Miracle-dz/UniFAR-FTUs huggingface dataset:
Seeking snow and breathing hard – Behavioral tactics in high elevation mammals to combat warming temperatures

The world glaciers and areas of persistent summer snowpack are being lost due to warming temperatures. For cold-adapted species, habitat features may offer opportunities for cooling during summer heat yet the loss of snow and ice may compromise derived thermoregulatory benefits. Herein we offer insights about habitat selection for snow and the extent to which other behavioral adjustments reduce thermal debt among high elevation mammals. Specifically, we concentrate on respiration in mountain goats (Oreamnos americanus), a species whose native distribution is currently tied to northern mountain ranges of North America, where large patches of persistent summer snow are declining, and which became extinct during geologically warmer epochs. To examine sensitivity to possible thermal stressors and use of summer snow cover, we tracked marked and unmarked mountain goats in Glacier National Park, Montana, USA, to test hypotheses about selection for cold microclimates including shade and snow during periods of relatively high temperature. To understand functional responses of habitat choices, we measured microhabitat temperatures and a component of goat physiology–breaths per minute–as an index for metabolic expenditure. Individuals 1) selected areas closer to snow on warmer summer days, and 2) on snow had a 15% mean reduction in respiration when accounting for other factors, which suggests remnant snow plays an important role in mediating effects of air temperature. The use of shade was not as an important variable in models explaining respiration. Despite the loss of 85% of glaciers in in Glacier National Park, summer’s remnant snow patches are an important reservoir by which animals reduce heat stress and potential hyperthermia. Our findings, when contextualized with behavioral strategies deployed by other high elevation mammalian taxa help frame how ambient temperatures may be modulated, and they offer a direct way by which to assess susceptibility to increasing heat in cold-adapted species.
Essential Contributions of Pathologists and Laboratory Physicians Leading to the Discovery of Insulin.

CONTEXT. — Frederick Banting, Charles Best, J. Bertrand Collip, and J. J. R. Macleod contributed to the discovery of insulin in 1921-1922. Recent advances in anatomic pathology, experimental pathology, and clinical pathology were necessary for the research in Toronto, Ontario, Canada, to begin and to succeed. OBJECTIVE. — To explore the role of pathology and laboratory medicine in laying the foundation for the discovery of insulin. DESIGN. — Available primary and secondary historical sources were reviewed. RESULTS. — During a 3-decade period, pathologists, through autopsy pathology and experimental animal studies, were able to provide solid evidence that the pancreatic islets were the source of the internal secretion responsible for proper carbohydrate metabolism. Banting, a surgeon with no previous research experience, read about these studies in a case report with an extensive literature review by pathologist Moses Barron; this piqued Banting's interest and caused him to approach Macleod, a Toronto physiology professor, with an idea that initiated the research. Advances in clinical laboratory medicine, which allowed them to measure blood glucose levels using small blood volumes, were critical to their success. CONCLUSIONS. — By 1921-1922, the pieces necessary to solve the puzzle were available. The primary reason that the time was ripe for the discovery was because of the contributions of pathologists and laboratory physicians in the preceding 3 decades. As the 100th anniversary approaches, our profession can take pride in its important contributions to the discovery of insulin, which is broadly recognized as one of the most important medical research advances of the 20th century.
Early detection of transcatheter heart valve dysfunction

ABSTRACT Introduction: Transcatheter aortic valve implantation therapy is spreading rapidly, representing the standard of care in inoperable and high-risk patients, and a valid alternative in intermediate- and low-risk patients with severe symptomatic aortic stenosis. In this subset, the development and validation of noninvasive, quantitative, in vivo imaging modality, to monitor possible valve dysfunction is mandatory, in order to plan timely therapeutic interventions before the onset of symptoms. Areas covered: The implantation of transcatheter heart valves (THV) is increasing rapidly. As a consequence, THV dysfunction will become a major cause of cardiovascular morbidity after TAVI. Emergency repeat aortic valve replacement surgery is associated with a high rate of mortality compared with elective repeat surgery. In this context, early detection of THV dysfunction is therefore highly desirable. The review aims to examine the different diagnostic method to early detect THV dysfunction. Expert opinion: Most promising innovations in the diagnosis of early detection of THV dysfunction are evaluated, and the future outlook is explored. Waiting for upcoming evidence about the utility of CT, CMR, and PET on early detection of THV dysfunction, tailoring echocardiogram follow-up based on patients’ characteristics is the desirable approach.
Colostral and mature breast milk protein compositional determinants in Qingdao, Wuhan and Hohhot: maternal food culture, vaginal delivery and neonatal gender.

BACKGROUND AND OBJECTIVES Breast milk proteins are essential to infants as they provide nutrition and protection. This study evaluated multiple factors that might influence breast milk proteins to identify the determinants that lead to inter-individual and longitudinal differences. METHODS AND STUDY DESIGN Five major breast milk proteins (β-casein, α-lactalbumin, lactoferrin, serum albumin and κ-casein) from breast milk samples collected from 55 mothers in three cities (Hohhot, Wuhan and Qingdao) in China were analyzed using a validated ultraperformance liquid chromatography-mass spectrometry method. Various factors were statistically evaluated for their associations with breast milk proteins: mother's age, parity, delivery mode, infant gender and infant birthweight. RESULTS Although decreased in concentrations, the proportions of β-casein and α-lactalbumin increased from colostrum (33.8% and 26.8%) to mature milk (40.3% and 31.6%), respectively. Mothers of older age were found to produce a lower concentration of total protein. Compared with vaginal delivery, caesarean section was associated with lower concentrations of κ-casein, lactoferrin and β-casein in mature milk. Infant gender influenced breast milk proteins in colostrum: mothers who delivered a girl tended to produce more κ-casein, lactoferrin and total protein. Furthermore, regional differences were found, and mothers from Hohhot produced significantly higher concentrations of α-lactalbumin and lactoferrin than those from Qingdao and Wuhan. This regional difference might be linked to the different dietary patterns of these mothers among cities. CONCLUSIONS Our study deepens the understanding of breast milk protein dynamics in Chinese population and provides evidence on potential determinants, which can serve as guidance for infant nutrition optimization.
Processing grapefruit juice with γ‐cyclodextrin attenuates its inhibitory effect on cytochrome P450 3A activity

Grapefruit (Citrus paradisi) juice enhances the oral bioavailability of drugs that are metabolized by intestinal cytochrome P450 3A4 (CYP3A4). Patients are advised to avoid drinking grapefruit juice to prevent this drug–grapefruit juice interaction. The aim of this study was to investigate whether processing grapefruit juice with cyclodextrins (CDs) would result in preventing or inhibiting this interaction.
Role of metabolomics-derived biomarkers to identify renal cell carcinoma: a comprehensive perspective of the past ten years and advancements

ABSTRACT Introduction: Renal cell carcinoma (RCC) is one of the most prevalent metabolic diseases and a leading cause of utmost mortality among men globally. In spite of extensive development in technology for biomarker discovery during the last 10 years, the currently used clinical biomarkers are still unable to detect RCC at early and progression stages. Hence, the development of new and precise biomarkers is most important to improve the clinical management of RCC and reduce the level of mortality. Area covered: For the detection of RCC at an early stage; a new branch of omics technology – metabolomics – has been introduced. Mainly two techniques (mass spectrometry and nuclear magnetic resonance spectroscopy) have been exploited to execute metabolomics. Precisely, metabolomics showed promising and powerful approach to identify novel RCC biomarker. The present review discussed and the literature search to narrate the outcomes of the past 10 years of studies related to RCC pathophysiology, metabolomics, advancements, and shortcomings. Expert opinion: Although, compared to mass spectrometric tactic, nuclear magnetic resonance is moving fast to achieve the aim and in vivo application for diagnosis and management of RCC, metabolomics-based research in RCC is still in its infancy stage.
Higher intakes of dietary vitamin D, calcium and dairy products are inversely associated with the risk of colorectal cancer: a case–control study in China

Abstract The effects of dietary vitamin D, Ca and dairy products intakes on colorectal cancer risk remain controversial. The present study investigated the association between these dietary intakes and the risk of colorectal cancer in Guangdong, China. From July 2010 to December 2018, 2380 patients with colorectal cancer and 2389 sex- and age-matched controls were recruited. Dietary intake data were collected through face-to-face interviews using a validated FFQ. Unconditional multivariable logistic regression models were used to calculate the OR and 95 % CI after adjusting for various confounders. Higher dietary vitamin D and Ca intakes were associated with 43 and 52 % reductions in colorectal cancer risk, with OR of 0·57 (95 % CI 0·46, 0·70) and 0·48 (95 % CI 0·39, 0·61), respectively, for the highest quartile (v. the lowest quartile) intakes. A statistically significant inverse association was observed between total dairy product intake and colorectal cancer risk, with an adjusted OR of 0·32 (95 % CI 0·27, 0·39) for the highest v. the lowest tertile. Subjects who drank milk had a 48 % lower risk of colorectal cancer than those who did not (OR 0·52, 95 % CI 0·45, 0·59). The inverse associations of dietary vitamin D, Ca, total dairy products and milk intakes with the risk of colorectal cancer were independent of sex and cancer site. Our study supports the protective effects of high dietary vitamin D, Ca and dairy products intakes against colorectal cancer in a Chinese population.
Ablation of persistent atrial fibrillation: Challenges and solutions

Catheter ablation is commonly used for treatment of persistent atrial fibrillation (AF). Pulmonary vein isolation (PVI) is still the cornerstone for the procedure, however, outcomes are consistently lower compared to paroxysmal AF. It is hypothesized that it could be due to lack of durable lesions or the presence of non‐PV targets that remain after PVI. Numerous advances in ablation catheter technologies and mapping systems may potentially achieve lower recurrence rates in the future. Ongoing research is required to discover the best technique for persistent AF ablation. The purpose of this review is to describe the new, developing technologies that may improve the outcome of this procedure in the persistent AF population.
The lived experiences of healthcare during pregnancy, birth, and three months after in women with type 1 diabetes mellitus

ABSTRACT Being pregnant, giving birth, and becoming a mother the first months after birth, is for women with type 1 diabetes mellitus (T1DM) a period of difficult challenges. In order to identify their need of support from healthcare, the aim of this study was to describe healthcare during pregnancy, labour, birth, and up to 12 weeks after birth as experienced by Swedish women with T1DM. We used a phenomenological reflective lifeworld research approach, and made 1-2 individual interviews with ten women in late pregnancy and/or 2-3 months after. Transcribed interviews were analysed through focusing on the meanings of the study phenomenon. The results revealed how the diabetes disease, as well as the risks and responsibility that comes with it, become more visible during the period in question, due to a constant monitoring, performed by the woman herself as well as by the healthcare professionals. The essential meaning of the phenomenon is a need to share the burden of risks and responsibilities with healthcare professionals. The complex situation that these women are in, both as experts on their illness and care and in need of care, requires a care that make women feel capable and responsible, but at the same time offers support and relieve them of their responsibility when needed.
Patient safety in primary health care and polypharmacy: cross-sectional survey among patients with chronic diseases*

Objective: to characterize and determine the polypharmacy prevalence in patients with chronic diseases and to identify the factors associated, in order to improvement of pharmaceutical care focused on patient safety. Methods: cross-sectional study included 558 patients, covered by primary health care, using a household and structured questionnaire. We analyzed the data on polypharmacy and its clinical and socioeconomic factors. Poisson regression analysis with robust variance was applied, with results expressed in prevalence ratio. Results: the results showed that polypharmacy (consumption of four or more drugs) was of 37.6%. The prevalence ratio analyses identified independent variables associated with polypharmacy: age (3.05), economic strata (0.33), way of medication acquisition through a combination of out-of-pocket and Brazilian public health system (1.44), diabetes and hypertension (2.11), comorbidities (coronary artery disease 2.26) and hospital admission (1.73). In the analyses, inappropriate medication use of the 278 patients (≥ 65 years) was associated with polypharmacy (prevalence ratio 4.04). Conclusion: polypharmacy study becomes an opportunity to guide the strategies for the patient safety to promote the medication without harm in chronic diseases.
Identification of Low-Abundance Lipid Droplet Proteins in Seeds and Seedlings1[OPEN]

Several previously unknown low-abundant lipid droplet proteins are identified in Arabidopsis thaliana seeds and seedlings by quantitative proteomics combined with two cell biological approaches. The developmental program of seed formation, germination, and early seedling growth requires not only tight regulation of cell division and metabolism, but also concerted control of the structure and function of organelles, which relies on specific changes in their protein composition. Of particular interest is the switch from heterotrophic to photoautotrophic seedling growth, for which cytoplasmic lipid droplets (LDs) play a critical role as depots for energy-rich storage lipids. Here, we present the results of a bottom-up proteomics study analyzing the total protein fractions and LD-enriched fractions in eight different developmental phases during silique (seed) development, seed germination, and seedling establishment in Arabidopsis (Arabidopsis thaliana). The quantitative analysis of the LD proteome using LD-enrichment factors led to the identification of six previously unidentified and comparably low-abundance LD proteins, each of which was confirmed by intracellular localization studies with fluorescent protein fusions. In addition to these advances in LD protein discovery and the potential insights provided to as yet unexplored aspects in plant LD functions, our data set allowed for a comparative analysis of the LD protein composition throughout the various developmental phases examined. Among the most notable of the alterations in the LD proteome were those during seedling establishment, indicating a switch in the physiological function(s) of LDs after greening of the cotyledons. This work highlights LDs as dynamic organelles with functions beyond lipid storage.
Simulated pollinator declines intensify selection on floral traits that facilitate selfing and outcrossing in Impatiens capensis.

PREMISE Anthropogenic environmental change is causing pollinator populations to decline. These declines should intensify selection for floral traits that facilitate outcrossing by making plants more attractive to pollinators and/or for floral traits that facilitate selfing in the absence of pollinators. However, the effect of pollinator declines on selection on floral traits could be modified by other environmental factors such as herbivores. METHODS We studied the effect of simulated pollinator declines on selection on floral traits of Impatiens capensis, a mixed-mating species that produces both obligately selfing cleistogamous flowers and primarily outcrossing chasmogamous flowers. We measured directional selection differentials via seeds per plant on two traits that facilitate outcrossing (chasmogamous flower size and number) and one trait that facilitates selfing (cleistogamous flower number) in ambient, reduced pollinator access, and reduced pollinator access combined with increased foliar herbivory treatments. RESULTS Reduced pollinator access intensified selection for larger chasmogamous flowers and more cleistogamous flowers. In contrast, increased herbivory did not affect selection on any floral trait. CONCLUSIONS Reduced pollinator access intensified selection for a trait that facilitates outcrossing, suggesting that even species such as I. capensis that can autonomously self-pollinate have the potential to respond to pollinator declines by evolving floral traits that reinforce interactions between plants and pollinators. However, reduced pollinator access also intensified selection for a trait that facilitates selfing, suggesting that I. capensis could adapt to pollinator declines by evolving floral traits that maintain the production of both selfed and outcrossed seeds.
Effectiveness of a Web-Based Tobacco Product use Prevention Videogame Intervention on Young Adolescents’ Beliefs and Knowledge

Background Preventing tobacco product initiation in youth is a critical need. While cigarette smoking among youth has been on the decline, tobacco use in other forms, such as e-cigarettes and vaping, continue to be a major concern. The purpose of this study was to conduct a real-world, quasi-experimental test of the effectiveness of a web-based videogame, smokeSCREEN, aimed at developing healthy beliefs and knowledge associated with tobacco product use prevention, including electronic cigarettes. Methods Adolescents (N = 560) aged 10–16 years were enrolled from schools and afterschool programs in a single-group pre–post study. Measures included a pre- and post-survey of beliefs and knowledge about tobacco product use. At post-survey, participants were asked questions regarding their gameplay experience. Paired responses for the tobacco product use in the beliefs and knowledge survey before and after the smokeSCREEN videogame intervention were compared using McNemar's test. Descriptive statistics were generated to assess overall participant gameplay experience. Results McNemar's test showed significant differences in the proportions of correct answers before (pre-survey) and after (post-survey) the intervention in seven out of eight belief questions (p < . 0001). It also suggested significant differences in the proportions of correct answers before (pre-survey) and after (post-survey) the intervention in all six knowledge questions (p < . 0001). Several gender and age differences were noted for belief and knowledge questions related to e-cigarettes and vaping. There was no association between gameplay duration at post-survey or to the answers of the beliefs or knowledge questions. Overall, participants reported that they enjoyed playing the game. Conclusions Findings suggest that the videogame intervention, smokeSCREEN, has a promising effect on participants’ beliefs and knowledge about tobacco product use, including electronic cigarettes and vaping, and is well accepted by adolescents.
Individual structural features constrain the mouse functional connectome

Significance The structural connectome is a key determinant of brain function and dysfunction. The connectome-based model approach aims to understand the functional organization of the brain by modeling the brain as a dynamical system, then studying how the functional architecture rises from the underlying structural skeleton. Here, taking advantage of mice studies, we systematically investigated the informative content of different structural features in explaining the emergence of the functional ones. We demonstrate that individual variations define a specific structural fingerprint with a direct impact upon the functional organization of individual brains stressing the importance of using individualized models to understand brain function. We show how limitations of connectome reconstruction with the diffusion-MRI method restrict our comprehension of the structural–functional relation. Whole brain dynamics intuitively depend upon the internal wiring of the brain; but to which extent the individual structural connectome constrains the corresponding functional connectome is unknown, even though its importance is uncontested. After acquiring structural data from individual mice, we virtualized their brain networks and simulated in silico functional MRI data. Theoretical results were validated against empirical awake functional MRI data obtained from the same mice. We demonstrate that individual structural connectomes predict the functional organization of individual brains. Using a virtual mouse brain derived from the Allen Mouse Brain Connectivity Atlas, we further show that the dominant predictors of individual structure–function relations are the asymmetry and the weights of the structural links. Model predictions were validated experimentally using tracer injections, identifying which missing connections (not measurable with diffusion MRI) are important for whole brain dynamics in the mouse. Individual variations thus define a specific structural fingerprint with direct impact upon the functional organization of individual brains, a key feature for personalized medicine.
Computational prediction of implantation outcome after embryo transfer

The aim of this study is to develop a computational prediction model for implantation outcome after an embryo transfer cycle. In this study, information of 500 patients and 1360 transferred embryos, including cleavage and blastocyst stages and fresh or frozen embryos, from April 2016 to February 2018, were collected. The dataset containing 82 attributes and a target label (indicating positive and negative implantation outcomes) was constructed. Six dominant machine learning approaches were examined based on their performance to predict embryo transfer outcomes. Also, feature selection procedures were used to identify effective predictive factors and recruited to determine the optimum number of features based on classifiers performance. The results revealed that random forest was the best classifier (accuracy = 90.40% and area under the curve = 93.74%) with optimum features based on a 10-fold cross-validation test. According to the Support Vector Machine-Feature Selection algorithm, the ideal numbers of features are 78. Follicle stimulating hormone/human menopausal gonadotropin dosage for ovarian stimulation was the most important predictive factor across all examined embryo transfer features. The proposed machine learning-based prediction model could predict embryo transfer outcome and implantation of embryos with high accuracy, before the start of an embryo transfer cycle.