Miracle-dz/UniFAR-FTUs huggingface dataset:
Preclinical evaluation of exemestane as a novel chemotherapy for gastric cancer

CYP19A1/aromatase (Ar) is a prognostic biomarker of gastric cancer (GCa). Ar is a critical enzyme for converting androstenedione to oestradiol in the steroidogenesis cascade. For decades, Ar has been targeted with Ar inhibitors (ARIs) in gynaecologic malignancies; however, it is unexplored in GCa. A single‐cohort tissue microarray examination was conducted to study the association between Ar expression and disease outcome in Asian patients with GCa. The results revealed that Ar was a prognostic promoter. Bioinformatics analyses conducted on a Caucasian‐based cDNA microarray databank showed Ar to be positively associated with GCa prognosis for multiple clinical modalities, including surgery, 5‐Fluorouracil (5‐FU) for adjuvant chemotherapy, or HER2 positivity. These findings imply that targeting Ar expression exhibits a potential for fulfilling unmet medical needs. Hence, Ar‐targeting compounds were tested, and the results showed that exemestane exhibited superior cancer‐suppressing efficacy to other ARIs. In addition, exemestane down‐regulated Ar expression. Ablating Ar abundance with short hairpin (sh)Ar could also suppress GCa cell growth, and adding 5‐FU could facilitate this effect. Notably, adding oestradiol could not prevent exemestane or shAr effects, implicating a nonenzymatic mechanism of Ar in cancer growth. Regarding translational research, treatment with exemestane alone exhibited tumour suppression efficacy in a dose‐dependent manner. Combining subminimal doses of 5‐FU and exemestane exerted an excellent tumour suppression effect without influencing bodyweight. This study validated the therapeutic potentials of exemestane in GCa. Combination of metronomic 5‐FU and exemestane for GCa therapy is recommended.
Evaluating PAD Requests in Psychiatry: The Importance of Involving Others

Kious and Battin (2019) explore the tension between physician-assisted dying (PAD) and prevention of suicide in psychiatry, and argue for the need for standards by which the severity of a person ’ s mental as well as phys-ical suffering could be evaluated in order to assess eligi-bility for PAD. We agree that a thorough evaluation is needed, but rather than standards, we argue that a pru-dent process is necessary in order to deal with the com-plexities around PAD in psychiatry. In this process, involving others is of vital importance. In our elabor-ation, we refer to the revised Dutch guideline for PAD in psychiatry, published by the Dutch Association for Psychiatry in 2018, as this guideline stresses that the assessment of a PAD request in psychiatry requires active involvement of the patient, other professionals, and family members (Dutch Association for Psychiatry 2018).
A Mechanism Study of Electroacupuncture for Dry Eye Syndrome by Targeting Conjunctival Cytokine Expressions

ABSTRACT Aim: To discuss the immunological mechanism in electroacupuncture (EA) treatment of dry eye syndrome (DES) by targeting the changes in conjunctival cytokine expression profile. Method: Eligible DES patients were randomized into an EA group (EAG) or an acupuncture group (AG). The ocular surface disease index (OSDI), amount of tear production, and tear film break-up time (BUT) were observed to evaluate the efficacy. Conjunctival cells were collected from both effective and invalid cases to observe the expressions of cytokines by protein microarray. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used for functional cluster and signaling pathway analysis of the differentially expressed proteins. Enzyme-linked immunosorbent assay (ELISA) was used to verify the specific differential proteins. Result: After treatment, OSDI dropped and BUT extended in both groups, and the tear production increased only in the EAG (all P < .01). Compared with the AG, the improvement in tear production was more significant in the EAG (P < .01). There were 17 differentially expressed conjunctival cytokines between the effective and invalid cases in the EAG, and those expressed higher than the limit of detection (LOD) included monocyte chemoattractant protein 1 (MCP-1), macrophage colony-stimulating factor (M-CSF), regulated on activation in normal T-cell expressed and secreted (RANTES) and tissue inhibitor of metalloproteinases 1 (TIMP-1). GO analysis showed that the differential cytokines were mainly involved in cellular interaction, signaling pathways and reactions to stimuli. KEGG analysis revealed that the signaling pathways of these cytokines were mainly responsible for interactions between cytokines or between cytokines and their receptors, such as Jak-STAT signaling pathway, chemokine signaling pathway, and tumor necrosis factor signaling pathway. Conclusion: EA can effectively treat DES by improving the symptoms, increasing tear secretion and extending BUT, which is possibly related to its regulation on the conjunctival cytokine expressions.
Posterior Pelvic Tilt From Supine to Standing in Patients With Symptomatic Developmental Dysplasia of the Hip

Pelvic sagittal inclination (PSI) significantly affects the femoral head coverage by the acetabulum in patients with developmental dysplasia of the hip (DDH), while no reports have quantified PSI in DDH patients in the supine and standing positions. Furthermore, little is known about how PSI changes after periacetabular osteotomies. Herein, PSI in the supine and standing positions was quantified in DDH patients preoperatively and postoperatively. Twenty‐five patients with DDH who had undergone periacetabular osteotomies were analyzed. The preoperative PSI and the PSI 2 years after surgery were measured in the supine and standing positions using the image registration technique between radiographs and computed tomographic images. The percentage of patients who showed PSI changes of more than 10° from the supine to the standing position was quantified. PSI changed 8.2 ± 5.0° posteriorly from the supine to the standing position during the preoperative period. Posterior pelvic tilt of more than 10° was found in nine cases (36%). Two years after periacetabular osteotomies, the postural PSI change was 7.1 ± 3.9° posteriorly. When the preoperative and postoperative PSI values were compared, PSI in the standing position did not differ (p = 0.20). Similarly, the amount of PSI change from the supine to standing position was not significantly different (p = 0.26). In conclusion, posterior pelvic tilt in the standing position was found preoperatively in symptomatic DDH patients, and it remained for 2 years after periacetabular osteotomies. This postural change in PSI does not seem to influence the outcome of periacetabular osteotomy. However, during preoperative planning, surgeons should recognize that acetabular anteversion or anterior acetabular coverage differs between the supine and standing positions in some patients with DDH. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:578–587, 2020
MicroRNA in Pancreatic Cancer: From Biology to Therapeutic Potential

Pancreatic cancer is one of the most aggressive malignancies, accounting for more than 45,750 deaths annually in the U.S. alone. The aggressive nature and late diagnosis of pancreatic cancer, coupled with the limitations of existing chemotherapy, present the pressing need for the development of novel therapeutic strategies. Recent reports have demonstrated a critical role of microRNAs (miRNAs) in the initiation, progression, and metastasis of cancer. Furthermore, aberrant expressions of miRNAs have often been associated with the cause and consequence of pancreatic cancer, emphasizing the possible use of miRNAs in the effective management of pancreatic cancer patients. In this review, we provide a brief overview of miRNA biogenesis and its role in fundamental cellular process and miRNA studies in pancreatic cancer patients and animal models. Subsequent sections narrate the role of miRNA in, (i) cell cycle and proliferation; (ii) apoptosis; (iii) invasions and metastasis; and (iv) various cellular signaling pathways. We also describe the role of miRNA’s in pancreatic cancer; (i) diagnosis; (ii) prognosis and (iii) therapeutic intervention. Conclusion section describes the gist of review with future directions.
RiceRelativesGD: a genomic database of rice relatives for rice research

Abstract Rice (Oryza sativa L.) is one of the most important crops worldwide. Its relatives, including phylogenetically related species of rice and paddy weeds with a similar ecological niche, can provide crucial genetic resources (such as resistance to biotic and abiotic stresses and high photosynthetic efficiency) for rice research. Although many rice genomic databases have been constructed, a database providing large-scale curated genomic data from rice relatives and offering specific gene resources is still lacking. Here, we present RiceRelativesGD, a user-friendly genomic database of rice relatives. RiceRelativesGD integrates large-scale genomic resources from 2 cultivated rice and 11 rice relatives, including 208 321 specific genes and 13 643 genes related to photosynthesis and responsive to external stimuli. Diverse bioinformatics tools are embedded in the database, which allow users to search, visualize and download the information of interest. To our knowledge, this is the first genomic database providing a centralized genetic resource of rice relatives. RiceRelativesGD will serve as a significant and comprehensive knowledgebase for the rice community.
Longitudinal changes in placental biomarkers in women with early versus late placental dysfunction

ABSTRACT Objective: To evaluate longitudinal changes of angiogenic biomarkers in early- (EO-PD) versus late-onset (LO-PD) placental dysfunction. Methods: Serum PlGF and sFlt-1 measured at different intervals in EO-PD (n= 43), LO-PD (n= 31) and controls (n = 133). Results: sFlt-1/PlGF ratio was higher at 16 weeks (30.6 vs 17.5), 20 weeks (29.3 vs 8.9) and 30 weeks (16.6 vs 6.7) in EO-PD vs controls (all p< 0.05), but not in LO-PD. Longitudinal changes for all intervals had higher AUC than single measurements. Conclusion: Longitudinal biomarker change between 12 and 30 weeks could improve prediction of EO-PD compared to single measurements.
Isolation of natural fungal pathogens from Marchantia polymorpha reveals antagonism between salicylic acid and jasmonate during liverwort-fungus interactions.

The evolution of adaptive interactions with beneficial, neutral and detrimental microbes was one of the key features enabling plant terrestrialization. Extensive studies have revealed conserved and unique molecular mechanisms underlying plant-microbe interactions across different plant species; however, most insights gleaned to date have been limited to seed plants. The liverwort Marchantia polymorpha, a descendant of early diverging land plants, is gaining in popularity as an advantageous model system to understand land plant evolution. However, studying evolutionary molecular plant-microbe interactions (EvoMPMI) in this model is hampered by the small number of pathogens known to infect M. polymorpha. Here, we describe four pathogenic fungal strains, Irpex lacteus MI1, Phaeophlebiopsis peniophoroides MI2, Bjerkandera adusta MI3, and Bjerkandera adusta MI4, isolated from diseased M. polymorpha. We demonstrate that salicylic acid (SA) treatment of M. polymorpha promotes infection of the I. lacteus MI1 that likely to adopt a necrotrophic lifestyle, while this effect is suppressed by co-treatment with the bioactive jasmonate in M. polymorpha, dinor-cis-12-oxo-phytodienoic acid (dn-cis-OPDA), suggesting that antagonistic interactions between SA and oxylipin pathways during plant-fungus interactions are ancient and were established already in liverworts.
Associations Between Classification Criteria Items in Systemic Lupus Erythematosus

A project aimed at developing new classification criteria for systemic lupus erythematosus (SLE) is based on weighted criteria that include both laboratory and clinical items. Combinations of certain symptoms may occur commonly in SLE, which provides an argument against independently counting these items. The current study was undertaken to evaluate the interrelationship between candidate criteria items in the International Early SLE cohort and in the Euro‐Lupus cohort.
Evaluation of Air Contamination in Orthopaedic Operating Theatres in Hospitals in Southern Italy: The IMPACT Project

Postoperative infections are a concern, especially in total knee and total hip arthroplasty. We evaluated the air quality in orthopaedic operating theatres in southeastern Italy to determine the level of bacterial contamination as a risk factor for postoperative infection. Thirty-five hospitals with operating theatres focused on total knee and total hip arthroplasty participated. We sampled the air passively and actively before surgeries began for the day (at rest) and 15 min after the surgical incision (in operation). We evaluated bacterial counts, particle size, mixed vs turbulent airflow systems, the number of doors, number of door openings during procedures and number of people in the operating theatre. We found no bacterial contamination at rest for all sampling methods, and significantly different contamination levels at rest vs in operation. We found no association between the number of people in the surgical team and bacteria counts for both mixed and turbulent airflow systems, and low bacterial loads, even when doors were always open. Overall, the air quality sampling method and type of ventilation system did not affect air quality.
Learning Needs of Pharmacists for an Evolving Scope of Practice

Around the world, changes in scope of practice regulations for pharmacists have been used as a tool to advance practice and promote change. Regulatory change does not automatically trigger practice change; the extent and speed of uptake of new roles and responsibilities has been slower than anticipated. A recent study identified 9 pre-requisites to practice change (the 9Ps of Practice Change). The objective of this study was to describe how educationalists could best apply these 9Ps to the design and delivery of continuing professional development for pharmacists. Twenty community pharmacists participated in semi-structured interviews designed to elicit their learning needs for scope of practice change. Seven supportive educational techniques were identified as being most helpful to promote practice change: (i) a coaching/mentoring approach; (ii) practice-based experiential learning; (iii) a longitudinal approach to instructional design; (iv) active demonstration of how to implement practice change; v) increased focus on soft-skills development; (vi) opportunities for practice/rehearsal of new skills; and (vii) use of a 360-degree feedback model. Further work is required to determine how these techniques can be best applied and implemented to support practice change in pharmacy.
Investigational fibroblast growth factor receptor 2 antagonists in early phase clinical trials to treat solid tumors

ABSTRACT Introduction: Fibroblast growth factor receptor 2 (FGFR2) is a highly conserved transmembrane tyrosine kinase receptor. FGFR2 dysregulation occurs in numerous human solid tumors and overexpression is closely associated with tumor progression. FGFR2 has recently been reported as a therapeutic target for cancer. Several targeted therapies are being investigated to disrupt FGFR2 activity; these include multi-target tyrosine kinase inhibitors (TKIs), pan-FGFR targeted TKIs and FGFR2 monoclonal antibodies. Areas: This review examines FGFR2 regulation and function in cancer and its potential as a target for cancer treatment. Expert opinion: Highly specific FGFR2 blockers have not yet been developed and moreover, resistance to FGFR2-targeted therapies is a challenge. More sophisticated patient selection strategies would help improve FGFR2-targeted therapies and combination therapy is considered the most promising approach for cancer patients with FGFR2 alterations.
Association between APOE polymorphisms and lipid profile in Mexican Amerindian population

Apolipoprotein E (ApoE) is a glycoprotein that plays an important role in lipid homeostasis at both cerebral and systemic levels. Moreover, the differential distribution of APOE gene alleles among different populations, means that ApoE isoforms could have different effects on lipids metabolism. The present study aims to evaluate the relationship between APOE gene alleles and the lipid profile in a Mexican Amerindian (MA) population.
Zoonotic tuberculosis in humans assessed by next-generation sequencing: an 18-month nationwide study in Lebanon

The World Health Organization (WHO) and other international organisations, including the Food and Agriculture Organization of the United Nations, the World Organisation for Animal Health and the International Union Against Tuberculosis and Lung Disease recently called for formally assessing and (re)prioritising the burden of zoonotic tuberculosis (TB) in people, due to Mycobacterium bovis [1, 2]. Its global contribution to human TB, otherwise principally caused by Mycobacterium tuberculosis, might be underestimated [2]. Nationally representative prevalence data are virtually non-existent on continents with the highest presumed burdens, i.e. in Africa and Asia [3]. In response to recent international calls, this study reveals the nationally representative prevalence of zoonotic tuberculosis in people in a non-high income country, highlighting the need for appropriate diagnostics and treatment of these patients http://bit.ly/2l3ydDh
A mutation in the catalytic domain of Cellulose synthase 6 halts its transport to the Golgi apparatus.

Cellulose microfibrils, which form the mechanical framework of the plant cell wall, are synthesized by the cellulose synthase complex in the plasma membrane. Here, we introduced point mutations into the catalytic domain of Cellulose synthase 6 (CESA6) in Arabidopsis to produce enhanced yellow fluorescent protein (EYFP)-tagged CESA6D395N, CESA6Q823E, and CESA6D395N+Q823E, which were exogenously produced in a cesa6 null mutant, prc1-1. Comparison of these mutants in terms of plant phenotype, cellulose content, cellulose synthase complex dynamics, and organization of cellulose microfibrils showed that prc1-1 expressing EYFP:CESA6D395N or CESA6D395N+Q823E was nearly the same as prc1-1, whereas prc1-1 expressing EYFP:CESA6Q823E was almost identical to wild type and prc1-1 expressing EYFP:WT CESA6, indicating that CESA6D395N and CESA6D395N+Q823E do not function in cellulose synthesis, while CESA6Q823E is still functionally active. Total internal reflection fluorescence microscopy and confocal microscopy were used to monitor the subcellular localization of these proteins. We found that EYFP:CESA6D395N and EYFP:CESA6D395N+Q823E were absent from subcellular regions containing the Golgi and the plasma membrane, and they appeared to be retained in the endoplasmic reticulum. By contrast, EYFP:CESA6Q823E had a normal localization pattern, like that of wild-type EYFP:CESA6. Our results demonstrate that the D395N mutation in CESA6 interrupts its normal transport to the Golgi and its eventual participation in cellulose synthase complex assembly.
The social construction of disability and the capabilities approach: Implications for nursing.

PROBLEM Improving the health and well-being of people with disabilities (PWD) should be included https://plato.stanford. edu/cgi-bin/encyclopedia/archinfo.cgi? entry=justice-distributivein any strategies aimed at eliminating health disparities and achieving health equity in the United States. However, practitioners and policymakers often overlook disability when considering health equity. This is problematic because structural injustices including social and environmental barriers frequently worsen health for PWD. A commitment to social justice, however, dictates that everyone should have equitable opportunities to participate in chosen aspects of life to the best of their abilities and desires. METHODS We use a critical commentary to provide suggestions for the nursing discipline. Specifically, we 1) position the disparities in health and well-being experienced by PWD as matters of equity and social justice, 2) describe Amartya Sen's capabilities approach, and 3) provide suggestions for incorporating tenets of the capabilities approach into nursing practice, research, and policy. CONCLUSION The capabilities approach can provide a useful framework to guide nursing practice, research, and policy in order to advance social justice for PWD.
Linkages between Respiratory Symptoms in Women and Biofuel Use: Regional Case Study of Rajasthan, India

Women in low and middle-income countries predominantly use biofuel for cooking, resulting in potential adverse health outcomes. In India, it is estimated that about 40% of total primary energy consumption is in the domestic sector with biofuels alone accounting for about 75% of domestic energy consumption. This study assesses linkages between wood consumption and perceptions of women’s health, combining results from a rapid assessment of eight rural districts in Rajasthan with a regression analysis of data from Rajasthan State (sample size 41,965 women) from the Demographic and Health Survey 7 dataset (2015–2016). The results of the rapid survey indicate that women who cook with biofuels perceive adverse health outcomes. Educational level, income, and age have an impact on fuel consumption and clean fuel purchased. The regression model drawing upon data on women at a regional level in Rajasthan yielded significant results suggesting a strong association between fuel type and symptoms of respiratory infection controlling for age and education. This research is timely as it provides valuable evidence for India’s Ujjawala Scheme which has the mandate of providing LPG connections to women from below the poverty line.
Image guidance used for large joint and bursa injections; a survey study

ABSTRACT Objectives To determine the current rates of use of available image guidance modalities for large joint and bursal injections, in addition to their relationships to physician demographics. Methods An electronic survey was sent to 3,400 members of the American Medical Society for Sports Medicine (AMSSM), examining types of guidance used for each large joint and bursal injection. Results A total of 674 sports medicine physicians responded to the survey. Intra-articular hip and glenohumeral joint injections were more commonly performed with ultrasound guidance, while palpation-guidance was more common with all other injections. Physicians who specialized in Physical Medicine & Rehabilitation (PM&R) were more likely to use ultrasound for trochanteric bursa (p = 0.007, OR = 4.16 [1.46–11.8]), while internal medicine-, pediatrics-, and family medicine-trained physicians were more likely to use palpation guidance for at least one joint (p < 0.05). Physicians with fewer years of experience were more likely to use ultrasound for glenohumeral joint injections (p ≤ 0.002 for all age groups with less than 20 years of experience, ORs ranging from 6.3 to 9.2). Conclusion Palpation-guidance is the most common technique used for large joint and bursal injections, other than for glenohumeral and hip joint injections. PM&R-trained physicians and those with less experience tend to use ultrasound more frequently.