tbuckley/cabot-search huggingface dataset:
Population Attributable Risks of Esophageal and Gastric Cancers
Authors: L. S. Engel, W.-H. Chow, T. L. Vaughan, M. D. Gammon, H. A. Risch, J. L. Stanford, J. B. Schoenberg, S. T. Mayne, R. Dubrow, H. Rotterdam, A. B. West, M. Blaser, W. J. Blot, M. H. Gail, J. F. Fraumeni
Journal: JNCI Journal of the National Cancer Institute (2003)

Background: Several risk factors have been identified for esophageal adenocarcinoma, gastric cardia adenocarcinoma, esophageal squamous cell carcinoma, and noncardia gastric adenocarcinoma, but no study has comprehensively examined their contributions to the cancer burden in the general population. Herein, we estimate the population attributable risks (PARs) for various risk factors observed in a multicenter population–based case–control study. Methods: We calculated PARs by using 293 patients with esophageal adenocarcinoma, 261 with gastric cardia adenocarcinoma, 221 with esophageal squamous cell carcinoma, 368 with noncardia gastric adenocarcinoma, and 695 control subjects. We included smoking for all four tumor types and Helicobacter pylori infection for noncardia gastric adenocarcinoma as established causal risk factors as well as several other factors for which causality is under evaluation. Results: Ever smoking, body mass index above the lowest quartile, history of gastroesophageal reflux, and low fruit and vegetable consumption accounted for 39.7% (95% confidence interval [CI] = 25.6% to 55.8%), 41.1% (95% CI = 23.8% to 60.9%), 29.7% (95% CI = 19.5% to 42.3%), and 15.3% (95% CI = 5.8% to 34.6%) of esophageal adenocarcinomas, respectively, with a combined PAR of 78.7% (95% CI = 66.5% to 87.3%). Ever smoking and body mass index above the lowest quartile were responsible for 45.2% (95% CI = 31.3% to 59.9%) and 19.2% (95% CI = 4.9% to 52.0%) of gastric cardia adenocarcinomas, respectively, with a combined PAR of 56.2% (95% CI = 38.1% to 72.8%). Ever smoking, alcohol consumption, and low fruit and vegetable consumption accounted for 56.9% (95% CI = 36.6% to 75.1%), 72.4% (95% CI = 53.3% to 85.8%), and 28.7% (95% CI = 11.1% to 56.5%) of esophageal squamous cell carcinomas, respectively, with a combined PAR of 89.4% (95% CI = 79.1% to 95.0%). Ever smoking, history of gastric ulcers, nitrite intake above the lowest quartile, and H. pylori infection were responsible for 18.3% (95% CI = 6.5% to 41.8%), 9.7% (95% CI = 5.4% to 16.8%), 40.7% (95% CI = 23.4% to 60.7%), and 10.4% (95% CI = 0.3% to 79.6%) of noncardia gastric adenocarcinomas, respectively, with a combined PAR of 59.0% (95% CI = 16.2% to 91.4%). Conclusion: In this population, a few known risk factors account for a majority of esophageal and gastric cancers. These results suggest that the incidence of these cancers may be decreased by reducing the prevalence of smoking, gastroesophageal reflux, and being overweight and by increasing the consumption of fruits and vegetables.
Complex formation of platelet thrombospondin with histidine-rich glycoprotein.
Authors: L L Leung, R L Nachman, P C Harpel
Journal: Journal of Clinical Investigation (1984)

Thrombospondin and histidine-rich glycoprotein are two proteins with diverse biological activities which have been associated with human platelets and other cell systems. Using an enzyme-linked immunosorbent assay, we have demonstrated that purified human platelet thrombospondin formed a complex with purified human plasma histidine-rich glycoprotein. The formation of the thrombospondin-histidine-rich glycoprotein complex was specific, concentration dependent, and saturable. Significant binding was detected when histidine-rich glycoprotein was incubated with thrombospondin immobilized on anti-thrombospondin IgG-coated plates, indicating that the observed complex formation was not due to a thrombospondin interaction with the plastic surface. Sucrose-density-gradient ultracentrifugation of a mixture of thrombospondin and histidine-rich glycoprotein also revealed the formation of fluid-phase complexes, with an estimated stoichiometry of 1 thrombospondin: 3.5 histidine-rich glycoprotein. Fibrinogen, which has been previously shown to bind to absorbed thrombospondin, did not inhibit the formation of the thrombospondin-histidine-rich glycoprotein complex. Histidine-rich glycoprotein complexed with thrombospondin was capable of binding heparin and neutralizing the anticoagulant activity of heparin in plasma. Specific complex formation between thrombospondin and histidine-rich glycoprotein may play a significant role in influencing platelet blood vessel wall interactions as well as modulating the association of various cells with the extracellular matrix.
Pretreatment of leukemic cells with low-dose decitabine markedly enhances the cytotoxicity of gemtuzumab ozogamicin
Authors: M Kurimoto, H Matsuoka, N Hanaoka, S Uneda, T Murayama, T Sonoki, H Nakakuma
Journal: Leukemia (2012)

Pretreatment of leukemic cells with low-dose decitabine markedly
Loss of tumor cell CCR4 expression upon leukemic change in adult T-cell leukemia/lymphoma
Authors: Kazunari Sugita, Takatoshi Shimauchi, Rieko Kabashima, Daiki Nakashima, Ryosuke Hino, Kenji Kabashima, Motonobu Nakamura, Yoshiki Tokura
Journal: Journal of the American Academy of Dermatology (2009)
Brain Aging in Very Old Men With Type 2 Diabetes
Authors: Esther S.C. Korf, Lon R. White, Ph Scheltens, Lenore J. Launer
Journal: Diabetes Care (2006)

Type 2 diabetes leads to cognitive impairment and dementia, which may reflect microvascular and macrovascular complications as well as neurodegenerative processes. There are few studies on the anatomical basis for loss of cognitive function in type 2 diabetes. The objective of this study was to investigate the association between type 2 diabetes and markers of brain aging on magnetic resonance images, including infarcts, lacunes, and white matter hyperintensities as markers of vascular damage and general and hippocampal atrophy as markers of neurodegeneration in Japanese-American men born between 1900 and 1919 and followed since 1965 in the Honolulu-Asia Aging Study.Prevalent and incident dementia was assessed. Associations between magnetic resonance imaging markers and diabetic status were estimated with logistic regression, controlling for sociodemographic and other vascular factors.The prevalence of type 2 diabetes in the cohort is 38%. Subjects with type 2 diabetes had a moderately elevated risk for lacunes (odds ratio [OR] 1.6 [95% CI 1.0-2.6]) and hippocampal atrophy (1.7 [0.9-2.9]). The risk for both hippocampal atrophy and lacunes/infarcts was twice as high in subjects with compared with those without type 2 diabetes. Among the group with type 2 diabetes, those with the longest duration of diabetes, those taking insulin, and those with complications had relatively more pathologic brain changes.There is evidence that older individuals with type 2 diabetes have an elevated risk for vascular brain damage and neurodegenerative changes. These pathological changes may be the anatomical basis for an increased risk of cognitive impairment or dementia in type 2 diabetes.
Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8–mediated apoptosis and down-regulation of c-FLIP protein
Authors: Jennifer L. Aron, Mark R. Parthun, Guido Marcucci, Shinichi Kitada, Andrew P. Mone, Melanie E. Davis, Tiansheng Shen, Timothy Murphy, Joseph Wickham, Chris Kanakry, David M. Lucas, John C. Reed, Michael R. Grever, John C. Byrd
Journal: Blood (2003)
Preference for involvement in treatment decisions and request for prognostic information in newly diagnosed patients with higher-risk myelodysplastic syndromes
Authors: F. Efficace, G. Gaidano, M. Sprangers, F. Cottone, M. Breccia, M.T. Voso, G. Caocci, R. Stauder, A.A. Di Tucci, G. Sanpaolo, D. Selleslag, E. Angelucci, U. Platzbecker, F. Mandelli
Journal: Annals of Oncology (2014)
Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngealtype
Authors: A. Hasbini, R. Mahjoubi, A. Fandi, N. Chouaki, A. Taamma, P. Lianes, H. Cortès-Funes, S. Alonso, J.P. Armand, E. Cvitkovic, E. Raymond
Journal: Annals of Oncology (1999)
Site and characteristics of electrolyte loss and effect of intraluminal glucose in experimental canine cholera
Authors: Charles C. J. Carpenter, R. Bradley Sack, John C. Feeley, Richard W. Steenberg
Journal: Journal of Clinical Investigation (1968)

The site and characteristics of gastrointestinal electrolyte loss were investigated in eight dogs with experimental cholera induced by orogastric administration of 6-hr broth cultures of Vibrio cholerae, strain Ogawa 395. In these animals, all electrolyte losses originated in the small bowel, predominantly from the jejunum and ileum. The bicarbonate concentration of the small bowel fluid showed a progressive increase from duodenum, where it was less than that of plasma, to the terminal ileum, where it was significantly greater than that of simultaneously obtained plasma.
Hiccups and Pharyngeal Stimulation
Authors: M. R. Salem
Journal: JAMA (1968)

To the Editor:—  Following the publication of our articles,  of Hiccups by Pharyngeal Stimulation in Anesthetized and Conscious Subjects ( 202 :32, 1967) and An Effective Method for the Treatment of Hiccups During Anesthesia ( Anesthesiology  28 :463, 1967), we were subjected to a great number of questions and comments from physicians, as well as laymen.  Some colleagues consider the technique of pharyngeal stimulation in halting hiccups to be almost 100% effective in their hands. One colleague mentioned to me in a letter that he has never seen it fail. Others believe that, although it is far superior to any other methods, they still see incidences of failures. Few colleagues, however, found variable degrees of success with this technique.  It seems to me at this point, that it is important to describe in detail some points in regard to the technique that may be of help to the physicians. We observed
A systematic review and meta-analysis of the association between depression and insulin resistance. Diabetes Care 2013;36:480–489
Authors: C Kan, N Silva, SH Golden, U Rajala, M Timonen, D Stahl, K Ismail
Journal: Diabetes Care (2013)

In the print version of the article listed above, there are two typographical errors in Table 1, where IR measure should have read as "Minimal model" for the depressed and healthy control subjects dataset in Chiba et al., 2000 and as "HOMA-IR" for the Timonen et al., 2007 study.All analyses were checked, and the correct datasets were used in the meta-analyses.The online version reflects these changes.
Prognostic Accuracy of Computed Tomography Findings for Patients With Laryngeal Cancer Undergoing Laryngectomy
Authors: Jonathan J. Beitler, Susan Muller, William J. Grist, Amanda Corey, Adam M. Klein, Michael M. Johns, Charles L. Perkins, Lawrence W. Davis, Unni Udayasanker, Jerome C. Landry, Dong M. Shin, Patricia A. Hudgins
Journal: Journal of Clinical Oncology (2010)

The indications for upfront laryngectomy in the management of laryngeal cancer are a functionless larynx and extralaryngeal extension. Practically, clinicians rely on imaging to predict which patients will have T4 disease. Our goal was to review the accuracy of preoperative computed tomography (CT) scanning in determining the necessity for initial laryngectomy for advanced laryngeal cancer.In total, 107 consecutive untreated laryngectomy specimens with high-quality, preoperative CT imaging interpreted by our neuroradiologists were reviewed. Radiographic findings, including sclerosis, invasion, penetration, extralaryngeal spread, and subglottic extension were correlated with pathologic findings. CT images were not reinterpreted, since our purpose was to assess the original interpretations.CT imaging reported 23 cases of thyroid cartilage penetration and 27 cases of extralaryngeal spread. Pathology reported 12 cases of thyroid cartilage invasion, 29 cases of penetration, and 45 cases of extralaryngeal disease. CT imaging identified 17 (59%) of 29 cases of pathologically documented thyroid cartilage penetration and 22 (49%) of 45 cases of pathologically documented extralaryngeal spread. Pathologically proven extralaryngeal spread without thyroid cartilage penetration occurred in 18 (40%) of 45 cases. The positive predictive values for thyroid cartilage penetration and extralaryngeal spread were 74% and 81%. Sclerosis was of limited value in predicting thyroid cartilage invasion or penetration. Cricoid or arytenoid destruction predicted for thyroid cartilage penetration at rates of 57% and 63%.CT imaging has clear limitations when deciding whether there is thyroid cartilage penetration or extralaryngeal spread of advanced laryngeal cancer. Extralaryngeal spread without thyroid cartilage penetration was more common than expected. Alternate methods of pretreatment assessment are needed.
Localized Infant Neuroblastomas Often Show Spontaneous Regression: Results of the Prospective Trials NB95-S and NB97
Authors: Barbara Hero, Thorsten Simon, Ruediger Spitz, Karen Ernestus, Astrid K. Gnekow, Hans-Guenther Scheel-Walter, Dirk Schwabe, Freimut H. Schilling, Gabriele Benz-Bohm, Frank Berthold
Journal: Journal of Clinical Oncology (2008)

The excellent prognosis of localized neuroblastoma in infants, the overdiagnosis observed in neuroblastoma screening studies, and several case reports of regression of localized neuroblastoma prompted us to initiate a prospective cooperative trial on observation of localized neuroblastoma without cytotoxic treatment.For infants with localized neuroblastoma without MYCN amplification, chemotherapy was scheduled only in cases with threatening symptoms; otherwise, the tumor was either resected or observed by ultrasound and magnetic resonance imaging (MRI).Of 340 eligible participants, 190 underwent resection, 57 were treated with chemotherapy, and 93 were observed with gross residual tumor. Of those 93 patients with unresected tumors, spontaneous regression was seen in 44, local progression in 28, progression to stage 4S in seven, and progression to stage 4 in four. Time to regression was quite variable, with first signs of regression noted 1 to 18 months after diagnosis and in 15 of 44 patients even after the first year of life. So far, complete regression was observed in 17 of 44 patients 4 to 20 months after diagnosis. Known clinical risk factors were not able to differentiate between patients with regression and regional or metastatic progression. Overall survival (OS; 3-year OS, 0.99 +/- 0.01) and metastases-free survival (rate at 3 years, 0.94 +/- 0.03) for patients with unresected tumors was excellent and was not different from patients treated with surgery or chemotherapy.Spontaneous regression is regularly seen in infants with localized neuroblastoma and is not limited to the first year of life. A wait-and-see strategy is justified in those patients.
The IκB Kinase β/Nuclear Factor κB Signaling Pathway Protects the Heart From Hemodynamic Stress Mediated by the Regulation of Manganese Superoxide Dismutase Expression
Authors: Shungo Hikoso, Osamu Yamaguchi, Yuko Nakano, Toshihiro Takeda, Shigemiki Omiya, Isamu Mizote, Manabu Taneike, Takafumi Oka, Takahito Tamai, Jota Oyabu, Yoshihiro Uno, Yasushi Matsumura, Kazuhiko Nishida, Keiichiro Suzuki, Mikihiko Kogo, Masatsugu Hori, Kinya Otsu
Journal: Circulation Research (2009)

Cardiomyocyte death plays an important role in the pathogenesis of heart failure. The nuclear factor (NF)-κB signaling pathway regulates cell death, however, the effect of NF-κB pathway on cell death can vary in different cells or stimuli. The purpose of the present study was to clarify the in vivo role of the NF-κB pathway in response to pressure overload. First, we subjected C57Bl6/J mice to pressure overload by means of transverse aortic constriction (TAC) and examined the activity of the NF-κB pathway in response to pressure overload. IκB kinase (IKK) and NF-κB were activated after TAC. Then, we investigated the role of the activation using cardiac-specific IKKβ-deficient mice (CKO). CKO displayed normal global cardiac structure and function compared with control littermates. We subjected CKO and control mice to pressure overload. One week after TAC, CKO showed cardiac dilation, dysfunction, and lung congestion, which are characteristics of heart failure. The number of apoptotic cells in the hearts of CKO mice increased significantly after TAC. The levels of manganese superoxide dismutase mRNA and protein expression in CKO after TAC were significantly attenuated compared with control mice. The levels of oxidative stress and c-Jun N-terminal kinase (JNK) activation in CKO after TAC were significantly greater than those in control mice. Isoproterenol-induced cell death of isolated adult CKO cardiomyocytes was inhibited by treatment with either a manganese superoxide dismutase mimetic or a JNK inhibitor. Thus, the IKKβ/NF-κB signaling pathway plays a protective role in cardiomyocytes because of the attenuation of oxidative stress and JNK activation in a setting of acute pressure overload.
Biomechanics of the head for Olympic boxer punches to the face
Authors: T J Walilko, D C Viano, C A Bir
Journal: British Journal of Sports Medicine (2005)

Objective: The biomechanics of the head for punches to the jaw and the risk of head injury from translational and rotational acceleration were studied. Methods: Seven Olympic boxers from five weight classes delivered 18 straight punches to the frangible face of the Hybrid III dummy. Translational and rotational head acceleration, neck responses, and jaw pressure distribution were measured. High speed video recorded each blow and was used to determine punch velocity. Equilibrium was used to determine punch force, energy transfer, and power. Results: Punch force averaged 3427 (standard deviation (SD) 811) N, hand velocity 9.14 (SD 2.06) m/s, and effective punch mass 2.9 (SD 2.0) kg. Punch force was higher for the heavier weight classes, due primarily to a higher effective mass of the punch. Jaw load was 876 (SD 288) N. The peak translational acceleration was 58 (SD 13) g , rotational acceleration was 6343 (SD 1789) rad/s 2 , and neck shear was 994 (SD 318) N. Conclusions: Olympic boxers deliver straight punches with high impact velocity and energy transfer. The severity of the punch increases with weight class.
Management of eucapnic obese patients with sleep disordered breathing (SDB)
Authors: Swapna Mandal, Rachel Harding, Carley King, Michelle Ramsay, Eui-Sik Suh, Nicholas Hart
Journal: European Respiratory Journal (2013)

INTRODUCTION: An increasing number of patients referred for investigation of obesity related respiratory failure(ORRF) demonstrate daytime eucapnia but with many becoming hypercapnic overnight.We investigated the clinical management of these patients. METHODS: Prospectively entered data from electronic patient records(Carevue, Phillips, USA) between January–December 2012 were reviewed.Obese patients with suspected obesity related respiratory failure were included in the analysis. RESULTS: 42 obese patients were assessed for ORRF. 28 (67%) patients had daytime eucapnia with confirmed obstructive sleep apnoea (OSA). Non-invasive ventilation(NIV) was given to 13(47%) patients; of these NIV was started as first line treatment in 9, whilst the remaining 4 were initiated on NIV due to failure of continuous positive airway pressure(CPAP).13(47%) were established on CPAP, of whom 8 were given CPAP immediately; the remainder started on CPAP after failing NIV.2(6%) were discharged without treatment as they could not tolerate CPAP or NIV.Compared to those initiated on CPAP, daytime eucapnic patients initiated on NIV had higher mean nocturnal TcCO2 (p 6kPa (p=0.002).

![Figure][1] 



CONCLUSION: These data suggest that daytime eucapnic OSA patients who become hypercapnic overnight may benefit from NIV.Future studies will need to determine the level of nocturnal hypercapnia at which patients would benefit from NIV rather than CPAP.

 [1]: pending:yes
CREB/CRTC-mediated regulation of transcription is important for regulatory T cells
Authors: Sabine Bartel, Marc Kästle, Oliver Eickelberg, Susanne Krauss-Etschmann
Journal: European Respiratory Journal (2014)

Background: Regulatory T cells (Treg) suppress inflammatory effector T-cells, are important for maintaining immune tolerance and ameliorate experimental allergic airway disease in an interleukin-10 dependent manner (Kearley et al .; J Exp. Med., 2005). In regulatory macrophages the transcription of IL-10 has been shown to be mediated by the transcription factor CREB together with its co-regulator CRTC3 (Clark et al., PNAS, 2012). Thus, we hypothesize that CREB/CRTC-mediated transcription might be essential for the function and formation of regulatory T cells.

Methods: CD4+CD25+ were isolated from spleens of female wildtype Balb/c mice by magnetic cell separation (MACS) (Miltenyl Biotech). Tregs were induced in vitro (iTreg) by treating CD4+CD25- cells with 2.5ng/ml TGF-β for 72h. We performed qRT-PCR and Western blot analysis of subcellular fractions. siRNA knock-down studies were done using peqFect siRNA transfection reagent and cells were then subjected to in vitro suppressor assays.

Results: The mRNA levels of CREB, CRTC1, -2, &-3 were increased 1.6-2-fold in nTregs (n=7) and in in vitro generated iTregs (n=4) compared to controls. Western blots of nTregs showed a 2-fold increase in CREB phosphorylation and also an increased nuclear translocation of CRTC1& -3 control cells (fold change= 1.5; n=4). CREB knockdown by siRNA lowered the in vitro FoxP3-induction by 60% (n=4) and slightly reduced the suppressive capacity (10%) of induced Tregs (n=2).

Conclusion: Our data point to an activation of CREB/CRTC-mediated transcription in naturally occurring as well as in in vitro induced Tregs. CREB knockdown reduced the formation of iTregs suggesting a possible role of this pathway in immune tolerance.
Outcomes of thoracic surgical interventions on ECMO patients: A 4 year experience
Authors: Pouya Youssefi, Tom Doyle, Karen Harrison-Phipps, John Pilling, Juliet King, Tom Routledge, Loic Lang-Lazdunski, Guy Glover, Chris Langrish, Nicholas Ioannou, Chris Meadows, Nicholas Barrett
Journal: International Journal of Surgery (2014)