Miracle-dz/UniFAR-FTUs huggingface dataset:
Presence or Absence of Significant HPVE4 Expression in High-grade Anal Intraepithelial Neoplasia With p16/Ki-67 Positivity Indicates Distinct Patterns of Neoplasia: A Study Combining Immunohistochemistry and Laser Capture Microdissection PCR

Progression of anal intraepithelial neoplasia (AIN) involves transition from productive to transforming human papillomavirus (HPV) infection. Grading aims to distinguish productive low-grade AIN from high-grade anal intraepithelial neoplasia (HGAIN) with risk of cancer. We describe immunohistochemical patterns in AIN adding a novel marker for initiation of the productive phase of the HPV life cycle (panHPVE4) to those for cell cycle activity (Ki-67) and transforming activity of HPVE7 gene (p16). We studied 67 anal biopsies for suspected anal neoplasia (17 normal, 15 AIN1, 20 AIN2, 15 AIN3) from 54 men who have sex with men at New York Presbyterian Hospital, USA. Two pathologists generated consensus AIN and immunogrades. Whole tissue and laser capture microdissection samples from multiple HPV-infected biopsies were tested for HPV with SPF10-PCR-DEIA-LiPA25, version 1. (Para)basal Ki-67 expression distinguished normal from AIN (≥lower-third Ki-67) with sensitivity 0.92 and specificity 1.0. Ki-67 did not distinguish grades of AIN. Null/patchy p16 versus diffuse ≥lower-third patterns discriminated HGAIN (sensitivity, 1.0; specificity, 0.84). There was marked heterogeneity in E4 expression within HGAIN. Most AIN2 (14/20) was E4+ versus 0/15 AIN3 (sensitivity, 0.70; specificity 1.0). HPV was detected in 63 (94%) biopsies, with 49 (77.8%) high-risk HPV+. HPV16 was the most frequent (13%). Multiple HPV genotypes were found in 15 (24%) biopsies and laser capture microdissection -polymerase chain reaction confirmed specific HPV types in E4 +/− AIN. Although Ki-67 discriminated AIN and p16 HGAIN, E4+/p16+ staining shows that most AIN2 is different from transformed AIN3 in showing both entry into productive HPV infection and transforming activity.
The importance of DNA repair for maintaining oocyte quality in response to anti-cancer treatments, environmental toxins and maternal ageing

BACKGROUND Within the ovary, oocytes are stored in long-lived structures called primordial follicles, each comprising a meiotically arrested oocyte, surrounded by somatic granulosa cells. It is essential that their genetic integrity is maintained throughout life to ensure that high quality oocytes are available for ovulation. Of all the possible types of DNA damage, DNA double-strand breaks (DSBs) are considered to be the most severe. Recent studies have shown that DNA DSBs can accumulate in oocytes in primordial follicles during reproductive ageing, and are readily induced by exogenous factors such as γ-irradiation, chemotherapy and environmental toxicants. DSBs can induce oocyte death or, alternatively, activate a program of DNA repair in order to restore genetic integrity and promote survival. The repair of DSBs has been intensively studied in the context of meiotic recombination, and in recent years more detail is becoming available regarding the repair capabilities of primordial follicle oocytes. OBJECTIVE AND RATIONALE This review discusses the induction and repair of DNA DSBs in primordial follicle oocytes. SEARCH METHODS PubMed (Medline) and Google Scholar searches were performed using the key words: primordial follicle oocyte, DNA repair, double-strand break, DNA damage, chemotherapy, radiotherapy, ageing, environmental toxicant. The literature was restricted to papers in the English language and limited to reports in animals and humans dated from 1964 until 2017. The references within these articles were also manually searched. OUTCOMES Recent experiments in animal models and humans have provided compelling evidence that primordial follicle oocytes can efficiently repair DNA DSBs arising from diverse origins, but this capacity may decline with increasing age. WIDER IMPLICATIONS Primordial follicle oocytes are vulnerable to DNA DSBs emanating from endogenous and exogenous sources. The ability to repair this damage is essential for female fertility. In the long term, augmenting DNA repair in primordial follicle oocytes has implications for the development of novel fertility preservation agents for female cancer patients and for the management of maternal ageing. However, further work is required to fully characterize the specific proteins involved and to develop strategies to bolster their activity.
Monitoring Viable Cells of the Biological Control Agent Lactobacillus plantarum PM411 in Aerial Plant Surfaces by Means of a Strain-Specific Viability Quantitative PCR Method

ABSTRACT A viability quantitative PCR (v-qPCR) assay was developed for the unambiguous detection and quantification of Lactobacillus plantarum PM411 viable cells in aerial plant surfaces. A 972-bp region of a PM411 predicted prophage with mosaic architecture enabled the identification of a PM411 strain-specific molecular marker. Three primer sets with different amplicon lengths (92, 188, and 317 bp) and one TaqMan probe were designed. All the qPCR assays showed good linearity over a 4-log range and good efficiencies but differed in sensitivity. The nucleic acid-binding dye PEMAX was used to selectively detect and enumerate viable bacteria by v-qPCR. The primer set amplifying a 188-bp DNA fragment was selected as the most suitable for v-qPCR. The performance of the method was assessed on apple blossoms, pear, strawberry, and kiwifruit leaves in potted plants under controlled environmental conditions, as well as pear and apple blossoms under field conditions, by comparing v-qPCR population estimations to those obtained by qPCR and specific plate counting on de Man-Rogosa-Sharpe (MRS)-rifampin. The population estimation did not differ significantly between methods when conditions were conducive to bacterial survival. However, under stressful conditions, differences between methods were observed due to cell death or viable-but-nonculturable state induction. While qPCR overestimated the population level, plate counting underestimated this value in comparison to v-qPCR. PM411 attained stable population levels of viable cells on the flower environment under high relative humidity. However, the unfavorable conditions on the leaf surface and the relatively dryness in the field caused an important decrease in the viable population. IMPORTANCE The v-qPCR method in combination with plate counting and qPCR is a powerful tool for studies of colonization and survival under field conditions, to improve formulations and delivery strategies of PM411, and to optimize the dose and timing of spray schedules. It is expected that PEMAX v-qPCR could also be developed for monitoring other strains on plant surfaces not only as biological control agents but also beneficial bacteria useful in the sustainable management of crop production.
Perspectives of Family Members on Using Technology in Youth Mental Health Care: A Qualitative Study

Background Information and communication technologies (ICTs) are increasingly recognized as having an important role in the delivery of mental health services for youth. Recent studies have evaluated young people’s access and use of technology, as well as their perspectives on using technology to receive mental health information, services, and support; however, limited attention has been given to the perspectives of family members in this regard. Objective The aim of this study was to explore the perspectives of family members on the use of ICTs to deliver mental health services to youth within the context of specialized early intervention for a first-episode psychosis (FEP). Methods Six focus groups were conducted with family members recruited from an early intervention program for psychosis. Twelve family members participated in the study (target sample was 12-18, and recruitment efforts took place over the duration of 1 year). A 12-item semistructured focus group guide was developed to explore past experiences of technology and recommendations for the use of technology in youth mental health service delivery. A qualitative thematic analysis guided the identification and organization of common themes and patterns identified across the dataset. Results Findings were organized by the following themes: access and use of technology, potential negative impacts of technology on youth in recovery, potential benefits of using technology to deliver mental health services to youth, and recommendations to use technology for (1) providing quality information in a manner that is accessible to individuals of diverse socioeconomic backgrounds, (2) facilitating communication with health care professionals and services, and (3) increasing access to peer support. Conclusions To our knowledge, this is among the first (or the first) to explore the perspectives of family members of youth being treated for FEP on the use of technology for mental health care. Our results highlight the importance of considering diverse experiences and attitudes toward the role of technology in youth mental health, digital literacy skills, phases of recovery, and sociodemographic factors when engaging family members in technology-enabled youth mental health care research and practice. Innovative methods to recruit and elicit the perspectives of family members on this topic are warranted. It is also important to consider educational strategies to inform and empower family members on the role, benefits, and use of ICTs in relation to mental health care for FEP.
&bgr;-arrestin 2 mediates cardiac ischemia-reperfusion injury via inhibiting GPCR-independent cell survival signalling

Aims Ischemic heart disease is a leading cause of morbidity and mortality worldwide. Although timely restoration of coronary blood flow (reperfusion) is the most effective therapeutics of myocardial infarction, reperfusion causes further cardiac damage, i.e. ischemia-reperfusion (I/R) injury. β-arrestins (Arrbs) have been traditionally defined as negative regulators of G protein-coupled receptor (GPCR) signalling, but recent studies have shown that they are essential for G protein-independent, GPCR-mediated biased signalling. Several ligands have been reported to be cardioprotective via Arrbs dependent pathway. However, it is unclear whether Arrbs exert receptor-independent physiological or pathological functions in the heart. Here, we sought to determine whether and how Arrbs play a role in regulating cardiomyocyte viability and myocardial remodelling following I/R injury. Methods and results The expression of β-arrestin 2 (Arrb2), but not β-arrestin 1 (Arrb1), is upregulated in rat hearts subjected to I/R injury, or in cultured neonatal rat cardiomyocytes treated with hypoxia-reoxygenation (H/R) injury. Deficiency of Arrb2 in cultured neonatal rat cardiomyocytes alleviates H/R-induced cardiomyocyte death and Arrb2-/- mice are resistant to myocardial damage caused by I/R injury. In contrast, upregulation of Arrb2 triggers cardiomyocyte death and exaggerates I/R (or H/R)-induced detrimental effects. Mechanically, Arrb2 induces cardiomyocyte death by interacting with the p85 subunit of PI3K, and negatively regulating the formation of p85-PI3K/CaV3 survival complex, thus blocking activation of PI3K-Akt-GSK3β cell survival signalling pathway. Conclusion We define an upregulation of Arrb2 as a pathogenic factor in cardiac I/R injury, and also reveal a novel GPCR-independent mechanism of Arrb2-mediated cell death signalling in the heart.
The impact of body mass index and height on the risk for glioblastoma and other glioma subgroups: a large prospective cohort study

Background Glioma comprises a heterogeneous group of mostly malignant brain tumors, whereof glioblastoma (GBM) represents the largest and most lethal subgroup. Body height and body mass index (BMI) are risk factors for other cancers, but no previous study has examined anthropometric data in relation to different glioma subgroups. Methods This prospective cohort study includes 1.8 million Norwegian women and men between ages 14 and 80 years at baseline. Body weight and height were measured, and incident cases of glioma were identified by linkage to the National Cancer Registry. Cox regression analyses were performed to evaluate risk for different glioma subgroups in relation to anthropometric measures. Results During 54 million person-years of follow-up, 4,382 gliomas were identified. Overweight and obesity were not associated with risk for any glioma subgroup. Height was positively associated with risk for GBM and all other gliomas (hazard ratio [HR] per 10 cm increase: 1.24; 95% confidence interval [CI], 1.17-1.31 and 1.18; 95% CI, 1.09-1.29) but not with the proxy for isocitrate dehydrogenase (IDH)-mutant glioma (HR, 1.09; 95% CI, 0.98-1.21). In further subgroup analyses, the effect of height on glioma risk varied significantly with positive associations for oligoastrocytoma (HR, 1.74; 95% CI, 1.20-2.53) and malignant glioma not otherwise specified (NOS) (HR, 1.42; 95% CI, 1.16-1.76, but not with diffuse astrocytoma (WHO grades II and III) or oligodendroglioma. Conclusion This epidemiologic study consolidates height as a risk factor for GBM and other gliomas. It further indicates that this association is not universal for gliomas but may differ between different glioma subgroups.
Understanding the emotions behind social images: Inferring with user demographics

Understanding the essential emotions behind social images is of vital importance: it can benefit many applications such as image retrieval and personalized recommendation. While previous related research mostly focuses on the image visual features, in this paper, we aim to tackle this problem by “linking inferring with users' demographics”. Specifically, we propose a partially-labeled factor graph model named D-FGM, to predict the emotions embedded in social images not only by the image visual features, but also by the information of users' demographics. We investigate whether users' demographics like gender, marital status and occupation are related to emotions of social images, and then leverage the uncovered patterns into modeling as different factors. Experiments on a data set from the world's largest image sharing website Flickr1 confirm the accuracy of the proposed model. The effectiveness of the users' demographics factors is also verified by the factor contribution analysis, which reveals some interesting behavioral phenomena as well.
Reduced Genetic Diversity in the Clown Anemonefish Amphiprion ocellaris in Exploited Reefs of Spermonde Archipelago, Indonesia

Populations of the clown anemonefish in Spermonde Archipelago, one of the main collection sites for ornamental fish in Indonesia, are potentially overfished, which might lead to a reduction in population size and genetic diversity. Loss of genetic diversity can reduce the adaptability, population persistence and productivity of the targeted species. Therefore, a study investigating the genetic diversity and its potential correlation to population densities of A. ocellaris was conducted. Two islands were chosen as study sites that differed in the degree of exploitation. Barrang Lompo has a high fishing pressure, whereas Samalona has less. Underwater visual censuses showed that population densities in Samalona were threefold higher than in Barrang Lompo (p = 0.005). Analysis of eight microsatellite loci in 364 tissue samples of A. ocellaris revealed that genetic diversity (numbers of alleles, private alleles, and allelic richness) was significantly reduced at the island with high fishing pressure. Allelic richness was also positively correlated with fish density (p < 0.05). These results indicate that ornamental fishery might be a factor contributing to the loss of genetic diversity in A. ocellaris. Therefore, the marine ornamental trade in Spermonde Archipelago needs to be managed (e.g. management of the fishing strategy, implementation of marine protected areas, regular monitoring and quota determination). Otherwise the populations of A. ocellaris might collapse.
Leptin and Leptin-to-Adiponectin Ratio Predict Adiposity Gain in Nonobese Children over a Six-Year Period

Abstract Background: Previous longitudinal studies have shown inconsistent results regarding the influence of adipokines on changes in weight and body fat. We aimed to determine the predictive value of serum leptin, adiponectin, and their ratio on subsequent changes in obesity measures in children. Methods: Two hundred forty-six obese and 532 nonobese children aged 6–11 years were remeasured for BMI and waist circumference after 6.4 ± 0.2 years. Z-score of BMI was used to standardize for age and sex. Obesity was defined using the international BMI cutoffs. Waist-to-height ratio (WHtR) was calculated to define central obesity using a boundary value of 0.5. Fasting serum leptin and adiponectin levels were measured at baseline. Results: Newly identified obese children had significantly higher levels of leptin and leptin-to-adiponectin ratio than nonobese children. There were lower adiponectin levels in boys with persistent obesity versus those with transient obesity. After adjusting for age, Tanner stage, and corresponding adiposity measures at baseline, leptin levels and leptin-to-adiponectin ratio were positively associated with BMI Z-score gain in girls and WHtR gain in boys. An inverse association between leptin and BMI Z-score gain was detected in boys. Stratified analyses revealed significant associations only in the nonobese and prepubertal group. There were no significant associations between adiponectin and changes in obesity measures. Conclusions: High leptin levels and leptin-to-adiponectin ratio are sex-specific predictors of obesity measures gain in nonobese and prepubertal children. Body composition measurement is necessary to assess fat mass growth and distribution during childhood and adolescence.
A Measure of Team Resilience: Developing the Resilience at Work Team Scale

Objective: This study develops, and initial evaluates, a new measure of team-based resilience for use in research and practice. Methods: We conducted preliminary analyses, based on a cross-sectional sample of 344 employees nested within 31 teams. Results: Seven dimensions were identified through exploratory and confirmatory factor analyses. The measure had high reliability and significant discrimination to indicate the presence of a unique team-based aspect of resilience that contributed to higher work engagement and higher self-rated team performance, over and above the effects of individual resilience. Multilevel analyses showed that team, but not individual, resilience predicted self-rated team performance. Conclusion: Practice implications include a need to focus on collective as well as individual behaviors in resilience-building. The measure provides a diagnostic instrument for teams and a scale to evaluate organizational interventions and research the relationship of resilience to other constructs.
A mechanistic spatio-temporal framework for modelling individual-to-individual transmission—With an application to the 2014-2015 West Africa Ebola outbreak

In recent years there has been growing availability of individual-level spatio-temporal disease data, particularly due to the use of modern communicating devices with GPS tracking functionality. These detailed data have been proven useful for inferring disease transmission to a more refined level than previously. However, there remains a lack of statistically sound frameworks to model the underlying transmission dynamic in a mechanistic manner. Such a development is particularly crucial for enabling a general epidemic predictive framework at the individual level. In this paper we propose a new statistical framework for mechanistically modelling individual-to-individual disease transmission in a landscape with heterogeneous population density. Our methodology is first tested using simulated datasets, validating our inferential machinery. The methodology is subsequently applied to data that describes a regional Ebola outbreak in Western Africa (2014-2015). Our results show that the methods are able to obtain estimates of key epidemiological parameters that are broadly consistent with the literature, while revealing a significantly shorter distance of transmission. More importantly, in contrast to existing approaches, we are able to perform a more general model prediction that takes into account the susceptible population. Finally, our results show that, given reasonable scenarios, the framework can be an effective surrogate for susceptible-explicit individual models which are often computationally challenging.
Fire forbids fifty-fifty forest

Recent studies have interpreted patterns of remotely sensed tree cover as evidence that forest with intermediate tree cover might be unstable in the tropics, as it will tip into either a closed forest or a more open savanna state. Here we show that across all continents the frequency of wildfires rises sharply as tree cover falls below ~40%. Using a simple empirical model, we hypothesize that the steepness of this pattern causes intermediate tree cover (30‒60%) to be unstable for a broad range of assumptions on tree growth and fire-driven mortality. We show that across all continents, observed frequency distributions of tropical tree cover are consistent with this hypothesis. We argue that percolation of fire through an open landscape may explain the remarkably universal rise of fire frequency around a critical tree cover, but we show that simple percolation models cannot predict the actual threshold quantitatively. The fire-driven instability of intermediate states implies that tree cover will not change smoothly with climate or other stressors and shifts between closed forest and a state of low tree cover will likely tend to be relatively sharp and difficult to reverse.
Semi-Global Leader-Following Consensus of Linear Multi-Agent Systems With Input Saturation via Low Gain Feedback

This paper investigates the problem of leader-following consensus of a linear multi-agent system on a switching network. The input of each agent is subject to saturation. Low gain feedback based distributed consensus protocols are developed. It is established that, under the assumptions that each agent is asymptotically null controllable with bounded controls and that the network is connected or jointly connected, semi-global leader-following consensus of the multi-agent system can be achieved. Numerical examples are presented to illustrate this result.