tbuckley/cabot-search huggingface dataset:
Adjuvanted influenza-H1N1 vaccination reveals lymphoid signatures of age-dependent early responses and of clinical adverse events
Authors: Olga Sobolev, Elisa Binda, Sean O'Farrell, Anna Lorenc, Joel Pradines, Yongqing Huang, Jay Duffner, Reiner Schulz, John Cason, Maria Zambon, Michael H Malim, Mark Peakman, Andrew Cope, Ishan Capila, Ganesh V Kaundinya, Adrian C Hayday
Journal: Nature Immunology (2016)
Behavioural interventions for diabetes yield modest benefits, reviews find
Authors: Michael McCarthy
Journal: BMJ (2015)

Patients with type 1 diabetes enrolled in behavioural programmes achieve only modest, short term improvements in glycaemic control, although patients with type 2 diabetes can achieve clinically important reductions in glycated haemoglobin (HbA1c) if enrolled in more intensive programmes, two new systematic reviews and meta-analyses have found. The studies were published in the Annals of Internal Medicine .

In the first study1 Jennifer Pillay, lead author, of the University of Alberta in Edmonton, Canada, analysed 35 prospective controlled trials that compared behavioural programmes with usual care, active controls, and other behavioural programmes. For the purpose of this study behavioural programmes were defined as diabetes specific programmes using repeated interactions with trained personnel, lasting at least four weeks, and including diabetes self management …
Genetic variation in STAT4 predicts response to interferon‐α therapy for hepatitis B e antigen‐positive chronic hepatitis B
Authors: De‐Ke Jiang, Xiaopan Wu, Ji Qian, Xiao‐Pin Ma, Jingmin Yang, Zhuo Li, Runhua Wang, Li Sun, Fang Liu, Pengyin Zhang, Xilin Zhu, Jia Wu, Kangmei Chen, Carly Conran, S. Lilly Zheng, Daru Lu, Long Yu, Ying Liu, Jianfeng Xu
Journal: Hepatology (2015)

Interferon (IFN)‐α is a first‐line therapy for chronic hepatitis B (CHB) patients but only initiates a response in a minority of patients. A genetic variant, rs7574865 in STAT4 , was recently reported to be associated with risk of developing CHB and hepatitis B virus‐related hepatocellular carcinoma. We aimed to determine whether this variant is associated with the response to IFNα treatment for hepatitis B e antigen (HBeAg)‐positive CHB patients. We studied 466 HBeAg‐positive CHB patients who received either IFNα‐2b (n = 224) or pegylated IFNα‐2a (n = 242) therapy for 48 weeks and were followed for an additional 24 weeks. The rate of sustained virologic response (SVR), defined as HBeAg seroconversion along with hepatitis B virus DNA level &lt;2000 copies/mL at week 72, was compared among patients with different genotypes of rs7574865. After 48 weeks of treatment and 24 weeks off treatment, the SVR rates in the IFNα‐2b and pegylated IFNα‐2a therapy groups were 30.4% and 28.9%, respectively. Compared to the rs7574865 GT/TT genotype, the GG genotype (a risk factor of CHB and hepatitis B virus‐related hepatocellular carcinoma) was significantly associated with a reduced SVR rate in both patients who received IFNα‐2b therapy (21.1% versus 37.2%, P = 0.01) and those who received pegylated IFNα‐2a therapy (18.0% versus 41.2%, P = 9.74 × 10 ‐5 ). In joint analysis of the 466 patients, the GG genotype was associated with an approximately half SVR rate compared to the GT/TT genotype (19.3% versus 39.1%, P = 4.15 × 10 ‐6 ). A multivariate logistic regression model including rs7574865 and clinical variables showed that rs7574865 was the most significant factor for the prediction of SVR. Conclusion: STAT4 rs7574865 is a reliable predictor of response to IFNα therapy for HBeAg‐positive CHB patients and may be used for optimizing the treatment of CHB. (H epatology 2016;63:1102–1111)
Biochemical and histochemical characterization of a murine tubular antigen.
Authors: I D Davis, T W LeBien, B J Lindman, J L Platt
Journal: Journal of the American Society of Nephrology (1991)

Cellular components of the developing fetal nephron express certain cell surface antigens at discrete stages of nephron development. To further evaluate the expression of antigens by tubular epithelium, a rat monoclonal antibody (BL26) was developed against murine fetal kidney. BL26 identified a differentiation antigen expressed by epithelial cells of the ureteric bud and late S-body in developing nephrons and by endothelium, mesangium, and distal tubular epithelium in mature nephrons. The polypeptide identified by BL26 was shown to be synthesized by fetal kidney and renal adenocarcinoma cells. The polypeptide contained no detectable carbohydrate modifications but was found in two isoforms, an acylated (26,000-Da) form and a nonacylated (24,000-Da) form. The murine antigen recognized by BL26 and the human CD9 moiety, an acylated polypeptide with a tissue distribution similar to that of the BL26 antigen, comigrated in polyacrylamide gels. We speculate that expression of the BL26 antigen and CD9 reflects processes relating to the activation of epithelial cells.
Not all NOTCH Is Created Equal: The Oncogenic Role of NOTCH2 in Bladder Cancer and Its Implications for Targeted Therapy
Authors: Tetsutaro Hayashi, Kilian M. Gust, Alexander W. Wyatt, Akihiro Goriki, Wolfgang Jäger, Shannon Awrey, Na Li, Htoo Zarni Oo, Manuel Altamirano-Dimas, Ralph Buttyan, Ladan Fazli, Akio Matsubara, Peter C. Black
Journal: Clinical Cancer Research (2016)

Recent molecular analyses of bladder cancer open the door to significant advances in targeted therapies. NOTCH has been identified as a tumor suppressor in bladder cancer, but prior reports have focused on NOTCH1 Here we hypothesized that NOTCH2 is an oncogene suitable for therapeutic targeting in bladder cancer.We studied genomic aberrations of NOTCH, compared survival and tumor progression according to NOTCH2 expression levels, and studied NOTCH2 function in vitro and vivoWe report a high rate of NOTCH2 copy number gain in bladder cancer. High NOTCH2 expression was identified especially in the basal subtype and in mesenchymal tumors. NOTCH2 activation correlated with adverse disease parameters and worse prognosis by immunohistochemistry. Forced overexpression of the intracellular domain of NOTCH2 (N2ICD) induced cell growth and invasion by cell-cycle progression, maintenance of stemness and epithelial-to-mesenchymal transition (EMT). These effects were abrogated by silencing of CSL, indicating that the effects were mediated through the canonical NOTCH signaling pathway. In an orthotopic xenograft model, forced overexpression of N2ICD increased growth, invasion, and metastasis. To explore the potential for therapeutic targeting of NOTCH2, we first silenced the receptor with shRNA and subsequently treated with a specific inhibitory antibody. Both interventions decreased cell growth, invasion, and metastasis in vitro and in the orthotopic xenograft model.We have demonstrated that NOTCH2 acts as an oncogene that promotes bladder cancer growth and metastasis through EMT, cell-cycle progression, and maintenance of stemness. Inhibition of NOTCH2 is a rational novel treatment strategy for invasive bladder cancer. Clin Cancer Res; 22(12); 2981-92. ©2016 AACR.
The impact of primary irradiation treatment of localized breast cancer on the ability to administer systemic adjuvant chemotherapy.
Authors: M E Lippman, A S Lichter, B K Edwards, C R Gorrell, T d'Angelo, E V DeMoss
Journal: Journal of Clinical Oncology (1984)

The impact of primary irradiation of localized breast cancer on the ability to administer Adriamycin-cytoxan adjuvant chemotherapy to patients with stage II breast cancer was examined. Patients were prospectively randomized to receive either irradiation or mastectomy as local therapy and did not differ with respect to other prognostic variables that might influence tolerance to chemotherapy. All of the patients received chemotherapy dose escalations (or reductions) until maximal tolerated drug doses were established. Patients receiving irradiation had minimally greater myelosuppression which was nearly totally explainable by lymphopenia. Irradiated patients required dose reduction nearly twice as often as mastectomy patients although commonly their dose could be reescalated. Patients managed with radiotherapy received slightly less drug than patients treated with mastectomy when treated to an identical degree of bone marrow suppression. The primary management of breast cancer by irradiation does not induce substantial changes in the ability of patients to tolerate adjuvant chemotherapy.
Abstract 4401: Tumor-associated antigen gene-loading polyplex micelle is a promising platform for anti-cancer DNA vaccine
Authors: Lin Cui, Kouichi Furugaki, Kensuke Osada, Kazunori Kataoka, Kenji Nakano
Journal: Cancer Research (2015)

Abstract Backgrounds: Polyplex micelle attracts an increasing attention as a gene carrier, because of efficient gene transduction and biocompatibility in vivo. In this study, we examined the potential of polyplex micelle carrying genes encoding tumor-associated antigen (TAA): squamous cell carcinoma antigen recognized by T cells-3, CD40L and GM-CSF as a DNA vaccine platform in mouse tumor models with different types of major histocompatibility antigen complex (MHC). Methods and Results: Intraperitoneal administration of polyplex micelles were predominantly distributed and expressed in the lymph nodes, spleen and liver. The triple DNA vaccine significantly prolonged the survival of mice harboring peritoneal dissemination of CT26 colorectal cancer compared with mock controls, of which long-survivor mice induced complete rejection of re-challenged CT26 tumors. The DNA vaccine also inhibited the growth and metastasis of subcutaneous CT26 and Lewis lung cancers in BALB/c and C57BL/6 mice, respectively, which represent different MHC haplotypes. The DNA vaccine highly stimulated both cytotoxic T lymphocyte and natural killer cell activities, and increased the infiltration of CD11c+-DC, CD4+ and CD8a+ T cells into tumors. Depletion of CD4+ or CD8a+ cells using their neutralizing antibodies deteriorated the anti-tumor efficacy of the DNA vaccine. Conclusions: TAA/CD40L+GM-CSF gene-loaded polyplex micelle is a novel vaccine platform to elicit tumor rejection immunity regardless of recipient's MHC-haplotype. Note: This abstract was not presented at the meeting. Citation Format: Lin Cui, Kouichi Furugaki, Kensuke Osada, Kazunori Kataoka, Kenji Nakano. Tumor-associated antigen gene-loading polyplex micelle is a promising platform for anti-cancer DNA vaccine. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4401. doi:10.1158/1538-7445.AM2015-4401
Ancient DNA and the rewriting of human history: be sparing with Occam’s razor
Authors: Marc Haber, Massimo Mezzavilla, Yali Xue, Chris Tyler-Smith
Journal: Genome biology (2016)

Ancient DNA research is revealing a human history far more complex than that inferred from parsimonious models based on modern DNA. Here, we review some of the key events in the peopling of the world in the light of the findings of work on ancient DNA.
Ibrutinib as Initial Therapy for Patients with Chronic Lymphocytic Leukemia
Authors: Jan A. Burger, Alessandra Tedeschi, Paul M. Barr, Tadeusz Robak, Carolyn Owen, Paolo Ghia, Osnat Bairey, Peter Hillmen, Nancy L. Bartlett, Jianyong Li, David Simpson, Sebastian Grosicki, Stephen Devereux, Helen McCarthy, Steven Coutre, Hang Quach, Gianluca Gaidano, Zvenyslava Maslyak, Don A. Stevens, Ann Janssens, Fritz Offner, Jiří Mayer, Michael O’Dwyer, Andrzej Hellmann, Anna Schuh, Tanya Siddiqi, Aaron Polliack, Constantine S. Tam, Deepali Suri, Mei Cheng, Fong Clow, Lori Styles, Danelle F. James, Thomas J. Kipps
Journal: New England Journal of Medicine (2015)

Chronic lymphocytic leukemia (CLL) primarily affects older persons who often have coexisting conditions in addition to disease-related immunosuppression and myelosuppression. We conducted an international, open-label, randomized phase 3 trial to compare two oral agents, ibrutinib and chlorambucil, in previously untreated older patients with CLL or small lymphocytic lymphoma.
From the picket line: junior doctors speak out
Authors: Gareth Iacobucci, Abi Rimmer
Journal: BMJ (2016)

<i>BMJ</i> reporters <b>Gareth Iacobucci</b> and <b>Abi Rimmer</b> spoke to junior doctors on the picket line at the Royal London Hospital during the 24 hour strike across England on Tuesday 12 January
Acute Kidney Injury
Authors: Anna Zuk, Joseph V. Bonventre
Journal: Annual Review of Medicine (2016)

Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD).
Cytoarchitecture of the entorhinal cortex in schizophrenia
Authors: M Akil, D A Lewis
Journal: American Journal of Psychiatry (1997)

The purpose of this study was to determine whether schizophrenia is associated with abnormalities in neuronal migration in the entorhinal cortex.Nissl-stained sections through three cytoarchitectonic subdivisions of the entorhinal cortex were examined in postmortem brain specimens from 10 schizophrenic subjects and 10 matched normal comparison subjects.No qualitative differences in cytoarchitecture were observed between the schizophrenic and comparison subjects.These findings do not replicate previous reports of cytoarchitectural disturbances in the entorhinal cortex of schizophrenic subjects and thus fail to support the hypothesis of abnormal neuronal migration in schizophrenia.
In children 18 years and under, what promotes recurrent shoulder instability after traumatic anterior shoulder dislocation? A systematic review and meta-analysis of risk factors
Authors: M Olds, K Donaldson, R Ellis, P Kersten
Journal: British Journal of Sports Medicine (2015)

Background Skeletal maturity and age-related changes in the composition of the glenoid labrum and joint capsule may influence rates of recurrent instability in children. We systematically review risk factors which predispose children to recurrent shoulder instability. Methods The systematic review-concerned studies published before May 2015. Statistical analysis was undertaken to compare rates of recurrence for each extracted risk factor. Pooled ORs were analysed using random effects meta-analysis. Results 6 retrospective cohort studies met the inclusion criteria. 8 risk factors were identified across the studies including age, sex, shoulder dominance and injury side, mechanism of injury, state of physis closure, and Hill-Sachs and Bankart lesions. The rate of recurrent instability was 73%. Children aged 14–18 years were 24 times more likely to experience recurrent instability than children aged 13 years and less (93% vs 40%; OR=24.14, 95% CI (3.71 to 156.99), Z=3.33, p=0.001, I 2 =6.83%). There was a non-significant trend indicating males were 3.4 times more likely to experience recurrent instability (OR=3.44, 95% CI (0.98 to 12.06), Z=1.93, p=0.053, I 2 =0%). Analysis of one study found that children with a closed physis are 14 times more likely to experience recurrent instability compared with those with an open physis (OR=14.0, 95% CI (1.46 to 134.25), Z=2.29, p=0.02, I 2 =0%) . Conclusions Male children aged 14 years and over had the greatest risk of recurrent shoulder instability following a first-time traumatic anterior shoulder dislocation. This meta-analysis summarises a mix of 6 acceptable and poor quality level III retrospective cohort studies. Further examination of this population with blinded prospective cohort studies will assist clinicians in the appropriate management of first-time traumatic anterior shoulder dislocation.
Response to Letters Regarding Article, “Prasugrel Plus Aspirin Beyond 12 Months Is Associated With Improved Outcomes After TAXUS Liberté Paclitaxel-Eluting Coronary Stent Placement”
Authors: Kirk N. Garratt, W. Douglas Weaver, Ronald G. Jenkins, Thomas K. Pow, Laura Mauri, Dean J. Kereiakes, Kenneth J. Winters, Thomas Christen, Dominic J. Allocco, David P. Lee
Journal: Circulation (2015)
Cyclophosphamide and fluorouracil combined with mitoxantrone versus doxorubicin for breast cancer: superiority of doxorubicin.
Authors: D J Stewart, W K Evans, F A Shepherd, K S Wilson, K I Pritchard, M E Trudeau, J J Wilson, K Martz
Journal: Journal of Clinical Oncology (1997)

PATIENTS AND METHODS We conducted a randomized, multicenter study of intravenous cyclophosphamide 500 mg/m2 plus fluorouracil 500 mg/m2 combined with either mitoxantrone (Novantrone, Lederle Cyanamid Canada Ltd, Willowdale, Ontario) 10 mg/m2 (CNF) or doxorubicin (Adriamycin, Adria Laboratories of Canada Ltd, Mississauga, Ontario) 50 mg/m2 (CAF) every 3 weeks in advanced breast cancer. RESULTS The response rate in 249 randomized patients was 36% with CNF (44 of 121) and 48% with CAF (62 of 128) (P = .054), with complete remissions in 10 patients (8.3%) on CNF and in 13 (10.2%) on CAF. If only fully assessable patients are considered, the response rate was 48% (44 of 91) with CNF and 60% (62 of 103) with CAF (P = .098). At time of analysis, all except 10 patients (one CNF and nine CAF) had died. The median survival time with CAF was longer than with CNF (15.2 v 10.9 months; P = .003), and time to progression was also longer with CAF (5.3 v 3.2 months; P &lt; .03). Survival differences remained significant (P = .006) if patients who failed to meet all eligibility criteria were excluded. Favorable prognostic factors for survival in a Cox regression model included good performance status (P &lt; .0001); less than two organ systems involved by tumor (P &lt; .0001); no involvement of lung, liver, or brain (P &lt; .003); involvement of bone or bone marrow (P &lt; .009), prior surgery for breast cancer (P &lt; .006); being premenopausal (P &lt; .03); &gt; or = 3 years from diagnosis until randomization on this study (P &lt; .03); and treatment with CAF (P &lt; .03). Alopecia &gt; or = grade 3 was reported in 55% of patients with CAF and 12% of patients with CNF (P &lt; .001), while other &gt; or = grade 3 toxicities did not differ significantly. Priestman-Baum quality-of-life assessment was comparable on the two study arms. CONCLUSION In patients with advanced breast cancer, CAF was associated with longer survival than was CNF, with an increase in alopecia, but not in other toxicities.
Evaluation of the extent of lymphadenectomy in a randomized trial of Western- versus Japanese-type surgery in gastric cancer.
Authors: A M Bunt, J Hermans, M C Boon, C J van de Velde, M Sasako, G J Fleuren, J A Bruijn
Journal: Journal of Clinical Oncology (1994)

In the context of a prospective, randomized trial of gastric cancer treatment, comparing Western surgical resection with limited lymphadenectomy (R1) versus Japanese surgical resection with extended lymphadenectomy (R2), we analyzed adherence to the specified surgical-pathologic guidelines.Following evaluation of 389 patients, we quantified noncompliance (ie, performance of less dissection than specified) and contamination (ie, performance of more extensive dissection than specified). Of 389 patients, pathologic data permitted identification of 237 eligible patients treated with curative intent.Noncompliance occurred in 84% of R1 and R2 cases, with magnitude significantly (P < .001) higher in R2 cases versus R1 cases. Contamination occurred in 48% of R1 cases and 52% of R2 cases, with the magnitude of contamination moderate and equally distributed between the two groups. The contamination in R1 resections and the noncompliance in R2 resections lead to a partial homogenization of the groups, undermining the likelihood of detecting any potential therapeutic advantage to R2 dissection.The observed tendency to perform R1 resections combined with insufficient retrieval of lymph nodes underlines the need for increased surgical-pathologic standardization in this trial. Potential remedies are discussed. Proper conduct of clinical trials requires reliable means of standardizing performance of the surgical-pathologic team, an elusive but important goal.
Favorable outcome of invasive aspergillosis in patients with acute leukemia.
Authors: P A Burch, J E Karp, W G Merz, J E Kuhlman, E K Fishman
Journal: Journal of Clinical Oncology (1987)

During a 2-year period, 15 of 110 patients (14%) admitted for intensive therapy of acute leukemia associated with prolonged deep granulocytopenia developed documented invasive aspergillosis (IA). Antemortem diagnosis was accomplished in 14, and 13 of 15 (87%) survived the infection. Because of the high success rate, we reviewed the courses of the 15 patients to assess factors associated with this favorable outcome. Eleven presented with pulmonary IA; early symptoms occurred at a mean 21.6 days of granulocytopenia (less than 100/muL) and included refractory fever in 14 and pulmonary signs or symptoms in 11. Primary necrotic chest wall lesions associated with Hickman catheters developed in four at a mean 11 days of granulocytopenia, followed by pulmonary involvement. All 15 patients had chest radiographs during granulocytopenia, with 14 (93%) demonstrating pulmonary infiltrates and/or nodules at a mean 20.6 days of aplasia. Nine patients had lung computerized tomography (CT) scans, revealing nodular infiltrates in one patient and a characteristic zone of low attenuation surrounding a mass-like infiltrate in seven other patients, which was found to be diagnostic of IA. Subsequent CT scans performed during and following bone marrow recovery showed progression to cavitation followed by either complete resolution or minimal pulmonary scarring. Eleven patients developed IA during empiric amphotericin B (Amp-B) therapy (0.5 mg/kg/d) for fever refractory to antibacterial antibiotics. Fourteen patients received high-dose Amp-B (1.0 to 1.5 mg/kg/d), which was started within a mean of 2.2 days of first clinical findings; 13 survived. Ten patients received 5-fluorocytosine in addition to high dose amp-B. Survival was similar regardless of presentation, as 91% with primary pulmonary IA and 75% presenting with chest wall lesions survived. All 13 surviving patients had complete granulocyte recovery at a mean 33.8 days. Nephrotoxicity (creatinine greater than 2.0 mg/dL) was observed in seven patients during therapy for IA, but was transient in all seven. We conclude IA can be successfully treated in the deeply granulocytopenic patient provided that it is recognized and treated early, and provided that antifungal therapy is aggressive and is continued until granulocyte recovery occurs.
Phytomolecule icaritin incorporated PLGA/TCP scaffold for steroid-associated osteonecrosis: Proof-of-concept for prevention of hip joint collapse in bipedal emus and mechanistic study in quadrupedal rabbits
Authors: Ling Qin, Dong Yao, Lizhen Zheng, Wai-Ching Liu, Zhong Liu, Ming Lei, Le Huang, Xinhui Xie, Xinluan Wang, Yang Chen, Xinsheng Yao, Jiang Peng, He Gong, James F. Griffith, Yanping Huang, Yongping Zheng, Jian Q. Feng, Ying Liu, Shihui Chen, Deming Xiao, Daping Wang, Jiangyi Xiong, Duanqing Pei, Peng Zhang, Xiaohua Pan, Xiaohong Wang, Kwong-Man Lee, Chun-Yiu Cheng
Journal: Biomaterials (2015)