tbuckley/cabot-search huggingface dataset:
Clinical Calculator Based on Molecular and Clinicopathologic Characteristics Predicts Recurrence Following Resection of Stage I-III Colon Cancer
Authors: Martin R. Weiser, Meier Hsu, Philip S. Bauer, William C. Chapman, Iván A. González, Deyali Chatterjee, Deepak Lingam, Matthew G. Mutch, Ajaratu Keshinro, Jinru Shia, Efsevia Vakiani, Tsuyoshi Konishi, Yoshifumi Shimada, Zsofia Stadler, Neil H. Segal, Andrea Cercek, Leonard Saltz, Rona Yaeger, Anna Varghese, Maria Widmar, Iris H. Wei, Emmanouil P. Pappou, J. Joshua Smith, Garrett Nash, Philip Paty, Julio Garcia-Aguilar, Mithat Gonen
Journal: Journal of Clinical Oncology (2021)

PURPOSE Clinical calculators and nomograms have been endorsed by the American Joint Committee on Cancer (AJCC), as they provide the most individualized and accurate estimate of patient outcome. Using molecular and clinicopathologic variables, a third-generation clinical calculator was built to predict recurrence following resection of stage I-III colon cancer. METHODS Prospectively collected data from 1,095 patients who underwent colectomy between 2007 and 2014 at Memorial Sloan Kettering Cancer Center were used to develop a clinical calculator. Discrimination was measured with concordance index, and variability in individual predictions was assessed with calibration curves. The clinical calculator was externally validated with a patient cohort from Washington University's Siteman Cancer Center in St Louis. RESULTS The clinical calculator incorporated six variables: microsatellite genomic phenotype; AJCC T category; number of tumor-involved lymph nodes; presence of high-risk pathologic features such as venous, lymphatic, or perineural invasion; presence of tumor-infiltrating lymphocytes; and use of adjuvant chemotherapy. The concordance index was 0.792 (95% CI, 0.749 to 0.837) for the clinical calculator, compared with 0.708 (95% CI, 0.671 to 0.745) and 0.757 (0.715 to 0.799) for the staging schemes of the AJCC manual's 5th and 8th editions, respectively. External validation confirmed robust performance, with a concordance index of 0.738 (95% CI, 0.703 to 0.811) and calibration plots of predicted probability and observed events approaching a 45° diagonal. CONCLUSION This third-generation clinical calculator for predicting cancer recurrence following curative colectomy successfully incorporates microsatellite genomic phenotype and the presence of tumor-infiltrating lymphocytes, resulting in improved discrimination and predictive accuracy. This exemplifies an evolution of a clinical calculator to maintain relevance by incorporating emerging variables as they become validated and accepted in the oncologic community.
National Psoriasis Foundation COVID-19 Task Force guidance for management of psoriatic disease during the pandemic: Version 2—Advances in psoriatic disease management, COVID-19 vaccines, and COVID-19 treatments
Authors: Joel M. Gelfand, April W. Armstrong, Stacie Bell, George L. Anesi, Andrew Blauvelt, Cassandra Calabrese, Erica D. Dommasch, Steven R. Feldman, Dafna Gladman, Leon Kircik, Mark Lebwohl, Vincent Lo Re, George Martin, Joseph F. Merola, Jose U. Scher, Sergio Schwartzman, James R. Treat, Abby S. Van Voorhees, Christoph T. Ellebrecht, Justine Fenner, Anthony Ocon, Maha N. Syed, Erica J. Weinstein, George Gondo, Sue Heydon, Samantha Koons, Christopher T. Ritchlin
Journal: Journal of the American Academy of Dermatology (2021)
Problematic Promotion of Medications by Nurse Ambassadors—Legal and Ethical Issues
Authors: Y. Tony Yang, Diana J. Mason
Journal: JAMA (2021)

Problematic Promotion of Medications by Nurse Ambassadors-Legal and Ethical IssuesA number of pharmaceutical companies offer nurse ambassador programs that typically involve companyemployed registered nurses who interact with patients to help facilitate the use of complicated medications that have been prescribed for the patient.However, some of these companies have been the subject of lawsuits alleging that their programs are inappropriately blurring the line between caregiver and marketer.In August 2020, the pharmaceutical company AbbVie agreed to pay California $24 million to settle a whistleblower case that involved its nurse ambassador program for adalimumab (Humira), while not admitting any wrongdoing. 1 Nurse ambassador programs in part aim to ensure that patients continue the use of costly medications and have provided incentives to physicians and other clinicians to prescribe the medication.The programs continue to be largely unregulated by the federal government, with US Department of Justice guidance suggesting that the program could have an important role in patient interactions in some cases. 2rse ambassador programs are not confined to AbbVie. 3 Companies such as Lilly, Gilead Sciences, Bayer, Amgen, AstraZeneca, Vanda Pharmaceuticals, Berlex, Pfizer, and EMD Serono have similar programs and sometimes refer to the nurses as patient or clinical "educators." 4 Although it is not known how many nurse ambassadors are currently employed in the United States or how many AbbVie employs, the company has nurse ambassador programs for 2 other medications (risankizumab-rzaa and glecaprevir/pibrentasvir). According to a report from 2018, one nurse reported that the company had 400 nurse ambassadors when she left the nurse ambassador program that year. 5he AbbVie-California settlement provides guidance at the state level and suggests that the programs can continue with some changes, but legal and ethical concerns remain.
25 years of anti-TNF treatment for inflammatory bowel disease: lessons from the past and a look to the future
Authors: Geert R D'Haens, Sander van Deventer
Journal: Gut (2021)

Anti-tumour necrosis factor (TNF) antibodies have been widely used for approximately 25 years now. The first clinical observations in patients with refractory Crohn’s disease rapidly responding to infliximab prompted accelerated clinical development and approval for this indication. However, many questions remained unanswered when this treatment came to market related to maintenance schedules, pharmacokinetics, toxicity and positioning. Many of these open questions were addressed by investigators and sponsors during more than two decades of clinical use. The authors were among the first to use infliximab in Crohn’s disease and felt that now is a good time to look back and draw lessons from the remarkable anti-TNF story. Even today, new insights continue to appear. But more importantly, what was learnt in the past 25 years has created a platform for future development of even stronger and safer therapies. We should not forget to learn from the past.
Maternal high-fat high-sucrose diet and gestational exercise modulate hepatic fat accumulation and liver mitochondrial respiratory capacity in mothers and male offspring
Authors: Jelena Stevanović-Silva, Jorge Beleza, Pedro Coxito, Susana Pereira, Hugo Rocha, Tiago Bordeira Gaspar, Fátima Gärtner, Rossana Correia, Maria João Martins, Tiago Guimarães, Sandra Martins, Paulo J. Oliveira, António Ascensão, José Magalhães
Journal: Metabolism (2021)

Maternal high-caloric nutrition and related gestational diabetes mellitus (GDM) are associated with a high-risk for developing metabolic complications later in life and in their offspring. In contrast, exercise is recognized as a non-pharmacological strategy against metabolic dysfunctions associated to lifestyle disorders. Therefore, we investigated whether gestational exercise delays the development of metabolic alterations in GDM mothers later in life, but also protects 6-week-old male offspring from adverse effects of maternal diet.Female Sprague-Dawley rats were fed with either control (C) or high-fat high-sucrose (HFHS) diet to induce GDM and submitted to gestational exercise during the 3 weeks of pregnancy. Male offspring were sedentary and fed with C-diet.Sedentary HFHS-fed dams exhibited increased gestational body weight gain (p < 0.01) and glucose intolerance (p < 0.01), characteristic of GDM. Their offspring had normal glucose metabolism, but increased early-age body weight, which was reverted by gestational exercise. Gestational exercise also reduced offspring hepatic triglycerides accumulation (p < 0.05) and improved liver mitochondrial respiration capacity (p < 0.05), contributing to the recovery of liver bioenergetics compromised by maternal HFHS diet. Interestingly, liver mitochondrial respiration remained increased by gestational exercise in HFHS-fed dams despite prolonged HFHS consumption and exercise cessation.Gestational exercise can result in liver mitochondrial adaptations in GDM animals, which can be preserved even after the exercise program cessation. Exposure to maternal GDM programs liver metabolic setting of male offspring, whereas gestational exercise appears as an important preventive tool against maternal diet-induced metabolic alterations.
Network for Biomarker Immunoprofiling for Cancer Immunotherapy: Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC)
Authors: Helen X. Chen, Minkyung Song, Holden T. Maecker, Sacha Gnjatic, David Patton, J. Jack Lee, Stacey J. Adam, Radim Moravec, Xiaole Shirley Liu, Ethan Cerami, James Lindsay, Ming Tang, F. Stephen Hodi, Catherine J. Wu, Ignacio I. Wistuba, Gheath Al-Atrash, Chantale Bernatchez, Sean C. Bendall, Stephen M. Hewitt, Elad Sharon, Howard Streicher, Rebecca A. Enos, Melissa D. Bowman, Valerie M. Tatard-Leitman, Beatriz Sanchez-Espiridion, Srinika Ranasinghe, Mina Pichavant, Diane M. Del Valle, Joyce Yu, Sylvie Janssens, Jenny Peterson-Klaus, Cathy Rowe, Gerold Bongers, Robert R. Jenq, Chia-Chi Chang, Jeffrey S. Abrams, Margaret Mooney, James H. Doroshow, Lyndsay N. Harris, Magdalena Thurin
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Immunoprofiling to identify biomarkers and integration with clinical trial outcomes are critical to improving immunotherapy approaches for patients with cancer. However, the translational potential of individual studies is often limited by small sample size of trials and the complexity of immuno-oncology biomarkers. Variability in assay performance further limits comparison and interpretation of data across studies and laboratories. Experimental Design: To enable a systematic approach to biomarker identification and correlation with clinical outcome across trials, the Cancer Immune Monitoring and Analysis Centers and Cancer Immunologic Data Commons (CIMAC-CIDC) Network was established through support of the Cancer MoonshotSM Initiative of the National Cancer Institute (NCI) and the Partnership for Accelerating Cancer Therapies (PACT) with industry partners via the Foundation for the NIH. Results: The CIMAC-CIDC Network is composed of four academic centers with multidisciplinary expertise in cancer immunotherapy that perform validated and harmonized assays for immunoprofiling and conduct correlative analyses. A data coordinating center (CIDC) provides the computational expertise and informatics platforms for the storage, integration, and analysis of biomarker and clinical data. Conclusions: This overview highlights strategies for assay harmonization to enable cross-trial and cross-site data analysis and describes key elements for establishing a network to enhance immuno-oncology biomarker development. These include an operational infrastructure, validation and harmonization of core immunoprofiling assays, platforms for data ingestion and integration, and access to specimens from clinical trials. Published in the same volume are reports of harmonization for core analyses: whole-exome sequencing, RNA sequencing, cytometry by time of flight, and IHC/immunofluorescence.
Audio Interview: Planning for the SARS-CoV-2 Vaccine Rollout
Authors: Eric J. Rubin, Lindsey R. Baden, Thomas H. Lee, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

Planning for the SARS-CoV-2 Vaccine Rollout In this audio interview conducted on January 6, 2021, the editors are joined by cardiologist and primary care physician Thomas H. Lee to discuss how heal...
Toward better governance of human genomic data
Authors: Kieran C. O’Doherty, Mahsa Shabani, Edward S. Dove, Heidi Beate Bentzen, Pascal Borry, Michael M. Burgess, Don Chalmers, Jantina De Vries, Lisa Eckstein, Stephanie M. Fullerton, Eric Juengst, Kazuto Kato, Jane Kaye, Bartha Maria Knoppers, Barbara A. Koenig, Spero M. Manson, Kimberlyn M. McGrail, Amy L. McGuire, Eric M. Meslin, Dianne Nicol, Barbara Prainsack, Sharon F. Terry, Adrian Thorogood, Wylie Burke
Journal: Nature Genetics (2021)
Role of core protein mutations in the development of occult HBV infection
Authors: Jingna Chen, Bochao Liu, Xi Tang, Xin Zheng, Jinhui Lu, Ling Zhang, Wenjing Wang, Daniel Candotti, Yongshui Fu, Jean-Pierre Allain, Chengyao Li, Linhai Li, Tingting Li
Journal: Journal of Hepatology (2021)
MO01.38 Registrational Dataset from the Phase 1/2 ARROW Trial of Pralsetinib (BLU-667) in Patients with Advanced RET Fusion+ Non-Small-Cell Lung Cancer (NSCLC)
Authors: J.F. Gainor, G. Curigliano, D.-W. Kim, D.H. Lee, B. Besse, C.S. Baik, R.C. Doebele, P. Cassier, G. Lopes, D.S.-W. Tan, E. Garralda, L. Paz-Ares, B.C. Cho, S.M. Gadgeel, M. Thomas, S.V. Liu, C. Clifford, H. Zhang, C.D. Turner, V. Subbiah
Journal: Journal of Thoracic Oncology (2021)
Herbal and Dietary Supplements-Induced Liver Injury in Latin America: Experience From the LATINDILI Network
Authors: Fernando Bessone, Miren García-Cortés, Inmaculada Medina-Caliz, Nelia Hernandez, Raymundo Parana, Manuel Mendizabal, Maria I. Schinoni, Ezequiel Ridruejo, Vinicius Nunes, Mirta Peralta, Genario Santos, Margarita Anders, Daniela Chiodi, Martin Tagle, Pedro Montes, Enrique Carrera, Marco Arrese, M. Isabel Lizarzabal, Ismael Alvarez-Alvarez, Estefania Caballano-Infantes, Hao Niu, Jose Pinazo, Maria R. Cabello, M. Isabel Lucena, Raúl J. Andrade
Journal: Clinical Gastroenterology and Hepatology (2021)
Quantitative profiling of N6-methyladenosine at single-base resolution in stem-differentiating xylem of Populus trichocarpa using Nanopore direct RNA sequencing
Authors: Yubang Gao, Xuqing Liu, Bizhi Wu, Huihui Wang, Feihu Xi, Markus V. Kohnen, Anireddy S. N. Reddy, Lianfeng Gu
Journal: Genome biology (2021)

Abstract There are no comprehensive methods to identify N 6 -methyladenosine (m 6 A) at single-base resolution for every single transcript, which is necessary for the estimation of m 6 A abundance. We develop a new pipeline called Nanom6A for the identification and quantification of m 6 A modification at single-base resolution using Nanopore direct RNA sequencing based on an XGBoost model. We validate our method using methylated RNA immunoprecipitation sequencing (MeRIP-Seq) and m 6 A-sensitive RNA-endoribonuclease–facilitated sequencing (m6A-REF-seq), confirming high accuracy. Using this method, we provide a transcriptome-wide quantification of m 6 A modification in stem-differentiating xylem and reveal that different alternative polyadenylation (APA) usage shows a different ratio of m 6 A.
Noninvasive Prediction of Occult Peritoneal Metastasis in Gastric Cancer Using Deep Learning
Authors: Yuming Jiang, Xiaokun Liang, Wei Wang, Chuanli Chen, Qingyu Yuan, Xiaodong Zhang, Na Li, Hao Chen, Jiang Yu, Yaoqin Xie, Yikai Xu, Zhiwei Zhou, Guoxin Li, Ruijiang Li
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Occult peritoneal metastasis frequently occurs in patients with advanced gastric cancer and is poorly diagnosed with currently available tools. Because the presence of peritoneal metastasis precludes the possibility of curative surgery, there is an unmet need for a noninvasive approach to reliably identify patients with occult peritoneal metastasis. <h3>Objective</h3> To assess the use of a deep learning model for predicting occult peritoneal metastasis based on preoperative computed tomography images. <h3>Design, Setting, and Participants</h3> In this multicenter, retrospective cohort study, a deep convolutional neural network, the Peritoneal Metastasis Network (PMetNet), was trained to predict occult peritoneal metastasis based on preoperative computed tomography images. Data from a cohort of 1225 patients with gastric cancer who underwent surgery at Sun Yat-sen University Cancer Center (Guangzhou, China) were used for training purposes. To externally validate the model, data were collected from 2 independent cohorts comprising a total of 753 patients with gastric cancer who underwent surgery at Nanfang Hospital (Guangzhou, China) or the Third Affiliated Hospital of Southern Medical University (Guangzhou, China). The status of peritoneal metastasis for all patients was confirmed by pathological examination of pleural specimens obtained during surgery. Detailed clinicopathological data were collected for each patient. Data analysis was performed between September 1, 2019, and January 31, 2020. <h3>Main Outcomes and Measures</h3> The area under the receiver operating characteristic curve (AUC) and decision curve were analyzed to evaluate performance in predicting occult peritoneal metastasis. <h3>Results</h3> A total of 1978 patients (mean [SD] age, 56.0 [12.2] years; 1350 [68.3%] male) were included in the study. The PMetNet model achieved an AUC of 0.946 (95% CI, 0.927-0.965), with a sensitivity of 75.4% and a specificity of 92.9% in external validation cohort 1. In external validation cohort 2, the AUC was 0.920 (95% CI, 0.848-0.992), with a sensitivity of 87.5% and a specificity of 98.2%. The discrimination performance of PMetNet was substantially higher than conventional clinicopathological factors (AUC range, 0.51-0.63). In multivariable logistic regression analysis, PMetNet was an independent predictor of occult peritoneal metastasis. <h3>Conclusions and Relevance</h3> The findings of this cohort study suggest that the PMetNet model can serve as a reliable noninvasive tool for early identification of patients with clinically occult peritoneal metastasis, which will inform individualized preoperative treatment decision-making and may avoid unnecessary surgery and complications. These results warrant further validation in prospective studies.
Optical Tissue Clearing: Illuminating Brain Function and Dysfunction
Authors: Xiaohan Liang, Haiming Luo
Journal: Theranostics (2021)

Tissue optical clearing technology has been developing rapidly in the past decade due to advances in microscopy equipment and various labeling techniques. Consistent modification of primary methods for optical tissue transparency has allowed observation of the whole mouse body at single-cell resolution or thick tissue slices at the nanoscale level, with the final aim to make intact primate and human brains or thick human brain tissues optically transparent. Optical clearance combined with flexible large-volume tissue labeling technology can not only preserve the anatomical structure but also visualize multiple molecular information from intact samples in situ. It also provides a new strategy for studying complex tissues, which is of great significance for deciphering the functional structure of healthy brains and the mechanisms of neurological pathologies. In this review, we briefly introduce the existing optical clearing technology and discuss its application in deciphering connection and structure, brain development, and brain diseases. Besides, we discuss the standard computational analysis tools for large-scale imaging dataset processing and information extraction. In general, we hope that this review will provide a valuable reference for researchers who intend to use optical clearing technology in studying the brain.
Clofarabin Added to Standard Treatment in Adult Patients with Newly Diagnosed ALL: First Results of the Randomized Phase III HOVON-100 Study
Authors: A. W. Rijneveld, Bronno van der Holt, Okke de Weerdt, Bart J. Biemond, Arjen van de Loosdrecht, Eefke Petersen, Mar Bellido, Harry C. Schouten, Walter J F M van der Velden, Dominik Selleslag, Martin R. Schipperus, Constantijn J.M. Halkes, Saskia Klein, Violaine Havelange, Marinus van Marwijk Kooij, Marie-Cecile Legdeur, Jeannine Refos, Vincent van der Velden, Jan J Cornelissen, Crista Homburg, Valerie de Haas, Dries Deeren, Alain Gaddiseur, Harm Sinnige, Dimitri Breems
Journal: Blood (2017)
The relationship between rowing-related low back pain and rowing biomechanics: a systematic review
Authors: Frank James Nugent, Anders Vinther, Alison McGregor, Jane S Thornton, Kellie Wilkie, Fiona Wilson
Journal: British Journal of Sports Medicine (2021)

Background Low back pain (LBP) is common in rowers. Understanding rowing biomechanics may help facilitate prevention and improve rehabilitation. Objectives To define the kinematics and muscle activity of rowers and to compare with rowers with current or LBP history. Design Systematic review. Data sources EMBASE, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, Web of Science and Scopus from inception to December 2019. Grey literature was searched. Study eligibility criteria Experimental and non-experimental designs. Methods Primary outcomes were kinematics and muscle activity. Modified Quality Index (QI) checklist was used. Results 22 studies were included (429 participants). Modified QI score had a mean of 16.7/28 points (range: 15–21). Thirteen studies investigated kinematics and nine investigated muscle activity. Rowers without LBP (‘healthy’) have distinct kinematics (neutral or anterior pelvic rotation at the catch, greater hip range of motion, flatter low back spinal position at the finish) and muscle activity (trunk extensor dominant with less flexor activity). Rowers with LBP had relatively greater posterior pelvic rotation at the catch, greater hip extension at the finish and less efficient trunk muscle activity. In both groups fatigue results in increased lumbar spine flexion at the catch, which is greater on the ergometer. There is insufficient evidence to recommend one ergometer type (fixed vs dynamic) over the other to avoid LBP. Trunk asymmetries are not associated with LBP in rowers. Conclusion Improving clinicians’ and coaches’ understanding of safe and effective rowing biomechanics, particularly of the spine, pelvis and hips may be an important strategy in reducing incidence and burden of LBP.