tbuckley/cabot-search huggingface dataset:
Gastrointestinal symptoms of 95 cases with SARS-CoV-2 infection
Authors: Lu Lin, Xiayang Jiang, Zhenling Zhang, Siwen Huang, Zhenyi Zhang, Zhaoxiong Fang, Zhiqiang Gu, Liangqing Gao, Honggang Shi, Lei Mai, Yuan Liu, Xianqi Lin, Renxu Lai, Zhixiang Yan, Xiaofeng Li, Hong Shan
Journal: Gut (2020)

To study the GI symptoms in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients.We analysed epidemiological, demographic, clinical and laboratory data of 95 cases with SARS-CoV-2 caused coronavirus disease 2019. Real-time reverse transcriptase PCR was used to detect the presence of SARS-CoV-2 in faeces and GI tissues.Among the 95 patients, 58 cases exhibited GI symptoms of which 11 (11.6%) occurred on admission and 47 (49.5%) developed during hospitalisation. Diarrhoea (24.2%), anorexia (17.9%) and nausea (17.9%) were the main symptoms with five (5.3%), five (5.3%) and three (3.2%) cases occurred on the illness onset, respectively. A substantial proportion of patients developed diarrhoea during hospitalisation, potentially aggravated by various drugs including antibiotics. Faecal samples of 65 hospitalised patients were tested for the presence of SARS-CoV-2, including 42 with and 23 without GI symptoms, of which 22 (52.4%) and 9 (39.1%) were positive, respectively. Six patients with GI symptoms were subjected to endoscopy, revealing oesophageal bleeding with erosions and ulcers in one severe patient. SARS-CoV-2 RNA was detected in oesophagus, stomach, duodenum and rectum specimens for both two severe patients. In contrast, only duodenum was positive in one of the four non-severe patients.GI tract may be a potential transmission route and target organ of SARS-CoV-2.
Expression patterns of immune checkpoints in acute myeloid leukemia
Authors: Cunte Chen, Chaofeng Liang, Shunqing Wang, Chi Leong Chio, Yuping Zhang, Chengwu Zeng, Shaohua Chen, Caixia Wang, Yangqiu Li
Journal: Journal of Hematology & Oncology (2020)

Abstract Immunotherapy with immune checkpoint inhibitors (ICIs) for solid tumors had significantly improved overall survival. This type of therapy is still not available for acute myeloid leukemia (AML). One major issue is the lack of knowledge for the expression patterns of immune checkpoints (IC) in AML. In this study, we first explored the prognostic value of ICs for AML patients by analyzing RNA-seq and mutation data from 176 AML patients from the Cancer Genome Atlas (TCGA) database. We further validated the results of the database analysis by analyzing bone marrow (BM) samples from 62 patients with de novo AML. Both TCGA data and validation results indicated that high expression of PD-1, PD-L1, and PD-L2 was associated with poor overall survival (OS) in AML patients. In addition, increased co-expression of PD-1/CTLA-4 or PD-L2/CTLA-4 correlated with poor OS in AML patients (3-year OS: TGCA data 30% vs 0% and 20% vs 0%, validation group 57% vs 31% and 57% vs 33%, respectively) ( P &lt; 0.05). Moreover, co-expression of PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 was found to correlate with poor OS in AML patients with FLT3 mut , RUNX1 mut , and TET2 mut , respectively. In conclusion, high expression of ICs in the BM leukemia cells of AML patients correlated with poor outcome. The co-expression patterns of PD-1/CTLA-4, PD-L2/CTLA-4, PD-1/PD-L1, PD-1/PD-L1/PD-L2, and PD-1/LAG-3 might be potential immune biomarkers for designing novel AML therapy.
Role of neoadjuvant chemotherapy in metastatic medulloblastoma: a comparative study in 92 children
Authors: Léa Guerrini-Rousseau, Rachid Abbas, Sophie Huybrechts, Virginie Kieffer-Renaux, Stéphanie Puget, Felipe Andreiuolo, Kévin Beccaria, Thomas Blauwblomme, Stéphanie Bolle, Frédéric Dhermain, Audrey Longaud Valès, Thomas Roujeau, Christian Sainte-Rose, Arnault Tauziede-Espariat, Pascale Varlet, Michel Zerah, Dominique Valteau-Couanet, Christelle Dufour, Jacques Grill
Journal: Neuro-Oncology (2020)

Abstract Background Previous pilot studies have shown the feasibility of preoperative chemotherapy in patients with medulloblastoma, but benefits and risks compared with initial surgery have not been assessed. Methods Two therapeutic strategies were retrospectively compared in 92 patients with metastatic medulloblastoma treated at Gustave Roussy between 2002 and 2015: surgery at diagnosis (n = 54, group A) and surgery delayed after carboplatin and etoposide-based neoadjuvant therapy (n = 38, group B). Treatment strategies were similar in both groups. Results The rate of complete tumor excision was significantly higher in group B than in group A (93.3% vs 57.4%, P = 0.0013). Postoperative complications, chemotherapy-associated side effects, and local progressions were not increased in group B. Neoadjuvant chemotherapy led to a decrease in the primary tumor size in all patients; meanwhile 4/38 patients experienced a distant progression. The histological review of 19 matched tumor pairs (before and after chemotherapy) showed that proliferation was reduced and histological diagnosis feasible and accurate even after neoadjuvant chemotherapy. The 5-year progression-free and overall survival rates were comparable between groups. Comparison of the longitudinal neuropsychological data showed that intellectual outcome tended to be better in group B (the mean predicted intellectual quotient value was 6 points higher throughout the follow-up). Conclusion Preoperative chemotherapy is a safe and efficient strategy for metastatic medulloblastoma. It increases the rate of complete tumor excision and may improve the neuropsychological outcome without jeopardizing survival. Key Points 1. Preoperative chemotherapy increases the rate of complete tumor removal. 2. No additional risk (toxic or disease progression) is linked to the delayed surgery. 3. Preoperative chemotherapy could have a positive impact on the neuropsychological outcome of patients.
Social distancing in covid-19: what are the mental health implications?
Authors: Ashwin Venkatesh, Shantal Edirappuli
Journal: BMJ (2020)

As of 1 April 2020, there have been 29 474 confirmed cases of covid-19 in the UK.1 As discussed by Mahase, the UK government has enforced “social distancing” measures to curb transmission, protect the vulnerable, and prevent saturation of the NHS.2 Social distancing has potential mental health implications—how can we mitigate these to bolster this essential …
A Systematic Review of Estimating Breast Cancer Recurrence at the Population Level With Administrative Data
Authors: Hava Izci, Tim Tambuyzer, Krizia Tuand, Victoria Depoorter, Annouschka Laenen, Hans Wildiers, Ignace Vergote, Liesbet Van Eycken, Harlinde De Schutter, Freija Verdoodt, Patrick Neven
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Exact numbers of breast cancer recurrences are currently unknown at the population level, because they are challenging to actively collect. Previously, real-world data such as administrative claims have been used within expert- or data-driven (machine learning) algorithms for estimating cancer recurrence. We present the first systematic review and meta-analysis, to our knowledge, of publications estimating breast cancer recurrence at the population level using algorithms based on administrative data. Methods The systematic literature search followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We evaluated and compared sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of algorithms. A random-effects meta-analysis was performed using a generalized linear mixed model to obtain a pooled estimate of accuracy. Results Seventeen articles met the inclusion criteria. Most articles used information from medical files as the gold standard, defined as any recurrence. Two studies included bone metastases only in the definition of recurrence. Fewer studies used a model-based approach (decision trees or logistic regression) (41.2%) compared with studies using detection rules without specified model (58.8%). The generalized linear mixed model for all recurrence types reported an accuracy of 92.2% (95% confidence interval = 88.4% to 94.8%). Conclusions Publications reporting algorithms for detecting breast cancer recurrence are limited in number and heterogeneous. A thorough analysis of the existing algorithms demonstrated the need for more standardization and validation. The meta-analysis reported a high accuracy overall, which indicates algorithms as promising tools to identify breast cancer recurrence at the population level. The rule-based approach combined with emerging machine learning algorithms could be interesting to explore in the future.
Notes from the Field: First Evidence of Locally Acquired Dengue Since 1944 — Guam, 2019
Authors: Stephanie Kern-Allely, Ann Pobutsky, W. Thane Hancock
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Local transmission of dengue virus on Guam was reported for the first time in 75 years. Transmission was likely driven by Aedes albopictus mosquitoes after the previously known vector, Aedes aegypti, was eradicated by the US military after World War II.
Reply
Authors: Manoj Kumar
Journal: Hepatology (2020)

Potential conflict of interest: Nothing to report. We thank Primignani et al. for taking interest in our article. We agree with their comments that the cutoffs of conventional tests and thromboelastography used in our study for transfusion of blood products is arbitrary. There are also no studies, to our knowledge, assessing whether blood products are actually needed in patients with cirrhosis in various clinical settings and with different degrees of coagulopathy. Appropriately designed studies are needed in the future to answer the following questions: What are the cutoffs for coagulation tests and viscoelastic hemostatic assays at which blood products should be transfused in patients with cirrhosis in different clinical settings (for patients undergoing invasive procedures, variceal and nonvariceal bleeding, and so on)? And if blood products are needed, can the currently used arbitrary cutoffs be relaxed?
Catcher in the rel: Nanoparticles-antibody conjugate as NF-κB nuclear translocation blocker
Authors: Yi-Ping Chen, Chien-Tsu Chen, Tsang-Pai Liu, Fan-Ching Chien, Si-Han Wu, Peilin Chen, Chung-Yuan Mou
Journal: Biomaterials (2020)

Transcription factor complex NF-κB (p65/p50) is localized to the cytoplasm by its inhibitor IκBα. Upon activation, the Rel proteins p65/p50 are released from IκBα and transported through nuclear pore to affect many gene expressions. While inhibitions of up or down stream signal pathways are often ineffective due to crosstalks and compensations, direct blocking of the Rel proteins p65/p50 has long been proposed as a potential target for cancer therapy. In this work, a nanoparticle/antibody complex targeting NF-κB is employed to catch the Rel protein p65 in perinuclear region and thus blocking the translocation near the nuclear pore gate. TAT peptide conjugated on mesoporous silica nanoparticles (MSN) help non-endocytosis cell-membrane transducing and converge toward perinuclear region, where the p65 specific antibody performed the targeting and catching against active NF-κB p65 effectively. The size of the p65 bound nanoparticle becomes too big to enter nucleus. Simultaneous treatment of mice with the hybrid MSN and doxorubicin conferred a significant therapeutic effect against 4T1 tumor-bearing mice. The new approach of anti-body therapy targeting on transcription factor with "nucleus focusing" and "size exclusion blocking" effects of the antibody-conjugated nanoparticle is general and may be applicable to modulating other transcription factors.
Gene signatures associated with genomic aberrations predict prognosis in neuroblastoma
Authors: Xiaoyan He, Chao Qin, Yanding Zhao, Lin Zou, Hui Zhao, Chao Cheng
Journal: Cancer Communications (2020)

Abstract Background Neuroblastoma (NB) is a heterogeneous disease with respect to genomic abnormalities and clinical behaviors. Despite recent advances in our understanding of the association between the genetic aberrations and clinical features, it remains one of the major challenges to predict prognosis and stratify patients for determining personalized therapy in this disease. The aim of this study was to develop an effective prognosis prediction model for NB patients. Methods We integrated diverse computational analyses to define gene signatures that reflect MYCN activity and chromosomal aberrations including deletion of chromosome 1p (Chr1p_del) and chromosome 11q (Chr11q_del) as well as chromosome 11q whole loss (Chr11q_wls). We evaluated the prognostic and predictive values of these signatures in seven NB gene expression datasets (the number of samples ranges from 94 to 498, with a total of 2120) generated from both RNA sequencing and microarray platforms. Results MYCN signature was a more effective prognostic marker than MYCN amplification status and MYCN expression. Similarly, the Chr1p_del score was more prognostic than Chr1p status. The activity scores of MYCN, Chr1p_del and Chr11q_del were associated with poor prognosis, while the Chr11q_wls score was linked to good outcome. We integrated the activity scores of MYCN, Chr1p_del, Chr11q_del, and Chr11q_wls and clinical variables into an integrative prognostic model, which displayed significant performance over the clinical variables or each genomic aberration alone. Conclusions Our integrative gene signature model shows a significantly improved forecast performance with prognostic and predictive information, and thereby can be served as a biomarker to stratify NB patients for prognosis evaluation and surveillance programs.
Treatment for Advanced Soft Tissue Sarcoma
Authors: Christina L. Roland, Sandra L. Wong
Journal: JAMA (2020)

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Quantifying the use of connected digital products in clinical research
Authors: Caroline Marra, Jacqueline L. Chen, Andrea Coravos, Ariel D. Stern
Journal: npj Digital Medicine (2020)

Over recent years, the adoption of connected technologies has grown dramatically, with potential for improving health care delivery, research, and patient experience. Yet, little has been documented about the prevalence and use of connected digital products (e.g., products that capture physiological and behavioral metrics) in formal clinical research. Using 18 years of data from ClinicalTrials.gov, we document substantial growth in the use of connected digital products in clinical trials (~34% CAGR) and show that these products have been used across all phases of research and by a diverse group of trial sponsors. We identify four distinct use cases for how such connected products have been integrated within clinical trial design and suggest implications for various stakeholders engaging in clinical research.
Physiological rationale of commonly used clinical exercise tests
Authors: Luis Puente-Maestu
Journal: Pulmonology (2020)

In order to measure cardiopulmonary performance for clinical and investigation purposes we need standardized tests which allow the comparison with standard values, between people, or individuals with themselves over time. The quest for the ideal exercise test has led to the development of several formats, the so called laboratory and field tests. Incremental exercise tests allow measurement of maximal exercise capacity and a host of submaximal variables of great interest. The physiological rationale of the tests and of the detection of interesting submaximal variables can be explained from the oxygen uptake and carbon dioxide output kinetic response to constant power exercise. When the muscles have to produce very high energy, the exercise is physiologically limited to relatively short duration. The minimum power at which an exercise can no longer be sustained for long periods of time is called critical power. Above critical power the time-power function shows a hyperbolic shape. This shape provides the rationale for understanding the properties, limitations and responsiveness to interventions of endurance tests such as constant power test on a cycle-ergometer or treadmill, endurance shuttle walk test and six-minute walk test.
Access to Transcatheter Aortic Valve Replacement Under New Medicare Surgical Volume Requirements
Authors: Michael P. Thompson, Alexander A. Brescia, Hechuan Hou, Francis D. Pagani, Devraj Sukul, Justin B. Dimick, Donald S. Likosky
Journal: JAMA Cardiology (2020)

This cohort study examines the frequency and characteristics of non–transcatheter aortic valve replacement (TAVR) hospitals that do or do not meet new surgical volume requirements compared with TAVR hospitals.
Treatment reality in elderly patients with advanced ovarian cancer: A prospective analysis of the OVCAD consortium.
Authors: Linn Lena Woelber, Christine Eulenburg, Ioana Braicu, Jalid Sehouli, Sandrina Lambrechts, Ignace B. Vergote, Gudrun Hager, Robert Zeillinger, Alain G Zeimet, Sven Mahner
Journal: Journal of Clinical Oncology (2012)

5058 Background: Approximately one third of women diagnosed with ovarian cancer are 70 years or older. Standard therapy of ovarian cancer including radical cytoreduction and combination chemotherapy has considerable morbidity and information regarding treatment reality in elderly patients with ovarian cancer is very limited. Methods: Patients with primary epithelial ovarian cancer FIGO-stages IIB-IV were prospectively included in 5 European cancer centers. All patients underwent surgery with the intent of maximal cytoreduction and platinum-based chemotherapy. To analyze treatment strategies and outcome in the elderly, patients were subdivided in &lt;70 years and ≥70 years of age and compared regarding clinicopathological variables and prognosis. Results: A total of 275 patients were included and followed for a median of 25 months. Median age of the total cohort was 58 (18-85) years with only 47 patients (17.1%) ≥70 years old. Age itself was not a prognostic factor for progression free survival (PFS) in multivariate analysis. 30-days mortality rate after primary surgery was 3.6% in elderly patients compared to 0.6% in patients &lt;70 years (p=0.153). Surgery was less radical in patients ≥70 (e.g. fewer lymph node dissections p&lt;0.001) and the percentage of patients with residual disease after surgery was higher in elderly (44.7%) compared to younger patients (28.5%) despite similar FIGO stage distribution (p=0.029). Furthermore, elderly received more often mono-chemotherapy (p&lt;0.001). Consequently, outcome was less favorable in patients ≥70 compared to patients &lt;70 years (75% overall survival 16 vs. 28 months; p=0.002 and median PFS 14 vs. 20 months; p=0.182). Conclusions: In this prospective European multicenter study, ovarian cancer patients age 70 and older were treated significantly less radical and had unfavorable outcome compared to younger patients. Specific trials for elderly patients focusing on surgical as well as chemotherapeutic aspects are therefore highly desirable to gain more information in an aging society.
Transplant eligibility in elderly multiple myeloma patients: Prospective external validation of the international myeloma working group frailty score and comparison with clinical judgment and other comorbidity scores in unselected patients aged 65‐75 years
Authors: Angelo Belotti, Rossella Ribolla, Valeria Cancelli, Claudia Crippa, Nicola Bianchetti, Samantha Ferrari, Chiara Bottelli, Chiara Cattaneo, Alessandra Tucci, Carmen De La Fuente Barrigon, Giuseppe Rossi
Journal: American Journal of Hematology (2020)

Abstract Autologous stem cell transplantation (ASCT) is feasible and effective in selected older patients with Multiple Myeloma, but specific criteria for evaluating ASCT eligibility in elderly patients are lacking. We evaluated 131 patients aged 65‐75 considered for ASCT at our center: The Charlson Comorbidity Index (CCI), Hematopoietic cell transplantation comorbidity index (HCT‐CI) and IMWG frailty score were obtained at diagnosis, but the intensity of treatment was left to physician's choice. The scores and age's impact on outcome was analyzed: 85 patients were judged transplant eligible, whereas 46 patients received a less intensive treatment (median follow up 27 months). No patients classified as frail had been considered eligible to ASCT with a worse outcome compared to fit and unfit patients (median PFS (progression free survival): 7.9 vs 32.9 and 29.6 months; P &lt; .001). PFS was superior in the ASCT group (35.6 vs 19.9 months, P .013). In the ASCT group, PFS was better in patients aged 65‐69 years than in patients ≥70 (51.5 vs 27.7 months, P .004). Indeed, in unfit patients aged ≥70 the PFS of the ASCT group was comparable to NO ASCT group (18 vs 27 months, P = .33) whereas in unfit patients aged 65‐69 PFS was superior in the ASCT group: 43.3 vs 18.4 months, P .01. ISS III and impaired functional status independently affected PFS in a multivariate analysis ( P .011 and P .006). While CCI and HCT‐CI did not predict different outcome in ASCT patients, the IMWG frailty score would be of help in identifying unfit patients aged 70‐75, whose outcome with ASCT selected by clinical judgment was no better than with less intensive treatments.