tbuckley/cabot-search huggingface dataset:
Haemodynamic effects of oral aminorex and amphetamine in unanaesthetized beagle dogs
Authors: J. A. Will, G. E. Bisgard
Journal: Thorax (1972)

<h3>Background</h3> Financial difficulties can precipitate and perpetuate mental health problems and are a predictor of chronic physical illness. The COVID-19 pandemic is an unprecedented public health crisis with profound health and socioeconomic impacts and the long-term consequences are yet to be seen. The poorest and most vulnerable groups are worst affected, further widening the health inequality gap. It is known that there is low uptake of universal and means-tested benefits in some communities. Various schemes have been put in place to improve uptake of benefits by co-locating welfare advice within health services. However, we need more research on how to do this most effectively to reach the populations most in need and to assess its impact on health, social and financial outcomes. <h3>Methods</h3> We conducted a critical systematic narrative synthesis review of relevant papers published between 2010–2020 using an evidence-led framework described by Rodgers et al. consisting of four elements used to characterise the approach: developing a theory; developing a preliminary synthesis; exploring relationships within and between studies; and assessing the robustness of the evidence. <h3>Results</h3> In total, 16,625 participants accessed and were supported by the welfare services, with £19,576,223 successfully claimed as one-off payments for participants. Participants benefitted from an additional £2,757 household income per annum and improved financial literacy. The services across this review generated an average of £21.95 of social, economic and environmental return on investment per £1 invested. Co-located welfare advice services actively incorporate elements of proportionate universalism and target those who are most at need of this support and who would not otherwise access the services. The services raised the profile of the importance and value of addressing social determinants of health with healthcare professionals and policy makers and de-stigmatising access to welfare services and being in receipt of benefits. Access to welfare services also produced demonstratable cost savings for the NHS. Welfare services facilitated more appropriate use of NHS resources, promoting access for those who needed it but were not accessing it and reducing the burden of welfare issues on healthcare practitioner's time. <h3>Discussion</h3> Overall, this review demonstrates significant financial gains for participants and for the first time demonstrates wider welfare benefits to participants, including access to housing, food, transport and employment. This contributes to the theory that these welfare services both directly and indirectly address social determinants of health thereby improving health and wellbeing and reducing health inequalities.
Onset of psoriasis with psoriatic arthropathy during rituximab treatment of non-Hodgkin lymphoma
Authors: F Mielke, J Schneider-Obermeyer, T Dorner
Journal: Annals of the Rheumatic Diseases (2008)

We have monitored a 66-year-old woman who was diagnosed with non-Hodgkin’s lymphoma (NHL) based on a biopsy of her right breast in June 2006. Her previous including family history was unremarkable. Following administration of the first two cycles of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), she developed asymmetric arthritis that affected the distal interphalangeal joints, the left shoulder and ankles with achillodynia in July/August 2006. Of note, these manifestations emerged within the first 6–8 weeks following the first rituximab exposure. Initially, acute gouty arthritis was suspected following chemotherapy, but normal levels of uric acid were found. She did not respond sufficiently to non-steroidal anti-inflammatory drugs (NSAIDs) and allopurinole and her arthritis progressed. Subsequently, widespread arthritis and …
Development of a Drug Screening Platform Based on Engineered Heart Tissue
Authors: Arne Hansen, Alexandra Eder, Marlene Bönstrup, Marianne Flato, Marco Mewe, Sebastian Schaaf, Bülent Aksehirlioglu, Alexander Schwörer, June Uebeler, Thomas Eschenhagen
Journal: Circulation Research (2010)

Tissue engineering may provide advanced in vitro models for drug testing and, in combination with recent induced pluripotent stem cell technology, disease modeling, but available techniques are unsuitable for higher throughput.Here, we present a new miniaturized and automated method based on engineered heart tissue (EHT).Neonatal rat heart cells are mixed with fibrinogen/Matrigel plus thrombin and pipetted into rectangular casting molds in which two flexible silicone posts are positioned from above. Contractile activity is monitored video-optically by a camera and evaluated by a custom-made software program. Fibrin-based mini-EHTs (FBMEs) (150 microL, 600 000 cells) were transferred from molds to a standard 24-well plate two hours after casting. Over time FBMEs condensed from a 12x3x3 mm gel to a muscle strip of 8 mm length and, depending on conditions, 0.2 to 1.3 mm diameter. After 8 to 10 days, FBMEs started to rhythmically deflect the posts. Post properties and the extent of post deflection allowed calculation of rate, force (0.1 to 0.3 mN), and kinetics which was validated in organ baths experiments. FBMEs exhibited a well-developed, longitudinally aligned actinin-positive cardiac muscle network and lectin-positive vascular structures interspersed homogeneously throughout the construct. Analysis of a large series of FBME (n=192) revealed high yield and reproducibility and stability for weeks. Chromanol, quinidine, and erythromycin exerted concentration-dependent increases in relaxation time, doxorubicin decreases in contractile force.We developed a simple technique to construct large series of EHT and automatically evaluate contractile activity. The method shall be useful for drug screening and disease modeling.
Smoking cessation prescribing practice after hospital discharge of pulmonary patients
Authors: Ika Pesic, Branka Bulajic-Subotic, Branislav Gvozdenovic, Nada Lazovic, Vladimir Zugic
Journal: European Respiratory Journal (2013)

Aim: The aim of the study was to assess how much pulmonologists in the discharge lists to inpatients prescribe the treatment of smoking cessation. Methods: We evaluated if pulmonologists prescribed smoking cessation treatment. Results: There were 5,924 hospitalized patients in 2005 and only 25% had defined the smoking status. Among them there were 60.1% smokers. In 2011, 30.2% out of the total of 3,909 hospitalized patients had described smoking status. There were 51.6% smokers in that year. Smoking cessation as the treatment measure was prescribed in only 5.6% of smokers in 2005, and in 7.2% in 2011. The lowest number of prescribed treatment measures of smoking cessation was found in the discharge lists of lung cancer patients 2005 – 0.4% and 2011 – 0.7%. Significantly more frequent (p<0.01) smoking cessation was prescribed in asthmatics 2005 – 20.8% and 2011 – 43.5%. It was not the case for COPD patients 2005 – 10.7% and 2011 – 11.9%, and those with other pulmonary diseases 2005 – 6.1% and 2011 – 5.2%. For tuberculosis patients in both 2005 and 2011 there were no prescribed smoking cessation treatment measures.

Conclusion: In every third discharge list for asthmatics we can find the prescribed treatment of smoking cessation. This can be explained by the fact that doctors believe that in this patient population smoking cessation shows the effect. There is a significant lack of prescribed treatment measure of smoking cessaiton in patients with lung cancer and those with COPD. More intensive effort is necessary in the doctors' education in regards to their approach to smoking pulmonary patients.
Co-occurring Genomic Alterations Define Major Subsets of <i>KRAS</i>-Mutant Lung Adenocarcinoma with Distinct Biology, Immune Profiles, and Therapeutic Vulnerabilities
Authors: Ferdinandos Skoulidis, Lauren A. Byers, Lixia Diao, Vassiliki A. Papadimitrakopoulou, Pan Tong, Julie Izzo, Carmen Behrens, Humam Kadara, Edwin R. Parra, Jaime Rodriguez Canales, Jianjun Zhang, Uma Giri, Jayanthi Gudikote, Maria A. Cortez, Chao Yang, Youhong Fan, Michael Peyton, Luc Girard, Kevin R. Coombes, Carlo Toniatti, Timothy P. Heffernan, Murim Choi, Garrett M. Frampton, Vincent Miller, John N. Weinstein, Roy S. Herbst, Kwok-Kin Wong, Jianhua Zhang, Padmanee Sharma, Gordon B. Mills, Waun K. Hong, John D. Minna, James P. Allison, Andrew Futreal, Jing Wang, Ignacio I. Wistuba, John V. Heymach
Journal: Cancer Discovery (2015)

The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma are poorly characterized. We performed an integrative analysis of genomic, transcriptomic, and proteomic data from early-stage and chemorefractory lung adenocarcinoma and identified three robust subsets of KRAS-mutant lung adenocarcinoma dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP), and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further revealed biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules, and improved relapse-free survival. Differences in drug sensitivity patterns were also observed; notably, KL cells showed increased vulnerability to HSP90-inhibitor therapy. This work provides evidence that co-occurring genomic alterations identify subgroups of KRAS-mutant lung adenocarcinoma with distinct biology and therapeutic vulnerabilities.Co-occurring genetic alterations in STK11/LKB1, TP53, and CDKN2A/B-the latter coupled with low TTF1 expression-define three major subgroups of KRAS-mutant lung adenocarcinoma with distinct biology, patterns of immune-system engagement, and therapeutic vulnerabilities.
The N Staging System in Nasopharyngeal Carcinoma with Radiation Therapy Oncology Group Guidelines for Lymph Node Levels Based on Magnetic Resonance Imaging
Authors: Yan-Ping Mao, Shao-Bo Liang, Li-Zhi Liu, Yong Chen, Ying Sun, Ling-Long Tang, Li Tian, Ai-Hua Lin, Meng-Zhong Liu, Li Li, Jun Ma
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To evaluate the prognostic value of variables including nodal size, level, laterality, extranodal neoplastic spread (ENS), and necrosis in patients with nasopharyngeal carcinoma (NPC) and further explore the feasibility of an N-staging system using Radiation Therapy Oncology Group (RTOG) guidelines for lymph node levels based on magnetic resonance imaging (MRI). Experimental Design: The MRI scans of 924 patients with histologically diagnosed nondisseminated NPC were reviewed retrospectively. The distribution of the tumors was mapped using RTOG guidelines and laterality. The multiplicity of each tumor was calculated, as well as the size and status of ENS and the necrosis of individual nodes. Results: Nodal level, cervical lymph node laterality, and ENS were independent prognostic factors for disease failure and distant failure in multivariate analyses. There was no significant difference in the hazard ratios (HR) for distant failure between level II and retropharyngeal, level Ib, level V, or level III involvement, whereas patients with level IV and supraclavicular fossa involvement had a significant increase in HRs. The subsets that made up a given N stage group had similar HRs for distant failure. Both the HRs for disease failure and distant failure by the proposed N staging system between one stage and the next were statistically significant (P &amp;lt; 0.05). The survival curves of disease-free survival and distant metastasis-free survival for all subclassifications of N stage showed significant difference from the adjacent stage (P &amp;lt; 0.05). The overall distribution pattern of the proposed N staging was more equitable than that of the 6th American Joint Committee on Cancer N staging. Conclusions: Nodal variables including level, cervical lymph node laterality, and ENS are independent prognostic factors for NPC. The proposed N staging system of NPC using RTOG guidelines based on MRI is highly predictive and may provide a more objective method for staging NPCs.
The occurrence of the HL-B alloantigens on the cells of unclassified acute lymphoblastic leukemias.
Authors: S M Fu, R J Winchester, H G Kunkel
Journal: The Journal of Experimental Medicine (1975)

Six cases of acute lymphoblastic leukemia were studied by a variety of T- and B-lymphocyte surface markers. Two appeared to represent T-cell leukemias with the lymphoblasts forming sheep erythrocyte rosettes. The other four lacked all the usual membrane markers. However, indirect immunofluorescence with alloantisera detected the presence of the Ia-related HL-B antigens on the cells of the latter four cases; these antigens were absent in the first two cases. The primary association of the HL-B antigens with B cells raises the possibility that the positive group of cases are of B-cell lineage.
Is Presence of Islet Autoantibodies at Birth Associated With Development of Persistent Islet Autoimmunity?
Authors: Heather M. Stanley, Jill M. Norris, Katherine Barriga, Michelle Hoffman, Liping Yu, Dongmei Miao, Henry A. Erlich, George S. Eisenbarth, Marian Rewers
Journal: Diabetes Care (2004)

OBJECTIVE—To determine whether the presence of islet autoantibodies in the umbilical cord blood is predictive of subsequent development of islet autoimmunity. RESEARCH DESIGN AND METHODS—Cord blood sera from 1,118 subjects from the Diabetes Autoimmunity Study in the Young (DAISY) cohort, as well as their venous blood samples taken at follow-up clinic visits, were tested for GAD65 autoantibodies (GAAs), insulin autoantibodies (IAAs), and IA-2 autoantibodies (IA-2As). Venous blood samples taken from mothers of cord blood autoantibody–positive children were analyzed for the same autoantibodies. RESULTS—At least one of three islet autoantibodies was present in 42 (3.7%) of the cord blood samples tested. The presence of cord blood autoantibodies did not predict the subsequent development of islet autoimmunity (adjusted hazard ratio = 0.73 [0.09, 5.88]). Discordance between cord blood and corresponding maternal autoantibodies was seen in 3 of 36 infants. A strong correlation between levels of autoantibody in cord blood and maternal circulation was found for GAA (r2 = 0.93, P &amp;lt; 0.001) and IAA (r2 = 0.89, P &amp;lt; 0.001) but not IA-2A (r2 = 0.05, P = 0.19). Cord blood autoantibodies in all but one subject disappeared by 9 months of age. CONCLUSIONS—The presence of cord blood autoantibodies is not predictive of subsequent development of islet autoimmunity. The majority of cord blood autoantibodies appear to result from maternal transmission.
Risk factors and kinetics of thrombocytopenia associated with bortezomib for relapsed, refractory multiple myeloma
Authors: Sagar Lonial, Edmund K. Waller, Paul G. Richardson, Sundar Jagannath, Robert Z. Orlowski, Cynthia R. Giver, David L. Jaye, Dixil Francis, Sara Giusti, Claire Torre, Bart Barlogie, James R. Berenson, Seema Singhal, David P. Schenkein, Dixie-Lee W. Esseltine, Jessica Anderson, Hugh Xiao, Leonard T. Heffner, Kenneth C. Anderson
Journal: Blood (2005)
An observational study of the prevalence and incidence of comorbid conditions in older women with breast cancer
Authors: M.D. Danese, C. O'Malley, K. Lindquist, M. Gleeson, R.I. Griffiths
Journal: Annals of Oncology (2011)

Longitudinal analyses of comorbid conditions in women with breast cancer are few.Using Surveillance, Epidemiology, and End Results-Medicare data, we included 51,950 women aged≥66 years with in situ and stage I to IV breast cancer diagnosed in 1998-2002. We identified the prevalence and incidence of 34 comorbid conditions in these women, as well as in a matched cohort without cancer whose rates were standardized to the age and race/ethnicity distribution of the cancer patients. We also estimated rates of office encounters and diagnostic or testing procedures during the 12 months before diagnosis.The prevalence of most conditions at diagnosis was comparable among breast cancer and noncancer patients. New conditions after diagnosis were more common in breast cancer patients, and the incidence rates increased with higher stage at diagnosis. Before diagnosis, women presenting with stage IV disease had 41% [95% confidence interval (CI) 38% to 43%] fewer physician encounters and 34% (95% CI 24% to 31%) fewer unique diagnostic tests than women diagnosed with carcinoma in situ.Many comorbid conditions are identified as a consequence of the breast cancer diagnosis. There appears to be an important contribution from a lack of interaction with the health care system before diagnosis.
The Eδ enhancer controls the generation of CD4−CD8− αβTCR-expressing T cells that can give rise to different lineages of αβ T cells
Authors: Iannis Aifantis, Craig H. Bassing, Annette I. Garbe, Katie Sawai, Frederick W. Alt, Harald von Boehmer
Journal: The Journal of Experimental Medicine (2006)

It is well established that the pre–T cell receptor for antigen (TCR) is responsible for efficient expansion and differentiation of thymocytes with productive TCRβ rearrangements. However, Ptcra- as well as Tcra-targeting experiments have suggested that the early expression of Tcra in CD4−CD8− cells can partially rescue the development of αβ CD4+CD8+ cells in Ptcra-deficient mice. In this study, we show that the TCR Eδ but not Eα enhancer function is required for the cell surface expression of αβTCR on immature CD4−CD8− T cell precursors, which play a crucial role in promoting αβ T cell development in the absence of pre-TCR. Thus, αβTCR expression by CD4−CD8− thymocytes not only represents a transgenic artifact but occurs under physiological conditions.
Risk Factors for Obesity in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study
Authors: Daniel M. Green, Cheryl L. Cox, Liang Zhu, Kevin R. Krull, Deo Kumar Srivastava, Marilyn Stovall, Vikki G. Nolan, Kirsten K. Ness, Sarah S. Donaldson, Kevin C. Oeffinger, Lillian R. Meacham, Charles A. Sklar, Gregory T. Armstrong, Leslie L. Robison
Journal: Journal of Clinical Oncology (2011)

Many Childhood Cancer Survivor Study (CCSS) participants are at increased risk for obesity. The etiology of their obesity is likely multifactorial but not well understood.
Genetic Ablation of Protein Tyrosine Phosphatase 1B Accelerates Lymphomagenesis of p53-Null Mice through the Regulation of B-Cell Development
Authors: Nadia Dubé, Annie Bourdeau, Krista M. Heinonen, Alan Cheng, Ailsa Lee Loy, Michel L. Tremblay
Journal: Cancer Research (2005)

Protein tyrosine phosphatase 1B (PTP1B) is involved in multiple signaling pathways by down-regulating several tyrosine kinases. For example, gene-targeting studies in mice have established PTP1B as a critical physiologic regulator of metabolism by attenuating insulin signaling. PTP1B is an important target for the treatment of diabetes, because the PTP1B null mice are resistant to diet-induced diabetes and obesity. On the other hand, despite the potential for enhanced oncogenic signaling in the absence of PTP1B, PTP1B null mice do not develop spontaneous tumors. Because the majority of human cancers harbor mutations in p53, we generated p53/PTP1B double null mice to elucidate the role of PTP1B in tumorigenesis. We show that genetic ablation of PTP1B in p53 null mice decreases survival rate and increases susceptibility towards the development of B lymphomas. This suggested a role for PTP1B in lymphopoiesis, and we report that PTP1B null mice have an accumulation of B cells in bone marrow and lymph nodes, which contributed to the increased incidence of B lymphomas. The mean time of tumor development and tumor spectrum are unchanged in p53-/-PTP1B+/- mice. We conclude that PTP1B is an important determinant of the latency and type of tumors in a p53-deficient background through its role in the regulation of B-cell development.
Dermatoscopy of flat pigmented facial lesions: diagnostic challenge between pigmented actinic keratosis and lentigo maligna
Authors: B.N. Akay, P. Kocyigit, A.O. Heper, C. Erdem
Journal: British Journal of Dermatology (2010)

The similarity between clinical pictures of pigmented actinic keratosis (PAK) and lentigo maligna (LM) is well known.To investigate the frequency of dermatoscopic findings suggestive of LM/lentigo maligna melanoma (LMM) in the other facial pigmented skin lesions (FPSL) and to assess the distinguishing dermoscopic criteria of PAK and LM.Eighty-nine FPSL were evaluated with conventional dermatoscopy. The lesions showing one or more dermatoscopic features considered as specific patterns for the diagnosis of LM/LMM, mainly slate-grey to black dots and globules, slate-grey areas, annular-granular pattern, asymmetrical pigmented follicular openings, black blotches, rhomboidal structures, hyperpigmented rim of follicular openings, slate-grey streaks and dark streaks, were included in the study selectively.PAK was diagnosed in 67, LM or LMM in 20 and lichen planus-like keratosis in two lesions, histopathologically. Eleven essential dermatoscopic features were observed in facial PAK: slate-grey dots (70%); annular-granular pattern (39%); rhomboidal structures (36%); pseudonetwork (36%); black globules (34%); slate-grey globules (33%); black dots (30%); asymmetrical pigmented follicular openings (25%); hyperpigmented rim of follicular openings (21%); slate-grey areas (18%); and streaks (3%).PAK has a striking similarity to LM/LMM in clinical and dermatoscopic features, thus representing a diagnostic challange. All dermatoscopic findings except black blotches were observed in PAK. As dermatoscopic diagnosis of a pigmented skin lesion cannot be based on the presence of a single criterion, we may conclude that histopathology still remains the gold standard for correct diagnosis.
Phase I Clinical Trial to Determine the Feasibility and Maximum Tolerated Dose of Panitumumab to Standard Gemcitabine-Based Chemoradiation in Locally Advanced Pancreatic Cancer
Authors: Annette A. van Zweeden, Hans J. van der Vliet, Johanna W. Wilmink, Martijn R. Meijerink, Otto W.M. Meijer, Anna M.E. Bruynzeel, Geertjan van Tienhoven, Elisa Giovannetti, Geert Kazemier, Maarten A.J.M. Jacobs, Henk M.W. Verheul
Journal: Clinical Cancer Research (2015)

Epidermal growth factor receptor (EGFR) inhibitors may improve both the therapeutic efficacy of radiotherapy and the radiosensitizing activity of gemcitabine. Based on this rationale and the nonoverlapping toxicity profiles of gemcitabine and the monoclonal EGFR antibody panitumumab, we designed a phase I trial to investigate the maximum-tolerated dose (MTD), safety, and activity of panitumumab added to gemcitabine-based chemoradiotherapy (CRT) in patients with locally advanced pancreatic cancer (LAPC).Patients with LAPC and WHO performance status 0 to 1 were treated with weekly panitumumab at four dose levels (1-2.5 mg/kg), combined with weekly gemcitabine 300 mg/m(2) and radiotherapy (50.4 Gy in 28 fractions) for 6 weeks, followed by gemcitabine 1,000 mg/m(2) weekly for 3 weeks every 4 weeks until disease progression or unacceptable toxicity. Each cohort was monitored during the combination therapy to establish dose limiting toxicity. Tumor evaluation was performed after CRT and during gemcitabine monotherapy.Fourteen patients were enrolled; 14 were evaluable for toxicity and 13 for response. The MTD for panitumumab was 1.5 mg/kg. Three of the 6 patients, treated at MTD, experienced grade 3 adverse events during the combination therapy; neutropenia (n = 2; 33%), fatigue (n = 1; 17%), nausea (n = 1; 17%), and vomiting (n = 1; 17%). Partial response was achieved by 3 patients (23%), 1 in each dose cohort. Median progression free survival of the three cohorts together was 8.9 months.The addition of panitumumab to gemcitabine-based chemoradiotherapy in LAPC has manageable toxicity and potential clinical efficacy.