Takshan/R1 huggingface dataset:
Preoperative thrombocytosis as a prognostic factor in endometrioid-type endometrial carcinoma.

BACKGROUND: The impact of preoperative thrombocytosis as a prognostic factor in endometrial carcinoma (EC) remains uncertain and has never been examined in Saudi Arabia. OBJECTIVES: To determine the prevalence of preoperative thrombocytosis (platelet count > 400 000/ μL), and its prognostic significance for clinicopathological factors and survival in Saudi patients with endometrioid-type EC. DESIGN: A retrospective cross-sectional study from January 2010 to December 2013. SETTING: A referral tertiary healthcare institute. PATIENTS AND METHODS: Patients who underwent staging surgery for primary endometrioid-type EC were retrospectively analyzed for perioperative details: age, preoperative platelet count, International Federation of Gynecology and Obstetrics (FIGO) stage, endometrioid grade, recurrence, disease-free survival (DFS) and overall survival (OS). Survival analysis was conducted using Kaplan-Meier estimates and a Cox proportional hazards model. MAIN OUTCOME MEASURES: Prevalence of preoperative thrombocytosis, DFS and OS. RESULTS: In 162 patients who met inclusion criteria, the frequency of preoperative thrombocytosis was 8.6% (n=14). Patients with advanced FIGO disease (stages III-IV) and recurrence had significantly higher mean preoperative platelet counts than patients with early FIGO disease (stages I-II) and no recurrence (P=.0080 and P=.0063, respectively). Patients with thrombocytosis had statistically significant higher rates of advanced FIGO stages III-IV disease, unfavorable grades II-III endometrioid histology and recurrence than patients with preoperative platelet counts.
New FIGO and Swedish intrapartum cardiotocography classification systems incorporated in the fetal ECG ST analysis (STAN) interpretation algorithm: agreements and discrepancies in cardiotocography classification and evaluation of significant ST events.

INTRODUCTION: The updated intrapartum cardiotocography (CTG) classification system by FIGO in 2015 (FIGO2015) and the FIGO2015-approached classification by the Swedish Society of Obstetricians and Gynecologist in 2017 (SSOG2017) are not harmonized with the fetal ECG ST analysis (STAN) algorithm from 2007 (STAN2007). The study aimed to reveal homogeneity and agreement between the systems in classifying CTG and ST events, and relate them to maternal and perinatal outcomes. MATERIAL AND METHODS: Among CTG traces with ST events, 100 traces originally classified as normal, 100 as suspicious and 100 as pathological were randomly selected from a STAN database and classified by two experts in consensus. Homogeneity and agreement statistics between the CTG classifications were performed. Maternal and perinatal outcomes were evaluated in cases with clinically hidden ST data (n = 151). A two-tailed p < 0.05 was regarded as significant. RESULTS: For CTG classes, the heterogeneity was significant between the old and new systems, and agreements were moderate to strong (proportion of agreement, kappa index 0.70-0.86). Between the new classifications, heterogeneity was significant and agreements strong (0.90, 0.92). For significant ST events, heterogeneities were significant and agreements moderate to almost perfect (STAN2007 vs. FIGO2015 0.86, 0.72; STAN2007 vs. SSOG2017 0.92, 0.84; FIGO2015 vs. SSOG2017 0.94, 0.87). Significant ST events occurred more often combined with STAN2007 than with FIGO2015 classification, but not with SSOG2017; correct identification of adverse outcomes was not significantly different between the systems. CONCLUSION: There are discrepancies in the classification of CTG patterns and significant ST events between the old and new systems. The clinical relevance of the findings remains to be shown.
Follow-Up Consultation Through a Healthcare Kiosk for Patients with Stable Chronic Disease in a Primary Care Setting: A Prospective Study.

INTRODUCTION: The global healthcare kiosk market is growing, and kiosks are projected to be a larger part of healthcare delivery in the coming decades. We developed an unmanned healthcare kiosk that automates the management of stable patients with chronic conditions to complement face-to-face primary care physician (PCP) visits. AIM: The aim of our study was to show that the kiosk could be a feasible means of delivering care for stable patients with chronic conditions and could generate cost savings for the management of patients with stable chronic disease. METHODS: We conducted a prospective single-arm study of 95 participants with well-controlled chronic cardiovascular diseases who visited our clinic in Singapore every 3 months for review and medication refill. During their subsequent appointments for chronic disease management at 3 and 6 months, participants used the kiosk instead of consulting a physician. All participants who used the kiosk were also evaluated by a nurse clinician (NC). The kiosk assessment of whether the patient was well controlled was then compared to the NC's assessment to determine rates of agreement. Patient satisfaction was evaluated through a questionnaire, and any adverse outcomes were documented. RESULTS: Cohen's κ for agreement between the kiosk and the NC assessment of patients' chronic care control was 0.575 (95% CI, 0.437-0.713). The modest agreement was due to differences in systolic blood pressure measurements between the kiosk and the NC. The 96% of participants who completed two kiosk visits were all satisfied with the kiosk as a care delivery alternative. None of the participants managed through the kiosk suffered any adverse outcomes. Use of the kiosk resulted in a reduction of 128 face-to-face PCP visits. CONCLUSIONS: Healthcare kiosks can potentially be used to complement primary care clinician visits for managing patients with stable chronic diseases and can generate cost savings.
BEReX: Biomedical Entity-Relationship eXplorer.

SUMMARY: Biomedical Entity-Relationship eXplorer (BEReX) is a new biomedical knowledge integration, search and exploration tool. BEReX integrates eight popular databases (STRING, DrugBank, KEGG, PhamGKB, BioGRID, GO, HPRD and MSigDB) and delineates an integrated network by combining the information available from these databases. Users search the integrated network by entering key words, and BEReX returns a sub-network matching the key words. The resulting graph can be explored interactively. BEReX allows users to find the shortest paths between two remote nodes, find the most relevant drugs, diseases, pathways and so on related to the current network, expand the network by particular types of entities and relations and modify the network by removing or adding selected nodes. BEReX is implemented as a standalone Java application. AVAILABILITY AND IMPLEMENTATION: BEReX and a detailed user guide are available for download at our project Web site (http://infos.korea.ac.kr/berex).
Migrant women's experiences, meanings and ways of dealing with postnatal depression: A meta-ethnographic study.

AIM: To conduct a meta-ethnographic study of the experiences, meanings and ways of 'dealing with' symptoms or a diagnosis of postnatal depression amongst migrant women living in high income countries. BACKGROUND: Prevalence of postnatal depression is highest amongst women who are migrants. Yet many women do not seek help for their symptoms and health services do not always respond appropriately to migrant women's needs. Studies have reported migrant women's experiences of postnatal depression and it is timely to synthesise findings from these studies to understand how services can be improved. DESIGN: A meta-ethnographic synthesis of 12 studies reported in 15 papers. DATA SOURCES: Five databases were searched for papers published between January 1999 and February 2016. REVIEW METHODS: The quality of included studies was assessed using the Critical Appraisal Skills Program tool. The synthesis process was guided by the seven steps of meta-ethnography outlined by Noblit and Hare. FINDINGS: Four key metaphors were identified: "I am alone, worried and angry-this is not me!"; ' Making sense of my feelings' 'Dealing with my feelings' and 'What I need to change the way I feel!'. Primarily women related their feelings to their position as a migrant and as women, often living in poor socio-economic circumstances and they were exhausted keeping up with expected commitments. Many women were resourceful, drawing on their personal strengths and family / community resources. All the studies reported that women experienced difficulties in accessing appropriate services. CONCLUSION: The meta-ethnographic study demonstrates the impact of migration on perinatal mental health, particularly for women lacking family support, who have no employment, a precarious migration status and/or relationship conflict. Migrant women are resourceful and this requires support through appropriate services. Further research is needed to evaluate effective support strategies for migrant women in the perinatal period.
Phase I study of oral rigosertib (ON 01910.Na), a dual inhibitor of the PI3K and Plk1 pathways, in adult patients with advanced solid malignancies.

PURPOSE: To determine the pharmacokinetics (PK), maximum tolerated dose (MTD), safety, and antitumor activity of an oral formulation of rigosertib, a dual phosphoinositide 3-kinase (PI3K) and polo-like kinase 1 (Plk1) pathway inhibitor, in patients with advanced solid malignancies. EXPERIMENTAL DESIGN: Patients with advanced solid malignancies received rigosertib twice daily continuously in 21-day cycles. Doses were escalated until intolerable grade ≥2 toxicities, at which point the previous dose level was expanded to define the MTD. All patients were assessed for safety, PK, and response. Urinary PK were performed at the MTD. Archival tumors were assessed for potential molecular biomarkers with multiplex mutation testing. A subset of squamous cell carcinomas (SCC) underwent exome sequencing. RESULTS: Forty-eight patients received a median of 2 cycles of therapy at 5 dose levels. Rigosertib exposure increased with escalating doses. Dose-limiting toxicities were hematuria and dysuria. The most common grade ≥2 drug-related toxicities involved urothelial irritation. The MTD is 560 mg twice daily. Activity was seen in head and neck SCCs (1 complete response, 1 partial response) and stable disease for ≥12 weeks was observed in 8 additional patients. Tumors experiencing ≥partial response had PI3K pathway activation, inactivated p53, and unique variants in ROBO3 and FAT1, two genes interacting with the Wnt/β-catenin pathway. CONCLUSIONS: The recommended phase II dose of oral rigosertib is 560 mg twice daily given continuously. Urinary toxicity is the dose-limiting and most common toxicity. Alterations in PI3K, p53, and Wnt/β-catenin pathway signaling should be investigated as potential biomarkers of response in future trials.
A stepped-wedge implementation and evaluation of the healthy active peaceful playgrounds for youth (HAPPY) intervention.

BACKGROUND: Increasing physical activity in children is a health priority. The Healthy Active Peaceful Playgrounds for Youth (HAPPY) study aimed to examine a multi-component playground intervention designed to increase the proportion of physical activity during recess and lunch of primary school students. METHODS: The 2016 Australian focused HAPPY Study was a 12-month, metropolitan primary school based intervention, which was evaluated using a stepped wedge design. The intervention combined teacher development, environmental modifications, and peer support, with the outcomes of increasing physical activity, and analysing students' sources of social support to be physically active. RESULTS: Between baseline and follow-up, the proportion of students involved in vigorous activities during recess and lunch times increased significantly from 15 to 25% (p < 0.001). No differences were recorded in sources of social support. CONCLUSIONS: The HAPPY project demonstrated an increase in the proportion of physical activity intensity during recess and lunch times in primary schools, although further investigation is required to determine what components of the study had the greatest effect. TRIAL REGISTRATION: This study was retrospectively registered with the Australian and New Zealand Clinical Trials Registry ACTRN12616000575437 . Date of registration: 4 May 2016.
They receive antenatal care in health facilities, yet do not deliver there: predictors of health facility delivery by women in rural Ghana.

BACKGROUND: Research has shown that use of antenatal services by pregnant women and delivery in health facilities with skilled birth attendants contribute to better delivery outcomes. However, a gap exists in Ghana between the use of antenatal care provided by health facilities and delivery in health facilities with skilled birth attendants by pregnant women. This study sought to identify the predictors of health facility delivery by women in a rural district in Ghana. METHODS: This was a cross-sectional study conducted in June 2016. Women who delivered in the past 6 months preceding the study were interviewed. Data on socio-demographic characteristics, use of antenatal care, place of delivery and reasons for home delivery were collected from study participants. Chi-square test and multiple logistic regression analysis were used to assess an association between women's socio-demographic and obstetric characteristics and place of delivery at 95% confidence interval. RESULTS: The study found that 98.8% of women received antenatal care services at least once during their recent pregnancy, and 67.9% attended antenatal care at least four times before delivery. However, 61.9% of the women delivered in a health facility with a skilled attendant. The frequently mentioned reason for home delivery was "unaware of onset of labour and delivery". The odds for delivery at a health facility were reduced among women with four living children [(AOR = 0.07, CI = 0.15-0.36, p = 0.001)], with no exposure to delivery care information [(AOR = 0.06, CI = 0.01-0.34, p = 0.002), who started their first ANC visit from the second trimester of pregnancy[(AOR = 0.003, CI = 0.01-0.15, p < 0.001)] and increased among women who made at least four ANC visits before delivery [(AOR = 17.53, CI = 6.89-44.61, p < 0.001)]. CONCLUSION: Findings from this study revealed a low rate of delivery at health facilities although visits to antenatal care sessions were high, an indication that there was the need to intensify health education on early initiation of antenatal care, signs of labour and delivery, and importance of health facility delivery.
Bull's eye maculopathy and subfoveal deposition in two mucopolysaccharidosis type I patients on long-term enzyme replacement therapy.

Purpose: To report retinal findings in two patients with mucopolysaccharidosis type I (MPS I) receiving human recombinant alpha-l-iduronidase (Laronidase) as enzyme replacement therapy. Observations: Patient 1 had visual acuity 20/20 right eye, 20/25 left eye and unremarkable anterior segment and retinal examination. Optical coherence tomography (OCT) scanning demonstrated parafoveal thinning and subfoveal hyperreflectant material. Patient 2 had visual acuity 20/20 both eyes, with dense nuclear cataract both eyes. Retinal examination demonstrated bull's eye maculopathy both eyes. OCT scanning confirmed parafoveal atrophy and demonstrated similar appearing subfoveal hyperreflectant material, more prominent than in case 1. Conclusions and importance: These two patients with MPS I receiving Laronidase treatment have developed bull's eye maculopathy changes and subfoveal deposition of hyperreflectant material despite excellent compliance and good tolerance of the standard dose of enzyme therapy for this disorder. Further studies are required to determine the nature of the material, the incidence and the effect of enzyme replacement therapy on these findings in patients with MPS I.
Ubiquitous giants: a plethora of giant viruses found in Brazil and Antarctica.

BACKGROUND: Since the discovery of giant viruses infecting amoebae in 2003, many dogmas of virology have been revised and the search for these viruses has been intensified. Over the last few years, several new groups of these viruses have been discovered in various types of samples and environments. In this work, we describe the isolation of 68 giant viruses of amoeba obtained from environmental samples from Brazil and Antarctica. METHODS: Isolated viruses were identified by hemacolor staining, PCR assays and electron microscopy (scanning and/or transmission). RESULTS: A total of 64 viruses belonging to the Mimiviridae family were isolated (26 from lineage A, 13 from lineage B, 2 from lineage C and 23 from unidentified lineages) from different types of samples, including marine water from Antarctica, thus being the first mimiviruses isolated in this extreme environment to date. Furthermore, a marseillevirus was isolated from sewage samples along with two pandoraviruses and a cedratvirus (the third to be isolated in the world so far). CONCLUSIONS: Considering the different type of samples, we found a higher number of viral groups in sewage samples. Our results reinforce the importance of prospective studies in different environmental samples, therefore improving our comprehension about the circulation anddiversity of these viruses in nature.
FGFR1 mRNA and protein expression, not gene copy number, predict FGFR TKI sensitivity across all lung cancer histologies.

PURPOSE: FGFR1 gene copy number (GCN) is being evaluated as a biomarker for FGFR tyrosine kinase inhibitor (TKI) response in squamous cell lung cancers (SCC). The exclusive use of FGFR1 GCN for predicting FGFR TKI sensitivity assumes increased GCN is the only mechanism for biologically relevant increases in FGFR1 signaling. Herein, we tested whether FGFR1 mRNA and protein expression may serve as better biomarkers of FGFR TKI sensitivity in lung cancer. EXPERIMENTAL DESIGN: Histologically diverse lung cancer cell lines were submitted to assays for ponatinib sensitivity, a potent FGFR TKI. A tissue microarray composed of resected lung tumors was submitted to FGFR1 GCN, and mRNA analyses and the results were validated with The Cancer Genome Atlas (TCGA) lung cancer data. RESULTS: Among 58 cell lines, 14 exhibited ponatinib sensitivity (IC50 values ≤ 50 nmol/L) that correlated with FGFR1 mRNA and protein expression, but not with FGFR1 GCN or histology. Moreover, ponatinib sensitivity associated with mRNA expression of the ligands, FGF2 and FGF9. In resected tumors, 22% of adenocarcinomas and 28% of SCCs expressed high FGFR1 mRNA. Importantly, only 46% of SCCs with increased FGFR1 GCN expressed high mRNA. Lung cancer TCGA data validated these findings and unveiled overlap of FGFR1 mRNA positivity with KRAS and PIK3CA mutations. CONCLUSIONS: FGFR1 dependency is frequent across various lung cancer histologies, and FGFR1 mRNA may serve as a better biomarker of FGFR TKI response in lung cancer than FGFR1 GCN. The study provides important and timely insight into clinical testing of FGFR TKIs in lung cancer and other solid tumor types.
Bioinformatics-driven discovery of rational combination for overcoming EGFR-mutant lung cancer resistance to EGFR therapy.

MOTIVATION: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Targeted tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) have been widely and successfully used in treating NSCLC patients with activating EGFR mutations. Unfortunately, the duration of response is short-lived, and all patients eventually relapse by acquiring resistance mechanisms. RESULT: We performed an integrative systems biology approach to determine essential kinases that drive EGFR-TKI resistance in cancer cell lines. We used a series of bioinformatics methods to analyze and integrate the functional genetics screen and RNA-seq data to identify a set of kinases that are critical in survival and proliferation in these TKI-resistant lines. By connecting the essential kinases to compounds using a novel kinase connectivity map (K-Map), we identified and validated bosutinib as an effective compound that could inhibit proliferation and induce apoptosis in TKI-resistant lines. A rational combination of bosutinib and gefitinib showed additive and synergistic effects in cancer cell lines resistant to EGFR TKI alone. CONCLUSIONS: We have demonstrated a bioinformatics-driven discovery roadmap for drug repurposing and development in overcoming resistance in EGFR-mutant NSCLC, which could be generalized to other cancer types in the era of personalized medicine. AVAILABILITY AND IMPLEMENTATION: K-Map can be accessible at: http://tanlab.ucdenver.edu/kMap. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Measuring patient activation: The utility of the Patient Activation Measure within a UK context-Results from four exemplar studies and potential future applications.

OBJECTIVE: Patient activation can be measured using the Patient Activation Measure (PAM) developed by Hibbard et al., however, little is known about the uses of the PAM in research and in practice. This study aims to explore its differing utility in four UK exemplar sites. METHODS: Data from four exemplars in a range of health settings with people living with long-term conditions (i.e. stroke or COPD) were evaluated. PAM scores were described and explored in relation to clinical and sociodemographic variables and outcome measures. RESULTS: PAM scores illustrated that most with COPD or stroke reported PAM levels of 3 or 4, indicating that they are engaging, but may need help to sustain their scores. The exemplars illustrate the utility of, and potential issues involved in, using PAM as a process/outcome measure to predict activation and the effectiveness of interventions, and as a tool to inform tailoring of targeted interventions. CONCLUSIONS: The PAM tool has been shown to be useful as an outcome measure, a screening tool to tailor education, or a quality indicator for delivery of care. PRACTICE IMPLICATIONS: However good demographic and patient history are needed to substantiate PAM scores. Further work is needed to monitor PAM prospectively.
Dual pharmacological targeting of the MAP kinase and PI3K/mTOR pathway in preclinical models of colorectal cancer.

BACKGROUND: The activation of the MAPK and PI3K/AKT/mTOR pathways is implicated in the majority of cancers. Activating mutations in both of these pathways has been described in colorectal cancer (CRC), thus indicating their potential as therapeutic targets. This study evaluated the combination of a PI3K/mTOR inhibitor (PF-04691502/PF-502) in combination with a MEK inhibitor (PD-0325901/PD-901) in CRC cell lines and patient-derived CRC tumor xenograft models (PDTX). MATERIALS AND METHODS: The anti-proliferative effects of PF-502 and PD-901 were assessed as single agents and in combination against a panel of CRC cell lines with various molecular backgrounds. Synergy was evaluated using the Bliss Additivity method. In selected cell lines, we investigated the combination effects on downstream effectors by immunoblotting. The combination was then evaluated in several fully genetically annotated CRC PDTX models. RESULTS: The in vitro experiments demonstrated a wide range of IC50 values for both agents against a cell line panel. The combination of PF-502 and PD-901 demonstrated synergistic anti-proliferative activity with Bliss values in the additive range. As expected, p-AKT and p-ERK were downregulated by PF-502 and PD-901, respectively. In PDTX models, following a 30-day exposure to PF-502, PD-901 or the combination, the combination demonstrated enhanced reduction in tumor growth as compared to either single agent regardless of KRAS or PI3K mutational status. CONCLUSIONS: The combination of a PI3K/mTOR and a MEK inhibitor demonstrated enhanced anti-proliferative effects against CRC cell lines and PDTX models.