tbuckley/cabot-search huggingface dataset:
Hepatocellular nodules expressing markers of hepatocellular adenomas in Budd-Chiari syndrome and other rare hepatic vascular disorders
Authors: Christine Sempoux, Valérie Paradis, Mina Komuta, Aileen Wee, Julien Calderaro, Charles Balabaud, Alberto Quaglia, Paulette Bioulac-Sage
Journal: Journal of Hepatology (2015)
Concomitant chemoradiotherapy followed, where feasible, by surgery for cancer of the esophagus.
Authors: G Ganem, B Dubray, Y Raoul, P Colin, E Bardet, J Y Douillard, M J Goudier, C Hennequin, S Walter, P Michel-Langlet, P Martin, D Maron, F Morvan, P Andolenko, J M Extra
Journal: Journal of Clinical Oncology (1997)

PURPOSE To conduct a multicenter phase II study of a concomitant combination of chemotherapy and radiotherapy followed by surgery, where feasible, in patients with nonmetastatic esophageal tumor, stratified on operability at diagnosis. METHODS Each cycle consisted of fluorouracil (5FU) 800 mg/m2/d by continuous intravenous (IV) infusion on days 1 to 5, cisplatin (CDDP) 50 mg/m2/d IV bolus on days 1 and 8, hydroxyurea (HU) 1.5 or 2 g/d orally on days 8 to 12 and concomitant radiotherapy 20 Gy in 10 fractions over 12 days. All patients were to receive two cycles on days 1 and 22. If feasible, surgery was performed 3 to 6 weeks after cycle two completion. Otherwise, a third cycle was administered. RESULTS Eighty-eight patients were included between September 1990 and September 1993. Of the 47 operable patients, 41 (87%) underwent surgery and 38 (81%) had a complete resection. No residual primary tumor was found in the surgical specimen in 17 cases (36%), and only microscopic foci in 13 (28%). Two-year overall and disease-free survival probabilities were 51% (95% confidence interval [CI]; 37 to 65) and 43% (95% CI, 28 to 57), respectively. Among the 41 inoperable patients, 12 (29%) became operable. Seven (17%) had complete resection, two incomplete resection, and three exploratory surgery. Two-year overall and disease-free survival probabilities were 29% (95% CI, 15 to 43) and 27% (95% CI, 13 to 40), respectively. Five deaths occurred during chemoradiotherapy, six postoperatively and four in patients with evidence of cancer. Five late complications (one myelopathy) were observed. CONCLUSION Despite a high histologic response rate in initially operable patients, overall survival was similar to that observed in other preoperative chemoradiation series because of substantial toxicity.
The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study
Authors: Elisa De Franco, Sarah E Flanagan, Jayne AL Houghton, Hana Lango Allen, Deborah JG Mackay, I Karen Temple, Sian Ellard, Andrew T Hattersley
Journal: The Lancet (2015)

Traditional genetic testing focusses on analysis of one or a few genes according to clinical features; this approach is changing as improved sequencing methods enable simultaneous analysis of several genes. Neonatal diabetes is the presenting feature of many discrete clinical phenotypes defined by different genetic causes. Genetic subtype defines treatment, with improved glycaemic control on sulfonylurea treatment for most patients with potassium channel mutations. We investigated the effect of early, comprehensive testing of all known genetic causes of neonatal diabetes.In this large, international, cohort study, we studied patients with neonatal diabetes diagnosed with diabetes before 6 months of age who were referred from 79 countries. We identified mutations by comprehensive genetic testing including Sanger sequencing, 6q24 methylation analysis, and targeted next-generation sequencing of all known neonatal diabetes genes.Between January, 2000, and August, 2013, genetic testing was done in 1020 patients (571 boys, 449 girls). Mutations in the potassium channel genes were the most common cause (n=390) of neonatal diabetes, but were identified less frequently in consanguineous families (12% in consanguineous families vs 46% in non-consanguineous families; p<0·0001). Median duration of diabetes at the time of genetic testing decreased from more than 4 years before 2005 to less than 3 months after 2012. Earlier referral for genetic testing affected the clinical phenotype. In patients with genetically diagnosed Wolcott-Rallison syndrome, 23 (88%) of 26 patients tested within 3 months from diagnosis had isolated diabetes, compared with three (17%) of 18 patients referred later (>4 years; p<0·0001), in whom skeletal and liver involvement was common. Similarly, for patients with genetically diagnosed transient neonatal diabetes, the diabetes had remitted in only ten (10%) of 101 patients tested early (<3 months) compared with 60 (100%) of the 60 later referrals (p<0·0001).Patients are now referred for genetic testing closer to their presentation with neonatal diabetes. Comprehensive testing of all causes identified causal mutations in more than 80% of cases. The genetic result predicts the best diabetes treatment and development of related features. This model represents a new framework for clinical care with genetic diagnosis preceding development of clinical features and guiding clinical management.Wellcome Trust and Diabetes UK.
Association of Tdap Vaccination With Acute Events and Adverse Birth Outcomes Among Pregnant Women With Prior Tetanus-Containing Immunizations
Authors: Lakshmi Sukumaran, Natalie L. McCarthy, Elyse O. Kharbanda, Michael M. McNeil, Allison L. Naleway, Nicola P. Klein, Michael L. Jackson, Simon J. Hambidge, Marlene M. Lugg, Rongxia Li, Eric S. Weintraub, Robert A. Bednarczyk, Jennifer P. King, Frank DeStefano, Walter A. Orenstein, Saad B. Omer
Journal: JAMA (2015)

The Advisory Committee on Immunization Practices (ACIP) recommends the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine for pregnant women during each pregnancy, regardless of prior immunization status.However, safety data on repeated Tdap vaccination in pregnancy is lacking.OBJECTIVE To determine whether receipt of Tdap vaccine during pregnancy administered in close intervals from prior tetanus-containing vaccinations is associated with acute adverse events in mothers and adverse birth outcomes in neonates. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study in 29 155 pregnant women aged 14 through 49 years from January 1, 2007, through November 15, 2013, using data from 7 Vaccine Safety Datalink sites in California, Colorado, Minnesota, Oregon, Washington, and Wisconsin.EXPOSURES Women who received Tdap in pregnancy following a prior tetanus-containing vaccine less than 2 years before, 2 to 5 years before, and more than 5 years before.MAIN OUTCOMES AND MEASURES Acute adverse events (fever, allergy, and local reactions) and adverse birth outcomes (small for gestational age, preterm delivery, and low birth weight) were evaluated.Women who were vaccinated with Tdap in pregnancy and had a prior tetanus-containing vaccine more than 5 years before served as controls.RESULTS There were no statistically significant differences in rates of medically attended acute adverse events or adverse birth outcomes related to timing since prior tetanus-containing vaccination.Outcome Time Since Prior Tetanus-Containing Vaccination, y <2 2-5 >5 (Control) Local reactions, rate/10 000 women 4.2 7.0 11.2 Adjusted risk ratio (95% CI) 0.49 (0.11-2.20) 0.77 (0.31-1.95) 1 [Reference] P value .35.59Preterm delivery, % 6.6 6.4 6.8 Adjusted risk ratio (95% CI) 1.15 (0.98-1.34) 1.06 (0.94-1.19) 1 [Reference] P value .08 .33Small for gestational age, % 9.0 8.7 9.1 Adjusted risk ratio (95% CI) 0.99 (0.87-1.13) 0.96 (0.87-1.06) 1 [Reference] P value .88.45CONCLUSIONS AND RELEVANCE Among women who received Tdap vaccination during pregnancy, there was no increased risk of acute adverse events or adverse birth outcomes for those who had been previously vaccinated less than 2 years before or 2 to 5 years before compared with those who had been vaccinated more than 5 years before.These findings suggest that relatively recent receipt of a prior tetanus-containing vaccination does not increase risk after Tdap vaccination in pregnancy.
Time course analysis of lung function and morphometric parameters in a murine model of emphysema
Authors: Clarice Olivo, Bruna Scarpa, Francine Almeida, Petra Arantes, Fernanda Lopes, Milton Martins
Journal: European Respiratory Journal (2011)

Proteolytic enzymes have been used to induce emphysema in rodents to study mechanisms of this disease pathogenesis. However, few studies have evaluated the time course of the development of pulmonary emphysema after nasal instillation of elastase.   Objectives:  To describe the progression of emphysema after porcine pancreatic elastase (PPE) nasal instillation in mice.   Methods:  64 adult male Balb/c mice received either a nasal drop of 50 μl (0.667 UI) of PPE (PPE) or saline (S) and were studied on days 1, 7, 14 and 21 after PPE instillation. For each time, we analyze airway resistance (RAW), tissue damping (Gtis) and tissue elastance (Htis). Inflammatory profile was performed in bronchoalveolar lavage (BAL) and both lungs were fixed with 10% buffered formalin infused through the trachea at 20cmH 2 O for 24h and paraffin embedded for measurements of mean linear intercept (Lm).   Results:  There was an increase in inflammatory cells in PPE groups since the 1st day, characterized by increase number of neutrophils and macrophages which remained until the 21th day. However the increase in lymphocytes became evident only at 7th day. We observed a decrease in Htis at 7th and 21th days, while there was an increase in Gtis at the 1st day and a decrease at the 21th day. We did not observe any differences for Raw values. The increase in Lm was observed in PPE group since the 1st day and was maintained throughout different times.   Conclusions:  In this experimental model we observed an earlier inflammatory process concomitant with alveolar enlargement, suggesting that protease-antiprotease imbalance influence the development of emphysema.Supported by FAPESP, LIMHC-FMUSP, CNPq, Brazil
Prospective multicentre PCR-based Aspergillus DNA screening in high-risk patients with and without primary antifungal mould prophylaxis
Authors: J. Springer, M. Lackner, D. Nachbaur, M. Girschikofsky, B. Risslegger, W. Mutschlechner, J. Fritz, W.J. Heinz, H. Einsele, A.J. Ullmann, J. Löffler, C. Lass-Flörl
Journal: Clinical Microbiology and Infection (2015)
Intracavitary chemotherapy with thiotepa in malignant pericardial effusions: an active and well-tolerated regimen.
Authors: M Colleoni, G Martinelli, F Beretta, C Marone, A Gallino, M Fontana, R Graffeo, G Zampino, T De Pas, G Cipolla, C Martinoni, A Goldhirsch
Journal: Journal of Clinical Oncology (1998)

PURPOSE Malignant pericardial effusion, although highly variable, is an uncommon complication of cancer. It is often associated with symptoms like dyspnea, chest pain, and cough, which may be severe and disabling. We analyzed the results of our current treatment policy to evaluate the effectiveness and tolerance of a new approach for this disorder. PATIENTS AND METHODS Patients with malignant pericardial effusions were treated with intracavitary thiotepa (15 mg on days 1, 3, and 5) through an indwelling pericardial cannula after extraction of as much pericardial fluid as possible on day 0. Responses were assessed by clinical examination, computed tomographic (CT) scan, and echocardiography before treatment, 1 month after treatment, and every 2 months thereafter. Twenty-three patients with malignant symptomatic pericardial effusion were treated and all were assessable for effectiveness and tolerance of the procedure. RESULTS Nine patients with breast cancer, 11 with lung cancer, two with an unknown primary tumor, and one with metastatic melanoma were treated. In all but three patients, systemic medical treatment was started after completion of intracavitary therapy. Nineteen patients responded to treatment (83%; 95% confidence interval, 61% to 95%) with a rapid improvement of symptoms. The median time to pericardial effusion progression was 8.9 months (range, 1 to 26). No significant side effects were registered, except one patient who had transient grade III thrombocytopenia and leukopenia and one patient who had grade I leukopenia. CONCLUSION A short course of intracavitary treatment with thiotepa is highly effective and well tolerated in the treatment of malignant pericardial effusion.
Refractory anemia with ring sideroblasts and <scp>RARS</scp> with thrombocytosis
Authors: Mrinal M. Patnaik, Ayalew Tefferi
Journal: American Journal of Hematology (2015)

Ring sideroblasts (RS) are erythroid precursors with abnormal perinuclear mitochondrial iron accumulation. Two myeloid neoplasms defined by the presence of RS, include refractory anemia with ring sideroblasts (RARS) and RARS with thrombocytosis (RARS-T).RARS is a lower risk myelodysplastic syndrome (MDS) with dysplasia limited to the erythroid lineage, <5% bone marrow (BM) blasts and ≥15% BM RS. RARS-T is a provisional entity in the MDS/MPN (myeloproliferative neoplasm) overlap syndromes, with diagnostic features of RARS, along with a platelet count ≥450 × 10(9)/L and large atypical megakaryocytes similar to those observed in BCR-ABL1 negative MPN. Mutations and Karyotype: Mutations in the SF3B1 gene are seen in ≥80% of patients with RARS and RARS-T, and strongly correlate with the presence of BM RS; RARS-T patients have additional mutations such as, JAK2V617F (∼60%), MPL (<5%), and CALR (<5%). Cytogenetic abnormalities are uncommon in both RARS and RARS-T.Most patients with RARS are stratified into lower risk groups by the International Prognostic Scoring System (IPSS) for MDS and the revised IPSS. Disease outcome in RARS-T is better than that of RARS, but worse than that of essential thrombocytosis. Both RARS and RARS-T have a low risk of leukemic transformation.Anemia and iron overload are complications in both diseases and are managed similar to lower risk MDS. Aspirin therapy is reasonable in RARS-T, especially in the presence of JAK2V617F, but the value of platelet-lowering drugs is uncertain. Case reports of RARS-T therapy with lenalidomide warrant additional studies.
Genetic variations in toll-like receptor pathway genes influence asthma and atopy
Authors: R. Tesse, R. C. Pandey, M. Kabesch
Journal: Allergy (2010)

Innate immunity is a pivotal defence system of higher organisms. Based on a limited number of receptors, it is capable of recognizing pathogens and to initiate immune responses. Major components of these innate immunity pathogen recognition receptors are the toll-like receptors (TLRs), a family of 11 in humans. They are all membrane bound and through dimerization and complex downstream signaling, TLRs elicit a variety of specific and profound effects. In recent years, the role of TLRs signaling was not only investigated in infection and inflammation but also in allergy. Fuelled by the hygiene hypothesis, which suggests that allergies develop because of a change in microbial exposure and associated immune signals early in life, it had been speculated that alterations in TLRs signaling could influence allergy development. Thus, TLR genes, genetic variations of these genes, and their association with asthma and other atopic diseases were investigated in recent years. This review provides an overview of TLR genetics in allergic diseases.
TGF-β1–induced migration of bone mesenchymal stem cells couples bone resorption with formation
Authors: Yi Tang, Xiangwei Wu, Weiqi Lei, Lijuan Pang, Chao Wan, Zhenqi Shi, Ling Zhao, Timothy R Nagy, Xinyu Peng, Junbo Hu, Xu Feng, Wim Van Hul, Mei Wan, Xu Cao
Journal: Nature Medicine (2009)
Abstract 5: Mcl-1-mediated resistance to ABT-263 is combated by mTOR inhibition in luminal breast cancers
Authors: Michelle M. Williams, Linus Lee, Violeta Sanchez, Meghan M. Morrison, Donna Hicks, Rebecca S. Cook
Journal: Cancer Research (2015)

Abstract We found that 8.1% of luminal breast cancer cases curated by The Cancer Genome Atlas (TCGA), harbor gene amplification of anti-apoptotic Bcl-2 family members, warranting further study of anti-apoptotic Bcl-2 family proteins (A1, Bcl-2, Bcl-xL, Bcl-w and Mcl-1) in luminal breast cancers. A complex balance of pro- and anti-apoptotic Bcl-2 proteins guides activation versus repression of the intrinsic apoptotic pathway, with overexpression of anti-apoptotic factors tipping the balance towards cell survival. This mechanism is commonly used by cancers to evade apoptosis. We used the BH3-mimetic ABT-263 to inhibit Bcl-2, Bcl-xL and Bcl-w in a panel of human luminal breast cancer lines, causing only modest apoptosis in monolayer and growth inhibition in three-dimensional (3D) matrix. Expression and activity of Mcl-1, another anti-apoptotic Bcl-2 family member, was rapidly upregulated in response to ABT-263 through increased cap-dependent MCL1 translation. Mcl-1 knock-down decreased tumor cell growth and improved ABT-263-mediated tumor cell killing. Inhibition of cap-dependent translation using the mTOR inhibitor RAD001/everolimus or the EIF4 complex inhibitor 4E1RCat blocked Mcl-1 induction in ABT-263 treated cells, enhancing apoptosis and growth inhibition. In vivo, single agent ABT-263 was ineffective at reducing tumor growth in xenografted human breast cancers and in transgenic WAP-Myc luminal mammary tumors. However, RAD001 decreased Mcl-1 levels and decreased WAP-Myc tumor growth by 40%. These results demonstrate that heightened cap-dependent translation of Mcl-1 prevents therapeutically induced tumor cell killing in ABT-263 treated luminal tumors, highlighting the importance of Mcl-1 regulation in therapeutic resistance, and identifying Mcl-1 as a potential therapeutic target in luminal breast cancers. These studies suggest that targeted inhibition of Mcl-1 alone or in combination with other Bcl-2 family inhibitors will enhance tumor cell killing in luminal breast cancers. Citation Format: Michelle M. Williams, Linus Lee, Violeta Sanchez, Meghan M. Morrison, Donna Hicks, Rebecca S. Cook. Mcl-1-mediated resistance to ABT-263 is combated by mTOR inhibition in luminal breast cancers. [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 5. doi:10.1158/1538-7445.AM2015-5
Evaluation of real time polymerase chain reaction in rapid diagnosis of exudative tubercular effusions
Authors: Balakrishnan Menon, Charanjeet Kaur
Journal: European Respiratory Journal (2011)

Introduction:  Exudative effusions are a common manifestation of tuberculosis. Real time Polymerase Chain Reaction (RT-PCR) has superior sensitivity, specificity, lower contamination and reduction in time to result in comparison to conventional methods.   Aims and objectives:  To evaluate the sensitivity of RT-PCR in cases of exudative effusions due to tuberculosis.   Methods:  RT-PCR was performed in 153 patients of exudative tubercular effusions. They consisted of 127 pleural effusions, 21 ascitic fluid and 5 pericardial effusions. All patients had positive Mantoux test with high protein and lymphocyte predominance in effusion. The subjects were positive by either ZN staining, Culture for AFB by growth on LJ medium or BACTEC, Interferon γ (INF-γ) or Adenosine Deaminase (ADA).  RT-PCR was performed by detecting amplification reaction for the insert element IS6110 of the  Mycobacterium tuberculosis  complex (Biotub-QT, Biotools Labs, Spain) using a real-time centrifugal amplifcation system (Rotor-Gene 3000, Corbett Research, Australia).   Results:  RT-PCR was positive in 134 of the 153 cases of exudative tubercular effusions (Sensitivity 87.6%). It was positive in 114 of 127 cases of pleural effusion (Sensitivity 89.7%), 17 out of 21 cases of ascitis and 3 of the 5 cases of pericardial effusion.  The sensitivity of ZN staining was 23.5%, Culture by LJ medium was 33.9% and BACTEC was 51.6%. ADA showed positivity in 144 of 153 cases (Sensitivity 94.1%) and INF-γ showed sensitivity of 83.6%.   Conclusion:  Real time PCR is valuable in the diagnosis of exudative tubercular effusions with a sensitivity of 87.6%. The diagnostic efficiency could be increased by combining RT-PCR with ADA or INF-γ.
Stress-associated erythropoiesis initiation is regulated by type 1 conventional dendritic cells
Authors: Taeg S. Kim, Mark Hanak, Paul C. Trampont, Thomas J. Braciale
Journal: Journal of Clinical Investigation (2015)

Erythropoiesis is an important response to certain types of stress, including hypoxia, hemorrhage, bone marrow suppression, and anemia, that result in inadequate tissue oxygenation. This stress-induced erythropoiesis is distinct from basal red blood cell generation; however, neither the cellular nor the molecular factors that regulate this process are fully understood. Here, we report that type 1 conventional dendritic cells (cDC1s), which are defined by expression of CD8α in the mouse and XCR1 and CLEC9 in humans, are critical for induction of erythropoiesis in response to stress. Specifically, using murine models, we determined that engagement of a stress sensor, CD24, on cDC1s upregulates expression of the Kit ligand stem cell factor on these cells. The increased expression of stem cell factor resulted in Kit-mediated proliferative expansion of early erythroid progenitors and, ultimately, transient reticulocytosis in the circulation. Moreover, this stress response was triggered in part by alarmin recognition and was blunted in CD24 sensor- and CD8α+ DC-deficient animals. The contribution of the cDC1 subset to the initiation of stress erythropoiesis was distinct from the well-recognized role of macrophages in supporting late erythroid maturation. Together, these findings offer insight into the mechanism of stress erythropoiesis and into disorders of erythrocyte generation associated with stress.
Evaluation of the relations between the obstructive sleep apnea syndrome and obesity by standard antropometric obesity indexes
Authors: Ender Levent, Akin Soylu, Nesrin Sariman, Sirin Yurtlu, Sümeyye Alparslan, Attila Saygi
Journal: European Respiratory Journal (2011)

Introduction: Obesity is an important risk factor in the development of obstructive sleep apnea syndrome (OSAS).  Aims and objectives: To investigate whether the general body adiposity or local lipoidosis was a risk factor in the evolution of OSAS by examining the relationships between the anthropometric obesity indexes such as waist (WC) and neck circumference index (NC), body mass index (BMI) and OSAS in Turkish adult population, and to access the possible differences by gender.  Methods: The records of 499 subjects were examined retrospectively. The data related to polysomnographic, demographic and anthropometric indexes of the subjects were recorded. The patients whose apnea-hypopnea index were ≥5 was determined as OSAS group.  Results: Of the subjects who underwent polysomnography; 431 (86.37%) were OSAS. The avarage BMI, NC and WC of OSAS group were statistically higher than the control group (p  According to logistic regression analysis; BMI, WC and NC enlargement were observed as significant risk factors for OSAS development. Risk coefficients were determined 5.53 for NC, 4.48 for WC and 2.22 for BMI.  Cut-off point values for anthropometric obesity indexes as OSAS determiner were recorded as below: BMI for male >27.77kg/m2 and female >28.93kg/m2, NC index for male >40cm and female >36cm, WC index for male >105cm and female >101cm.  Conclusions: BMI, WC and NC enlargement were determined as significant risk factors for OSAS development. This was an initial study to determine the cut-off points of which increase the OSAS risk in BMI, WC and NC index in Turkish adult population.