference ranges were established, the classification of maternal thyroid dysfunction varied considerably by analytical method and type of thyroid function test.
KORP-PL: a coarse-grained knowledge-based scoring function for protein-ligand interactions

MOTIVATION Despite the progress made in studying protein-ligand interactions and the widespread application of docking and affinity prediction tools, improving their precision and efficiency still remains a challenge. Computational approaches based on the scoring of docking conformations with statistical potentials constitute a popular alternative to more accurate but costly physics-based thermodynamic sampling methods. In this context, a minimalist and fast sidechain-free knowledge-based potential with a high docking and screening power can be very useful when screening a big number of putative docking conformations. RESULTS Here we present a novel coarse-grained potential defined by a 3D joint probability distribution function that only depends on the pairwise orientation and position between protein backbone and ligand atoms. Despite its extreme simplicity, our approach yields very competitive results with the state-of-the-art scoring functions, especially in docking and screening tasks. For example, we observed a two-fold improvement in the median 5% enrichment factor on the DUD-E benchmark compared to Autodock Vina results. Moreover, our results prove that a coarse sidechain-free potential is sufficient for a very successful docking pose prediction. AVAILABILITY The standalone version of KORP-PL with the corresponding tests and benchmarks are available at https://team.inria. fr/nano-d/korp-pl/ and https://chaconlab.org/modeling/korp-pl. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Parent Involvement in Adolescent Obesity Treatment: A Systematic Review

The optimal role for involving parents in adolescent obesity treatment remains unclear, and many opportunities for future research in this area are described. BrightcoveDefaultPlayer10.1542/6166445853001PEDS-VA_2019-3315 Video Abstract CONTEXT: Family-based lifestyle interventions are recommended for adolescent obesity treatment, yet the optimal role of parents in treatment is unclear. OBJECTIVE: To examine systematically the evidence from prospective randomized controlled and/or clinical trials (RCTs) to identify how parents have been involved in adolescent obesity treatment and to identify the optimal type of parental involvement to improve adolescent weight outcomes. DATA SOURCES: Data sources included PubMed, PsychINFO, and Medline (inception to July 2019). STUDY SELECTION: RCTs evaluating adolescent (12–18 years of age) obesity treatment interventions that included parents were reviewed. Studies had to include a weight-related primary outcome (BMI and BMI z score). DATA EXTRACTION: Eligible studies were identified and reviewed, following the Preferred Reporting for Systematic Review and Meta-Analyses guidelines. Study quality and risk of bias were evaluated by using the Cochrane Collaboration risk of bias tool. RESULTS: This search identified 32 studies, of which 23 were unique RCTs. Only 5 trials experimentally manipulated the role of parents. There was diversity in the treatment target (parent, adolescent, or both) and format (group sessions, separate sessions, or mixed) of the behavioral weight loss interventions. Many studies lacked detail and/or assessments of parent-related behavioral strategies. In ∼40% of unique trials, no parent-related outcomes were reported, whereas parent weight was reported in 26% and associations between parent and adolescent weight change were examined in 17%. LIMITATIONS: Only RCTs published in English in peer-reviewed journals were eligible for inclusion. CONCLUSIONS: Further research, with detailed reporting, is needed to inform clinical guidelines related to optimizing the role of parents in adolescent obesity treatment.
Directed Acyclic Graphs, Effect Measure Modification, and Generalizability.

Directed acyclic graphs (DAGs) have had a major impact on the field of epidemiology by providing straightforward graphical rules for determining when estimates are expected to lack causally interpretable internal validity. Much less attention has been paid, however, to what DAGs can tell researchers about effect measure modification and external validity. In this work, we describe two rules based on DAGs related to effect measure modification. Rule 1 states that if a variable, $P$, is conditionally independent of an outcome, $Y$, within levels of a treatment,$X$, then $P$ is not an effect measure modifier for the effect of $X$ on $Y$ on any scale. Rule 2 states that if $P$ is not conditionally independent of $Y$ within levels of $X$, and there are open causal paths from $X$ to $Y$ within levels of $P$, then $P$ is an effect measure modifier for the effect of $X$ on $Y$ on at least one scale (given no exact cancellation of associations). We then show how Rule 1 can be used to identify sufficient adjustment sets to generalize nested trials studying the effect of $X$ on $Y$ to the total source population or to those who did not participate in the trial.
Deep Reinforcement Learning Designed Shinnar-Le Roux RF Pulse Using Root-Flipping: DeepRFSLR

A novel approach of applying deep reinforcement learning to an RF pulse design is introduced. This method, which is referred to as DeepRFSLR, is designed to minimize the peak amplitude or, equivalently, minimize the pulse duration of a multiband refocusing pulse generated by the Shinar Le-Roux (SLR) algorithm. In the method, the root pattern of SLR polynomial, which determines the RF pulse shape, is optimized by iterative applications of deep reinforcement learning and greedy tree search. When tested for the designs of the multiband pulses with three and seven slices, DeepRFSLR demonstrated improved performance compared to conventional methods, generating shorter duration RF pulses in shorter computational time. In the experiments, the RF pulse from DeepRFSLR produced a slice profile similar to the minimum-phase SLR RF pulse and the profiles matched to that of the computer simulation. Our approach suggests a new way of designing an RF by applying a machine learning algorithm, demonstrating a “machine-designed” MRI sequence.
Reassessment of kidney function equations in predicting long‐term survival in cardiac surgery

Chronic kidney disease (CKD) is a risk factor for long‐term survival in cardiac surgery. The Cockcroft‐Gault, Modification of Diet in Renal Disease (MDRD) study, CKD Epidemiology Collaboration (CKD‐EPI), revised Lund‐Malmö (LM), and full age spectrum equations are used to estimate glomerular filtration rates (eGFR), but each have advantages and disadvantages. Our objective was to determine which equation better predicts long‐term survival.
Effects of Omega 3 Fatty Acids on Main Dimensions of Psychopathology

The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying their benefic properties are still partially unknown. These agents seem to express their action on the membrane phospholipid composition and permeability and modulation of second messenger cascades. In psychiatry, the efficacy and tolerability of omega-3 fatty acids were investigated in several psychiatric disorders, including major depression, bipolar disorder, personality disorders, high-risk conditions to develop psychosis, attention-deficit hyperactivity disorder, and autism spectrum disorders. Initial findings in this field are promising, and some relevant questions need to be addressed. In particular, the effects of these agents on the main symptom dimensions have to be investigated in a trans-diagnostic perspective. The present systematic review is aimed to examine the available data on the efficacy of omega-3 fatty acids on domains of psychotic symptoms, affective symptoms, impulsivity, and aggressiveness, and harmful behaviors, and suicide risk.
Cytokine‐related genes play critical roles in extrafollicular growth of follicular lymphoma cells

Follicular lymphoma (FL) is a germinal center‐derived B‐cell lymphoma that is known to proliferate in the intrafollicular region. However, lymphoma cells can be identified in the extrafollicular regions, which are related to disease dissemination. We purified the intrafollicular and extrafollicular regions of FL cells by laser microdissection and conducted microarray analysis in order to characterize the gene expression profiles of FL cells from both regions. BCL2 and genes of germinal B‐cell markers clearly separated intrafollicular and extrafollicular regions of reactive follicular hyperplasia, suggesting the adequacy of the current analysis. In FL cases, cytokine‐related genes were significantly enriched in extrafollicular regions compared with those in the intrafollicular regions. In intrafollicular regions of FL, cell‐cycle–related genes were enriched. We found that the FL cells in the extrafollicular region more strongly expressed IL3RA and CXCL12 than those of intrafollicular regions. The cytokines might be also derived from stroma cells in the extrafollicular regions, which may initiate activation and migration of the tumor cells to this region. Our results suggest that FL cell interaction with surrounding stroma cells plays an important role in the pathophysiology of FL and that such interactions should be a good target for therapy.
Complications After Soft Tissue With Plate vs Bony Mandibular Reconstruction: A Systematic Review and Meta-analysis

Objective Mandibular reconstruction for segmental defects is a well-studied topic. However, there are conflicting data on the risks of delayed plate-related complications. The objective of this systematic review and meta-analysis was to assess long-term plate-related complications following reconstruction of the mandible with soft tissue and a plate as compared with immediate vascularized bony reconstruction. Data Sources A medical librarian created search strategies with a combination of keywords and controlled vocabulary in Ovid Medline (1946–), Embase (1947–), Scopus (1960–), Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov. Review Methods Candidate articles were independently reviewed by 2 authors. Inclusion/exclusion criteria were uniformly applied. Articles were considered eligible if they included adequate reporting of plate extrusion and/or fracture and had follow-up ≥12 months. Results A total of 2379 patients were included. The risk of plate fracture was low in cases of soft tissue with a plate (5%; 95% CI, 0.03-0.08) and osseous reconstruction (1%). The risk of extrusion following soft tissue and plate reconstruction was 20% (95% CI, 0.15-0.27). In the osseous reconstruction group, the risk of extrusion was 10% (95% CI, 0.06-0.18). Revision surgery was performed twice as often following soft tissue with a plate as compared with vascularized bony reconstruction (32% [95% CI, 0.25-0.40] vs 14% [95% CI, 0.09-0.21], respectively). Conclusion Delayed plate-related complications remain a significant problem following segmental defect reconstruction. Soft tissue and plate reconstruction techniques may increase the risk of plate removal and revision surgery.
USP15 Deubiquitinates TUT1 Associated with RNA Metabolism and Maintains Cerebellar Homeostasis

Precise regulation of RNA metabolism is crucial for dynamic gene expression and controlling cellular functions. In the nervous system, defects in RNA metabolism are implicated in the disturbance of brain homeostasis and development. Here, we report that deubiquitinating enzyme, ubiquitin specific peptidase 15 (USP15), deubiquitinates terminal uridylyl transferase 1 (TUT1) and changes global RNA metabolism. We found that the expression of USP15 redistributes TUT1 from the nucleolus to nucleoplasm, resulting in the stabilization of U6 snRNA. ABSTRACT Precise regulation of RNA metabolism is crucial for dynamic gene expression and controlling cellular functions. In the nervous system, defects in RNA metabolism are implicated in the disturbance of brain homeostasis and development. Here, we report that deubiquitinating enzyme, ubiquitin specific peptidase 15 (USP15), deubiquitinates terminal uridylyl transferase 1 (TUT1) and changes global RNA metabolism. We found that the expression of USP15 redistributes TUT1 from the nucleolus to nucleoplasm, resulting in the stabilization of U6 snRNA. We also found that lack of the Usp15 gene induces an impairment in motor ability with an unconventional cerebellar formation. Moreover, inhibition of the USP15-TUT1 cascade triggered mild and chronic endoplasmic reticulum (ER) stress. Therefore, our results suggest that USP15 is crucial for mRNA metabolism and maintains a healthy brain. These findings provide a possibility that disturbance of the USP15-TUT1 cascade induces chronic and mild ER stress, leading to an acceleration of the neurodegenerative phenotype.
Targeting CARD9 with Small-Molecule Therapeutics Inhibits Innate Immune Signaling and Inflammatory Response to Pneumocystis carinii β-Glucans

Pneumocystis jirovecii, the opportunistic fungus that causes Pneumocystis pneumonia (PCP) in humans, is a significant contributor to morbidity and mortality in immunocompromised patients. Given the profound deleterious inflammatory effects of the major β-glucan cell wall carbohydrate constituents of Pneumocystis through Dectin-1 engagement and downstream caspase recruitment domain-containing protein 9 (CARD9) immune activation, we sought to determine whether the pharmacodynamic activity of the known CARD9 inhibitor BRD5529 might have a therapeutic effect on macrophage innate immune signaling and subsequent downstream anti-inflammatory activity. ABSTRACT Pneumocystis jirovecii, the opportunistic fungus that causes Pneumocystis pneumonia (PCP) in humans, is a significant contributor to morbidity and mortality in immunocompromised patients. Given the profound deleterious inflammatory effects of the major β-glucan cell wall carbohydrate constituents of Pneumocystis through Dectin-1 engagement and downstream caspase recruitment domain-containing protein 9 (CARD9) immune activation, we sought to determine whether the pharmacodynamic activity of the known CARD9 inhibitor BRD5529 might have a therapeutic effect on macrophage innate immune signaling and subsequent downstream anti-inflammatory activity. The small-molecule inhibitor BRD5529 was able to significantly reduce both phospho-p38 and phospho-pERK1 signaling and tumor necrosis factor alpha (TNF-α) release during stimulation of macrophages with Pneumocystis cell wall β-glucans.
No QTc Prolongation in Girls and Women with Turner Syndrome

Abstract Context Turner syndrome (TS) is a genetic condition that is reported to be associated with a prolonged rate-corrected QT (QTc) interval. Objectives To evaluate the prevalence of QTc prolongation in patients with TS, to compare their QTc intervals with healthy controls, and to investigate whether QTc prolongation is associated with a monosomy 45,X karyotype. Method Girls (n = 101) and women (n = 251) with TS visiting our center from 2004–2018 were included in this cross-sectional study. QT intervals of 12-leaded electrocardiograms were measured manually, using Bazett’s and Hodges formulas to correct for heart rate. A QTc interval of >450 ms for girls and >460 ms for women was considered prolonged. Corrected QT (QTc) intervals of patients with TS were compared to the QTc intervals of healthy girls and women from the same age groups derived from the literature. Results In total, 5% of the population with TS had a prolonged QTc interval using Bazett’s formula and 0% using Hodges formula. Mean QTc intervals of these patients were not prolonged compared with the QTc interval of healthy individuals from the literature. Girls showed shorter mean QTc intervals compared with women. We found no association between monosomy 45,X and prolongation of the QTc interval. Conclusions This study shows that the QTc interval in girls and women with TS is not prolonged compared with the general population derived from the literature, using both Bazett’s and Hodges formulas. Furthermore, girls show shorter QTc intervals compared with women, and a monosomy 45,X karyotype is not associated with QTc prolongation.
Resolving the Dust Bowl paradox of grassland responses to extreme drought

Significance During the Dust Bowl drought, central US grasslands responded unexpectedly to a decade of hot, dry conditions. Grass species adapted to high temperatures with higher water use efficiency (C4 grasses) decreased, while those preferring cooler climates (C3 grasses) increased. We reproduced this surprising response by experimentally imposing extreme drought in two native grasslands. Analysis of historical climate records revealed that during extreme drought years, the proportion of annual precipitation that occurs during cooler months increases. This previously unidentified shift in seasonal precipitation patterns during extreme drought years provides a mechanism for C3 grasses to increase despite overall hot, dry conditions. Thus, alterations in precipitation seasonality may be as important as reduced precipitation amount when forecasting ecosystem responses to extreme drought. During the 1930s Dust Bowl drought in the central United States, species with the C3 photosynthetic pathway expanded throughout C4-dominated grasslands. This widespread increase in C3 grasses during a decade of low rainfall and high temperatures is inconsistent with well-known traits of C3 vs. C4 pathways. Indeed, water use efficiency is generally lower, and photosynthesis is more sensitive to high temperatures in C3 than C4 species, consistent with the predominant distribution of C3 grasslands in cooler environments and at higher latitudes globally. We experimentally imposed extreme drought for 4 y in mixed C3/C4 grasslands in Kansas and Wyoming and, similar to Dust Bowl observations, also documented three- to fivefold increases in C3/C4 biomass ratios. To explain these paradoxical responses, we first analyzed long-term climate records to show that under nominal conditions in the central United States, C4 grasses dominate where precipitation and air temperature are strongly related (warmest months are wettest months). In contrast, C3 grasses flourish where precipitation inputs are less strongly coupled to warm temperatures. We then show that during extreme drought years, precipitation–temperature relationships weaken, and the proportion of precipitation falling during cooler months increases. This shift in precipitation seasonality provides a mechanism for C3 grasses to respond positively to multiyear drought, resolving the Dust Bowl paradox. Grasslands are globally important biomes and increasingly vulnerable to direct effects of climate extremes. Our findings highlight how extreme drought can indirectly alter precipitation seasonality and shift ecosystem phenology, affecting function in ways not predictable from key traits of C3 and C4 species.
Origami spring–inspired metamaterials and robots: An attempt at fully programmable robotics

Recent advances in three-dimensional printing technologies provide one way not only to speed up freeform fabrication but also to exert programmable control over mechanical properties. Besides, origami-inspired structures, origami-inspired metamaterials, and even origami-inspired robotics primarily demonstrate the promising potential for innovative inspirations of engineering solutions. The motivation of this work is to explore a fully programmable robotic perspective with a fusion of programmable metamaterials, programmable mechanics, and programmable fabrication. First, we proposed an illustrative roadmap for transforming an origami model into a fully programmable robotic system. Then, we introduced an origami spring model and revealed its shape-shifting geometry and intrinsic metamaterial mechanisms, especially the rarely switchable behavior from transverse compression to longitudinal stretchability, and the curvilinear deployment. Furthermore, we addressed the fabrication challenges of three-dimensional printable origami sheets considering three-dimensional printability, foldability with high elasticity, and good damage tolerance. Finally, we developed a fully soft manipulator in terms of the highly reversible compressibility of origami spring metamaterials. And we also devised a peristaltic crawling robot with undulatory movements induced by inclination deployment effect of origami spring metamaterials. Conceivably, the proposed fully programmable robotic system was demonstrated starting from programmable metamaterials, programmable mechanics, and programmable fabrication to programmable robotic behaviors. The contribution of this work also suggested that robotic morphing could be tunable by hierarchical programming from modeling and fabrication to actions.
Illness Uncertainty in Patients Awaiting Liver Transplant

Illness uncertainty is prevalent in patients awaiting liver transplant. We described high levels of illness uncertainty in these patients and examined relationships between uncertainty and person factors and the antecedents of uncertainty. Mishel uncertainty in illness scale was used to measure illness uncertainty. We used modes and interquartile range (IQR) to describe illness uncertainty levels in 115 patients. Multiple logistic and linear regression models estimated the associations of uncertainty with hypothesized antecedents. High total illness uncertainty score was reported by 15.6% of the patients. After adjusting for all variables, illness uncertainty was associated with two antecedents of uncertainty, low social well-being (OR = 0.816; p = .025) and low self-efficacy (OR = 0.931; p = .013). Complexity was negatively associated with social well-being; ambiguity and inconsistency were negatively associated with self-efficacy. One in seven patients experienced high illness uncertainty. Social well-being and self-efficacy were negatively related to illness uncertainty.