Takshan/R1 huggingface dataset:
The detection of 3 ambiguous type 2 vaccine-derived polioviruses (VDPV2s) in Uganda.

BACKGROUND: The Oral Polio Vaccine (OPV or Sabin) is genetically unstable and may mutate to form vaccine-derived polioviruses (VDPVs). METHODS: In 2014, two VDPVs type 2 were identified during routine surveillance of acute flaccid paralysis (AFP) cases. Consequently, a retrospective VDPV survey was conducted to ensure that there was no circulating VDPV in the country. All Sabin poliovirus isolates identified in Uganda 6 months before and 6 months after were re-screened; Sabin 1 and 3 polioviruses were re-screened for Sabin 2 and Sabin 2 polioviruses were re-screened for VDPVs type 2. The Poliovirus rRT-PCR ITD/VDPV 4.0 assay and sequencing were used respectively. RESULTS: The first two VDPVs type2 were identified in Eastern Uganda and the third was identified during the survey from South-western Uganda. These regions had low OPV coverage and poor AFP surveillance indicators. CONCLUSION: The retrospective VDPV survey was a useful strategy to screen for VDPVs more exhaustively. Supplementary surveillance methods need to be encouraged.
A Phase III Diagnostic Accuracy Study of a Rapid Diagnostic Test for Diagnosis of Second-Stage Human African Trypanosomiasis in the Democratic Republic of the Congo.

OBJECTIVES: To estimate the diagnostic accuracy of HAT Sero K-SeT for the field diagnosis of second-stage human African trypanosomiasis (HAT). DESIGN: A phase III diagnostic accuracy design. Consecutive patients with symptoms clinically suggestive of HAT were prospectively enrolled. We compared results of the index test HAT Sero K-SeT with those of a composite reference standard: demonstration of trypanosomes in cerebrospinal fluid (CSF), or trypanosomes detected in any other body fluid AND white blood cell count in CSF >5/μl. SETTING: Rural hospital in the Democratic Republic of the Congo. PARTICIPANTS: All patients above five years old presenting at Mosango hospital with a neurological problem of recent onset at the exclusion of trauma. INTERVENTIONS: n.a. MAIN OUTCOME MEASURES: Sensitivity and specificity of HAT Sero K-SeT test. RESULTS: The sensitivity of the HAT Sero K-SeT was 8/8 or 100.0% (95% confidence interval: 67.6 to 100.0%) and the specificity was 258/266 or 97.0% (94.2% to 98.5%). CONCLUSION: The high sensitivity of the HAT Sero K-SeT is in line with previously published estimates, though the sample of HAT cases in this study was small. The specificity estimate was very high and precise. This test, when negative, allows the clinician to rule out HAT in a clinical suspect in a hospital setting in this endemic region.
Targeting chemotherapy-resistant leukemia by combining DNT cellular therapy with conventional chemotherapy.

BACKGROUND: While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and contributes to disease relapse, and ultimately patient death. We have recently shown that allogeneic double negative T cells (DNTs) are able to target the majority of primary AML blasts in vitro and in patient-derived xenograft models. However, some primary AML blast samples are resistant to DNT cell therapy. Given the differences in the modes of action of DNTs and chemotherapy, we hypothesize that DNT therapy can be used in combination with conventional chemotherapy to further improve their anti-leukemic effects and to target chemotherapy-resistant disease. METHODS: Drug titration assays and flow-based cytotoxicity assays using ex vivo expanded allogeneic DNTs were performed on multiple AML cell lines to identify therapy-resistance. Primary AML samples were also tested to validate our in vitro findings. Further, a xenograft model was employed to demonstrate the feasibility of combining conventional chemotherapy and adoptive DNT therapy to target therapy-resistant AML. Lastly, blocking assays with neutralizing antibodies were employed to determine the mechanism by which chemotherapy increases the susceptibility of AML to DNT-mediated cytotoxicity. RESULTS: Here, we demonstrate that KG1a, a stem-like AML cell line that is resistant to DNTs and chemotherapy, and chemotherapy-resistant primary AML samples both became more susceptible to DNT-mediated cytotoxicity in vitro following pre-treatment with daunorubicin. Moreover, chemotherapy treatment followed by adoptive DNT cell therapy significantly decreased bone marrow engraftment of KG1a in a xenograft model. Mechanistically, daunorubicin increased the expression of NKG2D and DNAM-1 ligands on KG1a; blocking of these pathways attenuated DNT-mediated cytotoxicity. CONCLUSIONS: Our results demonstrate the feasibility and benefit of using DNTs as an immunotherapy after the administration of conventional chemotherapy.
Predictors of mortality in adults on treatment for human immunodeficiency virus-associated tuberculosis in Botswana: A retrospective cohort study.

Mortality in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly in sub-Saharan Africa. This study aimed to compare mortality and predictors of mortality in those who were antiretroviral therapy (ART) naïve to those with prior ART exposure. This retrospective cohort study was conducted in Serowe/Palapye District, Botswana, a predominantly urban district with a large burden of HIV-associated TB with a high case fatality. Between January 1, 2013 and December 31, 2013, patients confirmed with HIV-associated TB were enrolled and followed up. Kaplan-Meier and Cox proportional hazard modeling was undertaken to identify predictors of mortality, with ART initiation included as time-updated variable. Among the 300 patients enrolled in the study, 131 had started ART before TB diagnosis (44%). There were 45 deaths. There was no difference in mortality between ART-naïve patients and those with prior ART exposure. In the multivariate analysis, no ART use during TB treatment (hazard ratio [HR] = 5.6, 95% confidence interval [CI] = 2.9-11; P < .001), opportunistic infections other than TB (HR = 8.5, 95% CI = 4-18.4; P = .013), age ≥60 years (HR = 4.8, 95% CI = 1.8-13; P = .002), hemoglobin <10 g/dL (HR = 2.4, 95% CI = 1.3-4.5) and hepatotoxicity (HR = 5, 95% CI = 1.6-17; P = .007) were associated with increased mortality. In the subgroup analysis, among ART-naïve patients, no ART use during TB treatment (HR = 8.1, 95% CI = 3.4-19.4; P < .001), opportunistic infections other than TB (HR = 16, 95% CI = 6.2-42; P < .001), and hepatotoxicity (HR = 8.3, 95% CI = 2.6-27; P < .001) were associated with mortality. Among patients with prior ART exposure, opportunistic infections other than TB (HR = 6, 95% CI = 2.6-27; P < .001) were associated with mortality. Mortality in patients with HIV-associated TB is still high. To reduce mortality, close clinical monitoring of patients together with initiation of ART during TB treatment is indicated.
Diversity and evolution of the repetitive genomic content in Cannabis sativa.

BACKGROUND: The repetitive content of the genome, once considered to be "junk DNA", is in fact an essential component of genomic architecture and evolution. In this study, we used the genomes of three varieties of Cannabis sativa, three varieties of Humulus lupulus and one genotype of Morus notabilis to explore their repetitive content using a graph-based clustering method, designed to explore and compare repeat content in genomes that have not been fully assembled. RESULTS: The repetitive content in the C. sativa genome is mainly composed of the retrotransposons LTR/Copia and LTR/Gypsy (14% and 14.8%, respectively), ribosomal DNA (2%), and low-complexity sequences (29%). We observed a recent copy number expansion in some transposable element families. Simple repeats and low complexity regions of the genome show higher intra and inter species variation. CONCLUSIONS: As with other sequenced genomes, the repetitive content of C. sativa's genome exhibits a wide range of evolutionary patterns. Some repeat types have patterns of diversity consistent with expansions followed by losses in copy number, while others may have expanded more slowly and reached a steady state. Still, other repetitive sequences, particularly ribosomal DNA (rDNA), show signs of concerted evolution playing a major role in homogenizing sequence variation.
Scheduling of radiation with angiogenesis inhibitors anginex and Avastin improves therapeutic outcome via vessel normalization.

PURPOSE: To test whether a direct antiangiogenic peptide (anginex) and a vascular endothelial growth factor antibody (bevacizumab, Avastin) can transiently normalize vasculature within tumors to improve oxygen delivery, alleviate hypoxia, and increase the effect of radiation therapy. EXPERIMENTAL DESIGN: Tumor oxygenation levels, microvessel density and pericyte coverage were monitored in three different solid tumor models (xenograft human ovarian carcinoma MA148, murine melanoma B16F10, and murine breast carcinoma SCK) in mice. Multiple treatment schedules were tested in these models to assess the influence on the effect of radiation therapy. RESULTS: In all three tumor models, we found that tumor oxygenation levels, monitored daily in real time, were increased during the first 4 days of treatment with both anginex and bevacizumab. From treatment day 5 onward, tumor oxygenation in treated mice decreased significantly to below that in control mice. This "tumor oxygenation window" occurred in all three tumor models varying in origin and growth rate. Moreover, during the treatment period, tumor microvessel density decreased and pericyte coverage of vessels increased, supporting the idea of vessel normalization. We also found that the transient modulation of tumor physiology caused by either antiangiogenic therapy improved the effect of radiation treatment. Tumor growth delay was enhanced when single dose or fractionated radiotherapy was initiated within the tumor oxygenation window as compared with other treatment schedules. CONCLUSIONS: The results are of immediate translational importance because the clinical benefits of bevacizumab therapy might be increased by more precise treatment scheduling to ensure radiation is given during periods of peak radiosensitivity. The oxygen elevation in tumors by non-growth factor-mediated peptide anginex suggests that vessel normalization might be a general phenomenon of agents directed at disrupting the tumor vasculature by a variety of mechanisms.
Feasibility of a combined aerobic and cognitive training intervention on cognitive function in cancer survivors: a pilot investigation.

Background: Cancer-related cognitive impairment (CRCI) may negatively affect upwards of 75% of cancer patients. Exercise and cognitive training, independently, may increase functional capacity and aspects of cognitive function. Yet, combined training protocols have not been evaluated in cancer survivor populations. Therefore, the aim of this study was to explore the feasibility of a quasi-randomized, controlled, exploratory, repeated-measures aerobic and cognitive training intervention on cognitive function in participants undergoing treatment for cancer (N = 28). Methods: Pre- and post-physical and cognitive assessments were administered. A 36-session (approximately 12 weeks) computer-based cognitive (COG), aerobic (AER), cognitive and aerobic (AER + COG), and flexibility (CON) training intervention was completed. Dependent measures t tests and pre- to post percentages were then calculated to address within-group changes for each dependent variable. Results: Within-group measures revealed that the AER logical memory scores (pre- to post mean difference [2.3], 95.0% CI [0.9, 3.7], percentage change [32.7%]), delayed recall scores (pre- to post mean difference [2.1], 95.0% CI [0.3, 3.9], percentage change [27.2%]), block design scores (pre- to post mean difference [1.7], 95.0% CI [0.2, 3.2], percentage change [19.0%]), and letter-number sequencing scores (pre- to post mean difference [1.0], 95.0% CI [0.2, 1.8], percentage change [12.3%]) all increased. Aspects of verbal fluidity scores increased in the CON group. However, all cognitive scores (AER + COG and COG groups) failed to increase. Conclusions: Aerobic training for CRCI may positively impact cognitive function. Individually, these methods may appropriately address CRCI, but combined training of this nature may be too demanding for patients undergoing treatment for cancer. However, larger randomized trials are needed to substantiate this protocol in large-scale cancer rehabilitation centers.
psygenet2r: a R/Bioconductor package for the analysis of psychiatric disease genes.

Motivation: Psychiatric disorders have a great impact on morbidity and mortality. Genotype-phenotype resources for psychiatric diseases are key to enable the translation of research findings to a better care of patients. PsyGeNET is a knowledge resource on psychiatric diseases and their genes, developed by text mining and curated by domain experts. Results: We present psygenet2r, an R package that contains a variety of functions for leveraging PsyGeNET database and facilitating its analysis and interpretation. The package offers different types of queries to the database along with variety of analysis and visualization tools, including the study of the anatomical structures in which the genes are expressed and gaining insight of gene's molecular function. Psygenet2r is especially suited for network medicine analysis of psychiatric disorders. Availability and implementation: The package is implemented in R and is available under MIT license from Bioconductor (http://bioconductor.org/packages/release/bioc/html/psygenet2r.html). Contact: juanr.gonzalez@isglobal.org or laura.furlong@upf.edu. Supplementary information: Supplementary data are available at Bioinformatics online.
Variations in outcomes by residential location for women with breast cancer: a systematic review.

OBJECTIVES: To systematically assess the evidence for variations in outcomes at each step along the breast cancer continuum of care for Australian women by residential location. DESIGN: Systematic review. METHODS: Systematic searches of peer-reviewed articles in English published from 1 January 1990 to 24 November 2017 using PubMed, EMBASE, CINAHL and Informit databases. Inclusion criteria were: population was adult female patients with breast cancer; Australian setting; outcome measure was survival, patient or tumour characteristics, screening rates or frequencies, clinical management, patterns of initial care or post-treatment follow-up with analysis by residential location or studies involving non-metropolitan women only. Included studies were critically appraised using a modified Newcastle-Ottawa Scale. RESULTS: Seventy-four quantitative studies met the inclusion criteria. Around 59% were considered high quality, 34% moderate and 7% low. No eligible studies examining treatment choices or post-treatment follow-up were identified. Non-metropolitan women consistently had poorer survival, with most of this differential being attributed to more advanced disease at diagnosis, treatment-related factors and socioeconomic disadvantage. Compared with metropolitan women, non-metropolitan women were more likely to live in disadvantaged areas and had differing clinical management and patterns of care. However, findings regarding geographical variations in tumour characteristics or diagnostic outcomes were inconsistent. CONCLUSIONS: A general pattern of poorer survival and variations in clinical management for Australian female patients with breast cancer from non-metropolitan areas was evident. However, the wide variability in data sources, measures, study quality, time periods and geographical classification made direct comparisons across studies challenging. The review highlighted the need to promote standardisation of geographical classifications and increased comparability of data systems. It also identified key gaps in the existing literature including a lack of studies on advanced breast cancer, geographical variations in treatment choices from the perspective of patients and post-treatment follow-up.
Outcome of Patients With Small Vessel Vasculitis After Renal Transplantation: National Database Analysis.

Background: Small vessel vasculitis commonly affects the kidney and can progress to end-stage renal disease. The goal of this study is to compare outcomes of patients who received a renal transplant as a result of small vessel vasculitis (group A) with those who received kidney transplants because of other causes (group B). Methods: This is a retrospective analysis of United Network for Organ Sharing registry data for adult primary kidney transplants from January 2000 to December 2014. Group A patients (N = 2196) were compared with a group B (N = 6588); groups were case matched for age, race, sex, donor type, and year of transplant in a 1:3 ratio. Results: Renal and patient survivals were better in the group A (P < 0.001). New-onset diabetes after transplant developed in 8.3% of the group A and 11.3% of group B (P < 0.001). Seventeen (0.8%) patients in group A developed recurrent disease. Of these, 7 patients had graft failure, 3 of which were due to disease recurrence. Group A patients had significantly higher risk of developing posttransplant solid organ malignancies (11.3% vs 9.3%, P = 0.006) and lymphoproliferative disorder (1.3% vs 0.8%, P = 0.026). Independent predictors of graft failure and patient mortality were recipients' morbid obesity, diabetes, age, and dialysis duration (hazard ratio of 1.7, 1.4, 1.1/10 years, and 1.1/year for graft failure, and 1.7, 1.7, 1.6/10 years and 1.1/year for patient mortality, respectively). Conclusions: Renal transplantation in patients with has favorable long-term graft and patient outcomes with a low disease recurrence rate. However, they may have a higher risk of developing posttransplant malignancies.
Rcupcake: an R package for querying and analyzing biomedical data through the BD2K PIC-SURE RESTful API.

Motivation: In the era of big data and precision medicine, the number of databases containing clinical, environmental, self-reported and biochemical variables is increasing exponentially. Enabling the experts to focus on their research questions rather than on computational data management, access and analysis is one of the most significant challenges nowadays. Results: We present Rcupcake, an R package that contains a variety of functions for leveraging different databases through the BD2K PIC-SURE RESTful API and facilitating its query, analysis and interpretation. The package offers a variety of analysis and visualization tools, including the study of the phenotype co-occurrence and prevalence, according to multiple layers of data, such as phenome, exposome or genome. Availability and implementation: The package is implemented in R and is available under Mozilla v2 license from GitHub (https://github.com/hms-dbmi/Rcupcake). Two reproducible case studies are also available (https://github.com/hms-dbmi/Rcupcake-case-studies/blob/master/SSCcaseStudy_v01.ipynb, https://github.com/hms-dbmi/Rcupcake-case-studies/blob/master/NHANEScaseStudy_v01.ipynb). Contact: paul_avillach@hms.harvard.edu. Supplementary information: Supplementary data are available at Bioinformatics online.
Porosity analysis of MTA and Biodentine cements for use in endodontics by using micro-computed tomography.

Background: The purpose of this study is to compare the porosity of two repair cements, White ProRoot® MTA and Biodentine®. These samples were analyzed by using micro-computed microtomography. Material and Methods: Sixteen samples were used in the study that were divided according to the composition of the materials used. White ProRoot® MTA (n = 8) and Biodentine® (n = 8) were the samples prepared according to the manufacturer's instructions. They were placed in silicone molds of 5 ± 0.1mm in height and an internal diameter of 5 ± 0.1mm, 24 hours after its preparation, the samples were scanned through a micro-CT, the porosity results were analyzed statistically by independent "t" tests. Results: It is evident that Biodentine® has better porosity properties than ProRoot® MTA. The results of the study quantify a smaller number of pores per surface, a smaller volume in each pore per mm3 and a lower total porosity present in samples of Biodentine® unlike ProRoot® MTA samples which is larger in both. Conclusions: The results obtained in computerized microtomography endodontic biomaterial samples concluded that Biodentine® has a lower porosity than ProRoot® MTA. Key words:Porosity, microleakage, micro-CT, endodontic cements.
Viral Interactions with Host Cell Rab GTPases.

Viruses are obligate intracellular parasites that utilize cellular machinery for many aspects of their replication cycles. Enveloped viruses generally rely upon host vesicular trafficking machinery to direct their structural proteins and genomes to sites of virus replication, assembly, and budding. Rab GTPases have been implicated in the replication of many important viral pathogens infecting humans. This review provides a summary of virus-Rab protein interactions, with a particular focus on the role of Rab-related trafficking pathways on late events in the lifecycle of herpesviruses and of HIV-1.
The effect of a short animated educational video on knowledge among glaucoma patients.

Purpose: To evaluate the effectiveness of an educational video in increasing knowledge among glaucoma patients and to determine the factors that may influence a patient's level of knowledge. Patients and methods: This was a pre-post intervention study on adult glaucoma patients attending the outpatient service at King Khaled Eye Specialist Hospital. The intervention tested was a short educational video that was edited specifically for this study. All patients completed a pre-video and post-video knowledge questionnaire; moreover, sociodemographic and clinical characteristics were obtained. Results: The total number of patients included was 196. The mean age of patients was 55.7±15.5 years. Overall, 55.1% were males, 29.6% were illiterate, 85.2% resided in an urban area, 62.8% had a low income, and 41.8% were unemployed. The mean pre-intervention knowledge score was 6 out of 17, and the post-intervention score was 11.1 (P≤0.001). Predictors of a poor knowledge score were old age (>60 years), female sex, illiteracy, rural residence, low income, unemployment, and a negative family history of glaucoma. Conclusion: The evaluated video intervention was effective in a short-term increase in knowledge among glaucoma patients. This tool may serve as an alternative to traditional educational methods.