tbuckley/cabot-search huggingface dataset:
The global burden of tuberculosis mortality in children: a mathematical modelling study
Authors: Peter J Dodd, Courtney M Yuen, Charalambos Sismanidis, James A Seddon, Helen E Jenkins
Journal: The Lancet Global Health (2017)

Tuberculosis in children is increasingly recognised as an important component of the global tuberculosis burden, with an estimated 1 million cases in 2015. Although younger children are vulnerable to severe forms of tuberculosis disease, no age-disaggregated estimates of paediatric tuberculosis mortality exist, and tuberculosis has never been included in official estimates of under-5 child mortality. We aimed to produce a global mortality burden estimate in children using a complementary approach not dependent on vital registration data.In this mathematical modelling study, we estimated deaths in children younger than 5 years and those aged 5-14 years for 217 countries and territories using a case-fatality-based approach. We used paediatric tuberculosis notification data and HIV and antiretroviral treatment estimates to disaggregate the WHO paediatric tuberculosis incidence estimates by age, HIV, and treatment status. We then applied systematic review evidence on corresponding case-fatality ratios.We estimated that 239 000 (95% uncertainty interval [UI] 194 000-298 000) children younger than 15 years died from tuberculosis worldwide in 2015; 80% (191 000, 95% UI 132 000-257 000) of these deaths were in children younger than 5 years. More than 70% (182 000, 140 000-239 000) of deaths occurred in the WHO southeast Asia and Africa regions. We estimated that 39 000 (17%, 23 000-73 000) paediatric tuberculosis deaths worldwide were in children with HIV infections, with 31 000 (36%, 19 000-59 000) in the WHO Africa region. More than 96% (230 000, 185 000-289 000) of all tuberculosis deaths occurred in children not receiving tuberculosis treatment.Tuberculosis is a top ten cause of death in children worldwide and a key omission from previous analyses of under-5 mortality. Almost all these deaths occur in children not on tuberculosis treatment, implying substantial scope to reduce this burden.UNITAID, National Institutes of Health, and National Institute for Health Research.
Reduced immunoglobulin gene diversity in patients with Cornelia de Lange syndrome
Authors: Andrea Björkman, Likun Du, Mirjam van der Burg, Valerie Cormier-Daire, Guntram Borck, Juan Pié, Britt-Marie Anderlid, Lennart Hammarström, Lena Ström, Jean-Pierre de Villartay, David Kipling, Deborah Dunn Walters, Qiang Pan-Hammarström
Journal: Journal of Allergy and Clinical Immunology (2017)

B cells rely on a broad receptor repertoire to provide protection against a wide range of pathogens. This is in part achieved through V(D)J recombination, which, by assembling various combinations of variable (V), diversity (D), and joining (J) genes, creates different IgV regions.1 The recombination processes is initiated by recombination-activating gene (RAG) 1/RAG2 enzymes and requires a functional nonhomologous end-joining (NHEJ) machinery. B cells can further diversify their IgV regions through somatic hypermutation (SHM) to improve affinity between the antibody and antigen and switch the isotype of antibody produced by class-switch recombination (CSR).
Plasma cell deficiency in human subjects with heterozygous mutations in Sec61 translocon alpha 1 subunit (SEC61A1)
Authors: Desirée Schubert, Marie-Christine Klein, Sarah Hassdenteufel, Andrés Caballero-Oteyza, Linlin Yang, Michele Proietti, Alla Bulashevska, Janine Kemming, Johannes Kühn, Sandra Winzer, Stephan Rusch, Manfred Fliegauf, Alejandro A. Schäffer, Stefan Pfeffer, Roger Geiger, Adolfo Cavalié, Hongzhi Cao, Fang Yang, Yong Li, Marta Rizzi, Hermann Eibel, Robin Kobbe, Amy L. Marks, Brian P. Peppers, Robert W. Hostoffer, Jennifer M. Puck, Richard Zimmermann, Bodo Grimbacher
Journal: Journal of Allergy and Clinical Immunology (2017)

Primary antibody deficiencies (PADs) are the most frequent primary immunodeficiencies in human subjects. The genetic causes of PADs are largely unknown. Sec61 translocon alpha 1 subunit (SEC61A1) is the major subunit of the Sec61 complex, which is the main polypeptide-conducting channel in the endoplasmic reticulum membrane. SEC61A1 is a target gene of spliced X-box binding protein 1 and strongly induced during plasma cell (PC) differentiation.We identified a novel genetic defect and studied its pathologic mechanism in 11 patients from 2 unrelated families with PADs.Whole-exome and targeted sequencing were conducted to identify novel genetic mutations. Functional studies were carried out ex vivo in primary cells of patients and in vitro in different cell lines to assess the effect of SEC61A1 mutations on B-cell differentiation and survival.We investigated 2 families with patients with hypogammaglobulinemia, severe recurrent respiratory tract infections, and normal peripheral B- and T-cell subpopulations. On in vitro stimulation, B cells showed an intrinsic deficiency to develop into PCs. Genetic analysis and targeted sequencing identified novel heterozygous missense (c.254T>A, p.V85D) and nonsense (c.1325G>T, p.E381*) mutations in SEC61A1, segregating with the disease phenotype. SEC61A1-V85D was deficient in cotranslational protein translocation, and it disturbed the cellular calcium homeostasis in HeLa cells. Moreover, SEC61A1-V85D triggered the terminal unfolded protein response in multiple myeloma cell lines.We describe a monogenic defect leading to a specific PC deficiency in human subjects, expanding our knowledge about the pathogenesis of antibody deficiencies.
Effect of a Diet Relatively Low in Cystine on the Production of Spontaneous Mammary-Gland Tumors in Strain C3H Female Mice
Authors: Julius White, Howard B. Andervont
Journal: JNCI Journal of the National Cancer Institute (1943)

Effect of a Diet Relatively Low in Cystine on the Production of Spontaneous Mammary-Gland Tumors in Strain C3H Female Mice Julius White, Julius White senior biochemist Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard B. Andervont Howard B. Andervont principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 5, June 1943, Pages 449–451, https://doi.org/10.1093/jnci/3.5.449 Published: 01 June 1943
Progressive Hyperleukocytosis during Initial Therapy Is a Predictive Marker for Differentiation Syndrome and Early Mortality in Adult Patients with Acute Promyelocytic Leukemia
Authors: Jae-Ho Yoon, Heeje Kim, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho, Dong-Wook Kim, Jong-Wook Lee, Woo-Sung Min
Journal: Blood (2016)
Common Cardiovascular Complications of Cancer Therapy: Epidemiology, Risk Prediction, and Prevention
Authors: Vivek Narayan, Bonnie Ky
Journal: Annual Review of Medicine (2018)

There is growing awareness of the overlap between oncologic and cardiovascular (CV) diseases, including a wide range of CV effects of anticancer therapies. As novel anticancer therapeutics become available and cancer survival outcomes improve, the CV implications of cancer therapy become increasingly important. In addition to outlining the CV effects of commonly used cancer therapies and their consequences for long-term survivorship, this review highlights the recent efforts to improve the risk prediction and prevention of CV toxicity through the evaluation of sensitive measures for early toxicity detection and the implementation of cardioprotective strategies.
Role of MCM as an adjuvant to urine cytology in the diagnosis of bladder cancer.
Authors: Nadira Narine, Bensita M.V Thottakam, Alessia Donnini, Sushant Dhanvijay, Kasra Saeb-Parsy, Alex Wilson, Durgesh N Rana
Journal: Journal of Clinical Oncology (2012)

e15011 Background: Urine cytology, a cheap non invasive first line test (PAP) has traditionally been used for the diagnosis of urothelial carcinoma (UC) as it has excellent sensitivity for the detection of high grade and in situ lesions. However, sensitivity for low grade carcinoma is rather varied as this is a problematic area with various mimics leading to both over and under diagnoses. To overcome this dilemma, a number of biomarkers and molecular tests have been employed with mixed results and varied financial implications. We report on a relatively cheap and easily adopted in vitro diagnostic test, Minichromosome maintenance (MCM) proteins, as an adjuvant to cytology in the diagnosis of both low and high grade bladder cancer (BC). MCM proteins play an important regulatory role in eukaryotic DNA replication and is expressed only as normal cells progress from G0 into G1/S phase of the cell cycle. However, over expression has been demonstrated in neoplasia in a range of sites including urothelium. Methods: 106 patients from gross haematuria (GH, 39) and cystoscopic surveillance (CS, 67) clinics were investigated for newly diagnosed and recurrent BC respectively by MCM and cytology with histological outcome being used as the gold standard. Results: Using biopsy positive outcome, MCM and cytology had a sensitivity of 91.7%, specificity of 86.6%, PPV of 66.7% and NPV of 97.3%. There was noticeably improved correlation of MCM and cytology with increasing grade of BC (Table). Conclusions: We showed the combination of MCM and cytology to be highly sensitive and specific for the determination of CIS, G2, and G3 BC with improved detection of G1 bladder cancer. The combination of MCM and cytology suggests that this offers promise as a novel diagnostic biomarker in GH and CS patients. [Table: see text]
高容量神経インタフェイス用のダイヤモンドの成長と後処理の最適化【Powered by NICT】
Authors: Tong Wei, Fox Kate, Zamani Akram, M Turnley Ann, Ganesan Kumaravelu, Ahnood Arman, Cicione Rosemary, Meffin Hamish, Prawer Steven, Stacey Alastair, J Garrett David
Journal: Biomaterials (2016)
デュアルモード癌イメージングと画像誘導化学熱治療のためのハイブリッド異方性ナノ構造【Powered by NICT】
Authors: Zhang Ruiping, Cheng Kai, L Antaris Alexander, Ma Xiaowei, Yang Min, Ramakrishnan Sindhuja, Liu Guifeng, Lu Alex, Dai Hongjie, Tian Mei, Cheng Zhen
Journal: Biomaterials (2016)
MR-based respiratory and cardiac motion correction for PET imaging
Authors: Thomas Küstner, Martin Schwartz, Petros Martirosian, Sergios Gatidis, Ferdinand Seith, Christopher Gilliam, Thierry Blu, Hadi Fayad, Dimitris Visvikis, F. Schick, B. Yang, H. Schmidt, N.F. Schwenzer
Journal: Medical Image Analysis (2017)
Trial will make HIV prevention drugs available on NHS from September
Authors: Gareth Iacobucci
Journal: BMJ (2017)

Pre-exposure prophylaxis (PrEP) to prevent HIV infection will be available on the NHS when a landmark clinical trial starts in September 2017, NHS England has announced.

The three year trial will provide HIV prevention drugs to an estimated 10 000 people through sexual health clinics, which will identify eligible participants at risk of infection, including men, women, transgender people, and participants whose partner’s HIV is not known to be controlled by antiretroviral treatment.

The announcement comes after NHS England lost an appeal in 2016 against a High Court ruling that the NHS was responsible for commissioning PrEP for HIV prevention.1 NHS England had previously …
Photometric Histochemical Determination of Thymonucleic Acid in Experimental Epidermal Carcinogenesis&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: R. E. Stowell
Journal: JNCI Journal of the National Cancer Institute (1942)

Journal Article Photometric Histochemical Determination of Thymonucleic Acid in Experimental Epidermal Carcinogenesis Get access R. E. Stowell R. E. Stowell research associate, research fellow in cytology Barnard Free Skin and Cancer Hospital, Washington University, St. Louis Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 3, Issue 1, August 1942, Pages 111–121, https://doi.org/10.1093/jnci/3.1.111 Published: 01 August 1942
Prisoner of My Preconceptions
Authors: Jason Chertoff
Journal: JAMA (2017)

It was an unusually tranquil day in our medical intensive care unit (MICU). Ventilator alarms were not blaring, intravenous drips were not urgently beeping, and vital sign monitors were not alerting us to any unstable patients. Certainly this calm could not last for long—and it didn't.
癌関連遺伝子の高感度分析のための2輪駆動ベースDNAナノマシンとその検出可能性【Powered by NICT】
Authors: Xu Jianguo, Wu Zai-Sheng, Wang Zhenmeng, Li Hongling, Le Jingqing, Jia Lee
Journal: Biomaterials (2016)
INJURY RISK IS DIFFERENT BETWEEN MALE AND FEMALE ATHLETES DURING 14 INTERNATIONAL ATHLETICS CHAMPIONSHIPS
Authors: Pascal Edouard, Nina Feddermann-demont, Juan-Manuel Alonso, Pedro Branco, Astrid Junge
Journal: British Journal of Sports Medicine (2017)

Background During top-level international Athletics championships, injury risk was about 100 injuries per 1000 athletes for outdoor championships, and about 63 injuries per 1000 athletes for indoors championships. However, it is unclear whether male or female athletes differ in risk and/or characteristics of injuries. Objective To compare the incidences and characteristics of injuries that occurred during international Athletics championships between female and male athletes. Design Prospective study. Setting 14 international athletics championships from 2007 to 2014; Elite athletics level. Participants A total of 17592 registered athletes. Main Outcome Measurements Incidences of all (time-loss) injuries in male and female athletes. Results The rate of injuries per 1000 registered athletes was significantly higher in male (110.3±6.8) than in female (88.5±6.7) athletes (relative risk (RR)=1.25; 95% CI:1.13–1.37, small effect size). Male athletes incurred significantly more injuries in the thigh (RR=1.64; 95% CI:1.32–2.05, small), lower leg (RR=1.36; 95% CI:1.05–1.75, small) and hip/groin injuries (RR=2.26; 95% CI:1.31–3.88, moderate), more muscle strains (RR=1.64; 95% CI:1.33–2.04, small), cramps (RR=1.81; 95% CI:1.35–2.43, small), and especially more thigh strains (RR=1.66; 95% CI:1.25–2.19, small), but fewer stress fractures (RR=0.32; 95% CI:0.12–0.81, moderate) than female athletes. A higher injury risk of male than of female athletes was observed in sprints (RR=1.32; 95% CI:1.06–1.66, small), middle distance runs (RR=1.48; 95% CI:1.06–2.06, small), race walks (RR=2.55; 95% CI:1.27–5.10, moderate), and jumps (RR=2.13; 95% CI:1.53–2.97, moderate). No sex difference was found for cause and severity of injury. Conclusions During 14 top-level international Athletics championships, male athletes had higher risk of injuries than female athletes. Moreover, injury incidences differed between sexes for location, type, and discipline. Males suffered more thigh strains than female athletes. Prevention strategies will likely need to take sex into account and where appropriate, be adapted to the differences in injury characteristics between female and male athletes.
Abstract 11653: The Qualitative Grading of Aortic Valve Calcification in Severe Aortic Stenosis is Weakly Associated With Aortic Valve Weight and is Gender Dependent
Authors: Dragos Alexandru, Florentina Petillo, Simcha Pollack, Nathaniel Reichek, Eddy Barasch
Journal: Circulation (2015)

Background: In severe aortic stenosis (AS), qualitative estimation of aortic valve calcification (AVC) burden by echocardiography has diagnostic and prognostic value. Hypothesis: there is a weak association between a qualitative calcium score (QCS) by TEE and AV weight in severe AS. Methods: Between 2010-2014, of 719 pts who underwent surgical AVR for isolated severe AS, QCS was feasible in 483 (67%): mean age 76.7 ± 9.5 yrs, 59% males, EF 56 ±12%, AVAi 0.35 ±0.09 cm2/m2, AVW 2.45 ± 0.09 g, QCS 3.5± 0.57, 11% bicuspid valves . AVC was determined using short- and long-axis views and graded as mild (1) localized, small, nondense calcifications to severe (4) extensive thickening and calcification of all cusps. TEEs were done on the day of surgery and excised valves were weighed. Independent t-test, Fisher’s exact test, analysis of variance, and Pearson correlation were done as appropriate. Results: Intraclass correlations for intra and interobserver variability were 0.76 and 0.53 , respectively.The association between indices of AS severity and AVC burden, is stronger for AVW than for QCS (table).19 pts had QCS = 2, 183 = 3 and 280 = 4. A QCS of 2 to 4 corresponded to an AVW of 1 to 6 g. The correlation between QCS and AVW was 0.11, p=.01, and 0.09, p =.04 when controlling for age, sex and BSA. QCS-AVW association was gender dependent : for females (196), who had a lower severity of stenosis, r=0.23, p=0.001, for males (286), r=0.02, p=.68 with p =.02 for the difference. Conclusions: 1. In severe AS, QCS by TEE has limited reliability with no relationship with AVW in males and a weak one in females. 2. The utilization of QCS in severe AS even when employing TEE is weakly associated with total AVC burden and should probably be replaced by quantitative objective non- echocardiographic methods.
Ictal 18F-FDG PET/MRI in a Patient With Cortical Heterotopia and Focal Epilepsy
Authors: Ferdinando F. Calabria, Giuseppe Lucio Cascini, Antonio Gambardella, Angelo Labate, Andrea Cherubini, Domenico Gullà, Benedetta Tafuri, Umberto Sabatini, Virginia Vescio, Aldo Quattrone
Journal: Clinical Nuclear Medicine (2017)

A 19-year-old man with epilepsy underwent ictal F-FDG PET/MRI, showing a 5 mm heterotopic nodule in the periventricular white matter, adjacent to the frontal horn of the left lateral ventricle (SUVmax, 5.5; glucidic cerebral metabolic rate, 0.317 μmol/mL). A repeated F-FDG PET/MRI, during seizure freedom, showed, at visual analysis, subtle decrease of the nodule metabolism. SUVmax and glucidic cerebral metabolic rate were clearly reduced to 3.7 and 0.226, respectively. Ictal F-FDG PET/MRI could be useful in epilepsy because of the added value of SUVmax and cerebral metabolic rate of glucose analysis to understand the relationship between heterotopy and epilepsy.
Role of erosions typical of rheumatoid arthritis in the 2010 ACR/EULAR rheumatoid arthritis classification criteria: results from a very early arthritis cohort
Authors: Gina Hetland Brinkmann, Ellen S Norli, Pernille Bøyesen, Désirée van der Heijde, Lars Grøvle, Anne J Haugen, Halvor Nygaard, Olav Bjørneboe, Cathrine Thunem, Tore K Kvien, Maria D Mjaavatten, Elisabeth Lie
Journal: Annals of the Rheumatic Diseases (2017)

Objective To determine how the European League Against Rheumatism (EULAR) definition of erosive disease (erosion criterion) contributes to the number of patients classified as rheumatoid arthritis (RA) according to the 2010 American College of Rheumatology/EULAR RA classification criteria (2010 RA criteria) in an early arthritis cohort. Methods Patients from the observational study Norwegian Very Early Arthritis Clinic with joint swelling ≤16 weeks, a clinical diagnosis of RA or undifferentiated arthritis, and radiographs of hands and feet were included. Erosive disease was defined according to the EULAR definition accompanying the 2010 RA criteria. We calculated the additional number of patients being classified as RA based on the erosion criteria at baseline and during follow-up. Results Of the 289 included patients, 120 (41.5%) fulfilled the 2010 RA criteria, whereas 15 (5.2%) fulfilled only the erosion criterion at baseline. 118 patients had radiographic follow-up at 2 years, of whom 6.8% fulfilled the 2010 RA criteria and only one patient fulfilled solely the erosion criterion during follow-up. Conclusion Few patients with early arthritis were classified as RA based on solely the erosion criteria, and of those who did almost all did so at baseline.
06.05 Mesenchymal stem cell-derived exosomes and microvesicles exert similar immunomodulatory effect in collagen-induced arthritis
Authors: Stella Cosenza, Karine Toupet, Patricia Luz-Crawford, Christian Jorgensen, Danièle Noël
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Backgrounds and objectives</h3> Mesenchymal stem cells (MSC) are multipotent cells with immunomodulatory functions that are of interest for therapeutic purposes in osteoarticular autoimmune diseases such as rheumatoid arthritis (RA). These functions are primarily mediated by soluble mediators that can be released within extracellular vesicles (EV). EVs consist of three main populations: exosomes, microvesicles and apoptotic bodies that mirror the effect of parental cells but little is known about the respective role of the various subsets of EVs secreted by a specific cell type. The aim of this study was to compare the immunomodulatory effects of exosomes and microvesicles released by MSCs and determine whether a pre-activation of MSCs before EV purification impacts their function. <h3>Materials and methods</h3> Exosomes and microvesicles were isolated from culture supernatants of murine primary MSCs by differential ultracentrifugation at 100K and 18K, respectively. Size and structure of exosomes and microvesicles were evaluated by NTA and/or electron microscopy. Expression of membrane and endosomal markers was tested by flow cytometry and Western blot. Proliferation of freshly isolated murine splenocytes or subpopulations of immune cells was quantified after 72 hour of incubation with different quantities of EVs, using the Cell TiterGlo assay and cytometry. <i>In vivo</i>, EVs were injected systemically in the collagen-induced arthritis (CIA) model. <h3>Results</h3> MSC-derived exosomes were around 120 nm in diameter and expressed CD9, CD81, TSG101 markers while microvesicles comprised a heterogeneous population of vesicles from 165 to 500 nm in diameter and expressed CD29, CD44 and Sca1 membrane markers. Addition of microvesicles or exosomes in proliferative assays significantly inhibited the proliferation of CD8<sup>+</sup> T cells and increased Treg cell population with no effect on CD4<sup>+</sup>IFN<sup>+</sup> T cells. In addition, proliferation and activation of B lymphocyte were decreased. These effects were independent of MSC pre-activation. The immunomodulatory function of both types of EVs was also observed in the CIA model of inflammatory arthritis with a significant reduction of clinical symptoms. <h3>Conclusion</h3> Our data indicated that the immunosuppressive effect of MSCs is at least in part mediated by EVs with no major differential role of exosomes or microvesicles on inflammatory immune cells <i>in vitro</i> or <i>in vivo</i>.
Circulating vitamin D–binding protein and free 25-hydroxyvitamin D concentrations in patients with melanoma: A case-control study
Authors: Cristián Navarrete-Dechent, Constanza del Puerto, Montserrat Molgó, Sergio González, Guillermo Pérez-Mateluna, Pablo Uribe, Carlos A. Camargo, Arturo Borzutzky
Journal: Journal of the American Academy of Dermatology (2017)