tbuckley/cabot-search huggingface dataset:
Development of HIV self-testing services through youth engagement: a qualitative evaluation of a health designathon in Nigeria
Authors: Chisom Obiezu-Umeh, Titilola Gbajabiamila, Ucheoma Nwaozuru, Florida Uzoaru, Stacey Mason, David Oladele, Ifeoma Idigbe, Adesola Musa, Donaldson Conserve, Suzanne Nkengasong, Collins Airhihenbuwa, Oliver Ezechi, Joseph Tucker, Juliet Iwelunmor
Journal: The Lancet Global Health (2020)

BackgroundProviding a platform to engage young people as active participants and decision-makers in the design and delivery process of HIV testing efforts is critical to optimise uptake of HIV testing and other preventive services among this population. Designathon, an intensive team-based contest to crowdsource solutions, is a form of participatory approach that may increase the effectiveness of implementation strategies by fully engaging the end users in the design process. In this study, we explore strategies for HIV self-testing (HIVST) delivery developed at a designathon contest in Nigeria.MethodsThe 48-h HIVST designathon held from March 29 to March 31, 2019, in Lagos state, Nigeria, occurred in three phases. First, we solicited solutions from Nigerian youth on how to encourage self-testing for HIV and other sexually transmitted infections in a way that is low-cost, accessible, youth-friendly and confidential. Second, submissions were shortlisted by an advisory committee and the top teams were invited to compete at the designathon contest. Third, the top teams presented their strategies using the business model canvas (BMC) to an expert panel. The BMC included: (1) description of the value of the HIVST service; (2) how and where to deliver HIVST; and (3) youth-friendly HIVST service strategies. Thematic analysis was used to explore key elements of the business model canvas.FindingsOf the 127 submissions received, 13 teams (with a total of 42 participants) were selected to participate at the designathon. Participants' median age was 22·5 years (IQR 21–24 years) and 28 (67%) were male. Teams developed segment-specific approaches such as online (ie, unstructured supplementary service data (USSD) services, gamification) and offline (ie, vending machines, community youth mobilisers) options for distributing and promoting the HIVST kit to reach a wider range of young people in both urban and rural settings. Multi-stakeholder partnerships at the local, state, and federal level were identified as key implementation mechanisms to drive scale-up and sustainability efforts.InterpretationDesignathons are a feasible method of facilitating meaningful youth engagement to develop deployable strategies to increase the uptake of HIV testing in young people in Nigeria. Additional refinement and rigorous evaluations of the proposed strategies in practice is an important next step to assess the effectiveness and impact of the models.FundingEunice Kennedy Shriver National Institute of Child Health and Human Development Grant number: 1UG3HD096929 and NIAID K24AI143471
Re: MaryBeth B. Culp, Isabelle Soerjomataram, Jason A. Efstathiou, Freddie Bray, Ahmedin Jemal. Recent Global Patterns in Prostate Cancer Incidence and Mortality Rates. Eur Urol 2020;77:38–52
Authors: Ausvydas Patasius, Giedre Smailyte
Journal: European Urology (2019)
Mapping the burden of onchocercal skin disease*
Authors: M.E. Murdoch
Journal: British Journal of Dermatology (2020)

Onchocerciasis is a neglected tropical disease caused by a nematode parasite, Onchocerca volvulus, and transmitted by bites of Simulium blackflies which breed near fast-flowing rivers. In humans, thousands of microfilariae (immature worms) migrate to the skin and eyes where they cause pathology. Historically, much research was devoted to the serious effect of blindness, from which the disease earns its alternative name of ‘river blindness’. Mapping the burden of onchocercal skin disease (OSD) was expedited by the development of a clinical classification and grading system that facilitated comparison of data from different countries. After successful field testing in Nigeria, the classification scheme was used in a multicountry study in seven endemic sites, to estimate the true burden of OSD across Africa. High levels of OSD were found, affecting 28% of the population. A new control programme, the African Programme for Onchocerciasis Control (APOC) was launched in 20 countries using annual doses of ivermectin, donated by Merck & Co., Inc. The multicountry study also found a close correlation between the levels of itching and OSD with the level of endemicity, as determined by the prevalence of onchocercal nodules. This enabled APOC to use Rapid Epidemiological Mapping of Onchocerciasis, which entailed identifying likely vector breeding sites near rivers, then sampling 50 adult males in nearby villages to determine the prevalence of nodules and delineate which villages required treatment. Onchocerciasis is now targeted for elimination in Africa, and the challenge is to complete Onchocerciasis Elimination Mapping of hypoendemic areas using serology.
Impact of the COVID-19 Pandemic on Paediatric Urology Practice in Europe: A Reflection from the European Association of Urology Young Academic Urologists
Authors: Anne-Françoise Spinoit, Bernhard Haid, Manuela Hiess, Beatriz Banuelos, Lisette 't Hoen, Anna Radford, Mesrur Selçuk Silay
Journal: European Urology (2020)
Erratum: Corrigendum: Genome-wide analysis of mammalian promoter architecture and evolution
Authors: Piero Carninci, Albin Sandelin, Boris Lenhard, Shintaro Katayama, Kazuro Shimokawa, Jasmina Ponjavic, Colin A M Semple, Martin S Taylor, Pär G Engström G, Martin C Frith, Alistair R R Forrest, Wynand B Alkema, Sin Lam Tan, Charles Plessy, Rimantas Kodzius, Timothy Ravasi, Takeya Kasukawa, Shiro Fukuda, Mutsumi Kanamori-Katayama, Yayoi Kitazume, Hideya Kawaji, Chikatoshi Kai, Mari Nakamura, Hideaki Konno, Kenji Nakano, Salim Mottagui-Tabar, Peter Arner, Alessandra Chesi, Stefano Gustincich, Francesca Persichetti, Harukazu Suzuki, Sean M Grimmond, Christine A Wells, Valerio Orlando, Claes Wahlestedt, Edison T Liu, Matthias Harbers, Jun Kawai, Vladimir B Bajic, David A Hume, Yoshihide Hayashizaki
Journal: Nature Genetics (2007)
Complex Immune Dysregulation in COVID-19 Patients with Severe Respiratory Failure
Authors: Evangelos J. Giamarellos-Bourboulis, Mihai G. Netea, Nikoletta Rovina, Karolina Akinosoglou, Anastasia Antoniadou, Nikolaos Antonakos, Georgia Damoraki, Theologia Gkavogianni, Maria-Evangelia Adami, Paraskevi Katsaounou, Maria Ntaganou, Magdalini Kyriakopoulou, George Dimopoulos, Ioannis Koutsodimitropoulos, Dimitrios Velissaris, Panagiotis Koufargyris, Athanassios Karageorgos, Konstantina Katrini, Vasileios Lekakis, Mihaela Lupse, Antigone Kotsaki, George Renieris, Danai Theodoulou, Vassiliki Panou, Evangelia Koukaki, Nikolaos Koulouris, Charalambos Gogos, Antonia Koutsoukou
Journal: Cell Host & Microbe (2020)
The Relationship of JAM2 Polymorphisms and Graft-Versus-Host-Disease (GVHD) after Allogeneic Stem Cell Transplantation
Authors: Eunkyung Park, Sung-Hyo Park, Kyu-Hyoung Lim, Ji Ae Song, Inho Kim, Sung-Soo Yoon, Seonyang Park
Journal: Blood (2008)
Efficacy and Safety of 1:1 Fixed-Ratio Combination of Insulin Glargine and Lixisenatide Versus Lixisenatide in Japanese Patients With Type 2 Diabetes Inadequately Controlled on Oral Antidiabetic Drugs: The LixiLan JP-O1 Randomized Clinical Trial
Authors: Hirotaka Watada, Akane Takami, Robert Spranger, Atsushi Amano, Yasuhiro Hashimoto, Elisabeth Niemoeller
Journal: Diabetes Care (2020)

OBJECTIVE To assess the efficacy and safety of a 1:1 fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) versus lixisenatide (Lixi) in insulin-naive Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on oral antidiabetic drugs (OADs). RESEARCH DESIGN AND METHODS In this phase 3, open-label, multicenter trial, 321 patients with HbA1c≥7.5 to ≤10.0% (58–86 mmol/mol) and fasting plasma glucose (FPG) ≤13.8 mmol/L (250 mg/dL) were randomized 1:1 to iGlarLixi or Lixi for 52 weeks. The primary end point was change in HbA1c at week 26. RESULTS Change in HbA1c from baseline to week 26 was significantly greater with iGlarLixi (−1.58% [−17.3 mmol/mol]) than with Lixi (−0.51% [−5.6 mmol/mol]), confirming the superiority of iGlarLixi (least squares [LS] mean difference −1.07% [−11.7 mmol/mol], P &amp;lt; 0.0001). At week 26, significantly greater proportions of patients treated with iGlarLixi reached HbA1c &amp;lt;7% (53 mmol/mol) (65.2% vs. 19.4%; P &amp;lt; 0.0001), and FPG reductions were greater with iGlarLixi than Lixi (LS mean difference −2.29 mmol/L [−41.23 mg/dL], P &amp;lt; 0.0001). Incidence of documented symptomatic hypoglycemia (≤3.9 mmol/L [70 mg/dL]) was higher with iGlarLixi (13.0% vs. 2.5%) through week 26, with no severe hypoglycemic events in either group. Incidence of gastrointestinal events through week 52 was lower with iGlarLixi (36.0% vs. 50.0%), and rates of treatment-emergent adverse events were similar. CONCLUSIONS This phase 3 study demonstrated superior glycemic control and fewer gastrointestinal adverse events with iGlarLixi than with Lixi, which may support it as a new treatment option for Japanese patients with T2DM that is inadequately controlled with OADs.
Multiple Non-Linear Epitopes of ADAMTS13 Were Targeted by Anti- ADAMTS13 IgG in Patients with Acquired Idiopathic Thrombotic Thrombocytopenic Purpura
Authors: Dezhi Shang, Haifeng Wu, Spero Cataland, Charles L. Bennett, Hau C. Kwaan, X. Long Zheng
Journal: Blood (2008)
The EZH2–PHACTR2–AS1–Ribosome Axis induces Genomic Instability and Promotes Growth and Metastasis in Breast Cancer
Authors: Wenhui Chu, Xi Zhang, Lihua Qi, Yenan Fu, Peng Wang, Wei Zhao, Juan Du, Jing Zhang, Jun Zhan, Yunling Wang, Wei-Guo Zhu, Yu Yu, Hongquan Zhang
Journal: Cancer Research (2020)

Aberrant activation of histone methyltransferase EZH2 and ribosome synthesis strongly associate with cancer development and progression. We previously found that EZH2 regulates RNA polymerase III-transcribed 5S ribosomal RNA gene transcription. However, whether EZH2 regulates ribosome synthesis is still unknown. Here, we report that EZH2 promotes ribosome synthesis by targeting and silencing a long noncoding RNA PHACTR2-AS1. PHACTR2-AS1 directly bound ribosome DNA genes and recruited histone methyltransferase SUV39H1, which in turn triggered H3K9 methylation of these genes. Depletion of PHACTR2-AS1 resulted in hyperactivation of ribosome synthesis and instability of ribosomal DNA, which promoted cancer cell proliferation and metastasis. Administration of PHACTR2-AS1-30nt-RNA, which binds to SUV39H1, effectively inhibited breast cancer growth and lung metastasis in mice. PHACTR2-AS1 was downregulated in breast cancer patients, where lower PHACTR2-AS1 expression promoted breast cancer development and correlated with poor patient outcome. Taken together, we demonstrate that PHACTR2-AS1 maintains a H3K9 methylation-marked silent state of ribosomal DNA genes, comprising a regulatory axis that controls breast cancer growth and metastasis. SIGNIFICANCE: These findings reveal that EZH2 mediates ribosomal DNA stability via silencing of PHACTR2-AS1, representing a potential therapeutic target to control breast cancer growth and metastasis.
Microbiota-Related Metabolites and the Risk of Type 2 Diabetes
Authors: Jagadish Vangipurapu, Lilian Fernandes Silva, Teemu Kuulasmaa, Ulf Smith, Markku Laakso
Journal: Diabetes Care (2020)

Recent studies have highlighted the significance of the microbiome in human health and disease. Changes in the metabolites produced by microbiota have been implicated in several diseases. Our objective was to identify microbiome metabolites that are associated with type 2 diabetes.Our study included 5,181 participants from the cross-sectional Metabolic Syndrome in Men (METSIM) study that included Finnish men (age 57 ± 7 years, BMI 26.5 ± 3.5 kg/m2) having metabolomics data available. Metabolomics analysis was performed based on fasting plasma samples. On the basis of an oral glucose tolerance test, Matsuda ISI and disposition index values were calculated as markers of insulin sensitivity and insulin secretion. A total of 4,851 participants had a 7.4-year follow-up visit, and 522 participants developed type 2 diabetes.Creatine, 1-palmitoleoylglycerol (16:1), urate, 2-hydroxybutyrate/2-hydroxyisobutyrate, xanthine, xanthurenate, kynurenate, 3-(4-hydroxyphenyl)lactate, 1-oleoylglycerol (18:1), 1-myristoylglycerol (14:0), dimethylglycine, and 2-hydroxyhippurate (salicylurate) were significantly associated with an increased risk of type 2 diabetes. These metabolites were associated with decreased insulin secretion or insulin sensitivity or both. Among the metabolites that were associated with a decreased risk of type 2 diabetes, 1-linoleoylglycerophosphocholine (18:2) significantly reduced the risk of type 2 diabetes.Several novel and previously reported microbial metabolites related to the gut microbiota were associated with an increased risk of incident type 2 diabetes, and they were also associated with decreased insulin secretion and insulin sensitivity. Microbial metabolites are important biomarkers for the risk of type 2 diabetes.
Helen Salisbury: Who is vulnerable?
Authors: Helen Salisbury
Journal: BMJ (2020)

The Easter bank holidays were cancelled for general practices at short notice, to take the pressure off out-of-hours services in anticipation of a rise in demand. Most of my patients assumed that we were closed, so I spent the time trying to unravel the confusion generated by the government’s shielding programme. People who are at high risk of complications if they contract coronavirus have received a letter advising them to be in strict isolation for at least 12 weeks from the end of March.

The accuracy of the centrally generated lists depends partly on the quality of prior coding in GP notes, …
Underwater peroral endoscopic myotomy (u-POEM) after tension capnoperitoneum and capnothorax during POEM
Authors: Hugo Uchima, Juan Colan, Ingrid Marín, Vicente Moreno, Guillermo Larios, Rachid Tazi, Jordi Serra
Journal: Endoscopy (2020)

Severe peroral endoscopic myotomy (POEM)-related complications are uncommon (about 1.2 % [1]), and CO2-related complications are usually mild. Nevertheless, severe life-threatening complications such as tension capnothorax or capnoperitoneum with hemodynamic and respiratory compromise could develop. Underwater POEM, described by Binmoeller [2], could be used to prevent CO2-related complications.
Reply to ‘The case for evidence-based medicine for the association between hyperuricaemia and CKD’
Authors: Yuka Sato, Daniel I. Feig, Austin G. Stack, Duk-Hee Kang, Miguel A. Lanaspa, A. Ahsan Ejaz, L. Gabriela Sánchez-Lozada, Masanari Kuwabara, Claudio Borghi, Richard J. Johnson
Journal: Nature Reviews Nephrology (2020)
Abstract 14662: Treatment Combinations for Elderly Patients and Those With Comorbidities After an Acute Myocardial Infarction
Authors: Linnea A Polgreen, Nick Street, Sulyun Lee
Journal: Circulation (2019)

Introduction: Following an acute myocardial infarction (AMI), the elderly and patients with comorbidities often do not receive guideline-recommended treatment. Because such patients were generally ...
Quantitative analysis of interactive behavior of mitochondria and lysosomes using structured illumination microscopy
Authors: Qixin Chen, Xintian Shao, Mingang Hao, Hongbao Fang, Ruilin Guan, Zhiqi Tian, Miaoling Li, Chenran Wang, Liangnian Ji, Hui Chao, Jun-Lin Guan, Jiajie Diao
Journal: Biomaterials (2020)
The Genomics of Human Local Adaptation
Authors: Jasmin S. Rees, Sergi Castellano, Aida M. Andrés
Journal: Trends in Genetics (2020)

Modern humans inhabit a variety of environments and are exposed to a plethora of selective pressures, leading to multiple genetic adaptations to local environmental conditions. These include adaptations to climate, UV exposure, disease, diet, altitude, or cultural practice and have generated important genetic and phenotypic differences amongst populations. In recent years, new methods to identify the genomic signatures of natural selection underlying these adaptations, combined with novel types of genetic data (e.g., ancient DNA), have provided unprecedented insights into the origin of adaptive alleles and the modes of adaptation. As a result, numerous instances of local adaptation have been identified in humans. Here, we review the most exciting recent developments and discuss, in our view, the future of this field.
Implications of Preoperative Patient Frailty on Stratified Postoperative Mortality
Authors: Naomi M. Sell, Motaz Qadan, Julie K. Silver
Journal: JAMA Surgery (2020)

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NCOA3: A molecular prognostic marker for melanoma
Authors: J. Rangel, S. Torabian, L. Shaikh, M. Nosrati, J. R. Miller, R. W. Sagebiel, M. Kashani-Sabet
Journal: Journal of Clinical Oncology (2006)

8007 Background: Nuclear receptor coactivator-3 (NCOA3, also known as AIB1 or SRC-3), a member of the steroid receptor coactivator 1 family, has been shown to be amplified in human breast cancer. We recently identified NCOA3 as differentially expressed in metastatic melanomas by gene expression profiling, suggesting its role as a possible molecular prognostic factor. In this study, we assessed the prognostic significance of NCOA3 expression in a large melanoma patient cohort using tissue micro-arrays (TMAs). Methods: We used a commercially available antibody against NCOA3 to perform immunohistochemical analysis of NCOA3 expression in TMAs containing primary melanoma specimens from 353 patients seen at the UCSF Melanoma Center. Cases included clinicopathologic information (e.g., age, sex, tumor location, tumor thickness, Clark level and ulceration), as well as sentinel lymph node (SLN) status, and information regarding relapse-free (RFS) and disease-specific (DSS) survival. NCOA3 expression was assessed on a 4-point scale (0–3) by an observer blinded to patient outcomes. Results: High NCOA3 expression was significantly predictive of SLN metastasis by univariate logistic regression (p=0.015), and associated with a higher mean positive SLN count (p=0.03, Le test). Kaplan-Meier analysis demonstrated a significant association between increased NCOA3 expression and reduced RFS as well as DSS (p=0.024, and p=0.031 by log-rank test, respectively). Multivariate step-wise logistic regression analysis of 12 factors revealed NCOA3 expression, along with tumor thickness, age, vascular involvement, and Clark level to be independent predictors of SLN status. Multivariate Cox regression analysis showed the independent impact of NCOA3 expression on RFS and DSS with the inclusion of the AJCC factors tumor thickness, ulceration, Clark level, tumor location, patient age and sex. Conclusions: These results reveal NCOA3 to be a novel, independent marker of melanoma outcome, with a significant impact on SLN metastasis, RFS and DSS. No significant financial relationships to disclose.
D3Targets-2019-nCoV: a webserver for predicting drug targets and for multi-target and multi-site based virtual screening against COVID-19
Authors: Yulong Shi, Xinben Zhang, Kaijie Mu, Cheng Peng, Zhengdan Zhu, Xiaoyu Wang, Yanqing Yang, Zhijian Xu, Weiliang Zhu
Journal: Acta Pharmaceutica Sinica B (2020)

A highly effective medicine is urgently required to cure coronavirus disease 2019 (COVID-19). For the purpose, we developed a molecular docking based webserver, namely D3Targets-2019-nCoV, with two functions, one is for predicting drug targets for drugs or active compounds observed from clinic or in vitro/in vivo studies, the other is for identifying lead compounds against potential drug targets via docking. This server has its unique features, (1) the potential target proteins and their different conformations involving in the whole process from virus infection to replication and release were included as many as possible; (2) all the potential ligand-binding sites with volume larger than 200 Å3 on a protein structure were identified for docking; (3) correlation information among some conformations or binding sites was annotated; (4) it is easy to be updated, and is accessible freely to public (https://www.d3pharma.com/D3Targets-2019-nCoV/index.php). Currently, the webserver contains 42 proteins [20 severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) encoded proteins and 22 human proteins involved in virus infection, replication and release] with 69 different conformations/structures and 557 potential ligand-binding pockets in total. With 6 examples, we demonstrated that the webserver should be useful to medicinal chemists, pharmacologists and clinicians for efficiently discovering or developing effective drugs against the SARS-CoV-2 to cure COVID-19.
CA180-372: An International Collaborative Phase 2 Trial of Dasatinib and Chemotherapy in Pediatric Patients with Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL)
Authors: Stephen P. Hunger, Vaskar Saha, Meenakshi Devidas, Maria Grazia Valsecchi, Julie Gastier Foster, Gianni Cazzaniga, Shalini C. Reshmi, Michael Borowitz, Anthony Moorman, Nyla A. Heerema, Andrew J. Carroll, Phillip Barnette, M. Monica Monica Gramatges, Kelly Maloney, Weili Sun, Rene Swanink, Amanda Termuhlen, Mignon L. Loh, Elizabeth A. Raetz, Lewis B. Silverman, Martin Schrappe, Kirk R. Schultz, William Slayton, Diane Healey, Andrea Biondi
Journal: Blood (2017)
An International Multicenter Retrospective Comparison of Induction Chemoimmunotherapy Regimens on Outcomes in Patients with Transplant-Eligible Mantle Cell Lymphoma
Authors: Zi Yun Ng, Mark Bishton, David Ritchie, Robert Campbell, Michael P Gilbertson, Kate Hill, Sumita Ratnasingam, Anthony P Schwarer, Kate Manos, Sophie Shorten, Melissa Liet Hing Ng, Niles Elizabeth Nelson, Liu Xin, Sanjay De Mel, Tenny Sunny, Duncan Purtill, Michelle Poon, Anna M. Johnston, Tara Cochrane, Hui-Peng Lee, Greg Hapgood, Constantine S. Tam, Stephen Opat, Eliza A Hawkes, John F Seymour, Chan Yoon Cheah
Journal: Blood (2017)