tbuckley/cabot-search huggingface dataset:
Effects of Eculizumab Treatment on the Quality of Life in Patients with Paroxysmal Nocturnal Hemoglobinuria Treated in Japan
Authors: Yasutaka Ueda, Naoshi Obara, Yuji Yonemura, Hideyoshi Noji, Takahisa Matsuda, Hirozumi Akiyama, Takayuki Ikezoe, Shigeru Chiba, Yoshinobu Kanda, Tatsuya Kawaguchi, Tsutomu Shichishima, Hideki Nakakuma, Shinichiro Okamoto, Jun-Ichi Nishimura, Yuzuru Kanakura, Haruhiko Ninomiya
Journal: Blood (2017)
Molecular Determinants of Response to Anti–Programmed Cell Death (PD)-1 and Anti–Programmed Death-Ligand 1 (PD-L1) Blockade in Patients With Non–Small-Cell Lung Cancer Profiled With Targeted Next-Generation Sequencing
Authors: Hira Rizvi, Francisco Sanchez-Vega, Konnor La, Walid Chatila, Philip Jonsson, Darragh Halpenny, Andrew Plodkowski, Niamh Long, Jennifer L. Sauter, Natasha Rekhtman, Travis Hollmann, Kurt A. Schalper, Justin F. Gainor, Ronglai Shen, Ai Ni, Kathryn C. Arbour, Taha Merghoub, Jedd Wolchok, Alexandra Snyder, Jamie E. Chaft, Mark G. Kris, Charles M. Rudin, Nicholas D. Socci, Michael F. Berger, Barry S. Taylor, Ahmet Zehir, David B. Solit, Maria E. Arcila, Marc Ladanyi, Gregory J. Riely, Nikolaus Schultz, Matthew D. Hellmann
Journal: Journal of Clinical Oncology (2018)

Purpose Treatment of advanced non-small-cell lung cancer with immune checkpoint inhibitors (ICIs) is characterized by durable responses and improved survival in a subset of patients. Clinically available tools to optimize use of ICIs and understand the molecular determinants of response are needed. Targeted next-generation sequencing (NGS) is increasingly routine, but its role in identifying predictors of response to ICIs is not known. Methods Detailed clinical annotation and response data were collected for patients with advanced non-small-cell lung cancer treated with anti-programmed death-1 or anti-programmed death-ligand 1 [anti-programmed cell death (PD)-1] therapy and profiled by targeted NGS (MSK-IMPACT; n = 240). Efficacy was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and durable clinical benefit (DCB) was defined as partial response/stable disease that lasted > 6 months. Tumor mutation burden (TMB), fraction of copy number-altered genome, and gene alterations were compared among patients with DCB and no durable benefit (NDB). Whole-exome sequencing (WES) was performed for 49 patients to compare quantification of TMB by targeted NGS versus WES. Results Estimates of TMB by targeted NGS correlated well with WES (ρ = 0.86; P < .001). TMB was greater in patients with DCB than with NDB ( P = .006). DCB was more common, and progression-free survival was longer in patients at increasing thresholds above versus below the 50th percentile of TMB (38.6% v 25.1%; P < .001; hazard ratio, 1.38; P = .024). The fraction of copy number-altered genome was highest in those with NDB. Variants in EGFR and STK11 associated with a lack of benefit. TMB and PD-L1 expression were independent variables, and a composite of TMB plus PD-L1 further enriched for benefit to ICIs. Conclusion Targeted NGS accurately estimates TMB and elevated TMB further improved likelihood of benefit to ICIs. TMB did not correlate with PD-L1 expression; both variables had similar predictive capacity. The incorporation of both TMB and PD-L1 expression into multivariable predictive models should result in greater predictive power.
Brief Report: Group 3 Innate Lymphoid Cells in Human Enthesis
Authors: Richard J. Cuthbert, Evangelos M. Fragkakis, Robert Dunsmuir, Zhi Li, Mark Coles, Helena Marzo‐Ortega, Peter V. Giannoudis, Elena Jones, Yasser M. El‐Sherbiny, Dennis McGonagle
Journal: Arthritis & Rheumatology (2017)

Objective Group 3 innate lymphoid cells (ILC3s) play a pivotal role in barrier tissues such as the gut and the skin, two important sites of disease in spondyloarthritis (SpA). This study was undertaken to investigate whether normal or injured human enthesis, a key target tissue in early SpA, harbors ILC3s in entheseal soft tissue and adjacent perientheseal bone. Methods Interspinous ligament and spinous process bone from donors with no systemic inflammatory disease were collected, enzymatically digested, and immunophenotyped. The immunologic profile of entheseal cells was examined, and the transcriptional profile of sorted ILC3s was compared to that of ILC3s isolated from SpA synovial fluid (SF). To assess the ability of entheseal tissue to produce interleukin‐17 (IL‐17) and IL‐22, entheseal digests were stimulated with IL‐23 and IL‐1β. Osteoarthritic and ruptured Achilles tendon tissue was examined histologically. Results The proportion of ILCs in human entheseal soft tissue was higher than that in peripheral blood ( P = 0.008); entheseal soft tissue and perientheseal bone both had a higher proportion of NKp44+ ILC3s ( P = 0.001 and P = 0.043, respectively). Studies of retinoic acid receptor–related orphan nuclear receptor γt (RORγt), STAT3, and IL‐23 receptor transcript expression validated the entheseal ILC3 phenotype. Cytokine transcript expression was similar in ILC3s isolated from enthesis and from SpA SF. Stimulation of normal entheseal digests with IL‐23/IL‐1β led to up‐regulation of IL‐17A transcript, and histologic examination of injured/damaged entheses revealed the presence of RORγt‐expressing cells. Conclusion This work shows that human enthesis harbors a resident population of ILC3s, with the potential to participate in the pathogenesis of SpA.
Tobacco Product Use Among Military Veterans — United States, 2010–2015
Authors: Satomi Odani, Israel T. Agaku, Corinne M. Graffunder, Michael A. Tynan, Brian S. Armour
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In 2015, an estimated 18.8 million U.S. adults were military veterans (1). Although the prevalence of tobacco-attributable conditions is high among veterans (2), there is a paucity of data on use of tobacco products, other than cigarettes, in this population. To monitor tobacco product use among veterans, CDC analyzed self-reported current (i.e., past 30-day) use of five tobacco product types (cigarettes, cigars [big cigars, cigarillos, or little cigars], roll-your-own tobacco, pipes, and smokeless tobacco [chewing tobacco, snuff, dip, or snus]) from the National Survey on Drug Use and Health (NSDUH). Overall, 29.2% of veterans reported current use of any of the assessed tobacco products. Cigarettes were the most commonly used tobacco product (21.6%), followed by cigars (6.2%), smokeless tobacco (5.2%), roll-your-own tobacco (3.0%), and pipes (1.5%); 7.0% of veterans currently used two or more tobacco products. Within subgroups of veterans, current use of any of the assessed tobacco products was higher among persons aged 18-25 years (56.8%), Hispanics (34.0%), persons with less than a high school diploma (37.9%), those with annual family income <$20,000 (44.3%), living in poverty (53.7%), reporting serious psychological distress (48.2%), and with no health insurance (60.1%). By age and sex subgroups, use of any of the assessed tobacco products was significantly higher among all veteran groups than their nonveteran counterparts, except males aged ≥50 years. Expanding the reach of evidence-based tobacco control interventions among veterans could reduce tobacco use prevalence in this population.
The Fountain of Youth: Outcomes of Nonmyeloablative (NMA), HLA-Haploidentical Related (Haplo) Bone Marrow Transplantation (BMT) with Post-Transplantation Cyclophosphamide (PTCy) Best with Younger Donors Regardless of Relationship to Patient
Authors: Clio E Franklin, Margaret M. Showel, Hua-Ling Tsai, Ravi Varadhan, Shannon R. McCurdy, Douglas E. Gladstone, Richard J. Jones, Amy E. DeZern
Journal: Blood (2017)
Deuterostome Genomics: Lineage-Specific Protein Expansions That Enabled Chordate Muscle Evolution
Authors: Jun Inoue, Noriyuki Satoh
Journal: Molecular Biology and Evolution (2018)

Fish-like larvae were foundational to the chordate body plan, given the basal placement of free-living lancelets. That body plan probably made it possible for chordate ancestors to swim by beating a tail formed of notochord and bilateral paraxial muscles. In order to investigate the molecular genetic basis of the origin and evolution of paraxial muscle, we deduced the evolutionary histories of 16 contractile protein genes from paraxial muscle, based on genomic data from all five deuterostome lineages, using a newly developed orthology identification pipeline and a species tree. As a result, we found that more than twice as many orthologs of paraxial muscle genes are present in chordates, as in nonchordate deuterostomes (ambulacrarians). Orthologs of paraxial-type actin and troponin C genes are absent in ambulacrarians and most paraxial muscle protein isoforms diversified via gene duplications that occurred in each chordate lineage. Analyses of genes with known expression sites indicated that some isoforms were reutilized in specific muscles of nonvertebrate chordates via gene duplications. As orthologs of most paraxial muscle genes were present in ambulacrarians, in addition to expression patterns of related genes and functions of the two protein isoforms, regulatory mechanisms of muscle genes should also be considered in future studies of the origin of paraxial muscle.
Abstract 16074: Modeling a Novel Hypothetical Use of Postal Collection Boxes as Automated External Defibrillator Access Points
Authors: Sanjana Srinivasan, Carolyn G Vanek, David D Salcido
Journal: Circulation (2016)

Introduction:  Optimizing placement of Automated External Defibrillators (AED) can increase the chances of survival during an Out of Hospital Cardiac Arrest (OHCA). Using Postal Collection Boxes (PCB) as locations for AEDs could potentially enhance accessibility and streamline maintenance, although the impact of using these locations on OHCA bystander response times is not known. In the present study, we sought to investigate this AED location strategy with a map-based simulation approach.   Hypothesis:  We hypothesized that using PCBs for placement of public AEDs would decrease distance traveled to an OHCA compared to current public AED locations and that combining both locations would further decrease this distance. We also hypothesized that AEDs at PCBs would lead to an increase in AED coverage area.   Methods:  OHCAs locations between 2009-2014 were obtained from the Pittsburgh Site of the Resuscitation Outcome Consortium (n=2912). AED locations were collected from the HeartMap Challenge and the Pittsburgh Pulse Program (n=531). PCB locations were obtained from the United States Postal Service and geocoded (n=496) to latitude/longitude coordinates. Spatial analysis was conducted using Quantum GIS (QGIS). Linear distance from each OHCA to the nearest current AED, nearest PCB and nearest of either was calculated and converted into feet using MMQGIS. Average distance was compared between each method to determine whether current locations, PCBs, or the combination of the two offered a superior overall location strategy. AED coverage area was assessed as the proportion of census tracts that had an AED for each method.   Results:  Mean distance was 1449.22 feet (Median=1165.88 feet) from OHCA to nearest AED; 1168.05 feet (Median=747.48 feet) to the nearest PCB equipped with an AED, and 884.88 feet (Median=606.11 feet) the nearest AED or PCB. Of all OHCAs, 53.6% experienced a decrease in distance from an AED using PCBs as AED locations. AED coverage increased from 68.6% of all census tracts containing AEDS to 94.8% with the addition of PCBs.   Conclusion:  Overall distance decreases when using PCB as a possible source for an AED along with current locations. AED coverage increases when AEDs are located at PCBs.
Prexasertib, a cell cycle checkpoint kinase 1 and 2 inhibitor, in BRCA wild-type recurrent high-grade serous ovarian cancer: a first-in-class proof-of-concept phase 2 study
Authors: Jung-Min Lee, Jayakumar Nair, Alexandra Zimmer, Stanley Lipkowitz, Christina M Annunziata, Maria J Merino, Elizabeth M Swisher, Maria I Harrell, Jane B Trepel, Min-Jung Lee, Mohammad H Bagheri, Dana-Adriana Botesteanu, Seth M Steinberg, Lori Minasian, Irene Ekwede, Elise C Kohn
Journal: The Lancet Oncology (2018)
BGB-3111, a Highly Specific BTK Inhibitor, Is Well Tolerated and Highly Active in Chinese Patients with Relapsed/Refractory B-Cell Malignancies: Initial Report of a Phase 1 Trial in China
Authors: Jun Zhu, Jianyong Li, Jianfeng Zhou, Yuqin Song, Junyuan Qi, Wei Xu, Dengju Li, Mingyuan Sun, Ling Xue, Liudi Yang, Yinwei Zhang, Lai Wang, Jane Huang, Shibao Feng, Lugui Qiu
Journal: Blood (2017)
Methicillin-resistant <i>Staphylococcus aureus</i> causes sustained collecting lymphatic vessel dysfunction
Authors: Dennis Jones, Eelco F. J. Meijer, Cedric Blatter, Shan Liao, Ethel R. Pereira, Echoe M. Bouta, Keehoon Jung, Shan Min Chin, Peigen Huang, Lance L. Munn, Benjamin J. Vakoc, Michael Otto, Timothy P. Padera
Journal: Science Translational Medicine (2018)

Impairment in lymph flow caused by methicillin-resistant Staphylococcus aureus toxins persists after skin and soft tissue infections clear.
Poor access to GP services is not linked to frequent A&amp;E visits, finds study
Authors: Susan Mayor
Journal: BMJ (2018)

Poor access to GP services is not associated with increased visits to emergency departments, an analysis of data for London hospitals, which found patients using hospital emergency departments (EDs) more frequently also saw their GP more often, has shown.1

“This analysis provides strong evidence that increasing numbers of physical and mental morbidities drive attendance rates at EDs,” the researchers, led by Sally Hull from Queen Mary University of London, said.

Rates of attendance at EDs in the UK have increased steadily over the past 50 years and are highest in London, with 466 in every 1000 of …
Phenotypic Expression of Hypersensitivity Drug Reactions in Outpatient Infusion Centers, 1 Year Experience
Authors: Cintia A. Falck-Fuentes, Teodorikez W. Jimenez Rodriguez, Donna-Marie Lynch, Marlene Garcia-Neuer, Kathleen A. Marquis, Leila A. Alenazy, Mariana C. Castells
Journal: Journal of Allergy and Clinical Immunology (2018)
The Himba and Red Ochre—Aesthetics, Symbolism, and Adaptation
Authors: Jinal Gandhi, Apoorva Trivedi
Journal: JAMA Dermatology (2018)

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COMET: a multicomponent home-based disease-management programme <i>versus</i> routine care in severe COPD
Authors: Romain Kessler, Pere Casan-Clara, Dieter Koehler, Silvia Tognella, Jose Luis Viejo, Roberto W. Dal Negro, Salvador Díaz-Lobato, Karina Reissig, José Miguel Rodríguez González-Moro, Gilles Devouassoux, Jean-Michel Chavaillon, Pierre Botrus, Jean-Michel Arnal, Julio Ancochea, Anne Bergeron-Lafaurie, Carlos De Abajo, Winfried J. Randerath, Andreas Bastian, Christian G. Cornelissen, Georg Nilius, Joëlle B. Texereau, Jean Bourbeau
Journal: European Respiratory Journal (2018)

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients. The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s &lt;50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths. For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean± sd ) were 17.4±35.4 and 22.6±41.8, respectively (mean difference −5.3, 95% CI −13.7 to −3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p&lt;0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries. The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients.
Neoadjuvant plus adjuvant dabrafenib and trametinib versus standard of care in patients with high-risk, surgically resectable melanoma: a single-centre, open-label, randomised, phase 2 trial
Authors: Rodabe N Amaria, Peter A Prieto, Michael T Tetzlaff, Alexandre Reuben, Miles C Andrews, Merrick I Ross, Isabella C Glitza, Janice Cormier, Wen-Jen Hwu, Hussein A Tawbi, Sapna P Patel, Jeffrey E Lee, Jeffrey E Gershenwald, Christine N Spencer, Vancheswaran Gopalakrishnan, Roland Bassett, Lauren Simpson, Rosalind Mouton, Courtney W Hudgens, Li Zhao, Haifeng Zhu, Zachary A Cooper, Khalida Wani, Alexander Lazar, Patrick Hwu, Adi Diab, Michael K Wong, Jennifer L McQuade, Richard Royal, Anthony Lucci, Elizabeth M Burton, Sangeetha Reddy, Padmanee Sharma, James Allison, Phillip A Futreal, Scott E Woodman, Michael A Davies, Jennifer A Wargo
Journal: The Lancet Oncology (2018)
The asthma‐rhinitis multimorbidity is associated with IgE polysensitization in adolescents and adults
Authors: V. Siroux, N. Ballardini, M. Soler, C. Lupinek, A. Boudier, I. Pin, J. Just, R. Nadif, J. M. Anto, E. Melen, R. Valenta, M. Wickman, J. Bousquet
Journal: Allergy (2018)

Abstract Background Children with multimorbid asthma and rhinitis show IgE polysensitization to several allergen sources. This association remains poorly studied in adolescents and adults using defined allergen molecules. We investigated IgE sensitization patterns towards a broad panel of aeroallergen components in adults and adolescents with a focus on individuals with asthma and rhinitis multimorbidity. Methods IgE reactivity to 64 micro‐arrayed aeroallergen molecules was determined with the Me DALL ‐chip in samples from the French EGEA study (n = 840, age = 40.7 ± 17.1) and the Swedish population‐based birth cohort BAMSE (n = 786, age = 16 ± 0.26). The age‐ and sex‐adjusted associations between the number of IgE‐reactive allergen molecules (≥0.3 ISU ) and the asthma‐rhinitis phenotypes were assessed using a negative binomial model. Results Groups representing 4 phenotypes were identified: no asthma‐no rhinitis (A−R−; 30% in EGEA and 54% in BAMSE ), asthma alone (A+R−; 11% and 8%), rhinitis alone (A−R+; 15% and 24%) and asthma‐rhinitis (A+R+; 44% and 14%). The numbers of IgE‐reactive aeroallergen molecules significantly differed between phenotypes (median in A−R−, A+R−, A−R+ and A+R+: 0, 1, 2 and 7 in EGEA and 0, 0, 3 and 5 in BAMSE ). As compared to A−R− subjects, the adjusted ratio of the mean number of IgE‐reactive molecules was higher in A+R+ than in A+R− or A−R+ (10.0, 5.4 and 5.0 in EGEA and 7.2, 0.7 and 4.8 in BAMSE ). Conclusion The A+R+ phenotype combined the sensitization pattern of both the A−R+ and A+R− phenotypes. This multimorbid polysensitized phenotype seems to be generalizable to various ages and allergenic environments and may be associated with specific mechanisms.
Striate palmoplantar keratoderma resulting from a missense mutation in <i>DSG1</i>
Authors: D. Vodo, E.A. O'Toole, N. Malchin, A. Lahav, N. Adir, O. Sarig, K.J. Green, F.J.D. Smith, E. Sprecher
Journal: British Journal of Dermatology (2018)
Cancer-associated Fibroblast-derived IL-6 Promotes Head and Neck Cancer Progression via the Osteopontin-NF-kappa B Signaling Pathway
Authors: Xing Qin, Ming Yan, Xu Wang, Qin Xu, Xiaoning Wang, Xueqin Zhu, Jianbo Shi, Zhihui Li, Jianjun Zhang, Wantao Chen
Journal: Theranostics (2018)

Osteopontin (OPN), a chemokine-like protein, plays a crucial role in the proliferation and metastasis of various cancers.However, how tumor stroma modulates the expression of neoplastic OPN and the multifaceted roles of OPN in head and neck cancer (HNC) are unclear.In this study, we tried to investigate the bridging role of OPN between tumor stroma and cancer cells.Methods: Immunohistochemical staining and quantitative real-time PCR were used to detect OPN expression in HNC tissues, and the correlations between OPN expression and clinicopathologic features were then analyzed.We used a co-culture assay to study the modulatory role of IL-6 on OPN expression and immunoprecipitation analysis was used to determine the endogenous interaction between OPN and integrin αvβ3.Furthermore, a xenograft assay was carried out to confirm the tumor-promoting role and the potential therapeutic value of OPN in HNC.Results: We found that OPN was significantly up-regulated in HNCs, and the elevated OPN was correlated with poor prognosis.Moreover, we identified IL-6 secreted by cancer-associated fibroblasts (CAFs) as the major upstream molecule that triggers the induction of neoplastic OPN.As such, during the interaction of fibroblasts and cancer cells, the increased neoplastic OPN induced by stromal IL-6 accelerated the growth, migration and invasion of cancer cells.More importantly, we also showed that soluble OPN could promote HNC progression via the integrin αvβ3-NF-kappa B pathway, and the combination of OPN and IL-6 had a better prognostic and diagnostic performance in HNC than either molecule alone. Conclusion:Our study identified a novel modulatory role for OPN in HNC progression and further demonstrated that the combination of OPN and IL-6 might be a promising prognostic and diagnostic indicator as well as a potential cancer therapeutic target.
Genomic characterisation of human monkeypox virus in Nigeria
Authors: Ousmane Faye, Catherine B Pratt, Martin Faye, Gamou Fall, Joseph A Chitty, Moussa M Diagne, Michael R Wiley, Adesola F Yinka-Ogunleye, Sola Aruna, Ebitimitula N Etebu, Neni Aworabhi, Dimie Ogoina, Wari Numbere, Nwando Mba, Gustavo Palacios, Amadou A Sall, Chikwe Ihekweazu
Journal: The Lancet Infectious Diseases (2018)