jimnoneill/paper-to-field-training huggingface dataset:
Spliceosome Assembly Pathways for Different Types of Alternative Splicing Converge during Commitment to Splice Site Pairing in the A Complex

Differential splice site pairing establishes alternative splicing patterns resulting in the generation of multiple mRNA isoforms. This process is carried out by the spliceosome, which is activated by a series of sequential structural rearrangements of its five core snRNPs. To determine when splice sites become functionally paired, we carried out a series of kinetic trap experiments using pre-mRNAs that undergo alternative 5' splice site selection or alternative exon inclusion. We show that commitment to splice site pairing in both cases occurs in the A complex, which is characterized by the ATP-dependent association of the U2 snRNP with the branch point. Interestingly, the timing of splice site pairing is independent of the intron or exon definition modes of splice site recognition. Using the ATP analog ATPgammaS, we showed that ATP hydrolysis is required for splice site pairing independent from U2 snRNP binding to the pre-mRNA. These results identify the A complex as the spliceosomal assembly step dedicated to splice site pairing and suggest that ATP hydrolysis locks splice sites into a splicing pattern after stable U2 snRNP association to the branch point.

Topic: RNA Research and Splicing
Subfield: Molecular Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Electronic Medical Records National Data Asset

Data from hospital Electronic Medical Record (EMR) Systems is being transformed to an international gold standard Observational Medical Outcomes Partnership (<b>OMOP</b>) Common Data Model (CDM).Tools, mappings and experience gained will be made openly available, and a community of practice and a roadmap for continued national implementation will be built. The Data Asset will significantly improve the quality, accessibility and feasibility of EMR data warehouses by streamlining data governance, consent and ethics. We will convert three existing data warehouses from Queensland Health, Austin Health and Western Health so that they can be accessed through a common interface. Learnings from the <b>Cerner</b> conversions will then be applied to the conversion of other data warehouse platforms including the <b>EPIC</b> EMR system which will be investigated in collaboration with the Peter MacCallum Cancer Centre and the Royal Childrens Hospital.The dataset is based on Version 5.4 of the OMOP Common data model.Specifications of data model:https://ohdsi.github.io/CommonDataModel/cdm54.htmlIntegrated Data Governance, Digital Health, and the Common Data Model (OMOP-CDM)DOI:10.21203/rs.3.rs-3479039/v1Citation guidance here: https://ohdsi-australia.org/EMR2OMOP.html<br>

Topic: Infections and bacterial resistance
Subfield: Endocrinology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Aspirin Use and Colorectal Cancer Survival According to Tumor CD274 (Programmed Cell Death 1 Ligand 1) Expression Status

Purpose Blockade of the programmed cell death 1 (PDCD1, PD-1) immune checkpoint pathway can improve clinical outcomes in various malignancies. Evidence suggests that aspirin (a widely used nonsteroidal anti-inflammatory drug) not only prolongs colorectal cancer survival, but can also activate T cell–mediated antitumor immunity and synergize with immunotherapy through inhibition of prostaglandin E2 production. We hypothesized that the survival benefit associated with aspirin might be stronger in colorectal carcinoma with a lower CD274 (PDCD1 ligand 1, PD-L1) expression level that resulted in lower signaling of the immune checkpoint pathway. Patients and Methods Using data from 617 patients with rectal and colon cancer in the Nurses’ Health Study and the Health Professionals Follow-Up Study, we examined the association of postdiagnosis aspirin use with patient survival in strata of tumor CD274 expression status measured by immunohistochemistry. We used multivariable Cox proportional hazards regression models to control for potential confounders, including disease stage, microsatellite instability status, CpG island methylator phenotype, long interspersed nucleotide element-1 methylation, cyclooxygenase-2 (PTGS2), and CDX2 expression, and KRAS, BRAF, and PIK3CA mutations. Results The association of postdiagnosis aspirin use with colorectal cancer–specific survival differed by CD274 expression status ( P interaction &lt; .001); compared with aspirin nonusers; multivariable-adjusted hazard ratios for regular aspirin users were 0.16 (95% CI, 0.06 to 0.41) in patients with low CD274 and 1.01 (95% CI, 0.61 to 1.67) in patients with high CD274. This differential association seemed consistent in patients with microsatellite-stable or PIK3CA wild-type disease and in strata of PTGS2 expression, CDX2 expression, tumor-infiltrating lymphocytes, or prediagnosis aspirin use status. Conclusion The association of aspirin use with colorectal cancer survival is stronger in patients with CD274-low tumors than CD274-high tumors. Our findings suggest a differential antitumor effect of aspirin according to immune checkpoint status.

Topic: Cancer Immunotherapy and Biomarkers
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Feeling an outsider left in uncertainty – a phenomenological study on the experiences of older hospital patients

This paper starts from a care ethical perspective on care and reports on a phenomenological study into older patients’ experiences of hospitalisation. Although hospital care for older patients is at the centre of attention, questions what is at stake and what defines quality of care are rarely discussed with a view to the perspective of older patients themselves. The qualitative observational method of shadowing was used. Ten patients of 75 years old or older were shadowed from admission until discharge. The reflective lifeworld approach, based on phenomenological philosophy, was used to analyse the collected data. For the older patients included in the study, the essential meaning of hospitalisation can be described as feeling an outsider left in uncertainty . The word ‘left’ reveals how hospitalisation is experienced as a solitary struggle with various uncertainties that are related both to the hospital environment and to the patient's personal situation. The essential meaning is composed of the following three constituents: (i) staying in an inhospitable place, (ii) feeling constrained and (iii) experiencing disruption. The busy walking back and forth of care professionals and the functional character of involvement, restrain older patients from participating and make them feel abandoned. Feeling constrained reveals the feelings brought on by the ageing body which are emphasised by hospitalisation but often neglected by hospital staff. The failure of healthcare professionals to recognise and respond to who older patients are aside from their illness exacerbate the experience of disruptions. To improve care, hospital staff must be more sensitive to older patients’ uncertainties. Also, hospital staff should provide older patients with understandable information and explanation which besides offering patients the possibility to feel involved, meets their need for recognition.

Topic: Palliative Care and End-of-Life Issues
Subfield: Public Health, Environmental and Occupational Health
Field: Medicine
Domain: Health Sciences
Calculation of microdosimetric spectra for protons using Geant4-DNA and a <i>μ</i>-randomness sampling algorithm for the nanometric structures

Using Geant4-DNA to account for the stochastic nature of energy depositions due to physical interactions between radiation and matter, we calculated microdosimetry parameters concerning proton irradiation. By employing microdosimetry concepts in conjunction with simulation results of our previous work on radiation effects on the DNA, we pinpointed and quantified correlations between microdosimetry parameters and DNA damage. As such, for a volume with comparable mass and mean chord length to the DNA, we could observe the clear correspondence of the mean lineal and specific energy results with the double-strand-break yields of protons in Gy<sup>-1</sup>.Gbp<sup>-1</sup>.

Topic: Radiation Therapy and Dosimetry
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
A Case Report of Fragile X Syndrome with Fingers Anomaly

Fragile X Syndrome, the most common cause of inherited mental retardation, results from mutation in fragile X mental retardation gene (FMR1) on long arm of X chromosome, Xq27.3. Clinical features include moderate to severe mental retardation without neurologic deficit, long face, large ears, prominent jaw, macro-orchidism, attention deficit, behavior disorder and occasionally autistic behavior . Hyperextensible joints may also be seen in these patients. There is no other congenital malformation in fragile X syndrome. In this article we presented a 6 years old boy with fragile X syndrome who in addition to his characteristic clinical features had large thumbs and toes, which was disproportionate in size to his thumb nails and toe nails. In a case report from division of medical Genetics, Newyork Hospital in Cornell University, a twin brothers with fragile X syndrome also had cleft palate and ventricular septal defect . The diagnosis of this case was performed by culturing the patient’s peripheral blood lymphocytes in media lacking folate which expose the fragile X sites. The chromosomal analysis was performed using G-banding.

Topic: Genetics and Neurodevelopmental Disorders
Subfield: Genetics
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Comparison of eQTL Identification when using Single-end or Paired-\nend RNA-sequencing Data

RNA-sequencing of short 75-100 base pair reads is widely used by researchers to determine the expression levels of genes genome-wide in biological samples. Short read RNA-seq can be performed using paired-end (PE) or single-end (SE) sequencing, the former providing sequence from both ends of RNA fragments and therefore assumed to provide more accurate read alignments and estimates of gene expression. However, this assumption has not yet been fully tested in genetically diverse samples, and it is unclear how PE and SE RNA-seq agree or differ in their ability to detect expression quantitative trait loci (eQTL). To characterize these differences, we analyzed PE and SE RNA-seq data from 185 genetically diverse mouse embryonic stem cell lines mice to compare gene expression estimates and eQTL detections. Results show that genes uniquely identified by SE analysis were overrepresented for pseudogenes whereas genes uniquely identified by PE analysis were overrepresented for protein coding genes. Similar results were found in both expression and eQTL analysis. These results suggest that PE sequencing provides a more accurate alignment profile than SE sequencing, especially in diverse populations. Moreover, by limiting spurious read alignments to pseudogenes and correctly assigning more reads to more protein coding genes, PE sequencing results in fewer false positive eQTLs for pseudogenes and fewer false negative eQTLs for protein coding genes, and provides a more accurate understanding of gene regulatory variation compared to SE RNA-seq. Thus, we recommend that researchers use PE RNA-seq in eQTL mapping studies.

Topic: Genetic Mapping and Diversity in Plants and Animals
Subfield: Genetics
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Suicidality among homeless people: Testing the mediating effects of self-efficacy and depression

This cross-sectional study examined the mediating effect of PTSD on suicide ideation and suicide attempt through two mediators, self-efficacy and depression, among homeless adults. We recruited a non-random, purposive sample of 156 homeless adults from seven homeless people shelters in Kansas. SEM results suggest that self-efficacy and depression were significant mediators between PTSD and suicide ideation, but not between PTSD and suicide attempt. This study’s findings can be used to identify risk factors associated with suicidal behaviors that can be used to design service programs aimed at preventing suicidal ideation and attempt among people who are homeless.

Topic: Homelessness and Social Issues
Subfield: General Health Professions
Field: Health Professions
Domain: Health Sciences
The current status on secondary metabolites produced by fungi of the genus Diplodia associated with plants

Abstract Fungi of the genus Diplodia have a worldwide distribution and are typically associated with plants. Diplodia is well‐known for the diseases it causes on economically and ecologically relevant plants. In particular, this fungal genus is responsible of various symptoms of plant diseases, including shoot blights, dieback, cankers and fruit rots. In the last decades, literature concerning metabolites produced by Diplodia species has been significantly enriched by many reports dealing with the biosynthetic potential of this fungal genus. Several polyketide- and terpenoid-derived compounds have been reported, demonstrating the biosynthetic arsenal of this fungal genus. Investigations on the biological properties of compounds isolated from in vitro cultures of these fungi have proved a broad spectrum of biological functions. In particular, bioassays disclosed that antimicrobial and phytotoxic activities are the most notable bioactivities of secondary metabolites isolated from this genus. Hence, the present review is intended as reference guide to metabolites produced by fungi currently belong to the genus Diplodia , emphasizing the implication of their occurrence, absolute configuration determinations and the structure–activity relationships.

Topic: Plant Pathogens and Fungal Diseases
Subfield: Cell Biology
Field: Biochemistry, Genetics and Molecular Biology
Domain: Life Sciences
Mortalidad por desnutrición en Colombia durante la pandemia Covid19

Background and objectives: Malnutrition caused by low economic income is a social problem that involves malnutrition as a direct factor in increasing morbidity and mortality. Although malnutrition is considered a low prevalence event in Colombia, its impact is significant. Method: In this study, an ecological analysis was carried out using DANE data on mortality due to malnutrition in Colombia in 2020. Mortality rates per 100,000 people were calculated and compared according to sex and origin (departments). Findings: The results indicated that 1,756 people died from malnutrition in 2020, with a national mortality rate of 3.49 per 100,000 inhabitants. No significant variation in the rate was found. There were no significant differences in the rate according to sex. In Guainía, the mortality rate due to malnutrition was the highest, with 11.0 deaths per 100,000 inhabitants, while, in San Andrés, the rate was the lowest, with 1.57 deaths per 100,000 inhabitants. La Guajira registered the highest mortality rate due to malnutrition in the Caribbean region. Also, compared to the population of the Colombian capital, Bogotá, the population of the Colombian Caribbean presented a 4.62 times greater risk of death due to malnutrition. Conclusion: The findings highlight the importance of addressing the problem of malnutrition in Colombia, particularly in areas with high mortality rates. From an economic point of view, malnutrition has a significant impact on society. The premature death of people suffering from malnutrition means a loss of human and productive capital for the country. Furthermore, malnutrition can lead to disabilities and chronic diseases, which also have a negative impact on the economy.

Topic: Nutrition and Health in Aging
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Advance Directives for Patients With Breast Cancer: Applying the Right Info/Right Care/Right Patient/Right Time Oncology Model

Background Advance directives (AD) are an important component of life care planning for patients undergoing treatment for cancer; however, there are few effective interventions to increase AD rates. In this quality improvement project, the authors integrated AD counseling into a novel right info/right care/right patient/right time (4R) sequence of care oncology delivery intervention for breast cancer patients in an integrated health care delivery system. Methods The authors studied two groups of patients with newly diagnosed breast cancer who attended a multidisciplinary clinic and underwent definitive surgery at a single facility. The usual care (UC) cohort (N = 139) received care from October 1, 2019 to September 30, 2020. The 4R cohort (N = 141) received care from October 1, 2020 to September 30, 2121 that included discussing AD completion with a health educator prior to surgery. The authors used bivariate analyses to assess whether the AD intervention increased AD completion rates and to identify factors influencing AD completion. Results The UC and 4R cohorts were similar in age, gender, race/ethnicity, interpreter need, Elixhauser comorbidity index, National Comprehensive Cancer Network distress score ≥ 5, surgery type, stage, histology, grade, and Estrogen receptor/Progesterone receptor/ human epidermal growth factor receptor 2 (ER/PR/HER2) status. AD completion rates prior to surgery were significantly higher for the 4R vs UC cohort (73.8%, 95% confidence interval [CI] [66.5%-81.0%] vs 15.1%, 95% CI [9.2%-21.1%], p < .01) and did not significantly differ by age, race, need for interpreter, or distress scores. Conclusion Incorporation of a health educator discussion into a 4R care sequence plan significantly increased rates of time-sensitive AD completion.

Topic: Palliative Care and End-of-Life Issues
Subfield: Public Health, Environmental and Occupational Health
Field: Medicine
Domain: Health Sciences
Conceptions and values of the body in young adults of Northwestern Mexico / Concepciones y valoraciones del cuerpo en jóvenes del noroeste de México

Abstract Currently thinness is the ideal body (IB) while in western societies obesity has reached levels never seen before. This situation has influenced how men and women perceive their bodies. The aim of this paper was to describe conceptions and values of the IB as well as the perception and acceptance of the body in university students from the northwestern Mexico, a sociocultural context where obesity prevails. From a socio-anthropological approach, we worked with 308 university students among 18 and 24 years old (202 women and 106 men). The construct of IB matches with the socially accepted discourse based on aesthetic and health values. In general, participants expressed moderated body dissatisfaction and rejected obesity; the IB for women was slim, firm and curved while for men was muscled. Therefore, a gap was identified between what women and men want and perceive of their body image and self-acceptance, with clear differences by sex. Resumen Mientras que la delgadez actualmente constituye el ideal corporal (IDC) preponderante en las sociedades occidentales, la obesidad prevalece con niveles nunca antes vistos. Esto ha influido en cómo hombres y mujeres se perciben y viven su cuerpo. El objetivo de este estudio fue describir las concepciones y valoraciones del IDC y la percepción y aceptación del propio cuerpo en jóvenes universitarios del noroeste de México, un contexto sociocultural en el que prevalece la obesidad. A partir de una perspectiva socio-antropológica, se trabajó con 308 jóvenes universitarios, de entre 18 y 24 años de edad (202 mujeres y 106 hombres). La construcción del IDC en los jóvenes concuerda con el discurso aceptado y difundido socialmente, basado en valoraciones estéticas y de salud. En general, los jóvenes expresaron moderada insatisfacción corporal y rechazo de la obesidad; mientras que el IDC fue delgado y firme, curvilíneo para las mujeres, en tanto que fuerte y musculoso para los hombres. Por tanto, se identificó un desfase entre lo que ellos y ellas desean, lo que perciben de su imagen corporal y la propia aceptación, con claras diferencias por sexo.

Topic: Eating Disorders and Behaviors
Subfield: Clinical Psychology
Field: Psychology
Domain: Social Sciences
469 Efficacy of Biofeedback Therapy for Dyssynergic Constipation Among Elderly Patients

INTRODUCTION: The prevalence of constipation among older adults is estimated to be as high as 40% (Melton et al, 1996). Dyssynergic defecation (DD) is an important cause of constipation for a large proportion of these patients. While biofeedback (BFB) therapy has been shown to be highly effective in correcting DD, it involves operant conditioning which requires learning new techniques and few studies have looked at how older adults respond to BFB. METHODS: This is a retrospective analysis of age 65+ patients enrolled in BFB for DD between 2015 to 2018 at a tertiary referral motility program. For patients that had greater than two sessions, survey and high resolution anorectal manometry (HR-ARM) data were collected at baseline and during each BFB visit. 58 patients met criteria. ARM is utilized with sensors in the rectum and anal canal. Stool retention simulation is performed involving inflation of a rectal balloon during the BFB sessions. RESULTS: Patients described improvement in several meaningful clinical outcomes. The overall median education level was completed high school and some college. Mean global bowel satisfaction on a scale of 1 (very dissatisfied) to 10 (very satisfied) showed a statistically significant increase, 2.77 to 5.01 with BFB ( P ≤ 0.0001). In addition, the important symptom of a feeling of incomplete evacuation after stooling decreased from 95% down to 24% ( P = 0.0025). Most significantly, 79% of the age 65+ patients showed resolution of their dysyynergia on HR-ARM at their final session ( P = 0.0006). The defecation index (DI), intrarectal pressure divided by intra-anal pressure during simulated defecation, also trended towards improvement (0.564 to 0.681, P = 0.12). In terms of types of dyssynergia (1 through 4), subjects with defects in both propulsion and paradoxical contraction of sphincter muscles during defecation, i.e. type 2 dyssynergia, showed the most substantial objective gains in defecation index, with an average increase of 0.486, P -value 0.01 (2 vs 1) and 0.02 (2 vs 3). CONCLUSION: Biofeedback for DD shows meaningful improvement in both patient reported outcomes and objective manometric parameters in older adults. This is an important finding because our data supports the efficacy of BFB among older adults, across all levels of education. Given the profound burden of constipation with DD in older adults, we propose biofeedback therapy continue to be given strong consideration as first line therapy for this population.

Topic: Pelvic floor disorders treatments
Subfield: Rheumatology
Field: Medicine
Domain: Health Sciences
STUDIES ON THE EFFECTS OF MARINE PRODUCTS ON CHOLESTEROL METABOLISM-I

Some kinds of edible seaweeds are believed to have a favorable effect upon cholesterol metabolism. To prove the point, rats were fed ad libitum for 10 weeks with diet prepared for this purpose. The diet contained, at the rate of 5 per cent, green laver (Enteromorpha compressa), tangle (Laminaria japonica) or purple laver (Porphyra tenera) each dried and pulverized, with exogenous cholesterol. As shown in Table 4, the green and purple lavers could fairly reduce the plasma cholesterol. However, the tangle showed no effects. The seaweeds tested were not effective to reduce the liver cholesterol of the rats.

Topic: Fatty Acid Research and Health
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences