tbuckley/cabot-search huggingface dataset:
The pattern of brain metastasis in colorectal cancer: Efficacy of metastasectomy, chemotherapy.
Authors: Suleyman Yasin Goksu, Muhammad Shaalan Beg, Aravind Sanjeevaiah, Emrah Gumusgoz, David Hsieh, Muhammet Ozer, Amy Little Jones, Radhika Kainthla, Udit Verma, Salwan Al Mutar, Craig Olson, Javier Salgado Pogacnik, Nina Niu Sanford, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2021)

40 Background: Colorectal cancer patients with brain metastases experience poor outcomes; however treatment strategies are understudied. In this study, we investigated the impact of different treatments for colorectal cancer patients with brain metastases. Methods: We identified stage 4 colorectal adenocarcinoma patients with brain metastasis using the National Cancer Database diagnosed between 2010 and 2015. Patients with unknown survival data, other histologies, and multiple primary sites were excluded. Patients with and without brain metastasis were compared using the Chi-square test. Kaplan-Meier method was performed to calculate univariable overall survival (OS). We used the Cox regression model for multivariable analysis after adjusting by age, race/ethnicity, comorbidity score, surgery, chemotherapy, and radiotherapy. Results: Among 75,901 patients with stage 4 colorectal adenocarcinoma, 1.6% had brain metastasis. Patients with brain metastasis were more likely to have bone (23% vs. 5%, p &lt; 0.001) and lung metastasis (52% vs. 21%, p &lt; 0.001), but less likely to have liver metastasis (56% vs. 72%, p &lt; 0.001) compared to patients without brain metastasis. Patients with brain metastasis had higher KRAS mutation rate (54% vs. 43%, p &lt; 0.001). Patients with brain metastasis were more likely to be age ≥ 50 years (85% vs. 83%, p = 0.01), white race (76% vs. 71%, p = 0.001), and receive radiotherapy (63% vs. 12%, p &lt; 0.001). Total 26.4% of patients with brain metastasis underwent metastasectomy, and those patients had better OS compared to patients with non-metastasectomy (median OS 12 vs. 4 months, p &lt; 0.001). Median OS in all patients with brain metastasis was 5.5 months. Patients with brain metastasis who received multiagent chemotherapy had improved OS compared with patients who received single-agent chemotherapy (mOS 13 vs. 6 months, p &lt; 0.001). Patients with brain metastasis who received brain radiotherapy had better OS (mOS 6.3 vs. 3.7 months, p = 0.005) than those who did not. On multivariable analysis, metastasectomy (HR 0.65 95% CI [0.57-0.75]) and receipt of multiagent chemotherapy (HR 0.68 95% CI [0.54-0.86]) were associated with favorable prognosis, but brain radiotherapy was not (HR 1.04 95% CI [0.91-1.19]). Conclusions: Brain metastases are rare in colorectal cancer but portend poor survival. Lung and bone metastases are found more frequently in these patients. Treatment with metastasectomy or multiagent chemotherapy is associated with improved overall survival.
The family in exile: Cuban expatriates in the United States
Authors: R D Rumbaut, R G Rumbaut
Journal: American Journal of Psychiatry (1976)

For the nearly one million Cuban exiles in this country, the ordeal of expatriation has meant anguish and uprootedness, challenge and accomplishment. Several factors account for the comparatively successful aspects of their struggle: relatively high occupational and educational levels, formation of vigorous communities that permit the maintenance of a positive ethnic consciousness and the creation of strong social ties, and effectively organized reception by the United States. Expatriation is always traumatic and produces "casualties," but mastery of the struggles it involves can lead to personal growth and expanded horizons. The Cuban expatriate experience shows that the influx of large numbers of refugees can be a creative and enriching process for both the host country and the individual refugee.
Abstract 12551: Prevalence of Low Ankle-brachial Index in Patients With Atrial Fibrillation
Authors: Francesco Violi, Giovanni Davì, William Hiatt, Gregory Y Lip, Gino R Corazza, Francesco Perticone, Marco Proietti, Pasquale Pignatelli, Anna R Vestri, Stefania Basili, Arapacis Investigators
Journal: Circulation (2013)

Objectives: This study sought to explore the prevalence of Ankle/Brachial Index (ABI) ≤0.90 in patients with nonvalvular atrial fibrillation (AF) and its contribution to overall prevalence of cardi...
Tannic acid derivatives display anti-angiogenic properties in human breast cancer cells by interfering with CXCR4/SDF-1 interactions
Authors: Kevin Meier, Devin Twitchell, Byron Murray, Kim O’Neill
Journal: Cancer Research (2005)

5190  Angiogenesis involves the formation and stabilization of new blood vessels. Tumors rely on this process to meet their constantly increasing demands for nutrients and oxygen. Research has shown that stromal-cell derived factor-1_ (SDF-1_) is involved in angiogenesis by up regulating key angiogenic factors including vascular endothelial growth factor (VEGF), which in turn increases the cell membrane expression of CXCR4. Previous studies have shown that tannic acid inhibits the binding of SDF-1_ and CXCR4, decreasing the angiogenesis measured by the chicken choriallantoic membrane (CAM) assay. We hypothesize that 3 derivatives of tannic acid (ferulic acid, ellagic acid and gallic acid) will posses its same anti-angiogenic potential. Ferulic acid is a phenolic plant derived organic acid possessing antioxidant properties. It has also been demonstrated to boost the immune system and aide in the body’s protection against UV light. Gallic acid, a trihydroxybenzoic acid, is a natural antioxidant found in walnuts, tea leaves, oak bark and other plant extracts. Ellagic acid is a polyphenolic compound found in berries and known for its cancer fighting properties. In this study we use MDA-MB-231 and MDA-MB-435 (high CXCR4 expressing) and MCF-7 (low CXCR4 expressing) breast adenocarcinoma cell lines. Cells are placed on the CAM of fertilized chicken eggs at a concentration of 5 x 105 cells/20 _L with SDF-1_ (100 ng/mL), and derivative concentrations ranging from 5 _M to 25 _M. We then quantify angiogenesis using a novel analytical computer program, which measures blood vessel density, length, and branching points. Our controls were untreated eggs, eggs with the cancer cells only, and eggs with the cancer cells and SDF-1_. In this study we report optimal inhibition at a 5 _M concentration where tannic acid decreases blood vessel density by 65% (p ≤ 0.0244), blood vessel length by 71% (p≤ 0.000), and branching points by 70% (p≤ 0.000) in comparison to the SDF-1_ control in MDA-MB-435. Ferulic acid at the same concentration showed similar inhibition of angiogenesis, causing an 80% reduction in blood vessel density, a 48% reduction in branching points and a 70% decrease in blood vessel length. The other two derivatives show related trends in their anti-angiogenic capacity. MDA-MB-231 angiogenesis inhibition paralleled that of MDA-MB-435. On the other hand, the addition of tannic acid derivatives to MCF-7 showed little anti-angiogenic potential. We assume that this may be due to their low expression of CXCR4. Further research may be required to validate this hypothesis.
CRISPRi enables isoform-specific loss-of-function screens and identification of gastric cancer-specific isoform dependencies
Authors: Rebecca Davies, Ling Liu, Sheng Taotao, Natasha Tuano, Richa Chaturvedi, Kie Kyon Huang, Catherine Itman, Amit Mandoli, Aditi Qamra, Changyuan Hu, David Powell, Roger J. Daly, Patrick Tan, Joseph Rosenbluh
Journal: Genome biology (2021)

Abstract Introduction Genes contain multiple promoters that can drive the expression of various transcript isoforms. Although transcript isoforms from the same gene could have diverse and non-overlapping functions, current loss-of-function methodologies are not able to differentiate between isoform-specific phenotypes. Results Here, we show that CRISPR interference (CRISPRi) can be adopted for targeting specific promoters within a gene, enabling isoform-specific loss-of-function genetic screens. We use this strategy to test functional dependencies of 820 transcript isoforms that are gained in gastric cancer (GC). We identify a subset of GC-gained transcript isoform dependencies, and of these, we validate CIT kinase as a novel GC dependency. We further show that some genes express isoforms with opposite functions. Specifically, we find that the tumour suppressor ZFHX3 expresses an isoform that has a paradoxical oncogenic role that correlates with poor patient outcome. Conclusions Our work finds isoform-specific phenotypes that would not be identified using current loss-of-function approaches that are not designed to target specific transcript isoforms.
Development of small molecule STING agonists that can evoke host anti-cancer immune defences following local or systemic delivery
Authors: Nicole Haynes, Theresa Connor, Ben Morrow, Judy Doherty, Matthew Dennis, Jonathan Hubert, Sukhdeep Spall, Anthony Cuzzupe, Karen White, Susan Charman, Aaron Lock, Vicky Avery, Stewart Nuttall, Tom Peat, Olan Dolezal, Pat Pilling, Jezrael Revalde, Tin Yow, Greg Arndt, Hendrik Falk, Mark Devlin, Ian Street, Poh Khoo, Paul Stupple, Brendon Monahan
Journal: Journal for ImmunoTherapy of Cancer (2019)
FRI0173 Multiple antiphospholipid-antibody-tests improve the laboratory diagnostic in the antiphospholipid syndrome
Authors: R Wöhrle, T Matthias, M Oppermann, K Helmke
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Examining patients with clinical features of the antiphospholipid-antibody-syndrome (APS), anticardiolipin antibodies (aCL) and lupus anticoagulant (LA) tests are widely performed. Unfortunately some patients with typical symptoms of APS (i.e. thromboembolic and ischaemic events, pregnancy losses) have negative test results in the commonly performed assays. <h3>Objectives</h3> <h3>Methods</h3> Using a new ELISA-test-system (Aesku.lab Diagnostika GmbH, Wendelsheim, Germany) we examined sera of 102 patients (68 women, 34 men) with clinical symptoms of APS: 61 patients had a history of thromboembolic events, 44 of cerebrovascular insults, 6 women had pregnancy losses. The assay detects IgG- and IgM-class-antibodies against Phosphatidyl-Serine (PS), Phosphatidyl-Inositol (PI), Sphingomyelin (SM), Phosphatidyl-Ethanolamine (PE) and Phosphatidyl-Choline (PC) without cofactor and in combination with b2-glycoprotein I (b2-GP-I) respectively. <h3>Results</h3> Sera of 50 patients were completely negative in the LA- and aCL-tests, 17 patients had only low concentrations of aCL-antibodies. Of this 67 patients with negative or borderline results in the commonly performed tests, 39 (58%) were positive for other phospholipid-antibody-specificities, in 22 (33%) the antibody-concentrations were even high. Antibodies which were tested positive in 10 or more patients are shown in the table, every “+” indicates one patient. <h3>Conclusion</h3> As shown in the table, most of the phospholipid-antibody-specificities found in patients with negative or borderline results in LA- and aCL-tests are IgM-class antibodies independent from b2-glycoprotein I. Testing for these antibodies could be helpful for the diagnostic of patients with clinical features of the APS and negative results in the commonly performed tests, especially if there are no further risk factors for thromboembolic events or ischaemic insults.
PRISMA 2020 explanation and elaboration: updated guidance and exemplars for reporting systematic reviews
Authors: Matthew J Page, David Moher, Patrick M Bossuyt, Isabelle Boutron, Tammy C Hoffmann, Cynthia D Mulrow, Larissa Shamseer, Jennifer M Tetzlaff, Elie A Akl, Sue E Brennan, Roger Chou, Julie Glanville, Jeremy M Grimshaw, Asbjørn Hróbjartsson, Manoj M Lalu, Tianjing Li, Elizabeth W Loder, Evan Mayo-Wilson, Steve McDonald, Luke A McGuinness, Lesley A Stewart, James Thomas, Andrea C Tricco, Vivian A Welch, Penny Whiting, Joanne E McKenzie
Journal: BMJ (2021)

The methods and results of systematic reviews should be reported in sufficient detail to allow users to assess the trustworthiness and applicability of the review findings. The Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement was developed to facilitate transparent and complete reporting of systematic reviews and has been updated (to PRISMA 2020) to reflect recent advances in systematic review methodology and terminology. Here, we present the explanation and elaboration paper for PRISMA 2020, where we explain why reporting of each item is recommended, present bullet points that detail the reporting recommendations, and present examples from published reviews. We hope that changes to the content and structure of PRISMA 2020 will facilitate uptake of the guideline and lead to more transparent, complete, and accurate reporting of systematic reviews.
Notice of Retraction and Replacement. Stefan et al. Association of antibiotic treatment with outcomes in patients hospitalized for an asthma exacerbation treated with systemic corticosteroids. <i>JAMA Intern Med</i>. 2019;179(3):333-340
Authors: Mihaela S. Stefan, Penelope S. Pekow, Peter K. Lindenauer
Journal: JAMA Internal Medicine (2021)

Notice of Retraction and Replacement. Stefan et al. Association of antibiotic treatment with outcomes in patients hospitalized for an asthma exacerbation treated with systemic corticosteroids. JAMA Intern Med. 2019;179(3):333-340.
Abstract 3682: Mortality from Coronary Heart Disease in Subjects with Moderate Chronic Kidney Disease is Comparable with Subjects with Prior Myocardial Infarction and also Patients with Diabetes
Authors: Arash Rashidi, Ashwini R Sehgal, Andrew O’Connor
Journal: Circulation (2007)

Introduction. Chronic kidney disease (CKD) and DM are important CAD risk factors. Whether CKD is a cardiovascular risk equivalent, like DM, is the matter of debate. Hypothesis. Moderate CKD is a ca...
Usefulness of high-frequency Doppler ultrasound skin thickness measurement for disease staging and assessing treatment response in patients with scleredema: A case-control study
Authors: Priscila Giavedoni, María Pousa-Martínez, Ana Estany-Destal, Manuel Ginarte, Hugo Vázquez-Veiga, Lorena Tamez, José M. Mascaró
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 18893: ADP Receptor Inhibitor Therapy Use Beyond 12 Months in Community Practice: Results From the Translate-ACS Registry
Authors: Jonathan D Hansen, Lisa A McCoy, David J Cohen, Timothy D Henry, Gregg Fonarow, Mark B Effron, Marjorie E Zettler, Brian A Baker, Eric D Peterson, Tracy Y Wang
Journal: Circulation (2015)

Background: Prolonged use of ADP receptor inhibitors (ADPri) beyond 1 year following myocardial infarction (MI) and percutaneous coronary intervention (PCI) is supported by recent studies such as DAPT and PEGASUS. In community practice, how often and in which patients prolonged ADPri therapy is used is poorly understood. Methods: Using data from the TRANSLATE-ACS observational study, we examined prevalence of ADPri continuation beyond 1 year post-MI in routine US practice (2010-2012) and used multivariable logistic regression to identify patient characteristics associated with ADPri use beyond 1 year. Results: Of 8,749 patients alive and still on ADPri at 12 months post-MI, 6,627 (76%) were still on ADPri at the 15-month interview. ADPri use beyond 1 year occurred more frequently among black vs. white patients (82.7% vs. 75.1%), patients with prior PCI (85.4% vs. 73.2%) or prior CABG (87.0% vs. 74.5%), and those with multivessel disease (78.8% vs. 72.7%, p&lt;0.001 for all). Use of drug eluting stents did not affect likelihood of prolonged ADPri use, 77% in both groups (p= 0.98). Patients discharged on prasugrel/ticagrelor were less likely to continue their ADPri beyond 1 year than those discharged on clopidogrel (71.1% vs. 77.9%, p&lt;0.001). Unplanned coronary revascularization occurred more commonly within the first 1 year post-MI among patients who continued on ADPri beyond 1 year (14.3% vs. 4.6%, p&lt;0.001), but the rate of BARC 2+ bleeding was lower (19.9% vs. 22.3%, p=0.02) than those who stopped ADPri at 1 year. These variables remained independent factors associated with post-1 year ADPri continuation in multivariable modeling (Figure). Conclusion: In routine US practice, the majority of MI patients who underwent PCI were already receiving prolonged ADPri therapy beyond 1 year even before DAPT and PEGASUS trials. Post-discharge unplanned revascularization and bleeding appear to be the strongest predictors for and against prolonged ADPri use, respectively.
A phase I study of safety and immunogenicity of survivin long peptide vaccine (SurVaxM) in patients (pts) with metastatic neuroendocrine tumors (NETs).
Authors: Medhavi Gupta, Robert Alan Fenstermaker, Jing-Xin Qiu, Renuka V. Iyer
Journal: Journal of Clinical Oncology (2021)

TPS375 Background: Metastatic neuroendocrine tumors (NETs) have a poor prognosis and there are limited options after first-line treatment with somatostatin analogues (SSA)/chemotherapy. Therefore, new therapies are urgently needed. Survivin is an intracellular protein that alters cell division, function of cell death proteases and inhibits apoptosis. It is undetectable in adult cells and expressed in many tumors, making it an ideal target. SurVaxM is a 15 amino acid synthetic peptide vaccine. It stimulates antigen presentation via intracellular cell-surface target recognition and induces CD8+ &amp; CD4+ T cells and IgG production. It was well tolerated in a phase I trial in recurrent glioma pts (Fenstermaker et al., Neurooncol; 2014). Prelim analysis from a phase II study in glioma patients (pts) showed its efficacy (Ahluwalia et al., Neurooncol; 2018). Targeting survivin in NETs is based on our work with tissue microarrays from gastroenteropancreatic (GEP) and lung NETs that showed that its expression correlated with a worse overall survival (Hanif et al., Oncotarget; 2020). We have an ongoing single-arm phase I trial evaluating the safety and immunogenicity of SurVaxM in metastatic NETs. Methods: Ten eligible pts with any grade metastatic GEP/lung origin NETs that are survivin positive by immunohistochemistry and have progression on SSA within the last 6 months on two CT scans &gt;4 weeks apart per RECIST v1.1 are being enrolled. Pts receive a fixed dose of 500 mcg of SurVaxM in Montanide ISA 51 subcutaneously along with 100 mcg of GM-CSF q2 weeks X 4 doses. SSA is continued at the same dose as before. Pts free of progression and toxicity at 6 months get extra doses of SurVaxM q12 weeks, up to 1 year. Subjects are assessed continuously for safety per NCI CTCAEv5.0. Response assessment via CT scans per RECIST v1.1 q12 weeks. Primary objective is to assess safety of SurVaxM +/- SSA. Secondary objectives are to assess overall response rate, progression free survival, duration of response and vaccine immunological response (anti-survivin antibody titers and survivin-specific CD8 T-cell responses). Safety analysis is per Pocock stopping boundary with the assumption of true toxicity of 0.2 and unacceptable toxicity of 0.3 at a significance level of 0.05.To this date, eight patients were screened out of which five patients were enrolled. One patient did not meet the eligibility criterion due to negative survivin staining and the other two did not meet the RECIST v1.1 progression criterion. Of the five pts enrolled, two were of lung origin, two of GEP, and the remainder one of thymic origin. Three pts had high grade neuroendocrine carcinoma, one patient had atypical bronchial tumor and one with low-grade NET. Currently, two pts remain on the study. The enrollment is ongoing. The trial is funded by The Neuroendocrine Tumor Research Foundation.
Portal hypertensive biliopathy and bile duct varices presenting as jaundice
Authors: Gloria Tacchella, Odenca Gjermeni, Stefano Francesco Crinó, Armando Gabbrielli, Nicola Martinelli
Journal: Endoscopy (2021)

A 61-year-old woman with advanced alcoholic liver cirrhosis (Child – Pugh score: C, 10 points; MELD score: 24 points) developed evident jaundice with prevalent conjugated hyperbilirubinemia (bilirubin: total 12.0 mg/dL, direct 7.5 mg/dL). Aminotransferases were only mildly elevated (AST 76 U/L, ALT 40 U/L), while there was a predominant elevation of alkaline phosphatase (162 U/L) and γ-glutamyl transpeptidase (103 U/L). Routine laboratory analysis also showed anemia (hemoglobin 9.8 g/dL), thrombocytopenia (platelets 25 000 /μL), and prolonged prothrombin time (PT-INR 2.01). Ultrasonography showed dilated bile ducts. Magnetic resonance cholangiopancreatography (MRCP) revealed an abnormal biliary tree with multiple strictures and focal dilatations characterized by irregular contrast enhancement, potentially suggestive of intraductal malignancy, although no prominent obstruction was observed ([Fig. 1 a, b]). Radiographic features of portal hypertension with perigastric and perisplenic collaterals were also observed. Neither esophageal nor gastric varices were found by esophagogastroduodenoscopy, while congestive gastropathy was present. Endoscopic retrograde cholangiopancreatography (ERCP) was carried out with the aim of defining the diagnosis and facilitating biliary drainage. ERCP documented multiple narrowing of intra- and extrahepatic bile ducts without major stenosis ([Fig. 1 c]). The still unexplained biliary strictures prompted performance of peroral cholangioscopy ([Fig. 1 d]; [Video 1]). Biliary sphincterotomy was performed to be able to pass the cholangioscope. Peroral digital single-operator cholangioscopy (SpyGlass DS; Boston Scientific) revealed multiple bile duct varices (BDV) with red spots and microbleedings localized to the common bile duct, thereby defining a diagnosis of portal biliopathy. Neither a critical (i. e., clinically significant) stenosis nor blood clots causing obstruction were found. Therefore, no endoscopic treatment was performed. The patient remained clinically stable on follow-up, although no substantial improvement of jaundice was observed (bilirubin: total 13.2 mg/dL, direct 7.7 mg/dL). She accepted an offer to participate in a program of alcohol counseling and, finally, after 6 months of abstinence from alcohol, was considered for liver transplantation.
A glycopyrronium bromide 1% cream for topical treatment of primary axillary hyperhidrosis: efficacy and safety results from a phase IIIa randomized controlled trial*
Authors: C. Abels, M. Soeberdt, A. Kilic, H. Reich, U. Knie, C. Jourdan, K. Schramm, S. Heimstaedt‐Muskett, C. Masur, R.‐M. Szeimies
Journal: British Journal of Dermatology (2021)

Effective topical treatment options for patients with primary axillary hyperhidrosis (PAHH) are limited. A phase I trial showed promising results regarding the efficacy and safety of a topical cream containing glycopyrronium bromide (GPB).
Panniculitis As the First Clinical Manifestation of Myeloperoxidase–Positive Perinuclear Antineutrophil Cytoplasmic Antibody–Associated Vasculitis: Comment on the Article by Micheletti et al
Authors: D. Deleersnijder, P. De Haes, L. Peperstraete, J. Buelens, A. Betrains, D. Blockmans
Journal: Arthritis & Rheumatology (2021)