Miracle-dz/UniFAR-FTUs huggingface dataset:
Association analysis of the surfactant protein-C gene to childhood asthma

Abstract Objectives This study aims to describe the molecular variability in the SFTPC gene in a childhood chronic respiratory disease, asthma, in the Tunisian population and to identify the implications based on a case-control study of p.Thr138Asn (T138N) and p.Ser186Asn (S186N) variants. Methods We used direct sequencing for the genotyping of the SFTPC gene within 101 asthmatic children. The study of T138N and S186N variants in 110 controls is conducted by the PCR-RFLP technique. Results The molecular study revealed 26 variants including 24 intronic variations and 2 exonic variations (T138N and S186N) with respective frequencies of 16.8% and 18.3%. We conducted a case-control study of the two identified exonic variations. A different genotypic and allelic distribution between the two groups was noted. Only the T138N polymorphism showed a significant association with asthma disease (p < 1 0 −3). Statistical analysis elaborated four haplotypes with the following frequencies in patients vs controls: 138Thr-186Ser (79.5% vs 57.6%), 138Thr-186Asn (3.7% vs 7.8%), 138Asn-186Thr (2.2% vs 20.2%) and 138Asn-186Asn (14.6% vs 14.4%). A significant difference (p < 1 0 −3) was highlighted in haplotype distribution. The 138Asn-186Ser (OR [95%CI] = 0.14[0.04-0.54], p = 0.004, R2=0.93) and 138Thr-186Asn (OR [95%CI] = 0.35[0.12-0.54], p = 0.047, R2=0.88) haplotypes showed a negative association with asthma which may constitute a protective factor against the disease. Conclusion In Tunisia, this work constitutes the first report interested in the SFTPC gene and highlights the genetic variability of the SFTPC gene in asthma. Therefore, the case-controls analysis may be useful in the study of surfactant proteins dysfunction in chronic respiratory disease at an early age.
Assessing the Necessity of Routine Crossmatching for Blood Transfusion in Renal Transplantation

Introduction: Routine crossmatch of packed red blood cells (pRBCs) is completed preoperatively at many centers despite conflicting evidence on the incidence of blood transfusions with renal transplantation. In the current economic climate, resource adjudication should be judicious and medically appropriate. The objective of this study was to determine the incidence, timing, and predictors of early postoperative pRBC transfusion in patients undergoing renal transplantation. Methods: A retrospective review of all patients undergoing renal transplantation at our institution from January 2013 to May 2016 was performed. Demographic, biochemical, and clinical parameters were recorded. The primary outcome was early postoperative transfusion, defined as an intraoperative transfusion or within 2 days of surgery. Multivariable logistic regression was performed to identify associations with early postoperative transfusion. Results: We identified 428 patients during the study period (average age 55 years, 60% male, 30% obese, 67% deceased donor, and 43% preoperative antithrombotic use). Forty (9.3%) patients required early postoperative transfusion (mean: 2.8 pRBCs/transfusion) and most did not require blood urgently. Only 20 (4.7%) patients required a transfusion intraoperatively or on the same day of surgery. Lower preoperative hemoglobin (per g/L unit: odds ratio [OR]: 0.943), female gender (OR: 2.752), and preoperative antithrombotic use (OR 2.369) were associated with a need for early postoperative transfusion. Conclusion: Transfusion in the early postoperative period following renal transplantation was less than 10%, suggesting that routine crossmatch may not be necessary for all patients. Preoperative hemoglobin, female gender, and preoperative antithrombotic use were associated with increased risk and may be useful to risk-stratify patients who require crossmatch.
X chromosome studies and breast and ovarian carcinoma

Skewed somatic X inactivation (XCI), X-linked gene overexpression and abnormal X content have been associated with breast and ovarian cancer. Partial or complete reactivation of the inactive X in females may be a step in breast and ovarian cancer progression, leading to overexpression of some tumour enhancing gene. Markers of an X reactivation event were examined: X gene dosage, expression, and methylation in 8 ovarian cancer cell lines. Another marker of an X reactivation event, skewed XCI, was assayed in peripheral blood DNA from 106 breast and/or ovarian cancer patients (52 BRCA1 mutation carriers, 24 BRCA2 mutation carriers, 30 non-mutation carriers), 147 age-matched population controls. Combined RNA/DNA FISH was used to quantify the number of inactive Xs compared to total number of Xs. Five cell lines had increased X content. Three cell lines localized XIST to the presumptive inactive X; however the numbers of inactive Xs were variable. Expression levels of 8 X-linked genes were assessed by real-time PCR. Expression was inconsistent between different genes and among cell lines, ranging from a 2 to 300-fold increase compared to a control. Overall, expression was greatly increased for genes subject to inactivation but not increased in genes that escape inactivation for most ovarian cancer cell lines. Methylation at AR and FMR1 was quantified by a real-time PCR based assay and SNuPE respectively. Methylation was lower than expected for 7 of 8 ovarian cancer cell lines at AR or FMR1, while three cell lines had low or no methylation for both genes. Skewed XCI was evaluated using a methylation-based PCR assay at AR. There was no significant increase in skewing above 90% for any cancer group assayed. In addition, we assayed two
Improvement in parameters of quality of life and uterine volume reduction after uterine fibroid embolization

ABSTRACT Objective To evaluate improvement in quality of life, reduction of uterine volume, and the correlation between these two variables after uterine fibroid embolization. Methods Data on quality of life before and after uterine fibroid embolization were collected from 60 patients using the Uterine Fibroid Symptom – Quality of Life questionnaire. In 40 of these patients, uterine volume information on magnetic resonance imaging examinations performed before and after uterine fibroid embolization was collected, and compared using the nonparametric Wilcoxon test for paired data. Correlation between quality of life and uterine volume before and after procedure was measured using Spearman’s correlation coefficient. Results There was significant improvement in quality of life after uterine fibroid embolization on Uterine Fibroid Symptom – Quality of Life questionnaire, in both subscales scores and the total score. There was a significant median reduction of -37.4% after uterine fibroid embolization, but no correlations between uterine volume and quality of life scores were found before or after embolization. Conclusion Uterine embolization is an alternative to treat uterine fibroids, resulting in relief of symptoms and better quality of life. Although reduction in uterine volume plays an important role in the evaluation of therapeutic success, it does not necessarily have a definitive correlation with relief of symptoms.
High Prevalence of Falls Independent of Age in Adults Living With Chronic Pain

Supplemental Digital Content is available in the text. Objectives: High risks of falls have been reported in older adults with chronic pain but chronic pain similarly affects adults of all ages. This cross-sectional study aimed to determine the prevalence of falls and associated risk factors in adults of all ages living with chronic pain. Materials and Methods: Patient-reported data were analyzed from 591 adults with chronic pain enrolled in a local pain clinic between November 2017 and April 2019. Sociodemographic, history of falls, and biopsychosocial measures of pain were examined to identify and describe adults with chronic pain who fell in the previous year. Factors associated with falls were examined using logistic regression. Results: A total of 268 (45%) reported at least 1 fall in the previous year (fallers) where 194 (33%) fell in the previous 3 months, and 185 (31%) had multiple falls. The prevalence of falls in the previous year was over 37% across age groups. Overall, fallers were older, had greater pain severity and interference, lower physical function and pain self-efficacy, greater depression, more reported neuropathic pain, and had more pain sites compared with nonfallers. Number of pain sites reported (odds ratio=1.12; 95% confidence interval, 1.02-1.22) and lower physical function (odds ratio=0.96; 95% confidence interval, 0.94-0.99) were independently associated with falls. Discussion: A high prevalence of falls was found independent of age for adults with chronic pain. Although the risk of falls may increase with age, lower physical function and more pain sites are better indicators for falls. A better understanding of circumstances and consequences of falls in all adults with chronic pain is warranted.
Linking drought-induced xylem embolism resistance to wood anatomical traits in Neotropical trees.

Drought-induced xylem embolism is considered to be one of the main factors driving mortality in woody plants worldwide. Although several structure-functional mechanisms have been tested to understand the anatomical determinants of embolism resistance, there is a need to study this topic by integrating anatomical data for many species. We combined optical, laser, and transmission electron microscopy to investigate vessel diameter, vessel grouping, and pit membrane ultrastructure for 26 tropical rainforest tree species across three major clades (magnoliids, rosiids, and asteriids). We then related these anatomical observations to previously published data on drought-induced embolism resistance, with phylogenetic analyses. Vessel diameter, vessel grouping, and pit membrane ultrastructure were all predictive of xylem embolism resistance, but with weak predictive power. While pit membrane thickness was a predictive trait when vestured pits were taken into account, the pit membrane diameter-to-thickness ratio suggests a strong importance of the deflection resistance of the pit membrane. However, phylogenetic analyses weakly support adaptive co-evolution. Our results emphasize the functional significance of pit membranes for air-seeding in tropical rainforest trees, highlighting also the need to study their mechanical properties due to the link between embolism resistance and pit membrane diameter-to-thickness ratio. Finding support for adaptive co-evolution also remains challenging.
‘Employ Your Mind’: a pilot evaluation of a programme to help people with serious mental illness obtain and retain employment

Objective: Cognitive impairments contribute to difficulty in obtaining employment for people with severe mental illnesses (SMIs). We describe a pilot evaluation of a programme, Employ Your Mind (EYM), which integrates cognitive remediation therapy (CRT) with vocational rehabilitation. Method: Sixty participants with SMIs enrolled in EYM, a 6-month programme that combines CRT exercises, individual project work and group reflection sessions about social interaction and cognitive functioning. Participants completed assessments of cognitive function (Audio Recorded Cognitive Screen, Wechsler Digit Span Task), psychosocial function (Work and Social Adjustment Scale, General Self-Efficacy Scale) and abilities related to work (Dialogue about Working Ability, Self-Assessment of Thinking Skills) at baseline and postprogramme. Paired t-tests were used to compare assessments of participants who completed the programme between the two time points. Results: The programme was completed by 22 individuals. These individuals demonstrated significant improvement in cognitive function, social and work-related function, and subjective thinking ability after completing the EYM programme. Conclusion: The EYM programme is effective in improving cognition, impairments related to work and social function, and subjective thinking skills for some individuals with SMIs. Future evaluation of the programme should focus on enhanced retention and assessment of employment outcomes.
Metabolic Diversity and Therapeutic Potential of Holarrhena pubescens: An Important Ethnomedicinal Plant

Holarrhena pubescens is an important medicinal plant of the Apocynaceae family that is widely distributed over the Indian subcontinent. The plant is extensively used in Ayurveda and other traditional medicinal systems without obvious adverse effects. Beside notable progress in the biological and phytochemical evaluation of this plant over the past few years, comprehensive reviews of H. pubescens are limited in scope. It has economic importance due to the extensive use of seeds as an antidiabetic. Furthermore, the plant is extensively reported in traditional uses among the natives of Asia and Africa, while scientifical validation for various ailments has not been studied either in vitro or in vivo. This review aims to summarize information on the pharmacology, traditional uses, active constituents, safety and toxicity of H. pubescens. Chemical analysis of H. pubescens extracts revealed the presence of several bioactive compounds, such as conessine, isoconnessine, conessimine, conimine, conessidine, conkurchicine, holarrhimine, conarrhimine, mokluangin A-D and antidysentericine. Overall, this review covers the ethnopharmacology, phytochemical composition, and pharmacological potential of H. pubescens, with a critical discussion of its toxicity, biological activities (in vitro and in vivo), the mechanism of action, as well as suggestions for further basic and clinical research.
Cardboard floor: about the barriers for social progression and their impact on the representativeness of epidemiological studies

A continuum of socioeconomic status ranging from the least to the most privileged persons is evidenced in population studies, with profound implications for health and care.1 Individuals in the most disadvantaged social group suffer from extreme poverty and face several specific challenges to their health and healthcare.2 They frequently cannot meet their most basic needs (including their physiological needs, most acutely exemplified by homelessness) and are at a higher risk of health problems and accelerated ageing due to unhealthy habits (eg, unhealthy diet and drug consumption), harmful environmental and biological factors and social isolation.1–4 As a result, the most socially disadvantaged persons have higher rates of premature mortality, especially caused by suicide and violence, and higher prevalence of all types of diseases, particularly infectious diseases and mental disorders.2 5 Besides, care for chronic conditions is compromised for this population group, which relies to a substantial degree in emergency care, particularly in health systems that do not guarantee universal health coverage.5 Even considering the relative size of the most deprived extreme of the social continuum (eg, about 0.5% of the UK adult population in 2018 was considered homeless),6 the scale of …
Toward a More Valid Assessment of Behavioral Aggression: An Open Source Platform and an Empirically Derived Scoring Method for Using the Competitive Reaction Time Task (CRTT)

While the Competitive Reaction Time Task (CRTT) is the most used behavioral aggression paradigm, it is characterized by methodological heterogeneity and quantification strategies for its’ outcome are unstandardized. Therefore, the standards of measuring aggression should be improved. This article contributes on such an improvement by providing: (a) a freely available CRTT online administration program, and (b) a factor-analytically derived scoring method. Based on a combined sample (n = 423), a two-factor model was fit to the 30-trial CRTT version. The first factor included all trial scores subsequent to the first time the participant received aversive feedback (i.e., provoked factor) and the second factor included all trial scores prior to this first aversive feedback (i.e., unprovoked factor). Construct validity was evidenced based on the factors` differential relationship with self-reported aggression and narcissism. Our factor analytic findings empirically support the superiority of one of the existing CRTT scoring methods, that is, separately averaging all preprovocation versus all postprovocation trials. We discuss practical recommendations for CRTT users and outline future empirical avenues. This article aims at stimulating joint efforts to move toward standardization of CRTT implementation and outcome measure analysis.
COPD 2020: Changes and Challenges.

Alvar Agustı́, Claus Vogelmeier, and Rosa Faner Respiratory Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain; CIBER Enfermedades Respiratorias, Barcelona, Spain; Chair of the Board of Directors, Global Initiative for Chronic Obstructive Lung Disease (GOLD), Fontana, Wisconsin; Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Center for Lung Research (DZL), Marburg, Germany; and Chair of the Science Committee, Global Initiative for Chronic Obstructive Lung Disease (GOLD), Fontana, Wisconsin
Activity of NEO2734, a novel dual inhibitor of both BET and CBP-P300, in SPOP-mutated prostate cancer.

62 Background: We have previously reported that mutations in SPOP promote bromodomain and extra-terminal motif (BET) protein upregulation and BET inhibitor resistance in prostate cancer (Zhang et al., Nature Medicine 23(9):1055-1062, 2017). Other studies indicate that histone acetyltransferases (HATs) such as P300 are also upregulated in SPOP-mutated prostate cancer (Blattner et al., Cancer Cell 31: 436-451, 2017). Methods: We examined the anti-cancer effect of NEO2734 (Epigene Therapeutics Inc), a novel dual inhibitor of both BET and CBP-P300, in prostate cancer using cell line, organoid and patient-derived xenografts (PDX) as working models. We examined the anti-cancer effect of NEO2734 (Epigene Therapeutics Inc), a novel dual inhibitor of both BET and CBP-P300, in prostate cancer using cell line, organoid and patient-derived xenografts (PDX) as working models. Results: We demonstrated that while prostate cancer cell lines expressing F133V, the most frequent SPOP mutant, are very resistant to both BET inhibitor JQ1 and CBP/P300 inhibitor CPI-637, they are very sensitive to simultaneous cotreatment with JQ1 and CPI-637. Similarly, we demonstrated that F133V mutant cells are also very sensitive to NEO2734. We established PDX and organoid models from a patient with prostate cancer expressing a novel SPOP mutation Q165P. Computer simulation analysis reveals that the Q165P mutation causes larger conformational fluctuation, indicating that the structure of Q165P is less stable than that of wild type SPOP. Accordingly, co-immunoprecipitation assay showed that Q165P mutation impaired the dimerization ability of SPOP. We further showed that the Q165P mutant organoid was very sensitive to NEO2734 in vitro and the Q165P mutant PDX was very sensitive to NEO2734 in mice. Conclusions: These PDX-based pre-clinical studies indicate that the inhibition of both BET and CBP-P300, either by co-administration of two agents, or by treatment with the dual inhibitor, NEO2734, is effective in SPOP-mutated prostate cancer. These data provide a strong rationale for the inclusion of patients with SPOP-mutated prostate cancer in clinical studies of NEO2734.
Age-related hamster mitochondrial changes and oocyte changes following autologous platelet mitochondrial microinjection

AGE-RELATED HAMSTER MITOCHONDRIAL CHANGES AND OOCYTE CHANGES FOLLOWING AUTOLOGOUS PLATELET MITOCHONDRIAL MICROINJECTION Fang Li Old Dominion University, 2011 Director: Dr. R. James Swanson This study's objective was to verify age-related mitochondrial changes in oocytes from old hamsters compared with those from young hamsters. We used autologous platelet mitochondrial microinjection to improve the mitochondrial quality and quantity of aged oocytes to improve their pregnancy potential. Metaphase II oocytes were collected from super-ovulated female hamsters and prepared for biochemical and morphological analysis. Adenosine triphosphate (ATP) levels, mitochondrial DNA (mtDNA) number, reactive oxygen species (ROS) level and mitochondrial membrane potential (MMP) were determined in individual oocytes from young and old hamsters. Transmission electron microscopy (TEM) allowed evaluation of oocyte ultra-structure. In oocytes from old hamsters, ATP levels and mtDNA number were reduced an average of 35.4% and 51.8% respectively compared to young oocytes. Lower MMP and higher ROS levels were observed in oocytes from old hamsters compared with those from young hamsters. TEM analysis supported low mitochondrial quantity and increased mitochondrial electron density in old oocytes, along with collapsed cytoplasmic lamellae. When comparing platelet mitochondria between young and old hamsters, no significant difference was found in ATP level per mitochondrion or ultrastructure. After autologous platelet mitochondrial microinjection, ATP production increased significantly in the microinjected group, however mtDNA number and embryo development to blastocyst stage were not improved. MitoTracker Green FM (MGF) was used to help quantify mitochondria, but the results conflicted with mtDNA and TEM data, which suggests that MGF, as a MMP dependent reagent, is not an ideal method to reflect mitochondrial number. Our data suggest that (1) age-related morphological and functional mitochondrial changes occur in oocytes from old hamsters compared with young hamsters; (2) platelets can be used as a source for mitochondrial transfer; and (3) autologous platelet mitochondrial microinjection improves mitochondrial ATP production in old oocytes. The fact that no change in blastocyst development after microinjection was observed does not rule out that there might not be improvement of post-implantation embryo development. Therefore, further study will focus on effect of autologous platelet mitochondrial microinjection on post-implantation embryo development.
A comparative study of craniofacial measurements between Ryukyuan and mainland Japanese females using lateral cephalometric images

Using lateral cephalometric images, we compared the skeletal and soft tissue configurations of Ryukyuan and mainland Japanese females. We collected lateral cephalometric images of 30 females each from Okinawa Island and mainland Japan. Sixty landmarks were plotted on each image. Then, based on the coordinates of the landmarks, 68 distances and 34 angles were calculated according to orthodontic and anthropometric methods. We confirmed that the Ryukyuans have a smaller height in the upper and midfacial region than the mainland Japanese. Moreover, our findings indicate that, compared with the mainland Japanese females, the Ryukyuan females clearly have the following features: (1) a shallower mandibular notch, (2) an anterior-inclined symphysis of mandible, and (3) a smaller depth from upper lip to incisors. We also found that an anterior-inclined mandibular corpus and incisors are associated with a smaller distance between the surfaces of the upper lip and teeth and with a more protruded lip shape.