Miracle-dz/UniFAR-FTUs huggingface dataset:
A high-throughput method for unbiased quantitation and categorization of nuclear morphology

Abstract The physical arrangement of chromatin in the nucleus is cell type and species-specific, a fact particularly evident in sperm, in which most of the cytoplasm has been lost. Analysis of the characteristic falciform (“hook shaped”) sperm in mice is important in studies of sperm development, hybrid sterility, infertility, and toxicology. However, quantification of sperm shape differences typically relies on subjective manual assessment, rendering comparisons within and between samples difficult. We have developed an analysis program for morphometric analysis of asymmetric nuclei and characterized the sperm of mice from a range of inbred, outbred, and wild-derived mouse strains. We find that laboratory strains have elevated sperm shape variability both within and between samples in comparison to wild-derived inbred strains, and that sperm shape in F1 offspring from a cross between CBA and C57Bl6J strains is subtly affected by the direction of the cross. We further show that hierarchical clustering can discriminate distinct sperm shapes with greater efficiency and reproducibility than even experienced manual assessors, and is useful both to distinguish between samples and also to identify different morphological classes within a single sample. Our approach allows for the analysis of nuclear shape with unprecedented precision and scale and will be widely applicable to different species and different areas of biology.
Elgot Algebras † ( Extended Abstract )

Iterative algebras, i. e. , algebras A in which flat recursive equations e have unique solutions e, are generalized to Elgot algebras, where a choice e −→ e of solutions of all such equations e is specified. This specification satisfies two simple and well motivated axioms: functoriality (stating that solutions are “uniform”) and compositionality (stating how to perform simultaneous recursion). These two axioms stem canonically from Elgot’s iterative theories: We prove that the category of Elgot algebras is the Eilenberg–Moore category of the free iterative monad.
Low-intensity exercise delays the shivering response to core cooling.

Hypothermia can occur during aquatic exercise despite production of significant amounts of heat by the active muscles. Because the characteristics of human thermoregulatory responses to cold during exercise have not been fully elucidated, we investigated the effect of low-intensity exercise on the shivering response to core cooling in cool water. Eight healthy young men (24 ± 3 yr) were cooled through cool water immersion while resting (rest trial) and during loadless pedaling on a water cycle ergometer (exercise trial). Before the cooling, body temperature was elevated by hot water immersion to clearly detect a core temperature at which shivering initiates. Throughout the cooling period, mean skin temperature remained around the water temperature (25°C) in both trials, whereas esophageal temperature (Tes) did not differ between the trials (P > 0.05). The Tes at which oxygen uptake (V̇o2) rapidly increased, an index of the core temperature threshold for shivering, was lower during exercise than rest (36.2 ± 0.4°C vs. 36.5 ± 0.4°C, P < 0.05). The sensitivity of the shivering response, as indicated by the slope of the Tes-V̇o2 relation, did not differ between the trials (-441.3 ±177.4 ml·min-1·°C-1 vs. -411.8 ± 268.1 ml·min-1·°C-1, P > 0.05). The thermal sensation response to core cooling, assessed from the slope and intercept of the regression line relating Tes and thermal sensation, did not differ between the trials (P > 0.05). These results suggest that the core temperature threshold for shivering is delayed during low-intensity exercise in cool water compared with rest although shivering sensitivity is unaffected.
Safety of laparoscopic appendicectomy during pregnancy: a systematic review and meta‐analysis

Acute appendicitis is the most common non‐obstetric surgical presentation during pregnancy. There were concerns that laparoscopic appendicectomy increases the risk of foetal loss compared to an open approach. Therefore, with recent advances in perioperative care, it is likely the risk has changed. Here, we performed an updated meta‐analysis assessing the safety of laparoscopic appendicectomy in pregnant women.
Home Oxygen Therapy for Children. An Official American Thoracic Society Clinical Practice Guideline

Background: Home oxygen therapy is often required in children with chronic respiratory conditions. This document provides an evidence‐based clinical practice guideline on the implementation, monitoring, and discontinuation of home oxygen therapy for the pediatric population. Methods: A multidisciplinary panel identified pertinent questions regarding home oxygen therapy in children, conducted systematic reviews of the relevant literature, and applied the Grading of Recommendations, Assessment, Development, and Evaluation approach to rate the quality of evidence and strength of clinical recommendations. Results: After considering the panel's confidence in the estimated effects, the balance of desirable (benefits) and undesirable (harms and burdens) consequences of treatment, patient values and preferences, cost, and feasibility, recommendations were developed for or against home oxygen therapy specific to pediatric lung and pulmonary vascular diseases. Conclusions: Although home oxygen therapy is commonly required in the care of children, there is a striking lack of empirical evidence regarding implementation, monitoring, and discontinuation of supplemental oxygen therapy. The panel formulated and provided the rationale for clinical recommendations for home oxygen therapy based on scant empirical evidence, expert opinion, and clinical experience to aid clinicians in the management of these complex pediatric patients and identified important areas for future research.
Status of Cardiovascular Health in US Adults: Prevalence Estimates From the National Health and Nutrition Examination Surveys (NHANES) 2003–2008

Background— The American Heart Association's 2020 Strategic Impact Goals define a new concept, cardiovascular (CV) health; however, current prevalence estimates of the status of CV health in US adults according to age, sex, and race/ethnicity have not been published. Methods and Results— We included 14 515 adults (≥20 years of age) from the 2003 to 2008 National Health and Nutrition Examination Surveys. Participants were stratified by young (20–39 years), middle (40–64 years), and older (≥65 years) ages. CV health behaviors (diet, physical activity, body mass index, smoking) and CV health factors (blood pressure, total cholesterol, fasting blood glucose, smoking) were defined as poor, intermediate, or ideal. Fewer than 1% of adults exhibited ideal CV health for all 7 metrics. For CV health behaviors, nonsmoking was most prevalent (range, 60.2%–90.4%), whereas ideal Healthy Diet Score was least prevalent (range, 0.2%–2.6%) across groups. Prevalences of ideal body mass index (range, 36.5%–45.3%) and ideal physical activity levels (range, 50.2%–58.8%) were higher in young adults compared with middle or older ages. Ideal total cholesterol (range, 23.7%–36.2%), blood pressure (range, 11.9%–16.3%), and fasting blood glucose (range, 31.2%–42.9%) were lower in older adults compared with young and middle-aged adults. Prevalence of poor CV health factors was lowest in young age but higher at middle and older ages. Prevalence estimates by age and sex were consistent across race/ethnic groups. Conclusions— These prevalence estimates of CV health represent a starting point from which effectiveness of efforts to promote CV health and prevent CV disease can be monitored and compared in US adult populations.
Morphologic Analysis of Maxillary Sinus Floor and its Correlation to Molar Roots using Cone Beam Computed Tomography.

OBJECTIVE To analyse the anterior extension of the maxillary sinus, distribution of the sinus septa and vertical relationship between the maxillary sinus and molar roots using cone beam computed tomography (CBCT). METHODS Imaging data of 970 consecutive patients who underwent CBCT scans were retrospectively collected. The anterior border, septa distribution of the maxillary sinus and relationship between the maxillary sinus and molar roots were analysed. The root-sinus relationship was divided into three types; the roots protruding into the sinus or touching the floor without a bony barrier was defined as Type I root-sinus relationship. RESULTS Overall, 15.5% of the maxillary sinuses extended beyond the incisor region and 68.9% extended beyond the canine region. A bony septum of ≥ 2 mm was detected in 16.9% (328/1940) of the maxillary sinuses from 26.0% (252/970) of the patients. Among the 355 septa in the 328 sinuses with septa, 108 (30.4%) were located at the first and second premolar region, 180 (50.7%) at the first and second molar region and 67 (18.9%) posterior to the second molar. Among the first molars, a Type I root-sinus relationship was detected in 61.0% of palatine roots, 55.4% of distobuccal (DB) roots, and 52.7% of mesiobuccal (MB) roots. Moreover, among three-rooted second molars, a Type I relationship was detected in 62.0%, 58.2% and 45.8% of MB, DB and palatine roots, respectively. CONCLUSION The maxillary sinus can extend beyond the incisor region; approximately 1/6 of sinuses have bony septa; and 1/2 of molar roots protrude into the maxillary sinus or touch the sinus floor without a bony barrier.
Phytoextraction potential of soils highly polluted with cadmium using the cadmium/zinc hyperaccumulator Sedum plumbizincicola

Abstract A three-crop repeated phytoextraction experiment was conducted using four soils (S1–S4) highly polluted with cadmium (Cd) and two enhanced phytoextraction pot experiments using the most polluted soil (S4) to investigate the feasibility of Cd removal from highly polluted soils using the Cd/zinc (Zn)-hyperaccumulator Sedum plumbizincicola. Shoot biomass showed no significant difference during the repeated phytoextraction experiment on the four test soils and shoot Cd content showed a decreasing trend with the three consecutive crops in soils S1, S2, and S3 but not in soil S4. The Cd removal rates in soils S1, S2, S3, and S4 were 84.5, 81.6, 45.3, and 32.4%, respectively. Rice straw application increased Cd extraction efficiency by 42.6% but the addition of ethylenediaminedisuccinic acid, biochar or nitrogen had no effect on Cd remediation. Shoot Cd content increased significantly (1.57 and 1.71 times, respectively) at low (S0-1) and high (S0-2) sulfur addition rates. Soil extractable-Cd in S0-1 after the experiment showed no significant difference from the control but was 2.43 times higher in S0-2 than in the control. These results indicate that S. plumbizincicola shows good prospects for the phytoextraction of Cd from highly polluted soils and that the process can be enhanced by adding straw and/or sulfur to the soil.
Normative data and validation of the Italian translation of the Working Memory Questionnaire (WMQ)

Abstract Reliable and valid measures are necessary to assess subjective working memory complaints that can be distinct from objective memory performance. The Working Memory Questionnaire (WMQ) is a self-administered scale proposed by Vallat-Azouvi. It assesses the three different working memory domains (memory storage, attention, and executive functions) in accordance with Baddeley’s working memory model. Our aim was to propose an Italian translation of the WMQ and provide normative data. We collected normative data from 697 healthy Italian participants aged between 18 and 88 years. Percentiles and cutoff scores, taking into consideration age, gender, and education, were provided for the WMQ total scores and the three separate domains. The performance on the WMQ was influenced by age and education. In particular, age and education affected self-perceived working memory efficacy. Our data demonstrate a significant correlation between the WMQ and paper-and-pencil tests assessing working memory, attention, and executive functions. This study provides normative data that have been adjusted for relevant demographics and percentile grids in an Italian population. The results are in line with a previous French study that also supported the use of the WMQ as a valid prescreening instrument for working memory deficits in clinical practice.
Factors Affecting California College Students’ Attitudes Toward Assisted Dying

This study focuses on college students’ experiences and beliefs, which affect attitudes toward assisted dying. Of 324 students, 35% wanted the option of assisted dying for a family member with a life-threatening illness. Results of multiple logistic regression indicate students who favored assisted dying were significantly influenced by having a family member die, experiencing hospitalization, thinking about end-of-life issues, and being comfortable with palliative care. Belief in an afterlife and being a caregiver were negatively associated with assisted dying. Students need to receive training in end-of-life care issues, as increasingly professionals will face such requests.
A Comprehensive Analysis of Steroid Hormones and Progression of Localized High-Risk Prostate Cancer

Background: In men with localized prostate cancer who are undergoing radical prostatectomy (RP), it is uncertain whether their systemic hormonal environment is associated with outcomes. The objective of the study was to examine the association between the circulating steroid metabolome with prognostic factors and progression. Methods: The prospective PROCURE cohort was recruited from 2007 to 2012, and comprises 1,766 patients with localized prostate cancer who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry, and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models. Results: The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 (P = 0.0017; q = 0.026) and 1.24 (P = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; P = 0.057) and DHEA-S levels (HR = 1.43; P = 0.054). Conclusions: In men with localized prostate cancer, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease. Impact: The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.
Automatic brain lesion segmentation on standard MRIs of the human head: a scoping review protocol

Introduction Automatic brain lesion segmentation from medical images has great potential to support clinical decision making. Although numerous methods have been proposed, significant challenges must be addressed before they will become established in clinical and research practice. We aim to elucidate the state of the art, to provide a synopsis of competing approaches and identify contrasts between them. Methods and analysis We present the background and study design of a scoping review for automatic brain lesion segmentation methods for conventional MRI according to the framework proposed by Arksey and O’Malley. We aim to identify common image processing steps as well as mathematical and computational theories implemented in these methods. We will aggregate the evidence on the efficacy and identify limitations of the approaches. Methods to be investigated work with standard MRI sequences from human patients examined for brain lesions, and are validated with quantitative measures against a trusted reference. PubMed, IEEE Xplore and Scopus will be searched using search phrases that will ensure an inclusive and unbiased overview. For matching records, titles and abstracts will be screened to ensure eligibility. Studies will be excluded if a full paper is not available or is not written in English, if non-standard MR sequences are used, if there is no quantitative validation, or if the method is not automatic. In the data charting phase, we will extract information about authors, publication details and study cohort. We expect to find information about preprocessing, segmentation and validation procedures. We will develop an analytical framework to collate, summarise and synthesise the data. Ethics and dissemination Ethical approval for this study is not required since the information will be extracted from published studies. We will submit the review report to a peer-reviewed scientific journal and explore other venues for presenting the work.
Guidelines for interdomain traffic engineering

Network operators must have control over the flow of traffic into, out of, and across their networks. However, the Border Gateway Protocol (BGP) does not facilitate common traffic engineering tasks, such as balancing load across multiple links to a neighboring AS or directing traffic to a different neighbor. Solving these problems is difficult because the number of possible changes to routing policies is too large to exhaustively test all possibilities, some changes in routing policy can have an unpredictable effect on the flow of traffic, and the BGP decision process implemented by router vendors limits an operator's control over path selection.We propose fundamental objectives for interdomain traffic engineering and specific guidelines for achieving these objectives within the context of BGP. Using routing and traffic data from the AT&T backbone we show how certain BGP policy changes can move traffic in a predictable fashion, despite limited knowledge about the routing policies in neighboring AS's. Then, we show how operators can gain greater flexibility by relaxing some steps in the BGP decision process and ensuring that neighboring AS's send consistent advertisements at each peering location. Finally, we show that an operator can manipulate traffic efficiently by changing the routes for a small number of prefixes (or groups of related prefixes) that consistently receive a large amount of traffic.
MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis

Abstract Current research indicates that beta cell loss in type 2 diabetes may be attributed to beta cell dedifferentiation rather than apoptosis; however, the mechanisms by which this occurs remain poorly understood. Our previous study demonstrated that elevation of microRNA-24 (miR-24) in a diabetic setting caused beta cell dysfunction and replicative deficiency. In this study, we focused on the role of miR-24 in beta cell apoptosis and dedifferentiation under endoplasmic reticulum (ER) stress conditions. We found that miR-24 overabundance protected beta cells from thapsigargin-induced apoptosis at the cost of accelerating the impairment of glucose-stimulated insulin secretion (GSIS) and enhancing the presence of dedifferentiation markers. Ingenuity® Pathway Analysis (IPA) revealed that elevation of miR-24 had an inhibitory effect on XBP1 and ATF4, which are downstream effectors of two key branches of ER stress, by inhibiting its direct target, Ire1α. Notably, elevated miR-24 initiated another pathway that targeted Mafa and decreased GSIS function in surviving beta cells, thus guiding their dedifferentiation under ER stress conditions. Our results demonstrated that the elevated miR-24, to the utmost extent, preserves beta cell mass by inhibiting apoptosis and inducing dedifferentiation. This study not only provides a novel mechanism by which miR-24 dominates beta cell turnover under persistent metabolic stress but also offers a therapeutic consideration for treating diabetes by inducing dedifferentiated beta cells to re-differentiation.
Influence of the familial Alzheimer's disease–associated T43I mutation on the transmembrane structure and γ-secretase processing of the C99 peptide

Extracellular deposition of β-amyloid (Aβ) peptides in the brain is a hallmark of Alzheimer's disease (AD). Upon β-secretase–mediated cleavage of the β C-terminal fragment (β-CTF) from the Aβ precursor protein, the γ-secretase complex produces the Aβ peptides associated with AD. The familial T43I mutation within the transmembrane domain of the β-CTF (also referred to as C99) increases the ratio between the Aβ42 and Aβ40 peptides largely due to a decrease in Aβ40 formation. Aβ42 is the principal component of amyloid deposits within the brain parenchyma, and an increase in the Aβ42/Aβ40 ratio is correlated with early-onset AD. Using NMR and FTIR spectroscopy, here we addressed how the T43I substitution influences the structure of C55, the minimal sequence containing the entire extracellular and transmembrane (TM) domains of C99 needed for γ-secretase processing. 13C NMR chemical shifts indicated that the T43I substitution increases helical structure within the TM domain of C55. These structural changes were associated with a shift of the C55 dimer to the monomer and an increase in the tilt of the TM helix relative to the membrane normal in the T43I mutant compared with that of WT C55. The A21G (Flemish) mutation was previously found to increase secreted Aβ40 levels; here, we combined this mutation in the extracellular domain of C99 with T43I and observed that the T43I/A21G double mutant decreases Aβ40 formation. We discuss how the observed structural changes in the T43I mutant may decrease Aβ40 formation and increase the Aβ42/Aβ40 ratio.
Operative Management of Recurrent and Metastatic Adrenocortical Carcinoma: A Systematic Review

Metastatic adrenocortical carcinoma (ACC) is associated with a poor 5-year survival rate and high rate of recurrence. Outcomes after resection for patients with limited disease remain poorly described. We conducted a PubMed search for articles published between 1950 and 2017 using the terms “ACC,” “recurrence,” and “surgery. ” Patients with metastatic ACC at any anatomic site who had undergone surgical resection were included. Thirteen studies met the criteria. Patients were grouped according to the recurrence site. Pulmonary metastasectomy was reported in 50 patients with moderate complications and without perioperative mortality. Disease recurrence rates range from 25 to 42 per cent, with median overall survival of 40 to 50 months. Hepatic metastasectomy was reported in 108 patients with a single perioperative mortality. Disease recurrence rates range from 65 to 100 per cent, with median disease-free survival (DFS) and OS of five to nine months and 22 to 76 months. Peritoneal cytoreduction and heated intraperitoneal chemotherapy have been reported for 10 patients with minimal morbidity and without perioperative mortality. The disease recurrence rate was 70 per cent, with DFS of 19 months. For selected patients with recurrent ACC in the lungs, liver, or peritoneum, metastasectomy is safe and can be associated with prolonged survival. However, subsequent disease recurrence is common, and patients should be counseled accordingly.