Miracle-dz/UniFAR-FTUs huggingface dataset:
How Do Developers Fix Cross-Project Correlated Bugs? A Case Study on the GitHub Scientific Python Ecosystem

GitHub, a popular social-software-development platform, has fostered a variety of software ecosystems where projects depend on one another and practitioners interact with each other. Projects within an ecosystem often have complex inter-dependencies that impose new challenges in bug reporting and fixing. In this paper, we conduct an empirical study on cross-project correlated bugs, i.e., causally related bugs reported to different projects, focusing on two aspects: 1) how developers track the root causes across projects, and 2) how the downstream developers coordinate to deal with upstream bugs. Through manual inspection of bug reports collected from the scientific Python ecosystem and an online survey with developers, this study reveals the common practices of developers and the various factors in fixing cross-project bugs. These findings provide implications for future software bug analysis in the scope of ecosystem, as well as shed light on the requirements of issue trackers for such bugs.
Impact of HbA1c Testing at Point of Care on Diabetes Management

Diabetes is a highly prevalent disease also implicated in the development of several other serious complications like cardiovascular or renal disease. HbA1c testing is a vital step for effective diabetes management, however, given the low compliance to testing frequency and, commonly, a subsequent delay in the corresponding treatment modification, HbA1c at the point of care (POC) offers an opportunity for improvement of diabetes care. In this review, based on data from 1999 to 2016, we summarize the evidence supporting a further implementation of HbA1c testing at POC, discuss its limitations and propose recommendations for further development.
Polymorphisms and expression pattern of circular RNA circ-ITCH contributes to the carcinogenesis of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) ranks the sixth most common cancer and the third cause of cancer-related mortality worldwide. Recent studies identified that circ-ITCH Suppresses mutiple cancers proliferation via inhibiting the Wnt/beta-Catenin pathway. In current study, conducted a genetic association study together with epidemiological follow-up study to delineate the role of circ-ITCH in the development and progression of HCC. we found rs10485505 (adjusted OR =1.18; 95% CI=1.06-1.31; P value =3.1×10-3) and rs4911154 (adjusted OR =1.27; 95% CI=1.14-1.43; P value =3.7×10-5) were significantly associated with increased HCC risk. The expression level of circ-ITCH was significantly lower in HCC tissues, compared with that in adjacent tissues (P value < 0.001). Cox regression analysis indicated that high expression of circ-ITCH was associated with favorable survival of HCC (HR=0.45; 95% CI=0.29-0.68; P value < 0.001). These results indicate that circ-ITCH may have an inhibitory effect on HCC, and could serve as susceptibility and prognostic biomarkers for HCC patients.
Incidence of Ovarian, Peritoneal, and Fallopian Tube Carcinomas in the United States, 1995-2004

Objective: The objective of this analysis was to describe the distribution of pelvic carcinomas in the United States by demographic, pathologic, and clinical features. Methods: Carcinomas of the ovary (n = 112,541), peritoneum (n = 6,458), and fallopian tube (n = 3,479) were identified through 24 population-based registries in the United States during the period 1995 to 2004. Age-adjusted incidence rates were calculated per million population using counts derived from the 2000 U.S. census. Results: The age-adjusted incidence rate for ovarian carcinoma (119.9 per million) was substantially higher than for peritoneal (6.78 per million) or fallopian tube (3.72 per million) carcinomas. White women had the highest rates for all three malignancies. Rates for peritoneal carcinoma were lowest among Black women (2.88 per million) and rates for fallopian tube carcinoma were lowest among Hispanic women (2.45 per million). Serous carcinomas were the most commonly diagnosed histologic type for all anatomic sites. Peritoneal carcinomas were diagnosed at later ages (mean, 67 years) and more advanced stages (85% regional/distant) compared with fallopian tube carcinomas (mean, 64 years; 62% regional/distant) and ovarian carcinomas (mean, 63 years; 76% regional/distant). Incidence for all three pelvic carcinomas was lowest in the South. Time trend analyses between 1973 and 2005 exhibited a significant decline in ovarian carcinoma incidence and rises in the rates of peritoneal and fallopian tube cancers. Conclusions: Similarities in the incidence patterns for ovarian, peritoneal, and fallopian tube carcinomas support the likelihood of a common molecular pathogenesis. (Cancer Epidemiol Biomarkers Prev 2009;18(1):132–9)
Synergistic action of the MCL-1 inhibitor S63845 with current therapies in preclinical models of triple-negative and HER2-amplified breast cancer

The MCL-1 inhibitor S63845 is effective in combination with conventional therapy for targeting triple-negative and HER2-amplified breast cancer. Cutting off another tumor lifeline BH3 mimetics are drugs that inhibit the BCL-2 family of prosurvival proteins in cancer cells and thereby promote cancer cell death. Unfortunately, MCL-1, a member of this prosurvival family, can interfere with treatment because it is not sensitive to currently available BH3 mimetics. The MCL-1 inhibitor S63845 was developed to overcome this mechanism of treatment resistance, and Merino et al. examined the effectiveness of this drug in cell lines and xenografts derived from breast cancer patients. The authors demonstrated the drug’s efficacy in combination with several drugs that are already in clinical use and also identified a protein that can promote treatment resistance, which may help predict which patients are more likely to benefit from the new treatment. The development of BH3 mimetics, which antagonize prosurvival proteins of the BCL-2 family, represents a potential breakthrough in cancer therapy. Targeting the prosurvival member MCL-1 has been an area of intense interest because it is frequently deregulated in cancer. In breast cancer, MCL-1 is often amplified, and high expression predicts poor patient outcome. We tested the MCL-1 inhibitor S63845 in breast cancer cell lines and patient-derived xenografts with high expression of MCL-1. S63845 displayed synergistic activity with docetaxel in triple-negative breast cancer and with trastuzumab or lapatinib in HER2-amplified breast cancer. Using S63845-resistant cells combined with CRISPR (clustered regularly interspaced short palindromic repeats)–Cas9 (CRISPR-associated 9) technology, we identified deletion of BAK and up-regulation of prosurvival proteins as potential mechanisms that confer resistance to S63845 in breast cancer. Collectively, our findings provide a strong rationale for the clinical evaluation of MCL-1 inhibitors in breast cancer.
Identification of human cancers deficient in antigen processing

Intracellular antigens must be processed before presentation to CD8+ T cells by major histocompatibility complex (MHC) class I molecules. Using a recombinant vaccinia virus (Vac) to transiently express the Kd molecule, we studied the antigen processing efficiency of 26 different human tumor lines. Three cell lines, all human small cell lung carcinoma, consistently failed to process endogenously synthesized proteins for presentation to Kd-restricted, Vac-specific T cells. Pulse- chase experiments showed that MHC class I molecules were not transported by these cell lines from the endoplasmic reticulum to the cell surface. This finding suggested that peptides were not available for binding to nascent MHC molecules in the endoplasmic reticulum. Northern blot analysis of these cells revealed low to nondetectable levels of mRNAs for MHC-encoded proteasome components LMP-7 and LMP-2, as well as the putative peptide transporters TAP-1 and TAP-2. Treatment of cells with interferon gamma enhanced expression of these mRNAs and reversed the observed functional and biochemical deficits. Our findings suggest that downregulation of antigen processing may be one of the strategies used by tumors to escape immune surveillance. Potential therapeutic applications of these findings include enhancing antigen processing at the level of the transcription of MHC-encoded proteasome and transporter genes.
Understanding Insulin Endocrinology in Decapod Crustacea: Molecular Modelling Characterization of an Insulin-Binding Protein and Insulin-Like Peptides in the Eastern Spiny Lobster, Sagmariasus verreauxi

The insulin signalling system is one of the most conserved endocrine systems of Animalia from mollusc to man. In decapod Crustacea, such as the Eastern spiny lobster, Sagmariasus verreauxi (Sv) and the red-claw crayfish, Cherax quadricarinatus (Cq), insulin endocrinology governs male sexual differentiation through the action of a male-specific, insulin-like androgenic gland peptide (IAG). To understand the bioactivity of IAG it is necessary to consider its bio-regulators such as the insulin-like growth factor binding protein (IGFBP). This work has employed various molecular modelling approaches to represent S. verreauxi IGFBP and IAG, along with additional Sv-ILP ligands, in order to characterise their binding interactions. Firstly, we present Sv- and Cq-ILP2: neuroendocrine factors that share closest homology with Drosophila ILP8 (Dilp8). We then describe the binding interaction of the N-terminal domain of Sv-IGFBP and each ILP through a synergy of computational analyses. In-depth interaction mapping and computational alanine scanning of IGFBP_N’ highlight the conserved involvement of the hotspot residues Q67, G70, D71, S72, G91, G92, T93 and D94. The significance of the negatively charged residues D71 and D94 was then further exemplified by structural electrostatics. The functional importance of the negative surface charge of IGFBP is exemplified in the complementary electropositive charge on the reciprocal binding interface of all three ILP ligands. When examined, this electrostatic complementarity is the inverse of vertebrate homologues; such physicochemical divergences elucidate towards ligand-binding specificity between Phyla.
Investigating The Relationship between Attachment Styles and Coping Strategies with Students' Life Quality of Jondishapour Medical University of Ahvaz

The current research was done with the aim of investigating the relationship between Attachment Styles and coping strategies with life quality. The statistical population of the current research is all of the students of Jondishapour Medical University of Ahvaz in academic year of 2014-15. A sample with size of 200 was selected using multistage cluster sampling method. The research is correlational descriptive. The instruments of collecting data were: Adults Attachment Scale (RASS), the Coping with Stressful Events Scale-Short Form (CLSS-21), World Health Organization Quality of Life Questionnaire (WHOQOL-BREF), and a series of demographic questions. The data were analyzed using SPSS-18 and the statistical tests of Pearson correlation, multivariate regression analysis (ENTER). The results showed that 55% of variance of students' life quality can be explained in terms of their attachment style and coping style and it observed that there is a positive correlation between secure attachment style and problem-oriented coping style with life quality in students and there are negative correlations among other attachment styles (avoidance and ambivalent) and coping styles (emotion-oriented and avoidant-oriented) with life quality of students.
Cleavage and polyadenylation: Ending the message expands gene regulation

ABSTRACT Cleavage and polyadenylation (pA) is a fundamental step that is required for the maturation of primary protein encoding transcripts into functional mRNAs that can be exported from the nucleus and translated in the cytoplasm. 3′end processing is dependent on the assembly of a multiprotein processing complex on the pA signals that reside in the pre-mRNAs. Most eukaryotic genes have multiple pA signals, resulting in alternative cleavage and polyadenylation (APA), a widespread phenomenon that is important to establish cell state and cell type specific transcriptomes. Here, we review how pA sites are recognized and comprehensively summarize how APA is regulated and creates mRNA isoform profiles that are characteristic for cell types, tissues, cellular states and disease.
Evaluation of a Simpler Tool to Assess Nontechnical Skills During Simulated Critical Events

Introduction Management of critical events requires teams to employ nontechnical skills (NTS), such as teamwork, communication, decision making, and vigilance. We sought to estimate the reliability and provide evidence for the validity of the ratings gathered using a new tool for assessing the NTS of anesthesia providers, the behaviorally anchored rating scale (BARS), and compare its scores with those of an established NTS tool, the Anaesthetists' Nontechnical Skills (ANTS) scale. Methods Six previously trained raters (4 novices and 2 experts) reviewed and scored 18 recorded simulated pediatric crisis management scenarios using a modified ANTS and a BARS tool. Pearson correlation coefficients were calculated separately for the novice and expert raters, by scenario, and overall. Results The intrarater reliability of the ANTS total score was 0.73 (expert, 0.57; novice, 0.84); for the BARS tool, it was 0.80 (expert, 0.79; novice, 0.81). The average interrater reliability of BARS scores (0.58) was better than ANTS scores (0.37), and the interrater reliabilities of scores from novices (0.69 BARS and 0.52 ANTS) were better than those obtained from experts (0.47 BARS and 0.21 ANTS) for both scoring instruments. The Pearson correlation between the ANTS and BARS total scores was 0.74. Conclusions Overall, reliability estimates were better for the BARS scores than the ANTS scores. For both measures, the intrarater and interrater reliability was better for novices compared with domain experts, suggesting that properly trained novices can reliably assess the NTS of anesthesia providers managing a simulated critical event. There was substantial correlation between the 2 scoring instruments, suggesting that the tools measured similar constructs. The BARS tool can be an alternative to the ANTS scale for the formative assessment of NTS of anesthesia providers.
Associations of occupation, job control and job demands with intima-media thickness: The Multi-Ethnic Study of Atherosclerosis (MESA)

Objectives Occupation has been linked to cardiovascular disease (CVD) incidence and mortality, but few studies have investigated occupation in relation to early atherosclerotic disease. This study examined associations between various occupational characteristics and carotid artery intima-media thickness (IMT) in a multi-ethnic sample. Methods The Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6814 adults aged 45–84 years and free of clinical CVD (response rate 60%, 51% female). Questionnaire data were used to determine occupational group (managerial/professional, sales/office, service, blue-collar), psychosocial job characteristics (ie, job demands, job control) and other sociodemographic information. Results Common carotid artery (CCA)-IMT was greater for blue-collar jobs than for management/professional jobs (mean difference=0.012 mm, p=0.049) after adjustment for age, sex, race, place of birth (US or foreign born) and CVD risk factors. Compared to management/professional jobs, internal carotid artery (ICA)-IMT was greater for sales/office, service and blue-collar jobs (mean difference=0.071 mm, p<0.001; 0.057 mm, p=0.009; and 0.110 mm, p<0.001, respectively) after adjustment for age, sex, race and place of birth. The difference between blue-collar jobs and management/professional jobs remained significant after additional adjustment for CVD risk factors, income and education (mean difference=0.048 mm, p=0.045). Higher levels of control at work were associated with thinner CCA-IMT (mean difference=−0.009 mm, p=0.016, adjusted for age, sex, race and place of birth) but not with ICA-IMT. Job demands had no significant association with IMT. Conclusions Blue-collar jobs and low levels of job control were associated with the development of subclinical atherosclerosis.
Sex Peptide Is Required for the Efficient Release of Stored Sperm in Mated Drosophila Females

The Drosophila seminal fluid protein (SFP) sex peptide (SP) elicits numerous post-mating responses, including increased egg laying and decreased sexual receptivity, in the mated female. Unlike other SFPs, which are detectable in mated females for only a few hours post mating, SP is maintained—and its effects are sustained—for several days. The persistence of SP in the mated female's reproductive tract is thought to be a consequence of its binding to, and gradual release from, sperm in storage, which maintains SP's ability to act within the female reproductive tract. Recent studies have shown that several other SFPs, acting in a network, are needed for SP's localization to sperm and are necessary for the efficient release of sperm from storage. This result suggested an additional new role for SP modulating the release of sperm from storage. We tested for this possibility by examining sperm storage parameters in mated females that did not receive SP. We found that while sperm accumulation into storage was unaffected, sperm depletion from storage sites was significantly decreased (or impaired) in the absence of SP. Mates of males expressing a modified SP that is unable to be released from sperm showed a similar phenotype, indicating that release of sperm-bound SP is a necessary component of normal sperm depletion. Additionally, SP null males were more successful in a sperm competitive environment when they were first to mate, which is likely a consequence of higher retention of their sperm due to defective sperm release. Our findings illustrate a direct role for SP in the release of sperm from storage.
NR2B-Containing Receptors Mediate Cross Talk among Hippocampal Synapses

Under some conditions, synaptically released glutamate can exert long-range actions in the cortical microcircuitry. To what extent glutamate spillover leads to direct cross talk among individual synapses remains unclear. We recorded NMDAR-mediated EPSCs in acute hippocampal slices at 35°C by stimulating two independent pathways that converge on the same CA1 pyramidal cell. Activation of a conditioning pathway in the presence of the use-dependent blocker dizocilpine maleate (MK801) resulted in partial NMDA receptor (NMDAR) blockade in the other, silent pathway. This was accompanied by an increase in the rise time of the EPSCs in the conditioning (although not the silent) pathway, implying an increase in diffusional distance from release site to NMDARs. We estimated that up to ∼30% of NMDARs contributing to EPSCs were activated by glutamate released from multiple synaptic sources; however, NMDAR-mediated synaptic cross talk was undetectable when NR2B subunit-containing receptors were blocked (but could be rescued by blocking glutamate uptake). We propose that NR2B-containing NMDARs can detect glutamate arising from multiple synapses, whereas NR2A-containing NMDARs only normally mediate direct synaptic transmission. These NMDAR isoforms thus play complementary roles in sensing global and local glutamate signals, respectively.
Differentiating Speech Sound Disorders From Phonological Dialect Differences: Implications for Assessment and Intervention

B. Z. Pearson, S. L. Velleman, T. J. Bryant, and T. Charko (2009) demonstrated phonological differences in typically developing children learning African American English as their first dialect vs. General American English only. Extending this research to children with speech sound disorders (SSD) has key implications for intervention. A total of 148 children (4–12 years) with SSD, 72 learning only general American English and 76 learning African American English first, took the Dialect Sensitive Language Test (DSLT; H. Seymour, T. Roeper, & J. G. de Villiers, 2000) phonology subtest. Mismatches to target forms were categorized as phonotactic vs. segmental. The scores of the children with SSD were below Dialect Sensitive Language Test norms; overall dialect differences in mismatch frequency were not identified. However, individual consonants were mastered in different orders by dialect, even among children with SSD. Phonotactic vs. segmental dialect differences were emergent but nonsignificant at age 6 years. Intervention targets should be chosen per dialect-specific segmental orders of acquisition and phonotactic priorities.
A Btk transgene restores the antiviral TI‐2 antibody responses of xid mice in a dose‐dependent fashion

X‐linked agammaglobulinemia in humans and X‐linked immunodeficiency (xid) in mice are both caused by mutations in Bruton's tyrosine kinase (Btk). Xid mice lack the early T cell‐independent type 2 (TI‐2) antibody response to polio virus and to a recombinant vaccinia virus (Vacc‐IND‐G) expressing the neutralizing determinant of vesicular stomatitis virus (VSV). This response could be restored by introduction of one or two copies of a murine Btk cDNA transgene driven by the Ig heavy chain promoter plus enhancer and depended crucially on a sufficient Btk expression level. Introduction of the same transgene into wild‐type mice had little to no negative effect. The TI‐1 antibody response to VSV and the T cell‐dependent response to lymphocytic choriomeningitis virus were comparable in all mice tested. All mice analyzed eventually reached similar primary and memory antibody titers against all viruses independent of the mouse Btk genotype. These studies show that the xid mutation in mice has no dominant negative effect and that a transgene – even when not provided in the natural genetic context – may be able to restore functional defects resulting from genetic mutation.
Fluid Management With a Simplified Conservative Protocol for the Acute Respiratory Distress Syndrome*

Objectives:In the Fluid and Catheter Treatment Trial (FACTT) of the National Institutes of Health Acute Respiratory Distress Syndrome Network, a conservative fluid protocol (FACTT Conservative) resulted in a lower cumulative fluid balance and better outcomes than a liberal fluid protocol (FACTT Liberal). Subsequent Acute Respiratory Distress Syndrome Network studies used a simplified conservative fluid protocol (FACTT Lite). The objective of this study was to compare the performance of FACTT Lite, FACTT Conservative, and FACTT Liberal protocols. Design:Retrospective comparison of FACTT Lite, FACTT Conservative, and FACTT Liberal. Primary outcome was cumulative fluid balance over 7 days. Secondary outcomes were 60-day adjusted mortality and ventilator-free days through day 28. Safety outcomes were prevalence of acute kidney injury and new shock. Setting:ICUs of Acute Respiratory Distress Syndrome Network participating hospitals. Patients:Five hundred three subjects managed with FACTT Conservative, 497 subjects managed with FACTT Liberal, and 1,124 subjects managed with FACTT Lite. Interventions:Fluid management by protocol. Measurements and Main Results:Cumulative fluid balance was 1,918 ± 323 mL in FACTT Lite, –136 ± 491 mL in FACTT Conservative, and 6,992 ± 502 mL in FACTT Liberal (p < 0.001). Mortality was not different between groups (24% in FACTT Lite, 25% in FACTT Conservative and Liberal, p = 0.84). Ventilator-free days in FACTT Lite (14.9 ± 0.3) were equivalent to FACTT Conservative (14.6 ± 0.5) (p = 0.61) and greater than in FACTT Liberal (12.1 ± 0.5, p < 0.001 vs Lite). Acute kidney injury prevalence was 58% in FACTT Lite and 57% in FACTT Conservative (p = 0.72). Prevalence of new shock in FACTT Lite (9%) was lower than in FACTT Conservative (13%) (p = 0.007 vs Lite) and similar to FACTT Liberal (11%) (p = 0.18 vs Lite). Conclusions:FACTT Lite had a greater cumulative fluid balance than FACTT Conservative but had equivalent clinical and safety outcomes. FACTT Lite is an alternative to FACTT Conservative for fluid management in Acute Respiratory Distress Syndrome.