tbuckley/cabot-search huggingface dataset:
Recurrent fungal infections in a Chinese patient with <scp>CARD</scp> 9 deficiency and a review of 48 cases
Authors: C. Quan, X. Li, R.‐F. Shi, X.‐Q. Zhao, H. Xu, B. Wang, X.‐P. Wang, W.‐G. Hu, H. Cao, J. Zheng
Journal: British Journal of Dermatology (2018)

Deficiency of CARD9 (caspase recruitment domain‐containing protein 9) has been reported in individuals with recurrent and invasive fungal infections. We report on a patient who first had Trichosporon asahii affecting the skin then Candida albicans infections involving the digestive tract and knee joint, along with elevated serum IgE. After stimulation with C. albicans, peripheral blood mononuclear cells of this patient produced less tumour necrosis factor‐α, interferon‐γ and interleukin‐17 than those of healthy controls. Furthermore, the serum IgE levels of this patient were positively correlated with the severity of fungal infection during the course of treatment. Sanger sequencing identified one homozygous frameshift mutation (p.D274fsX60) in CARD9. We further performed a review including 48 cases with CARD9 deficiency. According to the data published previously, CARD9‐deficient patients demonstrated obviously elevated IgE in serum (median 1300 IU mL−1), which could distinguish them from otherwise healthy people with fungal infections (area under the curve 0·94, P < 0·001). Patients carrying the mutations Q289X and Q295X had a higher mortality rate (24% vs. 0%, P < 0·05). Patients with the mutations R18W, R35Q, R70W, G72S or Y91H in the CARD domain, and the nonsense mutation Q295X in the coiled‐coil domain, seemed to be more prone to Candida infections (90% vs. 20%, P < 0·005) and central nervous system infections (60% vs. 12%, P < 0·005).
Arrhythmias following Cardiac Valve Replacement
Authors: Rogersmith, Williamgrossman, Lewisjohnson, Hermansegal, Johncollins, Jamesdalen
Journal: Circulation (1972)

A prospective study of 50 consecutive patients undergoing cardiac valve replacement was designed to determine the incidence, types, and predisposing factors to postoperative arrhythmias. Patients were monitored continuously for the first 7 days following surgery. Thirty-seven patients (74%) experienced a total of 66 episodes of arrhythmia. Supra-ventricualr arrhythmias were the most common (43 of 66; 65%). The most frequent specific arrhythmia was atrial fibrillation (21 of 66; 32%). Arrhythmias occurred 77% of the time within the first 48 hours of surgery. Of 25 factors evaluated preoperatively in each patient, only two were found to predispose to postoperative arrhythmias. These were: (1) previous cardiac surgery; and (2) elevated blood urea nitrogen. There were four hospital deaths, representinig a hospital mortality of 8%. No deaths were due to a primary arrhythmia. It is concluded that whereas arrhythmias are a very common complication of cardiac valve replacement, early detection and treatment has l...
Abstract 5163: Rab11 regulates focal adhesion kinase dynamics in sarcoma cell migration
Authors: Ling-Yi Kao, Wan-Chen Wei, Hsiang-Ling Chiu, Yi-Che Wu, Wei-Ting Chao
Journal: Cancer Research (2018)

Abstract Focal adhesion (FA) turnover has been demonstrated to play an important role in controlling cell migration and cancer metastasis. FA disassembly was shown to be regulated by endocytosis during cell migration. Rabs are a kind of GTPase that participate in various cellular vesicle transports; however, whether the Rabs play a role in mediating vesicle transport for FA formation is not clear. This study focuses on Rab11, which plays a role in endosome recycling, and examines whether Rab11 has regulatory function in FA formation during cell migration. Wild-type and deficient Rab11 were transfected into human HT1080 fibrosarcoma cells, the cell migration ability was determined by trans-well assay, the localization of Rab11 and focal adhesion molecules were monitored by confocal microscopy and the in vivo study was carried out with subcutaneous xenograft mouse model to evaluate the effect of Rab11 on tumor growth. Results showed Rab11 deficiency inhibited sarcoma cell migration; the Rab11 was also found colocalized with recycled β1 integrin and affected focal adhesion formation. The live image results demonstrated the inactive GDP form Rab11 has no effect on random cell migration; however, the Rab11 knockdown inhibited random cell migration. We further used immunofluorescence and immunoprecipitation and identified the physical interaction of Rab11 and FAK. In the in vivo study, wild-type Rab11 transfected cells increased the tumor volume in xenograft mouse, but not in Rab11-deficient cells. Taken together, the results suggested Rab11 affected cell migration by regulating focal adhesion dynamics through integrin recycling and the effect of Rab11 may be through protein-protein interaction other than GTP activation. Citation Format: Ling-Yi Kao, Wan-Chen Wei, Hsiang-Ling Chiu, Yi-Che Wu, Wei-Ting Chao. Rab11 regulates focal adhesion kinase dynamics in sarcoma cell migration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5163.
Abstract 4219: Breast cancer distribution and survival among Buddhist and Muslim women in southern Thailand
Authors: Kali Defever, Katie M. Rentschler, Ana Khazan, Elizabeth Pinkerton, Shama Virani, Hutcha Sriplung, Judy Pang, Celina G. Kleer, Carlos F. Mendes de Leon, Justin A. Colacino, Laura S. Rozek
Journal: Cancer Research (2018)

Abstract Objective: Thailand is undergoing a period of rapid economic growth, which has led to an epidemiologic transition from infectious to chronic diseases such as cancer. Preliminary research shows a difference in rates of breast cancer incidence and mortality between Buddhist and Muslim women in southern Thailand. This study examines differences in breast cancer and potential explanations for this disparity. Methods: Demographic, diagnostic, and outcome data from breast cancer patients diagnosed from 2001-2015 were collected from a population-based cancer registry in southern Thailand and matched with formalin-fixed paraffin-embedded blocks from Songklanagarind Hospital. This region was selected due to the relatively high proportion of Muslim women. Of 424 cases selected, 369 were Buddhist and 55 were Muslim. Formalin-fixed paraffin-embedded blocks were sent to Michigan Medicine and histological and subtype analyses were performed by two pathologists. Statistical analysis was performed in RStudio using chi-square tests of independence, logistic regression, and Cox proportional hazards models. Results: Muslim women were generally diagnosed at a younger age than Buddhist women (Muslim mean: 46.6 years, Buddhist mean: 52.7 years) and with later stage cancers (Muslim: 36% stage 3 and 14% stage 4, Buddhist: 20% stage 3 and 8% stage 4). Buddhist and Muslim women had similar distributions of Luminal A and B subtypes, but Muslim women were more likely to be diagnosed with Triple Negative breast cancer (Muslim: 30%, Buddhist: 18%), the histological subtype with the worst prognosis. Invasive ductal carcinoma was most common in both groups, but Buddhists had more heterogeneity in subtypes. There were no significant differences in tumor histology or subtype by religion. Conclusions: These analyses show differences in the distribution of breast cancer between Buddhist and Muslim women. Muslim women are diagnosed younger with later stage breast cancers, and with histological differences, which generally lead to lower survival rates. Lack of statistical significance may be due to small sample size, necessitating further studies. Citation Format: Kali Defever, Katie M. Rentschler, Ana Khazan, Elizabeth Pinkerton, Shama Virani, Hutcha Sriplung, Judy Pang, Celina G. Kleer, Carlos F. Mendes de Leon, Justin A. Colacino, Laura S. Rozek. Breast cancer distribution and survival among Buddhist and Muslim women in southern Thailand [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4219.
Prevalence of Five Health-Related Behaviors for Chronic Disease Prevention Among Sexual and Gender Minority Adults — 25 U.S. States and Guam, 2016
Authors: Timothy J. Cunningham, Fang Xu, Machell Town
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In recent decades, public health awareness of health disparities among lesbian, gay, bisexual, and transgender (LGBT) populations has increased (1). Healthy People 2020 included objectives to improve health of LGBT persons.† Five key health-related behaviors were found to be likely associated with reduced all-cause mortality: never smoking, performing regular physical activity, consuming no or moderate amounts of alcohol, having a normal body weight, and obtaining sufficient sleep daily (2). CDC estimated these five health-related behaviors among adults aged ≥21 years by sexual orientation and transgender status using data from the 2016 Behavioral Risk Factor Surveillance System (BRFSS) in 25 U.S. states and Guam. Patterns of these five health-related behaviors varied by sexual orientation among men and women, and among transgender adults. Lesbian and bisexual women were less likely to engage in all five health-related behaviors than were heterosexual women (5.4% and 6.9%, respectively, versus 10.6%). Compared with cisgender§ adults, male-to-female transgender adults were less likely to engage in any two of five health-related behaviors (12.3% versus 18.6%). Male-to-female transgender adults, however, were more likely to engage in any three of five health-related behaviors than were female-to-male transgender adults (47.2% versus 28.2%). The number of health-related behaviors did not differ between gay or bisexual men and heterosexual men. Continued efforts are needed to target LGBT populations for overall well-being, including strategies for health promotion and engagement in health-related behaviors.
Inflammatory Cytokines Impair Endothelium-Dependent Dilatation in Human Veins In Vivo
Authors: KiranBhagat, PatrickVallance
Journal: Circulation (1997)

Background Endothelial dysfunction occurs in many diseases associated with increased cardiovascular risk. We examined the effects of pro-inflammatory cytokines on endothelial function. Methods and Results Subjects lay with one hand placed on an angled support. The diameter of a vein was recorded by measuring the linear displacement of a probe placed on the skin overlying the vein when the pressure in a congesting cuff placed around the upper arm was deflated from 40 to 0 mm Hg. A length of the vein was isolated by two wedges. TNF-α (1 ng), IL-1β (1 ng), or IL-6 (100 pg) were instilled for 1 hour, either individually or together. At the end of the hour, the wedges were removed and the vein reconnected with the circulation. Dose-response curves (bradykinin: 2, 4, and 8 pmol/min; arachidonic acid: 0.2, 2, and 20 nmol/min; and glyceryl trinitrate 1, 2, and 4 pmol/min) were constructed before and 1, 6, 24, and 48 hours after instillation. In another study, hydrocortisone (100 mg) was given 2 hours before the s...
Association of Intracranial Hemorrhage Risk With Non–Vitamin K Antagonist Oral Anticoagulant Use vs Aspirin Use
Authors: Wen-Yi Huang, Daniel E. Singer, Yi-Ling Wu, Chern-En Chiang, Hsu-Huei Weng, Meng Lee, Bruce Ovbiagele
Journal: JAMA Neurology (2018)

<h3>Importance</h3> Non–vitamin K antagonist oral anticoagulants (NOACs) might be an attractive choice for stroke prevention in people without atrial fibrillation who may harbor a potential source of cardiac emboli, but not if certain individual NOACs carry risks of intracranial hemorrhage that are heightened relative to aspirin. <h3>Objective</h3> To conduct a systematic review and meta-analysis of randomized clinical trials to assess the risk of intracranial hemorrhage with individual NOACs vs aspirin across all indications. <h3>Data Sources</h3> We searched PubMed, Embase, CENTRAL, and ClinicalTrials.gov from inception to May 28, 2018, with the terms<i>novel oral anticoagulants</i>,<i>non–vitamin K antagonist oral anticoagulants</i>,<i>direct oral anticoagulants</i>,<i>dabigatran</i>,<i>rivaroxaban</i>,<i>apixaban</i>,<i>edoxaban</i>,<i>warfarin</i>,<i>Coumadin</i>,<i>vitamin K antagonist</i>,<i>aspirin</i>,<i>acetylsalicylic acid</i>, or<i>ASA</i>, and<i>major bleeding</i>,<i>fatal bleeding</i>, or<i>intracranial hemorrhage</i>. We restricted our search to clinical trials on humans. There were no language restrictions. <h3>Study Selection</h3> Randomized clinical trials of 3 months or longer that included a comparison of the outcomes of NOAC use vs use of aspirin. <h3>Data Extraction and Synthesis</h3> Two investigators independently abstracted data from eligible studies. We computed a fixed-effect estimate based on the Mantel-Haenszel method. <h3>Main Outcomes and Measures</h3> Odds ratios (ORs) with 95% CI were used as a measure of the association of individual NOAC vs aspirin with the risk of intracranial hemorrhage. The hypothesis that intracranial hemorrhage risk would be higher with NOACs than aspirin was formulated during data collection. <h3>Results</h3> Our principal analysis included 5 randomized clinical trials comparing 1 or more NOACs with aspirin, with 39 398 individuals enrolled. Pooling the results from the fixed-effects model showed that a dose of 15 to 20 mg of rivaroxaban once daily was associated with an increased risk of intracranial hemorrhage (2 trials; OR, 3.31 [95% CI, 1.42 to 7.72]) compared with aspirin, while a 10-mg dose of rivaroxaban once daily or a 5-mg dose twice daily (3 trials; OR, 1.43 [95% CI, 0.93 to 2.21]) and a 5-mg dose of apixaban twice daily (1 trial; OR, 0.84 [95% CI, 0.38 to 1.88]) were not. <h3>Conclusions and Relevance</h3> A 15-mg to 20-mg dose of rivaroxaban once daily is associated with substantially increased risks of intracranial hemorrhage, while smaller daily doses of rivaroxaban and apixaban were not, implying that risk increase is dose dependent. It may be worthwhile to conduct randomized clinical trials comparing specific NOACs in specific doses (eg, apixaban, 5 mg twice daily) and aspirin in patients without atrial fibrillation, but with potential sources of cardiac emboli that could cause stroke.
Cardioversion Following Prosthetic Mitral Valve Replacement
Authors: Howardsemer, Herberthultgren, Robertkleiger, Blainebraniff
Journal: Circulation (1967)

Direct current conversion of atrial fibrillation has been attempted in 60 consecutive patients following prosthetic mitral valve replacement (Starr-Edwards prosthesis). Sinus rhythm was attained and persisted for at least 24 hours after the procedure in 68% (41 patients) and 40% of the entire group (24 patients) were still in normal sinus rhythm an average of 10 months later. Successful initial conversion and persistence of sinus rhythm occurred most frequently in patients whose duration of atrial fibrillation was less than 5 years and who had a small left atrium. Results differed little whether conversion was attempted 7 to 21 days or 1 to 15 months after open valve replacement. Atrial disease associated with a long period of antecedent atrial fibrillation and marked left atrial enlargement appeared to be the most important factors responsible for persistence of atrial fibrillation or early relapse. Attempts at cardioversion are recommended for all patients with persistent atrial fibrillation following m...
Abstract 16894: Initial in vivo Results of Cleveland Clinic Pediatric Continuous-Flow Total Artificial Heart Implant
Authors: Jamshid H Karimov, David Horvath, Nicole Byram, Gengo Sunagawa, Barry Kuban, Shengqiang Gao, Raymond Dessoffy, Kiyotaka Fukamachi
Journal: Circulation (2017)

Introduction: Heart transplantation in infants and children is an accepted therapy for congenital heart disease, but donor organ availability remains unstable. Mechanical circulatory support is ano...
Short Communication: Genetic Ablation of L-Type Ca2+ Channels Abolishes Depolarization-Induced Ca2+ Release in Arterial Smooth Muscle
Authors: MiguelFernández-Tenorio, PatriciaGonzález-Rodríguez, CristinaPorras, AntonioCastellano, SvenMoosmang, FranzHofmann, JuanUreña, JoséLópez-Barneo
Journal: Circulation Research (2010)

Rationale: In arterial myocytes, membrane depolarization-induced Ca2+ release (DICR) from the sarcoplasmic reticulum (SR) occurs through a metabotropic pathway that leads to inositol trisphosphate synthesis independently of extracellular Ca2+ influx. Despite the fundamental functional relevance of DICR, its molecular bases are not well known. Objective: Biophysical and pharmacological data have suggested that L-type Ca2+ channels could be the sensors coupling membrane depolarization to SR Ca2+ release. This hypothesis was tested using smooth muscle–selective conditional Cav1.2 knockout mice. Methods and Results: In aortic myocytes, the decrease of Ca2+ channel density was paralleled by the disappearance of SR Ca2+ release induced by either depolarization or Ca2+ channel agonists. Cav1.2 channel deficiency resulted in almost abolition of arterial ring contraction evoked by DICR. Ca2+ channel–null cells showed unaltered caffeine-induced Ca2+ release and contraction. Conclusion: These data suggest that Cav1....
Abstract 3058: Data and resource sharing: Advancing our understanding of glioblastoma
Authors: Hema A. Luchman, Fiona Coutinho, Samuel Weiss, Stand Up to Cancer Stem Cell Dream Team Consortium, Peter Dirks
Journal: Cancer Research (2018)

Abstract Glioblastoma multiforme (GBM), characterized by an aggressive clinical course, therapeutic resistance, and striking molecular heterogeneity, remains incurable. GBM has a median survival of only 12-15 months post-surgery in adults even with standard of care chemotherapy and radiation. Through a collaborative pan-Canadian Stand up to Cancer (SU2C) Stem Cell Dream Team effort, our group is focusing on brain tumour stem cells (BTSCs), a subpopulation of cells within tumours, which are hypothesized to drive tumour growth, relapse, and resistance to conventional chemotherapies. We are completing large-scale phenotypic cell biology, tumourigenicity, drug screening, and multi-platform ‘omic studies (genomics, bulk and single cell transcriptomics, epigenomics, metabolomics, proteomics, ATACseq) on a large number of adult GBM patient-derived BTSC cultures. Using both in vitro and in vivo approaches and the above multi-platform approaches, we are investigating the unique growth and stem cell characteristics of the BTSCs. In addition, we are using BTSC cultures to investigate drug response and genetic targeting approaches to identify new therapeutic strategies for clinical translation and understand mechanisms of resistance and recurrence. The wealth of information derived from this project is being integrated using systems biology approaches and will be shared in the public domain via data visualization and big data sharing platforms. Contemporaneously, we are depositing a number of well-characterized BTSC cultures in the American Type Culture Collection repository for unrestricted access to the scientific community. Our cross-Canada multi-disciplinary Cancer Stem Cell Dream Team, comprised of scientists, clinicians and patient advocates supports the ideal of data and resource sharing to help improve patient outcome for this devastating disease. Our goal is to provide the broader community of scientists, clinicians and patient groups an enduring resource and data sharing model to advance our understanding of glioblastoma. Citation Format: Hema A. Luchman, Fiona Coutinho, Samuel Weiss, Stand Up to Cancer Stem Cell Dream Team Consortium, Peter Dirks. Data and resource sharing: Advancing our understanding of glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3058.
Sympathetic Innervation of the Juxtaglomerular Cells of the Kidney
Authors: Janwågermark, Urbanungerstedt, Arneljungqvist
Journal: Circulation Research (1968)

Combination of a histochemical fluorescence method for biogenic monoamines and staining of juxtaglomerular cell granules demonstrated sympathetic nerve terminals in the rat kidney in the walls of the parts of the juxtaglomerular arterioles that contain granulated cells. This forms a morphological basis for a direct influence of sympathetic nervous activity on the liberation of renin. The juxtaglomerular granules were nonfluorescent, an indication that, in the rat, the granulated juxtaglomerular cells are not equivalent to mast cells.
Ischemic Preconditioning Upregulates Vascular Endothelial Growth Factor mRNA Expression and Neovascularization via Nuclear Translocation of Protein Kinase C ε in the Rat Ischemic Myocardium
Authors: HiroyukiKawata, Ken-ichiYoshida, AtsuhikoKawamoto, HideyukiKurioka, EijiTakase, YasunobuSasaki, KazuhitoHatanaka, MasahikoKobayashi, TakashiUeyama, ToshioHashimoto, KazuhiroDohi
Journal: Circulation Research (2001)

Abstract—Ischemic preconditioning (IP) exerts cardioprotection through protein kinase C (PKC) activation, whereas myocardial ischemia enhances vascular endothelial growth factor (VEGF) mRNA expression. However, the IP effect or the involvement of PKC on the VEGF expression is unknown in myocardial infarction. We investigated whether IP enhances VEGF gene expression and angiogenesis through PKC activation in the in vivo myocardial infarction model. Sprague-Dawley rats were assigned into the following 3 groups: the sham group; the IP group, which underwent 3 cycles of 3 minutes of ischemia and 5 minutes of reperfusion (IP procedure); and the non-IP group. The latter 2 groups were subsequently subjected to left anterior descending coronary artery occlusion. To examine the involvement of PKC, the PKC inhibitor chelerythrine (5 mg/kg) or bisindolylmaleimide (1 mg/kg) was injected intravenously before the IP procedures. PKCe was translocated to the nucleus after 10 minutes of ischemia after the IP procedure but...
Changes in Surface Expression of Platelet Membrane Glycoproteins and Progression of Heart Transplant Vasculopathy
Authors: SuzanneFateh-Moghadam, WolfgangBocksch, AndreasRuf, TimmDickfeld, MichaelSchartl, GiselaPogátsa-Murray, RolandHetzer, EckartFleck, MeinradGawaz
Journal: Circulation (2000)

Background—Transplant vasculopathy is the main limiting factor of the long-term success of heart transplantation. We sought to establish the role of platelets in the development and progression of transplant vasculopathy. Methods and Results—Platelet analysis and intracoronary ultrasound examination were performed in 78 heart transplant recipients. Quantitative intracoronary ultrasound was used to define the severity of disease at baseline (48.8±4.5 months after transplantation) and at 1-year follow-up. Platelet activation was assessed with the use of immunological surface markers of activation (ligand-induced binding site 1 [LIBS-1], P-selectin, GPIIb-IIIa) and flow cytometry. We found that LIBS-1 immunoreactivity was significantly increased in patients with diffuse disease when compared with focal transplant disease (median [quartile], 27[14, 64] versus 18[7.9, 47], P=0.04). In a logistic regression model, we found that LIBS-1 was an independent predictor for the presence and progression of diffuse tran...