tbuckley/cabot-search huggingface dataset:
Rituximab after Autologous Stem-Cell Transplantation in Mantle-Cell Lymphoma
Authors: Steven Le Gouill, Catherine Thieblemont, Lucie Oberic, Anne Moreau, Krimo Bouabdallah, Caroline Dartigeas, Gandhi Damaj, Thomas Gastinne, Vincent Ribrag, Pierre Feugier, Olivier Casasnovas, Hacène Zerazhi, Corinne Haioun, Hervé Maisonneuve, Roch Houot, Fabrice Jardin, Eric Van Den Neste, Olivier Tournilhac, Katell Le Dû, Franck Morschhauser, Guillaume Cartron, Luc-Matthieu Fornecker, Danielle Canioni, Mary Callanan, Marie C. Béné, Gilles Salles, Hervé Tilly, Thierry Lamy, Remy Gressin, Olivier Hermine
Journal: New England Journal of Medicine (2017)

Mantle-cell lymphoma is generally incurable. Despite high rates of complete response after initial immunochemotherapy followed by autologous stem-cell transplantation, patients have relapses. We investigated whether rituximab maintenance therapy at a dose of 375 mg per square meter of body-surface area administered every 2 months for 3 years after transplantation would prolong the duration of response.
Impaired lung repair during neutropenia can be reverted by matrix metalloproteinase-9
Authors: Jorge Blázquez-Prieto, Inés López-Alonso, Laura Amado-Rodríguez, Covadonga Huidobro, Adrián González-López, Wolfgang M Kuebler, Guillermo M Albaiceta
Journal: Thorax (2017)

Background Neutrophils may cause tissue disruption during migration and by releasing cytotoxic molecules. However, the benefits of neutrophil depletion observed in experimental models of lung injury do not correspond with the poor outcome of neutropenic patients. Methods To clarify the role of neutrophils during repair, mice with ventilator induced lung injury (VILI) were rendered neutropenic after damage, and followed for 48 hours of spontaneous breathing. Lungs were harvested and inflammatory mediators and matrix metalloproteinases measured. Bronchoalveolar lavage fluid (BALF) from ventilated patients with acute respiratory distress syndrome, with or without neutropenia, was collected, the same mediators measured and their effects in an ex vivo model of alveolar repair studied. Finally, neutropenic mice were treated after VILI with exogenous matrix metalloproteinase-9 (MMP-9). Results Lungs from neutropenic animals showed delayed repair and displayed higher levels of tumour necrosis factor α, interferon γ and macrophage inflammatory protein 2, and absence of MMP-9. BALF from ventilated neutropenic patients with acute respiratory distress syndrome showed similar results. BALFs from neutropenic patients yielded a delayed closure rate of epithelial wounds ex vivo, which was improved by removal of collagen or addition of exogenous MMP-9. Lastly, treatment of neutropenic mice with exogenous MMP-9 after VILI reduced tissue damage without modifying cytokine concentrations. Conclusion Release of MMP-9 from neutrophils is required for adequate matrix processing and lung repair.
Serum Polybrominated Biphenyls (PBBs) and Polychlorinated Biphenyls (PCBs) and Thyroid Function among Michigan Adults Several Decades after the 1973–1974 PBB Contamination of Livestock Feed
Authors: Melanie H. Jacobson, Lyndsey A. Darrow, Dana Boyd Barr, Penelope P. Howards, Robert H. Lyles, Metrecia L. Terrell, Alicia K. Smith, Karen N. Conneely, M. Elizabeth Marder, Michele Marcus
Journal: Environmental Health Perspectives (2017)

Background: In 1973–1974, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. Residents were enrolled in a registry assembled after the incident, and they and their children participated in follow-up studies to assess subsequent health outcomes. Objectives: We evaluated associations between serum PBBs and polychlorinated biphenyls (PCBs) and markers of thyroid function among Michigan adults. Methods: Serum concentrations of four PBB and four PCB congeners were measured at least once in 753 adults, including 79 women who participated in a 2004–2006 study and 683 women and men with follow-up during 2012–2015. Participants completed questionnaires on health conditions (including physician-diagnosed thyroid disease), behaviors, and demographics. Thyroid hormones were measured in a subset without thyroid disease (n=551). In multivariable linear regression models, PBB and PCB congener concentrations, on both the volume (nanogram/milliliter) and lipid (nanogram/gram lipid) basis, were assessed in relation to thyroid hormones. Logistic regression models were used to estimate associations between serum PBBs and PCBs and thyroid disease. Results: Thyroid disease was common (18% overall; 25% among women). Among women, all odds ratios (ORs) for PBB-153 and thyroid disease were positive for quintiles above the reference level, but estimates were imprecise and were without a monotonic increase. For an interquartile range (IQR) increase in PBB-153 (0.43 ng/mL), the OR (any thyroid disease)=1.12; (95% CI: 0.83, 1.52) (n=105 cases); for hypothyroidism, OR=1.35 (95% CI: 0.86, 2.13) (n=49 cases). There were 21 cases of thyroid disease in men [OR=0.69 (95% CI: 0.33); 1.44 for an IQR increase (0.75 ng/mL) in serum PBB-153]. PCB congeners were statistically significantly associated with greater total and free thyroxine and total triiodothyronine among women and with total and free triiodothyronine among men in lipid-standardized models. Conclusions: We found some evidence to support associations of PBBs and PCBs with thyroid disease and thyroid hormone levels. https://doi.org/10.1289/EHP1302
Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial
Authors: Yi-Long Wu, Ying Cheng, Xiangdong Zhou, Ki Hyeong Lee, Kazuhiko Nakagawa, Seiji Niho, Fumito Tsuji, Rolf Linke, Rafael Rosell, Jesus Corral, Maria Rita Migliorino, Adam Pluzanski, Eric I Sbar, Tao Wang, Jane Liang White, Sashi Nadanaciva, Rickard Sandin, Tony S Mok
Journal: The Lancet Oncology (2017)
National clinical practice guidelines for allergen immunotherapy: An international assessment applying <scp>AGREE</scp>‐<scp>II</scp>
Authors: D. E. S. Larenas‐Linnemann, D. Antolín‐Amérigo, C. Parisi, A. Nakonechna, J. A. Luna‐Pech, B. Wedi, I. Davila, M. Gómez, M. Levin, J. A. Ortega Martell, L. Klimek, N. Rosario, A. M. Muraro, I. Agache, J. Bousquet, A. Sheikh, O. Pfaar
Journal: Allergy (2017)

Abstract Background Since 1988, numerous allergen immunotherapy guidelines ( AIT ‐ GL s) have been developed by national and international organizations to guide physicians in AIT . Even so, AIT is still severely underused. Objective To evaluate AIT ‐ GL s with AGREE ‐ II , developed in 2010 by McMaster University methodologists to comprehensively evaluate GL quality. Methods Allergist, from different continents, knowledgeable in AIT and AGREE ‐ II trained were selected into the project team. The project received methodologists’ guidance. AIT ‐ GL s in any language were sought from 1980 to 2016; AIT ‐ GL s were AGREE II ‐evaluated by at least 2 team members, independently; discrepancies were resolved in a second round, by team discussion or methodologists’ consulting. Results We found 31 AIT ‐ GL s (15 post‐2010), ranging from local consensus reports to international position papers ( EAACI , AAAAI ‐ ACAAI , WAO ). Pre‐2010 GL s scored 1.6‐4.6 (23%‐67%) and post‐2010 GL s scored 2.1‐6 (30%‐86%), on a 7‐point Likert scale. The highest scores went to: German‐Austrian‐Swiss (6.0), Mexican (5.1), and the AAAAI / ACAAI AIT ‐ GL (4.7). These were also the only 3 GL s that received “yes” of both evaluators to the item: “I would recommend this GL for use.” The domains of “Stakeholder involvement” and “Rigor of Development” only scored 3/7, and “Applicability” scored the lowest. Strikingly, newer GL s only scored clearly better in “Editorial independence” and “Global evaluation.” Conclusions In AIT ‐ GL s, there is still a lot of room for improvement, especially in domains crucial for the dissemination. For some GL s, the “Scientific rigor” domain flawed. When resources are limited, transculturizing a high‐quality GL might be preferable over developing a GL from zero. Our study and AGREE ‐ II could help to select the best candidate. Clinical Implications We here evaluate allergen immunotherapy guideline ( AIT ‐ GL ) quality. Only high‐quality AIT ‐ GL s should be consulted for AIT management decisions. In low‐resource settings, transculturization of these is preferred over developing low‐quality guidelines.
NHS for sale
Authors: Fiona Godlee
Journal: BMJ (2017)

Selling off unused or underused estate sounds like a good idea for any organisation in need of funds, and the NHS is certainly that. The Naylor Review, published in March (doi:10.1136/bmj.j2072), concluded that a sale of NHS buildings and land would raise £5.7bn (€6.5bn; $7.7bn) and save a further £1bn a year. Along with government and private investment, a total of £10bn could be reinvested in the NHS. The government has yet to respond formally, but the prime minister has said that she supports …
Effects of Orally Ingested Arsenic on Respiratory Epithelial Permeability to Bacteria and Small Molecules in Mice
Authors: Michael W. Henderson, Jennifer H. Madenspacher, Gregory S. Whitehead, Seddon Y. Thomas, Jim J. Aloor, Kymberly M. Gowdy, Michael B. Fessler
Journal: Environmental Health Perspectives (2017)

Background: Arsenic exposure via drinking water impacts millions of people worldwide. Although arsenic has been associated epidemiologically with increased lung infections, the identity of the lung cell types targeted by peroral arsenic and the associated immune mechanisms remain poorly defined. Objectives: We aimed to determine the impact of peroral arsenic on pulmonary antibacterial host defense. Methods: Female C57BL/6 mice were administered drinking water with 0, 250 ppb, or 25 ppm sodium arsenite for 5 wk and then challenged intratracheally with Klebsiella pneumoniae, Streptococcus pneumoniae, or lipopolysaccharide. Bacterial clearance and immune responses were profiled. Results: Arsenic had no effect on bacterial clearance in the lung or on the intrapulmonary innate immune response to bacteria or lipopolysaccharide, as assessed by neutrophil recruitment to, and cytokine induction in, the airspace. Alveolar macrophage TNFα production was unaltered. By contrast, arsenic-exposed mice had significantly reduced plasma TNFα in response to systemic lipopolysaccharide challenge, together suggesting that the local airway innate immune response may be relatively preserved from arsenic intoxication. Despite intact intrapulmonary bacterial clearance during pneumonia, arsenic-exposed mice suffered dramatically increased bacterial dissemination to the bloodstream. Mechanistically, this was linked to increased respiratory epithelial permeability, as revealed by intratracheal FITC-dextran tracking, serum Club Cell protein 16 measurement, and other approaches. Consistent with barrier disruption at the alveolar level, arsenic-exposed mice had evidence for alveolar epithelial type 1 cell injury. Conclusions: Peroral arsenic has little effect on local airway immune responses to bacteria but compromises respiratory epithelial barrier integrity, increasing systemic translocation of inhaled pathogens and small molecules. https://doi.org/10.1289/EHP1878
Predictors of female genital organ involvement in radical cystectomy for urothelial carcinoma of the bladder: A single-center retrospective analysis of 112 female patients
Authors: Se Young Choi, Sangjun Yoo, Jae Hyeon Han, In Gab Jeong, Bumsik Hong, Jun Hyuk Hong, Hanjong Ahn, Choung-Soo Kim, Dalsan You
Journal: International Journal of Surgery (2017)
Cellular kinetics of CTL019 in relapsed/refractory B-cell acute lymphoblastic leukemia and chronic lymphocytic leukemia
Authors: Karen Thudium Mueller, Shannon L. Maude, David L. Porter, Noelle Frey, Patricia Wood, Xia Han, Edward Waldron, Abhijit Chakraborty, Rakesh Awasthi, Bruce L. Levine, J. Joseph Melenhorst, Stephan A. Grupp, Carl H. June, Simon F. Lacey
Journal: Blood (2017)
Development of resistance to <i>Mycobacterium tuberculosis</i> is manageable in hidradenitis suppurativa. Response to ‘Treatment of hidradenitis suppurativa with rifampicin: have we forgotten tuberculosis?’
Authors: J. Albrecht, S. Mehta, M. Bigby
Journal: British Journal of Dermatology (2017)

We read the letter by Mendes-Bastos et al. with concern.1 Simply testing patients for latent tuberculosis solves the problem, and the authors did not mention that rifampin is an acceptable monotherapy for latent tuberculosis.2 Hidradentitis suppurativa has the highest impact on quality of life of all dermatological diseases,3 and clindamycin and rifampin are a cornerstones of frequently failing therapy regimes.3 At the same time drug-resistant tuberculosis is a tremendous public health problem, particularly in China, the former Soviet Union, and India.

This article is protected by copyright. All rights reserved.
Conducting Science in Disasters: Recommendations from the NIEHS Working Group for Special IRB Considerations in the Review of Disaster Related Research
Authors: Joan P. Packenham, Richard T. Rosselli, Steve K. Ramsey, Holly A. Taylor, Alice Fothergill, Julia Slutsman, Aubrey Miller
Journal: Environmental Health Perspectives (2017)

Research involving human subjects after public health emergencies and disasters may pose ethical challenges.These challenges may include concerns about the vulnerability of prospective disaster research participants, increased research burden among disaster survivors approached by multiple research teams, and potentially reduced standards in the ethical review of research by institutional review boards (IRBs) due to the rush to enter the disaster field.The NIEHS Best Practices Working Group for Special IRB Considerations in the Review of Disaster Related Research was formed to identify and address ethical and regulatory challenges associated with the review of disaster research.The working group consists of a diverse collection of disaster research stakeholders across a broad spectrum of disciplines.The working group convened in July 2016 to identify recommendations that are instrumental in preparing IRBs to review protocols related to public health emergencies and disasters.The meeting included formative didactic presentations and facilitated breakout discussions using disaster-related case studies.Major thematic elements from these discussions were collected and documented into 15 working group recommendations, summarized in this article, that address topics such as IRB disaster preparedness activities, informed consent, vulnerable populations, confidentiality, participant burden, disaster research response integration and training, IRB roles/responsibilities, community engagement, and dissemination of disaster research results.
Portable Functional Neuroimaging as an Environmental Epidemiology Tool: A How-To Guide for the Use of fNIRS in Field Studies
Authors: Joseph M. Baker, Daniel Rojas-Valverde, Randall Gutiérrez, Mirko Winkler, Samuel Fuhrimann, Brenda Eskenazi, Allan L. Reiss, Ana M. Mora
Journal: Environmental Health Perspectives (2017)

Summary: The widespread application of functional neuroimaging within the field of environmental epidemiology has the potential to greatly enhance our understanding of how environmental toxicants affect brain function. Because many epidemiological studies take place in remote and frequently changing environments, it is necessary that the primary neuroimaging approach adopted by the epidemiology community be robust to many environments, easy to use, and, preferably, mobile. Here, we outline our use of functional near-infrared spectroscopy (fNIRS) to collect functional brain imaging data from Costa Rican farm workers enrolled in an epidemiological study on the health effects of chronic pesticide exposure. While couched in this perspective, we focus on the methodological considerations that are necessary to conduct a mobile fNIRS study in a diverse range of environments. Thus, this guide is intended to be generalizable to all research scenarios and projects in which fNIRS may be used to collect functional brain imaging data in epidemiological field surveys. https://doi.org/10.1289/EHP2049
Feasible and efficient identification of neoantigens for personalized cancer immunotherapy in advanced refractory epithelial cancer patients.
Authors: Fangjun Chen, Zhengyun Zou, Juan Du, Jia Wei, Jie Shao, Shu Su, Naiqing Ding, Qin Wang, Shujuan Zhou, Zhichen Sun, Baorui Liu
Journal: Journal of Clinical Oncology (2017)

3046 Background: Recent genomic and bioinformatic technological advances have made it possible to dissect the immune response to personalized neoantigens encoded by tumor-specific mutations.However, rapid and efficient identification of neoantigens is still fraught with difficulty, and a systematic evaluation of personalized neoantigens based immunotherapy in advanced refractory epithelial tumors is lacking. Methods: Tumor and ctDNA samples from 16 advanced epithelial cancer patients were underwent mutational profiling by cancer-associated genes panel. Neoantigens identification were performed by two strategies: As classic mode, somatic mutations were subjected to in silico analysis to predict potential high-affinity epitopes and mutated peptides were denovo synthesized; Hotspot mutations were matched to our customized driver mutation-derived neoantigens peptide library. Candidate neoepitopes were identified. Approximately 10 8 neoantigen loaded DC vaccine and 10 10 bulk T cells composed of 10 9 neoantigen reactive CD8+T cells were generated for personlized immunotherapy. Results: Among the sequenced patients, 3 of 4 patients who utilized the classic mode and 6 of 12 patients who performed customized neoantigens library have successfully identified 1~2 neoantigens recognized by autologous T cells, respectively. Subsequently, a total number of 6 patients received immunotherapy targeting personalized neoantigen. To date, one patient with metastatic thymoma is achieving a complete and durable response beyond 9 months. In addition, immune related partial response was observed in another advanced pancreatic cancer patient. The remaining 4 patients achieved prolonged stabilization of disease with median PFS of 8.6 months. Conclusions: Our costomized neoantigens library can provide a novel approach for neoantigens screening in advanced epithelial cancer patients. Besides, targeted sequencing is sufficient for somatic variant and neoantigen identification. The combination of two strategies can accelerate the neoantigen-based translational immunotherapy research into the paradigm of precision medicine.
First-line pembrolizumab in cisplatin-ineligible patients with locally advanced and unresectable or metastatic urothelial cancer (KEYNOTE-052): a multicentre, single-arm, phase 2 study
Authors: Arjun V Balar, Daniel Castellano, Peter H O'Donnell, Petros Grivas, Jacqueline Vuky, Thomas Powles, Elizabeth R Plimack, Noah M Hahn, Ronald de Wit, Lei Pang, Mary J Savage, Rodolfo F Perini, Stephen M Keefe, Dean Bajorin, Joaquim Bellmunt
Journal: The Lancet Oncology (2017)
Protocol II vs protocol III given twice during reinduction therapy in children with medium-risk ALL
Authors: Franco Locatelli, Maria Grazia Valsecchi, Anja Möricke, Martin Zimmermann, Bernd Gruhn, Andrea Biondi, Andreas E. Kulozik, Daniela Silvestri, Nicole Bodmer, Maria Caterina Putti, Stefan Burdach, Concetta Micalizzi, Andrea Teigler-Schlegel, Jörg Ritter, Andrea Pession, Gunnar Cario, Stefan Bielack, Giuseppe Basso, Thomas Klingebiel, Luciana Vinti, Carmelo Rizzari, Andishe Attarbaschi, Nicola Santoro, Rosanna Parasole, Georg Mann, Leonid Karawajew, Oskar A. Haas, Valentino Conter, Martin Schrappe
Journal: Blood (2017)
NHS bosses reject GPs’ request to close patient lists
Authors: Gareth Iacobucci
Journal: BMJ (2017)

A group of general practices in Folkestone, Kent, that applied to formally close their practice lists because of safety concerns have had their request knocked back by NHS bosses, The BMJ has learnt.

Earlier this month seven of eight practices in the town applied for permission to close their patient lists on the basis that they were “unable to take on more patients safely.” The action was triggered after one local practice was forced to hand its contract back to South Kent Coast Clinical Commissioning Group in May, prompting the CCG to order that the practice’s 4700 patients be reallocated to other local practices.

But the CCG rejected the practices’ application after a meeting held on Thursday 21 September. …
Image gallery: Black walnut staining: an unusual presentation of exogenous pigmentation
Authors: D. P. Patel, L. Castelo‐Soccio
Journal: British Journal of Dermatology (2017)

Dear Editor, A 9‐year‐old boy presented with a 3‐day history of asymptomatic brown patches that appeared suddenly on his feet (a). Diagnosis was unclear until the boy's father noticed the boy's socks had a similarly patterned stain (b). Further inquiry revealed the boy had been playing in a yard covered with fallen black walnuts. Three weeks later, the hyperpigmentation had self‐resolved. The black walnut tree (Juglans nigra) is native to eastern North America and is used for its dark‐stained wood and edible nuts.1 While historically it has been used for hair dye, no formal reports of use as skin dye exist. Our case highlights this unexpected source of exogenous pigmentation.
Circulating biomarkers in patients receiving neoadjuvant chemotherapy combined with sunitinib for locally advanced breast cancer.
Authors: Ursa Abigail Brown-Glaberman, Jennifer M. Specht, Maria Iannone, Brenda F. Kurland, Robert B. Livingston, Alison Stopeck
Journal: Journal of Clinical Oncology (2013)

1089 Background: Biomarkers to guide the use of antiangiogenic therapy are lacking. Circulating endothelial cells (CECs) and their progenitor cells (CEPs) are increased in cancer patients. VCAM is an endothelial protein increased in response to VEGF stimulation, while CAIX is elevated in states of hypoxia; both correlate with tumor aggressiveness. Methods: We examined these circulating biomarkers in a phase II neoadjuvant trial in 63 patients (pts) with locally advanced HER2 negative breast cancer treated with 12 weeks (wks) of paclitaxel (T) plus sunitinib (S) followed by 15 wks of daily oral cyclophosphamide and weekly doxorubicin plus daily G-CSF (AC+G-CSF). Toxicity and clinical outcomes are reported as a separate abstract. Blood was collected at baseline, wk 12 and pre-surgery. For this analysis, responders were defined as patients with a pathologic complete response (pCR) and/or MDACC CPS+EG score ≤ 2 (a validated score combining clinical and pathologic results for predicting survival in the neoadjuvant setting). Plasma VCAM and CAIX levels were measured by ELISA using commercially available validated kits and CEC/CEPs by flow cytometry in our laboratory as previously published. Results: 28 (44%) pts were responders. CECs decreased significantly in response to T+S (p = 0.04) but not further with AC+G-CSF. No significant changes were seen in CEPs. VCAM and CAIX levels increased in pts with baseline levels below the median in response to T+S (VCAM p = 0.0003, CAIX p = 0.009). ER negative tumors had higher levels of plasma VCAM and CAIX at baseline compared to ER positive tumors (VCAM p = 0.01, CAIX p = 0.1). Lower baseline levels of VCAM and CAIX were associated with both response and pCR. VCAM and CAIX levels were correlated at baseline (r = 0.4, p = 0.01). Conclusions: CEC, VCAM, and CAIX levels significantly changed after treatment with T + S. Higher baseline levels of VCAM and CAIX were associated with ER negative tumors and lower response rates. Our results suggest that elevated baseline VCAM and CAIX levels are associated with more aggressive biology, and may correspond to less (not more) favorable outcome with the addition of a targeted antiangiogenic agent. Clinical trial information: NCT00513695.
Tetrahydrobiopterin-dependent eNOS coupling determines vascular remodeling through accelerated endothelial regeneration
Authors: Z A Ali, N J Alp, Y H Hu, Q Z Xiao, A L Tatham, J P deBono, R Rinze, G Douglas, A M Akhtar, Greaves, Q B Xu, K M Channon
Journal: Journal of the American College of Cardiology (2007)