tbuckley/cabot-search huggingface dataset:
Association Between Gut Microbiota and Symptomatic Hand Osteoarthritis: Data From the Xiangya Osteoarthritis Study
Authors: Jie Wei, Chenhong Zhang, Yuqing Zhang, Weiya Zhang, Michael Doherty, Tuo Yang, Guangju Zhai, Abasiama D. Obotiba, Houchen Lyu, Chao Zeng, Guanghua Lei
Journal: Arthritis & Rheumatology (2021)

Systemic inflammatory factors have been implicated in symptomatic hand osteoarthritis (OA). Gut microbiome dysbiosis promotes systemic inflammation. The aim of this study was to examine the association between the gut microbiome and the presence of symptomatic hand OA in a population-based study.Study participants were subjects of the Xiangya Osteoarthritis Study, a community-based observational study conducted in the Hunan Province of China. Symptomatic hand OA was defined as the presence of both symptoms and radiographic OA in the same hand. The gut microbiome was analyzed using 16S ribosomal RNA gene sequencing in stool samples. We examined the relation of α-diversity, β-diversity, relative abundance of taxa, and potential bacterial functional pathways to symptomatic hand OA.A total of 1,388 participants (mean age 61.3 years, 57.4% women) were included in the study, of whom 72 had symptomatic hand OA (prevalence of symptomatic hand OA 5.2%). Beta-diversity of the gut microbiome, but not α-diversity, was significantly associated with the presence of symptomatic hand OA (P = 0.003). Higher relative abundance of the genera Bilophila and Desulfovibrio as well as lower relative abundance of the genus Roseburia was associated with symptomatic hand OA. Most functional pathways (i.e., those annotated in the KEGG Ortholog hierarchy) that were observed to be altered in participants with symptomatic hand OA belonged to the amino acid, carbohydrate, and lipid metabolic pathways.This large, population-based study provides the first evidence that alterations in the composition of the gut microbiome were observed among study participants who had symptomatic hand OA, and a low relative abundance of Roseburia but high relative abundance of Bilophila and Desulfovibrio at the genus level were associated with prevalent symptomatic hand OA. These findings may help investigators understand the role of the microbiome in the development of symptomatic hand OA and could contribute to potential translational opportunities.
Errors in Introduction, Results Section, and Table and Omitted Caption for Figure
Journal: JAMA Network Open (2021)

Adrienne V. Nickles, MPH; Adam Oostema, MD; Justin Allen, BA, EMT-P; Suzanne L. O’Brien, MSN, RN, ANVP; Stacie L. Demel, DO, PhD; Mathew J. Reeves, PhD
Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs
Authors: Amy K. LeBlanc, Christina N. Mazcko, Aswini Cherukuri, Erika P. Berger, William C. Kisseberth, Megan E. Brown, Susan E. Lana, Kristen Weishaar, Brian K. Flesner, Jeffrey N. Bryan, David M. Vail, Jenna H. Burton, Jennifer L. Willcox, Anthony J. Mutsaers, J. Paul Woods, Nicole C. Northrup, Corey Saba, Kaitlin M. Curran, Haley Leeper, Heather Wilson-Robles, Brandan G. Wustefeld-Janssens, Stephanie Lindley, Annette N. Smith, Nikolaos Dervisis, Shawna Klahn, Mary Lynn Higginbotham, Raelene M. Wouda, Erika Krick, Jennifer A. Mahoney, Cheryl A. London, Lisa G. Barber, Cheryl E. Balkman, Angela L. McCleary-Wheeler, Steven E. Suter, Olya Martin, Antonella Borgatti, Kristine Burgess, Michael O. Childress, Janean L. Fidel, Sara D. Allstadt, Daniel L. Gustafson, Laura E. Selmic, Chand Khanna, Timothy M. Fan
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. Patients and Methods: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. Results: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively. Conclusions: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.
P85.02 NGS could not Replace FISH Regarding to MET Amplification as an Optimal Biomarker
Authors: L. Peng, A. Li, S. Liu, H. Sun, M. Zheng, J. Zhou, J. Zhang, X. Zhang, Q. Zhou, W. Zhong, X. Yang, H. Tu, J. Su, H. Yan, L. Gou, H. Gao, Y. Wu
Journal: Journal of Thoracic Oncology (2021)
Abstract 12215: Platelet Inhibition of Ticagrelor versus Clopidogrel in Diabetic Patients After Elective Percutaneous Coronary Intervention for Stable Coronary Artery Disease
Authors: Zhenyu Liu, Ran Tian, Yang Wang, Qian Chen, Jingyi Li, Lihong Xu, Shuyang Zhang
Journal: Circulation (2019)

Background: In patients undergoing elective percutaneous coronary intervention (PCI) for stable coronary artery disease (SCAD), those with diabetes have poor therapeutic response to clopidogrel. Th...
P86.08 Phase 2 Study of Zenocutuzumab (MCLA-128), a Bispecific HER2/HER3 Antibody in NRG1 Fusion-Positive Advanced Solid Tumors
Authors: A. Schram, T. Macarulla, E. O’Reilly, J. Rodon, B. Wolpin, S. Ou, D. Kim, J.C. Yang, J. Lam, A. De Langen, V. Boni, G. Cerea, M. Duruisseaux, E. Felip, S. Liu, G. O'Kane, F. Senecal, M. Nagasaka, J. Starr, E. Wasserman, A. Drilon
Journal: Journal of Thoracic Oncology (2021)
Acute Knee Injuries in Children and Adolescents
Authors: James MacDonald, Richard Rodenberg, Emily Sweeney
Journal: JAMA Pediatrics (2021)

Knee injuries in children and adolescents are exceedingly common. When an active youth presents complaining of knee pain, the treating pediatrician should be comfortable with forming a working differential diagnosis and should be able to manage many such injuries or recognize when it is necessary to make an appropriate referral.Knee injuries typically present after acute trauma. Appreciating the likely etiologies pertaining to a particular case is best achieved with a thorough history and physical examination. This review discusses the etiologies of acute injuries including fractures that are unique to skeletally immature individuals, patellar dislocations, ligamentous injuries, and meniscal tears. Imaging findings and management of these conditions are also reviewed.This review summarizes the more common acute knee injuries seen in active children and adolescents. Given how frequently such conditions present, this overview of diagnosis and management will provide a useful resource for the nonspecialist.
Recombinant vaccine containing an RBD-Fc fusion induced protection against SARS-CoV-2 in nonhuman primates and mice
Authors: Shihui Sun, Lei He, Zhongpeng Zhao, Hongjing Gu, Xin Fang, Tiecheng Wang, Xiaolan Yang, Shaolong Chen, Yongqiang Deng, Jiangfan Li, Jian Zhao, Liang Li, Xinwang Li, Peng He, Ge Li, Hao Li, Yuee Zhao, Chunrun Gao, Xiaoling Lang, Xin Wang, Guoqiang Fei, Yan Li, Shusheng Geng, Yuwei Gao, Wenjin Wei, Zhongyu Hu, Gencheng Han, Yansong Sun
Journal: Cellular and Molecular Immunology (2021)
Association of Vitamin D Levels, Race/Ethnicity, and Clinical Characteristics With COVID-19 Test Results
Authors: David O. Meltzer, Thomas J. Best, Hui Zhang, Tamara Vokes, Vineet M. Arora, Julian Solway
Journal: JAMA Network Open (2021)

Deficient (ie, <20 ng/mL) or insufficient (ie, 20 to <30 ng/mL) 25-hydroxyvitamin D (also known as calcifediol) levels are more common in Black individuals than White individuals and are associated with increased coronavirus disease 2019 (COVID-19) risk. Whether COVID-19 risk is associated with differences in vitamin D levels of 30 ng/mL or greater is not known.
Inherited glycosylphosphatidylinositol defects cause the rare Emm-negative blood phenotype and developmental disorders
Authors: Romain Duval, Gaël Nicolas, Alexandra Willemetz, Yoshiko Murakami, Mahmoud Mikdar, Cedric Vrignaud, Hisham Megahed, Jean-Pierre Cartron, Cecile Masson, Samer Wehbi, Bérengere Koehl, Marie Hully, Karine Siquier, Nicole Chemlay, Agnes Rotig, Stanislas Lyonnet, Yves Colin, Giulia Barcia, Vincent Cantagrel, Caroline Le Van Kim, Olivier Hermine, Taroh Kinoshita, Thierry Peyrard, Slim Azouzi
Journal: Blood (2021)
P49.03 Chemoradiation with Cisplatin-Etoposide versus Carboplatin-Etoposide in Limited-Stage Small Cell Lung Cancer
Authors: B. Pellini, S. Hasan, P. Samson, N. Earland, J. Ward, S. Waqar, M. Baggstrom, C.G. Robinson, R. Govindan, S. Devarakonda, D. Morgensztern
Journal: Journal of Thoracic Oncology (2021)
FP13.02 Pembrolizumab + Pemetrexed-Platinum vs Pemetrexed-Platinum for Metastatic NSCLC: 4-Year Follow-up From KEYNOTE-189
Authors: J. Gray, D. Rodríguez-Abreu, S.F. Powell, M.J. Hochmair, S. Gadgeel, E. Esteban, E. Felip, G. Speranza, F. De Angelis, M. Dómine, S.Y. Cheng, H.G. Bischoff, N. Peled, M. Reck, R. Hui, E.B. Garon, M. Boyer, T. Kurata, J. Yang, E. Jensen, F. Souza, M.C. Garassino
Journal: Journal of Thoracic Oncology (2021)
Clinical Outcomes With Abemaciclib After Prior CDK4/6 Inhibitor Progression in Breast Cancer: A Multicenter Experience
Authors: Seth A. Wander, Hyo S. Han, Mark L. Zangardi, Andrzej Niemierko, Veronica Mariotti, Leslie S.L. Kim, Jing Xi, Apurva Pandey, Siobhan Dunne, Azadeh Nasrazadani, Avinash Kambadakone, Casey Stein, Maxwell R. Lloyd, Megan Yuen, Laura M. Spring, Dejan Juric, Irene Kuter, Ioannis Sanidas, Beverly Moy, Therese Mulvey, Neelima Vidula, Nicholas J. Dyson, Leif W. Ellisen, Steven Isakoff, Nikhil Wagle, Adam Brufsky, Kevin Kalinsky, Cynthia X. Ma, Joyce O’Shaughnessy, Aditya Bardia
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6i) are widely used as first-line therapy for hormone receptor–positive metastatic breast cancer (HR+ MBC). Although abemaciclib monotherapy is also FDA-approved for treatment of disease progression on endocrine therapy, there is limited insight into the clinical activity of abemaciclib after progression on prior CDK4/6i. Patients and Methods: We identified patients with HR+ MBC from 6 cancer centers in the United States who received abemaciclib after disease progression on prior CDK4/6i, and abstracted clinical features, outcomes, toxicity, and predictive biomarkers. Results: In the multicenter cohort, abemaciclib was well tolerated after a prior course of CDK4/6i (palbociclib)-based therapy; a minority of patients discontinued abemaciclib because of toxicity without progression (9.2%). After progression on palbociclib, most patients (71.3%) received nonsequential therapy with abemaciclib (with ≥1 intervening non-CDK4/6i regimens), with most receiving abemaciclib with an antiestrogen agent (fulvestrant, 47.1%; aromatase inhibitor, 27.6%), and the remainder receiving abemaciclib monotherapy (19.5%). Median progression-free survival for abemaciclib in this population was 5.3 months and median overall survival was 17.2 months, notably similar to results obtained in the MONARCH-1 study of abemaciclib monotherapy in heavily pretreated HR+/HER2-negative CDK4/6i-naïve patients. A total of 36.8% of patients received abemaciclib for ≥6 months. There was no relationship between the duration of clinical benefit while on palbociclib and the subsequent duration of treatment with abemaciclib. RB1 , ERBB2 , and CCNE1 alterations were noted among patients with rapid progression on abemaciclib. Conclusions: A subset of patients with HR+ MBC continue to derive clinical benefit from abemaciclib after progression on prior palbociclib. These results highlight the need for future studies to confirm molecular predictors of cross-resistance to CDK4/6i therapy and to better characterize the utility of abemaciclib after disease progression on prior CDK4/6i.
Paediatric tuberculosis during universal and selective Bacillus Calmette–Guérin vaccination policy: a nationwide population-based retrospective study, Finland, 1995–2015
Authors: Antti Kontturi, Satu Kekomäki, Hanna Soini, Jukka Ollgren, Eeva Salo
Journal: Eurosurveillance (2021)

Introduction In 2006, the Bacillus Calmette–Guérin (BCG) vaccination policy in Finland changed from universal to selective. Aim We assessed the impact of the policy change on tuberculosis (TB) morbidity in children under 5 years and epidemiological trends of paediatric TB in Finland. Methods We conducted a nationwide, population-based, retrospective registry study of all newly diagnosed active TB cases younger than 15 years in Finland from 1995 to 2015 by linking data from the National Infectious Diseases Register, Finnish Care Register for Health Care, medical patient records and Finnish Population Information System. We compared the TB incidence rate ratio of under 5 year-olds with universal and selective BCG vaccinations with a Poisson log-linear model and analysed incidence trends among those younger than 15 years with a negative binomial model. Results We identified 139 paediatric TB cases: 50 native (including 24 second-generation migrants) and 89 foreign-born children. The TB rate of under 5 year-olds remained stable after changing to selective BCG vaccination (incidence rate ratio (IRR): 1.3; 95% confidence interval (CI): 0.7–2.3). TB rate in the native population under 15 years increased slightly (IRR = 1.06; 95% CI: 1.01–1.11). Discussion Paediatric TB cases in Finland were concentrated in families with migrant background from high-TB incidence countries. The native TB morbidity in under 5-year-olds did not increase after the BCG policy revision, suggesting that selective vaccinations can prevent TB in the most vulnerable age group in low-incidence settings. Second-generation migrants under 15 years in Finland with high TB risk are probably increasing.
JAMA deputy editor resigns after critics hit out at podcast on structural racism
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

The deputy editor of the journal JAMA has resigned after a podcast on structural racism in medicine was widely criticised and a petition calling for an investigation into the broadcast attracted more than 2000 signatures.1

The podcast was published on 23 February and has since been withdrawn. But a tweet to promote the episode, which has been deleted, said, “No physician is racist, so how can there be structural racism in health care? An explanation of the idea by doctors for doctors in this user-friendly podcast.”

Both JAMA ’s editor, Howard Bauchner, and James Madara, head of the American Medical Association, which publishes the journal, have apologised for the broadcast, saying, “Comments made in the podcast were inaccurate, offensive, hurtful, and inconsistent with the standards of JAMA …
Kssd: sequence dimensionality reduction by k-mer substring space sampling enables real-time large-scale datasets analysis
Authors: Huiguang Yi, Yanling Lin, Chengqi Lin, Wenfei Jin
Journal: Genome biology (2021)

Abstract Here, we develop k -mer substring space decomposition (Kssd), a sketching technique which is significantly faster and more accurate than current sketching methods. We show that it is the only method that can be used for large-scale dataset comparisons at population resolution on simulated and real data. Using Kssd, we prioritize references for all 1,019,179 bacteria whole genome sequencing (WGS) runs from NCBI Sequence Read Archive and find misidentification or contamination in 6164 of these. Additionally, we analyze WGS and exome runs of samples from the 1000 Genomes Project.
P48.04 IMfirst; Phase IIIB Safety Study of Atezolizumab Plus Chemotherapy in a Real World Population of Untreated ES-SCLC
Authors: R. Garcia Campelo, J. De Castro Carpeño, M. Cobo Dols, A. Moreno Vega, M. Majem Tarruella, E. Arriola Aperribay, L. Crama, P. Ruiz Gracia, M. Dómine Gómez
Journal: Journal of Thoracic Oncology (2021)
P03.05 CANOPY-N: Neoadjuvant Canakinumab and Pembrolizumab in Patients With Surgically Resectable Non-Small Cell Lung Cancer
Authors: J. Lee, M. Tsuboi, P. Garrido, E.S. Kim, T. Dong, C. Blin, V. Rodrik-Outmezguine, B. Mookerjee, V. Passos, T. Mok
Journal: Journal of Thoracic Oncology (2021)
The impact of social and physical distancing measures on COVID-19 activity in England: findings from a multi-tiered surveillance system
Authors: Jamie Lopez Bernal, Mary A Sinnathamby, Suzanne Elgohari, Hongxin Zhao, Chinelo Obi, Laura Coughlan, Vasileios Lampos, Ruth Simmons, Elise Tessier, Helen Campbell, Suzanna McDonald, Joanna Ellis, Helen Hughes, Gillian Smith, Mark Joy, Manasa Tripathy, Rachel Byford, Filipa Ferreira, Simon de Lusignan, Maria Zambon, Gavin Dabrera, Kevin Brown, Vanessa Saliba, Nick Andrews, Gayatri Amirthalingam, Sema Mandal, Michael Edelstein, Alex J Elliot, Mary Ramsay
Journal: Eurosurveillance (2021)

Background A multi-tiered surveillance system based on influenza surveillance was adopted in the United Kingdom in the early stages of the coronavirus disease (COVID-19) epidemic to monitor different stages of the disease. Mandatory social and physical distancing measures (SPDM) were introduced on 23 March 2020 to attempt to limit transmission. Aim To describe the impact of SPDM on COVID-19 activity as detected through the different surveillance systems. Methods Data from national population surveys, web-based indicators, syndromic surveillance, sentinel swabbing, respiratory outbreaks, secondary care admissions and mortality indicators from the start of the epidemic to week 18 2020 were used to identify the timing of peaks in surveillance indicators relative to the introduction of SPDM. This timing was compared with median time from symptom onset to different stages of illness and levels of care or interactions with healthcare services. Results The impact of SPDM was detected within 1 week through population surveys, web search indicators and sentinel swabbing reported by onset date. There were detectable impacts on syndromic surveillance indicators for difficulty breathing, influenza-like illness and COVID-19 coding at 2, 7 and 12 days respectively, hospitalisations and critical care admissions (both 12 days), laboratory positivity (14 days), deaths (17 days) and nursing home outbreaks (4 weeks). Conclusion The impact of SPDM on COVID-19 activity was detectable within 1 week through community surveillance indicators, highlighting their importance in early detection of changes in activity. Community swabbing surveillance may be increasingly important as a specific indicator, should circulation of seasonal respiratory viruses increase.
Pharmaceutical cocrystals: A review of preparations, physicochemical properties and applications
Authors: Minshan Guo, Xiaojie Sun, Jiahui Chen, Ting Cai
Journal: Acta Pharmaceutica Sinica B (2021)

Pharmaceutical cocrystals are multicomponent systems in which at least one component is an active pharmaceutical ingredient and the others are pharmaceutically acceptable ingredients. Cocrystallization of a drug substance with a coformer is a promising and emerging approach to improve the performance of pharmaceuticals, such as solubility, dissolution profile, pharmacokinetics and stability. This review article presents a comprehensive overview of pharmaceutical cocrystals, including preparation methods, physicochemical properties, and applications. Furthermore, some examples of drug cocrystals are highlighted to illustrate the effect of crystal structures on the various aspects of active pharmaceutical ingredients, such as physical stability, chemical stability, mechanical properties, optical properties, bioavailability, sustained release and therapeutic effect. This review will provide guidance for more efficient design and manufacture of pharmaceutical cocrystals with desired physicochemical properties and applications.
Multi-organ Coordination of Lipoprotein Secretion by Hormones, Nutrients and Neural Networks
Authors: Priska Stahel, Changting Xiao, Avital Nahmias, Lili Tian, Gary Franklin Lewis
Journal: Endocrine Reviews (2021)

Abstract Plasma triglyceride-rich lipoproteins (TRL), particularly atherogenic remnant lipoproteins, contribute to atherosclerotic cardiovascular disease. Hypertriglyceridemia may arise in part from hypersecretion of TRLs by the liver and intestine. Here we focus on the complex network of hormonal, nutritional, and neuronal interorgan communication that regulates secretion of TRLs and provide our perspective on the relative importance of these factors. Hormones and peptides originating from the pancreas (insulin, glucagon), gut [glucagon-like peptide 1 (GLP-1) and 2 (GLP-2), ghrelin, cholecystokinin (CCK), peptide YY], adipose tissue (leptin, adiponectin) and brain (GLP-1) modulate TRL secretion by receptor-mediated responses and indirectly via neural networks. In addition, the gut microbiome and bile acids influence lipoprotein secretion in humans and animal models. Several nutritional factors modulate hepatic lipoprotein secretion through effects on the central nervous system. Vagal afferent signaling from the gut to the brain and efferent signals from the brain to the liver and gut are modulated by hormonal and nutritional factors to influence TRL secretion. Some of these factors have been extensively studied and shown to have robust regulatory effects whereas others are “emerging” regulators, whose significance remains to be determined. The quantitative importance of these factors relative to one another and relative to the key regulatory role of lipid availability remains largely unknown. Our understanding of the complex interorgan regulation of TRL secretion is rapidly evolving to appreciate the extensive hormonal, nutritional, and neural signals emanating not only from gut and liver but also from the brain, pancreas, and adipose tissue.
P03.04 Phase II Study of TKIs as Neo(adjuvant) Therapy in Stage II–III Resectable NSCLC with ALK, ROS1, NTRK or BRAFV600 Alterations
Authors: J. Lee, I. Wistuba, C. Ngiam, W. Yu, K. Schulze, M. Rocha, I. Bara, D. Carbone, B. Johnson, D. Kwiatkowski, M.S.K. Center, J. Chaft
Journal: Journal of Thoracic Oncology (2021)