Miracle-dz/UniFAR-FTUs huggingface dataset:
PGPM_A_331431 1425..1440

1Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, 510060, People’s Republic of China Background: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype and is associated with poor prognosis. The aberrant expression of circadian genes contributes to the origin and progression of breast cancer. The present study was designed to explore the potential function and prognosis value of circadian genes in TNBC. Methods: The transcriptome data of circadian genes were downloaded from The Cancer Genomic Atlas (TCGA), GSE25066 and GSE31448 datasets. The differential expressed circadian genes between non-TNBC and TNBC patients were analysed by Wilcoxon test. Univariate and multivariate Cox regression analyses were employed to identify the prognostic circadian genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) were performed to study the biological functions of ARNTL2. The composition of 22 immune cells in the tumour samples was estimated with CIBERSORT algorithm. The correlations between ARNTL2 expression and tumour-infiltrating immune cells were evaluated by Spearman correlation coefficient. Results: A total of 8 circadian genes were found to be differentially expressed between nonTNBC and TNBC, but only ARNTL2 has prognostic value. Multivariate Cox analysis identified that ARNTL2 was an independent prognosis factor for overall survival and relapse-free survival in TNBC patients. Functionally, ARNTL2 was mainly involved in immune response processes such as positive regulation of cytokine production, regulation of innate immune response, and cellular responses to molecules of bacterial origin. High expression of ARNTL2 was positively correlated with activated CD4 memory T cells, activated mast cells, and neutrophil infiltration and the expression of markers of neutrophils (ITGAM), dendritic cells (HLA-DRA, HLA-DPA1, ITGAM), Th1 (IL1B, STAT1), Th2 (IL13), Th17 (STAT3) and mast cells (TPSB2, TPSAB1). Conclusion: ARNTL2 may be linked with the functional modulation of the tumour immune microenvironment and serve as a potential biomarker for predicting the prognosis of TNBC patients.
Modiﬁed energy settings are mandatory to minimize oesophageal injury using the novel multipolar irrigated radiofrequency ablation catheter for pulmonary vein isolation

The multipolar irrigated radiofrequency (RF) ablation catheter (nMARQ TM ) is a novel tool for pulmonary vein isolation (PVI). We investigated the incidence of thermal oesophageal injury (EI) using the nMARQ TM for PVI. withtheinitialablationproto-col. However, the incidence of thermal EI can be sigiﬁcantly reduced with limited power and RF application time at the posterior left atrium. - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Keywords
High-Throughput Screening Identi ﬁ es Idasanutlin as a Resensitizing Drug for Venetoclax-Resistant Neuroblastoma Cells A C

, ABSTRACT ◥ Neuroblastoma tumors frequently overexpress the anti-apoptotic protein B-cell lymphoma/leukemia 2 (BCL-2). We previously showed that treating BCL-2 – dependent neuroblastoma cells with the BCL-2 inhibitor venetoclax results in apoptosis, but unfortunately partial therapy resistance is observed. The current study describes the identi ﬁ cation of drugs capable of resensitizing venetoclax-resistant neuroblastoma cells to venetoclax. To examine these effects, venetoclax resistance was induced in BCL-2 – dependent neuroblastoma cell lines KCNR and SJNB12 by continuous exposure to high venetoclax concentrations. Non-resistant and venetoclax-resistant neuroblastoma cell lines were exposed to a 209-compound library in the absence and presence of venetoclax to identify compounds that were more effective in the venetoclax-resistant cell lines under venetoclax pressure. Top hits were further validated in combination with venetoclax using BCL-2 – dependent neuroblastoma model systems. Overall, high-throughput drug screening identi ﬁ ed the MDM2 inhibitor idasanutlin as a promising resensitizing agent for venetoclax-resistant neuroblastoma cell lines. Idasanutlin treatment induced BAX-mediated apoptosis in venetoclax-resistant neuroblastoma cells in the presence of venetoclax, whereas it caused p21-mediated growth arrest incontrol cells. In vivo combination treatment showed tumor regression and superior ef ﬁ cacy over single-agent therapies in a BCL-2 – dependent neuroblastoma cell line xenograft and a patient-derived xenograft. However, xenografts less dependent on BCL-2 were not sensitive to venetoclax – idasanutlin combination therapy. This study demonstrates that idasanutlin can overcome resistance to the BCL-2 inhibitor venetoclax in preclinical neuroblastoma model systems, which supports clinical development of a treatment strategy combining the two therapies.
Astigmatism – Definition, Etiology, Classification, Diagnosis and Non-Surgical Treatment

1.1 Definition Astigmatism (from the Greek “a” meaning absence and “stigma” meaning point) is a refractive error (ametropia) that occurs when parallel rays of light entering the nonaccommoding eye are not focused on the retina [American Academy of Ophthalmology (AAO), 2007]. Astigmatism occurs when incident light rays do not converge at a single focal point. The cornea of the normal eye has a uniform curvature, with resulting equal refracting power over its entire surface. Most astigmatic corneas are normal also. In some individuals, however, the cornea is not uniform and the curvature is greater in one meridian (plane) than another, much like a football as a rugby ball. Light rays refracted by this cornea are not brought to a single point focus, and retinal images from objects both distant and near are blurred and may appear broadened or elongated. This refractive error is called astigmatism [AAO, 2007]. As concept astigmatism is at least 200 years old; as name, more than 150. Javal ascribes the concept to T. Young in 1800 and the name to W. Whewell. Bannon and Walseh give an early history [Harris, 2000]. Total astigmatism can be divided into corneal (or keratometric) astigmatism, lenticular astigmatism, and retinal astigmatism. Most astigmatism is corneal in origin. Lenticular astigmatism is a result of uneven curvature and differing refractive indices within the crystalline lens [Abrams, 1993]. It is well accepted that there is some relationship between the eye’s corneal and internal astigmatism. In 1890, Javal proposed a rule that predicted the total astigmatism of the eye based on the corneal astigmatism [Grosvenor, 1978; Read et al, 2007]. Javal’s rule states: At = k + p(Ac) Where At is the total astigmatism and Ac is the corneal astigmatism. The terms k and p are constants approximated by 0.5 and 1.25, respectively. Grosvenor, Quintero and Perrigin [Grosvenor et al, 1988] suggested a simplification of Javal’s rule and proposed a simplified Javal’s rule of At = Ac – 0.5, that was supported by Keller and colleagues [Keller et al, 1996]. It should be pointed out to the reader that with modern topographers and aberrometerss it is possible to measure corneal and internal astigmatism and such estimations like Javal’s rule are clinically less relevant. Kelly, Mihashi and Howland [Kelly et al, 2004] suggested that the horizontal/vertical astigmatism compensation is an active process determined through a fine-tuning,
Chemical and Nutritional Evaluation of Complementary Food from Blends of Quality Protein Maize and Conophor nuts ( Tetracarpidium

Complementary food was formulated from Quality protein Maize (QPM) and Conophor Nuts ( Tetracarpidum conophorum ). The effectiveness of the blend in meeting nutritional requirement in complementary diet was investigated. Proximate composition of the samples were evaluated which include crude protein, fat, moisture
The Study of Diverse Personalities that Hinder Harmony across Engineering Team

Working together harmoniously in an engineering team is crucial to achieve success and is essential to the team members' wellbeing. This study examines what types of personalities hinder the harmony across engineering teams and explores how to maintain harmony across engineering teams with diverse personalities. Consequently, the data is collected from experienced engineering team leaders as well as an experienced psychologist. This study shows that in the engineering industry personalities are looked at from a different perspective and their characteristics are perceived from a business point-of-view as opposed to the literature in which judgments are made upon the personality description.
Making the Match or Breaking it? Values, Perceptions, and Obstacles of Trainees Applying into Physician-Scientist Training Programs.

Background. Replenishing the physician-scientist workforce remains a central mission of medical education, but the hemorrhaging of qualified trainees threatens the physician-scientist role. Among the barriers facing physician-scientists is the game-like model of residency matching, which applies several flawed assumptions regarding the comparability of applicants' qualifications, cohort size, and the institutional breadth of applicant training needs. Methods. The current report summarizes the collective views and experiences of physician-scientist trainees following the 2021-2022 application cycle of physician-scientist training programs (PSTPs). We obtained survey-based feedback by 27 PSTP applicants from 17 U.S. medical universities, among whom 85% matched into a PSTP. Results. 93% PSTP applicants recognized scientific community as the most important feature of postgraduate training, and 65% of respondents found waiting for interviews as the most stressful aspect of the application cycle. Half of the survey respondents perceived at least one NRMP policy violation by a PSTP, most of which occurred during post-interview communication. Specifically, 93% respondents were contacted by a PSTP following interviews, and one-third admitted feeling pressured into sharing their rank preference during these interactions. Conversely, 65% of applicants visited at least one program or following interviews. Conclusion. Overall, we believe the values and needs of physician-scientist trainees are poorly represented by the current PSTP selection framework, including inconsistent timelines and communication throughout the process. We therefore propose a series of modifications that, if implemented, would better equip applicants to gauge programs according to the clinical, scientific, and academic communities that we seek to join as physician-scientists.
EFFECT OF EGYPTIAN GOOSEBERRY ECOTYPES ( Phyllanthus atropurpureus L.) AND GROWTH REGULATORS ON DIRECT MICROPROPAGATION, CALLUS INDUCTION, TOTAL ALKALOIDS AND PHENOLIC CONTENT

The effect of different Egyptian P. atropurpureus ecotypes (Sharkia, Ismailia and Cairo) and growth regulators on direct pathway (micro propagation), indirect pathway (callus induction), as well as alkaloids and phenolic content were determined. Murashige and skoog (MS) medium supplemented with four different growth regulators was applied for micro propagation, i.e. M0: (without hormone), M1: 1 mg/l Benzyl Adenine (BA), M2: 2 mg/l (BA), and M3: 4 mg/l (BA). Four different growth regulators for rooting, i.e. M0 (without hormone), M4: 0.50 mg/l Indol buteric acid (IBA) + 0.50 mg/l Indol acetic acid (IAA), M5: 1 mg/l (IBA) and M6: 2 mg/l (IBA). As well as four different growth regulators for callus induction, i.e. M0: (without hormone), M7: 2 mg/l 1-Naphthalen acetic acid (NAA) + 0.2 mg/l (BA), M8: 1 mg/l 2, 4 Dichlorophenoxy acetic acid (2, 4-D) and M9: 2 mg/l (2, 4-D). The results showed that Sharkia ecotype gave highly genetic response for micro propagation (2.91 shoots) followed by Ismailia, medium (M1) gave highly genetic response for micro propagation (2.66 shoots) followed by M0, and the interaction between Sharkia ecotype and medium (M1) gave significant for shoot number, shoot length, fresh weight, dry weight, shooting percentages, leaf number and internode number. Sharkia ecotype gave highly genetic response for rooting (4.33 roots) followed by Ismailia, medium (M4) gave highly genetic response for rooting (2.4 roots) followed by M0, and the interaction between Sharkia ecotype and medium (M4) was significant for root number, root length and rooting percentages. Sharkia ecotype gave highly genetic response for callus induction frequencies (88.8%) followed by Ismailia, medium (M8) gave highly genetic response for callus induction frequencies (81.4%) followed by M9, and the interaction between Sharkia ecotype and medium (M8) gave significant for callus fresh weight, callus dry weight, callus induction frequency and callusing Initiation time/day. Total alkaloids content (TAC) was estimated using spectrophotometer with bromocresol green (BCG) in three different parts (leaf, stem and callus). The results showed that Ismailia ecotype gave highly genetic response for TAC (1.60 mg/g) followed by Sharkia, stem gave highly genetic response for TAC (0.86 mg/g) followed by leaf. Total phenolic content (TPC) was estimated using spectrophotometer with folin- ciocalteu method in the whole plant. The results showed that Ismailia ecotype was the highest significant for TPC (2.513 mg/g) followed by Sharkia. Cairo ecotype was the lowest value in TAC and TPC.
The Influence of Early-Life Events on Human Capital, Health Status, and Labor Market Outcomes Over the Life Course

Using nationally representative data from the US, this study provides evidence on the relationship between early life conditions and cognition, human capital accumulation, labor market outcomes, and health status in adulthood. We find that poor health at birth and limited parental resources (including low income, lack of health insurance, and unwanted pregnancy) interfere with cognitive development and health capital in childhood, reduce educational attainment, and lead to worse labor market and health outcomes in adulthood. These effects are substantial, and they are robust to the inclusion of sibling fixed effects and an extensive set of controls. The results reveal that low birth weight ages you by 12 years, increases the odds of dropping out of high school by one-third, lowers labor force participation by 5 percentage points, and reduces labor market earnings by roughly 15 percent. Not only are socioeconomic factors determinants of poor birth outcomes, but they also influence the lasting impacts of poor infant health when it occurs. In particular, the negative long-run consequences of low birth weight are larger among children whose parents did not have health insurance. While poor birth outcomes reduce human capital
Distinct Mg 2 -dependent Steps Rate Limit Opening and Closing of a Single CFTR Cl (cid:3) Channel

The roles played by ATP binding and hydrolysis in the complex mechanisms that open and close cystic ﬁbrosis transmembrane conductance regulator (CFTR) Cl (cid:3) channels remain controversial. In this work, the contributions made by ATP and Mg 2 (cid:2) ions to the gating of phosphorylated cardiac CFTR channels were evaluated separately by measuring the rates of opening and closing of single channels in excised patches exposed to solutions in which [ATP] and [Mg 2 (cid:2) ] were varied independently. Channel opening was found to be rate-limited not by the binding of ATP alone, but by a Mg 2 (cid:2) -dependent step that followed binding of both ATP and Mg 2 (cid:2) . Once a channel had opened, sudden withdrawal of all Mg 2 (cid:2) and ATP could prevent it from closing for tens of seconds. But subsequent exposure of such an open channel to Mg 2 (cid:2) ions alone could close it, and the closing rate increased with [Mg 2 (cid:2) ] over the micromolar range (half maximal at (cid:2) 50 (cid:4) M [Mg 2 (cid:2) ]). A simple interpretation is that channel closing is stoichiometrically coupled to hydrolysis of an ATP molecule that remains tightly associated with the open CFTR channel despite continuous washing. If correct, that ATP molecule appears able to reside for over a minute in the catalytic site that controls channel closing, implying that the site must entrap, or have an intrinsi-cally high apparent afﬁnity for, ATP, even without a Mg 2 (cid:2) ion. Such stabilization of the open-channel conformation of CFTR by tight binding, or occlusion, of an ATP molecule echoes the stabilization of the active conformation of a G protein by GTP.
New Insight into the In Situ SO 2 Poisoning Mechanism over Cu-SSZ-13 for the Selective Catalytic Reduction of NO x with NH 3

: To reveal the nature of SO 2 poisoning over Cu-SSZ-13 catalyst under actual exhaust conditions, the catalyst was pretreated at 200 and 500 ◦ C in a ﬂow containing NH 3 , NO, O 2 , SO 2 , and H 2 O. Brunner − Emmet − Teller (BET), X-ray di ﬀ raction(XRD), thermo gravimetric analyzer (TGA), ultraviolet Raman spectroscopy (UV Raman), temperature-programmed reduction with H 2 (H 2 -TPR), temperature-programmed desorption of NO + O 2 (NO + O 2 -TPD), NH 3 -TPD, in situ di ﬀ use reﬂectance infrared Fourier transform spectroscopy (in situ DRIFTS), and an activity test were utilized to monitor the changes of Cu-SSZ-13 before and after in situ SO 2 poisoning. According to the characterization results, the types and generated amount of sulfated species were directly related to poisoning temperature. Three sulfate species, including (NH 4 ) 2 SO 4 , CuSO 4 , and Al 2 (SO 4 ) 3 , were found to form on CZ-S-200, while only the latter two sulfate species were observed over CZ-S-500. Furthermore, SO 2 poisoning had a negative e ﬀ ect on low-temperature selective catalytic reduction (SCR) activity, which was mainly due to the sulfation of active sites, including Z 2 Cu, ZCuOH, and Si-O(H)-Al. In contrast, SO 2 poisoning had a positive e ﬀ ect on high-temperature SCR activity, owing to the inhibition of the NH 3 oxidation reaction. The above ﬁndings may be a useful guideline to design excellent SO 2 -resistant Cu-based zeolite catalysts.
Activation of PPAR (cid:1) and PPAR (cid:2) by Environmental Phthalate Monoesters

Phthalate esters are widely used as plasticizers in the manufac-ture of products made of polyvinyl chloride. Mono-(2-ethylhexyl)-phthalate (MEHP) induces rodent hepatocarcinogenesis by a mechanism that involves activation of the nuclear transcription factor peroxisome proliferator-activated receptor-alpha (PPAR (cid:1) ). MEHP also activates PPAR-gamma (PPAR (cid:2) ), which contributes to adipocyte differentiation and insulin sensitization. Human exposure to other phthalate monoesters, including metabolites of di- n -butyl phthalate and butyl benzyl phthalate, is substantially higher than that of MEHP, prompting this investigation of their potential for PPAR activation, assayed in COS cells and in PPAR-responsive liver (PPAR (cid:1) ) and adipocyte (PPAR (cid:2) ) cell lines. Monobenzyl phthalate (MBzP) and mono- sec -butyl phthalate (MBuP) both increased the COS cell transcriptional activity of mouse PPAR (cid:1) , with effective concentration for half-maximal response (EC 50 ) values of 21 and 63 (cid:3) M, respectively. MBzP also activated human PPAR (cid:1) (EC 50 (cid:4) 30 (cid:3) M) and mouse and human PPAR (cid:2) (EC 50 (cid:4) 75–100 (cid:3) M). MEHP was a more potent PPAR activator than MBzP or MBuP, with mouse PPAR (cid:1) more sensitive to MEHP (EC 50 (cid:4) 0.6 (cid:3) M) than human PPAR (cid:1) (EC 50 (cid:4) 3.2 (cid:3) M). MEHP activation of PPAR (cid:2) required somewhat higher concentrations, EC 50 (cid:4) 10.1 (cid:3) M (mouse PPAR (cid:2) ) and 6.2 (cid:3) M (human PPAR (cid:2) ). No signiﬁcant PPAR activation was observed with the monomethyl, mono- n -butyl, dimethyl, or diethyl esters of phthalic acid. PPAR (cid:1) activation was veriﬁed in FAO rat liver cells stably transfected with PPAR (cid:1) , where expression of several endogenous PPAR (cid:1) target genes was induced by MBzP, MBuP, and MEHP. Similarly, activation of endogenous PPAR (cid:2) target genes was ev-idenced for all three phthalates by the stimulation of PPAR (cid:2) dependent adipogenesis in the 3T3-L1 cell differentiation model. These ﬁndings demonstrate the potential of environmental phthalate monoesters for activation of rodent and human PPARs and may help to elucidate the molecular basis for the adverse health effects proposed to be associated with human phthalate exposure.
The Effect of Applying Mind Mapping Method in Writing Descriptive Text

Writing is one of the four aspects of language skills that a person must possess. By writing, someone can generate interesting ideas and then pour them into writing. The mind mapping method is applied to see how the method influences writing student description texts. This study aims to identify the effect of the mind mapping method on writing descriptive texts for students of SMK Muhammadiyah Tidore Kepulauan. The subjects are students of class XI for the 2020/2021 school year. This study uses a quantitative design. The instrument used by researchers is a test. The analysis technique used to measure student work is by using descriptive text rubrics. The implementation of learning to write descriptive text using the mind mapping method in class XI students is carried out effectively, smoothly, and thoroughly, which can be seen from the seriousness of the students in participating in learning. Previously students were bored, but when learning was done using the mind mapping method, students were enthusiastic and very creative in making mind maps and concentrated very much on writing a descriptive text. The mind mapping method has a positive influence on writing the descriptive text for class XI students of SMK Muhammadiyah Tidore Kepulauan. This can be seen in the learning outcomes that the scores of the results of writing the descriptive text of students using the mind mapping method have increased between the pre-test and post-test scores, the pre-test average score is 51,3 while the post-test average score is 90,6.