tbuckley/cabot-search huggingface dataset:
Optimizing treatment for COVID-19using computational modeling: Implications for cancerpatients
Authors: C. Voutouri, M. Nikmaneshi, M. Khandekar, A. B. Patel, A. Verma, S. Dutta, T. Stylianopoulos, L. L. Munn, R. K. Jain
Journal: Clinical Cancer Research (2020)

Emerging retrospective analyses show that cancer patients are more likely to develop severe COVID-19  Thecauses for these worse outcomes are unclear, but data suggest that cancer therapies, which can suppress theimmune system, are not responsible for increased COVID-19 severity  An alternative hypothesis is that commonmolecular pathways are altered in cancer and COVID-19, resulting in worsened disease outcomes  Our previouswork demonstrated that activated renin angiotensin signaling (RAS) modulates the tumor microenvironment, resulting in worse outcomes and therapy resistance  Inhibition of this pathway using angiotensin receptor blockers(ARBs) or angiotensin converting enzyme inhibitors (ACEIs) can improve the outcomes of cancer therapies Similarly, there is great interest in understanding the implications of RAS in COVID-19 progression because a keycomponent of this system, ACE2, is also the docking site for the SARS-CoV-2 virus  Indeed, multiple clinical trialsare currently evaluating whether ARBs/ACEIs benefit or harm COVID-19 patients  To help guide administration ofthese drugs, we adapted our existing computational modeling framework of the cancer microenvironment usingavailable data to simulate COVID-19 progression in patients  Using a systems biology approach, we mechanisticallymodeled the interaction of the RAS and coagulation pathways with COVID-19 infection  We further explored theefficacy of various antiviral, antithrombotic, and RAS-targeted treatment regimens to identify synergisticcombinations as well as optimal schedules for therapy  The system is complex, given that viral binding of ACE2interferes with its antiinflammatory signaling  When ACE2 is bound by the virus, its local activity decreases, leadingto immune dysregulation and risk of coagulopathy, predictors of COVID-19 severity and mortality  To optimizecombination treatments for cancer patients who contract COVID-19, multiple simulations were run by combiningdifferent therapeutics currently in clinical trials to predict their effects on viral load, thrombosis, oxygen saturation, and cytokine levels  These include ARBs, ACEIs, antiviral drugs, antithrombotic agents, and anti-inflammatory drugs(e g , anti-IL6/6R)  Our simulations predict that i) there is an optimal timing for treatment with antiviral drugs such asremdesivir, related to immune activation;ii) combinations of antiviral and antithrombotic drugs are able to preventlung damage, increase blood oxygen levels, and inhibit thromboembolic events;and iii) RAS modulators can have apositive effect when added to the treatment regimen  Effective strategies for COVID-19 treatment identified by this insilico analysis will be further analyzed in combination with cancer therapeutics (e g , immune checkpoint blockers, chemotherapy) to provide guidelines for optimal clinical management of both cancer and COVID-19
Adjuvant therapeutic plasma exchange in septic shock
Authors: Sascha David, Christian Bode, Christian Putensen, Tobias Welte, Klaus Stahl, Markus Busch, Hermann Haller, Marius M. Hoeper, Felix Lehmann, Julius J. Schmidt, Bernhard M. W. Schmidt, Benjamin Seeliger, Andrea Sauer, Philipp Wand, Olaf Wiesner, Heiner Wedemeyer
Journal: Intensive Care Medicine (2021)
Abstract 15646: The Survey of Long-Term Clinical Outcomes From the Therapeutic Angiogenesis by Cell Transplantation in Japan
Authors: Kazuhisa Kondo, Kenji Yanishi, Ryo Hayashida, Rei Shibata, Toyoaki Murohara, Satoaki Matoba
Journal: Circulation (2017)

Introduction: The findings from the Therapeutic Angiogenesis by Cell Transplantation trial demonstrated the feasibility and safety in patients with critical limb ischemia (CLI). This study aimed to...
Issues for the next generation of base rate research
Authors: Jonathan J. Koehler
Journal: Behavioral and Brain Sciences (1996)

Abstract Commentators agree that simple conclusions about a general base rate fallacy are not appropriate. It is more constructive to identify conditions under which base rates are differentially weighted. Commentators also agree that improving the ecological validity of the research is desirable, although this is less important to those interested exclusively in psychological processes. The philosophers and ecologists among the commentators offer a kinder perspective on base rate reasoning than the psychologists. My own perspective is that the interesting questions (both psychological and normative/prescriptive) are best answered through empirical studies that use real-world performance standards.
AGIG chemo-immunotherapy in patients with advanced pancreatic cancer: A single-arm, single-center, phase II study.
Authors: Wangshu Dai, Xin Qiu, Changchang Lu, Zhengyun Zou, Huizi Sha, Weiwei Kong, Baorui Liu, Juan Du
Journal: Journal of Clinical Oncology (2021)

384 Background: To date, chemotherapy remains the only effective treatment of unresectable pancreatic adenocarcinoma. In the last few years, the interest in the use of immunological anticancer strategies is greatly increased. AGIG is a novel chemo-immunotherapy regimen that combines nab-paclitaxel + gemcitabine chemotherapy with sequential recombinant interleukin-2 and granulocyte-macrophage colony stimulating factor (GM-CSF) therapy. We conducted a single-arm prospective phase II study to determine the efficacy and safety of the first-line treatment of advanced pancreatic cancer with AGIG regimen. Methods: Nab-paclitaxel (120 mg/m 2 ) and gemcitabine (1000 mg/m 2 ) were administered intravenously to all patients on days 1 and 8 triweekly, interleukin-2 and GM-CSF (100 µg) were administered subcutaneously on days 3-5 after chemotherapy. The primary end point was ORR by the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included safety profile, progression-free survival (PFS), overall survival (OS). Patients’ conditions and the efficacy and safety were assessed every 4 cycles. Results: Between 11/2018 and 01/2020, 64 patients were enrolled. In the 64 evaluable patients, the ORR and DCR were 43.75% and 76.6%, respectively. The median follow-up time was 12.1 (range 7.1–22.4) months, the median PFS was 5.7 (range 1.63–15.8) months, and the median OS was 14.2 (range 2.9–22.0) months. The most common adverse event was fever (75%). The incidence of grade 3/4 neutropenia was 4.69%. In subgroup analyses, we found that eosinophil count in the blood elevated three times higher than baseline level predicted a longer survival. Conclusions: The AGIG Chemo-immunotherapy regimen has presented encouraging ORR, OS, and manageable toxicities as first-line therapy for advanced pancreatic cancer. This regimen may be a novel reliable therapeutic option for patients with preserved performance status. The improvement of treatment efficiency may be related to the activation of non-specific immune response. Clinical trial information: NCT0376867. Research Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School. [Table: see text]
Safety profile of immune checkpoint inhibitors versus sorafenib as first-line treatment in advanced hepatocellular carcinoma: A meta-analysis of randomized controlled trials.
Authors: Alessandro Rizzo, Giorgio Frega, Angela Dalia Ricci, Andrea Palloni, Simona Tavolari, Giovanni Brandi
Journal: Journal of Clinical Oncology (2021)

315 Background: Systemic treatment with tyrosine kinase inhibitors such as sorafenib represents the mainstay of advanced-stage hepatocellular carcinoma (HCC). However, survival outcomes remain disappointing, mostly because of the onset of acquired resistance and a suboptimal safety profile, which frequently requires treatment modifications and early discontinuation of treatment – thus, interfering with compliance and long-term outcomes of patients. With immune checkpoint inhibitors (ICIs) quickly expanding as a novel therapeutic option in advanced HCC, the toxicity profiles of these agents should be kept in mind. We performed a meta-analysis with the aim to compare all-grade (G) adverse drug events (ADEs) of ICIs (alone or in combination with other anticancer agents) versus sorafenib monotherapy across randomized controlled trials (RCTs) of first-line treatment for advanced HCC. Methods: Eligible studies included RCTs comparing ICIs versus sorafenib as first-line treatment in HCC. Safety profile from each selected study was investigated for all-G most common ADEs. Outcomes of interest were as follows: pruritus, diarrhea, hand-foot skin reaction (HFSR), fatigue, aspartate aminotransferase (AST) increase, rash, hypertension and decreased appetite. Results were compared by calculating odds ratios (ORs) with 95% confidence intervals (CIs); ORs were combined with Mantel-Haenszel method. All statistical analyses were performed using R studio software. Results: Two RCTs (CheckMate 459, IMbrave 150) involving 1,228 patients were included in the analysis. Patients treated with ICIs showed higher risk of pruritus (OR 1.99, 95% CI = 1.22-3.24) while sorafenib treatment was associated with higher risk of diarrhea (OR 0.26, 95% CI = 0.18-0.37) and HFSR (OR 0.01, 95% CI = 0-0.04). Conversely, no statistically significant differences were observed in terms of fatigue (OR 0.84, 95% CI = 0.45-1.58), AST increase (OR 1.21, 95% CI = 0.78-1.88), rash (OR 0.71, 95% CI = 0.46-1.11), hypertension (OR 0.28, 95% CI = 0.01-9.76) and decreased appetite (OR 0.41, 95% CI = 0.14-1.21) between the two groups. Conclusions: Although the substantial heterogeneities affecting our analyses, ICIs appear feasible in advanced HCC, being endowed with an acceptable safety profile. Beyond activity and efficacy, careful consideration should be given to toxicity while choosing the appropriate first-line treatment in advanced HCC.
SAT0387 ROLE OF HLA-B27 IN THE COMORBIDITIES OBSERVED IN AXIAL SPONDYLOARTHRITIS: DATA FROM COMOSPA
Authors: M. Arévalo, C. López-Medina, M. Moreno, A. Moltó, F. U. Pilar, E. Collantes-Estévez, J. Gratacos-Masmitja
Journal: Annals of the Rheumatic Diseases (2020)

Background: Comorbidities have merged as an important field in Spondyloarthritis, however there is few data about its relationship to genetic factors such as HLA-B27. Objectives: To analyze the potential association between the presence of HLA-B27 and the different comorbidities observed in axSpA patients. Methods: A comparative cross-sectional study including axSpA patients from COMOSPA registry. COMOSPA is a worldwide registry that includes a wide set of anthropometric and clinical variables from 3984 patients with spondyloarthritis. The registry also includes the most frequent comorbidities observed in spondyloarthitis such as obesity, hypertension, diabetes, hyperlipidemia, heart ischemic disease, stroke, renal failure, neoplasms, peptic ulcer, diverticulitis, chronic obstructive pulmonary disease, and the presence of osteoporosis. A descriptive analysis and a multiple logistic regression model was performed including all variables assessed. Results: 2370 patients fulfilled ASAS criteria of axSpA patients and were included in the study. 1858 (78.4%) of them were HLA-B27 positive. HLA-B27 positive axSpA patients presented significantly higher percentage of male sex, longer disease duration, higher percentage of definite Ankylosing Spondylitis, higher CRP levels, and were also more frequent tobacco consumers and excessive alcohol intakers compared to the negatives. However, disease activity measured by BASDAI, BASFI and ASDAS-CRP were all significantly higher in the HLA-B27 negative patients compared to the positive ones. The only association observed between any comorbidity and presence of gen HLA-B27 was the presence of osteoporosis. This association was independently significant even after adjusting in the multivariate analysis for all variables assessed. Conclusion: The association observed between the gen HLA-B27 and the presence of osteoporosis in axSpA patients could be of great relevance given the impact of osteoporosis in the phenotypical frame of axSpA patients. Disclosure of Interests: Marta Arévalo: None declared, Clementina López-Medina: None declared, Mireia Moreno: None declared, Anna Moltó Grant/research support from: Pfizer, UCB, Consultant of: Abbvie, BMS, MSD, Novartis, Pfizer, UCB, Font Ugalde Pilar: None declared, Eduardo Collantes-Estévez Grant/research support from: ROCHE and Pfizer., Speakers bureau: ROCHE, Lilly, Bristol and Celgene., Jordi Gratacos-Masmitja Grant/research support from: a grant from Pfizzer to study implementation of multidisciplinary units to manage PSA in SPAIN, Consultant of: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly, Speakers bureau: Pfizzer, MSD, ABBVIE, Janssen, Amgen, BMS, Novartis, Lilly
Trial in progress: A feasibility study of multi-platform profiling using biospecimens from patients with resected biliary tract cancer.
Authors: Adam Diehl, William Proctor Harris, Gentry Teng King
Journal: Journal of Clinical Oncology (2021)

TPS359 Background: Biliary tract cancers (BTC) are rare malignancies with a high recurrence rate after resection of localized disease. FDA-approved systemic therapies for advanced disease are limited to combination chemotherapy and FGFR inhibitors for FGFR2-altered BTC. The tools of personalized medicine may guide management and expand treatment options for this disease. In multiple tumor types, circulating tumor DNA (ctDNA) has shown significant predictive power for recurrence after resection, but its utility has not yet been established in BTC. Organoid drug sensitivity screening may also inform and expand treatment options, particularly for patients without targetable mutations on next generation sequencing (NGS). Prospective concordance between organoid drug sensitivity and in vivo clinical responses to a given drug is needed to establish the value of this testing in BTC. We designed a clinical trial to determine the feasibility and physician-assessed utility of multi-platform profiling of resected BTC. Methods: This is an observational, non-randomized feasibility study to assess the ability to obtain NGS, ctDNA monitoring, and organoid drug sensitivity screening on patients with resected localized BTC. Secondary endpoints include physician-adjudicated utility of the profiling results for patient management, prospective concordance of organoid drug sensitivity with in vivo drug activity, and value of ctDNA in prediction of recurrence or response to therapy. Key eligibility criteria include a biopsy or clinical presentation consistent with BTC (excluding mixed HCC-cholangiocarcinoma), surgical candidacy for resection of measurable disease, and no prior targeted or investigational therapies. ctDNA is collected pre- and post-operatively, during adjuvant chemotherapy, during surveillance for up to 5 years and during systemic therapy for recurrent disease. Physician surveys are conducted before and after receipt of profiling results and then at time points where a change in management would be considered. Enrollment began in July 2020 with 5 of a planned 20 patients enrolled at the time of submission. Clinical trial information: NCT04561453.
10-Year natural course of early hip osteoarthritis in middle-aged persons with hip pain: a CHECK study
Authors: Annemaria C. van Berkel, Dieuwke Schiphof, Jan H. Waarsing, Jos Runhaar, John M. van Ochten, Patrick J.E. Bindels, Sita M.A. Bierma-Zeinstra
Journal: Annals of the Rheumatic Diseases (2021)

Objective To explore the natural course of hip osteoarthritis (OA) in a population of first-time presenters with hip complaints. Methods Data were collected at baseline and after 2, 5, 8 and 10 years on participants from the Cohort Hip and Cohort Knee study with early symptomatic hip OA. Descriptive statistics were used to analyse the natural course of the hip complaints with respect to clinical signs and symptoms, physical functioning and radiographic osteoarthritis (ROA) features. Results In total, 588 participants were included with hip complaints and 86% completed the 10-year follow-up. The 10-year follow-up showed that 12% (69 participants) underwent hip replacement (HR), an increase of ROA of the hip (Kellgren and Lawrence score≥2) from 19% to 49%, and an increase in clinical hip OA according to the American College of Rheumatology criteria from 27% to 43%. All Western Ontario and McMaster Osteoarthritis Index subscales and physical activity remained on average constant during the 10-year follow-up for those who did not undergo an HR. The use of pain medication increased from 43% at baseline to 50% after 10 years. Conclusion One out of nine participants with early hip problems received an HR during the 10-year follow-up. Prevalence of clinical hip OA and hip ROA increased steadily during the 10-year follow-up. Overall, we observed more hip OA, but fewer or stable complaints with respect to clinical signs and symptoms, and physical functioning. So it could be cautiously concluded that after 10 years, first-time presenters with hip complaints either received an HR or their symptoms remained stable.
Tissue Engineering: Engineering Silk Fibroin‐Based Nerve Conduit with Neurotrophic Factors for Proximal Protection after Peripheral Nerve Injury (Adv. Healthcare Mater. 2/2021)
Authors: Cristiana R. Carvalho, Wei Chang, Joana Silva‐Correia, Rui L. Reis, Joaquim M. Oliveira, Joachim Kohn
Journal: Advanced Healthcare Materials (2021)

The incorporation and delivery of neurotrophic factors that stimulate nerve repair in previously developed tunable enzymatically crosslinked silk fibroin-based conduits are presented. In article number 2000753 by Joaquim M. Oliveira and co-workers, glial cell line-derived neurotrophic factor (GDNF), acting upon motor and sensory neurons, also instigating angiogenesis, uses these conduits as a platform for its controlled delivery, enhancing motor and sensory regeneration both in vivo and in vitro.
SAT0128 Patterns of cognitive impairment in behÇet’s disease
Authors: G Triolo, R Monastero, G Lopez, M Mannino, A Ferrante, F Ciccia, E Giardina, R Camarda
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Cognitive dysfunction is a common finding in patients with Behçet's disease. <h3>Objectives</h3> The pattern of neuropsychological dysfunction in patients with Behçet's disease (BD) was examined. The influence of current or past clinically overt central nervous system involvement, disease activity, corticosteroid use, HLA B51 allele, and anxiety and depression levels were evaluated. <h3>Methods</h3> Twenty-two BD patients fulfilling the criteria of the International Study Group for Behçet Disease, and twenty-two healthy controls, similar for age, gender and education were included in the study. Patients and controls underwent to a standardised battery of neuropsychological and psychological tests. Disease activity was assessed by using the Behçet Current Activity Index (BCAI). The current daily dosage of prednisone (mg/day) was recorded. <h3>Results</h3> Cognitive impairment was identified in 41.0% (9) of patients with BD (p &lt; 00008 vs. control). A significantly greater proportion of patients with BD than controls was impaired in tasks assessing attention, episodic memory, semantic and visuospatial abilities (P from &lt; 0.05 to &lt; 0.005). As concern psychological distress BD subjects were significantly more anxious (P &lt; 0.005) and depressed (P &lt; 0.01) than healthy controls. The presence of current or past clinically overt central nervous system involvement, current steroid medication, disease activity, HLA B51 positivity, and psychological distress could not account for these findings. <h3>Conclusion</h3> Cognitive dysfunction is a common finding in BD patients. Our series suggest that BD can be associated with a specific pattern of cognitive deficit, involving mainly long-term verbal and visuospatial abilities.
Magnetothermal Miniature Reactors Based on Fe<sub>3</sub>O<sub>4</sub> Nanocube‐Coated Liquid Marbles
Authors: Hualin Li, Peng Liu, Renardi Gunawan, Zemenu Mengistie Simeneh, Chen Liang, Xi Yao, Mengsu Yang
Journal: Advanced Healthcare Materials (2021)

Abstract Liquid marbles have recently attracted much interest in various scientific fields because of their isolated environment and robustness. However, conventional liquid marbles lack a reliable heating mechanism, which is critical in many potential applications. Here, the development of iron oxide (Fe 3 O 4 ) nanocube‐coated liquid marbles (iNLMs), which can be homogeneously heated with an alternating magnetic field (AMF) to as high as 86 °C, is reported. Through tuning the power of the AMF, the iNLMs canbe heated to desired temperatures in controllable patterns. Furthermore, multicenter and selective heating is realized based on the unique magnetothermal properties of iNLMs. As heatable miniature reactors, the iNLMs are further demonstrated to facilitate the kinetic study of temperature‐dependent chemical reactions. DNA amplification is successfully performed in liquid marbles, achieving a 25% superior amplification rate compared with that in a common thermal cycler. These results confirm the feasibility of coating liquid marbles with Fe 3 O 4 nanocubes to form delicate magnetothermal miniature reactors, which provides a reliable method of applying liquid marbles in areas such as biosensor technology, point‐of‐care testing, and theranostics.
Chitinase 3 like 1 is a regulator of smooth muscle cell physiology and atherosclerotic lesion stability
Authors: Pavlos Tsantilas, Shen Lao, Zhiyuan Wu, Anne Eberhard, Greg Winski, Monika Vaerst, Vivek Nanda, Ying Wang, Yoko Kojima, Jianqin Ye, Alyssa Flores, Kai-Uwe Jarr, Jaroslav Pelisek, Hans-Henning Eckstein, Ljubica Matic, Ulf Hedin, Philip S Tsao, Valentina Paloschi, Lars Maegdefessel, Nicholas J Leeper
Journal: Cardiovascular Research (2021)

Abstract Aims Atherosclerotic cerebrovascular disease underlies the majority of ischaemic strokes and is a major cause of death and disability. While plaque burden is a predictor of adverse outcomes, plaque vulnerability is increasingly recognized as a driver of lesion rupture and risk for clinical events. Defining the molecular regulators of carotid instability could inform the development of new biomarkers and/or translational targets for at-risk individuals. Methods and results Using two independent human endarterectomy biobanks, we found that the understudied glycoprotein, chitinase 3 like 1 (CHI3L1), is up-regulated in patients with carotid disease compared to healthy controls. Further, CHI3L1 levels were found to stratify individuals based on symptomatology and histopathological evidence of an unstable fibrous cap. Gain- and loss-of-function studies in cultured human carotid artery smooth muscle cells (SMCs) showed that CHI3L1 prevents a number of maladaptive changes in that cell type, including phenotype switching towards a synthetic and hyperproliferative state. Using two murine models of carotid remodelling and lesion vulnerability, we found that knockdown of Chil1 resulted in larger neointimal lesions comprised by de-differentiated SMCs that failed to invest within and stabilize the fibrous cap. Exploratory mechanistic studies identified alterations in potential downstream regulatory genes, including large tumour suppressor kinase 2 (LATS2), which mediates macrophage marker and inflammatory cytokine expression on SMCs, and may explain how CHI3L1 modulates cellular plasticity. Conclusion CHI3L1 is up-regulated in humans with carotid artery disease and appears to be a strong mediator of plaque vulnerability. Mechanistic studies suggest this change may be a context-dependent adaptive response meant to maintain vascular SMCs in a differentiated state and to prevent rupture of the fibrous cap. Part of this effect may be mediated through downstream suppression of LATS2. Future studies should determine how these changes occur at the molecular level, and whether this gene can be targeted as a novel translational therapy for subjects at risk of stroke.