Miracle-dz/UniFAR-FTUs huggingface dataset:
Competing Risks Analysis of Correlated Failure Time Data

Summary We develop methods for competing risks analysis when individual event times are correlated within clusters. Clustering arises naturally in clinical genetic studies and other settings. We develop a nonparametric estimator of cumulative incidence, and obtain robust pointwise standard errors that account for within‐cluster correlation. We modify the two‐sample Gray and Pepe–Mori tests for correlated competing risks data, and propose a simple two‐sample test of the difference in cumulative incidence at a landmark time. In simulation studies, our estimators are asymptotically unbiased, and the modified test statistics control the type I error. The power of the respective two‐sample tests is differentially sensitive to the degree of correlation; the optimal test depends on the alternative hypothesis of interest and the within‐cluster correlation. For purposes of illustration, we apply our methods to a family‐based prospective cohort study of hereditary breast/ovarian cancer families. For women with BRCA1 mutations, we estimate the cumulative incidence of breast cancer in the presence of competing mortality from ovarian cancer, accounting for significant within‐family correlation.
Learning and Teaching With Loss: Meeting the Needs of Refugee Children Through Narrative Inquiry

ABSTRACT Providing refugee students with a safe and welcoming classroom environment is critical for school success but largely dependent on teachers’ knowledge, values, practices, and attitudes. This qualitative study juxtaposes the experience of one refugee students’ experience in the school system and one beginning teachers’ experience in working with and meeting the psychosocial and educational needs of refugee students in the classroom. Using narrative inquiry, from the perspective of a refugee student and a beginning teacher, this study identifies themes and key issues related to teaching refugee students. These experiences are compared to the current literature on refugee education to highlight the beliefs and values that teachers bring to their practice. Findings reveal that there are gaps in beginning teachers’ knowledge about who refugees are, their experiences, and how best to support them in the classroom. Some teachers also held negative attitudes and perspective of refugee students and failed to develop a nuanced perspective of diversity and multiculturalism. This study also shows how narrative inquiry, in the formal of a personal history account, can be used as tool to surface, challenge, and overcome negative stereotypes, biases, and assertions that prevent teachers from effectively supporting their students.
Antibiotic compounds from Bacillus: why are they so amazing?

The constant increase of multi-drug resistant patho gens stimulates research, more than ever, to identify and develop new antibacterial compounds . The recent advances in genome sequencing have highlighted the genus Bacillus as an unexpected source of antibiotic-like compoun ds. This review focus on the different class of antimicrobial molec ules produce by Bacillus genus such as polyketides, nonribosomal peptide, bacteriocins as well as other unusual peptides.
HLA-DRB1*0407 and *1304 are risk factors for scleroderma renal crisis.

OBJECTIVE To examine the predictive role of HLA genetic markers in scleroderma renal crisis (SRC), beyond the known clinical correlates, in a large population of patients with systemic sclerosis (SSc). METHODS SSc patients from the Scleroderma Family Registry and DNA Repository, the Genetics versus Environment in Scleroderma Outcomes Study, and the rheumatology division registry at the University of Texas Health Science Center at Houston were included in the study. Relevant clinical data were obtained by chart review, and autoantibodies were detected utilizing commercially available kits. HLA class II genotyping was performed on extracted and purified genomic DNA. RESULTS Overall, 1,519 SSc patients were included in the study, of whom 90 (6%) had developed SRC. Among the 90 patients with SRC, the diffuse cutaneous disease subtype was found in 76%, antitopoisomerase antibodies (antitopo) in 9%, anticentromere antibodies (ACAs) in 2%, and anti-RNA polymerase III (anti-RNAP III) in 50% of patients. In multivariate analyses of clinical and demographic parameters, diffuse disease type and anti-RNAP III were strong risk factors for the presence of SRC, whereas ACAs and antitopo were protective. In the final multivariate analysis, which included HLA alleles, HLA-DRB1*0407 (odds ratio [OR] 3.21, 95% confidence interval [95% CI] 1.27-8.08; P = 0.013) and DRB1*1304 (OR 4.51, 95% CI 1.30-15.65; P = 0.018) were identified as independent risk factors for SRC. Only 3 clinical characteristics, diffuse disease type, anti-RNAP III, and ACAs, remained significantly associated with SRC in the final model. CONCLUSION The results of this study suggest that DRB1*0407 and *1304 are independent risk factors, beyond the known clinical correlates, for the development of SRC.
A Modified Acetylcholine Receptor δ-Subunit Enables a Null Mutant to Survive Beyond Sexual Maturation

The contraction of skeletal muscle is dependent on synaptic transmission through acetylcholine receptors (AChRs) at the neuromuscular junction (NMJ). The lack of an AChR subunit causes a fetal akinesia in humans, leading to death in the first trimester and characteristic features of Fetal Akinesia Deformation Sequences (FADS). A corresponding null mutation of the δ-subunit in zebrafish (sofa potato; sop) leads to the death of embryos around 5 d postfertilization (dpf). In sop−/− mutants, we expressed modified δ-subunits, with one (δ1YFP) or two yellow fluorescent protein (δ2YFP) molecules fused at the intracellular loop, under the control of an α-actin promoter. AChRs containing these fusion proteins are fluorescent, assemble on the plasma membrane, make clusters under motor neuron endings, and generate synaptic current. We screened for germ-line transmission of the transgene and established a line of sop−/− fish stably expressing the δ2YFP. These δ2YFP/sop−/− embryos can mount escape behavior close to that of their wild-type siblings. Synaptic currents in these embryos had a smaller amplitude, slower rise time, and slower decay when compared with wild-type fish. Remarkably, these embryos grow to adulthood and display complex behaviors such as feeding and breeding. To the best of our knowledge, this is the first case of a mutant animal corresponding to first trimester lethality in human that has been rescued by a transgene and survived to adulthood. In the rescued fish, a foreign promoter drove the transgene expression and the NMJ had altered synaptic strength. The survival of the transgenic animal delineates requirements for gene therapies of NMJ.
Serum Vitamin D and Risk of Bladder Cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial

Background: The one previous prospective study of vitamin D status and risk of urinary bladder cancer found that male smokers with low serum 25-hydroxy-vitamin D [25(OH)D] were at a nearly two-fold increased risk. We conducted an analysis of serum 25(OH)D and risk of bladder cancer in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Study and examined whether serum vitamin D binding protein (DBP) concentration confounded or modified the association. Methods: Three hundred and seventy-five cases of bladder cancer were matched 1:1 with controls based on age (±5 years), race, sex, and date of blood collection (±30 days). Conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI) of bladder cancer by prediagnosis levels of 25(OH)D. Results: We found no strong or statistically significant association between serum 25(OH)D and bladder cancer risk (Q1 vs. Q4: OR, 0.84; 95% CI, 0.52–1.36; Ptrend = 0.56). Further adjustment for, or stratification by, serum DBP did not alter the findings, nor was there a main effect association between DBP and risk. Conclusion: In contrast to an earlier report, we observed no association between vitamin D status and risk of bladder cancer; this difference could be due to the inclusion of women and nonsmokers in the current study population or due to the differences in the distribution of vitamin D concentrations between the two study populations. Impact: These findings may contribute to future meta-analyses and help elucidate whether the vitamin D–bladder cancer association varies across populations. Cancer Epidemiol Biomarkers Prev; 21(7); 1222–5. ©2012 AACR.
H‐2 class I knockout, HLA‐A2.1‐transgenic mice: a versatile animal model for preclinical evaluation of antitumor immunotherapeutic strategies

H‐2 class I‐negative, HLA‐A2.1‐transgenic HHD mice were used for a comparative evaluation of the immunogenicity of HLA‐A2.1‐restricted human tumor‐associated cytotoxic T lymphocyte (CTL) epitopes. A hierarchy was established among these peptides injected into mice in incomplete Freund's adjuvant which correlates globally with their capacity to bind and stabilize HLA‐A2.1 molecules. Co‐injection of a helper peptide enhanced most CTL responses. In contrast, classical HLA class I‐transgenic mice which still express their own class I molecules did not, in most cases, develop HLA‐A2.1‐restricted CTL responses under the same experimental conditions. Different monoepitope immunization strategies of acceptable clinical usage were compared in HHD mice. Recombinant Ty‐virus‐like particles, or DNA encoding epitopes fused to the hepatitis B virus middle envelope protein gave the best results. Using this latter approach and a melanoma‐based polyepitope construct, CTL responses against five distinct epitopes could be elicited simultaneously in a single animal. Thus, HHD mice provide a versatile animal model for preclinical evaluation of peptide‐based cancer immunotherapy.
Brn3a and Brn3b knockout mice display unvaried retinal fine structure despite major morphological and numerical alterations of ganglion cells

Ganglion cells (GCs), the retinal output neurons, receive synaptic inputs from bipolar and amacrine cells in the inner plexiform layer (IPL) and send information to the brain nuclei via the optic nerve. Although GCs constitute less than 1% of the total retinal cells, they occur in numerous types and are the first neurons formed during retinal development. Using Brn3a and Brn3b mutant mice in which the alkaline phosphatase gene was knocked‐in (Badea et al. [Neuron] 2009;61:852–864; Badea and Nathans [Vision Res] 2011;51:269–279), we studied the general effects after gene removal on the retinal neuropil together with the consequences of lack of development of large numbers of GCs onto the remaining retinal neurons of the same class. We analyzed the morphology, number, and general architecture of various neuronal types presynaptic to GCs, searching for changes secondary to the decrement in the number of their postsynaptic partners, as well as the morphology and distribution of retinal astrocytes, for their strong topographical relation to GCs. We found that, despite GC losses, retinal organization in Brn3 null mice is remarkably similar to that of wild‐type controls. J. Comp. Neurol. 527:187–211, 2019. © 2016 Wiley Periodicals, Inc.
COMPARISON RESULTS FOR ELLIPTIC VARIATIONAL INEQUALITIES RELATED TO GAUSS MEASURE

In this article, we study linear elliptic variational inequalities that are defined on a possibly unbounded domain and whose ellipticity condition is given in terms of the density of Gauss measure. Using the notion of rearrangement with respect to the Gauss measure, we prove a comparison result with a problem of the same type defined in a half space, with data depending only on the first variable.
Memory Bias for Self-Relevant Information of People with Different Self-Esteem

Self-esteem is not only high or low,but also has different types in each level.Memory bias lies not only among groups,but also in groups themselves. However,very few researches are paid enough attention to these issues.4(types of self-esteem)×2(valence of words) mixed design was mainly adopted in this study to explore different memory bias of self-relevant information of 184 participants with different self-esteem,in which types of self-esteem were divided according to the consistency between explicit self-esteem,measured with Rosenberg(1965) Self-Esteem Scale,and implicit self-esteem,measured with Implicit Association Test.The results were as follows:(1) participants with high explicit self-esteem had more positive memory bias than those with low self-esteem;while those with low implicit self-esteem had less positive or negative memory bias than those with low self-esteem. (2) for the memory bias as a kind of difference in groups,all groups had positive bias;for the bias as a kind of difference among groups,participants with fragile high self-esteem had more positive bias,but those with low self-esteem had no obvious negative bias either.These results indicate that people with different self-esteem,in different levels or different types,have different memory bias of self-relevant information.
A review of the literature analyzing benefits and concerns of infliximab biosimilar CT-P13 for the treatment of rheumatologic diseases: focus on interchangeability

The introduction of biological agents drastically changed the treatment paradigm of inflammatory arthritides, ameliorating the natural history of the diseases but concomitantly increasing the drug costs due to the manufacturing process. On this concern, biosimilar drugs may represent a valid option for reducing this elevated cost and increasing the availability of these highly effective treatments. Recently, CT-P13, the first biosimilar of infliximab, has been approved with the same indications established for the reference product (RP), and its daily use is progressively increasing. However, the experience with biosimilar drugs in the field of rheumatology is still limited, raising potential doubts and concerns on their correct management in real-life settings. Comparability analysis between CT-P13 and its RP was evaluated in equivalence randomized controlled trials (RCTs) – PLANETRA and PLANETAS – performed on patients with rheumatoid arthritis and axial spondylitis, respectively. CT-P13 and RP showed similar profile in terms of quality, biological activity, safety, immunogenicity, and efficacy. However, the interchangeability between infliximab RP and its biosimilar still represents the most challenging issue because of a lack of a long-lasting experience. To date, reassuring preliminary data on this topic were reported in open-label extensions of PLANETRA and PLANETAS RCTs and in ongoing real-life observational studies. These findings, taken all together, significantly affect the landscape of biosimilar regulatory pathways and strongly support CT-P13 introduction as a great opportunity for expanding the accessibility to these very effective and high-cost therapies.
Infection and smoking are associated with decreased plasma concentration of the anti-aging protein, α-klothoa

Abstract Objective: The objective of this study was to determine whether maternal plasma concentrations of soluble α-klotho are different between women with microbial invasion of the intra-amniotic cavity (MIAC) and those without MIAC among preterm labor and intact membranes (PTL) or preterm prelabor rupture of membranes (pPROM). Methods: A cross-sectional study was conducted to include women in the following groups: i) PTL with MIAC (n=14); ii) PTL without MIAC (n=79); iii) pPROM with MIAC (n=30); and iv) pPROM without MIAC (n=33). MIAC was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Amniotic fluid samples were obtained within 48 h of maternal blood collection. Plasma concentration of soluble α-klotho was determined by ELISA. Results: i) The median plasma concentration (pg/mL) of soluble α-klotho was significantly lower in patients with MIAC than in those without MIAC (787.0 vs. 1117.8; P<0.001). ii) Among patients with PTL, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (787.0 vs. 1138.9; P=0.007). iii) Among patients with pPROM, those with MIAC had a lower median plasma concentration (pg/mL) of soluble α-klotho than those without MIAC (766.4 vs. 1001.6; P=0.045). iv) There was no significant difference in the median plasma concentration of soluble α-klotho between PPROM without MIAC and PTL without MIAC (1001.6 pg/mL vs. 1138.9 pg/mL, respectively; P=0.5). v) After adjustment for potential confounders (maternal age, tobacco use, gestational age at venipuncture), soluble α-klotho remained significantly associated with MIAC (P=0.02); and vi) Among patients without MIAC, smoking was significantly associated with a lower median plasma concentration soluble α-klotho than in non-smokers (794.2 pg/mL vs. 1382.0 pg/mL, respectively; P<0.001); however, this difference was not observed in patients with MIAC. Conclusions: Intra-amniotic infection occurring at preterm gestations (regardless of membrane status) was associated with a decrease in maternal plasma concentrations of soluble α-klotho. Moreover, among patients without infection, the plasma concentration of α-klotho was lower in smokers.
A contrastive study of vowel [] between Standard Putonghua and Shanghai Putonghua

[],a very controversial vowel in Mandarin,has recently been shown to be a diphthong,a finding based on a large amount of acoustic and articulatory data.It is however absent in Shanghai dialect.Such difference is assumed to have some effect on Shanghai dialect speakers in their acquisition of Standard Putonghua(SP). This paper reports a contrastive study involving 54 instances of [] pronounced by 20 SP speakers and 150 instances of [] pronounced by 51 Shanghai dialect(SD)speakers in NOKIA-CASS corpus.Findings are as follows:(1)In the F1-F2 vowel charts,the position of [] in SD male speakers is located higher than those in SP ones,while in SD female speakers it is more front.But there is a general trend in both SD male and female speakers that the heavier the accent,the higher and more front the position of []. (2)Compared with SP,the third formant of [] falls much slower in SD.Meanwhile,the heavier the accent,the slower F3 falls. (3)The comparative duration of heavier accents in SD is longer than in SP.
Happiness and Depression in Adolescence after Maternal Smoking during Pregnancy: Birth Cohort Study

Background Prenatal cigarette smoke exposure may have adverse psychological effects on offspring. The objective was to assess the association between parental smoking during pregnancy and offspring happiness at age 18, as well as depression. Methodology Participants were part of a birth cohort study in Pelotas, Brazil (5,249 participants). Happiness was measured by the Subjective Happiness Scale, a Likert-like scale with four questions generating a score from 1 to 7, with ≥ 6 indicating "happiness". Depression was measured using the Mini International Psychiatric Interview. ​Results About one third of mothers reported having smoked during pregnancy and 4.6% reported smoking 20 or more cigarettes a day. The prevalence of happiness was 32.2% (95% CI 30.8; 33.7), depression 6.8% (95% CI 6.1; 7.6), and simultaneous happiness and depression less than 1%. The prevalence of offspring happiness decreased as smoking in pregnancy increased, even after control for confounding variables, showing an OR = 0.79 [95% CI 0.55; 1.13]. The opposite happened to depression; the prevalence of offspring depression increased as smoking in pregnancy increased (<20 cigarettes/day OR = 1.38 [95% CI 1.03; 1.84] and ≥20 cigarettes/day OR = 2.11[95% CI 1.31; 3.40]. Smoking by the partner was associated with decreased offspring happiness after adjustment for confounders, but did no show association with offspring depression. Conclusions Offspring were less likely to be happy and more likely to be depressed if their mother smoked during pregnancy, and less likely to be happy if their father smoked during mother’s pregnancy. Although we can not affirm that this is a “causal pathway”, public policies to reduce smoking in pregnancy could improve the health of the offspring in the short and long term.
The role of knee alignment in disease progression and functional decline in knee osteoarthritis.

CONTEXT Knee osteoarthritis (OA) is a leading cause of disability in older persons. Few risk factors for disease progression or functional decline have been identified. Hip-knee-ankle alignment influences load distribution at the knee; varus and valgus alignment increase medial and lateral load, respectively. OBJECTIVE To test the hypotheses that (1) varus alignment increases risk of medial knee OA progression during the subsequent 18 months, (2) valgus alignment increases risk of subsequent lateral knee OA progression, (3) greater severity of malalignment is associated with greater subsequent loss of joint space, and (4) greater burden of malalignment is associated with greater subsequent decline in physical function. DESIGN AND SETTING Prospective longitudinal cohort study conducted March 1997 to March 2000 at an academic medical center in Chicago, Ill. PARTICIPANTS A total of 237 persons recruited from the community with primary knee OA, defined by presence of definite tibiofemoral osteophytes and at least some difficulty with knee-requiring activity; 230 (97%) completed the study. MAIN OUTCOME MEASURES Progression of OA, defined as a 1-grade increase in severity of joint space narrowing on semiflexed, fluoroscopically confirmed knee radiographs; change in narrowest joint space width; and change in physical function between baseline and 18 months, compared by knee alignment at baseline. RESULTS Varus alignment at baseline was associated with a 4-fold increase in the odds of medial progression, adjusting for age, sex, and body mass index (adjusted odds ratio [OR], 4.09; 95% confidence interval [CI], 2.20-7.62). Valgus alignment at baseline was associated with a nearly 5-fold increase in the odds of lateral progression (adjusted OR, 4.89; 95% CI, 2.13-11.20). Severity of varus correlated with greater medial joint space loss during the subsequent 18 months (R = 0.52; 95% CI, 0.40-0.62 in dominant knees), and severity of valgus correlated with greater subsequent lateral joint space loss (R = 0.35; 95% CI, 0.21-0.47 in dominant knees). Having alignment of more than 5 degrees (in either direction) in both knees at baseline was associated with significantly greater functional deterioration during the 18 months than having alignment of 5 degrees or less in both knees, after adjusting for age, sex, body mass index, and pain. CONCLUSION This is, to our knowledge, the first demonstration that in primary knee OA varus alignment increases risk of medial OA progression, that valgus alignment increases risk of lateral OA progression, that burden of malalignment predicts decline in physical function, and that these effects can be detected after as little as 18 months of observation.