Miracle-dz/UniFAR-FTUs huggingface dataset:
Postselection Inference in Structural Equation Modeling

Abstract Most statistical inference methods were established under the assumption that the fitted model is known in advance. In practice, however, researchers often obtain their final model by some data-driven selection process. The selection process makes the finally fitted model random, and it also influences the sampling distribution of the estimator. Therefore, implementing naive inference methods may result in wrong conclusions—which is probably a prime source of the reproducibility crisis in psychological science. The present study accommodates three valid state-of-the-art postselection inference methods for structural equation modeling (SEM) from the statistical literature: data splitting (DS), postselection inference (PoSI), and the polyhedral (PH) method. A simulation is conducted to compare the three methods with the commonly used naive procedure under selection events made by L1-penalized SEM. The results show that the naive method often yields incorrect inference, and that the valid methods control the coverage rate in most cases with their own pros and cons. Real world data examples show the practical use of the valid inference methods.
Mutations in RHOT1 Disrupt Endoplasmic Reticulum–Mitochondria Contact Sites Interfering with Calcium Homeostasis and Mitochondrial Dynamics in Parkinson's Disease

Abstract Aims: The outer mitochondrial membrane protein Miro1 is a crucial player in mitochondrial dynamics and calcium homeostasis. Recent evidence indicated that Miro1 mediates calcium-induced mitochondrial shape transition, which is a prerequisite for the initiation of mitophagy. Moreover, altered Miro1 protein levels have emerged as a shared feature of monogenic and sporadic Parkinson's disease (PD), but, so far, no disease-associated variants in RHOT1 have been identified. Here, we aim to explore the genetic and functional contribution of RHOT1 mutations to PD in patient-derived cellular models. Results: For the first time, we describe heterozygous RHOT1 mutations in two PD patients (het c.815G>A; het c.1348C>T) and identified mitochondrial phenotypes with reduced mitochondrial mass in patient fibroblasts. Both mutations led to decreased endoplasmic reticulum-mitochondrial contact sites and calcium dyshomeostasis. As a consequence, energy metabolism was impaired, which in turn caused increased mitophagy. Innovation and Conclusion: Our study provides functional evidence that ROTH1 is a genetic risk factor for PD, further implicating Miro1 in calcium homeostasis and mitochondrial quality control.
Obesity in psoriatic arthritis

Abstract Obesity is a common cardiovascular risk factor in psoriatic disease. Although the prevalence of obesity is high, the factors associated with it in patients with psoriatic arthritis (PsA) are poorly understood. We aimed to analyze the frequency and obesity-associated factors in a cohort of PsA. This retrospective cross-sectional study included 290 consecutive patients with PsA according to CASPAR criteria. Three-hundred ten psoriatic patients without arthritis and 600 outpatients without inflammatory conditions were used as comparison populations. The factors associated with obesity were analyzed first using conditional logistic regression. The significant factors in this first model were introduced in a multivariate model using a backward step approach. This series included 159 men (54.8%) and 131 women (45.2%), with an average age of 54 ± 12 years. Obesity was more common both in psoriasis (36.5% vs 22%, OR 2.1 [95%CI: 1.5–2.8), P < . 01]) and PsA (27.6% vs 22%, OR 1.4 [95%CI: 1.0–1.9], P < .05) than in the non-inflammatory population. Obesity was more frequent in psoriasis (36.5%) than in PsA (27.6%), OR 1.5 95% CI: 1.1 to 2.1, P < . 05. After correcting for age, sex, disease duration, and other confounders, independent associations with obesity (P < .05) were: PsA family history (OR 3.6, 95%CI: 1.1–12.4), evolution as axial disease (OR 4.4, 95%CI: 1.0–15.4), and dyslipidemia (OR 3.5, 95%CI: 1.5–8.6). Obesity is common in psoriatic disease, but much more frequent among patients with cutaneous than joint disease. Patients who present with spondylitis during evolution are more prone to this comorbidity, and therefore, should be closely monitored to correct this eventuality in a timely manner.
Prognostic impact of leukocytosis in intracerebral hemorrhage

Abstract Background: Intracerebral hemorrhage (ICH) is correlated with high rate of death and poor outcome. Leukocytes participate in secondary brain injury in ICH. It is still not clear that whether leukocytosis can predict outcome in ICH. This study was performed to summarize that current evidences about the association between baseline leukocytosis and outcome in ICH patients in a systematic review and meta-analysis. Methods: Published studies were searched in 5 databases. Original studies about association between baseline leukocytosis and outcome in ICH were included. Pooled odds ratios (ORs) and their 95% confidence intervals (CIs) were achieved to evaluate the association between leukocytosis and prognosis. Results: A total of 19 eligible studies with 6417 patients were analyzed in this study. Meta-analysis showed baseline leukocyte count increase was significantly associated with worse overall (OR = 1.13, 95% CI 1.05–1.21, P = .001), short-term (OR = 1.20, 95% CI 1.05–1.38, P = .009), and long-term functional outcome (OR = 1.12, 95% CI 1.04–1.20, P = .004). Baseline leukocytosis defined by cut-off values had significant association with worse overall functional outcome (OR = 1.95, 95% CI 1.01–3.76, P = .046). Baseline leukocyte count increase was significantly associated with higher overall (OR = 1.10, 95% CI 1.02–1.18, P = .011) and long-term mortality (OR = 1.12, 95% CI 1.03–1.22, P = .007). Baseline leukocytosis defined by cut-off values was significantly associated with higher overall (OR = 1.67, 95% CI 1.23–2.27, P = .001) and short-term mortality (OR = 1.74, 95% CI 1.12–2.70, P = .014). Conclusion: Baseline leukocytosis could be helpful in predicting prognosis in ICH patients. However, its prognostic value should be verified by further studies.
A School Nurse Application of the ECHO Model

Type I diabetes (T1D) is one of the most common childhood diseases and Type 2 diabetes (T2D) is increasing at alarming rates. Given that children spend a great percentage of their time in school, this setting is a critical environment for models of care that lead to better management of this and other health conditions. The School Nurses Managing Diabetes Care ECHO was offered to Colorado school nurses to build their capacity in providing evidence-based management of T1D. The purpose of this effort was to (1) determine whether or not the model could be used as a tool of collaboration and dissemination for school nurses across Colorado and (2) assess the effectiveness of the “School Nurses Managing Diabetes Care” ECHO learning series. Post-series survey results demonstrated a 25% increase in self-efficacy ratings, moving learners from “average among my peers” toward “competent. ” Additionally, all respondents planned to make one or more practice changes to improve care for students with T1D. Expanding the use of the ECHO model to implement intensive management of children and youth with T1D is critically important as rates of this and other chronic conditions continue to increase.
P‐glycoprotein (MDR1/ABCB1) controls brain accumulation and intestinal disposition of the novel TGF‐β signaling pathway inhibitor galunisertib

Galunisertib (LY2157299), a promising small‐molecule inhibitor of the transforming growth factor‐beta (TGF‐β) receptor, is currently in mono‐ and combination therapy trials for various cancers including glioblastoma, hepatocellular carcinoma and breast cancer. Using genetically modified mouse models, we investigated the roles of the multidrug efflux transporters ABCB1 and ABCG2, the OATP1A/1B uptake transporters and the drug‐metabolizing CYP3A complex in galunisertib pharmacokinetics. In vitro, galunisertib was vigorously transported by human ABCB1, and moderately by mouse Abcg2. Orally administered galunisertib (20 mg/kg) was very rapidly absorbed. Galunisertib brain‐to‐plasma ratios were increased by ~24‐fold in Abcb1a/1b−/− and Abcb1a/1b;Abcg2−/− mice compared to wild‐type mice, but not in single Abcg2−/− mice, whereas galunisertib oral availability was not markedly affected. However, recovery of galunisertib in the small intestinal lumen was strongly reduced in Abcb1a/1b−/− and Abcb1a/1b;Abcg2−/− mice. Oral coadministration of the ABCB1/ABCG2 inhibitor elacridar boosted galunisertib brain accumulation in wild‐type mice to equal the levels seen in Abcb1a/1b;Abcg2−/− mice. Oatp1a/1b deficiency did not alter oral galunisertib pharmacokinetics or liver distribution. Cyp3a−/− mice showed a 1.9‐fold higher plasma AUC0–1 hr than wild‐type mice, but this difference disappeared over 8 hr. Also, transgenic human CYP3A4 overexpression did not significantly alter oral galunisertib pharmacokinetics. Abcb1 thus markedly restricts galunisertib brain penetration and affects its intestinal disposition, possibly through biliary excretion. Elacridar coadministration could fully inhibit both processes, without causing acute toxicity. Moreover, mouse Cyp3a, but not human CYP3A4, may eliminate galunisertib at high plasma concentrations. These insights may help to guide the further clinical development and application of galunisertib.
Thiol/Disulfide Homeostasis in Patients with Molar Pregnancies

Abstract Introduction: We aimed to investigate serum dynamic thiol and disulfide levels in patients with molar pregnancy (MP), and compare these concentrations with those of healthy pregnant women. Materials and Methods: Forty-one patients who were diagnosed with MP and 41 gestational age-matched healthy pregnant women were included in this prospective study. MP cases were separated in two groups as complete hydatidiform mole (CHM) and partial hydatidiform mole (PHM). Demographic features and thiol/disulfide homeostasis were recorded for each woman. Results: There was a significant correlation between the decrease in the total thiol and native thiol levels in MP patients. However, no significant difference was observed between CHM and PHM groups in terms of serum disulfide levels. Conclusion: OS is increased in MPs both in complete and partial moles, as determined by thiol/disulfide analysis.
Changes in socio-economic patterns of energy consumption and insufficient energy intake across India from 1993–94 to 2011–12

Abstract Objective: To assess whether disparities in energy consumption and insufficient energy intake in India have changed over time across socio-economic status (SES). Design: This cross-sectional, population-based survey study examines the relationship between several SES indicators (i.e. wealth, education, caste, occupation) and energy consumption in India at two time points almost 20 years apart. Household food intake in the last 30 d was assessed in 1993–94 and in 2011–12. Average dietary energy intake per person in the household (e.g. kilocalories) and whether the household consumed less than 80 % of the recommended energy intake (i.e. insufficient energy intake) were calculated. Linear and relative risk regression models were used to estimate the relationship between SES and average energy consumed per day per person and the relative risk of consuming an insufficient amount of energy. Setting: Rural and urban areas across India. Participants: A nationally representative sample of households. Results: Among rural households, there was a positive association between SES and energy intake across all four SES indicators during both survey years. Similar results were seen for energy insufficiency vis-à-vis recommended energy intake levels. Among urban households, wealth was associated with energy intake and insufficiency at both time points, but there was no educational patterning of energy insufficiency in 2011–12. Conclusions: Results suggest little overall change in the SES patterning of energy consumption and percentage of households with insufficient energy intake from 1993–94 to 2011–12 in India. Policies in India need to improve energy intake among low-SES households, particularly in rural areas.
Translational approach to apathy‐like behavior in mice: From the practical point of view

Apathy is a pervasive clinical phenomenon that deserves more attention at the translational and pre‐clinical levels. To study apathy‐like behavior in mice, we relied on an operational definition of apathy: the quantitative reduction of voluntary, goal‐directed behaviors. We recently found that the chronic loss of function of a specific cell type (striatal dopamine receptor type 2‐expressing medium spiny neurons, D2‐MSN) in a restricted region (the ventrolateral striatum, VLS) was sufficient to induce apathy‐like behavior in a food‐seeking operant task. We further showed that VLS D2‐MSN are activated at the preparatory period, and that optogenetic inhibition of VLS D2‐MSN during that period resulted in transient decreases in instrumental motivation, strengthening the hypothesis that VLS D2‐MSN mediate apathy‐like behavior in mice. Mice bearing VLS D2‐MSN dysfunction can thus be regarded as an apathy model for future translational studies.
The long and winding road to pathogen reduction of platelets, red blood cells and whole blood

Pathogen reduction technologies (PRTs) have been developed to further reduce the current very low risks of acquiring transfusion‐transmitted infections and promptly respond to emerging infectious threats. An entire portfolio of PRTs suitable for all blood components is not available, but the field is steadily progressing. While PRTs for plasma have been used for many years, PRTs for platelets, red blood cells (RBC) and whole blood (WB) were developed more slowly, due to difficulties in preserving cell functions during storage. Two commercial platelet PRTs use ultra violet (UV) A and UVB light in the presence of amotosalen or riboflavin to inactivate pathogens’ nucleic acids, while a third experimental PRT uses UVC light only. Two PRTs for WB and RBC have been tested in experimental clinical trials with storage limited to 21 or 35 days, due to unacceptably high RBC storage lesion beyond these time limits. This review summarizes pre‐clinical investigations and selected outcomes from clinical trials using the above PRTs. Further studies are warranted to decrease cell storage lesions after PRT treatment and to test PRTs in different medical and surgical conditions. Affordability remains a major administrative obstacle to PRT use, particularly so in geographical regions with higher risks of transfusion‐transmissible infections.
MDP: A PARADIGM FOR COMMUNICATION AND COMPUTATION IN MOBILE CLUSTER

The proposed work explores the interprocess communication across communicating parallel tasks in a mobile cluster. The process which is linked with specific mobile or static nodes will not be resilient to the changing conditions of the mobile cluster. The proposed Mobile Distributed Pipes (MDP) model enables the location independent intertask communication among the processes executing in static and mobile nodes. This novel approach enables the migration of communicating parallel tasks during runtime, which occurs according to the context and location requirements. A transparent programming model for a parallel solution to Iterative Mobile Grid Computations (IMGC) using MDP is also proposed. The proposed model is resilient to the heterogeneity of nodes such as static or mobile and the changing conditions in the mobile cluster because of mobility. The design of runtime and functional library support for the proposed model is also presented.
Impact of BRAF V600E and TERT promoter mutations on response to therapy in papillary thyroid cancer.

In this study, we examined the relationship between coexisting BRAF V600E and TERT promoter mutations in papillary thyroid cancer (PTC) and response to therapy. PTC cases (n = 568) with known BRAF and TERT status, diagnosed from 2000-2012 and actively monitored at one institution, were reviewed retrospectively. Associations between BRAF V600E and TERT promoter mutations and clinicopathological features, TNM stage, initial risk, response to therapy, follow-up, and final disease outcome were assessed according to American Thyroid Association (ATA) criteria (2015) and the American Joint Committee on Cancer/Tumor-Node-Metastasis (8th edition) staging system. Median follow-up was 120 months. TERT promoter mutations (any type) were detected in 13.5% (77/568) of PTC cases with known BRAF status. The C228T and C250T TERT hotspot mutations were found in 54 (9.5%) and 23 (4%) patients, respectively, and 22 other TERT promoter alterations were identified. Coexisting BRAF V600E and TERT hotspot promoter mutations were detected in 9.5% (54/568) of patients, and significantly associated with older patient age (p = 0.001), gross extrathyroidal extension (p = 0.003), tumor stage pT3-4 (p = 0.005), stage II-IV (p = 0.019), intermediate or high initial risk (p = 0.003), worse than excellent response to primary therapy (p = 0.045), recurrence (p = 0.015), and final outcome of no remission (p = 0.014). We conclude that coexisting BRAF V600E and TERT mutations in patients with PTC are associated with poor initial prognostic factors and clinical course, and may be useful for predicting worse response to therapy, recurrence, and poor outcome.
Tobacco smoke exposure and the risk of childhood acute lymphoblastic leukemia and acute myeloid leukemia

Abstract Objective: Tobacco smoke contains carcinogens known to damage somatic and germ cells. In this study, we investigated the effect of tobacco smoking on the risk of childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML). Methods: Information about tobacco smoking exposures of the mother before, during, and after pregnancy was collected via PubMed, Embase, and Web of Science databases through November 5, 2018. We performed to evaluate the association between smoking exposure and the risk of childhood ALL and AML. Study selection, data abstraction, and quality assessment were performed by 2 independent reviewers. Random effects models were used to obtain summary odds ratios (ORs) and 95% confidence intervals (CIs). Results: Nineteen case–control studies of childhood leukemia (age < 15 years) conducted in 9 countries from 1974 to 2018. Maternal smoking exposures did not a significant association with childhood ALL (OR = 1.004, 95% CI 0.953–1.058, P = .881) and AML (OR = 0.92, 95% CI 0.815–1.038, P = .177) during exposure time windows. However, there was an association with paternal smoking and ALL (OR = 1.15, 95% CI 1.038–1.275, P = .007). Paternal smoking in AML showed there was no association with smoking exposures and childhood AML (OR = 1.133, 95% CI 0.943–1.362, P = .181). Next, maternal daily cigarettes consumption showed no associations with ALL (OR = 1.08, 95% CI 1.000–1.168, P = .051) during pregnancy. No association with maternal daily smoking and AML (OR = 0.909, 95% CI 0.682–1.211, P = .514). Paternal daily cigarettes consumption was associated with increased risks of childhood ALL (OR = 1.200, 95% CI 1.112–1.302, P = .000). The higher consumption of paternal smoking (more than 10 per day) was significantly related to childhood ALL. Paternal daily smoking consumption also was related to AML (OR = 1.242, 95% CI 1.031–1.496, P = .022). Conclusion: Maternal smoking before, during, or after pregnancy was not associated with childhood ALL or AML. However, paternal smoking was related to a significantly elevated risk of childhood ALL during pregnancy, but not for AML. Maternal daily smoking consumption was not associated with ALL or AML during pregnancy. The higher consumption of paternal smoking were, the higher the risk of childhood ALL or AML.
Effect of Entomopathogenic Nematodes on the Fitness Cost of Resistance to Bt Toxin Cry1Ac in Pink Bollworm (Lepidoptera: Gelechiidae)

Abstract The widespread use of crop plants genetically engineered to produce toxins from the bacterium Bacillus thuringiensis (Bt) imposes selection on insect populations to evolve resistance. The pink bollworm, Pectinophora gossypiella (Saunders) (Lepidoptera: Gelechiidae), is a major pest of cotton in the southwestern United States that is currently controlled with transgenic cotton that produces Bt toxin Cry1Ac. Previously reported theoretical work suggests that, in conjunction with a high dose/refuge strategy, fitness costs of Bt resistance can slow or prevent the evolution of resistance. We report here that the entomopathogenic nematode Steinernema riobrave (Rhabditida: Steinernematidae) increased the fitness cost of resistance to Cry1Ac in P. gossypiella. Mortality of P. gossypiella from fourth instar to adult eclosion was significantly higher for a Bt-resistant strain than a susceptible strain in tests with two to 14 infective juveniles of S. riobrave per larva, but it did not differ between strains when nematodes were absent. Nematodes established in P. gossypiella larvae at all concentrations tested, and nematode reproduction in infected P. gossypiella larvae occurred at nematode concentrations of four to 14 infective juveniles per larva. Our results suggest that incorporation of entomopathogenic nematodes into an integrated resistance management strategy could help to delay pest resistance to Bt toxins.
Components of the Triarchic Model of Psychopathy and the Five-Factor Model Domains Share Largely Overlapping Nomological Networks

The triarchic model of psychopathy is a recently developed model of psychopathy that identifies three primary domains: Boldness, Meanness, and Disinhibition. These traits overlap substantially with general and pathological five-factor model of personality (Boldness = low Neuroticism + high Extraversion; Meanness = low Agreeableness; Disinhibition = low Conscientiousness). In the current study (total N = 1,266), we compare domains from the triarchic model of psychopathy and five-factor model in relation to self- and informant-report of external criteria (e.g., pathological traits, antisocial behavior), and quantified their absolute similarity using a profile-matching approach. The corresponding traits from these models show large interrelations and very similar convergent and divergent relations, suggesting that unaltered traits from one can be considered excellent representations of the other. Results are discussed in terms of the benefits of using a unifying trait-based model to study psychopathy, as well as personality disorders more broadly.
Latest Insights on Adenovirus Structure and Assembly

Adenovirus (AdV) capsid organization is considerably complex, not only because of its large size (~950 A) and triangulation number (pseudo T = 25), but also because it contains four types of minor proteins in specialized locations modulating the quasi-equivalent icosahedral interactions. Up until 2009, only its major components (hexon, penton, and fiber) had separately been described in atomic detail. Their relationships within the virion, and the location of minor coat proteins, were inferred from combining the known crystal structures with increasingly more detailed cryo-electron microscopy (cryoEM) maps. There was no structural information on assembly intermediates. Later on that year, two reports described the structural differences between the mature and immature adenoviral particle, starting to shed light on the different stages of viral assembly, and giving further insights into the roles of core and minor coat proteins during morphogenesis [1,2]. Finally, in 2010, two papers describing the atomic resolution structure of the complete virion appeared [3,4]. These reports represent a veritable tour de force for two structural biology techniques: X-ray crystallography and cryoEM, as this is the largest macromolecular complex solved at high resolution by either of them. In particular, the cryoEM analysis provided an unprecedented clear picture of the complex protein networks shaping the icosahedral shell. Here I review these latest developments in the field of AdV structural studies.