tbuckley/cabot-search huggingface dataset:
The Effects of the COVID-19 pandemicon cancer patient encounters
Authors: J. W. London, E. Fazio-Eynullayeva, M. Palchuk, C. Mossop, P. Sankey, C. McNair
Journal: Clinical Cancer Research (2020)

The outbreak of COVID-19 has upended the health care industry and the world as a whole, with the full effectsunlikely to be realized for years to come  Unfortunately, cancer patients are likely to be disproportionately impactedby the pandemic, and there are a number of key efforts under way to explore this, including the COVID-19 andCancer Consortium (CCC19) and the ASCO Survey on COVID-19 in Oncology registries  However, there have beenfew studies to quantify the immediate impact COVID-19 has had on deviation from normal cancer care, as well asdeclines in screening efforts  Less screening may lead to delayed diagnoses and poorer future outcomes  We wereable to leverage an existing health research network platform (TriNetX) to create a cohort of 20 different institutionsacross the US representing over 29 million patients  We initially focused on all patients with ICD-10 diagnostic codesfor neoplasms (C00-D49)  Key findings include a marked decrease in the number of patients having neoplasm-related encounters for March and April of 2020 when compared to the same months in 2019, with January andFebruary remaining largely unchanged  Specifically, comparing April 2020 to April 2019, we observed roughly a-56 9% drop in the number of patients with a neoplasm-related encounter and a -74 0% drop in the number ofpatients seen for the first time (e g , screening, initial diagnosis, second opinion, treatment initiation)  Similar trends were observed when querying for patients with encounters related exclusively to malignant neoplasms (ICD-10 C00-C96)  Site-specific malignancies were also analyzed, with melanoma, breast cancer, and prostate cancer displayingthe largest decline in patients seen, and lung cancer, colorectal cancer, and hematologic cancers the smallest drop  Finally, changes in screening were investigated, with breast cancer screening falling by -89 2% and colorectalcancer screening by -84 5% in April of 2020 compared to 2019  Ultimately, these analyses validate the vital need tostudy and monitor the effect of COVID-19 on cancer patients moving forward, and provide the largest study toquantify the changes in cancer encounters due to the pandemic to date
Burden and Risk of Neurological and Cognitive Impairment in Pediatric Sickle Cell Anemia in Uganda (BRAIN SAFE): Interim Overall Results
Authors: Nancy S. Green, Deogratias Munube, Ezekiel Mupere, Robert Opoka, Phillip Kasirye, Paul Bangirana, Linda Rosset Buluma, Sarah Kiguli, Michael Kawooya, Samson K. Lubowa, Heather Ann Hume, Jose Gutierrez, Philip LaRussa, Frank Minja, Richard Idro
Journal: Blood (2017)
Comprehensive metabolic profiling of Parkinson’s disease by liquid chromatography-mass spectrometry
Authors: Yaping Shao, Tianbai Li, Zheyi Liu, Xiaolin Wang, Xiaojiao Xu, Song Li, Guowang Xu, Weidong Le
Journal: Molecular Neurodegeneration (2021)

Abstract Background Parkinson’s disease (PD) is a prevalent neurological disease in the elderly with increasing morbidity and mortality. Despite enormous efforts, rapid and accurate diagnosis of PD is still compromised. Metabolomics defines the final readout of genome-environment interactions through the analysis of the entire metabolic profile in biological matrices. Recently, unbiased metabolic profiling of human sample has been initiated to identify novel PD metabolic biomarkers and dysfunctional metabolic pathways, however, it remains a challenge to define reliable biomarker(s) for clinical use. Methods We presented a comprehensive metabolic evaluation for identifying crucial metabolic disturbances in PD using liquid chromatography-high resolution mass spectrometry-based metabolomics approach. Plasma samples from 3 independent cohorts ( n = 460, 223 PD, 169 healthy controls (HCs) and 68 PD-unrelated neurological disease controls) were collected for the characterization of metabolic changes resulted from PD, antiparkinsonian treatment and potential interferences of other diseases. Unbiased multivariate and univariate analyses were performed to determine the most promising metabolic signatures from all metabolomic datasets. Multiple linear regressions were applied to investigate the associations of metabolites with age, duration time and stage of PD. The combinational biomarker model established by binary logistic regression analysis was validated by 3 cohorts. Results A list of metabolites including amino acids, acylcarnitines, organic acids, steroids, amides, and lipids from human plasma of 3 cohorts were identified. Compared with HC, we observed significant reductions of fatty acids (FFAs) and caffeine metabolites, elevations of bile acids and microbiota-derived deleterious metabolites, and alterations in steroid hormones in drug-naïve PD. Additionally, we found that L-dopa treatment could affect plasma metabolome involved in phenylalanine and tyrosine metabolism and alleviate the elevations of bile acids in PD. Finally, a metabolite panel of 4 biomarker candidates, including FFA 10:0, FFA 12:0, indolelactic acid and phenylacetyl-glutamine was identified based on comprehensive discovery and validation workflow. This panel showed favorable discriminating power for PD. Conclusions This study may help improve our understanding of PD etiopathogenesis and facilitate target screening for therapeutic intervention. The metabolite panel identified in this study may provide novel approach for the clinical diagnosis of PD in the future.
OP0025 Glucosamine sulfate inhibits nitric oxide and stromelysin production in cartilage cultures and reverses il-1 inhibition of osteoarthritic articular cartilage synthesis
Authors: I Yaron, I Shirazi, R Judovich, M Yaron
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Glucosamine sulfate is used for the management of osteoarthritis of the knee. The mechanism of its effects needs clarification. <h3>Objectives</h3> To evaluate the effects of glucosamine sulfate on the production of nitric oxide (NO) and stromelysin (MMP3) and cartilage synthesis in human osteoarthritic cartilage in the presence of IL-1b or LPS. <h3>Methods</h3> Cartilage was obtained in the operation theatre from patients undergoing total knee replacement for osteoarthritis, cut into small pieces and cultured in the presence or absence of IL-1b or LPS. NO in culture media was measured with the Griess reagent, MMP-3 by ELISA and cartilage synthesis by <sup>35</sup>S incorporation. <h3>Results</h3> IL-1b (1 ng/ml) and LPS (3μg/ml) stimulated NO release in human osteoarthritic cartilage cultures about four fold. Glucosamine sulfate (1μg/ml, 10μg/ml, 100μg/ml) inhibited stimulated NO production in a dose dependent manner, reaching statistical significance (p &lt; 0.05) at 100μg/ml glucosamine sulfate (60% and 38% inhibition respectively). Glucosamine sulfate (100μg/ml) significantly (p &lt; 0.05) inhibited MMP-3 release in IL-1b and LPS stimulated cartilage cultures. IL-1b and LPS inhibited cartilage synthesis by 70% and 50% respectively (p &lt; 0.001). Glucosamine sulfate reversed this inhibition in a dose dependent manner reaching statistical significance (p &lt; 0.05) at 10μg/ml glucosamine sulfate. <h3>Conclusion</h3> Glucosamine sulfate may protect human osteoarthritic articular cartilage by inhibiting local NO and MMP-3 production and by reversing IL-1b inhibition of cartilage synthesis.
Abstract 16157: Causes and Comorbidities of Hospitalized Heart Failure in 8 Countries
Authors: Sophia Emmons-Bell, Catherine Johnson, Simon Yadgir, Spencer James, Gregory A Roth
Journal: Circulation (2019)

Background: Public health policies to reduce the burden of heart failure require a better understanding of what risks and diseases cause myocardial dysfunction. For the Global Burden of Disease (GB...
In-Hospital Mortality and Cost of Allogeneic Hematopoietic Cell Transplant (HCT) in Adult Acute Myeloid Leukemia: National Inpatient Sample (NIS) Years 2002-2013
Authors: Urshila Durani, Ronald S Go, Ankit Kansagra, Hassan B. Alkhateeb, Mark R. Litzow, William J. Hogan
Journal: Blood (2017)
Delivering health and nutrition interventions for women and children in different conflict contexts: a framework for decision making on what, when, and how
Authors: Michelle F Gaffey, Ronald J Waldman, Karl Blanchet, Ribka Amsalu, Emanuele Capobianco, Lara S Ho, Tanya Khara, Daniel Martinez Garcia, Samira Aboubaker, Per Ashorn, Paul B Spiegel, Robert E Black, Zulfiqar A Bhutta, Zulfiqar Bhutta, Robert Black, Karl Blanchet, Ties Boerma, Michelle Gaffey, Ana Langer, Paul Spiegel, Ronald Waldman, Paul Wise
Journal: The Lancet (2021)
Abstract 12300: Sirtuin 1 Prevents Age-associated Aortic Valve Calcification in vivo
Authors: Zhejun Cai, Jianfang Wang, Ming Liu, Tan Yuan, Fei Li
Journal: Circulation (2019)

Introduction: Aortic valve (AoV) calcification and its subsequent aortic stenosis have been linked with increased morbidity, without effective pharmacological intervention. Epidemic studies reveal ...
Targeting cancer stem cells with a pan-BCL-2 inhibitor in preclinical and clinical settings in patients with gastroesophageal carcinoma
Authors: Shumei Song, Qiongrong Chen, Yuan Li, Guang Lei, Ailing Scott, Longfei Huo, Cordelia Y Li, Jeannelyn Santiano Estrella, Arlene Correa, Melissa Pool Pizzi, Lang Ma, Jiankang Jin, Bin Liu, Ying Wang, Lianchun Xiao, Wayne L Hofstetter, Jeffrey H Lee, Brian Weston, Manoop Bhutani, Namita Shanbhag, Randy L Johnson, Boyi Gan, Shaozhong Wei, Jaffer A Ajani
Journal: Gut (2021)

Objective Gastro-oesophageal cancers (GEC) are resistant to therapy and lead to poor prognosis. The cancer stem cells (CSCs) and antiapoptotic pathways often confer therapy resistance. We sought to elucidate the antitumour action of a BCL-2 inhibitor, AT101 in GEC in vitro, in vivo and in a clinical trial. Methods Extensive preclinical studies in vitro and in vivo were carried out to establish the mechanism action of AT101 on targeting CSCs and antiapoptotic proteins. A pilot clinical trial in patients with GEC was completed with AT-101 added to standard chemoradiation. Results Overexpression of BCL-2 and MCL-1 was noted in gastric cancer tissues (GC). AT-101 induced apoptosis, reduced proliferation and tumour sphere formation in MCL-1/BCL-2 high GC cells. Interestingly, AT101 dramatically downregulated genes ( YAP-1/Sox9 ) that control CSCs in GEC cell lines regardless of BCL-2/MCL-1 expression. Addition of docetaxel to AT-101 amplified its antiproliferation and induced apoptosis effects. In vivo studies confirmed the combination of AT101 and docetaxel demonstrated stronger antitumour activity accompanied with significant decrease of CSCs biomarkers (YAP1/SOX9). In a pilot clinical trial, 13 patients with oesophageal cancer (EC) received AT101 orally concurrently with chemoradiation. We observed dramatic clinical complete responses and encouraging overall survival in these patients. Clinical specimen analyses revealed that AT-101 dramatically reduced the expression of CSCs genes in treated EC specimens indicating antitumour activity of AT101 relies more on its anti-CSCs activity. Conclusions Our preclinical and clinical data suggest that AT-101 overcomes resistance by targeting CSCs pathways suggesting a novel mechanism of action of AT101 in patients with GEC.
Association of Non–High-Density Lipoprotein Cholesterol Measured in Adolescence, Young Adulthood, and Mid-Adulthood With Coronary Artery Calcification Measured in Mid-Adulthood
Authors: Matthew K. Armstrong, Brooklyn J. Fraser, Olli Hartiala, Marie-Jeanne Buscot, Markus Juonala, Feitong Wu, Juha Koskinen, Nina Hutri-Kähönen, Mika Kähönen, Tomi P. Laitinen, Terho Lehtimäki, Jorma S. A. Viikari, Olli T. Raitakari, Costan G. Magnussen
Journal: JAMA Cardiology (2021)

Elevated non-high-density lipoprotein cholesterol (non-HDL-C) is associated with the presence of coronary artery calcification (CAC), a marker of heart disease in adulthood. However, the relative importance of non-HDL-C levels at specific life stages for CAC remains unclear.
SAT0097 DO COMORBIDITIES IMPACT PERSISTENCE OF FIRST TUMOR NECROSIS FACTOR INHIBITOR TREATMENT IN RHEUMATOID ARTHRITIS? DATA FROM TURKBIO
Authors: T. Yüce İnel, S. B. Kocaer, Y. Erez, S. Gulle, A. Karakas, A. Köken Avşar, S. Uslu, G. Can, İ. Sari, M. Birlik, E. Dalkiliç, Y. Pehlivan, S. Akar, B. Goker, G. Yildirim Cetin, S. Haznedaroglu, Ş. Yavuz, T. Pirildar, H. Direskeneli, N. Akkoc, F. Onen
Journal: Annals of the Rheumatic Diseases (2020)

Background: Studies indicate that patients with rheumatoid arthritis (RA) are at increased risk of developing several comorbid disorders. Comorbidities affect treatment decisions, the effectiveness of the treatment, quality of life, RA prognosis, and survival rate [1]. Objectives: The aim of this study to investigate the impact of comorbidity on the first TNF inhibitor treatment persistence in RA. Methods: In the TURKBIO database, patients with an ICD 10-diagnosis of RA (M05 or M06) who started TNF inhibitor therapy between January 2011 and June 2019 were enrolled. Demographic and clinical characteristics, acute phase reactants, disease activity scores (DAS 28 CRP, HAQ, CDAI, VAS global), initial comorbidities and numbers, drug persistence, were evaluated. Kaplan-Meier plots and Cox proportional hazard regression analyses were performed. Results: A total of 1172 patients &gt;18 years of age treated with TNF-α inhibitors were included in the study. The most prevalent comorbidities were: hypertension in 262 patients (32.6%), obesity in 254 (32.6%), osteoporosis in 178 (22.3%), chronic lung disease in 143 (17.9%) and depression in 126 (15.8%). The baseline characteristics are summarised in Table 1. The presence of comorbidity did not affect the survival rate of the first TNF inhibitor therapy in the RA patients (p: 0.65). Comorbidities had no effect on DAS28 CRP (&gt; 1.2 reduction) responses at 6 and 12 months of treatment (p: 0.18, p: 0.83, respectively). As the mean disease duration increases, the persistence of the first TNF inhibitor decreases by 5%. Conclusion: This study demonstrated the increasing burden of comorbidities in RA. However, it suggested that the presence and number of comorbidities did not influence the rate of persistence in the first TNF inhibitor drug and the response to treatment. References: [1] Gabriel, S.E. and K. Michaud, Epidemiological studies in incidence, prevalence, mortality, and comorbidity of the rheumatic diseases. Arthritis research &amp; therapy, 2009. 11 (3): p. 229. Disclosure of Interests: None declared
Hormonal Therapy for Prostate Cancer
Authors: Kunal Desai, Jeffrey M McManus, Nima Sharifi
Journal: Endocrine Reviews (2021)

Huggins and Hodges demonstrated the therapeutic effect of gonadal testosterone deprivation in the 1940s and therefore firmly established the concept that prostate cancer is a highly androgen-dependent disease. Since that time, hormonal therapy has undergone iterative advancement, from the types of gonadal testosterone deprivation to modalities that block the generation of adrenal and other extragonadal androgens, to those that directly bind and inhibit the androgen receptor (AR). The clinical states of prostate cancer are the product of a superimposition of these therapies with nonmetastatic advanced prostate cancer, as well as frankly metastatic disease. Today's standard of care for advanced prostate cancer includes gonadotropin-releasing hormone agonists (e.g., leuprolide), second-generation nonsteroidal AR antagonists (enzalutamide, apalutamide, and darolutamide) and the androgen biosynthesis inhibitor abiraterone. The purpose of this review is to provide an assessment of hormonal therapies for the various clinical states of prostate cancer. The advancement of today's standard of care will require an accounting of an individual's androgen physiology that also has recently recognized germline determinants of peripheral androgen metabolism, which include HSD3B1 inheritance.
Association of early recurrence within one year of liver transplant for hepatocellular carcinoma with poor survival.
Authors: Bryan Cho Wing Li, Joanne Wing Yan Chiu, Thomas Yau, Roland Ching-Yu Leung, Vikki Tang, Kit Bong Shing, Gin Wai Kwok, Tan To Cheung, Wong Hoi She, Ka Wing Ma
Journal: Journal of Clinical Oncology (2021)

296 Background: Treatment of hepatocellular carcinoma (HCC) recurrences following liver transplant is challenging. All the clinical trials of systemic therapies for advanced HCC excluded patients with any history of organ transplant. Here we review outcome, and the safety and efficacy of the application of systemic medical therapies in this clinical setting. Methods: This is a retrospective cross-sectional study of consecutive adult patients with recurrence of HCC following liver transplant for the indication of treatment of HCC in Queen Mary Hospital from January 2005 to January 2018. Results: Forty-three consecutive patients with a recurrence of HCC following liver transplant were identified from 2005 to 2018. Median survival from diagnosis of recurrence was 17 months (CI 11.3, 22.7). Early recurrence within 12 months of transplant was associated with a significantly worse median survival of 10 months CI 8.5, 11.4) compared to 26 months (CI 18.8, 33.2) when recurrences occurred after 12 months from transplant (p&lt; 0.001) after adjustment with peritumoural vascular invasion, first line therapy with sorafenib, any second line therapy and use of mTOR inhibitors as immunosuppressants, with a hazard ratio of 0.104 (log-rank test, p&lt;0.001). 41 patients who received medical systemic therapies, 34 (79.1% ) received sorafenib as the first line systemic therapy. 47.1% (N= 16) received subsequent lines of systemic therapies (ranging from 1 to 4 lines). Hand-foot syndrome was most common among the adverse events and it was observed in 34.7% patients treated with sorafenib. It led to dose interruptions in 8.8 % of patients who were given sorafenib. 26.7% had grade 1 diarrhoea. 14.3% had grade 1 transaminase rise. Conclusions: Early recurrence within one year from transplant was the most significant risk factor. Treatment efficacy and adverse events and tolerability of sorafenib were comparable with those in the setting of advanced HCC without transplant.
Real-world outcomes of patients with intrahepatic cholangiocarcinoma treated with trans-arterial radioembolization: Results from the CIRSE Registry for SIR-Spheres Therapy (CIRT), a large European prospective multi-center observational study.
Authors: Thomas Helmberger, Dirk Arnold, Tugsan Balli, Rita Golfieri, Maciej Pech, Maxime Ronot, Niels de Jong, Bruno Sangro
Journal: Journal of Clinical Oncology (2021)

308 Background: Trans-arterial radioembolization (TARE) is a treatment option for patients with intrahepatic cholangiocarcinoma (ICC). The CIRSE Registry for SIR-Spheres Therapy (CIRT) is the first European prospective multi-centre observational study designed to evaluate the clinical outcomes of patients treated with TARE with SIR-Spheres Y90 resin microspheres for ICC in the multi-institutional real-life clinical setting. The study was conducted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Methods: Patients were enrolled prospectively between Jan 2015 and 31 Dec 2017. Eligible patients were adults treated with TARE with Y90 resin microspheres for ICC. Data on baseline characteristics and treatment intention/clinical context and dosimetry were collected, as well as follow-up data (every 3 months; for 24 months after treatment), including overall survival (OS), (hepatic) progression-free survival [(h)PFS], safety and Global Health Status (GHS, using the European Organisation for the Research and Treatment of Cancer QLQ-C30). Results: 120 patients were included from 18 sites in 8 European countries. Median age was 63 years (range: 29-86) and 54.2% were male. Median tumour to liver percentage was 12.8%. Median prescribed activity was 1.32 GBq for whole liver treatments (n = 49), 1.20 GBq for right lobe treatments (n = 56) and 0.82 GBq for left lobe treatments (n = 51). 97.5% of the delivered activity was within 90% of the prescribed activity. TARE treatment as a first line (L1) global strategy was applied in 39.1%, 27.4% as second line (after systemic therapy). Treatment intention was predominantly palliative (69.2%) or tumour shrinkage (20.8%). Median OS was 14.7 months (95% confidence interval (CI) 10.9 – 17.9). Median PFS was 5.7 months (95% CI 3.9 – 7.5), whereas hPFS was 6.2 months (95% CI 4.1 – 8.5). Mean GHS was 59.3 at baseline, 61.0 after 3 months, 56.0 at 6 months, 54.4 at 9 months and 63.0 after 1 year. Severe adverse events (grade 3 and 4) were found in 13 (10.8%) patients: (abdominal pain 3.3%, fatigue 1.7%, gastrointestinal ulceration 0.8%, gastritis 0.8%, radiation cholecystitis 0.8%, radiation-induced liver disease 1.7%, other 5.8%). Detailed subgroup analyses are currently being performed. Updated data describing OS, PFS and hPFS for L1 TARE vs TARE after systemic chemotherapy, as well as prognostic factors for OS, PFS and hPFS will be shown. Conclusions: The results from this large prospective multi-centre observational study shows that in the real-world context, TARE is applied early and successfully in the treatment pathway. TARE is shown to be an effective and safe treatment with no meaningful deterioration of quality of life. Clinical trial information: NCT02305459.
Genetic underpinnings of risky behaviour relate to altered neuroanatomy
Authors: Gökhan Aydogan, Remi Daviet, Richard Karlsson Linnér, Todd A. Hare, Joseph W. Kable, Henry R. Kranzler, Reagan R. Wetherill, Christian C. Ruff, Philipp D. Koellinger, Gideon Nave
Journal: Nature Human Behaviour (2021)