tbuckley/cabot-search huggingface dataset:
Global, national, and urban burdens of paediatric asthma incidence attributable to ambient NO2 pollution: estimates from global datasets
Authors: Pattanun Achakulwisut, Michael Brauer, Perry Hystad, Susan C Anenberg
Journal: The Lancet Planetary Health (2019)

BackgroundPaediatric asthma incidence is associated with exposure to traffic-related air pollution (TRAP), but the TRAP-attributable burden remains poorly quantified. Nitrogen dioxide (NO2) is a major component and common proxy of TRAP. In this study, we estimated the annual global number of new paediatric asthma cases attributable to NO2 exposure at a resolution sufficient to resolve intra-urban exposure gradients.MethodsWe obtained 2015 country-specific and age-group-specific asthma incidence rates from the Institute for Health Metrics and Evaluation for 194 countries and 2015 population counts at a spatial resolution of 250 × 250 m from the Global Human Settlement population grid. We used 2010–12 annual average surface NO2 concentrations derived from land-use regression at a resolution of 100 × 100 m, and we derived concentration-response functions from relative risk estimates reported in a multinational meta-analysis. We then estimated the NO2-attributable burden of asthma incidence in children aged 1–18 years in 194 countries and 125 major cities at a resolution of 250 × 250 m.FindingsGlobally, we estimated that 4·0 million (95% uncertainty interval [UI] 1·8–5·2) new paediatric asthma cases could be attributable to NO2 pollution annually; 64% of these occur in urban centres. This burden accounts for 13% (6–16) of global incidence. Regionally, the greatest burdens of new asthma cases associated with NO2 exposure per 100 000 children were estimated for Andean Latin America (340 cases per year, 95% UI 150–440), high-income North America (310, 140–400), and high-income Asia Pacific (300, 140–370). Within cities, the greatest burdens of new asthma cases associated with NO2 exposure per 100 000 children were estimated for Lima, Peru (690 cases per year, 95% UI 330–870); Shanghai, China (650, 340–770); and Bogota, Colombia (580, 270–730). Among 125 major cities, the percentage of new asthma cases attributable to NO2 pollution ranged from 5·6% (95% UI 2·4–7·4) in Orlu, Nigeria, to 48% (25–57) in Shanghai, China. This contribution exceeded 20% of new asthma cases in 92 cities. We estimated that about 92% of paediatric asthma incidence attributable to NO2 exposure occurred in areas with annual average NO2 concentrations lower than the WHO guideline of 21 parts per billion.InterpretationEfforts to reduce NO2 exposure could help prevent a substantial portion of new paediatric asthma cases in both developed and developing countries, and especially in urban areas. Traffic emissions should be a target for exposure-mitigation strategies. The adequacy of the WHO guideline for ambient NO2 concentrations might need to be revisited.FundingGeorge Washington University.
Scabies polymerase chain reaction with standardized dry swab sampling: an easy tool for cluster diagnosis of human scabies
Authors: P. Delaunay, A.L. Hérissé, L. Hasseine, C. Chiaverini, A. Tran, C. Mary, P. Del Giudice, P. Marty, M. Akhoundi, T. Hubiche
Journal: British Journal of Dermatology (2019)

Expert visualization of Sarcoptes scabiei remains essential for diagnosing human scabies, but access to said experts can be difficult. Polymerase chain reaction (PCR) is a specific tool for the detection and confirmation of S. scabiei but has poor sensitivity. To evaluate PCR as a diagnostic method for scabies using nonexpert‐dependent standardized sampling. The dry swab was systematically rubbed across the front of both wrists, the eight interdigital spaces and on any suspected scabies lesions in all patients referred for scabies. A new PCR‐based diagnostic test was run on the samples. All patients underwent clinical and dermoscopic examination. Scabies diagnosis was confirmed when dermoscopic examination was positive or the patient had typical clinical signs of scabies. Of 183 suspected cases of scabies, 164 patients were sampled, 87 had confirmed scabies (dermoscopy positive n = 87, typical clinical signs n = 1) and 77 did not. Of the 87 patients with proved scabies, 33 patients had positive scabies PCR, resulting in a 37·9% [95% confidence interval (CI) 28·4–48·4%] sensitivity and a 61·7% (95% CI 52·4–72·7%) negative predictive value. None of the 77 patients ruled out for scabies had a positive PCR result. This method is nontraumatic, repeatable and non‐expert‐dependent. It shows sensitivity similar to previous studies involving expert skin scraping. However, this method facilitates the multiplication of sampling, which increased the sensitivity for cluster scabies diagnosis. This method may be suitable as a first‐line diagnosis tool where a large cluster scabies outbreak is suspected. What's already known about this topic? Scabies diagnosis requires expertise. Scabies polymerase chain reaction (PCR) is specific but has poor sensitivity. Poor sensitivity is the consequence of the low efficiency of sampling methods. What does this study add? This PCR‐based diagnostic method based on nontraumatic standardized skin sampling is not expert‐dependent and is reproducible. This diagnostic method may be relevant as a non‐expert sentinel diagnosis tool in large clusters where a scabies outbreak is suspected.
THU-212-Reactivation of occult HBV infection in HIV treated for HCV: A retrospective study
Authors: Bianca Granozzi, Viola Guardigni, Lorenzo Badia, Silvia Galli, Giulia Piazza, Isabella Bon, Irene Zaghi, Pierluigi Viale, Gabriella Verucchi
Journal: Journal of Hepatology (2019)
Larger household size is associated with an increased proportion of regulatory T cells in cord blood
Authors: F. Collier, A. Ponsonby, M. O'Hely, M. L. Tang, K. J. Allen, L. C. Harrison, J. B. Carlin, R. Saffery, P. D. Sly, S. Ranganathan, P. J. Vuillermin
Journal: Allergy (2018)
Sorafenib Induces Pyroptosis in Macrophages and Triggers Natural Killer Cell–Mediated Cytotoxicity Against Hepatocellular Carcinoma
Authors: Carina Hage, Sabine Hoves, Léanne Strauss, Stefan Bissinger, Ylva Prinz, Thomas Pöschinger, Fabian Kiessling, Carola H. Ries
Journal: Hepatology (2019)

Antiangiogenic and cytotoxic effects are considered the principal mechanisms of action of sorafenib, a multitarget kinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC). We report that sorafenib also acts through direct immune modulation, indispensable for its antitumor activity. In vivo cell depletion experiments in two orthotopic HCC mouse models as well as in vitro analysis identified macrophages (MΦ) as the key mediators of the antitumoral effect and demonstrate a strong interdependency of MΦ and natural killer (NK) cells for efficient tumor cell killing. Caspase 1 analysis in sorafenib‐treated MΦ revealed an induction of pyroptosis. As a result, cytotoxic NK cells become activated when cocultured with sorafenib‐treated MΦ, leading to tumor cell death. In addition, sorafenib was found to down‐regulate major histocompatibility complex class I expression of tumor cells, which may reduce the tumor responsiveness to immune checkpoint therapies and favor NK‐cell response. In vivo cytokine blocking revealed that sorafenib efficacy is abrogated after inhibition of interleukins 1B and 18. Conclusion : We report an immunomodulatory mechanism of sorafenib involving MΦ pyroptosis and unleashing of an NK‐cell response that sets it apart from other spectrum kinase inhibitors as a promising immunotherapy combination partner for the treatment of HCC.
Correlation between D-dimer levels and clinical stage of solid tumors.
Authors: Ayten Can, Yildiz Tutuncu, Sualp Tansan
Journal: Journal of Clinical Oncology (2015)

e22223 Background: More recently, studies have reported that the activation of coagulation and fibrinolysis may play important role in tumor progression. The process of blood coagulation results in conversion of ﬁbrinogen into ﬁbrin by thrombin and subsequent ﬁbrin polymerization. D-dimer is a final product of ﬁbrin degradation. In this retrospective analysis we looked into the relationship between plasma D-dimer levels with clinical stage and tumor markers of solid cancers. Methods: 55 lung, 50 breast, 26 colon, 18 pancreas and 12 ovarian cancers patients who were seen at Tansan Oncology Clinic were inculuded in the analysis. Tumor stages were evaluated according to the TNM classification. Plasma levels of D-dimer, CA 15-3, CA 125 and CEA were measured using ELFA (Vidas Biomerieux). Results: Plasma D-dimer level was highest at clinical stage IV (mean±SD; 1880,28±1708,74 ng/ml) than other stages [stage I, II and III (mean±SD); ng/ml 645.07±507,02; 684,88±547,44; 1724,1±1584,91 respectively]. D-dimer levels were significantly correlated with clinical stage, platelet count, CEA, and CA 125 (r = 0.419, p < 0.0001; r = 0.365, p < 0.0001; r = 0.546, p = 0.007 and r = 0.727, p = 0.01, respectively). There was no correlation between D- dimer level and CA 15-3. Conclusions: It appears that plasma D-dimer levels are positively correlated with clinical stage. High plasma D-dimer levels may be a marker for advanced stage solid cancers.
Cancer-selective nanoparticles for combinatorial siRNA delivery to primary human GBM in vitro and in vivo
Authors: Kristen L. Kozielski, Alejandro Ruiz-Valls, Stephany Y. Tzeng, Hugo Guerrero-Cázares, Yuan Rui, Yuxin Li, Hannah J. Vaughan, Marissa Gionet-Gonzales, Casey Vantucci, Jayoung Kim, Paula Schiapparelli, Rawan Al-Kharboosh, Alfredo Quiñones-Hinojosa, Jordan J. Green
Journal: Biomaterials (2019)
Deep learning versus human graders for classifying diabetic retinopathy severity in a nationwide screening program
Authors: Paisan Ruamviboonsuk, Jonathan Krause, Peranut Chotcomwongse, Rory Sayres, Rajiv Raman, Kasumi Widner, Bilson J. L. Campana, Sonia Phene, Kornwipa Hemarat, Mongkol Tadarati, Sukhum Silpa-Archa, Jirawut Limwattanayingyong, Chetan Rao, Oscar Kuruvilla, Jesse Jung, Jeffrey Tan, Surapong Orprayoon, Chawawat Kangwanwongpaisan, Ramase Sukumalpaiboon, Chainarong Luengchaichawang, Jitumporn Fuangkaew, Pipat Kongsap, Lamyong Chualinpha, Sarawuth Saree, Srirut Kawinpanitan, Korntip Mitvongsa, Siriporn Lawanasakol, Chaiyasit Thepchatri, Lalita Wongpichedchai, Greg S. Corrado, Lily Peng, Dale R. Webster
Journal: npj Digital Medicine (2019)

Deep learning algorithms have been used to detect diabetic retinopathy (DR) with specialist-level accuracy. This study aims to validate one such algorithm on a large-scale clinical population, and compare the algorithm performance with that of human graders. A total of 25,326 gradable retinal images of patients with diabetes from the community-based, nationwide screening program of DR in Thailand were analyzed for DR severity and referable diabetic macular edema (DME). Grades adjudicated by a panel of international retinal specialists served as the reference standard. Relative to human graders, for detecting referable DR (moderate NPDR or worse), the deep learning algorithm had significantly higher sensitivity (0.97 vs. 0.74, p < 0.001), and a slightly lower specificity (0.96 vs. 0.98, p < 0.001). Higher sensitivity of the algorithm was also observed for each of the categories of severe or worse NPDR, PDR, and DME (p < 0.001 for all comparisons). The quadratic-weighted kappa for determination of DR severity levels by the algorithm and human graders was 0.85 and 0.78 respectively (p < 0.001 for the difference). Across different severity levels of DR for determining referable disease, deep learning significantly reduced the false negative rate (by 23%) at the cost of slightly higher false positive rates (2%). Deep learning algorithms may serve as a valuable tool for DR screening.
THU-236-Integration of HBV DNA near cancer-related genes in HBsAg-negative hepatocellular carcinoma patients
Authors: Danny Wong, Ching Yan Serene Cheng, Lung-Yi Mak, Wai Pan To, Tan-to Cheung, Wai-Kay Seto, Yan Yue James Fung, Kwan Man, Ching Lung Lai, Man-Fung Yuen
Journal: Journal of Hepatology (2019)
Evaluation of CXCR4 expression on tumor and circulating tumor cells (CTCs) as predictive response marker for CXCR4 antagonist LY2510924 in combination with carboplatin-etoposide in extensive-disease small cell lung cancer (ED-SCLC).
Authors: Ravi Salgia, R. Waide Weaver, Michael McCleod, John R Stille, S. Betty Yan, Stephanie Roberson, Oday Hamid, John Polzer, Amy Flynt, Eyas Raddad, David R. Spigel
Journal: Journal of Clinical Oncology (2015)

7567 Background: Small cell lung cancer (SCLC) can express CXCR4 chemokine receptor, and inhibition potentially synergizes with cytotoxic and targeted therapeutics in vitro in SCLC. Baseline CXCR4 expression on tumor tissue or CTCs may help predict response to treatment with CXCR4 antagonist LY2510924 (LY). Methods: In an open-label, randomized phase 2 study (NCT01439568), patients (pts) with ED-SCLC received up to six 21-day cycles (C) of carboplatin (Day [D] 1) and etoposide (D1-3) (SOC) alone or in combination with 20 mg qd sc LY (D1-7) (LY+SOC). Exploratory analyses evaluated CXCR4 expression on available baseline tumor tissue (IHC H-score) and on CTCs collected at baseline, C1D7, and C2D1 (CellSearch). Receiver operating characteristic (ROC) curves and their AUCs (95% CIs) were generated to determine optimal cutoff values for CXCR4 expression on tissue and CTCs and number of CTCs as predictors of 6-month progression-free survival (PFS). Hazard ratios (HRs) through 4 months (end of treatment), using the optimal cutoffs at baseline, were generated. Results: 90 pts were randomized to SOC (N = 43) or LY+SOC (N = 47). Optimal ROC cutoffs were ≥ 210 (H-score) for CXCR4+ tissue ( ≥ 210: N = 31, < 210: N = 38; AUC = 0.631 [0.496, 0.765]); ≥ 7% CXCR4+ on CTCs ( ≥ 7%: N = 44, < 7%: N = 26; AUC = 0.702 [0.577, 0.828]); and ≥ 6 CTCs/7.5 mL blood ( ≥ 6: N = 60, < 6: N = 18; AUC = 0.607 [0.471, 0.742]). In evaluating pts with a baseline value above each optimal cutoff, the HR (95% CI) was 0.787 (0.211, 2.933) for CXCR4+ tissue (LY+SOC: N = 16, SOC: N = 15); 0.476 (0.147, 1.548) for % CXCR4+ on CTCs (LY+SOC: N = 20, SOC: N = 24); and 0.403 (0.151, 1.076) for CTCs (LY+SOC: N = 31, SOC: N = 29). For pts considered high risk (ie, ≥ 6 CTCs and ≥ 7% CXCR4+ CTCs), the HR was 0.489 (0.150, 1.589) (LY+SOC: N = 18, SOC: N = 23). Conclusions: Selected ED-SCLC pts with high levels of CTCs and/or CXCR4 expression on CTCs and/or tumor tissue at baseline may benefit by the addition of LY to SOC. Further investigation of LY in a preselected pt population is warranted. Clinical trial information: NCT01439568.
Overview: a current perspective on twin studies of schizophrenia
Authors: Kenneth S. Kendler
Journal: American Journal of Psychiatry (1983)

The author reviews the results of twin studies of schizophrenia from the perspective of recent advances in our understanding of the twin method and of the transmission of schizophrenia. The evidence suggests that twin studies of schizophrenia are not likely to be substantially biased by the greater similarity in social environment of identical versus fraternal twins. Raw concordance figures from twin studies of schizophrenia are quite variable. When models to estimate the etiologic importance of genetic factors are applied to these figures, the results from all studies are similar. According to these models, genetic factors are as etiologically important in schizophrenia as in such medical conditions as diabetes and hypertension. Twin studies of schizophrenia probably provide a valid measure of the major etiologic role genetic factors play in schizophrenia.
GS-11-Baseline neutrophil-to-lymphocyte ratio indicates both prevalent and incident infection and acute kidney injury, and is related to corticosteroid Lille response in alcoholic hepatitis
Authors: Ewan Forrest, Natasha Storey, Rohit Sinha, Stephen Atkinson, Nikhil Vergis, Michael Allison, Paul Richardson, Steven Masson, Mark Thursz, Peter Hayes
Journal: Journal of Hepatology (2019)
THU-149-Efficiency and safety of direct acting antivirals in chronic hepatitis C patients infected with genotype 2 and 3 in Turkey
Authors: Behice Kurtaran, Figen Sarýgül, Mehmet Çabalak, Sibel Kaya, Nagehan Didem Sarý, Hasan Karsen, Esra Zerdali, Rahmet Güner, Kamuran Türker, Nevin İnce, Fehmi Tabak, Hepcturkey Study Group
Journal: Journal of Hepatology (2019)
PS-146-Intestinal mucus and vascular barrier: FxR-modulated entry sites for pathological bacterial translocation in liver cirrhosis independent from portal hypertension and lymphatic route
Authors: Reiner Wiest, Marcel Sorribas, Bathi Yilmaz, David Stutz, Yannick Noser, Andrea De Gottardi, Sheida Moghadamrad, Mohsin Hassan, Agustin Albillos, Maria Rescigno
Journal: Journal of Hepatology (2019)
Surgery—10 000 Lancets later
Authors: None The Lancet
Journal: The Lancet (2015)

It is a happy coincidence that this year's surgery-themed issue, published ahead of the American College of Surgeons' Clinical Congress (in Chicago, IL, USA, on Oct 4–8), is also our 10 000th issue. Thomas Wakley, the founder of The Lancet and a surgeon himself, was an ardent critic of the prevailing surgical establishment. He published the lectures of the eminent surgeon Sir Astley Cooper on the theory and practice of surgery to make these widely accessible in the hope "that mystery and concealment will no longer be encouraged".
Antibody–Drug Conjugates: Future Directions in Clinical and Translational Strategies to Improve the Therapeutic Index
Authors: Steven Coats, Marna Williams, Benjamin Kebble, Rakesh Dixit, Leo Tseng, Nai-Shun Yao, David A. Tice, Jean-Charles Soria
Journal: Clinical Cancer Research (2019)

Abstract Since the first approval of gemtuzumab ozogamicin (Mylotarg; Pfizer; CD33 targeted), two additional antibody–drug conjugates (ADC), brentuximab vedotin (Adcetris; Seattle Genetics, Inc.; CD30 targeted) and inotuzumab ozogamicin (Besponsa; Pfizer; CD22 targeted), have been approved for hematologic cancers and 1 ADC, trastuzumab emtansine (Kadcyla; Genentech; HER2 targeted), has been approved to treat breast cancer. Despite a clear clinical benefit being demonstrated for all 4 approved ADCs, the toxicity profiles are comparable with those of standard-of-care chemotherapeutics, with dose-limiting toxicities associated with the mechanism of activity of the cytotoxic warhead. However, the enthusiasm to develop ADCs has not been dampened; approximately 80 ADCs are in clinical development in nearly 600 clinical trials, and 2 to 3 novel ADCs are likely to be approved within the next few years. While the promise of a more targeted chemotherapy with less toxicity has not yet been realized with ADCs, improvements in technology combined with a wealth of clinical data are helping to shape the future development of ADCs. In this review, we discuss the clinical and translational strategies associated with improving the therapeutic index for ADCs.
Bionic Poly(γ‐Glutamic Acid) Electrospun Fibrous Scaffolds for Preventing Hypertrophic Scars
Authors: Tingting Xu, Rong Yang, Xuebin Ma, Wei Chen, Shuai Liu, Xin Liu, Xiaojun Cai, Hong Xu, Bo Chi
Journal: Advanced Healthcare Materials (2019)

Abstract Hypertrophic scarring (HS) remains a great challenge in wound dressing. Although various bionic extracellular matrix (ECM) biomaterials have been designed towards HS treatment, not all biomaterials can synergize biological functions and application functions in wound repair. Bionic scar‐inhibiting scaffolds, loaded with biomolecules or drugs, become promising strategies for scarless skin regeneration. In this work, inspired by the physicochemical environment of ECM, a versatile fabrication of poly(γ‐glutamic acid) based on electrospun photocrosslinkable hydrogel fibrous scaffolds incorporated with ginsenoside Rg3 (GS‐Rg3) is developed for tissue repair and wound therapy. Decorated with adhesive peptide, bionic fibrous scaffolds can accelerate fibroblasts to sprout and grow, forming organized space‐filling basement that gradually fills a depression before wound close up in the early stage. Additionally, by sustained release of GS‐Rg3 in late stage, fibrous scaffolds promote scarless wound healing in vivo as evidenced by the promotion of cell communication and skin regeneration, as well as the subsequent decrease of angiogenesis and collagen accumulation. These ECM‐inspired fibrous scaffolds, therefore, offer new perspectives on accelerated wound healing and tissue regeneration.
PS-189-Toronto HCC risk index and albumin predict low risk of hepatocellular carcinoma after sustained virological response in hepatitis C infection
Authors: Jason Lau, Lisette Krassenburg, Wayel R. Zanjir, Firas Georgie, Orlando Cerocchi, Emily Stotland, Heidy Morales, Harry Janssen, Bettina Hansen, Jordan Feld
Journal: Journal of Hepatology (2019)
Concerns regarding the recommendations of the British Society of Gastroenterology’s lower GI bleeding guidelines
Authors: Ajay M Verma, Neeraj Bhala, Andrew Chilton, Benjamin R Disney
Journal: Gut (2019)

We are writing with regard to the recently published British Society of Gastroenterology (BSG) lower GI bleeding (LGIB) guidelines.1 We have significant concerns about some of the recommendations.

The quick reference flowchart suggests that patients with stable LGIB (shock index <1), classed as having a major (risk scored) bleed, should be admitted for a lower GI endoscopy on the next available list. This is inconsistent with the main body of the guideline which states: a colonoscopy on the next available list. We find this recommendation concerning, particularly as it has implications for endoscopy unit resources, inpatient services, and patient safety. Delivering urgent inpatient colonoscopy in this cohort of patients is logistically challenging.

Is a colonoscopy necessary for all? The acute LGIB national audit showed that 73.9% of patients presented with rectal …
Survival and late effects in the risk-stratified hepatoblastoma patients treated by JPLT-2 protocol.
Authors: Eiso Hiyama, Sho Kurihara, Yuka Ueda, Tomoro Hishiki, Kohmei Ida, Tomoko Iehara, Takaharu Oue, Michihiro Yano, Kenichiro Watanabe, Ken Hoshino, Katsuyoshi Ko, Yukichi Tanaka
Journal: Journal of Clinical Oncology (2015)

10021 Background: The Japanese Study Group for Pediatric Liver Tumor (JPLT) has conducted cooperative treatment studies on hepatoblastoma (HB) since 1991. The main aim in JPLT-2 study launched in 1999 and closed in 2012 to evaluate the efficacy of cisplatin/pirarubicin in risk-stratified HB. This protocol was launched in 1999 and closed in 2012 to evaluate the cure rate of risk-stratified HB: standard risk HB (a tumor involving three or fewer sectors of the liver), intermediate risk HB (a tumor involving all sectors of the liver or invasion into portal or hepatic vein) and high risk HB (a tumor involving all sectors of the liver or with metastasis). Methods: Until 2012, 385 HB children who were younger than 15 years of age were eligible for inclusion in the JPLT2 study in which the cisplatin/pirarubicin regimen (CITA) is kept as the first line. In this study, we examined the outcome and late effects of the HB patients by the risk-stratified three groups (standard, intermediate and high risk groups). Results: Among 385 cases, PRETEXT I was 31, II was 120, III was 145, and IV was 89 including 86 cases (18%) with metastatic tumors. The 3-year EFS/OS of the cases with standard risk HB were 94/82%, while those of the cases with Intermediate and high risk HB was 64/49% and 34/28%, respectively. Except for 40 cases who underwent primary resection, complete resection of primary after CITA was performed 86% of standard risk, 66% of intermediate risk and 56% of high risk patients. And the late phase complications were 5 cases with maldevelopment, 17 with cardiac complications, 26 with ototoxicity and 5 with second malignancies. Conclusions: As compared with other multicenter cooperative protocols, CITA regimens achieved similar rates of survival and resectability in standard risk patients. More promising strategies including adequate liver transplantation and new targeting drugs should be developed for intermediate and high risk HBs. Clinical trial information: UMIN000001116.