Miracle-dz/UniFAR-FTUs huggingface dataset:
Multi-center investigation of the clinical and pathological characteristics of inflammatory breast cancer based on Chinese Society of Breast Surgery (CSBrs-007)

Abstract Background Inflammatory breast cancer (IBC) is an aggressive type of cancer with poor prognosis and outcomes. This study aimed to investigate clinicopathological features, molecular characteristics, and treatments among Chinese patients diagnosed with IBC. Methods We collected data of 95 patients with IBC who were treated by members of the Chinese Society of Breast Surgery, from January 2017 to December 2018. The data, including demographic characteristics, pathological findings, surgical methods, systemic treatment plans, and follow-up, were obtained using a uniform electronic questionnaire. The clinicopathological features of different molecular types in patients without distant metastases were compared using the Kruskal-Wallis (H) test followed by post hoc analyses. Results Lymph node metastasis was noted in 75.8% of all patients, while distant metastasis was noted in 21.4%. Pathological findings indicated invasive ductal and lobular carcinomas in 86.8% and 5.3% of cases, respectively. Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2−) (41.5%) and HR−/HER2+ (20.1%) were the most common biologic subtypes, followed by HR+/HER2+ (19.1%) and HR−/HER2− (19.1%). Stage III IBC was treated via pre-operative neoadjuvant chemotherapy in 87.7% of the cases, predominantly using anthracycline and taxanes. A total of 91.9% of patients underwent surgical treatment. Among them, 77.0% of the patients underwent modified radical mastectomy, 8.1% of whom also underwent immediate breast reconstruction. The Kruskal-Wallis test revealed that the efficacy of chemotherapy significantly differed among those with HR+/HER2− and HR−/HER2− tumors (adjusted P = 0.008), and Ki-67 expression significantly differed in HR−/HER2+ and HR+/HER2+ molecular subtypes (adjusted P = 0.008). Conclusion Our study provides novel insight into clinicopathological characteristics and treatment status among patients with IBC in China, and might provide a direction and basis for further studies. Trial registration chictr.org.cn, No. ChiCTR1900027179; http://www.chictr.org.cn/showprojen.aspx? proj=45030
Low serum calcium and phosphorus and their clinical performance in detecting COVID‐19 patients

This study aimed to evaluate the clinical performance of low serum calcium and phosphorus in discriminative diagnosis of the severity of patients with coronavirus disease 2019 (COVID‐19). We conducted a single‐center hospital‐based study and consecutively recruited 122 suspected and 104 confirmed patients with COVID‐19 during January 24 to April 25, 2020. Clinical risk factors of COVID‐19 were identified. The discriminative power of low calcium and phosphorus regarding the disease severity was evaluated. Low calcium and low phosphorus are more prevalent in severe or critical COVID‐19 patients than moderate COVID‐19 patients (odds ratio [OR], 15.07; 95% confidence interval [CI], 1.59–143.18 for calcium; OR, 6.90; 95% CI, 2.43–19.64 for phosphorus). The specificity in detecting the severe or critical patients among COVID‐19 patients reached 98.5% (95% CI, 92.0%–99.7%) and 84.8% (95% CI, 74.3%–91.6%) by low calcium and low phosphorus, respectively, albeit with suboptimal sensitivity. Calcium and phosphorus combined with lymphocyte count could obtain the best discriminative performance for the severe COVID‐19 patients (area under the curve [AUC] = 0.80), and combined with oxygenation index was promising (AUC = 0.71). Similar discriminative performances of low calcium and low phosphorus were found between suspected and confirmed COVID‐19 patient. Low calcium and low phosphorus could indicate the severity of COVID‐19 patients, and may be utilized as promising clinical biomarkers for discriminative diagnosis.
Kinetic modeling of H2O2 dynamics in the mitochondria of HeLa cells

Hydrogen peroxide (H2O2) promotes a range of phenotypes depending on its intracellular concentration and dosing kinetics, including cell death. While this qualitative relationship has been well established, the quantitative and mechanistic aspects of H2O2 signaling are still being elucidated. Mitochondria, a putative source of intracellular H2O2, have recently been demonstrated to be particularly vulnerable to localized H2O2 perturbations, eliciting a dramatic cell death response in comparison to similar cytosolic perturbations. We sought to improve our dynamic and mechanistic understanding of the mitochondrial H2O2 reaction network in HeLa cells by creating a kinetic model of this system and using it to explore basal and perturbed conditions. The model uses the most current quantitative proteomic and kinetic data available to predict reaction rates and steady-state concentrations of H2O2 and its reaction partners within individual mitochondria. Time scales ranging from milliseconds to one hour were simulated. We predict that basal, steady-state mitochondrial H2O2 will be in the low nM range (2–4 nM) and will be inversely dependent on the total pool of peroxiredoxin-3 (Prx3). Neglecting efflux of H2O2 to the cytosol, the mitochondrial reaction network is expected to control perturbations well up to H2O2 generation rates ~50 μM/s (0.25 nmol/mg-protein/s), above which point the Prx3 system would be expected to collapse. Comparison of these results with redox Western blots of Prx3 and Prx2 oxidation states demonstrated reasonable trend agreement at short times (≤ 15 min) for a range of experimentally perturbed H2O2 generation rates. At longer times, substantial efflux of H2O2 from the mitochondria to the cytosol was evidenced by peroxiredoxin-2 (Prx2) oxidation, and Prx3 collapse was not observed. A refined model using Monte Carlo parameter sampling was used to explore rates of H2O2 efflux that could reconcile model predictions of Prx3 oxidation states with the experimental observations.
Influence of Different Sweeteners on the Stability of Anthocyanins from Cornelian Cherry Juice

Cornelian cherries are red fruits which can be considered as a valuable dietary source of antioxidant biologically active compounds, especially anthocyanins. The purpose of the present study was to investigate the anthocyanins degradation process in Cornelian cherry juice supplemented with different sweeteners. Four formulations of Cornelian cherry juice were prepared using different sugars (sucrose, fructose) or artificial sweeteners (aspartame and acesulfame potassium). The obtained juices were stored at three distinct temperatures (2 °C, 25 °C, and 75 °C) in order to evaluate the effects of the sweetener and storage conditions on the pigment stability. The rate constants (k) and the half time values (t1/2) of the degradation processes were determined. The highest stability was observed for the anthocyanins from the unsweetened juice stored at 2 °C (k = 0.5·10−3 h−1), while the most accelerated degradation was registered for the fructose sweetened juice stored at 75 °C (k = 91.65·10−3 h−1). The presence of the different sweeteners in the Cornelian cherry juice affects their pigment stability during storage. The highest change in the retention of anthocyanins was determined by the presence of fructose, while acesulfame potassium had the less deleterious effect.
Genomic expression assay testing among American Indian and Alaska Native women with breast cancer

Breast cancer is one of the most common causes of cancer mortality for all women, including American Indian and Alaska Native (AI/AN) women. The use of the 21‐gene recurrence score (RS) appears to be predictive of the benefit of chemotherapy for women with estrogen receptor (ER)–positive breast cancer. The objective of the current study was to compare RS testing between AI/AN and non‐Hispanic White (NHW) women with breast cancer.
Pre-Exercise Nutrition Habits and Beliefs of Endurance Athletes Vary by Sex, Competitive Level, and Diet

Abstract Objective The purpose of this study was to determine the self-reported beliefs and practices relating to pre-exercise nutrition intake among endurance athletes of varying ages and competitive levels and examine differences based on sex, competitive level, and habitual dietary pattern. Method An anonymous online survey was circulated internationally in English and completed by 1950 athletes of varying competitive levels (51.0% female, mean age 40.9 years [range 18:78]). Survey questions included training background, determinants of pre-exercise nutrition intake and composition, and timing relative to exercise. Results Prior to morning exercise, 36.4%, 36.0%, and 27.6% of athletes consumed carbohydrate-containing food/drinks before almost every workout, some of the time, and never/rarely, respectively, with significant effects of sex (p < 0.001, Cramer’s V (ϕc) = 0.15) and competitive level (p < 0.001, ϕc = 0.09). Nutritional intake before exercise varied based on workout duration for 47.6% of athletes, with significant effects of sex (ϕc = 0.15) and habitual diet (ϕc = 0.19), and based on workout intensity for 39.1% of athletes, with significant effects of sex (ϕc = 0.13) and habitual diet (ϕc = 0.17, all p < 0.001). Additionally, 89.0% of athletes reported using at least some type of dietary supplement (including caffeine from coffee/tea) within 1 hour before exercise. Conclusions Overall, nearly all factors measured relating to pre-exercise nutrition intake varied by sex, competitive level, habitual dietary pattern, and/or intensity/duration of the training session and suggest a large number of athletes may not be following current recommendations for optimizing endurance training adaptations.
Cellular Microenvironment Stiffness Regulates Eicosanoid Production and Signaling Pathways.

Pathological changes in the biomechanical environment are implicated in the progression of idiopathic pulmonary fibrosis (IPF). Stiffened matrix augments fibroblast proliferation, differentiation and activates transforming growth factor beta-1 (TGF-β1). Stiffened matrix impairs the synthesis of the anti-fibrogenic lipid mediator prostaglandin E2 (PGE2) and reduces the expression of the rate-limiting prostanoid biosynthetic enzyme, cyclooxygenase-2 (COX-2). We now show that prostaglandin E synthase (PTGES), the final enzyme in the PGE2 biosynthetic pathway is expressed at lower levels in the lungs of IPF patients. We also show substantial induction of COX-2, PTGES, Prostaglandin E receptor 4 (EP4) and cytosolic phospholipase A2 (cPLA2) expression in human lung fibroblasts cultured in soft collagen hydrogels or in spheroids compared with conventional culture on stiff plastic culture plates. Induction of COX-2 and cPLA2 expression in spheroid cultures was prevented by the p38 mitogen-activated protein kinase inhibitor, SB203580. The induction of prostanoid biosynthetic enzyme expression was accompanied by an increase in PGE2 levels only in non-IPF derived fibroblast spheroids. Our study reveals an extensive dysregulation of prostanoid biosynthesis and signalling pathways in IPF-derived fibroblasts which are only partially abrogated by culture in soft microenvironments.
Classroom Active Breaks to Increase Children’s Physical Activity: A Cross-Sectional Study in the Province of Naples, Italy

Background: Classroom Active Breaks (CABs), short active sessions integrated in the school time, have been recognized as a promising tool to reduce sedentary behavior and increase Physical Activity (PA) levels in children. “AulAttiva” is a six-month CABs-based program implemented in primary schools of the province of Naples. The aim of this study was to evaluate its effectiveness by comparing PA and sedentary time of participating pupils respect to a control group, considering also their weight status. Methods: Four third-grade classes, each from 4 schools out of 32 participating in AulAttiva, and 4 third-grade classes, each from 4 schools out of 74 that did not take part, were randomly selected. Finally, 58 children composed the intervention group and 57 the control group. Age, gender, weight and height were registered for each participant. Weight status was classified as non-overweight and overweight/obesity. Sedentary time and PA were assessed through accelerometers along a school day. Results: Light PA was 4 min higher in the AulAttiva group with respect to controls (p = 0.046). Within the non-overweight children, the AulAttiva group spent less time in sedentary behavior and more time in light and total PA than controls. No significant differences were found between the overweight/obese subgroups. Conclusions: The results support the effectiveness of CABs in increasing PA during the school day. Greater effects were registered among normal weight pupils, suggesting the possible influence of weight status on children’s participation to the intervention. Further studies are needed to improve the compliance of overweight/obese children to this intervention.
Neuromodulation for Apathy in Alzheimer’s Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study

Background: Apathy, a profound loss of motivation, initiation, and goal directed cognition, is a common comorbidity of Alzheimer’s disease (AD). The presence of apathy is associated with rapid progression of AD, long-term impairment, disability, and higher mortality. Pharmacological treatments of apathy are limited. Objective: The primary objective was to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for apathy in AD. Methods: A randomized, double-blind, parallel-arm, sham-controlled pilot study was conducted in subjects with AD and apathy (N = 20). Subjects were randomized to rTMS or sham treatment (5 days/week) for four weeks. Primary outcome, apathy evaluation scale-clinician version (AES-C), and secondary outcome measures, modified-Mini Mental State Examination (3MS), instrumental activities of daily living (IADL), and clinical global impression (CGI), were assessed at baseline and four weeks. Follow-up visits were conducted at 8 and 12 weeks to test the durability of effects of intervention. Results: Mean age was 77.3 (±7.2) years, 80% were Caucasians and 10% were females. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment (–10.1 (–15.9 to –4.3); t (16) = –3.69; p = 0.002) at 4 weeks. There was also significantly greater improvement in 3MS (6.9 (1.7 to 12.0); t (15) = 2.85; p = 0.012), IADL (3.4 (1.0 to 5.9); χ21 = 7.72; p = 0.006), CGI-S (1.4 (0.5 to 2.3), t (16) = 3.29; p = 0.005), and CGI-I (–2.56 (–3.5 to –1.6), t (17) = –5.72; p < 0.001) for rTMS compared to the sham at 4 weeks. The effects of rTMS were durable at 12 weeks. Conclusion: rTMS may be safely used in subjects with AD and may improve apathy, function, and some aspects of cognition.
Characterization and Bio-Accessibility Evaluation of Olive Leaf Extract-Enriched “Taralli”

Olive leaves are rich in many compounds precious for human health. Due to this property, the current study was aimed to valorize the extract from this by-product in a cereal-based food, very popular all around the world, the “taralli”. To this aim, ultrasound-assisted extraction was applied to dried olive leaves to obtain the extract, used as “taralli” ingredient, instead of white wine. The “taralli” with and without extract was subjected to in vitro digestion to assess the quantity of polyphenolic compounds released in the gastrointestinal tract to become available for absorption. Total content of phenols and flavonoids, as well as the antioxidant capacity, was measured on both cooked and uncooked samples, before and after digestion. In addition, High-Performance Liquid Chromatography with Diode-Array Detection (HPLC-DAD) of the three most abundant polyphenols present in olive leaf extracts, such as oleuropein, hydroxytyrosol, and verbascoside, was carried out at the three stages of the digestion process. The results showed that the substitution of white wine with olive leaf extract increased the total content of polyphenols and flavonoids and the antioxidant capacity. Bio-accessibility of the main phenolic compounds demonstrated that oleuropein resisted slightly after gastric digestion but was almost completely degraded in the intestinal phase, while hydroxytyrosol and verbascoside were not resistant to the digestion process from the gastric phase.
Oxygen- and pH-Dependent Photophysics of Fluorinated Fluorescein Derivatives: Non-Symmetrical vs. Symmetrical Fluorination

Fluorescein, and derivatives of fluorescein, are often used as fluorescent probes and sensors. In systems where pH is a variable, protonation/deprotonation of the molecule can influence the pertinent photophysics. Fluorination of the xanthene moiety can alter the molecule’s pKa such as to render a probe whose photophysics remains invariant over a wide pH range. Di-fluorination is often sufficient to accomplish this goal, as has been demonstrated with compounds such as Oregon Green in which the xanthene moiety is symmetrically difluorinated. In this work, we synthesized a non-symmetrical difluorinated analog of Oregon Green which we call Athens Green. We ascertained that the photophysics and photochemistry of Athens Green, including the oxygen-dependent photophysics that results in the sensitized production of singlet oxygen, O2(a1Δg), can differ appreciably from the photophysics of Oregon Green. Our data indicate that Athens Green will be a more benign fluorescent probe in systems that involve the production and removal of O2(a1Δg). These results expand the available options in the toolbox of fluorescein-based fluorophores.
Piperine: A review of its biological effects

Medicinal plants have been used for years as a source of food, spices, and, in traditional medicine, as a remedy to numerous diseases. Piper nigrum, belonging to the family Piperaceae is one of the most widely used spices all over the world. It has a distinct sharp flavor attributed to the presence of the phytochemical, piperine. Apart from its use as a spice, P. nigrum is frequently used for medicinal, preservation, and perfumery purposes. Black pepper contains 2–7.4% of piperine, varying in content is associated with the pepper plant. Piperine displays numerous pharmacological effects such as antiproliferative, antitumor, antiangiogenesis, antioxidant, antidiabetic, anti‐obesity, cardioprotective, antimicrobial, antiaging, and immunomodulatory effects in various in vitro and in vivo experimental trials. Furthermore, piperine has also been documented for its hepatoprotective, anti‐allergic, anti‐inflammatory, and neuroprotective properties. This review highlights and discusses the medicinal and health‐promoting effects of piperine, along with possible mechanisms of its action in health promotion and disease prevention. In addition, the present review summarizes the recent literature related to piperine as a therapeutic agent against several diseases.
Stress and sex determination in fish: from brain to gonads.

Fish present remarkable malleability regarding gonadal sex fate. This phenotypic plasticity enables an organism to adapt changes in the environment by responding with different phenotypes. The gonad and the brain present this extraordinary plasticity. These organs are involved in the response to environmental stressors to direct the gonadal fate, inducing sex change or sex reversal in hermaphroditic and gonochoristic fish, respectively. The presence of such molecular and endocrine plasticity gives this group a large repertoire of possibilities against a continuously changing environment, resulting in the highest radiation of reproduction strategies described in vertebrates. In this review, we provide a broad and comparative view of tremendous radiation of sex determination mechanisms to direct gonadal fate. New results have established that the driving mechanism involves early response to environmental stressors by the brain plus high plasticity of gonadal differentiation and androgens as by-products of stress inactivation. In addition to the stress axis, another two major axes - the hypothalamic-pituitary-gonadal axis and the hypothalamic-pituitary-thyroid axis, which are well known to participate in the regulation of reproduction - have been proposed as reinforcing the brain-gonadal interrelationships in the fate of the gonad.
Morphology of the avian yolk sac

The avian yolk sac is a multifunctional extraembryonic organ that serves not only as a site of nutrient (yolk) absorption, but also for early hemopoiesis, and formation of blood vessels. Although the yolk sac membrane being specialized to function as an extraembryonic absorptive organ, it is neither morphologically nor functionally part of the embryonic gut. Yolk absorption is by the phagocytic activity of the extraembryonic endoderm. I used cryohistology and resin embedding histology of complete developmental series of Japanese quail to document the development of the avian yolk sac and changes of the microscopic anatomy throughout development. This material is complemented by complete series of MRT‐scans of live ostrich embryos from beginning of incubation through hatching. Considerable changes of size and shape of the yolk mass are documented and discussed as resulting from water flux from albumen to yolk associated with the biochemical activation of yolk sac proteins. During embryogenesis, the yolk sac endoderm forms villi that increase the absorptive surface and reach into the yolk ball. The histology of the absorptive epithelium is specialized for phagocytic absorption of yolk. During early developmental stages, the extraembryonic endoderm is single layered, but it eventually becomes several layers thick during later stages. The extraembryonic mesoderm forms an extensive layer of hematopoietic tissue; deep in this tissue lie the yolk sac vessels. During late stages of development, the erythropoietic tissue disappears, blood vessels are obliterated, and the yolk sac epithelium becomes apoptotic. Results are discussed in the light of the evolutionary history and phylogeny of the amniote egg.