Takshan/R1 huggingface dataset:
Elevated Adenylyl Cyclase 9 Expression Is a Potential Prognostic Biomarker for Patients with Colon Cancer.

BACKGROUND Adenylyl cyclase 9 (ADCY9) is an enzyme that modulates signal transduction by producing the second messenger, cyclic adenosine monophosphate (cAMP). The aim of the present study was to investigate the association of ADCY9 expression with clinicopathological features and disease-free survival of colon cancer patients. MATERIAL AND METHODS Immunohistochemistry staining with ADCY9 antibody was performed on a tissue microarray. Immunoreactivity scores (IRS) were recorded and applied for association analysis. ADCY9 mRNA expression and clinicopathogical information were also extracted from TCGA colon cancer dataset and analyzed using univariate and multivariate Cox proportional hazards models.   RESULTS ADCY9 IRS was significantly higher (P=0.002) in tumor tissues (6.40±1.26, n=200) than in adjacent normal samples (4.13±0.83, n=8). The IRS and mRNA expression of ADCY9 were correlated to colon cancer TNM staging. Longer disease-free survival was observed in patients with lower ADCY9 expression (P=0.001). In the multivariate models, ADCY9 expression level (hazard ratio [HR] 5.495, 95% confidence interval [CI] 1.753-17.227, P=0.003), and distant metastasis (HR 4.329, 95% CI 1.374-13.636, P=0.012) were still associated with disease-free survival. CONCLUSIONS High ADCY9 expression is a poor prognostic factor for disease-free survival in colon cancer.
Management of severe childhood pneumonia by day care approach in developing countries.

Background: Pneumonia is a major cause of child mortality among children under 5 years, worldwide. Pneumonia infection may be caused by bacteria, viruses, or fungi in single or in both lungs. According to recent criteria developed by the World Health Organization(WHO) in September (2013), pneumonia can be classified into severe pneumonia, pneumonia and no pneumonia. Most of the deaths occur from severe pneumonia. Methods: Disease management of severe childhood pneumonia requires early identification,prompt referral and the availability of intensive quality care. Under 5 years old children with severe pneumonia should receive day care, with antibiotic treatment, feeding, and supportive care with similar 24-hour hospital treatment. Results: Considering that difficulties, International Centre for Diarrheal Disease Research,Bangladesh (ICDDR, B) initiated Day Care Approach (DCA) model, as an innovative, safe,effective and less expensive alternative to hospital management of severe childhood pneumonia. A 24 months old girl came to the health care center with severe breathing difficulty, cough,history of fever and head nodding. The management described below was continued daily until there was clinical improvement; no fever, no fast breathing, no lower chest wall in drawing, no danger signs, no rales on auscultation, and no hypoxemia. Conclusion: Considering the WHO case management protocol for severe pneumonia, DCA recommends that diagnosis of severe pneumonia should be based primarily on visible clinical parameters. On that basis, severe childhood pneumonia can be successfully managed at daycare clinics including for children with hypoxemia who is required prolong (4-6 hours) oxygen therapy.
Lipidomics reveals altered biosynthetic pathways of glycerophospholipids and cell signaling as biomarkers of the polycystic ovary syndrome.

Purpose: In this work, a non-targeted approach was used to unravel changes in the plasma lipidome of PCOS patients. The aim is to offer new insights in PCOS patients strictly selected in order to avoid confounding factors such as dyslipemia, obesity, altered glucose/insulin metabolism, cardiovascular disease, or cancer. Results: Multivariate statistics revealed a specific lipidomic signature for PCOS patients without associated pathologies. This signature implies changes, mainly by down-regulation, in glycerolipid, glycerophospholipid and sphingolipid metabolism suggesting an altered biosynthetic pathway of glycerophospholipids and cell signaling as second messengers in women with PCOS. Conclusions: Our study confirms that a lipidomic approach discriminates a specific phenotype from PCOS women without associated pathologies from healthy controls. Methods: In a cross-sectional pilot study, data were obtained from 34 subjects, allocated to one of two groups: a) lean, healthy controls (n = 20), b) PCOS patients (n = 14) with diagnosis based on hyperandrogenaemia, oligo-anovulation and abnormal ovaries with small follicular cysts. A detailed biochemical characterization was made and lipidomic profiling was performed via an untargeted approach using LC-ESI-QTOF MS/MS.
Responding effectively to adult mental health patient feedback in an online environment: A coproduced framework.

BACKGROUND: Responding to online patient feedback is considered integral to patient safety and quality improvement. However, guidance on how to respond effectively is limited, with limited attention paid to patient perceptions and reactions. OBJECTIVES: To identify factors considered potentially helpful in enhancing response quality; coproduce a best-practice response framework; and quality-appraise existing responses. DESIGN: A four-stage mixed methodology: (i) systematic search of stories published on Care Opinion about adult mental health services in the South West of England; (ii) collaborative thematic analysis of responses to identify factors potentially helpful in enhancing response quality; (iii) validation of identified factors by a patient-carer group (n = 12) leading to the coproduction of a best-practice response framework; and (iv) quality appraisal of existing responses. RESULTS: A total of 245 stories were identified, with 183 (74.7%) receiving a response. Twenty-four (9.8%) had been heard but not yet responded to. 1.6% (n = 4/245) may lead to a change. Nineteen factors were considered influential in response quality. These centred around seven subject areas: (i) introductions; (ii) explanations; (iii) speed of response; (iv) thanks and apologies; (v) response content; (vi) signposting; and (vii) response sign-off that were developed into a conceptual framework (the Plymouth, Listen, Learn and Respond framework). Quality appraisal of existing responses highlighted areas for further improvement demonstrating the framework's utility. CONCLUSION: This study advances existing understanding by providing previously unavailable guidance. It has clear practical and theoretical implications for those looking to improve health-care services, patient safety and quality of care. Further validation of the conceptual framework is encouraged.
Targeting acute myeloid leukemia with a small molecule inhibitor of the Myb/p300 interaction.

The transcription factor Myb plays a key role in the hematopoietic system and has been implicated in the development of leukemia and other human cancers. Inhibition of Myb is therefore emerging as a potential therapeutic strategy for these diseases. However, due to lack of suitable inhibitors the feasibility of therapeutic approaches based on Myb inhibition has not been explored. We have identified the triterpenoid Celastrol as a potent low-molecular weight inhibitor of the interaction of Myb with its cooperation partner p300. We demonstrate that Celastrol suppresses the proliferative potential of acute myeloid leukemia (AML) cells while not affecting normal hematopoietic progenitor cells. Furthermore, Celastrol prolongs the survival of mice in a model of an aggressive AML. Overall, our work demonstrates the therapeutic potential of a small-molecule inhibitor of the Myb/p300 interaction for the treatment of AML and provides a starting point for the further development of Myb-inhibitory compounds for the treatment of leukemia and, possibly, other tumors driven by deregulated Myb.
Stepped-wedge randomised trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation: study protocol for a randomized controlled trial.

BACKGROUND: Laparoscopic ventral mesh rectopexy (LVMR) is an established treatment for external full-thickness rectal prolapse. However, its clinical efficacy in patients with internal prolapse is uncertain due to the lack of high-quality evidence. METHODS: An individual level, stepped-wedge randomised trial has been designed to allow observer-blinded data comparisons between patients awaiting LVMR with those who have undergone surgery. Adults with symptomatic internal rectal prolapse, unresponsive to prior conservative management, will be eligible to participate. They will be randomised to three arms with different delays before surgery (0, 12 and 24 weeks). Efficacy outcome data will be collected at equally stepped time points (12, 24, 36 and 48 weeks). The primary objective is to determine clinical efficacy of LVMR compared to controls with reduction in the Patient Assessment of Constipation Quality of Life (PAC-QOL) at 24 weeks serving as the primary outcome. Secondary objectives are to determine: (1) the clinical effectiveness of LVMR to 48 weeks to a maximum of 72 weeks; (2) pre-operative determinants of outcome; (3) relevant health economics for LVMR; (4) qualitative evaluation of patient and health professional experience of LVMR and (5) 30-day morbidity and mortality rates. DISCUSSION: An individual-level, stepped-wedge, randomised trial serves the purpose of providing an untreated comparison for the active treatment group, while at the same time allowing the waiting-listed participants an opportunity to obtain the intervention at a later date. In keeping with the basic ethical tenets of this design, the average waiting time for LVMR (12 weeks) will be shorter than that for routine services (24 weeks). TRIAL REGISTRATION: ISRCTN registry, ISRCTN11747152 . Registered on 30 September 2015. The trial was prospectively registered (first patient enrolled on 21 March 2016).
A New Gall Midge Species of Asphondylia (Diptera: Cecidomyiidae) Inducing Flower Galls on Clinopodium nepeta (Lamiaceae) From Europe, Its Phenology, and Associated Fungi.

A new gall midge, Asphondylia nepetae sp. n. Viggiani (Diptera: Cecidomyiidae), causing flower gall on Clinopodium nepeta (L.) Kuntze (Lamiaceae), is described from Europe. The morphological characteristics of adult, larvae, and pupa are described and illustrated. Molecular approach (by sequencing 28S-D2, ITS2, and COI) confirmed that A. nepetae is a distinct species. The development of the gall is always associated with the presence of the fungus Botryosphaeria dothidea (Moug.: Fr.) Ces. and De Not. ( Botryosphaeriales: Botryosphaeriaceae). The new species can complete several generations per year, on the flowers of the same host plant and its adults emerge from late spring to autumn. Pupae overwinter inside peculiar flower galls in a state of quiescence. The impact of the pest is highly variable with a percentage of flowers infested that ranged between 3 and 57.5% in the sampled years. Insect mortality was, at least in part, due to parasitoids that attack the young stages of the midge. Among them, the dominant species was Sigmophora brevicornis (Panzer) (Chalcidoidea: Eulophidae).
Basic taste processing recruits bilateral anteroventral and middle dorsal insulae: An activation likelihood estimation meta-analysis of fMRI studies.

BACKGROUND AND PURPOSE: Numerous task-based functional magnetic resonance imaging (fMRI) studies have reported the locations of basic taste representations in the human brain, but they usually employed a limited number of subjects (<20) with different methodologies and stimuli. Moreover, the reported brain regions were sometimes inconsistent. Thus, we aimed at performing a meta-analysis of the published data to identify locations consistently activated across studies, and performed a connectivity analysis to reveal how these taste processing regions connect with other brain regions. MATERIALS AND METHODS: A meta-analysis was performed based on 34 experiments, with 238 total participants in 16 studies, to establish the activation likelihood estimation (ALE) of taste-mediated regional activation. Meta-analytic connectivity modeling (MACM) and data stored in BrainMap database were employed to reveal the functional connectivity of the regions identified by ALE with other brain regions, across all types of experiments that caused activation among healthy subjects. RESULTS: ALE identified nine activated clusters in bilateral anteroventral and middle dorsal insulae, bilateral thalamus and caudate, bilateral pre-/postcentral gyrus, and right hippocampus. The concurrence between studies was moderate, with at best 38% of experiments contributed to the significant clusters activated by taste stimulation. Sweet taste was the predominant contributing taste. MACM revealed that at least 50% of the nine clusters coactivated with the middle cingulate cortex, medial frontal gyrus, inferior parietal lobule, and putamen. CONCLUSION: Results suggested that fMRI studies have reported reproducible patterns of activations across studies. The basic taste stimulations resulted in activations in a mostly bilateral network. Moreover, they were connected with cognitive and emotional relevant brain regions.
High resolution time-intensity recording with synchronized solution delivery system for the human dynamic taste perception.

BACKGROUND: Time-intensity sensory evaluation of human taste perception is useful to know the feedback of a taste stimulus from tongue. However, it has not been profiled together with reaction time under the constant stimulating tongue in high time resolution. NEW METHOD: We first made intra-oral device to deliver taste solution to anterior, lateral and posterior tongue in standardized condition. Second, we developed a time-intensity sensory evaluation meter linked to synchronized taste solution delivery system. Time-intensity profiles were recorded in higher temporal resolution than our past study. Third, we analyzed the corrected taste quality reaction time from raw sensory perception data, and following sensory evaluation profile. RESULTS: The new method acquired taste sensory evaluation data with 1 ms temporal resolution and found the reaction timing was 908 ms, the corrected taste quality reaction time was 712 ms, maximum intensity was 3.47, and corrected time to reach maximum intensity was 1312 ms. The coefficient of variation ranged from 0.007 to 0.236 indicating low variance. COMPARISON WITH EXISTING METHODS: Time-intensity sensory evaluation in this study did not sacrifice the feature of raw data. The relative comparison of time-intensity sensory profile among subjects will be available in this system in future study, while it was still difficult to define the absolute value of reaction time. CONCLUSIONS: Our method could gather real-time feedback for the time-intensity sensory evaluation of a taste stimulus under the standardized stimulating tongue. This could be useful for establishing database of time-intensity sensory profiles for comparison of delicate taste perceptions.
Predictors of anti-VEGF drug-induced hypertension using different hypertension criteria: a secondary analysis of the COMPARZ study.

Background: There is inconsistency in the criteria used to define anti-vascular endothelial growth factor (VEGF) drug-induced hypertension (AVEGF-HT) in published studies. It is unknown whether specific patient characteristics similarly predict AVEGF-HT using different criteria. Methods: We assessed the associations between clinical and demographic factors (n = 22) and AVEGF-HT, using six criteria based on predefined on-treatment blood pressure (BP) thresholds or absolute BP elevations versus baseline, in a post hoc analysis of a phase III trial of 1102 patients with renal cell carcinoma (RCC) randomized to pazopanib or sunitinib (COMPARZ study). Results: The cumulative incidence of AVEGF-HT at any time while on treatment ranged between 14.8% [criterion: grade ⩾3 toxicity, National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0] and 58.8% (criterion: absolute systolic BP increase ⩾20 mmHg versus baseline). After adjusting for anti-VEGF treatment and baseline BP, the number of significant (p < 0.05) predictors ranged between one (criterion: absolute systolic BP increase ⩾20 mmHg, on-treatment systolic BP ⩾140 mmHg and diastolic BP ⩾90 mmHg) and nine (criterion: grade ⩾3 toxicity, NCI CTCAE v3.0). Age, use of antidiabetic drugs and use of antihypertensive drugs each significantly predicted four AVEGF-HT criteria. By contrast, sex, smoking, heart rate, proteinuria, Karnofsky performance status, and use of thiazide diuretics did not predict any criterion. Conclusions: There was a significant variability in the incidence, number and type of predictors of AVEGF-HT, using six different criteria, in a post hoc analysis of the COMPARZ study. The use of specific criteria might affect the assessment of the interaction between anti-VEGF drugs, AVEGF-HT and cancer outcomes.
Genetic variants of RNASE3 (ECP) and susceptibility to severe malaria in Senegalese population.

BACKGROUND: Severe forms of malaria (SM) are an outcome of Plasmodium falciparum infection and can cause death especially in children under 4 years of age. RNASE3 (ECP) has been identified as an inhibitor of Plasmodium parasites growth in vitro, and genetic analysis in hospitalized Ghanaian subjects has revealed the RNASE3 +371G/C (rs2073342) polymorphism as a susceptibility factor for cerebral malaria. The +371 C allele results in an Arg/Thr mutation that abolishes the cytotoxic activity of the ECP protein. The present study aims to investigate RNASE3 gene polymorphisms and their putative link to severe malaria in a malaria cohort from Senegal. METHODS/RESULTS: Patients enrolled from hospitals were classified as having either uncomplicated (UM) or severe malaria (SM). The analysis of the RNASE3 gene polymorphisms was performed in 241 subjects: 178 falciparum infected (96 SM, 82 UM) and 63 non-infected subjects as population control group (CTR). Six frequent SNPs (MAF > 3%) were identified, and one SNP was associated with malaria severity by performing a logistic regression analysis SM vs.UM: RNASE3 +499G/C (rs2233860) under age, sex as covariates and HbS/HbC polymorphisms adjustment (p = 0.003, OR 0.43, CI 95% 0.20-0.92). The polymorphisms: +371G/C (rs2073342), +499G/C (rs2233860) and +577A/T (rs8019343) defined a haplotype risk (G-G-T) for malaria severity (Fisher exact test, p = 0.03) (OR 4.1, IC 95% (1.1-14.9). CONCLUSION: In addition to the previously described association of +371G/C polymorphism in Ghanaians cohort, the RNASE3 +499G/C polymorphism was associated with susceptibility to SM in a Senegalese population. The haplotype +371G/+499G/+577T defined by RNASE3 polymorphisms was associated with severity. The genetic association identified independently in the Senegalese population provide additional evidence of a role of RNASE3 (ECP) in malaria severity.
Direct serogrouping of Dichelobacter nodosus from Victorian farms using conventional multiplex polymerase chain reaction.

OBJECTIVE: Dichelobacter nodosus is the causative agent of footrot in sheep. Ovine footrot is a major problem in Australia that results in large economic losses and a represents a very significant animal welfare issue. D. nodosus is divided into 10 serogroups (A-I, M), based on sequence variation in the type IV fimbriae gene, fimA. Control of the bacteria is possible through use of serogroup-specific vaccination, however traditional identification of the serogroups of D. nodosus on infected sheep is time-consuming and costly. With the aim of reducing time and cost, a PCR assay was used to identify serogroups of D. nodosus directly from foot swabs of infected sheep in Victoria. RESULTS: It was shown that serogroup B was most common (10 locations), followed by A, G and H (4 locations), I and C (2 locations), D, E and F (1 location). Infections with multiple serotypes were observed in 50% of farms, with the remaining 50% having only a single serogroup detected. The ability to identify serogroups quickly and cheaply direct from foot swabs will aid the understanding of the epidemiology of D. nodosus and support control programs.
Rediscovered parasitism of Andrena savignyi Spinola (Hymenoptera, Andrenidae) by Stylops (Strepsiptera, Stylopidae) and revised taxonomic status of the parasite.

Parasitism of Andrena (Suandrena) savignyi Spinola (Hymenoptera: Andrenidae) by Stylops Kirby (Strepsiptera: Stylopidae) has been recorded only once, and from an individual collected in Egypt almost a century ago, with the parasite described as Stylops savignyi Hofeneder. The recent rediscovery of this Stylops from an individual of Andrena savignyi permits a reinterpretation of the species and its affinities among other Stylops. The bee was collected at flowers of Zilla spinosa (Turra) Prantl. ( Brassicaceae) in Amariah, Riyadh, Kingdom of Saudi Arabia. Based on DNA barcode sequences from material sampled across Africa, Asia, and Europe, it is apparent that Stylops savignyi is conspecific with Stylops nassonowi Pierce, and we accordingly synonymize this name (syn. n.), with the latter representing the senior and valid name for the species. A differential diagnosis is provided for Stylops nassonowi and the morphology of the female is described, as well as the first instars.
Novel soil-inhabiting clades fill gaps in the fungal tree of life.

BACKGROUND: Fungi are a diverse eukaryotic group of degraders, pathogens, and symbionts, with many lineages known only from DNA sequences in soil, sediments, air, and water. RESULTS: We provide rough phylogenetic placement and principal niche analysis for >40 previously unrecognized fungal groups at the order and class level from global soil samples based on combined 18S (nSSU) and 28S (nLSU) rRNA gene sequences. Especially, Rozellomycota (Cryptomycota), Zygomycota s.lat, Ascomycota, and Basidiomycota are rich in novel fungal lineages, most of which exhibit distinct preferences for climate and soil pH. CONCLUSIONS: This study uncovers the great phylogenetic richness of previously unrecognized order- to phylum-level fungal lineages. Most of these rare groups are distributed in different ecosystems of the world but exhibit distinct ecological preferences for climate or soil pH. Across the fungal kingdom, tropical and non-tropical habitats are equally likely to harbor novel groups. We advocate that a combination of traditional and high-throughput sequencing methods enable efficient recovery and phylogenetic placement of such unknown taxonomic groups.
Nanocall: an open source basecaller for Oxford Nanopore sequencing data.

MOTIVATION: The highly portable Oxford Nanopore MinION sequencer has enabled new applications of genome sequencing directly in the field. However, the MinION currently relies on a cloud computing platform, Metrichor (metrichor.com), for translating locally generated sequencing data into basecalls. RESULTS: To allow offline and private analysis of MinION data, we created Nanocall. Nanocall is the first freely available, open-source basecaller for Oxford Nanopore sequencing data and does not require an internet connection. Using R7.3 chemistry, on two E.coli and two human samples, with natural as well as PCR-amplified DNA, Nanocall reads have ∼68% identity, directly comparable to Metrichor '1D' data. Further, Nanocall is efficient, processing ∼2500 Kbp of sequence per core hour using the fastest settings, and fully parallelized. Using a 4 core desktop computer, Nanocall could basecall a MinION sequencing run in real time. Metrichor provides the ability to integrate the '1D' sequencing of template and complement strands of a single DNA molecule, and create a '2D' read. Nanocall does not currently integrate this technology, and addition of this capability will be an important future development. In summary, Nanocall is the first open-source, freely available, off-line basecaller for Oxford Nanopore sequencing data. AVAILABILITY AND IMPLEMENTATION: Nanocall is available at github.com/mateidavid/nanocall, released under the MIT license. CONTACT: matei.david@oicr.on.caSupplementary information: Supplementary data are available at Bioinformatics online.