tbuckley/cabot-search huggingface dataset:
Complementary Medicine, Refusal of Conventional Cancer Therapy, and Survival Among Patients With Curable Cancers
Authors: Skyler B. Johnson, Henry S. Park, Cary P. Gross, James B. Yu
Journal: JAMA Oncology (2018)

There is limited information on the association among complementary medicine (CM), adherence to conventional cancer treatment (CCT), and overall survival of patients with cancer who receive CM compared with those who do not receive CM.To compare overall survival between patients with cancer receiving CCT with or without CM and to compare adherence to treatment and characteristics of patients receiving CCT with or without CM.This retrospective observational study used data from the National Cancer Database on 1 901 815 patients from 1500 Commission on Cancer-accredited centers across the United States who were diagnosed with nonmetastatic breast, prostate, lung, or colorectal cancer between January 1, 2004, and December 31, 2013. Patients were matched on age, clinical group stage, Charlson-Deyo comorbidity score, insurance type, race/ethnicity, year of diagnosis, and cancer type. Statistical analysis was conducted from November 8, 2017, to April 9, 2018.Use of CM was defined as "Other-Unproven: Cancer treatments administered by nonmedical personnel" in addition to at least 1 CCT modality, defined as surgery, radiotherapy, chemotherapy, and/or hormone therapy.Overall survival, adherence to treatment, and patient characteristics.The entire cohort comprised 1 901 815 patients with cancer (258 patients in the CM group and 1 901 557 patients in the control group). In the main analyses following matching, 258 patients (199 women and 59 men; mean age, 56 years [interquartile range, 48-64 years]) were in the CM group, and 1032 patients (798 women and 234 men; mean age, 56 years [interquartile range, 48-64 years]) were in the control group. Patients who chose CM did not have a longer delay to initiation of CCT but had higher refusal rates of surgery (7.0% [18 of 258] vs 0.1% [1 of 1031]; P < .001), chemotherapy (34.1% [88 of 258] vs 3.2% [33 of 1032]; P < .001), radiotherapy (53.0% [106 of 200] vs 2.3% [16 of 711]; P < .001), and hormone therapy (33.7% [87 of 258] vs 2.8% [29 of 1032]; P < .001). Use of CM was associated with poorer 5-year overall survival compared with no CM (82.2% [95% CI, 76.0%-87.0%] vs 86.6% [95% CI, 84.0%-88.9%]; P = .001) and was independently associated with greater risk of death (hazard ratio, 2.08; 95% CI, 1.50-2.90) in a multivariate model that did not include treatment delay or refusal. However, there was no significant association between CM and survival once treatment delay or refusal was included in the model (hazard ratio, 1.39; 95% CI, 0.83-2.33).In this study, patients who received CM were more likely to refuse additional CCT, and had a higher risk of death. The results suggest that mortality risk associated with CM was mediated by the refusal of CCT.
Intravenous fosfomycin in patients with liver disease for extensively drug-resistant Gram-negative bacteria
Authors: Athina Pyrpasopoulou, Georgia Pitsava, Elias Iosifidis, George Imvrios, Eleni Massa, Eleni Mouloudi, Ioannis Goulis, Eleni Chatzidrosou, Charalampos Antachopoulos, Ioannis Fouzas, Emmanuel Roilides
Journal: Journal of Infection (2018)
Cardioprotection by Ischemic Postconditioning Is Lost in Aged and STAT3-Deficient Mice
Authors: KerstinBoengler, AstridBuechert, YvonneHeinen, ChristinRoeskes, DeniseHilfiker-Kleiner, GerdHeusch, RainerSchulz
Journal: Circulation Research (2008)

The cardioprotection by ischemic preconditioning is lost in aged wild-type and in STAT3 (signal transducer and activator of transcription 3)-deficient mice. The aim of the present study was to analyze whether or not ischemic postconditioning (iPoco) was effective in aged mice hearts and whether iPoco was dependent on STAT3. Young (3 months) and aged (>13 months) C57Bl6/J mice underwent 30 minutes of ischemia and 2 hours of reperfusion without or with iPoco (3 cycles of 10 seconds of ischemia/10 seconds of reperfusion [3×10] or 5 cycles of 5 seconds of ischemia/5 seconds of reperfusion [5×5] at the beginning of reperfusion). In young mice, both iPoco3×10 and iPoco5×5 reduced infarct size (IS), whereas in aged mice, only iPoco5×5 was effective in reducing IS. In young mice, iPoco3×10 increased the phosphorylated over total STAT3 (phosphorylated STAT3/STAT3) ratio at 10 minutes of reperfusion in the postconditioned anterior wall compared with the control posterior wall. In aged mice hearts, total STAT3 and p...
The lipocalin beta-lactoglobulin accumulates in stable dust: potential implications for the allergy- and asthma-protective effect
Authors: I Pali-Schöll, F. Roth-Walter, G. Hofstetter, S. Hann, S. Ahlers, Moussa S. Afify, T. Wittek, D. Vercelli, Erika von Mutius, E. Jensen-Jarolim
Journal: Allergy (2017)
Abstract 15324: Peri-Procedural Anticoagulation Regimen Influences the Clinical Course of Migraine in Atrial Fibrillation Patients With or Without Pre-Existent Migraine
Authors: Sanghamitra Mohanty, Prasant Mohanty, Neal Rutledge, Luigi Di Biase, Chintan Trivedi, Pasquale Santangeli, Rong Bai, Amin Al-Ahmad, John D Burkhardt, Joseph Gallinghouse, Rodney Horton, Javier Sanchez, Shane Bailey, Patrick Hranitzky, Jason Zagrodzky, Andrea Natale
Journal: Circulation (2014)

Introduction:  Isolated reports on migraine prophylaxis using anti-coagulant warfarin are found in the literature. Effective anticoagulation to reduce the risk of thromboembolism is an important part of management of atrial fibrillation (AF), more so when the patients receive ablative therapy for AF. However, limited data is available on the impact of anticoagulation therapy during the ablation procedure on the trajectory of migraine. Therefore, we evaluated the influence of peri-procedural warfarin regimen on the clinical course of migraine in AF patients with or without migraine history, undergoing catheter ablation.   Methods:  Forty patients with (group 1, 64±8 years, male 78%) and 85 (group 2, 61±10 years, male 73%) without migraine history undergoing AF-ablation were enrolled. Migraine status was evaluated using a standardized questionnaire. Diffusion MRI (dMRI) of brain was performed for all at pre- and 24-hour post-procedure.   Results:  Catheter ablation was performed either with (88, 70%) or without (37, 30%) continuous warfarin treatment. Fifty-four patients (11 and 43 from group 1 and 2 respectively) had subtherapeutic INR on procedure day. At 17 ± 5 months follow-up, among group 1 population, 25 (63%) reported no migraine, 10 (25%) had    Conclusion:  Catheter ablation performed under therapeutic INR was not accompanied with incident migraine or worsening of existing migraine. On the other hand, suboptimal anticoagulation showed association with new migraine, aggravation of pre-existent headache, and post-procedural cerebral infarcts.
Prior Statin Therapy Is Associated With a Decreased Rate of Severe Sepsis
Authors: YanivAlmog, AlexanderShefer, VictorNovack, NimrodMaimon, LeonidBarski, MirunaEizinger, MichaelFriger, LiorZeller, AbrahamDanon
Journal: Circulation (2004)

Background— Statins have anti-inflammatory properties that are independent of their lipid-lowering abilities. We hypothesized that statin therapy before the onset of an acute bacterial infection may have a protective effect against severe sepsis. The aim of this study was to determine whether patients treated with statins develop severe sepsis less frequently. Methods and Results— In this prospective observational cohort study, consecutive patients admitted with presumed or documented acute bacterial infection were enrolled. The primary outcomes were the rate of severe sepsis and intensive care unit (ICU) admission. Of the 361 patients enrolled, 82 (22.7%) were treated with statins before their admission. Both groups had a similar severity of illness on admission. Severe sepsis developed in 19% of patients in the no-statin group and in only 2.4% of the statin group (P<0.001). Statin treatment was associated with a relative risk of developing severe sepsis of 0.13 (95% CI, 0.03 to 0.52) and an absolute ris...
LPS inactivation by a host lipase allows lung epithelial cell sensitization for allergic asthma
Authors: Guojun Qian, Wei Jiang, Benkun Zou, Jintao Feng, Xiaofang Cheng, Jie Gu, Tianqing Chu, Chen Niu, Rui He, Yiwei Chu, Mingfang Lu
Journal: The Journal of Experimental Medicine (2018)

Allergic asthma is a chronic inflammatory disease primarily mediated by Th2 immune mechanisms. Numerous studies have suggested that early life exposure to lipopolysaccharide (LPS) is negatively associated with allergic asthma. One proposed mechanism invokes desensitization of lung epithelial cells by LPS. We report here that acyloxyacyl hydrolase (AOAH), a host lipase that degrades and inactivates LPS, renders mice more susceptible to house dust mite (HDM)-induced allergic asthma. Lung epithelial cells from Aoah-/- mice are refractory to HDM stimulation, decreasing dendritic cell activation and Th2 responses. Antibiotic treatment that diminished commensal LPS-producing bacteria normalized Aoah-/- responses to HDM, while giving LPS intrarectally ameliorated asthma. Aoah-/- mouse feces, plasma, and lungs contained more bioactive LPS than did those of Aoah+/+ mice. By inactivating commensal LPS, AOAH thus prevents desensitization of lung epithelial cells. An enzyme that prevents severe lung inflammation/injury in Gram-negative bacterial pneumonia has the seemingly paradoxical effect of predisposing to a Th2-mediated airway disease.
Strong Association of the HLA-DR/DQ Locus with Childhood Steroid-Sensitive Nephrotic Syndrome in the Japanese Population
Authors: Xiaoyuan Jia, Tomoko Horinouchi, Yuki Hitomi, Akemi Shono, Seik-Soon Khor, Yosuke Omae, Kaname Kojima, Yosuke Kawai, Masao Nagasaki, Yoshitsugu Kaku, Takayuki Okamoto, Yoko Ohwada, Kazuhide Ohta, Yusuke Okuda, Rika Fujimaru, Ken Hatae, Naonori Kumagai, Emi Sawanobori, Hitoshi Nakazato, Yasufumi Ohtsuka, Koichi Nakanishi, Yuko Shima, Ryojiro Tanaka, Akira Ashida, Koichi Kamei, Kenji Ishikura, Kandai Nozu, Katsushi Tokunaga, Kazumoto Iijima
Journal: Journal of the American Society of Nephrology (2018)

Background Nephrotic syndrome is the most common cause of chronic glomerular disease in children. Most of these patients develop steroid-sensitive nephrotic syndrome (SSNS), but the loci conferring susceptibility to childhood SSNS are mainly unknown. Methods We conducted a genome-wide association study (GWAS) in the Japanese population; 224 patients with childhood SSNS and 419 adult healthy controls were genotyped using the Affymetrix Japonica Array in the discovery stage. Imputation for six HLA genes ( HLA-A , -C, -B , -DRB1 , -DQB1 , and -DPB1 ) was conducted on the basis of Japanese-specific references. We performed genotyping for HLA-DRB1 /- DQB1 using a sequence-specific oligonucleotide-probing method on a Luminex platform. Whole-genome imputation was conducted using a phased reference panel of 2049 healthy Japanese individuals. Replication was performed in an independent Japanese sample set including 216 patients and 719 healthy controls. We genotyped candidate single-nucleotide polymorphisms using the DigiTag2 assay. Results The most significant association was detected in the HLA-DR/DQ region and replicated (rs4642516 [minor allele G], combined P allelic =7.84×10 −23 ; odds ratio [OR], 0.33; 95% confidence interval [95% CI], 0.26 to 0.41; rs3134996 [minor allele A], combined P allelic =1.72×10 −25 ; OR, 0.29; 95% CI, 0.23 to 0.37). HLA-DRB1*08:02 ( Pc =1.82×10 −9 ; OR, 2.62; 95% CI, 1.94 to 3.54) and HLA-DQB1*06:04 ( Pc =2.09×10 −12 ; OR, 0.10; 95% CI, 0.05 to 0.21) were considered primary HLA alleles associated with childhood SSNS. HLA-DRB1*08:02-DQB1*03:02 ( Pc =7.01×10 −11 ; OR, 3.60; 95% CI, 2.46 to 5.29) was identified as the most significant genetic susceptibility factor. Conclusions The most significant association with childhood SSNS was detected in the HLA-DR/DQ region. Further HLA allele/haplotype analyses should enhance our understanding of molecular mechanisms underlying SSNS.
Enhanced Basal Activity of a Cardiac Ca2+ Release Channel (Ryanodine Receptor) Mutant Associated With Ventricular Tachycardia and Sudden Death
Authors: DaweiJiang, BailongXiao, LinZhang, S.R. WayneChen
Journal: Circulation Research (2002)

Mutations in the human cardiac Ca2+ release channel (ryanodine receptor, RyR2) gene have recently been shown to cause effort-induced ventricular arrhythmias. However, the consequences of these disease-causing mutations in RyR2 channel function are unknown. In the present study, we characterized the properties of mutation R4496C of mouse RyR2, which is equivalent to a disease-causing human RyR2 mutation R4497C, by heterologous expression of the mutant in HEK293 cells. [3H]ryanodine binding studies revealed that the R4496C mutation resulted in an increase in RyR2 channel activity in particular at low Ca2+ concentrations. This increased basal channel activity remained sensitive to modulation by caffeine, ATP, Mg2+, and ruthenium red. In addition, the R4496C mutation enhanced the sensitivity of RyR2 to activation by Ca2+ and by caffeine. Single-channel analysis showed that single R4496C mutant channels exhibited considerable channel openings at low Ca2+ concentrations. HEK293 cells transfected with mutant R44...
Abstract 267: Assessing Public Perceptions of Cardiopulmonary Resuscitation and Bystander Willingness to Act in Out-of-Hospital Cardiac Arrest: A Qualitative Study
Authors: Lindsay Cheskes, Katie Dainty, Dorcas Beaton, Janet Parsons, Laurie J Morrison
Journal: Circulation (2013)

Background: Bystander cardiopulmonary resuscitation (CPR) improves the odds of survival from out-of-hospital cardiac arrest (OHCA). Despite this, bystander CPR rates are considerably lower in most Canadian communities compared to their international counterparts. Lay public understanding of OHCA and willingness to perform CPR remains poorly understood within a Canadian context. Objectives: 1)To explore public knowledge and perceptions of OHCA and CPR. 2)To identify barriers and enablers to engaging community members in performing CPR. 3)To better understand experiences with CPR education. Methods: 21 semi-structured interviews were conducted with members of the general public. Sampling was purposeful using a maximum variation technique. A range of past CPR training experiences, ethnicities and ages were represented in the sample. Interviews were audio-taped and transcribed verbatim for analysis. An inductive thematic analysis of the data was undertaken and a coding framework developed. Codes were grouped into themes and a concept map was elucidated. Analysis occurred alongside data collection to monitor emerging themes. Results: 5 themes were identified: 1) knowledge 2) barriers 3) lack of social obligation and responsibility 4) psychological factors and implications and 5) education. Participants frequently wrongly conflated the symptoms of OHCA and those of heart attack; they also overestimated survival rates from OHCA. Many participants articulated the steps of CPR, yet said they would look to others to help first. Concerns about inadequate knowledge/training, causing harm, being watched by others or doing something wrong/missing a step were expressed. Personal safety and concerns about mouth-to-mouth breathing were common. Altruistic values such as a desire to save another person’s life seem to be the primary motivator to providing help. Participants called for simplified education regarding recognition and basic science of OHCA, AEDs and hands-on CPR practice. Conclusion: This study illuminates important issues surrounding the performance of bystander CPR. This work informed a larger survey to investigate these phenomena at the national level, with a view towards launching new or tailoring existing community interventions.
Change in biomarkers of type-2 inflammation following severe exacerbations of asthma
Authors: Ruth Semprini, Nick Shortt, Stefan Ebmeier, Alex Semprini, Rachel Varughese, Cecile T J Holweg, John G Matthews, James Fingleton, Mark Weatherall, Richard Beasley, Irene Braithwaite
Journal: Thorax (2018)

We investigated the time course of change of type-2 asthma biomarkers after a severe asthma exacerbation. Blood eosinophils were lowest immediately after treatment was initiated (0.07 vs 0.33×109/L, p<0.001) while serum IgE levels were at their highest (339 vs 249 U/L, p<0.001). Fractional exhaled Nitric Oxide levels were lowest 2 weeks after treatment (23 vs 33 ppb, p=0.06) and serum periostin levels were lowest 1 week after treatment (45·9 vs 50·9 ng/mL, p<0.001). A delay of 4-8 weeks following a severe exacerbation is required if these biomarkers are used to guide the ongoing management of patients with asthma. TRIAL REGISTRATION NUMBER: Post-results; The Australia New Zealand Trial Registry, >ACTRN12614000443695.
Abstract 15009: A Novel Role of Coronary Pericytes in Sunitinib Induced Cardiotoxicity
Authors: Vishnu Chintalgattu, Meredith L. Rees, James C. Culver, Aditya Goel, Tilahu Jiffar, Jianhu Zhang, Kenneth Dunner, Shibani Pati, Florio Monica, James A. Bankson, Renata Pasqualini, Wadih Arap, Nathan S. Bryan, Robert R. Langley, Michael E. Kupferman, Mark L Entman, Mary E. Dickinson, Aarif Y. Khakoo
Journal: Circulation (2012)

Introduction:  Sunitinib malate (SM), an anti-cancer receptor tyrosine kinase inhibitor, causes cardiac dysfunction in a significant number of cancer patients (up to 20%) through a poorly understood mechanism. Using cardiac specific PDGFRβ KO mice we previously reported that PDGFRβ, the main target of SM, plays a crucial role in coronary microvascular and cardiac dysfunction.   We hypothesized  that treatment with SM and CP673451 (CP), another small molecule PDGFR inhibitor, would phenocopy PDGFRβ KO mice with respect to coronary microvascular and cardiac dysfunction. We also tested if co-administration of thalidomide (TM), a reported vascular maturing agent (by inducing microvascular pericyte (PC) proliferation), was cardio-protective in SM induced cardiotoxicity.   Methods:  Mice were divided into 6 groups for the following treatments: Vehicle Control (Ctl), SM (40mg/kg/day), SM+TM, (75mg/kg/alternate days), CP (40mg/kg/day), Ctl-transverse aortic constriction (Ctl-TAC), and SM-TAC for 14-21 days. MRI and Ultrasound were used to measure left ventricular ejection fraction (LVEF) and coronary flow reserve (CFR), respectively. NG2 and CD31 were used as markers for immunohistochemical assessment of coronary PC and endothelial cells, respectively.   Results:  Mice treated with SM display significant loss of coronary microvascular PC (NG2/CD31; SM 27%, Ctl 100%; p in vitro  PC death in a PDGFRβ dependent fashion.   Conclusion:  Our findings suggest that the loss of coronary pericytes may be the primary cause of SM induced cardiotoxicity. Our data also suggests that treatment with TM (or other vascular maturing agents) may be a clinical approach for preventing cardiotoxicity due to SM and other anti-cancer agents targeting PDGFR.
A Novel Inhibitor Targets Both Wnt Signaling and ATM/p53 in Colorectal Cancer
Authors: Jiongjia Cheng, Mary Dwyer, Karl J. Okolotowicz, Mark Mercola, John R. Cashman
Journal: Cancer Research (2018)

For 2017, the estimated lifetime risk of developing colorectal cancer was 1 in 22. Even though preventative colonoscopy screening and standard-of-care surgery, radiation, and chemotherapy have decreased the death rate from colorectal cancer, new therapies are needed for metastatic colorectal cancer. Here, we developed a novel small molecule, compound 2, that inhibited proliferation and viability of human colorectal cancer cells (HCT-116, DLD-1, SW480, and 10.1). Compound 2 inhibited cell migration, invasion, and epithelial-mesenchymal transition processes and potently increased cell apoptosis in human colorectal cancer cells. Compound 2 also modulated mitotic stress signaling, leading to both inhibition of Wnt responsiveness and stabilization and activation of p53 to cause cell-cycle arrest. In mouse xenografts, treatment with compound 2 (20 mg/kg/day, i.p.) induced cell death and inhibited tumor growth more than four-fold compared with vehicle at day 34. Neither acute cytotoxicity nor toxicity in animals (up to 1,000 mg/kg, i.p.) were observed for compound 2 To our knowledge, compound 2 is the first reported potent small molecule that inhibits Wnt/β-catenin signaling, activates p53 signaling regardless of p53 mutation status, and binds microtubules without detectable toxicity. Thus, compound 2 offers a novel mechanism of action and a new strategy to treat colorectal cancer.Significance: These findings identify a potent small molecule that may be therapeutically useful for colon cancer that works by inhibiting Wnt/β-catenin signaling, activating p53, and binding microtubules without detectable toxicity. Cancer Res; 78(17); 5072-83. ©2018 AACR.
The secreted glycolytic enzyme GPI/AMF stimulates glioblastoma cell migration and invasion in an autocrine fashion but can have anti-proliferative effects
Authors: Annegret Kathagen-Buhmann, Cecile L Maire, Jonathan Weller, Alexander Schulte, Jakob Matschke, Mareike Holz, Keith L Ligon, Markus Glatzel, Manfred Westphal, Katrin Lamszus
Journal: Neuro-Oncology (2018)

Aerobic glycolysis confers several advantages to tumor cells, including shunting of metabolites into anabolic pathways. In glioblastoma cells, hypoxia induces a flux shift from the pentose phosphate pathway toward glycolysis and a switch from proliferation to migration. The mechanistic link between glycolysis and migration is poorly understood. Since glucose-6-phosphate isomerase (GPI) is identical to the secreted cytokine autocrine motility factor (AMF), we investigated whether GPI/AMF regulates glioblastoma cell invasion.The expression and hypoxic regulation of GPI/AMF and its receptor AMFR were analyzed in glioblastoma tissue and cell lines. Functional effects were studied in vitro and in xenograft models.High GPI/AMF expression in glioblastomas was found to be associated with a worse patient prognosis, and levels were highest in hypoxic pseudopalisades. Hypoxia upregulated both GPI/AMF and AMFR expression as well as GPI/AMF secretion in vitro. GPI/AMF stimulated cell migration in an autocrine fashion, and GPI/AMF expression was upregulated in migratory cells but reduced in rapidly proliferating cells. Knockdown or inhibition of GPI/AMF reduced glioblastoma cell migration but in part stimulated proliferation. In a highly invasive orthotopic glioblastoma model, GPI/AMF knockdown reduced tumor cell invasion but did not prolong survival. In a highly proliferative model, knockdown tumors were even larger and more proliferative than controls; however, perivascular invasion, provoked by simultaneous bevacizumab treatment, was reduced.GPI/AMF is a potent motogen for glioblastoma cells, explaining in part the association between glycolysis and migration. Targeting GPI/AMF is, however, problematic, since beneficial anti-invasive effects may be outweighed by unintended mitogenic effects.1.Increased glycolysis is linked with increased cell migration and invasion in glioblastoma cells. 2.The glycolysis enzyme GPI/AMF may serve as a target for antimetabolic and anti-invasive therapy. 3.Despite reducing tumor invasion, GPI/AMF targeting may have unwanted growth stimulatory effects.
Letter by Morel et al Regarding Article, “Ischemic Postconditioning During Primary Percutaneous Coronary Intervention: The Effects of Postconditioning on Myocardial Reperfusion in Patients With ST-Segment Elevation Myocardial Infarction (POST) Randomized Trial”
Authors: OlivierMorel, MalakAbbas, ValérieSchini-Kerth
Journal: Circulation (2014)
Long-Term Active Surveillance of Screening Detected Subsolid Nodules is a Safe Strategy to Reduce Overtreatment
Authors: Mario Silva, Mathias Prokop, Colin Jacobs, Giovanni Capretti, Nicola Sverzellati, Francesco Ciompi, Bram van Ginneken, Cornelia M Schaefer-Prokop, Carlotta Galeone, Alfonso Marchianò, Ugo Pastorino
Journal: Journal of Thoracic Oncology (2018)