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A very important function of an issue tracking system is to assign labels to issue reports, such as bug, feature, enhancement, etc., in order to categorize issues to facilitate various development activities. In practice, it is very common that an issue has multiple labels. However, current works are mainly based on single-label prediction, which are not suitable for just-in-time multi-labeling services, due to the low efficiency. Therefore, in this paper, we propose MULA, a just-in-time MUlti-LAbeling system, which learns and automatically assigns multiple labels to issue reports. We have built a dataset with 81,601 entries and 11 labels, as the first benchmark for this task, and implemented a GitHub app. To the best of our knowledge, this is the first work and tool for online multi-labeling GitHub issues based on their categories. We conduct a comprehensive empirical study, including comparisons with five commonly adopted labeling models that show the superiority of MULA, as well as an evaluation that shows high consistency between MULA’s suggestions and developers’ opinions. [ABSTRACT FROM AUTHOR]

Unsupervised machine learning is the training of an artificial intelligence system using information that is neither classified nor labeled, with a view to modeling the underlying structure or distribution in a dataset. Since unsupervised machine learning systems are widely used in many real-world applications, assessing the appropriateness of these systems and validating their implementations with respect to individual users’ requirements and specific application scenarios/contexts are indisputably two important tasks. Such assessments and validation tasks, however, are fairly challenging due to the absence of a priori knowledge of the data. In view of this challenge, in this article, we develop a METamorphic Testing approach to assessing and validating unsupervised machine LEarning systems, abbreviated as mettle. Our approach provides a new way to unveil the (possibly latent) characteristics of various machine learning systems, by explicitly considering the specific expectations and requirements of these systems from individual users’ perspectives. To support mettle, we have further formulated 11 generic metamorphic relations (MRs), covering users’ generally expected characteristics that should be possessed by machine learning systems. We have performed an experiment and a user evaluation study to evaluate the viability and effectiveness of mettle. Our experiment and user evaluation study have shown that, guided by user-defined MR-based adequacy criteria, end users are able to assess, validate, and select appropriate clustering systems in accordance with their own specific needs. Our investigation has also yielded insightful understanding and interpretation of the behavior of the machine learning systems from an end-user software engineering's perspective, rather than a designer's or implementor's perspective, who normally adopts a theoretical approach. [ABSTRACT FROM AUTHOR]

Pyridine Nucleotide-Disulphide Oxidoreductase Domain 2 (PYROXD2), a Hepatitis B virus X protein (HBx)-interacting protein, is significantly down-regulated in hepatocellular carcinoma (HCC), however its exact biological function remains unclear. The aim of this study is to investigate the subcellular localization and biological function of PYROXD2 in hepatic cells. The results showed that PYROXD2 was imported to the mitochondrial inner membrane/matrix by Tom40 and Tim23, but not Mia40. PYROXD2 151-230aa might be the mitochondrial targeting sequence. PYROXD2 interacted with complex IV subunit COX5B. Knockout of PYROXD2 decreased MMP, intracellular ROS, complex IV activity, cell proliferation, ATP content and mtDNA copy number, but increased mtROS levels and the number of immature mitochondria. In summary, our data illustrated that PYROXD2 localizes to the mitochondrial inner membrane/matrix, and it plays important roles in regulating mitochondrial function. • PYROXD2 is a new protein located in the inner mitochondrial membrane/matrix fraction and interacted with COX5B. • The import of PYROXD2 to mitochondria is dependent on its mitochondrial targeting sequence 151-230 aa. • PYROXD2 plays important roles in the regulation of mitochondrial function. [ABSTRACT FROM AUTHOR]

Summary: Background: Emergence of highly inflammatory genital dermatophyte infections has been reported from Southeast Asia. In view of this, knowledge of the non‐outbreak fungal flora of the genitals is required as a baseline study. Objectives: We present our 12‐year experience in a tertiary clinic with the diagnosis of scrotal fungal infections. Methods: A retrospective review was performed of patients with a diagnosis of scrotal fungal infections proven by direct microscopy and culture. Clinical, mycological and treatment data were collected. Results: In total, 35 male patients were identified, of which 27 concerned dermatophyte infections and eight were yeasts. Nannizzia gypsea was the most common agent (48.6%), presenting as thick pseudomembraneous lesions limited to the scrotum. Trichophyton rubrum (22.9%) and Epidermophyton floccosum (5.7%) mainly presented erythematous, dry and scaly lesions and involving more sites besides the scrotum. Candida albicans (n = 3), C. glabrata (n = 2), C. guilliermondii (n = 1) and Trichosporon asteroides (n = 1), presented various lesions. Sports, sweating and concurrent tineas are hypothesised as predisposing factors. Conclusions: The prevalent causative agent of scrotum infections is N. gypsea, but wide species diversity is observed. All infections show mild skin inflammation. It is suggested that this genital fungal flora represents the current situation prior to clonal dermatophyte outbreaks. [ABSTRACT FROM AUTHOR]

Summary: Introduction: Neck skin aging is of particular interest to skin scientists and dermatologists because of the increasing demand for neck wrinkle improvement. This study aimed to determine the neck aging features of Chinese women and to investigate the clinical alterations and mechanical, topographical, and biophysical properties of neck skin. Methods: A total of 450 Chinese women (age range: 16‐66 years) were clinically examined and graded by the same dermatologist using standardized photographs. The skin properties were assessed by noninvasive skin measuring devices. Results: The results showed that different neck aging signs, including the horizontal neck fold, neck sagging, hollowing of emaciated neck, platysmal bands, and neck texture, appeared in different ages, and all of them worsened age‐dependently since they manifested. The skin elasticity markedly changed before the onset of most of the aging signs and showed a negative correlation with both age and the severity of these signs. Transepidermal water loss (TEWL) was positively correlated with age, whereas hydration and pH were not significantly correlated with age. We also found that wrinkles (SEw) and average roughness (Ra) were significantly correlated with age. SEw, smoothness, the average depth of roughness (Rz), TEWL, and erythema index were significantly and positively correlated with the severity of the horizontal neck fold, neck sagging, hollowing of emaciated neck, and platysmal bands. Conclusion: This is the first study to emphasize that age causes diverse changes in Chinese women's neck skin. The changes in skin elasticity may effectively predict neck aging before the onset of most of the neck aging signs. [ABSTRACT FROM AUTHOR]

Key message: Prolonged hypomethylation of DNA leads to telomere truncation correlated with increased telomere recombination, transposon mobilization and stem cell death.Abstract: Epigenetic pathways, including DNA methylation, are crucial for telomere maintenance. Deficient in DNA Methylation 1 (DDM1) encodes a nucleosome remodeling protein, required to maintain DNA methylation in Arabidopsis thaliana. Plants lacking DDM1 can be self-propagated, but in the sixth generation (G6) hypomethylation leads to rampant transposon activation and infertility. Here we examine the role of DDM1 in telomere length homeostasis through a longitudinal study of successive generations of ddm1-2 mutants. We report that bulk telomere length remains within the wild-type range for the first five generations (G1–G5), and then precipitously drops in G6. While telomerase activity becomes more variable in later generation ddm1-2 mutants, there is no correlation between enzyme activity and telomere length. Plants lacking DDM1 also exhibit no dysregulation of several known telomere-associated transcripts, including TERRA. Instead, telomere shortening coincides with increased G-overhangs and extra-chromosomal circles, consistent with deletional recombination. Telomere shortening also correlates with transcriptional activation of retrotransposons, and a hypersensitive DNA damage response in root apical meristems. Since abiotic stresses, including DNA damage, stimulate homologous recombination, we hypothesize that telomere deletion in G6 ddm1-2 mutants is a by-product of elevated genome-wide recombination in response to transposon mobilization. Further, we speculate that telomere truncation may be beneficial in adverse environmental conditions by accelerating the elimination of stem cells with aberrant genomes. [ABSTRACT FROM AUTHOR]

Telomeres are the essential nucleoprotein structures that provide a physical cap for the ends of linear chromosomes. The highly conserved CST (CTC1/STN1/TEN1) protein complex facilitates telomeric DNA replication and promotes telomere stability. Here we report three unexpected properties of Arabidopsis thaliana TEN1 that indicate it possesses functions distinct from other previously characterized telomere proteins. First, we show that telomeres in ten1 mutants are highly sensitive to thermal stress. Heat shock causes abrupt and dramatic loss of telomeric DNA in ten1 plants, likely via deletional recombination. Second, we show that AtTEN1 has the properties of a heat-shock induced molecular chaperone. At elevated temperature, AtTEN1 rapidly assembles into high molecular weight homo-oligomeric complexes that efficiently suppress heat-induced aggregation of model protein substrates in vitro. Finally, we report that AtTEN1 specifically protects CTC1 from heat-induced aggregation in vitro, and from heat-induced protein degradation and loss of telomere association in vivo. Collectively, these observations define Arabidopsis TEN1 as a highly dynamic protein that works in concert with CTC1 to preserve telomere integrity in response to environmental stress. [ABSTRACT FROM AUTHOR]

Minor ST-T abnormalities are common on the resting electrocardiogram of otherwise healthy persons, but the long-term importance of these findings has not been extensively evaluated, especially in women. In a prospective study, 7,985 women and 9,630 men (aged 40 to 64 years at baseline) without other electrocardiographic abnormalities and free of previous coronary heart disease (CHD) were studied using Cox regression for 22-years of follow-up. Primary outcomes were death from CHD and total cardiovascular disease (CVD); total mortality was a secondary outcome. Minnesota Code was employed to assess the presence or absence of electrocardiographic abnormalities. Analyses compared persons with minor Minnesota Code ST-segment (codes 4–3 or 4–4) or T-wave findings (codes 5–3 or 5–4) to those with normal electrocardiographic findings. In combined analyses of men and women adjusted for age, isolated minor T-wave abnormality, minor ST-segment depression, or a combination of minor ST-segment and T-wave abnormalities were each associated with increased mortality risks. For CHD mortality, hazard ratios (HRs) ranged from 1.60 to 2.10; for CVD mortality, HRs ranged from 1.50 to 1.95; and for total mortality, HRs ranged from 1.31 to 1.50 (p <0.05 for all HRs). In separate analyses by gender adjusted for age, increased risks were observed for combined ST-T-wave abnormalities in both genders for CHD and CVD mortality (HR 1.72 to 1.75 for men, p <0.05; HR 2.07 to 2.51 for women, p <0.001). These data indicate that nonspecific (minor) ST-segment depression and/or T-wave abnormalities have a long-term prognostic impact for CHD and CVD death in middle-aged women and men and can be considered markers of heightened CHD and CVD risk. [Copyright &y& Elsevier]

Background: The absence of heterozygosity (AOH) is a kind of genomic change characterized by a long contiguous region of homozygous alleles in a chromosome, which may cause human genetic disorders. However, no method of low-pass whole genome sequencing (LP-WGS) has been reported for the detection of AOH in a low-pass setting of less than onefold. We developed a method, termed CNVseq-AOH, for predicting the absence of heterozygosity using LP-WGS with ultra-low sequencing data, which overcomes the sparse nature of typical LP-WGS data by combing population-based haplotype information, adjustable sliding windows, and recurrent neural network (RNN). We tested the feasibility of CNVseq-AOH for the detection of AOH in 409 cases (11 AOH regions for model training and 863 AOH regions for validation) from the 1000 Genomes Project (1KGP). AOH detection using CNVseq-AOH was also performed on 6 clinical cases with previously ascertained AOHs by whole exome sequencing (WES). Results: Using SNP-based microarray results as reference (AOHs detected by CNVseq-AOH with at least a 50% overlap with the AOHs detected by chromosomal microarray analysis), 409 samples (863 AOH regions) in the 1KGP were used for concordant analysis. For 784 AOHs on autosomes and 79 AOHs on the X chromosome, CNVseq-AOH can predict AOHs with a concordant rate of 96.23% and 59.49% respectively based on the analysis of 0.1-fold LP-WGS data, which is far lower than the current standard in the field. Using 0.1-fold LP-WGS data, CNVseq-AOH revealed 5 additional AOHs (larger than 10 Mb in size) in the 409 samples. We further analyzed AOHs larger than 10 Mb, which is recommended for reporting the possibility of UPD. For the 291 AOH regions larger than 10 Mb, CNVseq-AOH can predict AOHs with a concordant rate of 99.66% with only 0.1-fold LP-WGS data. In the 6 clinical cases, CNVseq-AOH revealed all 15 known AOH regions. Conclusions: Here we reported a method for analyzing LP-WGS data to accurately identify regions of AOH, which possesses great potential to improve genetic testing of AOH. [ABSTRACT FROM AUTHOR]

Background: The current ISO guidelines for minimal erythema dose (MED) determination require assessment of erythema area of UV‐irradiated skin sites. However, this parameter has not been adequately quantified in daily practice. The aims of this study were to investigate the dose response on the unprotected skin sites by quantifying the erythema area and intensity and to show the potential for improving the precision and consistency of MEDu determination by developing predictive models. Methods: Standard radiation tests were conducted on the back of 31 healthy Chinese volunteers and the MEDu site of each subject was clinically determined by dermatologists. Images of test sites were captured 24 h after radiation, and the erythema area (%EA) and intensity (∆a*) were measured by image analysis. The data were fitted to a logistic 3P function to obtain dose–response curves, and a set of logit (inverse‐logistic) models were then derived. An erythema area threshold of %EA = 52% was established to predict MEDu based on the clinical endpoints defined by ISO 24444:2019. Results: Analysis of the clinically determined MEDu sites revealed wide ranges of %EA (62.3 ± 15% SD) and ∆a* (2.96 ± 0.92 SD). The dose response fitted well to a logistic 3P model (mean R2 = 0.965 and 0.975 for %EA and ∆a*, respectively). Applying the area threshold, values of MEDu were determined by the logit model for the test population, which significantly improved the consistency of MEDu determination (52 ± 0% SD and 2.73 ± 0.61 SD for %EA and ∆a*, respectively). Conclusion: This study demonstrated that the dose response of UV‐induced erythema can be quantified and modeled once the erythema area and intensity are measured. The results of this study show the potential to improve the precision and consistency of MEDu determination in an SPF test. The similar potential in photodermatological, therapeutic, and diagnostic applications was also implied. [ABSTRACT FROM AUTHOR]

Although there have been some studies about changes of skin erythema and pigmentation following ultraviolet radiation in other races, the relevant data in Chinese have never been achieved. Thus, we evaluated the long-time course of skin erythema, pigmentation and hydration changes after different doses of solar-simulated ultraviolet ( SSUV) irradiation in 26 Chinese women for 168 days. The erythema index increased abruptly and peaked during 3 days of SSUV exposure, then slowly returned to the baseline level starting at day 7 and completely recovered during 168-day course of this study only in one minimal erythema doses ( MED) SSUV irradiation. The melanin index started to slowly increase at day 3 of SSUV exposure, peaking at day 14 and gradually returned to the baseline level thereafter, but did not return to the baseline level during 168-day course in all doses. Skin hydration slowly declined at day 3 of exposure, hitting the lowest point at day 7, then slowly recovered starting at day 14 and completely returned to the baseline level at day 28 only in 1.5 MED. These results will serve as baseline data on Chinese skin and provide useful references for the treatment of serious skin photodamage in Chinese. [ABSTRACT FROM AUTHOR]

[Display omitted] • A polygonal MDF and preferred ion lists were used for progressive data acquisition. • Deep learning-assisted MDF combined with GNPS for compound identification. • 116 compounds containing 86 alkaloids were identified in PCC. Advanced analytical methods are often required for detailed and comprehensive interpretation of the complex traditional Chinese medicine system. Phellodendri Chinensis Cortex (PCC) is a common herb involving alkaloids as its main active constituent. The systemic characterization of alkaloids in PCC was carried out by an intelligent process combining polygonal mass defect filtering (p-MDF) with preferred ion lists based on high-resolution mass spectrometry. Firstly, the combination of p-MDF and preferred ion lists was used for data acquisition. Secondly, the mass spectrometry data sets were classified by the deep learning-assisted MDF method for manual annotation, including alkaloids and other components. The characteristic diagnosis ions and neutral loss fragments were also used to assist the manual annotation. Subsequently, the Global Natural Product Social platform was employed for automated annotation. A total of 116 compounds from PCC were identified, containing 86 alkaloids, 1 amino acid, 9 phenylpropanoids, 2 triterpenoids, 13 fatty acids and 5 others. The established strategy provided a powerful guide for the chemical characterization of complex herbal substrates. [ABSTRACT FROM AUTHOR]

Ischemia-reperfusion (IR) injury is a main cause to and the mechanism of necrosis after flap transplantation. Researches were hardly conducted on the role and possible mechanism of keratinocyte growth factor (KGF) in association with IR flap injury. A CoCl 2 -stimulated hypoxia cell model was established to investigate the effects of KGF on cell viability, apoptosis, cell cycle, and reactive oxygen species level. The experiments were performed by cell counting kit-8 and flow cytometry as required. Meanwhile, the expressions of cell cycle-related and nuclear factor E2–related factor 2 (Nrf2) signaling–related genes were determined using quantitative real-time PCR and Western blot. The right dorsolateral areas of Institute of Cancer Research mice were marked as flaps, the pedicle of which formed an IR process through clamping and loosening. Tissue morphologies were observed using hematoxylin and eosin staining 24 h after the surgery. The effects of KGF on cell apoptosis and associated genes expressions were studied by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling, immunohistochemistry, and Western blot. HaCAT cells treated with 40 μM CoCl 2 could not only reduce cell viability, promote cell apoptosis, arrest G1 phase of cell cycle and increase the activity of reactive oxygen species but also downregulate the expressions of c-myc, c-fos, transforming growth factor-α, Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase. Additional recombinant human KGF, on one hand, could protect the cells from hypoxia injury. On the other hand, recombinant human KGF could significantly inhibit cell apoptosis, increase KGF activity, and increase the Nrf2, heme oxygenase-1, and gamma-glutamyl cysteine synthetase proteins levels in IR flap tissues. KGF played an important role in protecting mice flaps from IR injury, and the possible mechanism was involved in activating the Nrf2 signaling. [ABSTRACT FROM AUTHOR]

Excessive sun exposure can cause sunburn, suntan, skin photoaging, and even skin cancer. Skin photoaging conflicts with the human pursuit of a young and beautiful appearance. Some research data indicate that the incidence of skin cancer in the Chinese has been increasing, although it remains lower than in whites. To estimate the prevalence of sun protection used on Chinese children aged 3-13 years and identify its predictors, a population-based cross-sectional questionnaire was given to 3684 parents/guardians of children in Guangzhou, China, of which 3083 questionnaires were returned. Of those returned, 35.5% of parents/guardians reported regularly using sun protection on their children and the primary reason cited was to prevent sunburn. Hats and handheld umbrellas were the most frequently used measures; sunscreen was less common, and when used, 48.8% of parents/guardians still reapplied sunscreen on their children every 2.0-3.0 h. Parental age, parents using sun protection measures themselves when outdoors, and the child's sex were factors associated with regular use of sun protection on children. These results suggest that sun protection campaigns targeted toward parents and children need to be conducted in Guangzhou, or throughout China, to strengthen awareness about sun protection and address any inadequate protocols of sun protection. [ABSTRACT FROM AUTHOR]

Objective To investigate genetic polymorphisms of HPRTB, DXS6803 and DXS6809 STR loci in Tianjin Han female population, and to provide experimental data in the prenatal diagnosis of aneuploidies accurately and rapidly. Methods A total of 150 blood samples were collected in Tianjin Han population. QF-PCR and capillary electrophoresis were used in this study. The relevant data were analyzed by ABI Prism GeneMapper v3.0 software. Two homozygotes were selected from each locus for sequencing. The frequencies of the genotypes were checked using Chi-square test to verify Hardy-Weinberg Equilibrium. Data of genetic polymorphisms were calculated by PowerStatsV 12 software. Results A total of 150 samples were successfully amplified in 24 hours. The 10, 6 and 10 alleles and 22, 12 and 29 genotypes were found respectively in HPRTB, DXS6803 and DXS6809 loci. The most common alleles were 14, 13 and 14. The higher frequencies of genotypes were 14- 14, 12- 13 and 13- 14. No significant deviations from the Hardy- Weinberg equilibrium were observed in these three STR loci (X2=10.554, 5.783 and 15.355, respectively, P > 0.05). Values of He were 0.748, 0.649 and 0.806 for these three STR loci respectively. Values of Ho were 0.607, 0.700 and 0.713 respectively. Values of PIC were 0.706, 0.599 and 0.775 respectively. Values of PD were 0.894, 0.814 and 0.931 respectively. And values of PE were 0.299, 0.428 and 0.449 respectively. Conclusion HPRTB, DXS6803 and DXS6809 STR loci were highly polymorphic, which are favorable genetic markers on chromosome X and can be used in rapid prenatal genetic diagnosis. [ABSTRACT FROM AUTHOR]

Minor ST-T abnormalities are common on the resting electrocardiogram of otherwise healthy persons, but the long-term importance of these findings has not been extensively evaluated, especially in women. In a prospective study, 7,985 women and 9,630 men (aged 40 to 64 years at baseline) without other electrocardiographic abnormalities and free of previous coronary heart disease (CHD) were studied using Cox regression for 22-years of follow-up. Primary outcomes were death from CHD and total cardiovascular disease (CVD); total mortality was a secondary outcome. Minnesota Code was employed to assess the presence or absence of electrocardiographic abnormalities. Analyses compared persons with minor Minnesota Code ST-segment (codes 4-3 or 4-4) or T-wave findings (codes 5-3 or 5-4) to those with normal electrocardiographic findings. In combined analyses of men and women adjusted for age, isolated minor T-wave abnormality, minor ST-segment depression, or a combination of minor ST-segment and T-wave abnormalities were each associated with increased mortality risks. For CHD mortality, hazard ratios (HRs) ranged from 1.60 to 2.10; for CVD mortality, HRs ranged from 1.50 to 1.95; and for total mortality, HRs ranged from 1.31 to 1.50 (p <0.05 for all HRs). In separate analyses by gender adjusted for age, increased risks were observed for combined ST-T-wave abnormalities in both genders for CHD and CVD mortality (HR 1.72 to 1.75 for men, p <0.05; HR 2.07 to 2.51 for women, p <0.001). These data indicate that nonspecific (minor) ST-segment depression and/or T-wave abnormalities have a long-term prognostic impact for CHD and CVD death in middle-aged women and men and can be considered markers of heightened CHD and CVD risk. [ABSTRACT FROM AUTHOR]

: ObjectivesThe goal of this study was to determine the presence and correlates of change (Δ) in left ventricular (LV) mass by echocardiography in young adults.: BackgroundLeft ventricular mass is known to be a powerful independent predictor for cardiovascular disease events in adults. However, little is known about Δ in LV mass over time in young adults.: MethodsCoronary Artery Risk Development in Young Adults (CARDIA) is a multicenter, longitudinal, population-based study of black and white men and women who were ages 23 to 35 at the time of their initial two-dimensionally directed M-mode echocardiography exam (year 5); half the cohort had a repeat echocardiography exam five years later (year 10). Data were analyzed from 1,189 participants who had paired echocardiography studies. To minimize reader variability, blinded measurements on initial and repeat echocardiography were performed nearly contemporaneously by the same reader.: ResultsIn multilinear regression analyses, significant (p < 0.05) predictors of year 10 two-dimensional guided M-mode LV mass included initial LV mass, initial body mass index (BMI) and change in BMI for all race/gender subgroups. Initial systolic blood pressure (SBP) was a significant predictor of year 10 LV mass in white men and black women; change in SBP was significant in black women with a trend towards significance in white women. Left ventricular mass remained constant in all race/gender subgroups, except black women, where it increased (by 5.9 g [mean]). Black women also had the largest increases in BMI and SBP. In black women, a five-year weight gain of 20 pounds and a 15-mm Hg increase in SBP would be expected to be associated with a 9% to 12% increase in LV mass.: ConclusionsParticularly in black women, weight and blood pressure control may be important community health and treatment goals to prevent LV hypertrophy. [Copyright &y& Elsevier]

Presents a study which examined the associations of single and multiple nonspecific minor ST segment or T-wave abnormalities (ST-T abnormalities) in five years with long-term mortality due to myocardial infarction, coronary heart disease, cardiovascular disease and other causes in middle aged men. Participants in the study; Results; Conclusions.