Miracle-dz/UniFAR-FTUs huggingface dataset:
Grief and Loss Among Veterans With Spinal Cord Injury: A Qualitative Study

Abstract Purpose The objective of this study was to understand veteran perspectives of grief/loss associated with their spinal cord injury (SCI). Design/Methods Qualitative descriptive design using semistructured interviews with veterans with SCI (n = 15) was performed using interview questions informed by the literature. Analysis was conducted using a deductive/inductive approach. Results The 15 participants’ mean age was 64 years; six had paraplegia, eight had tetraplegia, one had unknown level of injury, six were ambulatory, and nine were not ambulatory. The grief/loss experience was individual and constant, consisting of seven phases: experiencing shock, releasing emotion, withdrawing, focusing on losses, problem solving, realizing strength and motivation, and accepting a new life. Veteran coping strategies used in each phase of the grief experience were also identified, as well as triggers that increased or decreased the grief/loss experience. Conclusions/Clinical Relevance A better understanding of veterans living with SCI grief experience, coping strategies, and triggering events can help healthcare providers support veterans with SCI.
The Human Phenotype Ontology in 2021

Abstract The Human Phenotype Ontology (HPO, https://hpo.jax.org) was launched in 2008 to provide a comprehensive logical standard to describe and computationally analyze phenotypic abnormalities found in human disease. The HPO is now a worldwide standard for phenotype exchange. The HPO has grown steadily since its inception due to considerable contributions from clinical experts and researchers from a diverse range of disciplines. Here, we present recent major extensions of the HPO for neurology, nephrology, immunology, pulmonology, newborn screening, and other areas. For example, the seizure subontology now reflects the International League Against Epilepsy (ILAE) guidelines and these enhancements have already shown clinical validity. We present new efforts to harmonize computational definitions of phenotypic abnormalities across the HPO and multiple phenotype ontologies used for animal models of disease. These efforts will benefit software such as Exomiser by improving the accuracy and scope of cross-species phenotype matching. The computational modeling strategy used by the HPO to define disease entities and phenotypic features and distinguish between them is explained in detail.We also report on recent efforts to translate the HPO into indigenous languages. Finally, we summarize recent advances in the use of HPO in electronic health record systems.
Histone Variant H2A.J Marks Persistent DNA Damage and Triggers the Secretory Phenotype in Radiation-Induced Senescence

Irreparable double-strand breaks (DSBs) in response to ionizing radiation (IR) trigger prolonged DNA damage response (DDR) and induce premature senescence. Profound chromatin reorganization with formation of senescence-associated heterochromatin foci (SAHF) is an essential epigenetic mechanism for controlling the senescence-associated secretory phenotype (SASP). To decipher molecular mechanisms provoking continuous DDR leading to premature senescence, radiation-induced DSBs (53BP1-foci) and dynamics of histone variant H2A.J incorporation were analyzed together with chromatin re-modeling in human fibroblasts after IR exposure. High-resolution imaging by transmission electron microscopy revealed that persisting 53BP1-foci developed into DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS), consistently located at the periphery of SAHFs. Quantitative immunogold-analysis by electron microscopy revealed that H2A.J, steadily co-localizing with 53BP1, is increasingly incorporated into DNA-SCARS during senescence progression. Strikingly, shRNA-mediated H2A.J depletion in fibroblasts modified senescence-associated chromatin re-structuring and abolished SASP, thereby shutting down the production of inflammatory mediators. These findings provide mechanistic insights into biological phenomena of SASP and suggest that H2A.J inhibition could ablate SASP, without affecting the senescence-associated growth arrest.
Structure and Biochemical Characteristics of the Methyltransferase Domain of RNA Capping Enzyme from African Swine Fever Virus

African swine fever (ASF) is a highly contagious hemorrhagic viral disease in pigs that is caused by African swine fever virus (ASFV). There have been no effective drugs or vaccines for protection against ASFV infection until now. ABSTRACT African swine fever virus (ASFV) is a complex nucleocytoplasmic large DNA virus (NCLDV) that causes a devastating swine disease, and the development of effective anti-ASFV vaccines and drugs is urgently needed. The process of mRNA 5′-end capping is a common characteristic in eukaryotes and many viruses, and the cap structure is required for mRNA stability and efficient translation. The ASFV protein pNP868R was found to have guanylyltransferase (GTase) activity involved in mRNA capping. Here, we report the crystal structure of the pNP868R methyltransferase (MTase) domain (termed pNP868RMT) in complex with S-adenosyl-l-methionine (AdoMet). The structure shows the characteristic core fold of the class I MTase family, and the AdoMet is bound in a negative, deep groove. Remarkably, the N-terminal extension of pNP868RMT is ordered and far away from the AdoMet-binding site, distinct from the close conformation over the active site of the poxvirus RNA capping D1 subunit or the largely disordered conformation in most cellular RNA capping MTases. Structure-based mutagenesis studies based on the pNP868RMT-cap analog complex model revealed essential residues involved in substrate recognition and binding. Functional studies suggest that the N-terminal extension may play an essential role in substrate recognition instead of AdoMet binding. A positively charged path stretching from the N-terminal extension to the region around the active site was suggested to provide a favorable electrostatic environment for the binding and approaching of substrate RNA to the active site. Our structure and biochemical studies provide novel insights into the methyl transfer process of the mRNA cap catalyzed by pNP868R. IMPORTANCE African swine fever (ASF) is a highly contagious hemorrhagic viral disease in pigs that is caused by African swine fever virus (ASFV). There have been no effective drugs or vaccines for protection against ASFV infection until now. The protein pNP868R was predicted to be responsible for the process of mRNA 5′-end capping in ASFV, which is essential for mRNA stability and efficient translation. Here, we solved the high-resolution crystal structure of the methyltransferase (MTase) domain of pNP868R. The MTase domain structure shows a canonical class I MTase family fold, and the AdoMet binds into a negative pocket. Structure-based mutagenesis studies revealed critical and conserved residues involved in AdoMet binding and substrate RNA binding. Notably, both the conformation and the role in MTase activities of the N-terminal extension are distinct from those of the previously characterized poxvirus MTase domain. Our structure-function studies provide the basis for potential anti-ASFV inhibitor design targeting the critical enzyme.
ISOLATION and CHARACTERIZATION of MANGO PEEL PECTINS

An efficient method for manufacture of pectin from Totapuri mango peels was standardized by studying various factors that govern the recovery and quality of pectin. Among the different organic and inorganic acids, 0.05 N HCl was found to be the best for recovery of pectin from mango peels. Optimum yield of pectin was obtained by taking two extractions each for one-hour duration employing a peel: extractant ratio of 1:2 and by alcohol precipitation method. Dried mango peels could be stored for six months at ambient conditions (14.5-33.9C) without any significant effect on the recovery of pectin. Pectin extract, an intermediate product in the manufacture of pectin, could be stored for one month either at low temperature (6C +/- 2) or at ambient conditions (24.5-33.0C) by the addition of 700 ppm SO2 with minimum loss in the recovery of pectin. Using the optimum extracting conditions about 20.8% (DWB) of purified pectin was obtained from mango peels. The powdered pectin could be stored for over 6 months without any deterioration in quality when packed in airtight containers at ambient conditions.
New 1,3,4-Oxadiazole Derivatives of Pyridothiazine-1,1-Dioxide with Anti-Inflammatory Activity

Numerous studies have confirmed the coexistence of oxidative stress and inflammatory processes. Long-term inflammation and oxidative stress may significantly affect the initiation of the neoplastic transformation process. Here, we describe the synthesis of a new series of Mannich base-type hybrid compounds containing an arylpiperazine residue, 1,3,4-oxadiazole ring, and pyridothiazine-1,1-dioxide core. The synthesis was carried out with the hope that the hybridization of different pharmacophoric molecules would result in a synergistic effect on their anti-inflammatory activity, especially the ability to inhibit cyclooxygenase. The obtained compounds were investigated in terms of their potencies to inhibit cyclooxygenase COX-1 and COX-2 enzymes with the use of the colorimetric inhibitor screening assay. Their antioxidant and cytotoxic effect on normal human dermal fibroblasts (NHDF) was also studied. Strong COX-2 inhibitory activity was observed after the use of TG6 and, especially, TG4. The TG11 compound, as well as reference meloxicam, turned out to be a preferential COX-2 inhibitor. TG12 was, in turn, a non-selective COX inhibitor. A molecular docking study was performed to understand the binding interaction of compounds at the active site of cyclooxygenases.
Synovial Fluid Neutrophils From Patients With Juvenile Idiopathic Arthritis Display a Hyperactivated Phenotype

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. The predominant subtypes, oligoarticular and polyarticular JIA, are traditionally considered to be autoimmune diseases with a central role for T cells and autoantibodies. Mounting evidence suggests an important role for neutrophils in JIA pathogenesis. We undertook this study to investigate the phenotypic features of neutrophils present in the blood and inflamed joints of patients.
Cost-effectiveness analysis of magnetic resonance-guided focused ultrasound ablation for palliation of refractory painful bone metastases

Abstract Objective The aim of this study was to determine if magnetic resonance-guided focused ultrasound (MRgFUS) is cost-effective compared with medication, for refractory pain from bone metastases in the United States. Methods We constructed a Markov state transition model using TreeAge Pro software (TreeAge Software, Inc., Williamstown, MA, USA) to model costs, outcomes, and the cost-effectiveness of a treatment strategy using MRgFUS for palliative treatment of painful bone metastases compared with a Medication Only strategy (Figure 1). Model transition state probabilities, costs (in 2018 US$), and effectiveness data (quality-adjusted life-years [QALYs]) were derived from available literature, local expert opinion, and reimbursement patterns at two U.S. tertiary academic medical centers actively performing MRgFUS. Costs and QALYs, discounted at three percent per year, were accumulated each month over a 24-month time horizon. One-way and probabilistic sensitivity analyses were performed. Results In the base-case analysis, the MRgFUS treatment strategy costs an additional $11,863 over the 2-year time horizon to accumulate additional 0.22 QALYs, equal to a $54,160/QALY ICER, thus making MRgFUS the preferred strategy. One-way sensitivity analyses demonstrate that for the base-case analysis, the crossover point at which Medication Only would instead become the preferred strategy is $23,341 per treatment. Probabilistic sensitivity analyses demonstrate that 67 percent of model iterations supported the conclusion of the base case. Conclusions Our model demonstrates that MRgFUS is cost-effective compared with Medication Only for palliation of painful bone metastases for patients with medically refractory metastatic bone pain across a range of sensitivity analyses.
Association between Antibody Responses to Epstein-Barr Virus Glycoproteins, Neutralization of Infectivity, and the Risk of Nasopharyngeal Carcinoma

Epstein-Barr virus (EBV) is a human oncogenic gammaherpesvirus that infects over 90% of humans in the world and is causally associated with a spectrum of epithelial and B-cell malignancies such as nasopharyngeal carcinoma (NPC). A prophylactic vaccine against EBV is called for, but no approved vaccine is available yet. ABSTRACT While Epstein-Barr virus (EBV) is the major cause of nasopharyngeal carcinoma (NPC), the value of the humoral immune response to EBV glycoproteins and NPC development remains unclear. Correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC requires systematic study. Here, we applied a cytometry-based method and enzyme-linked immunosorbent assay to measure neutralization of infectivity and antibody response to EBV glycoproteins (gH/gL, gB, gp350, and gp42) of plasma samples from 20 NPC cases and 20 high-risk and 20 low-risk healthy controls nested within a screening cohort in Sihui, southern China. We found that NPC cases have similar plasma neutralizing activity in both B cells and epithelial cells and EBV glycoprotein-specific IgA and IgG antibody levels compared with those of healthy controls. Significant correlations were observed between gH/gL IgG and gB IgG and the neutralizing ability against EBV infection of epithelial cells and B cells. These results indicate that a high level of glycoprotein antibodies may favor protection against primary EBV infection, instead of being low-risk biomarkers for NPC in long-term EBV-infected adults. In conclusion, this study provides novel insights into the humoral immune response to EBV infection and NPC development, providing valuable leads for future research that is important for prevention and treatment of EBV-related diseases. IMPORTANCE Epstein-Barr virus (EBV) is a human oncogenic gammaherpesvirus that infects over 90% of humans in the world and is causally associated with a spectrum of epithelial and B-cell malignancies such as nasopharyngeal carcinoma (NPC). A prophylactic vaccine against EBV is called for, but no approved vaccine is available yet. Therefore, EBV remains a major public health concern. To facilitate novel vaccines and therapeutics for NPC, it is of great importance to explore the impact of humoral immune response to EBV glycoproteins before the development of NPC. Therefore, in this study, we systematically assessed the correlation between antiglycoprotein antibody levels, neutralization of EBV infectivity, and the risk of NPC development. These results provide valuable information that will contribute to designing effective prevention and treatment strategies for EBV-related diseases such as NPC.
The Microcellular Structure of Injection Molded Thick-Walled Parts as Observed by In-Line Monitoring

The aim of the study was to detect the influence of nitrogen pressure on the rheological properties and structure of PA66 GF30 thick-walled parts, produced by means of microcellular injection molding (MIM), using the MuCell® technology. The process was monitored in-line with pressure and temperature sensors assembled in the original injection mold. The measured data was subsequently used to evaluate rheological properties inside an 8.4 mm depth mold cavity. The analysis of the microcellular structure was related to the monitored in-line pressure and temperature changes during the injection process cycle. A four-times reduction of the maximum filling pressure in the mold cavity for MIM was found. At the same time, the holding pressure was taken over by expanding cells. The gradient effect of the cells distribution and the fiber arrangement in the flow direction were observed. A slight influence of nitrogen pressure on the cells size was found. Cells with a diameter lower than 20 µm dominate in the analyzed cases. An effect of reduction of the average cells size in the function of distance to the gate was observed. The creation of structure gradient and changes of cells dimensions were evaluated by SEM images and confirmed with the micro CT analysis.
Theory and Simulation of Gas Diffusion in Cholesteric Liquid Crystal Films

Abstract Theory and simulation of the dynamical phenomena that characterizes gas diffusion in a cholesteric film are presented. A classical mass transfer theory for cholesteric liquid crystals was used to construct a model that describes the one dimensional transient gas diffusion in a film. The boundary conditions that describe the concentration and orientation conditions in a gas-liquid crystal surface were obtained using the Euler-Lagrange equations for surface reorientations. Numerical solutions to the coupled mass transfer-orientation equations are presented and used to develop a comprehensive view of the phenomena. The main governing parameters that control gas diffusion in a cholesteric film are identified. Two different regimes are identified: (i) diffusion limited regime, and (ii) orientation limited regime. The diffusion limited regime is characterized by strong concentration-orientation couplings, enhanced mass transfer, and up-hill diffusion. The orientation limited regime is characterized by .
Perceived stress and associated factors among healthcare workers in a primary healthcare setting: the Psychological Readiness and Occupational Training Enhancement during COVID-19 Time (PROTECT) study.

INTRODUCTION Disease outbreaks such as the coronavirus disease 2019 (COVID-19) pandemic significantly heighten the psychological stress of healthcare workers (HCWs). The objective of this study was to understand the factors contributing to the perceived stress levels of HCWs in a public primary care setting during the COVID-19 pandemic, including their training, protection and support (TPS), job stress (JS), and perceived stigma and interpersonal avoidance. METHODS This cross-sectional study using an electronic self-administered questionnaire was conducted at the National Healthcare Group Polyclinics in March 2020. Data was collected anonymously. Analysis was performed using regression modelling. RESULTS The response rate was 69.7% (n = 1,040). The mean perceived stress level of HCWs in various departments ranged from 17.2 to 20.3. Respondents who reported higher perceived stress were those who made alternative living arrangements, were more affected by the current pandemic, reported higher JS and were Muslims. Respondents who reported lower perceived stress were those who had been through the severe acute respiratory syndrome epidemic in 2003 and H1N1 pandemic in 2009 as HCWs, and those who had higher confidence in the organisation's TPS. CONCLUSION All HCWs, regardless of scope of work, were similarly stressed by the current pandemic compared to the general population. Improving the confidence of HCWs in their training, protection and the support of personal protective equipment, and retaining experienced HCWs who can provide advice and emotional support to younger colleagues are important. Adequate psychological support for HCWs in the pandemic can be transformed into reserves of psychological resilience for future disease outbreaks.
Depression, smoking, and lung cancer risk over 24 years among women

Background Studies evaluating depression's role in lung cancer risk revealed contradictory findings, partly because of the small number of cases, short follow-up periods, and failure to account for key covariates including smoking exposure. We investigated the association of depressive symptoms with lung cancer risk in a large prospective cohort over 24 years while considering the role of smoking. Methods Women from the Nurses' Health Study completed measures of depressive symptoms, sociodemographics, and other factors including smoking in 1992 (N = 42 913). Depressive symptoms were also queried in 1996 and 2000, whereas regular antidepressant use and physician-diagnosed depression were collected starting in 1996. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) of lung cancer risk until 2016. Results We identified 1009 cases of lung cancer. Women with the highest v. lowest level of depressive symptoms had an increased lung cancer risk (HRsociodemographics-adjusted = 1.62, 95% CI 1.34–1.95; HRfully-adjusted = 1.25, 95% CI 1.04–1.51). In a test of mediation, lifetime pack-years of smoking accounted for 38% of the overall association between depressive symptoms and disease risk. When stratifying by smoking status, the elevated risk was evident among former smokers but not current or never smokers; however, the interaction term suggested no meaningful differences across groups (p = 0.29). Results were similar or stronger when considering time-updated depression status (using depressive symptoms, physician diagnosis, and regular antidepressant use) and chronicity of depressive symptoms. Conclusions These findings suggest that greater depressive symptoms may contribute to lung cancer incidence, directly and indirectly via smoking habits, which accounted for over a third of the association.
rHDL modeling and the anchoring mechanism of LCAT activation

Lecithin:cholesterol-acyl transferase (LCAT) plays a major role in cholesterol metabolism as it is the only extracellular enzyme able to esterify cholesterol. LCAT activity is required for lipoprotein remodeling and, most specifically, for the growth and maturation of HDLs. In fact, genetic alterations affecting LCAT functionality may cause a severe reduction in plasma levels of HDL-cholesterol with important clinical consequences. Although several hypotheses were formulated, the exact molecular recognition mechanism between LCAT and HDLs is still unknown. We employed a combination of structural bioinformatics procedures to deepen the insights into the HDL-LCAT interplay that promotes LCAT activation and cholesterol esterification. We have generated a data-driven model of reconstituted HDL (rHDL) and studied the dynamics of an assembled rHDL::LCAT supramolecular complex, pinpointing the conformational changes originating from the interaction between LCAT and apolipoprotein A-I (apoA-I) that are necessary for LCAT activation. Specifically, we propose a mechanism in which the anchoring of LCAT lid to apoA-I helices allows the formation of a hydrophobic hood that expands the LCAT active site and shields it from the solvent, allowing the enzyme to process large hydrophobic substrates.