Miracle-dz/UniFAR-FTUs huggingface dataset:
The impact of COVID-19 on palliative care workers across the world: A qualitative analysis of responses to open-ended questions

Abstract Objective With over two million deaths and almost 100 million confirmed cases, the COVID-19 pandemic has caused a “tsunami of suffering. ” Health care workers, including palliative care workers, have been severely impacted. This study explores how the COVID-19 pandemic has impacted palliative care workers around the world and describes the coping strategies they have adopted to face their specific situation. Method We conducted a qualitative analysis of written, unstructured comments provided by respondents to a survey of IAHPC members between May and June 2020. Free text was exported to MAX QDA, and a thematic analysis was performed by reading the comments and developing a coding frame. Results Seventy-seven palliative care workers from 41 countries submitted at least one written comment, resulting in a data corpus of 10,694 words and a total of 374 coded comments. Eight main themes are emerged from the analysis: palliative care development, workforce impact, work reorganization, palliative care reconceptualization, economic and financial impacts, increased risk, emotional impact, and coping strategies. Significance of results The pandemic has had a huge impact on palliative care workers including their ability to work and their financial status. It has generated increased workloads and placed them in vulnerable positions that affect their emotional well-being, resulting in distress and burnout. Counseling and support networks provide important resilience-building buffers. Coping strategies such as team and family support are important factors in workers’ capacity to adapt and respond. The pandemic is changing the concept and praxis of palliative care. Government officials, academia, providers, and affected populations need to work together to develop, and implement steps to ensure palliative care integration into response preparedness plans so as not to leave anyone behind, including health workers.
Development of a novel, fully human, anti-PCSK9 antibody with potent hypolipidemic activity by utilizing phage display-based strategy

Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates serum LDL cholesterol (LDL-C) levels by facilitating the degradation of the LDL receptor (LDLR) and is an attractive therapeutic target for hypercholesterolemia intervention. Herein, we generated a novel fully human antibody with favourable druggability by utilizing phage display-based strategy. Methods A potent single-chain variable fragment (scFv) named AP2M21 was obtained by screening a fully human scFv phage display library with hPCSK9, and performing two in vitro affinity maturation processes including CDR-targeted tailored mutagenesis and cross-cloning. Thereafter, it was transformed to a full-length Fc-silenced anti-PCSK9 antibody FAP2M21 by fusing to a modified human IgG1 Fc fragment with L234A/L235A/N297G mutations and C-terminal lysine deletion, thus eliminating its immune effector functions and mitigating mAb heterogeneity. Findings Our data showed that the generated full-length anti-PCSK9 antibody FAP2M21 binds to hPCSK9 with a KD as low as 1.42 nM, and a dramatically slow dissociation rate (koff, 4.68 × 10−6 s−1), which could be attributed to its lower binding energy (-47.51 kcal/mol) than its parent counterpart FAP2 (-30.39 kcal/mol). We verified that FAP2M21 potently inhibited PCSK9-induced reduction of LDL-C uptake in HepG2 cells, with an EC50 of 43.56 nM. Further, in hPCSK9 overexpressed C57BL/6 mice, a single tail i.v. injection of FAP2M21 at 1, 3 and 10 mg/kg, dose-dependently up-regulated hepatic LDLR levels, and concomitantly reduced serum LDL-C by 3.3% (P = 0.658, unpaired Student's t-test), 30.2% (P = 0.002, Mann-Whitney U-test) and 37.2% (P = 0.002, Mann-Whitney U-test), respectively. Interpretation FAP2M21 with potent inhibitory effect on PCSK9 may serve as a promising therapeutic agent for treating hypercholesterolemia and associated cardiovascular diseases.
Analysis of Polymer Drag Reduction Mechanisms from Energy Budgets

Abstract The transfer of energy in drag reducing viscoelastic flows is analyzed through a sequence of energetic budgets that include the mean and turbulent kinetic energy, and the mean polymeric energy and mean elastic potential energy. Within the context of single-point statistics, this provides a complete picture of the energy exchange between the mean, turbulent and polymeric fields. The analysis utilizes direct simulation data of a fully developed channel flow at a moderately high friction Reynolds number of 1000 and at medium (30%) and high (58%) drag reduction levels using a FENE-P polymeric model. Results show that the primary effect of the interaction between the turbulent and polymeric fields is to transfer energy from the turbulence to the polymer, and that the magnitude of this transfer does not change between the low and high drag reduction flows. This one-way transfer, with an amplitude independent of the drag reduction regime, comes in contradiction with the purely elastic coupling which is implicit within the elastic theory of the polymer drag reduction phenomenon by Tabor and De Gennes (Europhys. Lett. 2, pp. 519–522, 1986).
Comment on “Fatigability: A Prognostic Indicator of Phenotypic Aging”

© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. Letter to the Editor
Population genetic structure and association mapping for iron toxicity tolerance in rice

Iron (Fe) toxicity is a major abiotic stress which severely reduces rice yield in many countries of the world. Genetic variation for this stress tolerance exists in rice germplasms. Mapping of gene(s)/QTL controlling the stress tolerance and transfer of the traits into high yielding rice varieties are essential for improvement against the stress. A panel population of 119 genotypes from 352 germplasm lines was constituted for detecting the candidate gene(s)/QTL through association mapping. STRUCTURE, GenAlEx and Darwin softwares were used to classify the population. The marker-trait association was detected by considering both the Generalized Linear Model (GLM) and Mixed Linear Model (MLM) analyses. Wide genetic variation was observed among the genotypes present in the panel population for the stress tolerance. Linkage disequilibrium was detected in the population for iron toxicity tolerance. The population was categorized into three genetic structure groups. Marker-trait association study considering both the Generalized Linear Model (GLM) and Mixed Linear Model (MLM) showed significant association of leaf browning index (LBI) with markers RM471, RM3, RM590 and RM243. Three novel QTL controlling Fe-toxicity tolerance were detected and designated as qFeTox4.3, qFeTox6.1 and qFeTox10.1. A QTL reported earlier in the marker interval of C955-C885 on chromosome 1 is validated using this panel population. The present study showed that QTL controlling Fe-toxicity tolerance to be co-localized with the QTL for Fe-biofortification of rice grain indicating involvement of common pathway for Fe toxicity tolerance and Fe content in rice grain. Fe-toxicity tolerance QTL qFeTox6.1 was co-localized with grain Fe-biofortification QTLs qFe6.1 and qFe6.2 on chromosome 6, whereas qFeTox10.1 was co-localized with qFe10.1 on chromosome 10. The Fe-toxicity tolerance QTL detected from this mapping study will be useful in marker-assisted breeding programs.
Using Bayes theorem to estimate positive and negative predictive values for continuously and ordinally scaled diagnostic tests

Positive predictive values (PPVs) and negative predictive values (NPVs) are frequently reported to put estimates of accuracy of a diagnostic test in clinical context and to obtain risk estimates for a given patient taking into account baseline prevalence in the population. In order to calculate PPV and NPV, tests with ordinally or continuously scaled results are commonly dichotomized at the expense of a loss of information.
Grinding Effect on Some Pharmaceutical Properties of Drugs by Adding β-Cyclodextrin

AbstractThe effect of grinding on the physicochemical properties of ground mixtures of crystalline drugs (acetaminophen, warfarin, indomethacin, diazepam and hydrocortisone acetate) with 3-cyclodextrin was studied by IR analysis, x-ray diffraction method and thermal analysis. The crystallinities of drugs decreased with increasing grinding time and became amorphous or nearly amorphous, which depended on drug moiety and cavity size of 3-cyclodextrin. The result indicates that acetaminophen became amorphous and only formed an inclusion complex in the ground mixture with 3-cyclodextrin, although all five drugs interacted with 3-cyclodextrin in water. The dissolution rate of drugs from the ground mixtures was shown to be higher than that of the ground drug, crystalline drug or physical mixture, while the dissolution rate of the inclusion complex was the very highest. Physicochemical stability of the ground mixtures stored under 40°C and 75% RH condition was measured by differential scanning calorimetry. In the.
The Physics and Chemistry of Color: The Fifteen Causes of Color

Preface to the Second Edition.Preface to the First Edition. Acknowledgments for the Second Edition. Acknowledgments for the First Edition. LIGHT AND COLOR. Some Fundamentals: Color, Light, and Interactions. COLOR INVOLVING VIBRATIONS AND SIMPLE EXCITATIONS. Color Produced by Incandescence. Color Produced by Gas Excitations. Color Produced by Vibrations and Rotations. COLOR INVOLVING LIGAND FIELD EFFECTS. Color Caused by Transition Metals in a Ligand Field. COLOR INVOLVING MOLECULAR ORBITALS. Color in Organic Molecules. Charge Transfer Color. COLOR INVOLVING BAND THEORY. Color in Metals and Semiconductors. Color Centers. COLOR INVOLVING GEOMETRICAL AND PHYSICAL OPTICS. Dispersive Refraction and Polarization. Scattering and Nonlinear Effects. Interference and Diffraction. COLOR--RELATED TOPICS. Colorants of Many Types. Vision, Luminescence, Lasers, and Related Topics. Appendix A: Units, Chromaticity, and Color Order Systems. Appendix B: Incandescence Equations. Appendix C: Atoms and Simple Molecules. Appendix D: Crystal Fields, Ligand Fields, and Molecular Orbitals. Appendix E: Band Theory. Appendix F: Prism, Thin Film, and Layer Diffraction Grating. Appendix G: Recommendations for Additional Reading. Index.
Genome‐wide association mapping identifies novel loci underlying fire blight resistance in apple

Fire blight, caused by epiphytotic gram‐negative bacteria Erwinia amylovora, is the most destructive bacterial disease of apple (Malus spp.). Genetic mechanisms of fire blight resistance have mainly been studied using traditional biparental quantitative trait loci (QTL) mapping approaches. Here, we use large‐scale historic shoot and blossom fire blight data collected over multiple years and genotyping‐by‐sequencing (GBS) markers to identify significant marker–trait associations in a diverse set of 566 apple [Malus domestica (Suckow) Borkh. ] accessions. There was large variation in fire blight resistance and susceptibility in these accessions. We identified 23 and 38 QTL significantly (p < .001) associated with shoot and blossom blight resistance, respectively. The QTL are distributed across all 17 chromosomes of apple. Four shoot blight and 19 blossom blight QTL identified in this study colocalized with previously identified QTL associated with resistance to fire blight or apple scab. Using transcriptomics data of two apple cultivars with contrasting fire blight responses, we also identified candidate genes for fire blight resistance that are differentially expressed between resistant and susceptible cultivars and located within QTL intervals for fire blight resistance. However, further experiments are needed to confirm and validate these marker–trait associations and develop diagnostic markers before use in marker‐assisted breeding to develop apple cultivars with decreased fire blight susceptibility.
MicroRNA-34a-5p serves as a tumor suppressor by regulating the cell motility of bladder cancer cells through matrix metalloproteinase-2 silencing

Bladder cancer (BC), a common urologic cancer, is the fifth most frequently diagnosed tumor worldwide. hsa-miR-34a displays antitumor activity in several types of cancer. However, the functional mechanisms underlying hsa-miR-34a in BC remains largely unknown. We observed that hsa-mir-34a levels were significantly and negatively associated with clinical disease stage as well as regional lymph node metastasis in human BC. In a series of in vitro investigations, overexpression of hsa-miR-34a inhibited cell migration and invasion in BC cell lines 5637 and UMUC3 as detected by Transwell assays. We further found that hsa-miR-34a inhibited cell migration and invasion by silencing matrix metalloproteinase-2 (MMP-2) expression and thus interrupting MMP-2-mediated cell motility. Our analysis of BC datasets from The Cancer Genome Atlas database revealed a negative correlation between hsa-miR-34a and MMP-2. Moreover, higher MMP-2 protein expression was observed in the BC tissues when compared with that noted in the normal tissue. MMP-2 levels were also significantly associated with clinical disease stage and poor survival rate in human BC. These findings indicate that MMP-2 plays a critical role in regulating BC progression. Therefore, hsa-miR-34a is a promising treatment to target MMP-2 for the prevention and inhibition of cell migration and invasion in BC.
A Prospective Phase II Randomized Trial of Proton Radiotherapy vs. Intensity Modulated Radiotherapy for Patients with Newly Diagnosed Glioblastoma.

BACKGROUND To determine if proton radiotherapy (PT), compared to intensity modulated radiotherapy (IMRT), delayed time to cognitive failure in patients with newly diagnosed glioblastoma. METHODS Eligible patients were randomized unblinded to PT vs. IMRT. The primary endpoint was time to cognitive failure. Secondary endpoints included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported outcomes. RESULTS A total of 90 patients were enrolled and 67 were evaluable with median follow-up of 48.7 months (range 7.1-66.7). There was no significant difference in time to cognitive failure between treatment arms (HR, 0.88; 95% CI, 0.45 to 1.75; P=0.74). PT was associated with a lower rate of fatigue (24% vs. 58%, P=0.05), but otherwise there were no significant differences in patient-reported outcomes at 6 months. There was no difference in PFS (HR, 0.74; 95% CI, 0.44 to 1.23; P=0.24) or OS (HR, 0.86; 95% CI, 0.49 to 1.50; P=0.60). However, PT significantly reduced the radiation dose for nearly all structures analyzed. The average number of grade 2 or higher toxicities was significantly higher in patients who received IMRT (mean 1.15, range 0-6) compared to PT (mean 0.35, range 0-3; P=0.02). CONCLUSIONS In this signal seeking phase II trial, PT was not associated with a delay in time to cognitive failure but did reduce toxicity and patient reported fatigue. Larger randomized trials are needed to determine the potential of PT such as dose escalation for glioblastoma and cognitive preservation in patients with lower grade gliomas with a longer survival time.
GASC1 promotes glioma progression by enhancing NOTCH1 signaling

Recent studies have reported that gene amplified in squamous cell carcinoma 1 (GASC1) is involved in the progression of several types of cancer. However, whether GASC1 promotes glioma progression remains unknown. Therefore, the present study aimed to investigate the effect of GASC1 exposure on glioma tumorigenesis. The western blot demonstrated that grade III and IV glioma tissues exhibited a higher mRNA and protein expression of GASC1. Moreover, CD133+ U87 or U251 cells from magnetic cell separation exhibited a higher GASC1 expression. Invasion Transwell assay, clonogenic assay and wound healing assay have shown that GASC1 inhibition using a pharmacological inhibitor and specific short hairpin (sh)RNA suppressed the invasive, migratory and tumorsphere forming abilities of primary culture human glioma cells. Furthermore, GASC1-knockdown decreased notch receptor (Notch) responsive protein hes family bHLH transcription factor 1 (Hes1) signaling. GASC1 inhibition reduced notch receptor 1 (NOTCH1) expression, and a NOTCH1 inhibitor enhanced the effects of GASC1 inhibition on the CD133+ U87 or U251 cell tumorsphere forming ability, while NOTCH1 overexpression abrogated these effects. In addition, the GASC1 inhibitor caffeic acid and/or the NOTCH1 inhibitor DAPT (a γ-Secretase Inhibitor), efficiently suppressed the human glioma xenograft tumors. Thus, the present results demonstrated the importance of GASC1 in the progression of glioma and identified that GASC1 promotes glioma progression, at least in part, by enhancing NOTCH signaling, suggesting that GASC1/NOTCH1 signaling may be a potential therapeutic target for glioma treatment.
Determination of Trace Impurities in Graphite and Silicon Carbide by Total Reflection X-ray Fluorescence Spectrometry after Homogeneous Liquid–Liquid Extraction

Using homogeneous liquid-liquid extraction as a pre-concentration method, a determination orocedure of trace impurities (Fe, Ni and Cu) by total reflection X-ray fluorescence (TXRF) analysis was developed and optimized for graphite and silicon carbide samples. The samples were decomposed by alkali fusion. The residue was dissolved in a mixture of pentadeca-fluorooctanoic acid (PFOA), acetone and water, and the analytes were homogeneously dispersed by the aid of phenanthroline (phen). After phase separation with pH-adjustment, a portion of the sedimented water-immiscible liquid was pipetted on the polyester film that covered a silicon wafer sample-carrier. Then, the droplet was dried in a vacuum and analyzed by TXRF. Analytical values in the sub-ppm or ppm level were well agreed with the certified values of the standard samples or the values observed by ICP-OES for a few samples.
Very high coronary artery calcium (CAC ≥ 1000) and association with CVD events, non-CVD outcomes, and mortality: Results from the Multi-Ethnic Study of Atherosclerosis (MESA)

Background— There are limited data on the unique CVD, non-CVD, and mortality risks of primary prevention individuals with very high coronary artery calcium (CAC≥1000), especially in comparison to rates observed in secondary prevention populations. Methods— Our study population consisted of 6814 ethnically diverse individuals age 45-84 years, free of known CVD from the Multi-Ethnic Study of Atherosclerosis (MESA), a prospective, observational, community-based cohort. Mean follow-up time was 13.6±4.4 years. Hazard ratios of CAC≥1000 were compared to both CAC=0 and CAC 400-999 for CVD, non-CVD, and mortality outcomes using Cox proportional hazards regression adjusted for age, sex, and traditional risk factors. Using a sex-adjusted logarithmic model, we calculated event rates in MESA as a function of CAC, and compared to those observed in the placebo group of stable secondary prevention patients in the FOURIER clinical trial. Results— Compared to CAC 400–999, those with CAC≥1000 (N=257) had greater mean number of coronary vessels with CAC (3.4±0.5), greater total area of CAC (586.5±275.2 mm 2 ), similar CAC density, and more extensive extra-coronary calcification. After full-adjustment, CAC≥1000 demonstrated a 4.71-(3.63–6.11), 7.57-(5.50–10.42), 4.86-(3.32–7.11), and 1.94-fold (1.57–2.41) increased risk for all CVD events, all CHD events, hard CHD events, and all-cause mortality, respectively, compared to CAC=0 and a 1.65-(1.25–2.16), 1.66-(1.22–2.25), 1.51-(1.03–2.23), and 1.34-fold (1.05–1.71) increased risk compared to CAC 400–999. With increasing CAC, hazard ratios increased for all event types, with no apparent upper CAC threshold. CAC≥1000 was associated with a 1.95-(1.57–2.41) and 1.43-fold (1.12–1.83) increased risk for a first non-CVD event compared to CAC=0 and CAC 400–999, respectively. CAC=1000 corresponded to an annualized 3-point MACE rate of 3.4 per 100 person-years, similar to that of the total FOURIER population (3.3), and higher than lower risk FOURIER subgroups. Conclusions— Individuals with very high CAC (≥1000) are a unique population at substantially higher risk for CVD events, non-CVD outcomes, and mortality than those with lower CAC, and similar 3-point MACE rates as a stable treated secondary prevention population. Future guidelines should consider a less distinct stratification algorithm between primary vs. secondary prevention patients in guiding aggressive preventive pharmacotherapy.
On the joint role of non-Hispanic Black race/ethnicity and weight status in predicting postmenopausal weight gain

Objectives To determine how baseline weight status contributes to differences in postmenopausal weight gain among non-Hispanic Blacks (NHBs) and non-Hispanic Whites (NHWs). Methods Data were included from 70,750 NHW and NHB postmenopausal women from the Women’s Health Initiative Observational Study (WHI OS). Body Mass Index (BMI) at baseline was used to classify women as having normal weight, overweight, obese class I, obese class II or obese class III. Cox proportional hazards was used to estimate the hazard of a 10% or more increase in weight from baseline. Results In both crude and adjusted models, NHBs were more likely to experience ≥10% weight gain than NHWs within the same category of baseline weight status. Moreover, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain in both crude and adjusted models. Age-stratified results were consistent with overall findings. In all age categories, NHBs who were normal weight at baseline were most likely to experience ≥10% weight gain. Based on the results of adjusted models, the joint influence of NHB race/ethnicity and weight status on risk of postmenopausal weight gain was both sub-additive and sub-multiplicative. Conclusion NHBs are more likely to experience postmenopausal weight gain than NHWs, and the disparity in risk is most pronounced among those who are normal weight at baseline. To address the disparity in postmenopausal obesity, future studies should focus on identifying and modifying factors that promote weight gain among normal weight NHBs.