tbuckley/cabot-search huggingface dataset:
Spatial scale in analysis of the dental plaque microbiome
Authors: Gary G. Borisy, Alex M. Valm
Journal: Periodontology 2000 (2021)

Abstract Ecologists have long recognized the importance of spatial scale in understanding structure‐function relationships among communities of organisms within their environment. Here, we review historical and contemporary studies of dental plaque community structure in the context of three distinct scales: the micro (1‐10 µm), meso (10‐100 µm) and macroscale (100 µm to ≥1 cm). Within this framework, we analyze the compositional nature of dental plaque at the macroscale, the molecular interactions of microbes at the microscale, and the emergent properties of dental plaque biofilms at the mesoscale. Throughout our analysis of dental plaque across spatial scales, we draw attention to disease and health‐associated structure‐function relationships and include a discussion of host immune involvement in the mesoscale structure of periodontal disease–associated biofilms. We end with a discussion of two filamentous organisms, Fusobacterium nucleatum and Corynebacterium matruchotii , and their relevant contributions in structuring dental plaque biofilms.
Skill levels and gains in university STEM education in China, India, Russia and the United States
Authors: Prashant Loyalka, Ou Lydia Liu, Guirong Li, Elena Kardanova, Igor Chirikov, Shangfeng Hu, Ningning Yu, Liping Ma, Fei Guo, Tara Beteille, Namrata Tognatta, Lin Gu, Guangming Ling, Denis Federiakin, Huan Wang, Saurabh Khanna, Ashutosh Bhuradia, Zhaolei Shi, Yanyan Li
Journal: Nature Human Behaviour (2021)
Evaluation of Compliance With Legal Requirements Under the FDA Amendments Act of 2007 for Timely Registration of Clinical Trials, Data Verification, Delayed Reporting, and Trial Document Submission
Authors: Nicholas J. DeVito, Ben Goldacre
Journal: JAMA Internal Medicine (2021)

This cross-sectional study evaluates clinical trials’ rates of compliance with the legal requirements of the US Food and Drug Administration’s Amendments Act of 2007 for timely registration of clinical trials, data verification, delayed reporting, and trial document submission.
Kidney Failure Prediction Models: A Comprehensive External Validation Study in Patients with Advanced CKD
Authors: Chava L. Ramspek, Marie Evans, Christoph Wanner, Christiane Drechsler, Nicholas C. Chesnaye, Maciej Szymczak, Magdalena Krajewska, Claudia Torino, Gaetana Porto, Samantha Hayward, Fergus Caskey, Friedo W. Dekker, Kitty J. Jager, Merel van Diepen
Journal: Journal of the American Society of Nephrology (2021)

Significance Statement Most kidney failure prediction models have been developed and validated in cohorts of patients with a wide range of disease severity, without accounting for the competing risk of death. Models recommended by guidelines, currently used in the clinic, have not undergone a head-to-head comparison. This study provides a comprehensive external validation of kidney failure prediction tools in two cohorts of patients with advanced CKD, taking the competing risk of death into account. Models that predict over a longer time frame of 5 years overestimate risk due to the competing risk of death. In patients with advanced CKD, the eight-variable 2-year Kidney Failure Risk Equation is recommended for short-term predictions surrounding preparation for RRT. The 4-year Grams model, which accounts for competing risk, is most suitable for longer-term predictions. Background Various prediction models have been developed to predict the risk of kidney failure in patients with CKD. However, guideline-recommended models have yet to be compared head to head, their validation in patients with advanced CKD is lacking, and most do not account for competing risks. Methods To externally validate 11 existing models of kidney failure, taking the competing risk of death into account, we included patients with advanced CKD from two large cohorts: the European Quality Study (EQUAL), an ongoing European prospective, multicenter cohort study of older patients with advanced CKD, and the Swedish Renal Registry (SRR), an ongoing registry of nephrology-referred patients with CKD in Sweden. The outcome of the models was kidney failure (defined as RRT-treated ESKD). We assessed model performance with discrimination and calibration. Results The study included 1580 patients from EQUAL and 13,489 patients from SRR. The average c statistic over the 11 validated models was 0.74 in EQUAL and 0.80 in SRR, compared with 0.89 in previous validations. Most models with longer prediction horizons overestimated the risk of kidney failure considerably. The 5-year Kidney Failure Risk Equation (KFRE) overpredicted risk by 10%–18%. The four- and eight-variable 2-year KFRE and the 4-year Grams model showed excellent calibration and good discrimination in both cohorts. Conclusions Some existing models can accurately predict kidney failure in patients with advanced CKD. KFRE performed well for a shorter time frame (2 years), despite not accounting for competing events. Models predicting over a longer time frame (5 years) overestimated risk because of the competing risk of death. The Grams model, which accounts for the latter, is suitable for longer-term predictions (4 years).
Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in <i>ROS1</i> Fusion–Positive Lung Cancer
Authors: Jessica J. Lin, Noura J. Choudhury, Satoshi Yoda, Viola W. Zhu, Ted W. Johnson, Ramin Sakhtemani, Ibiayi Dagogo-Jack, Subba R. Digumarthy, Charlotte Lee, Andrew Do, Jennifer Peterson, Kylie Prutisto-Chang, Wafa Malik, Harper G. Hubbeling, Adam Langenbucher, Adam J. Schoenfeld, Christina J. Falcon, Jennifer S. Temel, Lecia V. Sequist, Beow Y. Yeap, Jochen K. Lennerz, Alice T. Shaw, Michael S. Lawrence, Sai-Hong Ignatius Ou, Aaron N. Hata, Alexander Drilon, Justin F. Gainor
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Current standard initial therapy for advanced, ROS proto-oncogene 1, receptor tyrosine kinase fusion (ROS1)-positive (ROS1+) non–small cell lung cancer (NSCLC) is crizotinib or entrectinib. Lorlatinib, a next-generation anaplastic lymphoma kinase/ROS1 inhibitor, recently demonstrated efficacy in ROS1+ NSCLC, including in crizotinib-pretreated patients. However, mechanisms of lorlatinib resistance in ROS1+ disease remain poorly understood. Here, we assessed mechanisms of resistance to crizotinib and lorlatinib. Experimental Design: Biopsies from patients with ROS1+ NSCLC progressing on crizotinib or lorlatinib were profiled by genetic sequencing. Results: From 55 patients, 47 post-crizotinib and 32 post-lorlatinib biopsies were assessed. Among 42 post-crizotinib and 28 post-lorlatinib biopsies analyzed at distinct timepoints, ROS1 mutations were identified in 38% and 46%, respectively. ROS1 G2032R was the most commonly occurring mutation in approximately one third of cases. Additional ROS1 mutations included D2033N (2.4%) and S1986F (2.4%) post-crizotinib and L2086F (3.6%), G2032R/L2086F (3.6%), G2032R/S1986F/L2086F (3.6%), and S1986F/L2000V (3.6%) post-lorlatinib. Structural modeling predicted ROS1L2086F causes steric interference to lorlatinib, crizotinib, and entrectinib, while it may accommodate cabozantinib. In Ba/F3 models, ROS1L2086F, ROS1G2032R/L2086F, and ROS1S1986F/G2032R/L2086F were refractory to lorlatinib but sensitive to cabozantinib. A patient with disease progression on crizotinib and lorlatinib and ROS1 L2086F received cabozantinib for nearly 11 months with disease control. Among lorlatinib-resistant biopsies, we also identified MET amplification (4%), KRAS G12C (4%), KRAS amplification (4%), NRAS mutation (4%), and MAP2K1 mutation (4%). Conclusions: ROS1 mutations mediate resistance to crizotinib and lorlatinib in more than one third of cases, underscoring the importance of developing next-generation ROS1 inhibitors with potency against these mutations, including G2032R and L2086F. Continued efforts are needed to elucidate ROS1-independent resistance mechanisms.
Risk of mortality in patients infected with SARS-CoV-2 variant of concern 202012/1: matched cohort study
Authors: Robert Challen, Ellen Brooks-Pollock, Jonathan M Read, Louise Dyson, Krasimira Tsaneva-Atanasova, Leon Danon
Journal: BMJ (2021)

To establish whether there is any change in mortality from infection with a new variant of SARS-CoV-2, designated a variant of concern (VOC-202012/1) in December 2020, compared with circulating SARS-CoV-2 variants.
Questionnaire as an alternative of skin prick tests to differentiate allergic from non‐allergic rhinitis in epidemiological studies
Authors: Marine Savouré, Jean Bousquet, Emilie Burte, Jocelyne Just, Isabelle Pin, Valérie Siroux, Laurent Orsi, Bénédicte Jacquemin, Rachel Nadif
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK+ ALCL: results of COG trial ANHL12P1
Authors: Eric J. Lowe, Anne F. Reilly, Megan S. Lim, Thomas G. Gross, Lauren Saguilig, Donald A. Barkauskas, Rui Wu, Sarah Alexander, Catherine M. Bollard
Journal: Blood (2021)
The International Association for the Study of Lung Cancer Global Survey on Programmed Death-Ligand 1 Testing for NSCLC
Authors: Mari Mino-Kenudson, Nolwenn Le Stang, Jillian B. Daigneault, Andrew G. Nicholson, Wendy A. Cooper, Anja C. Roden, Andre L. Moreira, Erik Thunnissen, Mauro Papotti, Giuseppe Pelosi, Noriko Motoi, Claudia Poleri, Elisabeth Brambilla, Mary Redman, Deepali Jain, Sanja Dacic, Yasushi Yatabe, Ming Sound Tsao, Fernando Lopez-Rios, Johan Botling, Gang Chen, Teh-Ying Chou, Fred R. Hirsch, Mary Beth Beasley, Alain Borczuk, Lukas Bubendorf, Jin-Haeng Chung, David Hwang, Dongmei Lin, John Longshore, Masayuki Noguchi, Natasha Rekhtman, Lynette Sholl, William Travis, Akihiko Yoshida, Murry W. Wynes, Ignacio I. Wistuba, Keith M. Kerr, Sylvie Lantuejoul
Journal: Journal of Thoracic Oncology (2021)
Abstract LT010: Pleiotrophin drives pro-metastatic immune niche within breast tumor microenvironment
Authors: Debolina Ganguly, Noah Sorrelle, Adrian Dominguez, Jason Toombs, Marcel Schmidt, Fa Valdes Mora, David Gallego Ortega, Anton Wellstein, Rolf A. Brekken
Journal: Cancer Research (2021)

Abstract Background: Pleiotrophin (PTN), a heparin binding cytokine important during embryonic development, is expressed at elevated levels in several cancers, including breast cancer. High PTN expression in serum and tumor tissues of breast cancer patients correlates with worse outcome. Previous studies indicate PTN contributes to angiogenesis, hematopoiesis, and inflammation; however, the function of PTN in breast cancer progression and metastasis has not been elucidated. Methods: The effect of anti-PTN therapy (mAb; 3B10) on breast tumor progression and pulmonary metastasis was evaluated in four preclinical models of breast cancer: 4T1, E0771, Met-1, MMTV-PyMT. In addition, the effect of global loss of PTN using Ptn-deficient mice was evaluated in two murine models of breast cancer. Tissues from these experiments were analyzed by RNAseq and histology for changes in angiogenesis, hematopoiesis, immune cell infiltration, and cytokine/chemokine expression. Findings: TCGA data shows high PTN expression correlates with poor survival of Stage IV breast cancer patients. Furthermore, our data indicate that: a) blocking PTN pharmacologically or genetically results in a significant reduction of lung metastasis in multiple preclinical mouse models of breast cancer, b) scRNAseq and dual FISH-IHC (fluorescence in-situ hybridization and immunohistochemistry) demonstrates that endothelial cells and select population of tumor cells express PTN in the tumor microenvironment (TME), c) inhibition of PTN results in a decrease in overall inflammation with a particular decrease in neutrophil populations at primary and secondary tumor sites, d) in a genetically engineered mouse model (GEMM) of breast cancer, MMTV-PyMT, PTN expression is enriched at the metastatic site. Conclusion: Our data suggests that PTN is important in driving a pro-metastatic immune niche within the TME that promotes tumor cell escape from the primary tumor and survival of metastatic cancer cells in secondary sites. Additionally, our studies highlight that inhibition of PTN has potential to reduce metastatic burden in breast cancer and suggest that future studies testing the combination of PTN inhibition with standard chemotherapy or immune therapy are warranted. Citation Format: Debolina Ganguly, Noah Sorrelle, Adrian Dominguez, Jason Toombs, Marcel Schmidt, Fa Valdes Mora, David Gallego Ortega, Anton Wellstein, Rolf A. Brekken. Pleiotrophin drives pro-metastatic immune niche within breast tumor microenvironment [abstract]. In: Proceedings of the AACR Virtual Special Conference on the Evolving Tumor Microenvironment in Cancer Progression: Mechanisms and Emerging Therapeutic Opportunities; in association with the Tumor Microenvironment (TME) Working Group; 2021 Jan 11-12. Philadelphia (PA): AACR; Cancer Res 2021;81(5 Suppl):Abstract nr LT010.
Efficacy of immune checkpoint blockade in patients with advanced upper tract urothelial cancer and mismatch repair deficiency or microsatellite instability (MSI).
Authors: Alexander Andreev-Drakhlin, Amishi Yogesh Shah, Ana Cecilia Adriazola, Leah Shaw, Lidia Lopez, Marihella James, Surena F. Matin, Omar Alhalabi, Jianjun Gao, Arlene O. Siefker-Radtke, Sangeeta Goswami, Lianchun Xiao, Aradhana M. Venkatesan, Matthew T Campbell
Journal: Journal of Clinical Oncology (2021)

487 Background: Tumors deficient in DNA mismatch repair (dMMR) exhibit a microsatellite unstable phenotype characterized by high tumor mutational burden and an immunogenic tumor microenvironment. Despite the histology-agnostic approval of pembrolizumab for advanced dMMR/MSI cancers, responsiveness of dMMR/MSI upper tract urothelial cancers (UTUC) to immune checkpoint (IC) blockade remains largely unknown. Methods: Consecutive records of patients (pts) from a single institution with locally advanced unresectable or metastatic dMMR/MSI UTUC who received IC therapy were analyzed. The primary endpoint was assessment of objective response rate (ORR) using RECIST v1.1. Secondary endpoints were progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier technique. dMMR/MSI status was evaluated by immunohistochemistry (IHC) and/or polymerase chain reaction (PCR). Results: Ten pts were identified with locally advanced unresectable (N = 3) or metastatic (N = 7) dMMR/MSI UTUC who received therapy with IC blockade (pembrolizumab = 7, nivolumab = 2, atezolizumab = 1). Median age was 65.5 (range = 46 – 90). Six pts were male. Seven pts had germline dMMR. MSI was detected by PCR in three pts and dMMR by IHC in seven pts (PMS2/MLH1 loss = 4, MSH2 loss = 1, MLH1 loss = 1, MSH6 loss = 1). Five pts received systemic chemotherapy (2 cisplatin based, 1 carboplatin based, 2 other) prior to IC therapy with two pts (40%) achieving partial response (PR). At a median follow-up of 15.5 months (range: 2 – 43 months), all pts were alive, and none experienced disease progression. PFS and OS at 15.5 months were 100%. The observed ORR was 90% (CI, 55.5%, 99.8%), including 8 pts who achieved complete remission (CR). The median time to best response was 4 months (range: 2 – 8 months). Toxicity leading to treatment discontinuation: 1 (grade 3) pancytopenia, 1 (grade 2) pneumonitis, 1 (grade 2) SICCA-like symptoms. Conclusions: Immunotherapy with IC inhibitors demonstrates excellent clinical activity in advanced dMMR/MSI UTUC. Further studies integrating these agents earlier in the disease course are warranted in this rare but important subgroup. Given the extremely high complete response rate in this population consideration of preference to IC therapy as initial therapy should be entertained if these findings are validated.
Impact Of History Of Autoimmune Disease On Survival In Multiple Myeloma and Monoclonal Gammopathy Of Undetermined Significance: A Population-Based Study
Authors: Ebba K Lindqvist, Ingemar Turesson, Ola Landgren, Sigrún H Lund, Lynn Goldin, Magnus Bjorkholm, Sigurdur Y Kristinsson
Journal: Blood (2013)
Fruit and Vegetable Intake and Mortality
Authors: Dong D. Wang, Yanping Li, Shilpa N. Bhupathiraju, Bernard A. Rosner, Qi Sun, Edward L. Giovannucci, Eric B. Rimm, JoAnn E. Manson, Walter C. Willett, Meir J. Stampfer, Frank B. Hu
Journal: Circulation (2021)

The optimal intake levels of fruit and vegetables for maintaining long-term health are uncertain.
Utilization and survival outcomes between definitive versus conservative treatments among elderly men with high-risk prostate cancer.
Authors: Sagar Anil Patel, Hiram Alberto Gay, Jeff M. Michalski, Brian Christopher Baumann, Randall Brenneman, Bruce Warren Hershatter, Ashesh B. Jani, Benjamin Walker Fischer-Valuck
Journal: Journal of Clinical Oncology (2021)

204 Background: Prostate cancer (PCa) is the second leading cause of cancer death in men &gt; 80 years old. However, studies have shown that older men are less likely to undergo curative treatment for localized PCa, possibly due to competing comorbidities or inability to accurately estimate life expectancy. Herein, we investigate utilization trends and survival outcomes amongst guideline-supported treatment options in elderly men with high-risk PCa in the United States. Methods: Men ≥ 80 years diagnosed with high-risk PCa (cT3-4 or Gleason 8-10 or PSA &gt; 20) between 2004-2016 were analyzed from the National Cancer Database. Those missing risk-stratification or treatment data were excluded. Eligible patients were grouped based on their primary treatment modality: no treatment (observation), androgen deprivation therapy (ADT) alone, radiation therapy (RT) alone, RT + ADT, or radical prostatectomy (RP). Cochran-Armitage was used to evaluate treatment trends over time, and multivariable logistic regression was used to identify sociodemographic predictors of treatment. Overall survival (OS) between treatments was evaluated using Kaplan-Meier, log-rank, and multivariable Cox proportional hazards. Results: With a median follow up of 42 months, 19,920 men were eligible for analysis. The most utilized treatment modality was RT+ADT (37.2%), followed by ADT alone (29.4%), observation (23.9%), RT alone (7.8%), and RP (1.7%). There was a significant increase in use of RT+ADT and RT alone (p &lt; 0.001) and decrease in use of ADT alone and observation ( p&lt; 0.001); no change was seen in RP use. There was no OS difference between observation versus ADT alone (aHR 1.04, 95% CI 0.99-1.09, p = 0.11). Definitive local treatment was associated with improved OS compared to ADT alone (RT+ADT: aHR 0.48, 95% CI 0.46-0.50, p &lt; 0.0001; RT alone: aHR 0.54, 95% CI 0.50-0.59, p &lt; 0.0001; RP: aHR 0.50, 95% CI 0.42-0.59, p &lt; 0.0001). Black men and uninsured status were independently associated with lower likelihood of undergoing definitive treatment (i.e. RT+ADT, RT, or RP). Conclusions: For men ≥ 80 years old with high-risk PCa in this large US registry, definitive local therapy using RT +/- ADT or RP was associated with a 50% reduction in overall mortality compared to observation or ADT alone. Less than half of men in this time period underwent a definitive treatment, and Black and uninsured men remained at particularly high risk of undertreatment.
Organ-on-a-chip platforms for evaluation of environmental nanoparticle toxicity
Authors: Rick Xing Ze Lu, Milica Radisic
Journal: Bioactive Materials (2021)

Despite showing a great promise in the field of nanomedicine, nanoparticles have gained a significant attention from regulatory agencies regarding their possible adverse health effects upon environmental exposure. Whether those nanoparticles are generated through intentional or unintentional means, the constant exposure to nanomaterials can inevitably lead to unintended consequences based on epidemiological data, yet the current understanding of nanotoxicity is insufficient relative to the rate of their emission in the environment and the lack of predictive platforms that mimic the human physiology. This calls for a development of more physiologically relevant models, which permit the comprehensive and systematic examination of toxic properties of nanoparticles. With the advancement in microfabrication techniques, scientists have shifted their focus on the development of an engineered system that acts as an intermediate between a well-plate system and animal models, known as organ-on-a-chips. The ability of organ-on-a-chip models to recapitulate in vivo like microenvironment and responses offers a new avenue for nanotoxicological research. In this review, we aim to provide overview of assessing potential risks of nanoparticle exposure using organ-on-a-chip systems and their potential to delineate biological mechanisms of epidemiological findings.
COVID-19 Vaccination Manifesting as Incidental Lymph Nodal Uptake on 18F-FDG PET/CT
Authors: Najeeb Ahmed, Samreen Muzaffar, Corinne Binns, Muhammad Waqas Ilyas, Sharjeel Usmani
Journal: Clinical Nuclear Medicine (2021)

Abstract Benign uptake on 18 F-FDG PET can be seen with inflammatory conditions. We report a case of an 86-year-old woman with successfully treated nasal melanoma who underwent routine follow-up 18 F-FDG PET, day 6 after the second dose of Pfizer-BioNTech COVID-19 vaccine inoculated in the left deltoid muscle. 18 F-FDG PET showed increase tracer uptake in the left deltoid muscle and in 2 normal-sized left subpectoral nodes. These findings were considered secondary to vaccination. With the current drive of global COVID-19 immunization, this case highlights the importance of documenting vaccination history at the time of scanning to avoid false-positive results.