Miracle-dz/UniFAR-FTUs huggingface dataset:
Benign breast disease increases breast cancer risk independent of underlying familial risk profile: Findings from a Prospective Family Study Cohort

Benign breast disease (BBD) is an established breast cancer (BC) risk factor, but it is unclear whether the magnitude of the association applies to women at familial or genetic risk. This information is needed to improve BC risk assessment in clinical settings. Using the Prospective Family Study Cohort, we used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of BBD with BC risk. We also examined whether the association with BBD differed by underlying familial risk profile (FRP), calculated using absolute risk estimates from the Breast Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA) model. During 176,756 person‐years of follow‐up (median: 10.9 years, maximum: 23.7) of 17,154 women unaffected with BC at baseline, we observed 968 incident cases of BC. A total of 4,704 (27%) women reported a history of BBD diagnosis at baseline. A history of BBD was associated with a greater risk of BC: HR = 1.31 (95% CI: 1.14–1.50), and did not differ by underlying FRP, with HRs of 1.35 (95% CI: 1.11–1.65), 1.26 (95% CI: 1.00–1.60), and 1.40 (95% CI: 1.01–1.93), for categories of full‐lifetime BOADICEA score <20%, 20 to <35%, ≥35%, respectively. There was no difference in the association for women with BRCA1 mutations (HR: 1.64; 95% CI: 1.04–2.58), women with BRCA2 mutations (HR: 1.34; 95% CI: 0.78–2.3) or for women without a known BRCA1 or BRCA2 mutation (HR: 1.31; 95% CI: 1.13–1.53) (pinteraction = 0.95). Women with a history of BBD have an increased risk of BC that is independent of, and multiplies, their underlying familial and genetic risk.
Construction of saliency map and hybrid set of features for efficient segmentation and classification of skin lesion

Skin cancer is being a most deadly type of cancers which have grown extensively worldwide from the last decade. For an accurate detection and classification of melanoma, several measures should be considered which include, contrast stretching, irregularity measurement, selection of most optimal features, and so forth. A poor contrast of lesion affects the segmentation accuracy and also increases classification error. To overcome this problem, an efficient model for accurate border detection and classification is presented. The proposed model improves the segmentation accuracy in its preprocessing phase, utilizing contrast enhancement of lesion area compared to the background. The enhanced 2D blue channel is selected for the construction of saliency map, at the end of which threshold function produces the binary image. In addition, particle swarm optimization (PSO) based segmentation is also utilized for accurate border detection and refinement. Few selected features including shape, texture, local, and global are also extracted which are later selected based on genetic algorithm with an advantage of identifying the fittest chromosome. Finally, optimized features are later fed into the support vector machine (SVM) for classification. Comprehensive experiments have been carried out on three datasets named as PH2, ISBI2016, and ISIC (i.e., ISIC MSK‐1, ISIC MSK‐2, and ISIC UDA). The improved accuracy of 97.9, 99.1, 98.4, and 93.8%, respectively obtained for each dataset. The SVM outperforms on the selected dataset in terms of sensitivity, precision rate, accuracy, and FNR. Furthermore, the selection method outperforms and successfully removed the redundant features.
A longitudinal study of polysomnographic variables in patients with mild cognitive impairment converting to Alzheimer's disease

The main condition at increased risk of dementia is considered to be mild cognitive impairment. Mild cognitive impairment has been defined as a transitional state between normal aging and dementia, of which it may represent a prodrome. The aim of our study was to evaluate whether sleep variables (both conventional and microstructural ones) in subjects with mild cognitive impairment correlate with conversion to dementia. Nineteen subjects with amnestic mild cognitive impairment (mean age 68.5 ± 7.0 years) and 11 cognitively intact healthy elderly individuals (mean age 69.2 ± 12.6 years) underwent ambulatory polysomnography for the evaluation of nocturnal sleep architecture and cyclic alternating pattern parameters. Amnestic mild cognitive impairment subjects were clinically and cognitively re‐evaluated after 2 years, during routine follow‐up, and further classified as amnestic mild cognitive impairment converters (that is, patients developing Alzheimer's disease, N = 11) and amnestic mild cognitive impairment non‐converters. Compared with healthy elderly individuals, amnestic mild cognitive impairment showed disrupted sleep with decreased rapid eye movement sleep, cyclic alternating pattern rate and cyclic alternating pattern slow‐wave‐related phases (A1 index). Standard sleep architecture analysis did not show significant differences between the two subgroups of amnestic mild cognitive impairment, whereas cyclic alternating pattern analysis showed that cyclic alternating pattern rate, A1 index and A3 index are significantly reduced in converters compared with non‐converters. Our data confirm that in amnestic mild cognitive impairment subjects there is a sleep impairment, particularly when considering more refined sleep parameters and that sleep variables at baseline are different among converters versus non‐converters at the 2‐year follow‐up. Specific sleep alterations might represent potential further biomarkers for the diagnosis and prognosis of early‐phase cognitive impairment.
Toxicologic Pathology Forum*: Opinion on Integrating Innovative Digital Pathology Tools in the Regulatory Framework

Digital pathology is defined as the ability to examine digitized microscopic slides and to generate qualitative and quantitative data. The field of digital pathology is rapidly evolving and has the potential to revolutionize toxicologic pathology. Techniques such as automated 2-D image analysis, whole slide imaging, and telepathology are already considered “mature” technologies and have been used for decades in exploratory studies; however, many organizations are reluctant to use digital pathology in regulatory toxicology studies. Innovative technologies using digitized slides including high-content imaging modalities and artificial intelligence are still under development but are increasingly used in toxicologic pathology. While software validation requirements are already described, clear guidance for application of these rules to the digital pathology field are few and the acceptance of these technologies by regulatory authorities remains necessary for successful adoption of digital pathology into the mainstream of toxicologic pathology. This topic was discussed during a roundtable at the 2018 Annual Congress of the French Society of Toxicologic Pathology. This opinion article summarizes the discussion regarding the current questions and challenges on the integration of innovative digital pathology tools within a good laboratory practice framework and is meant to stimulate further discussion among the toxicologic pathology community. *This is an opinion article submitted to the Toxicologic Pathology Forum and does not constitute an official position of the Society of Toxicologic Pathology or the journal Toxicologic Pathology. The views expressed in this article are those of the authors and do not necessarily represent the policies, positions, or opinions of their respective agencies and organizations. The Toxicologic Forum is designed to stimulate broad discussion of topics relevant to regulatory issues in Toxicologic pathology. Readers of Toxicologic Pathology are encouraged to send their thoughts on these articles or ideas for new topics to toxicologicpathologyforum@toxpath.org.
Influence of work excitement and workplace violence on professional commitment and turnover intention among hospital nurses.

AIM AND OBJECTIVES This study aimed to determine the influence of work excitement, workplace violence and the violence prevention climate on professional commitment and turnover intention. BACKGROUND Workplace violence can easily cause the quality of nursing care to decline. Improvements in the working environment and working conditions can improve nurses' professional commitment and satisfaction. DESIGN A cross-sectional multicentre study with convenience sampling was conducted. We have complied with the guidelines of STROBE Checklist in presenting this research. METHODS Out of 900 questionnaires, 696 were deemed valid for analysis (77.33%). This study collected data on sociodemographic information, experiences of workplace violence, professional commitment, work excitement, violence prevention climate and turnover intention. RESULTS The results show that professional commitment has a significant effect on turnover intention. Professional commitment positively influences work excitement, especially when the work is challenging and varied. It also indirectly influences turnover intention by generating work excitement. Workplace violence introduces an interactive moderating effect on the relationship between professional commitment and work excitement. A violence prevention climate changes the interactive moderating effect of workplace violence on professional commitment, which in turn influences turnover intention. CONCLUSIONS Positive work experience, institutional organisational policies and support systems are the mediating and moderating factors in the relationship between professional commitment and turnover intention. Nurses expect organisations to maintain good staff relations, provide a positive working environment and learning opportunities and strengthen communication channels, all of which affect nurse retention. RELEVANCE TO CLINICAL PRACTICE Workplace violence is a serious crisis that can lead to turnover intention among hospital nurses. To enhance interpersonal relationships in the workplace and improve nurse retention, hospitals should schedule an adequate amount of staff and provide sufficient equipment and supplies to create a safe and positive work environment.
Cognitive Functioning in Patients with Pediatric-Onset Multiple Sclerosis, an Updated Review and Future Focus

Pediatric-onset multiple sclerosis (POMS) is relatively rare, but as technology and neuroimaging advance, an increasing number of cases are identified, and our understanding of how multiple sclerosis (MS) impacts the developing brain improves. There are consistent findings in the literature highlighting the impact of MS and other demyelinating diseases on cognitive functioning and cognitive development. We also have a better understanding of how POMS impacts psychosocial functioning and functional outcomes in daily living. This paper hopes to review findings associated with cognitive and psychosocial functioning in patients with POMS, as well as explore more recent advances in the field and how they relate to cognitive and psychosocial outcomes. We also discuss the ongoing need for future studies with a focus on better understanding deficits and disease correlates, but also preventative measures and potential rehabilitation.
LRP1 deficiency in microglia blocks neuro‐inflammation in the spinal dorsal horn and neuropathic pain processing

Following injury to the peripheral nervous system (PNS), microglia in the spinal dorsal horn (SDH) become activated and contribute to the development of local neuro‐inflammation, which may regulate neuropathic pain processing. The molecular mechanisms that control microglial activation and its effects on neuropathic pain remain incompletely understood. We deleted the gene encoding the plasma membrane receptor, LDL Receptor‐related Protein‐1 (LRP1), conditionally in microglia using two distinct promoter‐Cre recombinase systems in mice. LRP1 deletion in microglia blocked development of tactile allodynia, a neuropathic pain‐related behavior, after partial sciatic nerve ligation (PNL). LRP1 deletion also substantially attenuated microglial activation and pro‐inflammatory cytokine expression in the SDH following PNL. Because LRP1 shedding from microglial plasma membranes generates a highly pro‐inflammatory soluble product, we demonstrated that factors which activate spinal cord microglia, including lipopolysaccharide (LPS) and colony‐stimulating factor‐1, promote LRP1 shedding. Proteinases known to mediate LRP1 shedding, including ADAM10 and ADAM17, were expressed at increased levels in the SDH after PNL. Furthermore, LRP1‐deficient microglia in cell culture expressed significantly decreased levels of interleukin‐1β and interleukin‐6 when treated with LPS. We conclude that in the SDH, microglial LRP1 plays an important role in establishing and/or amplifying local neuro‐inflammation and neuropathic pain following PNS injury. The responsible mechanism most likely involves proteolytic release of LRP1 from the plasma membrane to generate a soluble product that functions similarly to pro‐inflammatory cytokines in mediating crosstalk between cells in the SDH and in regulating neuropathic pain.
Bee and floral traits affect the characteristics of the vibrations experienced by flowers during buzz pollination

ABSTRACT During buzz pollination, bees use their indirect flight muscles to produce vibrations that are transmitted to the flowers and result in pollen release. Although buzz pollination has been known for >100 years, we are still in the early stages of understanding how bee and floral characteristics affect the production and transmission of floral vibrations. Here, we analysed floral vibrations produced by four closely related bumblebee taxa (Bombus spp.) on two buzz-pollinated plants species (Solanum spp.). We measured floral vibrations transmitted to the flower to establish the extent to which the mechanical properties of floral vibrations depend on bee and plant characteristics. By comparing four bee taxa visiting the same plant species, we found that peak acceleration, root mean-squared acceleration (RMS) and frequency vary between bee taxa, but that neither bee size (intertegular distance) nor flower biomass (dry mass) affects peak acceleration, RMS or frequency. A comparison of floral vibrations of two bee taxa visiting flowers of two plant species showed that, while bee species affects peak acceleration, RMS and frequency, plant species only affects acceleration (peak acceleration and RMS), not frequency. When accounting for differences in the transmission of vibrations across the two types of flower, using a species-specific ‘coupling factor’, we found that RMS acceleration and peak displacement do not differ between plant species. This suggests that bees produce the same initial acceleration in different plants but that transmission of these vibrations through the flower is affected by floral characteristics. Highlighted Article: Buzz-pollinating bumblebees differ in the type of vibrations produced while visiting the same flower, and floral species affects the transmission properties of those vibrations.
Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population

Background Influenza vaccines are important for prevention of influenza-associated hospitalization. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness evaluations in hospitalized populations. Methods Serum specimens collected at admission from adults hospitalized for treatment of acute respiratory illnesses during two influenza seasons were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated the suitability of these specimens as proxies for pre-infection immune status, and measured associations between antibody titers and influenza vaccination and infection Results Specimens were collected within 3 days of illness onset from 65% of participants; geometric mean titers (GMTs) did not vary by day of collection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated participants. HAI titers against the 2014-2015 A(H3N2) vaccine strain did not correlate with protection from infection with antigenically-drifted A(H3N2) viruses that circulated that season. In contrast, higher HAI titers against the A(H1N1)pdm09 vaccine strain were associated with reduced odds of A(H1N1)pdm09 infection in 2015-2016. Conclusions Serum collected after hospital admission can be used to assess correlates of protection against influenza infection. Broader implementation of similar studies would provide an opportunity to understand the successes and shortcomings of current influenza vaccines.
Efficacy and acceptability of psychosocial interventions in asylum seekers and refugees: systematic review and meta-analysis

Abstract Aims In the past few years, there has been an unprecedented increase in the number of forcibly displaced migrants worldwide, of which a substantial proportion is refugees and asylum seekers. Refugees and asylum seekers may experience high levels of psychological distress, and show high rates of mental health conditions. It is therefore timely and particularly relevant to assess whether current evidence supports the provision of psychosocial interventions for this population. We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) assessing the efficacy and acceptability of psychosocial interventions compared with control conditions (treatment as usual/no treatment, waiting list, psychological placebo) aimed at reducing mental health problems in distressed refugees and asylum seekers. Methods We used Cochrane procedures for conducting a systematic review and meta-analysis of RCTs. We searched for published and unpublished RCTs assessing the efficacy and acceptability of psychosocial interventions in adults and children asylum seekers and refugees with psychological distress. Post-traumatic stress disorder (PTSD), depressive and anxiety symptoms at post-intervention were the primary outcomes. Secondary outcomes include: PTSD, depressive and anxiety symptoms at follow-up, functioning, quality of life and dropouts due to any reason. Results We included 26 studies with 1959 participants. Meta-analysis of RCTs revealed that psychosocial interventions have a clinically significant beneficial effect on PTSD (standardised mean difference [SMD] = −0.71; 95% confidence interval [CI] −1.01 to −0.41; I2 = 83%; 95% CI 78–88; 20 studies, 1370 participants; moderate quality evidence), depression (SMD = −1.02; 95% CI −1.52 to −0.51; I2 = 89%; 95% CI 82–93; 12 studies, 844 participants; moderate quality evidence) and anxiety outcomes (SMD = −1.05; 95% CI −1.55 to −0.56; I2 = 87%; 95% CI 79–92; 11 studies, 815 participants; moderate quality evidence). This beneficial effect was maintained at 1 month or longer follow-up, which is extremely important for populations exposed to ongoing post-migration stressors. For the other secondary outcomes, we identified a non-significant trend in favour of psychosocial interventions. Most evidence supported interventions based on cognitive behavioural therapies with a trauma-focused component. Limitations of this review include the limited number of studies collected, with a relatively low total number of participants, and the limited available data for positive outcomes like functioning and quality of life. Conclusions Considering the epidemiological relevance of psychological distress and mental health conditions in refugees and asylum seekers, and in view of the existing data on the effectiveness of psychosocial interventions, these interventions should be routinely made available as part of the health care of distressed refugees and asylum seekers. Evidence-based guidelines and implementation packages should be developed accordingly.
Analgesic Potentials of Preoperative Oral Pregabalin, Intravenous Magnesium Sulphate and their Combination in Acute Post-thoracotomy Pain.

OBJECTIVES To investigate the effects of the preoperative combination of oral pregabalin and intravenous magnesium sulphate as analgesic adjuvants in post thoracotomy pain. METHODS One hundred and twenty patients with ASA physical status II were allocated randomly into one of four groups. Group MP received 300▒mg pregabalin orally and an intravenous (IV) infusion of magnesium sulphate 50▒mg/kg mixed with 200▒mL normal saline (NS); Group P received 300▒mg pregabalin orally and 200▒mL NS infusion; Group M received an IV infusion of magnesium sulphate 50▒mg/kg mixed with 200▒mL NS and a placebo capsule; and Group C received placebo capsule and an IV infusion of 200▒mL NS. All medications were given 1 hour before surgery in all groups. In the first 24 hours postoperatively, total morphine consumption, the visual analogue scale (0-10 VAS) - used as a pain measurement tool - and postoperative nausea and vomiting (PONV) were assessed . RESULTS The total morphine consumption in the 1st 24 hours postoperatively decreased significantly in group MP (28.47±5.76▒mg) compared with group P (33.97±6.34▒mg), group M (40.87±4.4▒mg) and group C (42.2±6.1▒mg), respectively. VAS scores were in the accepted range (≤4) in the four groups throughout the first 24 hours, as all patients were on patient controlled analgesia (PCA). However, there was a statistically significant difference at 0 and 4 hours postoperatively in favor of groups MP and P. PONV decreased significantly in groups MP, P and M in comparison to group C (P <0.001). CONCLUSION The combined preoperative single dose of Pregabalin and magnesium sulphate is an effective method for attenuating postoperative pain and total morphine consumption in patients undergoing thoracotomy.
A gene regulatory architecture that controls region‐independent dynamics of oligodendrocyte differentiation

Oligodendrocytes (OLs) facilitate information processing in the vertebrate central nervous system via axonal ensheathment. The structure and dynamics of the regulatory network that mediates oligodendrogenesis are poorly understood. We employed bioinformatics and meta‐analysis of high‐throughput datasets to reconstruct a regulatory network underpinning OL differentiation. From this network, we identified families of feedforward loops comprising the transcription factors (TFs) Olig2, Sox10, and Tcf7l2 and their targets. Among the targets, we found eight other TFs related to OL differentiation, suggesting a hierarchical architecture in which some TFs (Olig2, Sox10, and Tcf7l2) regulate via feedforward loops the expression of others (Sox2, Sox6, Sox11, Nkx2‐2, Nkx6‐2, Hes5, Myt1, and Myrf). Model simulations with a kinetic model reproduced the mechanisms of OL differentiation only when in the model, Sox10‐mediated repression of Tcf7l2 by miR‐338/miR‐155 was introduced, a prediction confirmed in genetic functional experiments. Additional model simulations suggested that OLs from dorsal regions emerge through BMP/Sox9 signaling.