tbuckley/cabot-search huggingface dataset:
Genetic variation in cervical preinvasive and invasive disease: a genome-wide association study
Authors: Sarah J Bowden, Barbara Bodinier, Ilkka Kalliala, Verena Zuber, Dragana Vuckovic, Triada Doulgeraki, Matthew D Whitaker, Matthias Wielscher, Rufus Cartwright, Konstantinos K Tsilidis, Phillip Bennett, Marjo-Riitta Jarvelin, James M Flanagan, Marc Chadeau-Hyam, Maria Kyrgiou
Journal: The Lancet Oncology (2021)

BackgroundMost uterine cervical high-risk human papillomavirus (HPV) infections are transient, with only a small fraction developing into cervical cancer. Family aggregation studies and heritability estimates suggest a significant inherited genetic component. Candidate gene studies and previous genome-wide association studies (GWASs) report associations between the HLA region and cervical cancer. Adopting a genome-wide approach, we aimed to compare genetic variation in women with invasive cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 with that in healthy controls.MethodsWe did a GWAS in a cohort of unrelated European individuals using data from UK Biobank, a population-based cohort including 273 377 women aged 40–69 years at recruitment between March 13, 2006, and Oct 1, 2010. We used an additive univariate logistic regression model to analyse genetic variants associated with invasive cervical cancer or CIN3. We sought replication of candidate associations in FinnGen, a large independent dataset of 128 123 individuals. We also did a two-sample mendelian randomisation approach to explore the role of risk factors in the genetic risk of cervical cancer.FindingsWe included 4769 CIN3 and invasive cervical cancer case samples and 145 545 control samples in the GWAS. Of 9 600 464 assayed and imputed single-nucleotide polymorphisms (SNPs), six independent variants were associated with CIN3 and invasive cervical cancer. These included novel loci rs10175462 (PAX8; odds ratio [OR] 0·87, 95% CI 0·84–0·91; p=1·07 × 10−9) and rs27069 (CLPTM1L; 0·88, 0·84–0·92; p=2·51 × 10−9), and previously reported signals at rs9272050 (HLA-DQA1; 1·27, 1·21–1·32; p=2·51 × 10−28), rs6938453 (MICA; 0·79, 0·75–0·83; p=1·97 × 10−17), rs55986091 (HLA-DQB1; 0·66, 0·60–0·72; p=6·42 × 10−28), and rs9266183 (HLA-B; 0·73, 0·64–0·83; p=1·53 × 10−6). Three SNPs were replicated in the independent Finnish dataset of 1648 invasive cervical cancer cases: PAX8 (rs10175462; p=0·015), CLPTM1L (rs27069; p=2·54 × 10−7), and HLA-DQA1 (rs9272050; p=7·90 × 10−8). Mendelian randomisation further supported the complementary role of smoking (OR 2·46, 95% CI 1·64–3·69), older age at first pregnancy (0·80, 0·68–0·95), and number of sexual partners (1·95, 1·44–2·63) in the risk of developing cervical cancer.InterpretationOur results provide new evidence for the genetic susceptibility to cervical cancer, specifically the PAX8, CLPTM1L, and HLA genes, suggesting disruption in apoptotic and immune function pathways. Future studies integrating host and viral, genetic, and epigenetic variation, could further elucidate complex host–viral interactions.FundingNIHR Imperial BRC Wellcome 4i Clinician Scientist Training Programme.
Differing circadian patterns of symptom onset in subgroups of patients with acute myocardial infarction.
Authors: AHjalmarson, E AGilpin, PNicod, HDittrich, HHenning, REngler, A RBlacky, S CSmith, FRicou, JRoss
Journal: Circulation (1989)

Circadian variation of the onset of acute myocardial infarction has been noted in many studies and may carry important pathophysiologic implications. However, only a few previous studies have attempted subgroup analyses. In 4,796 patients with documented acute myocardial infarction, the time of symptom onset was recorded. As in other studies, the peak of onset occurred in the morning from 6:01 AM to 12:00 noon, and 28% of the population (1.16 times the average percentage for the other time periods) experienced symptom onset in that period (p less than 0.001). There was a second, lower peak (25%) in the evening between 6:01 PM and 12:00 midnight, which was also observed in some previous studies. We sought to determine whether or not the presence of subgroups with specific clinical characteristics would exhibit different patterns and thereby contribute to these peaks in the overall population. In patients with a history of congestive heart failure (n = 606) or with non-Q wave infarction (n = 832), a pronoun...
Shall The Journal be Removed to Washington?
Authors: J. T. McShane
Journal: JAMA (1891)

<h3>To the Editor:</h3> —IfThe Journalshould be moved to Washington City I am fearful much of its life and vigor would be lost. Business activity is contagious, and in Chicago we have the benefit of the stimulus of this kind of an epidemic all the time. Carmel, Ind., Feb. 23, 1891.
Q fever endocarditis in Queensland.
Authors: H GWilson, G HNeilson, E GGalea, GStafford, M FO'Brien
Journal: Circulation (1976)

Thirteen patients with proven Q fever endocarditis and three additional patients with probable endocarditis are reviewed. The most helpful diagnostic test is the demonstration of a high complement fixing antibody titre to Phase 1 antigen of Coxiella burneti. The macroscopic pathology of the aortic valve is described and includes aneurysmal pockets in the aortic wall and valve annulus which are demonstrable angiographically. Evidence is presented that the infection may be controlled by prolonged tetracycline therapy and that this is accompanied by a falling antibody titre to Phase 1 antigen. Valve replacement is undertaken only for symptomatic and hemodynamic indications. The combined tetracycline therapy and valve replacement have produced a fall in titres with eradication of infection and palliation of the cardiac disability in all patients followed for long periods.
Impact of Covid-19 Outbreak on Clinical Practice and Training of Young Gastroenterologists: a European Survey
Authors: G Marasco, OM Nardone, M Maida, I Boskoski, L Pastorelli, F Scaldaferri
Journal: Endoscopy (2021)

Aims SARS-CoV-2 disease (COVID-19) is a major challenge for the healthcare system and physicians, imposing changes in daily clinical activity. We aimed to describe what European trainees and young gastroenterologists know about COVID-19 and identify training gaps to implement educational programs.
Group‐2 Innate Lymphoid Cells Promote HCC Progression Through CXCL2‐Neutrophil‐Induced Immunosuppression
Authors: Xingyuan Xu, Longyun Ye, Qi Zhang, Hang Shen, Shanshan Li, Xiaoyu Zhang, Mao Ye, Tingbo Liang
Journal: Hepatology (2021)

Due to their inherent characteristics, the function of group-2 innate lymphoid cells (ILC2s) varies in a context-dependent manner. ILC2s are involved in certain liver diseases; however, their involvement in HCC is unknown. In the present study, we assessed the role of an HCC-derived ILC2 population in tumor progression.Through FACS and single-cell RNA sequencing, we discovered that ILC2s were highly enriched in human HCC and correlated significantly with tumor recurrence and worse progression-free survival as well as overall survival in patients. Mass cytometry identified a subset of HCC-derived ILC2s that had lost the expression of killer cell lectin-like receptor subfamily G, member 1 (KLRG1). Distinct from their circulating counterparts, these hepatic ILC2s highly expressed CD69 and an array of tissue resident-related genes. Furthermore, reduction of E-cadherin in tumor cells caused the loss of KLRG1 expression in ILC2s, leading to their increased proliferation and subsequent accumulation in HCC sites. The KLRG1- ILC2 subset showed elevated production of chemotaxis factors, including C-X-C motif chemokine (C-X-C motif) ligand (CXCL)-2 and CXCL8, which in turn recruited neutrophils to form an immunosuppressive microenvironment, leading to tumor progression. Accordingly, restoring KLRG1 in ILC2s, inhibiting CXCL2 in ILC2s, or depleting neutrophils inhibited tumor progression in a murine HCC model.We identified HCC-associated ILC2s as an immune regulatory cell type that promotes tumor development, suggesting that targeting these ILC2s might lead to new treatments for HCC.
Effects of sodium pentobarbital anesthesia on left ventricular function and distribution of cardiac output in dogs, with particular reference to the mechanism for tachycardia.
Authors: W TManders, S FVatner
Journal: Circulation Research (1976)

Sodium pentobarbital (PB), 30 mg/kg, iv, was administered to 30 conscious dogs instrumented for measurement of cardiac output and regional blood flow distribution, left ventricular (LV) diameter, LV pressure, dP/dt, and dD/dt, i.e., velocity of myocardial fiber shortening. Ventilation was controlled during anesthesia to maintain arterial blood gases at control values for conscious dogs. The anesthetic produced an initial transient, peripheral vasodilation but the steady state effects 15-30 minutes later were characterized by slight reductions in mesenteric flow and cardiac output and increases in mesenteric and systemic resistances, whereas iliac and renal resistances were not significantly different from control. When heart rate rose, PB increased end-systolic diameter and decreased coronary resistance, LV end-diastolic diameter, dP/dt/P (42%), and shortening velocity (36%). When heart rate was controlled, PB still increased end-systolic diameter and decreased shortening velocity and dP/dt/P, as occurred...
Idiosyncratic reactions to carbamazepine mimicking viral infection in children.
Authors: C Brain, B Mac Ardle, S Levin
Journal: BMJ (1984)

Idiosyncratic reactions to carbamazepine mimicking viral infection in childrenAdverse reactions to carbamazepine include rashes, lymphadenopathy, hepatosplenomegaly,l and bone marrow depression ranging from mild leucopenia to aplastic anaemia.2Such reactions are rare in children.Mild leucopenia does not indicate withdrawal of the drug, but more serious bone marrow and systemic effects do.We report two cases in which the initial presentation mimicked viral infection and was associated with profound neutropenia. Case reportsCase 1-A 1 year old girl with poorly controlled myoclonic and complex partial epilepsy developed fever and cervical lymphadenopathy eight weeks after carbamazepine had been added to her treatment.Five days later her neutrophil count had fallen from 1-72 x 109/1 to 0-25 x 109/1 and the carbama- zepine was stopped.After three further days the neutrophil count had returned to 1-8 x 109/1 and her clinical illness resolved.She was subsequently chal- lenged with carbamazepine; after six days her neutrophil count had fallen to 0-85 X 109/1, increasing to 3 X 109/1 five days after the drug was stopped.Case 2-A 6 year old girl with myoclonic and complex partial epilepsy developed an itchy maculopapular rash on her trunk, scalp, palms, and soles two weeks after her treatment was changed from phenytoin to carbamazepine.Palatal petechiae, cervical and inguinal lymphadenopathy, and (subsequently) hepatosplenomegaly were also found.A blood film showed "atypical lymphocytes," but there was no neutropenia (neutrophils 5-78 X 109/1).Monospot and serial viral titres were negative, as were other indices of infection.A week later she became anorectic and lethargic.The rash had faded and become pigmented, but the lymphadenopathy and hepato-
Control of the Na-Ca exchanger in isolated heart cells. I. Induction of Na-Na exchange in sodium-loaded cells by intracellular calcium.
Authors: R AHaworth, A BGoknur, D RHunter
Journal: Circulation Research (1991)

Isolated adult rat heart cells in suspension were loaded with sodium by incubation with ouabain in the absence of calcium for 30 minutes. Addition of low levels of calcium induced accelerated rates of sodium influx and efflux, as measured with 22Na. The magnitude of calcium-induced 22Na efflux was 50-fold greater than the net rate of calcium uptake and required extracellular sodium, but not extracellular calcium, once some calcium was taken up. Calcium did not induce 86Rb efflux. The accelerated rate of 22Na efflux was prevented by verapamil, but verapamil was ineffective when added after calcium. Addition of EGTA after calcium reversed the effect of calcium, but only after incubation. Dichlorobenzamil, unlike verapamil, both prevented and reversed the induction of sodium fluxes by calcium. We conclude 1) that intracellular calcium induces Na-Na exchange through the Na-Ca exchanger in sodium-loaded cells exposed to calcium; and 2) that Na-Na exchange can be activated by calcium that enters the cell throug...
Myocyte cell loss and myocyte cellular hyperplasia in the hypertrophied aging rat heart.
Authors: PAnversa, TPalackal, E HSonnenblick, GOlivetti, L GMeggs, J MCapasso
Journal: Circulation Research (1990)

To determine the effects of age on the myocardium, the functional and structural characteristics of the heart were studied in rats at 4, 12, 20, and 29 months of age. Mean arterial pressure, left ventricular pressure and its first derivative (dP/dt), and heart rate were comparable in rat groups up to 20 months. During the interval from 20 to 29 months, elevated left ventricular end-diastolic pressure and decreased dP/dt indicated that a significant impairment of ventricular function occurred with senescence. In the period between 4 and 12 months, a reduction of nearly 19% in the total number of myocytes was measured in both ventricles. In the subsequent ages, similar decreases in myocyte cell number were found in the left ventricle, whereas in the right ventricle, the initial loss was fully reversed by 20 months. Moreover, from 20 to 29 months, a 59% increase in the aggregate number of myocytes occurred in the right ventricular myocardium. In the left ventricle, a 3% increment was also seen, but this smal...
カテーテルアブレーションにより根治した僧帽弁輪後壁側起源のRepetilive Monomorphic VTの一例
Authors: 関口幸夫, 鈴木篤, 岡田寛之, 横山泰広, 佐藤明, 青沼和隆, 野上昭彦, 家坂義人, 磯部光章
Journal: Circulation (2002)
Sex-associated differences in left ventricular function in aortic stenosis of the elderly.
Authors: J DCarroll, E PCarroll, TFeldman, D MWard, R MLang, DMcGaughey, R BKarp
Journal: Circulation (1992)

BACKGROUNDIn aortic stenosis, the response of the left ventricle to pressure overload varies from compensated hypertrophy to overt heart failure. The determinants of left ventricular adaptation are poorly understood.METHODS AND RESULTSLeft ventricular function was compared to assess the role of sex in 34 women and 29 men 60 years or older with both hemodynamic and echocardiographic data characteristic of severe aortic stenosis and no important coronary artery disease. Despite a similar degree of left ventricular outflow obstruction in women versus men (aortic valve area 0.54 +/- 0.20 versus 0.59 +/- 0.19 cm2, NS), the left ventricle of women had a greater fractional shortening (37 +/- 12 versus 25 +/- 12%, p = 0.001), achieved a smaller end-systolic chamber size (1.82 +/- 0.64 versus 2.17 +/- 0.65 cm/m2, p = 0.04), and generated more pressure (210 +/- 35 versus 182 +/- 29 mm Hg, p = 0.001) with a greater maximum positive dP/dt (2.153 +/- 794 versus 1,595 +/- 384 mm Hg/sec, p = 0.02). The men had a lower c...
Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure. Evidence for abnormalities unrelated to blood flow.
Authors: B MMassie, MConway, BRajagopalan, RYonge, SFrostick, JLedingham, PSleight, GRadda
Journal: Circulation (1988)

Previous studies with 31P nuclear magnetic resonance have demonstrated that patients with chronic congestive heart failure often exhibit increased glycolytic metabolism and impaired oxidative phosphorylation in exercising skeletal muscle, but the mechanism for these changes remains unresolved. This study was conducted to determine whether these abnormalities result from impaired blood flow or oxygen delivery. Nine patients with mild-to-moderate congestive heart failure and nine age- and size-matched, healthy control volunteers were studied during repetitive submaximal finger flexion exercise under aerobic and ischemic conditions. Skeletal muscle metabolism was assessed by 31P nuclear magnetic resonance of the flexor digitorum superficialis muscle. During steady-state aerobic exercise at 33% of each subject's predetermined maximum workload, the patients with congestive heart failure exhibited significantly lower pH values (6.65 +/- 0.22 vs. 6.97 +/- 0.09, p less than 0.002) and phosphocreatine concentratio...
Intestinal microvascular growth during maturation in diabetic juvenile rats.
Authors: J LUnthank, H GBohlen
Journal: Circulation Research (1988)

To determine if intestinal microvascular growth is impaired in diabetic juvenile animals, a segment of the terminal ileum was marked and the microvasculature of this segment observed at the age of 5 weeks and again at the age of 10-11 weeks in normal and diabetic Sprague Dawley rats. Diabetes was induced by streptozotocin after the first observation period and the plasma glucose concentration exceeded 500 mg% by the age of 10-11 weeks. Microvascular growth was quantitated by measurements of the number, length, and maximally dilated inner diameters of specific arterioles and by intercapillary distances in the marked intestinal region at both ages. Although intestinal enlargement was much greater in diabetics, there was no change in the number of arterioles during maturation and intercapillary distances were equivalent in diabetic and normal rats. In normal and diabetic animals, the arteriolar length increased to match bowel elongation, however, increases in bowel and arteriolar lengths in diabetic animals ...
173P Evaluating the content validity, clarity, and relevance of the PROMIS-physical function (PROMIS-PF)-8C and non-small cell lung cancer (NSCLC)-Symptom assessment questionnaire (NSCLC-SAQ) in adults with epidermal growth factor receptor (EGFR)-mutated NSCLC
Authors: M.K. Horn, K. Liu, S.D. Mathias, H.H. Colwell, T. Li, P. Mahadevia, R.F. Pierson
Journal: Journal of Thoracic Oncology (2021)
Decreased STAT1 Expression by Promoter Methylation in Squamous Cell Carcinogenesis
Authors: Sichuan Xi, Kevin F. Dyer, Mark Kimak, Qing Zhang, William E. Gooding, J. Richard Chaillet, Raymond Liu Chai, Robert E. Ferrell, Beth Zamboni, Jennifer Hunt, Jennifer Rubin Grandis
Journal: JNCI Journal of the National Cancer Institute (2006)

Dysregulation of signal transducers and activators of transcription (STATs) is associated with many cancers, but no role of STAT1 in human tumor progression has been demonstrated.We compared STAT1 protein expression in squamous cell carcinoma of the head and neck (SCCHN) tumors (n = 28) and normal oropharyngeal mucosa samples (n = 10) from patients without cancer as assessed by immunoblotting. Stable clones were established from SCCHN 1483 cells that were transfected with a STAT1 expression construct; cell growth and cisplatin-induced apoptosis of the clones and vector control-transfected 1483 cells were compared using trypan blue exclusion and Annexin V staining and expression of the cyclin-dependent kinase inhibitor p21 was assayed by immunoblotting. The growth of STAT1-overexpressing SCCHN 1483 xenograft tumors was compared with that of xenograft tumors derived from cells transfected with vector control DNA. DNA from SCCHN tumors (n = 16) and paired peripheral blood lymphocytes were analyzed for STAT1 mutations and promoter methylation using methylation-specific polymerase chain reaction and bisulfite sequencing. SCCHN cell lines (PCI-15b, 1483, and UM-22B) were treated with the demethylating agent azacytidine alone or in combination with the cytotoxic drug cisplatin, and expression of STAT1 and p21 were monitored by immunoblotting. All statistical tests were two-sided.STAT1 levels were statistically significantly lower in the SCCHN tumors than normal mucosa (median = 0.8 relative units versus 2.4, difference = 1.6, 95% confidence interval [CI] = 1.3 to 2.0, P < .001). Overexpression of STAT1 abrogated the growth of SCCHN cells and xenograft tumors and increased p21 expression. STAT1 expression levels of the tumors with STAT1 promoter methylation (n = 12) were lower than those of tumors (n = 4) without promoter methylation of STAT1 (P = .008). Azacytidine treatment increased expression of STAT1 and p21 in SCCHN cell lines and increased apoptosis in cisplatin-treated 1483 cells compared with cisplatin treatment alone (mean = 61.3% versus 25.8%, difference = 35.5%, 95% CI = 24.5% to 43.4%; P = .028).STAT1 can function as a tumor suppressor in SCCHN cells. Silencing of the STAT1 gene via promoter methylation may contribute to SCCHN tumor cell growth.
Abstract 17412: Ultrasound-Mediated S100A6 Gene Therapy Ameliorates Ischemia-Reperfusion Injury
Authors: Azadeh Mofid, Paul J Lee, Michael A Kuliszewski, Nadav S Newman, Dmitriy Rudenko, Hao H Chen, Christine Liao, Vanessa Shen, Thomas G Parker, Howard Leong-Poi
Journal: Circulation (2012)

Introduction: Myocardial ischemia-reperfusion (I/R) produces cellular damage, apoptosis and necrosis. S100A6, a member of EF-hand Ca2+-binding proteins, is upregulated after I/R, and over-expressio...
Long-Term Malignancy in Small Pancreatic Cystic Lesions Without Worrisome Features or High Stigmata
Authors: M Lindo Ricce, A Guardiola-Arévalo, Ortega A Repiso, R Gómez-Rodriguez
Journal: Endoscopy (2021)

Aims The malignancy risk of small pancreatic cystic lesions (PCLs) without worrisome features or high-risk stigmata remains unclear for that reason the aim of this study is to elucidate their natural history.
Impact On Nutritional Status Of Eus-Guided Gastroenterostomy In Patients With A Malignant Duodenal Stenosis
Authors: E Perez-Cuadrado Robles, G Perrod, H Benosman, E Moati, E Coffin, J Taieb, C Cellier, G Rahmi
Journal: Endoscopy (2021)

Aims The endoscopic ultrasound guided gastroenterostomy (EUS-GE) is an alternative to the duodenal stent in patients with a malignant stenosis. This challenging technique may have larger patency times with a lower reintervention rate compared to duodenal stents at expenses of a higher intraoperative complication rate. However, the impact on nutritional status in these patients is unknown.
Coronary capillaries in patients with congestive cardiomyopathy or angina pectoris with patent main coronary arteries. Ultrastructural morphometry of endomyocardial biopsy samples.
Authors: MMosseri, JSchaper, DAdmon, YHasin, M SGotsman, DSapoznikov, J GPickering, RYarom
Journal: Circulation (1991)

BACKGROUNDThe coronary microvasculature may be abnormal even in the presence of angiographically normal epicardial arteries. Abnormalities of small coronary vessels have been invoked as a cause of angina.METHODS AND RESULTSTo quantitatively evaluate the morphology of capillaries in patients with idiopathic dilated cardiomyopathy (DCM) or the syndrome of angina and small vessel disease (SVD), we performed electron microscopic morphometry of capillaries in right ventricular biopsy samples taken from 32 patients. Ten had angina, normal epicardial coronary arteries, and evidence for SVD; 12 had DCM; and 10 had normal hearts. In patients with DCM, the ratio of microvessels to myocytes was not different than that of controls (0.49 +/- 0.06 versus 0.51 +/- 0.05). Mean cross-sectional areas of the capillaries (lumen plus wall) and lumen were significantly greater than those of controls (45.3 +/- 15.1 versus 22.7 +/- 8.3 micron 2, p less than 0.001; 17.6 +/- 6.9 versus 11.6 +/- 6.2 micron 2, p less than 0.05, resp...