tbuckley/cabot-search huggingface dataset:
Alcohol Use Disorder and Risk of Suicide in a Swedish Population-Based Cohort
Authors: Alexis C. Edwards, Henrik Ohlsson, Jan Sundquist, Kristina Sundquist, Kenneth S. Kendler
Journal: American Journal of Psychiatry (2020)

The authors examined the association between alcohol use disorder (AUD) and risk of suicide, before and after accounting for psychiatric comorbidity, and assessed the extent to which the observed association is due to a potentially causal mechanism or genetic and familial environmental confounding factors that increase risk for both.Longitudinal population-wide Swedish medical, criminal, and pharmacy registries were used to evaluate the risk of death by suicide as a function of AUD history. Analyses employed prospective cohort and co-relative designs, including data on 2,229,880 native Swedes born between 1950 and 1970 and observed from age 15 until 2012.The lifetime rate of suicide during the observation period was 3.54% for women and 3.94% for men with AUD, compared with 0.29% and 0.76% of women and men, respectively, without AUD. In adjusted analyses, AUD remained robustly associated with suicide: hazard ratios across observation periods ranged from 2.61 to 128.0 among women and from 2.44 to 28.0 among men. Co-relative analyses indicated that familial confounding accounted for some, but not all, of the observed association. A substantial and potentially causal relationship remained after accounting for a history of other psychiatric diagnoses.AUD is a potent risk factor for suicide, with a substantial association persisting after accounting for confounding factors. These findings underscore the impact of AUD on suicide risk, even in the context of other mental illness, and implicate the time frame shortly after a medical or criminal AUD registration as critical for efforts to reduce alcohol-related suicide.
FLCN-regulated miRNAs suppressed reparative response in cells and pulmonary lesions of Birt-Hogg-Dubé syndrome
Authors: Haiyan Min, Dehua Ma, Wei Zou, Yongzheng Wu, Yibing Ding, Chengchu Zhu, Anqi Lin, Shiyu Song, Qiao Liang, Baofu Chen, Bin Zhang, Yueming Wan, Minhua Ye, Yanqing Pan, Yanting Wen, long Yi, Qian Gao
Journal: Thorax (2020)

Background Birt-Hogg-Dubé Syndrome (BHDS) characterised by skin fibrofolliculomas, kidney tumour and pulmonary cysts/pneumothorax is caused by folliculin (FLCN) germline mutations. The pathology of both neoplasia and focused tissue loss of BHDS strongly features tissue-specific behaviour of the gene. Isolated cysts/pneumothorax is the most frequent atypical presentation of BHDS and often misdiagnosed as primary spontaneous pneumothorax (PSP). Deferential diagnosis of BHDS with isolated pulmonary presentation (PSP-BHD) from PSP is essential in lifelong surveillance for developing renal cell carcinoma. Methods The expression profiles of microRNAs (miRNAs) in cystic lesions of PSP-BHD and PSP were determined via microarray. The selected upregulated miRNAs were further confirmed in the plasma of an expanded cohort of PSP-BHD patients by reverse transcription quantitative PCR (RT-qPCR). Their diagnostic accuracy was evaluated. Moreover, the cellular functions and targeted signalling pathways of FLCN-regulated miRNAs were assessed in various cell lines and in the lesion tissue contexts. Results Cystic lesions of PSP-BHD and PSP showed different miRNAs profiles with a significant upregulation of miR-424–5p and let-7d-5p in PSP-BHD. The combination of the two effectively predicted BHDS patients. In vitro studies revealed a suppressive effect of FLCN on miR-424–5p and let-7d-5p expressions specifically in lung epithelial cells. The ectopic miRNAs triggered epithelial apoptosis and epithelial transition of mesenchymal cells and suppressed the reparative responses in cells and tissues with FLCN deficiency. Conclusion The upregulation of miR-424–5p and let-7d-5p by FLCN deficiency occurred in epithelial cells and marked the PSP-BHD condition, which contributed to a focused degenerative pathology in the lung of PSP-BHD patients.
A randomized phase III multicenter trial of neoadjuvant docetaxel plus cisplatin and 5-fluorouracil (TPF) versus neoadjuvant PF in patients with locally advanced unresectable squamous cell carcinoma of the head and neck (SCCHN). Final analysis of EORTC 24971
Authors: E. Remenar, C. Van Herpen, J. Germa Lluch, S. Stewart, T. Gorlia, M. Degardin, J. Bernier, C. Spirlet, J. B. Vermorken
Journal: Journal of Clinical Oncology (2006)

5516 Background: So far, the Wayne State regimen combining 100 mg/m 2 cisplatin on day 1 and 1000 mg/m 2 /d continuous infusion 5-fluorouracil over 5 days (PF), is the gold standard in advanced SCCHN. Improvement of PF induction chemotherapy by adding a taxane has been suggested from phase II studies and 2 randomized phase III trials. We now report the final analysis of EORTC 24971. Methods: Eligible were patients (pts) with unresectable stage III/IV SCCHN (no distant metastases), 18 to 70 yrs of age, PS≤1, and adequate hematologic, renal and hepatic function. Pts were stratified by primary disease site (oral cavity, oropharynx, hypopharynx, larynx) and treatment center and randomized to PF (as above) or TPF (T 75 mg/m 2 /1h, P 75 mg/m 2 /1h, both d1, F 750 mg/m 2 /d, d1–5) q 3 wks, for 4 cycles unless progression (PD) or unacceptable toxicity, or refusal. Thereafter (interval 4–7 wks), all pts not in PD received radiotherapy (RT: conventional [66–70 Gy], accelerated [max. 70 Gy] / hyperfractionated [max. 74 Gy]). Surgery was allowed before RT (neck) or 3 months after RT (primary, neck). Primary endpoint was progression-free survival (PFS), and 348 pts and 260 events were needed to detect a 50% increase in median PFS (10 vs 15 mo) with 85% power. Results: Between April 1999 and March 2002, 358 pts were accrued (181 PF, 177 TPF). At a median follow-up (FUP) of 32 mo, PFS was significantly improved with TPF (HR 0.72, p = 0.0071; median 8.2 vs 11.0 mo). A 51 mo median FUP showed an overall survival (OS) benefit with TPF (HR 0.71, p = 0.0052; median 14.2 vs 18.6 mo). Estimated 3-yr survival rates are 23.9% (95% CI: 17.9%;30.5%) for PF and 36.5% (29.3%;43.6%) for TPF. Response rate also favored TPF (53.6% vs 67.8%, p = 0.006). There was more severe (G3+4) leucopenia (41.6% vs 22.9%) and neutropenia (76.9% vs 52.5%) with TPF, and more severe thrombocytopenia with PF (17.9% vs 5.2%). Severe alopecia occured more with TPF (55.5% vs 11.7%); hearing loss (2.8% vs 0%) and toxic death (7.8% vs 3.7%) more with PF. Conclusions: TPF (→ RT) is superior to PF (→ RT) for PFS, OS (including long-term), response rate, and is better tolerated. [Table: see text]
DIAGNOSTIC IMPACT AND PROGNOSTIC VALUE OF CARDIAC MRI IN PATIENTS WITH VENTRICULAR ARRHYTHMIAS
Authors: Yin Ge, Panagiotis Antiochos, Iqra Qamar, Ayako Seno, Michael L. Steigner, Ayaz Aghayev, Ron Blankstein, William Stevenson, Michael Jerosch-Herold, Raymond Y. Kwong
Journal: Journal of the American College of Cardiology (2020)
Causes of discontinuation of intraperitoneal chemotherapy in patients with ovarian cancer.
Authors: Mercedes Tamburelli, Gabriela Gatica, Susana Sena, Javier Omar Castillo, Fernanda Roca, Carlos Arturo Bas, Gonzalo Gomez-Abuin
Journal: Journal of Clinical Oncology (2012)

e15570 Background: Intraperitoneal chemotherapy (IP) showed benefit in efficacy in patients with ovarian cancer but with high rates of complications and/or toxicity. We reviewed our experience and the identification of factors for discontinuing treatment. Methods: We conducted a retrospective review of electronic medical records of patients undergoing IP catheter placement at our medical center from May 2006 to December 2012; our institutional protocol for stages II/III ovarian carcinoma after optimal surgical resection is the following: 2 cycles of IV carboplatin/paclitaxel follow by 4 cycles of IP chemotherapy (paclitaxel 135 mg/m 2 day 1 IV, cisplatin 75mg/m 2 day 2 IP, paclitaxel 60mg/m 2 day 8 IP). For statistical analysis, we used Fisher's exact test. Results: Thirty-seven patients underwent IP catheter placement. Median follow-up was 31.2 months. Eight patients did not receive IP chemotherapy: 3 patients for stage I, 2 patients stage IV, 1 patient synchronous breast cancer, one for unusual histology, and 1 patient for partial bowel obstruction. IP chemotherapy was administered to 29 patients. In total, 94 cycles IP chemotherapy were given with a median of 3 cycles per patient. IP chemotherapy was completed as planned in 24 patients (82.7%). The reason for treatment discontinuation: abdominal pain in 2 patients, extravasation in 1 patient, one patient due to peptic stricture, and other for esophageal ulcer. Grade 3-4 toxicity for IP chemotherapy was observed in 20% of patients. Median body mass index (BMI) was 24.3. IP chemotherapy was completed as planned in 94% of patients with BMI&lt;25 and in 64% of patients with BMI&gt; 25, p &lt;0.05. Conclusions: This modified IP chemotherapy regimen is feasible with acceptable toxicity. Most patients completed the scheduled treatment with IP. BMI &gt; 25 was identified as a possible risk factor for discontinuation of treatment.
Abstract 10622: Frailty Evaluation Using Machine Learning Modeling for Preoperative Walking Ability in Cardiac Patients
Authors: Hirotada Masuda, Hidetsugu Asanoi, Shigeru Miyagawa, Kenta Masada, Ai Kawamura, Takuji Kawamura, Koichi Maeda, Satoshi Kainuma, Daisuke Yoshioka, Keiwa Kin, Kazuo Shimamura, Hiroki Hata, Yasushi Yoshikawa, Takayoshi Ueno, Koichi Toda, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2019)

Background: Frailty, a strong predictor of postoperative mortality, has been evaluated using some validated charts. However, the subjective nature of these charts are insufficient for precise frail...
TREATMENT INTENSIFICATION WITH NOVEL ANTIDIABETIC AGENTS INFLUENCES PLATELET REACTIVITY AND FUNCTIONALITY PARAMETERS IN MALE PATIENTS WITH TYPE 2 DIABETES
Authors: Evanthia Bletsa, Gerasimos Siasos, Panagiota K. Stampouloglou, Evangelos Oikonomou, Alexis S. Antonopoulos, Nikolaos Gouliopoulos, Vasiliki Tsigkou, Konstantinos Mourouzis, Marina Zaromytidou, Konstantinos Batzias, Stavroula Paschou, Andromachi Vryonidou, Athanasia Thanopoulou, Nikolaos Tentolouris, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2020)
Multiplexed capture of spatial configuration and temporal dynamics of locus-specific 3D chromatin by biotinylated dCas9
Authors: Xin Liu, Yong Chen, Yuannyu Zhang, Yuxuan Liu, Nan Liu, Giovanni A. Botten, Hui Cao, Stuart H. Orkin, Michael Q. Zhang, Jian Xu
Journal: Genome biology (2020)

Abstract The spatiotemporal control of 3D genome is fundamental for gene regulation, yet it remains challenging to profile high-resolution chromatin structure at cis -regulatory elements (CREs). Using C-terminally biotinylated dCas9, endogenous biotin ligases, and pooled sgRNAs, we describe the dCas9-based CAPTURE method for multiplexed analysis of locus-specific chromatin interactions. The redesigned system allows for quantitative analysis of the spatial configuration of a few to hundreds of enhancers or promoters in a single experiment, enabling comparisons across CREs within and between gene clusters. Multiplexed analyses of the spatiotemporal configuration of erythroid super-enhancers and promoter-centric interactions reveal organizational principles of genome structure and function.
Covid-19: UK budget gives £94 a week statutory sick pay to self-isolators and their carers
Authors: Elisabeth Mahase
Journal: BMJ (2020)

As part of its 2020 budget the UK government will extend statutory sick pay of £94.25 (€108; $121) a week to include people advised to self-isolate because of covid-19 and to those caring for them.

The medical evidence necessary to claim sick pay will also be relaxed in relation to covid-19, meaning that people will not require a GP’s “fit” note. Instead, people will be able to get a notification from NHS 111 when they are advised to self-isolate, which they can use as evidence where necessary. “This notification would meet employers’ need for evidence, whilst taking pressure away from general practices,” the budget plan said.1

The budget …
AN INCREASING BURDEN OF DISEASE OVER THE LAST DECADE: TRENDS IN EMERGENCY DEPARTMENT VISITS AND SUBSEQUENT HOSPITALIZATIONS AMONG PATIENTS WITH VENTRICULAR ASSIST DEVICES IN THE UNITED STATES
Authors: Jonathan Edelson, Jonathan Edwards, Hannah Katcoff, Antara Mondal, Nosheen Reza, Heather Griffis, Danielle Burstein, Matthew J. O'Connor, Joseph Rossano, Edo Birati, Kimberly Lin
Journal: Journal of the American College of Cardiology (2020)
Development of a nomogram to predict for all-cause and cancer-specific mortality in high-risk prostate cancer treated by external beam radiotherapy and androgen deprivation.
Authors: Rahul D. Tendulkar, Michael W. Kattan, Changhong Yu, Chandana A. Reddy, Kevin L. Stephans, Patrick Kupelian, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2013)

e16004 Background: Men receiving high dose external beam radiotherapy (EBRT) and androgen deprivation therapy (ADT) for high risk prostate cancer (HRPC) have other competing causes of mortality, however predictive schema do not account for patient-related co-morbidities. We aim to create nomograms estimating all-cause mortality (ACM) and prostate cancer-specific mortality (PCSM) in this population. Methods: 660 patients with HRPC defined by NCCN guidelines were treated with EBRT ≥74 Gy and ADT from 1996-2009. The probabilities of death from prostate cancer and other causes were estimated by cumulative incidence function. Multivariable Cox proportional hazards regression and competing risks regression analyses were used for modeling ACM and PCSM respectively. Deaths from other causes were treated as competing risks for PCSM. Missing values in the predictors were multiply imputed before conducting multivariable regression analysis. Variables investigated were age, clinical T stage, prostate specific antigen (PSA), Gleason score, race, family history, duration of ADT, body mass index (BMI), Charlson co-morbidity index score, coronary artery disease, and smoking pack-years. The stepdown method was used to make parsimonious models based on the rank of the predictive ability of each variable with respect to each endpoint. The final nomograms were internally validated by assessing the discrimination and calibration with bootstrap resamples. Results: At last follow up, there were 199 deaths. The 10-year cumulative incidence of death from prostate cancer was 14% and from other causes was 26%. The variables that predicted for 10-year ACM included age, PSA, BMI, Charlson score, and smoking pack-years. The ACM nomogram achieved a concordance index of 0.672. The variables that predicted for PCSM included Gleason score, PSA, race, and duration of ADT. The nomogram concordance index for PCSM was 0.673. The calibrations for both ACM and PCSM appear reasonable. Conclusions: We have developed nomograms that predict for ACM and PCSM in men with aggressive prostate cancer and competing risks of death. External validation may be useful.
The efficacy of antiepidermal growth factor receptor monoclonal antibodies for patients with <i>KRAS</i> G13D mutations and chemorefractory metastatic colorectal cancer.
Authors: Kohei Akiyoshi, Yasuhide Yamada, Naoki Takahashi, Yoshitaka Honma, Satoru Iwasa, Ken Kato, Tetsuya Hamaguchi, Yasuhiro Shimada
Journal: Journal of Clinical Oncology (2012)

527 Background: The treatment benefits of epidermal growth factor receptor (EGFR) monoclonal antibodies for patients with KRAS mutations have not been demonstrated. However, some studies have suggested that all KRAS mutations are not equivalent, and that KRAS G13D mutations might have some survival benefit. Methods: We retrospectively analyzed the efficacy and toxicity of treatment with EGFR monoclonal antibody in 8 patients with KRAS G13D mutations and 5-FU/oxaliplatin/irinotecan (CPT) refractory metastatic colorectal cancer compared with 94 KRAS wild type patients at the National Cancer Center Hospital. Results: Eight patients with KRAS G13D mutations were treated with anti-EGFR monoclonal antibodies between July, 2009 and July, 2011. The median age was 66 (42-70); male/female 6/2; PS was 0/1/2, 2/5/1; treatment regimen was cetuximab/ cetuximab+CPT/ panitumumab+CPT, 2/5/1. Response rate (RR) was 12.5% and disease control rate (DCR) was 50.0% with 1 PR, 3 SD, and 4 PD. The PR case treated with cetuximab+CPT showed marked regression of tumor and long duration of treatment (9 months). The progression free survival (PFS) of 2 SD cases was 4.2 and 3.9 months. The other SD case is now on treatment. The median PFS of the 8 patients was 2.1 months (95% confidence interval [CI]: 0.0-5.2). The median overall survival (OS) has not been reached. Grade 3/4 toxicities included 1 hypomagnesemia G4 and 1 rash acneiform G3. Meanwhile, 94 KRAS wild type patients treated with anti EGFR monoclonal antibodies had an RR of 22.3% and DCR was 66.0% with 21 PR, 41 SD, 30 PD, and 2 NE. PFS was 5.6 months (95% CI: 4.9-6.3) and OS was 8.6 months (95% CI: 6.5-10.7). Conclusions: In this analysis, we identified one PR to anti-EGFR monoclonal antibody in a patient with KRAS G13D mutation and chemo-refractory metastatic colorectal cancer. However, we were unable to demonstrate equivalent efficacy in patients with KRAS G13D mutations and KRAS wild type patients. Further studies are needed to evaluate the efficacy and prognosis for this treatment.
Superiority of bi-dimensional measurements compared to RECIST in measuring response of metastatic brain tumors
Authors: M. R. Kilpatrick, N. U. Linn, J. K. Smith, E. P. Winer, E. Bullitt, L. A. Carey, M. G. Ewend
Journal: Journal of Clinical Oncology (2006)

1542 Background: Criteria for measuring response rates of brain metastases are not well established. Unilateral (RECIST), and bilateral (WHO) criteria were developed to approximate tumor volume, which is the gold standard but difficult to measure. We compared WHO and RECIST criteria to volumetrics in patients with metastatic breast cancer lesions in the brain treated with lapatinib. Methods: MRI data from 20 patients enrolled in a prospective phase II study at UNC-Chapel Hill, the Dana-Farber/Harvard Cancer Center, and Georgetown were retrospectively analyzed. Post-gadolinium MRI images were analyzed at baseline and at 2 month intervals over a 7 month period. 196 lesions were analyzed for tumor size using one-dimensional (single greatest diameter), bidimensional (product of 2 longest diameters in perpendicular dimensions), and volume (calculated with an institutionally-derived software program) measurements. Tumor response was classified according to WHO and RECIST criteria. Progressive disease required a &gt;20% increase, partial response &gt;30% decrease, and stable disease for those in between. Similar definitions for volume measurements were used. Results: 3 of 20 patients were excluded as the diffuse metastatic nature of their tumors and small size prevented application of the RECIST or WHO measurement criteria. RECIST correctly predicted volumetric response or progression in 12/17 cases, but was delayed by either one or two scan cycles in reaching that conclusion in 3 of these 12 cases. WHO criteria correlated with volumetrics in 16/17 cases with a delay of one scan interval in a single case. The delay in correct identification of response category was particularly noticeable in identifying progressive disease with RECIST as compared to volumetrics. RECIST was only 50% specific for progressive disease at the time that progression was documented with volume. WHO was 90% specific. Both methods were sensitive to clinical benefit (SD + PR) (RECIST 86%; WHO 100%). Conclusions: For metastatic brain tumors that are large enough to be measured with linear criteria, WHO bidimensional criteria appear superior to unidimensional RECIST measurements in predicting volumetric response of tumors. Supported by EB000219-NIBIB and UNC Breast SPORE CA58223. No significant financial relationships to disclose.
CGMP LEVEL IN PULMONARY ARTERIAL HYPERTENSION VS. PULMONARY HYPERTENSION DUE TO HEART FAILURE WITH PRESERVED EJECTION FRACTION, BOTH AT REST AND AT PEAK EXERCISE
Authors: Arif Albulushi, Daniel Zolty, Kajari Dhar, Adam Burdorf, Douglas Stoller, Marshall Hyden, Marshall Hyden, Brian Lowes, Ronald Zolty
Journal: Journal of the American College of Cardiology (2020)
Expression of transcription factor Scratch2 in colorectal cancer.
Authors: Krasimir Ivanov, Nikola Kolev, Anton Tonev, Peter Ghenev, Nedyalka Zgurova, Georgi Ivanov, Tanya Kirilova, Valentin Ignatov, Aleksandar Zlatarov, Anton Tonchev
Journal: Journal of Clinical Oncology (2013)

e14669 Background: The Scratch genes constitute an independent subgroup of the Snail superfamily of transcription factors (TFs). Vertebrates contain 2 Snail and 2 Scratch genes (Scrt1 and Scrt2). Members of the Snail/Scratch superfamilies are characterized by a having both zinc finger domains, which mediate DNA-binding and a SNAG domain that is necessary for the transcriptional repression. Under normal conditions, the Scratch genes are expressed exclusively in the nervous system, where they regulate cortical neurogenesis (Paul, Tonchev, et al. Cerebral Cortex 2012, Epub ahead of print; doi: 10.1093/cercor/bhs356). However, expression of Scrt2 under pathological conditions is poorly characterized, especially in humans. Methods: We investigated the expression of Scrt2 by immunohistochemistry in 50 primary or metastatic (hepatic metastasis) colorectal cancer biopsies acquired through routine operations at the Department of General Surgery, Medical University-Varna, Bulgaria. We also evaluated the histological type and clinical stage of the tumors. Results: We found that both the primary and the metastatic tumor strongly expressed Scrt2 protein. Interestingly, the expression was mostly in the cytoplasm, in accordance with the reported pattern in the developing cortex (Paul, Tonchev, et al. Cerebral Cortex 2012, Epub ahead of print; doi: 10.1093/cercor/bhs356). Notably, in the hepatic metastatic tumors, we found no or scarce expression in the normal hepatic parenchyma surrounding the tumor, while a strong expression in the colorectal cancer metastasis. Conclusions: Scrt2 represents a putative novel marker for colorectal cancer. Detailed correlation of the clinical parameters, such as patient survival, and the expression level of Scrt2 might yield novel prognostic value of this TF in the pathogenesis of colorectal cancer.
AUTOLOGOUS STEM CELL THERAPY FOR SINGLE RIGHT VENTRICULAR DYSFUNCTION AFTER FONTAN OPERATION: PHASE I SAFETY AND FEASIBILITY STUDY OF INTRACORONARY INFUSION OF BONE MARROW-DERIVED MONONUCLEAR CELLS
Authors: Muhammad Yasir Qureshi, Nathaniel Taggart, Allison K. Cabalka, Donald Hagler, Shakila Khan, Kimberly Holst, Timothy Olson, Patrick O'Leary, Susana Cantero-Peral, Timothy J. Nelson
Journal: Journal of the American College of Cardiology (2020)
HIGH INCIDENCE OF ELEVATED BLOOD PRESSURE AMONG COLLEGIATE FEMALE ATHLETES AT PRE-PARTICIPATION PHYSICAL EVALUATION
Authors: Cecil Rambarat, Fred Reifsteck, Yasmeen Taha, James Clugston, Eileen Handberg, Joan Street, Monica Towns, Matthew Kelling, Michelle Dimza, Carl J. Pepine, Matthew W. Martinez, Katherine Edenfield
Journal: Journal of the American College of Cardiology (2020)
USEFULNESS OF CARDIAC REHABILITATION WITH ASSISTANCE FROM HYBRID ASSISTIVE LIMB (HAL) IN PATIENTS WITH CHRONIC HEART FAILURE
Authors: Hidenori Kato, Akira Koike, Longmei Wu, Hiroki Watanabe, Kosuke Hayashi, Hiroshi Kubota, Hirotomo Konno, Isao Nishi, Hiroaki Kawamoto, Akira Sato, Akira Matsumura, Kazutaka Aonuma, Yoshiyuki Sankai, Masaki Ieda
Journal: Journal of the American College of Cardiology (2020)