Miracle-dz/UniFAR-FTUs huggingface dataset:
Advances in cyclin-dependent kinase inhibitors for the treatment of melanoma

ABSTRACT Introduction: Despite the recent advances in the treatment of malignant melanoma with immunotherapy and BRAF/MEK targeted agents, advanced disease still beholds a poor prognosis for a significant proportion of patients. Cyclin-dependent kinase (CDK) inhibitors have been investigated as novel melanoma therapeutics throughout a range of phase 1 and 2 trials, as single agents and in combination with established treatments. Areas covered: This article summarizes the rationale for, and development of CDK inhibitors in melanoma, with their evolution from pan-CDK inhibitors to highly specific agents, throughout clinical trials and finally their potential future use. Expert opinion: Whilst CDK inhibitors have been practice changing in breast cancer management, their efficacy is yet to be proven in melanoma. Combination with BRAF/MEK inhibitors has been hindered by dose-limiting toxicities, but their role may yet to be found within the spectrum of biomarker-derived personalized melanoma management. The effect that CDK inhibitors can have as an adjunct to immunotherapy also remains to be seen.
Metabolic compromise in women with PCOS: earlier than expected.

METHODS Polycystic ovary syndrome (PCOS) is an endocrinopathy with unknown pathophysiology among women of reproductive age. Several studies have been conducted to determine the prevalence of metabolic syndrome (MetS) among PCOS patients. Recent studies have reported varied prevalence of metabolic syndrome (MetS) in women with PCOS. The aim of this study is to determine if women with PCOS are at a higher risk of MetS or some degree of metabolic compromise. This is an observational study. A total of 96 women diagnosed with PCOS (according to the Rotterdam consensus criteria) were included. Variables of diagnostic criteria for MetS according to the ATP III were analyzed at the first consultation. Data analysis was performed using Epi Info™ 7.2. 2.16. RESULTS We assessed the prevalence of obesity, blood pressure, glucose intolerance, and dyslipidemia in 96 women with PCOS and an average age of 28 (17-39) years. Forty percent of the women had BMI <25 kg/m2; 85.4% had blood pressure <130/85 mm Hg; 22.9% had HDL cholesterol >50 mg/dl, 57.3% had triglycerides <150 mg/dl, 63.5% had fasting glucose <100 mg/dl. According to the ATP III criteria for MetS, 8.33% met none of the criteria, 19.79% met one criterion, 15.63% two criteria, 41.67% 3 criteria, 13.54% 4 criteria, and 1.04% met the 5 criteria. CONCLUSION Considering the high prevalence of MetS or altered metabolic components in PCOS patients at the moment of the diagnosis, its regular screening is necessary to reduce the mortality and morbidity rates in these women.
Calmodulinopathies: throwing back the veil on the newest life-threatening genetic arrhythmia syndrome

Purpose of review This review provides a basic understanding of the calmodulin gene and its role in calcium homeostasis. We outline the functional effects and clinical expression of CALM mutations and review disease expression and management. Recent findings Calmodulinopathies are rare life-threatening arrhythmia syndromes affecting young individuals. They are caused by mutations in any of the three genes (CALM 1-3) that encode calmodulin (CaM), a ubiquitously expressed Ca2+ signaling protein with multiple targets that in the heart, modulates several ion channels. Patients express varied phenotypes: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, sudden death, idiopathic ventricular fibrillation, hypertrophic cardiomyopathy, or mixed disease. This is severe disease. Over half of 2019 International Calmodulin Registry patients experienced recurrent cardiac events despite management strategies that included: monotherapy and combination therapy with beta blockers, sodium channel blockers, other antiarrhythmics, sympathetic denervation, and pacing. Induced pluripotent stem cell-derived cardiomyocytes from patients harboring CALM mutations have provided a platform for better understanding pathogenic mechanisms and avenues for therapy. Summary Calmodulinopathies are among the more novel inherited arrhythmia syndromes. These are rare but highly lethal diseases with diverse clinical expressions. The practicing electrophysiologist should be aware these conditions, how to recognize them clinically, and understand the challenges in management.
Efficacy of LGBTQI cultural competency training for oncology social workers

Abstract Purpose Oncology social workers rarely receive training on the health care needs of lesbian, gay, bisexual, transgender, queer, and intersex (LGBTQI) cancer patients. This study examined the efficacy of an intensive workshop that aimed to increase the knowledge, confidence, and clinical preparedness of social workers supporting LGBTQI cancer patients. Methods A workshop consisting of didactic and interactive content was provided to an opt-in sample of social workers (n = 26). Demographic questions, past exposure to LGBTQI patients and training, and self-reported behaviors were measured at baseline. Paired t-tests compared changes in confidence in learning objectives as well as self-reported knowledge, attitudinal awareness, and clinical preparedness based on the lesbian, gay, bisexual, transgender development of clinical skills scale. Results Results showed statistically significant changes in two of three learning objectives (p = 0.001) and in two subscales of the LGBT-DOCSS (p < 0.001). Conclusions Oncology social workers can benefit from opportunities for learning specific to LGBTQI health.
Integrated Double Estimator Architecture for Reinforcement Learning

Estimation bias is an important index for evaluating the performance of reinforcement learning (RL) algorithms. The popular RL algorithms, such as <inline-formula> <tex-math notation="LaTeX">$Q$ </tex-math></inline-formula>-learning and deep <inline-formula> <tex-math notation="LaTeX">$Q$ </tex-math></inline-formula>-network (DQN), often suffer overestimation due to the maximum operation in estimating the maximum expected action values of the next states, while double <inline-formula> <tex-math notation="LaTeX">$Q$ </tex-math></inline-formula>-learning (DQ) and double DQN may fall into underestimation by using a double estimator (DE) to avoid overestimation. To keep the balance between overestimation and underestimation, we propose a novel integrated DE (IDE) architecture by combining the maximum operation and DE operation to estimate the maximum expected action value. Based on IDE, two RL algorithms: 1) integrated DQ (IDQ) and 2) its deep network version, that is, integrated double DQN (IDDQN), are proposed. The main idea of the proposed RL algorithms is that the maximum and DE operations are integrated to eliminate the estimation bias, where one estimator is stochastically used to perform action selection based on the maximum operation, and the convex combination of two estimators is used to carry out action evaluation. We theoretically analyze the reason of estimation bias caused by using nonmaximum operation to estimate the maximum expected value and investigate the possible reasons of underestimation existence in DQ. We also prove the unbiasedness of IDE and convergence of IDQ. Experiments on the grid world and Atari 2600 games indicate that IDQ and IDDQN can reduce or even eliminate estimation bias effectively, enable the learning to be more stable and balanced, and improve the performance effectively.
Characterization and expression of gene encoding HMGR from Tripterygium wilfordii_

【Objective】 This study aimed to clone the gene encoding HMGR,the rate-limiting enzyme in the plant terpenoid biosynthetic pathway from Tripterygium wilfordii,analyze its expression in suspension cell induced by chitosan with different concentrations,and improve the understanding of biosynthesis of terpenoid alkaloids in T.wilfordii. 【Method】 The degenerate primers were synthesized based on the encoding sequence of the rate-limiting enzyme HMGR reported in GenBank and full-length hmgr cDNA sequence in the leaves of T.wilfordii was cloned by RT-PCR,5′-RACE and 3′-RACE.Bioinformatics analysis was used to identify the rate-limiting enzyme structure and functions of HMGR.Semi-quantitative RT-PCR was carried out to compare the expression of the hmgr gene in suspension cell and HPLC was used to determine the content of three secondary metabolites(triptolide,wilforgine and wilforine) after being induced by oligosaccharide with different concentrations of oligosaccharide. 【Result】 A full-length cDNA encoding HMGR with a ORF of 1 860 bp and a total of 579 amino acids was obtained.Bioinformatics analysis revealed that the deduced HMGR had extensive homology with HMGRs of other plants.The molecular weight of the protein was 61.678 ku,the isoelectric point of HMGR was 6.98 and the stability index was 41.33. The protein was unstable.This protein contained two NADP(H)-binding sites(DAMGMNM and VGTVGGGT) and two HMG-CoA-binding sites(EMPVGYVQIP and TTEGCLVA). Gene expression by semi-quantative RT-PCR showed that the highest HMGR expression occured in T.wilfordii induced for 12 hours by oligosaccharide with a concentration of 50 mg/L.This concentration also played significant role in accumulation of triptolide,wilforgine and wilforine. 【Conclusion】 HMGR in T.wilfordii may be the rate-limiting enzyme in MVA pathway and the gene encoding HMGR can stimulate the biosynthesis of terpenoids.
Profiles of Health-Related Quality of Life and Their Relationships With Happiness, Physical Activity, and Fitness

ABSTRACT Purpose: Health-related quality of life (HRQOL) reflects a perceived sense of physical and mental well-being over time, encompassing both physical health and psychosocial health. Although these two health concepts have been often examined as a whole, few studies have explored the possibility of mixed profiles. We designed this study to identify Chinese adolescents’ HRQOL profiles and their associations with happiness, physical activity, and fitness. Method: 544 high-school students completed validated Chinese-version questionnaires assessing HRQOL, happiness, and physical activity behavior while their fitness level was evaluated based on China National Fitness Test Program. A two-step cluster analysis and MANOVAs were conducted. Results: We identified four distinct clusters: low HRQOL, psychosocial health-oriented, physical health-oriented, and high HRQOL. There were significant differences among clusters in happiness, physical activity, and fitness, with “high HRQOL” group being the most adaptive cluster while “low HRQOL” group the least. Both psychosocial health-oriented and physical health-oriented clusters demonstrated dimension-related features. Conclusion: Health-related quality of life in Chinese adolescents is a multidimensional construct. Although its physical and psychosocial functioning are often interacted, different dimensions have unique but specified roles. Particularly, physical functioning might not only be associated with physical and health condition but also with positive emotion, especially when psychosocial satisfaction is lacking. It is important to pay specific attention to the interactions among the dimensions and how the interactions combine and function together to influence adolescents’ behavior.
The growth pattern of two species of Schima

The growth patterns of two closely related deciduous tree species, Schiina u'allzchii (at 100 m and 1600 in altitude), and S. khasiana (at 1900 m) in Meghalaya, north-eastern India, were compared. Both species conform to Rauh's model of architectLure. Sylleptic lateral branches formed on S. khasiana during periods of vigorous growth of the main shoot. Although stem extension and leaf production were continuous throughout the growing season, they exhibited (endogenous') periodicity which was most marked in S. wallichi, at lower altitude. Schimia wallich;; at lower altitude had the fastest turnover of leaves. THE DYNAMICS OF SHOOT INITIATION AND EXPANSION in tropical trees has been studied qualitatively by Halle and Martin (1968) for rubber, Borchert (1969) for Oreopanax, Gill and Tomlinson (1971) for Rhizophora, and Hall6 et al. (1978), but the morphometric analysis of growth characteristics of tropical trees has received relatively little attention (Fisher 1978, Borchert and Slade 1981). Many studies (Njoku 1963, Frankie et al. 1974) have shown close correlations between the growth of tropical deciduous trees and seasonal climatic changes (e.g., leaf fall/drought relationships). However, correlations between phenological events and environmental change are often difficult to determine in evergreen forests (e.g., Alvim 1964), and the environmental cues may depend upon interaction with internal controls (Borchert 1978). MATERIALS AND STUDY SITES The two species of Schima Reinw. ex. Blume (Ternstroemiaceae) studied, S. wallichii (DC) Korth and S. khasiana Dyer, are important timber trees of north-east India. Schima wallichii ranges in altitude from 100 to 1600 m, while S. khasiana is restricted to 1600 to 1900 m. These secondary successional trees follow slash and burn fallows, coppice well, and are dispersed by light, windblown seeds. They mature at an average height of 25 to 30 m and 12 to 20 m at lower and higher elevations, respectively. Whitmore (1975) observed S. wallichii colonizing man-made clearings in lowland and lower montane forests of Malaya and considered it a marginal pioneer. Schima wallichii was studied at Shillong (25034'N, 91056'E, alt. 1600 m) and Burnihat (90 km North of Shillong, alt. 100 m). Schima khasiana was studied at Upper Shillong (10 km South of Shillong, alt. 1900 m). The study areas have four distinct seasons: a monsoon season of heavy rain during May to September; a transitional period of low rainfall in October and November; a "winter" season during December to February with scattered rainfall; and a dry "summer" during March and April. Average annual rainfall during the study period was 2350, 1800, and 1550 mm at Upper Shillong, Shillong, and Burnihat, respectively. The average maximum and minimum temperatures for the monsoon and winter seasons, respectively, were 16-22? C and 2-15? C at Upper Shillong (Fig. la), 16-24? C and 6-16? C at Shillong, and 24-32? C and 12-24? C at Burnihat.
Nitrogen isotope fractionation and amino acid turnover rates in the Pacific white shrimp Litopenaeus vannamei

: Fluctuations in an animal’s trophic position (TP) can indicate changes within an ecosystem. Traditionally, bulk tissue or whole animal nitrogen (N) isotope analysis has been used to determine an animal’s TP, but there are limitations to the application of this approach. Amino acid compound-specific isotope analysis (AA-CSIA) can be used to determine TP based on the difference between the δ 15 N values of certain amino acids, commonly glutamic acid and phenylalanine. The rate at which 15 N is incorporated into amino acids is largely unknown, and this may affect the accuracy of relative TP estimates especially during periods of ecosystem change or ontogenetic changes in diet. To study amino acid turnover rates, the diet of the Pacific white shrimp Lito penaeus vannamei was changed in the laboratory from an unlabeled diet (7.2‰) to a 15 N-enriched diet (24‰), and animals were sampled over the course of 7 wk. AA-CSIA revealed that turnover times of amino acids vary considerably, with some amino acids having much more rapid turnover than others. The TP of L. vannamei (using δ 15 N values of glutamic acid and phenylalanine) over the course of the experiment remained constant, and shrimp TP averaged 2.14 ± 0.15 (mean ± SD, n = 7) relative to its diet, which was as expected. Our results indicate that the δ 15 N values of glutamic acid and phenylalanine can be used to accurately determine TP even while shrimp are undergoing a change to a diet with a different δ 15 N value.
Beobachtung der Entstehung von kleinen rundlichen Zellen aus den Fibrocyten in dem an der Ohrmuschel des Kaninchens angebrachten durchsichtigen Fenster nach intravenöser Injektion des Extraktes eines giftigen Unkrautes Houttuynia cordata

In Japan wird die Houttuynia cordata von altersher zur Beschleunigung der Eiterung der Furunkel benutzt. Nach der Injektion ihres Extraktes in die Vene des Kaninchens wurde im durchsichtigen Fenster des Ohres die Umwandlung der Fibrocyten in Fibrohistiocyten und in kleine rundliche Zellen (Monocyten und leukocytenahnliche Zellen) beobachtet.
Molecular origin of negative component of Helmholtz capacitance at electrified Pt(111)/water interface

Change in water chemisorption in response to electrode potential leads to negative capacitance in electric double layer. Electrified solid/liquid interfaces are the key to many physicochemical processes in a myriad of areas including electrochemistry and colloid science. With tremendous efforts devoted to this topic, it is unexpected that molecular-level understanding of electric double layers is still lacking. Particularly, it is perplexing why compact Helmholtz layers often show bell-shaped differential capacitances on metal electrodes, as this would suggest a negative capacitance in some layer of interface water. Here, we report state-of-the-art ab initio molecular dynamics simulations of electrified Pt(111)/water interfaces, aiming at unraveling the structure and capacitive behavior of interface water. Our calculation reproduces the bell-shaped differential Helmholtz capacitance and shows that the interface water follows the Frumkin adsorption isotherm when varying the electrode potential, leading to a peculiar negative capacitive response. Our work provides valuable insight into the structure and capacitance of interface water, which can help understand important processes in electrocatalysis and energy storage in supercapacitors.
Educational intervention with serial album about pregnant women positioning for spinal anesthesia: randomized clinical trial.

OBJECTIVE To evaluate effectiveness of using educational intervention serial album to positioning pregnant women for spinal anesthesia. METHOD Randomized clinical trial with 90 women casually assigned to control (CG) and intervention group (IG), in a maternity hospital located in Northeast region of Brazil. The primary endpoint was "achieve correct positioning to perform spinal anesthesia"; and secondary, "how number of spinal cord puncture attempts". Effectiveness was verified using the chi-square test, Fisher's exact test and likelihood ratio. RESULTS The positioning was correct in 37 women in each group. There was an association between women in control group remaining still, relaxing shoulders and flexing the spine; and women in intervention group should remain still and relax the shoulders; furthermore there was a statistical association achieved by correct positioning and the number of attempts to access the lumbar puncture. CONCLUSION Educational intervention with serial album was effective and contributed to immobility and positioning of pregnant women. Brazilian Registry of Clinical Trials (RBR-3Z7SRD).
Compartment-specific transcriptomics of ozone-exposed murine lungs reveals sex and cell type-associated perturbations relevant to mucoinflammatory lung diseases.

Ozone is known to cause lung injury and resident cells of the respiratory tract, i.e., epithelial cells and macrophages, respond to inhaled ozone in a variety of ways that affect their survival, morphology, and functioning. However, a complete understanding of the sex-associated and the cell type-specific gene expression changes in response to ozone exposure is still limited. Through transcriptomics, we aimed to analyze gene expression alterations and associated enrichment of biological pathways enrichment in three distinct cell type-enriched compartments of ozone-exposed murine lungs. We sub-chronically exposed adult males and females to 0.8ppm ozone or filtered air. RNA-Seq was performed on airway epithelium-enriched airways, parenchyma, and purified airspace macrophages. Differential gene expression and biological pathway analyses were performed and supported by cellular and immunohistochemical analyses. While a majority of differentially expressed genes (DEGs) in ozone-exposed versus air-exposed groups were common between both sexes, sex-specific DEGs were also identified in all the three tissue compartments. As compared to ozone-exposed males, ozone-exposed females had significant alterations in gene expression in three compartments. Pathways relevant to cell division and DNA repair were enriched in the ozone-exposed airways indicating ozone-induced airway injury and repair which was further supported by immunohistochemical analyses. In addition to cell division and DNA repair pathways, inflammatory pathways were also enriched within the parenchyma supporting contribution by both epithelial and immune cells. Finally, immune response and cytokine-cytokine receptor interactions were enriched in macrophages, indicating ozone-induced macrophage activation. Lastly, our analyses also revealed ozone-induced upregulation of mucoinflammation- and mucous cell metaplasia-associated pathways.
Studies on the heterotrophic bacteria in the gastrointestinal tract of fishes. III. The fluctuation of the fecal flora of goldfish Carassius auratus.

Fecal pellets from 4 goldfish specimens were successively analyzed to obtain the knowledge on the fluctuation of the fecal flora.Aeromonas hydrophila and Bacteroides type A were predominant components in all fish specimens, Enterobacteriaceae and Pseudomonas were also predominant ones in specific individuals, whereas these were detected in 25 to 80% of fecal samples in other individuals. Aeromonas punctata, Flavobacterium, Staphylococcres and Clostridium occurred pre-dominantly in several cases, The remaining components were occasionally isolated at low bacterial densities. It was shown from the above results that each fish individual had a character of fecal flora and that there is a great day-to-day variation of the fecal flora of goldfish.
Agrobacterium mediated transfer of nptII and gus genes in Camellia assamica

The present work is an attempt to develop transgenic hairy root system in Camellia assamica, using leaves infected by Agrobacterium rhizogenes strain LBA9402, harboring binary vector (pART27 and pBI121) carrying β-glucuronidase (gus) as reporter gene and neomycin phosphotransferase (nptII) as selection marker. The transformed hairy roots were grown in phytohormone free MS media in the presence of kanamycin 50 µg/ml. The incorporation and expression of foreign genes were checked by initial gus assay followed by PCR analysis for the presence of nptII and β-glucuronidase (gus) gene. This protocol therefore facilitates the study of gene expression system in general and for root functional genomics in particular, giving scope for transgenic hairy roots as future explants for secondary metabolite production and plantlet regeneration. Key words: Agrobacterium rhizogenes, transformation, Camellia assamica, nptII, β-glucuronidase (gus).