tbuckley/cabot-search huggingface dataset:
The CICERO (Collaboration In COPD ExaceRbatiOns) Clinical Research Collaboration
Authors: Wim Janssens, Mona Bafadhel
Journal: European Respiratory Journal (2020)

Marcus Tullius Cicero was a famous Roman (b. 106 BC) with enterprise in politics, philosophy and oration. Cicero was recognised as a forefather of modernising Latin and Latin prose and for providing the building blocks of many European languages. His most famous of works De Officis was the second book to be printed in Europe after the Gutenberg Bible (c1455), establishing his relevance to both the European and global community. One of Cicero's most famous quotes is "Quousque tandem abutere, patientia nostra" said to Lucius Sergius Catilina (b. 108 BC) upon exposure of the plot to overthrow Rome (c. 63 BC). " When, do you mean to stop abusing our patience", the translation of Cicero's most famous quote, is highly relevant when pointing to the necessity and urgency of this new Clinical Research Collaboration (CRC). CICERO is a new Clinical Research Collaboration (CRC), studying severe exacerbations of COPD <http://bit.ly/30K2BDi> This article was written on behalf of the CICERO Clinical Research Collaboration members. Founding members: Pierre Regis-Burgel, France; Marco Contoli, Italy; Lowie Van Fleteren, Sweden; Arturo Huerta Garcia, Spain; Frits Franssen, The Netherlands; Neil Greening, UK; Timm Greulich, Germany; Jennifer Quint, UK; Henrik Watz, Germany. Young investigators: Sanjay Ramakrishnan, Australia; Iwein Gyselinck, Belgium; Andreas Halner, UK; Kristina Vermeersch, Belgium. Advisory panel: Richard Albert, USA; Christine Jenkins, Australia; Claus Vogelmeier, Germany. Patient and European Lung Foundation representatives: Philip Collis; Hilma Bolsman; Courtney Coleman. Supporting industry partners: AstraZeneca; GlaxoSmithKline; Roche.
Abstract P301: Differences in Stress Related Behavior According to Age of Immigration: Insight From the Africans in America Study
Authors: Thomas Hormenu, Arsene F Hobabagabo, Elyssa Shoup, Christopher W Dubose, Anne E Sumner
Journal: Circulation (2020)

Background: Adjusting to the stress of life in the United States is associated with unhealthy assimilation behaviors, such as cigarette smoking and alcohol consumption. Allostatic load score (ALS) is a measure of the accumulative effect of stress due to overactivation of the hypothalamic-pituitary-adrenal (HPA) and sympathetic adrenal medullary (SAM) axes. It is unknown if stress related behaviors vary according to whether immigration occurred as a child (&lt;18y) or as an adult (≥18y). Objective: Our goal was to measure stress by ALS in 382 African-born blacks living in the Washington, DC metropolitan area (age 39±10y, range 20 to 65y) and compare social and behavioral factors in Africans who migrated to the United States as children versus as adults. Methods: ALS was calculated using 10 biomarkers from the 3 physiological systems affected by the HPA and SAM axes: cardiovascular (systolic BP, diastolic BP, pulse, cholesterol, HDL, homocysteine), metabolic (BMI, A1C, albumin) and inflammatory (hsCRP). One point was assigned if a variable was determined to be in the high-risk range and 0 if not. High-risk was defined by being in the highest quartile for the population distribution of each variable, except for albumin and HDL, which required the lowest quartile. Results: Of the 382 enrollees, 18% (68/382) came to the United States as children and 82% (314/382) were adults. Compared to adulthood immigrants, childhood immigrants were younger (31±9 vs. 41±10y, P &lt;0.001) and had been in the United States longer (22±9 vs.11±10y, P &lt;0.001). After adjusting for age, ALS was similar in the child and adult immigrants (2.6±0.02 vs.2.6±0.01, P =0.84). Alcohol intake was higher in immigrants who came as children than immigrants who came as adults (40% vs. 25%, P =0.02). Cigarette smoking, sedentary behavior and number of meals outside of the home all tended to be higher in the childhood immigrants ( P &lt;0.2). In addition, childhood immigrants were more likely to self-identify as African-Americans than Africans (16% vs. 7%, P =0.05). Conclusion: Independent of whether Africans came to the United States as children or adults, degree of stress as measured by ALS is similar. However, Africans who arrived as children were more likely to develop unhealthy assimilation behaviors. Whether these behaviors are due to longer duration of stay in the United States or a generational difference remains to be determined.
Abstract P3-08-39: Pathological complete response following neoadjuvant chemotherapy in operable breast cancer patients: Is obesity a predictive factor?
Authors: Haiyun Wang, Shijia Zhang, Douglas Yee, Heather Beckwith, David Potter, Anne Blaes
Journal: Cancer Research (2020)

Abstract Background: Overweight and obesity are associated with greater disease-specific mortality and overall mortality in cancer patients. Neoadjuvant chemotherapy offers a unique setting to assess breast cancer chemosensitivity in vivo, and thus can help us understand why obesity is associated with poor prognosis in breast cancer patients. The effect of increased Body mass index (BMI) in breast cancer patients undergoing neoadjuvant chemotherapy remains controversial. Purpose: To review and analyze the association between BMI and pathological complete response (pCR) rate for operable breast cancer after neoadjuvant chemotherapy (NACT). Data sources: Pub Med and Cochrane Database to December 31, 2018 Study selection: We included observational studies and randomized trials that evaluated association of BMI with pCR in operable breast cancer patients that underwent NACT. Data extraction and analysis: Two authors independently extracted data and rated study quality; discrepancies were resolved through consensus. Results: We identified 13 studies including a total of 14179 women with operable breast cancer who underwent NACT. Among them, two studies were pooled analysis of prospective clinical trials (10622 patients); the rest were retrospective case control studies (3557 patients). The influence of categorical BMI on pCR after NACT was analyzed. All studies provided data with BMI divided into two subgroups (BMI &amp;lt;25 vs BMI ≥25). Pooled analyses demonstrated overweight/obese women were less likely to achieve pCR after NACT when compared with women in the under-/normal weight group, OR=0.77 (95% CI: 0.71, 0.84). 10 studies provided data with BMI divided into three groups (BMI &amp;lt;25, 25 ≤BMI&amp;lt; 30, BMI ≥30). Pooled analyses showed compared to under-/normal weight group, both overweight (OR= 0.81 95% CI: 0.72, 0.89) and obese (OR = 0.62 95% CI: 0.54, 0.69) groups were less likely to achieve pCR to NACT. We were not able to perform pooled analysis of association between BMI and pCR in subtypes of breast cancer based on hormone receptor and HER-2 status; as only two studies provided these data and breast cancer subtypes were defined differently. There was moderate heterogeneity in between these studies. Conclusion: Overweight and obese breast cancer patients had lower pCR rates compared to those with under-/normal weight. Further prospective studies may help to confirm this finding and to clarify underlying mechanisms. Citation Format: Haiyun Wang, Shijia Zhang, Douglas Yee, Heather Beckwith, David Potter, Anne Blaes. Pathological complete response following neoadjuvant chemotherapy in operable breast cancer patients: Is obesity a predictive factor? [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-39.
Nasal Deformity in Granulomatosis with Polyangiitis
Authors: Federica Bello, Filippo Fagni
Journal: New England Journal of Medicine (2020)

A 42-year-old man presented with cough and shortness of breath. Physical examination showed a saddle-nose deformity, and CT showed destruction of the structural bones of the midface that had resulted in the formation of a large nasal cavity. A diagnosis of granulomatosis with polyangiitis was made.
METTL14 suppresses proliferation and metastasis of colorectal cancer by down-regulating oncogenic long non-coding RNA XIST
Authors: Xiao Yang, Sen Zhang, Changyu He, Pei Xue, Luyang Zhang, Zirui He, Lu Zang, Bo Feng, Jing Sun, Minhua Zheng
Journal: Molecular Cancer (2020)

Abstract Background N6-methyladenosine (m6A) is the most prevalent RNA epigenetic regulation in eukaryotic cells. However, understanding of m6A in colorectal cancer (CRC) is very limited. We designed this study to investigate the role of m6A in CRC. Methods Expression level of METTL14 was extracted from public database and tissue array to investigate the clinical relevance of METTL14 in CRC. Next, gain/loss of function experiment was used to define the role of METTL14 in the progression of CRC. Moreover, transcriptomic sequencing (RNA-seq) was applied to screen the potential targets of METTL14. The specific binding between METTL14 and presumed target was verified by RNA pull-down and RNA immunoprecipitation (RIP) assay. Furthermore, rescue experiment and methylated RNA immunoprecipitation (Me-RIP) were performed to uncover the mechanism. Results Clinically, loss of METTL14 correlated with unfavorable prognosis of CRC patients. Functionally, knockdown of METTL14 drastically enhanced proliferative and invasive ability of CRC cells in vitro and promoted tumorigenicity and metastasis in vivo. Mechanically, RNA-seq and Me-RIP identified lncRNA XIST as the downstream target of METTL14. Knockdown of METTL14 substantially abolished m6A level of XIST and augmented XIST expression. Moreover, we found that m6A-methylated XIST was recognized by YTHDF2, a m6A reader protein, to mediate the degradation of XIST . Consistently, XIST expression negatively correlated with METTL14 and YTHDF2 in CRC tissues. Conclusion Our findings highlight the function and prognostic value of METTL14 in CRC and extend the understanding of the importance of RNA epigenetics in cancer biology.
A phase II study of XL999 in patients (pts) with NSCLC
Authors: R. J. March, B. Mirtsching, S. Modi, M. Wertheim
Journal: Journal of Clinical Oncology (2007)

18112 Background: XL999 is a potent spectrum-selective inhibitor of receptor tyrosine kinases including VEGFR2/KDR, FGFR1/3, PDGFR-β, FLT3, RET, KIT, &amp; SRC. A Ph 1 clinical study in pts w/advanced malignancies evaluating weight-based (0.2 - 6.4 mg/kg) &amp; fixed dose (200 mg &amp; 160 mg) XL999 administered by 4hr IV infusion on a wkly or every other wk schedule has shown preliminary evidence of anti- tumor activity (3 PRs &amp; 10 pts w/SD lasting 3–26 + months). The safety profile was characterized by hypertension &amp; cardiovascular changes including EKG, LVEF decrease &amp;/or cardiac enzyme elevation following 1 st dose administration. DLTs were cardiac failure &amp; transaminase elevation. A dose of 2.4 mg/kg/wk was selected for phase II evaluation. Methods: The 1 objectives of this phase II study are to determine the RR &amp; to further evaluate the safety &amp; tolerability of XL999. Adult pts w/NSCLC (stage IIIB with malignant effusion, stage IV, or recurrent) &amp; previously treated with no more than 2 prior systemic cytotoxic chemotherapy regimens, including a platinum-or taxane-containing regimen, &amp; no more than one prior target agent targeting VEGF or EGFR, are eligible. Additional inclusion criteria include ECOG PS 0–1 &amp; absence of known brain metastases. Pts with LVEF&lt;50% or below lower limits of normal or with significant cardiovascular abnormalities are excluded. Tumor response is assessed every 8 wks by RECIST criteria. XL999 is administered wkly at 2.4 mg/kg as a 4hr IV infusion. Results: Nine pts received XL999. Three pts remain on study drug. One pt has a confirmed PR with complete resolution of a 2cm lung nodule. Another has a total reduction of 23% in multiple hepatic lesions (by RECIST). A third pt continues with SD for 3.5 months. Six pts with PD are discontinued. AEs reported in at least 2 pts were grade 1 diarrhea, fatigue, anorexia, &amp; dizziness. Grade 3 AEs included 1 report each of N/V. No Grade 4 or 5 AEs or serious cardiac AEs have been reported. Conclusions: Wkly IV dose at 2.4 mg/kg appears generally well-tolerated &amp; shows preliminary evidence of anti-tumor activity in advanced NSCLC pts refractory to multiple prior anti-cancer therapies. No significant financial relationships to disclose.
A phase II trial of oxaliplatin and docetaxel in patients with androgen independent prostate cancer (AIPC) who have progressed to two prior regimens of chemotherapy
Authors: T. Feinstein, L. J. Appleman, D. M. Friedland, S. A. Jacobs, W. A. Ferri, M. F. Earle, K. D. Hyoung, H. Strausser, S. Corgnati, G. S. Chatta
Journal: Journal of Clinical Oncology (2007)

15545 Background: Single agent docetaxel has demonstrated survival benefit in AIPC. In a phase I study of single agent oxaliplatin at our institution, two patients with AIPC experienced a substantial and durable reduction in PSA. Thus, we hypothesised that a combination of oxaliplatin and docetaxel maybe beneficial in AIPC. Methods: This single arm phase II trial in patients with previously treated (0–2 regimens) and progressive AIPC commenced in June 2005, with the objectives of evaluating PSA response rates, progression free survival, and the toxicity (tolerance/safety) of the regimen. In patients with soft tissue disease, measurable responses were assessed by RECIST criteria. Using Simon stage II design, a total of 37 patients with AIPC will be accrued. No prior treatment with platinum was allowed. Treatment consisted of oxaliplatin (110 mg/m 2 ) and docetaxel (60 mg/m 2 ), administered intravenously every 21 days for a maximum of 6 cycles. Results: 27 men have been enrolled to date: median age 66 yrs (56–84). 21 of 27 men have completed at least two cycles of the above regimen, and are evaluable. Prior therapies included antiandrogens (100%); ketaconazole (14%); docetaxel alone or in combination (27%); anthracyclines (27%); and vaccine (5%). Median PSA at baseline was 88 ng/ml (range 2.2–3559.4). 62% of patients received all six cycles. PSA declines of ≥50% were noted in 11 of 21 patients: 3 of 8 responders being chemo-naïve; and 8 of 13 with prior chemotherapy exposure. In addition, 4 of 11 patients with measurable disease at baseline, had a partial response. Treatment was well tolerated with no treatment-related deaths. The most significant grade 3/4 adverse event (AE) was neutropenia (43%). Grade 2 or less fatigue (66%), neuropathy (53%) diarrhea (47%), nausea (41%), anorexia (29%), thrombocytopenia (12%) and anemia (6%). Conclusions: The combination of oxaliplatin and docetaxel has promising activity in both chemo-naïve and previously treated AIPC. This 2-stage study will accrue a total of 37 patients. Final analysis will include time to progression, duration of response, and median survival. [Table: see text]
Abstract 39: Development of a Hypoglycemia Prediction Model for Veterans With Diabetes Using Supervised Machine Learning Applied to Electronic Health Record Data
Authors: Sridharan Raghavan, Wenhui Liu, Anna Baron, David Saxon, Meg Plomondon, Michael Ho, Liron Caplan
Journal: Circulation (2020)

Accurate assessment of hypoglycemia risk is critical for treatment selection in individuals with diabetes and cardiovascular disease (CVD) - patients for whom hypoglycemia is particularly harmful. We developed and validated a hypoglycemia prediction model in diabetes patients with and without CVD using data routinely available in electronic health records (EHR) and compared performance to a published prediction model. We studied 128,893 US Veterans with diabetes and angiographic assessment of CVD from 2005 to 2018. We used a random 2/3 of the sample for model development and the remaining 1/3 for validation. The primary outcome was severe hypoglycemia based on a previously validated algorithm that uses diagnosis codes and glucose measurements. We evaluated 33 potential predictors, including demographics, diabetes-related variables, comorbidities, and CVD risk factors. We sequentially used two machine learning algorithms for model development. First, we used multivariable adaptive regression splines, which can accommodate interactions and non-linearities for continuous variables, to select predictors. Second, we used adaptive elastic net, which can accommodate time-to-event outcomes, to fit a model with the selected variables. We tested model discrimination using the area under the ROC curve (AUC) and calibration by plotting predicted versus observed event rates in the independent validation cohort. The best-fitting prediction model included 18 predictors; a history of hypoglycemia was the strongest predictor (Table). In external validation, AUC was 0.729 for 2-year events, and the slope of the calibration curve was 1.05, exceeding performance of the published model in this patient population for both discrimination and calibration (Table). Conclusions: Applying supervised machine learning to EHR data may provide an efficient approach to tailoring prediction of preventable clinical outcomes, e.g., hypoglycemia, for high risk patients receiving care in an integrated healthcare system.
Summit on drug deaths ends with no agreement
Authors: Bryan Christie
Journal: BMJ (2020)

Two days of talks in Glasgow have shown that UK politicians are as far apart as ever in developing a shared approach to tackling record numbers of drug related deaths.

Activists campaigning for better services for drug users are angry that a UK summit ended with no action, only promises of further talks. “This isn’t a game. People’s lives are at stake,” said Annemarie Ward of the charity Faces and Voices of Recovery UK. “We need to see action, not just a talking shop that makes politicians feel better about themselves.”

Drug related deaths are at an all time high in …
Abstract P208: Dietary Acculturation Impacts the Gut Microbiome in a Diverse U.S. Population
Authors: Brandilyn Peters, Stella Yi, Jeannette Beasley, Emilia Cobbs, Hee Sun Choi, Dia Beggs, Richard B Hayes, Jiyoung Ahn
Journal: Circulation (2020)

Introduction: Risk of chronic diseases such as obesity, diabetes, and cardiovascular disease are known to increase with duration and generations of U.S. residence, though it remains unclear how living in the U.S. negatively impacts immigrant health. Hypothesis: We hypothesize that dietary acculturation, or shifting of dietary patterns towards a native U.S. pattern, contributes to the disease risk transition in immigrants, via modulation of the gut microbiome. Methods: We characterized disparities in the gut microbiome between racially/ethnically diverse U.S. immigrant and U.S.-born groups, and determined the impact of dietary acculturation on the microbiome. Stool samples were collected from 863 U.S. residents, including U.S.-born (315 White, 93 Black, 40 Hispanic) and foreign-born (105 Hispanic, 264 Korean) groups. We determined dietary acculturation from dissimilarities based on food frequency questionnaires ( Figure 1a ), and used 16S rRNA gene sequencing to characterize the microbiome. Results: Gut microbiome composition differed across study groups, with the largest difference between foreign-born Koreans and U.S.-born Whites ( Figure 1b ). Bacteroides plebeius , a seaweed-degrading bacterium, was strongly enriched in foreign-born Koreans, while Prevotella copri and Bifidobacterium adolescentis were strongly enriched in foreign-born Koreans and Hispanics, compared with U.S.-born Whites. Dietary acculturation in foreign-born participants was associated with specific sub-operational taxonomic units (s-OTUs), resembling abundance in U.S.-born Whites ( Figure 1c-d ); e.g., a Bacteroides plebeius s-OTU was depleted in highly diet-acculturated Koreans. Conclusions: Dietary acculturation may result in loss of native species in immigrants. Longitudinal research is necessary to determine the role that acculturation-related microbiome changes may play in immigrant and racial/ethnic health disparities.
Abstract 19606: Clinical Significance of Re-worsening Left Ventricular Function in Patients With Dilated Cardiomyopathy
Authors: Takeru Nabeta, Takayuki Inomata, Mayu Yazaki, Yuichiro Iida, Yuki Ikeda, Shunsuke Ishii, Takashi Naruke, Junya Ako
Journal: Circulation (2017)

Background: Improved left ventricular (LV) function after pharmacotherapy is known to be associated with favorable prognosis in patients with dilated cardiomyopathy (DCM). However, the clinical sig...
Abstract 245: Role of the Resuscitation Champion on Survival Outcomes for In-Hospital Cardiac Arrest
Authors: Jesse Chan, Brahmajee K Nallamothu, Yuanyuan Tang, Paul Chan
Journal: Circulation (2019)

Background: Hospitals vary markedly in survival rates for their patients with in-hospital cardiac arrest (IHCA). Although many sites have resuscitation champions, whether a resuscitation champion’s clinical background and intensity of engagement distinguishes sites with higher cardiac arrest survival rates remains unknown. Methods: We conducted a nationwide survey of adult hospitals participating in GWTG-Resuscitation to elicit detailed information on resuscitation practices, including of their resuscitation champion. Risk-standardized survival rates for IHCA for 2016-2017 were calculated for each hospital, and these were then used to categorize hospitals into quintiles of performance. The association between a resuscitation champion’s clinical background and intensity of engagement (categorized as very active non-physician champion, very active physician champion, and all others) and quintiles of survival was evaluated using multivariable hierarchical proportional odds logistic regression models. Results: Overall, 200 of 218 eligible adult hospitals (91.7%) completed the study survey and 190 facilities with &gt; 10 cases comprised the final study cohort. Risk-standardized survival rates after IHCA varied substantially (median: 24.7%; range: 9.2% to 37.5%). One-third (63/190 [33.2%]) of hospitals had a very active non-physician champion, 29 (15.3%) had a very active physician champion, and the remaining 98 (51.2%) had a resuscitation champion not perceived to be very active or had no champion. Compared to sites with very active non-physician champions, those with a very active physician champion had 5-fold higher odds (adjusted OR, 5.15 [95% CI: 2.13-12.5]) of being in a higher survival quintile category, whereas there was no difference in survival outcomes between sites with less active or no resuscitation champions and very active non-physician champions (adjusted OR, 0.94 [95% CI: 0.52-1.77]) . Conclusions: Although most hospitals have resuscitation champions, the background and engagement level of a resuscitation champion is a critical factor in a hospital’s survival outcomes for IHCA. Hospitals with the highest survival rates for IHCA are more likely to have very active physician resuscitation champions.