tbuckley/cabot-search huggingface dataset:
KEAP1 and TP53 Frame Genomic, Evolutionary, and Immunologic Subtypes of Lung Adenocarcinoma With Different Sensitivity to Immunotherapy
Authors: Stefano Scalera, Marco Mazzotta, Giacomo Corleone, Francesca Sperati, Irene Terrenato, Eriseld Krasniqi, Laura Pizzuti, Maddalena Barba, Patrizia Vici, Enzo Gallo, Simonetta Buglioni, Paolo Visca, Edoardo Pescarmona, Daniele Marinelli, Francesca De Nicola, Ludovica Ciuffreda, Frauke Goeman, Maurizio Fanciulli, Raffaele Giusti, Andrea Vecchione, Ruggero De Maria, Federico Cappuzzo, Paolo Marchetti, Gennaro Ciliberto, Marcello Maugeri-Saccà
Journal: Journal of Thoracic Oncology (2021)
Mobile Telemedicine for Buprenorphine Treatment in Rural Populations With Opioid Use Disorder
Authors: Eric Weintraub, Chamindi Seneviratne, Jessica Anane, Kelly Coble, Jessica Magidson, Sarah Kattakuzhy, Aaron Greenblatt, Christopher Welsh, Alexander Pappas, Terri L. Ross, Annabelle M. Belcher
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The demand for medications for opioid use disorder (MOUD) in rural US counties far outweighs their availability. Novel approaches to extend treatment capacity include telemedicine (TM) and mobile treatment on demand; however, their combined use has not been reported or evaluated. <h3>Objective</h3> To evaluate the use of a TM mobile treatment unit (TM-MTU) to improve access to MOUD for individuals living in an underserved rural area. <h3>Design, Setting, and Participants</h3> This quality improvement study evaluated data collected from adult outpatients with a diagnosis of OUD enrolled in the TM-MTU initiative from February 2019 (program inception) to June 2020. Program staff traveled to rural areas in a modified recreational vehicle equipped with medical, videoconferencing, and data collection devices. Patients were virtually connected with physicians based more than 70 miles (112 km) away. Data analysis was performed from June to October 2020. <h3>Intervention</h3> Patients received buprenorphine prescriptions after initial teleconsultation and follow-up visits from a study physician specialized in addiction psychiatry and medicine. <h3>Main Outcomes and Measures</h3> The primary outcome was 3-month treatment retention, and the secondary outcome was opioid-positive urine screens. Exploratory outcomes included use of other drugs and patients' travel distance to treatment. <h3>Results</h3> A total of 118 patients were enrolled in treatment, of whom 94 were seen for follow-up treatment predominantly (at least 2 of 3 visits [&gt;50%]) on the TM-MTU; only those 94 patients' data are considered in all analyses. The mean (SD) age of patients was 36.53 (9.78) years, 59 (62.77%) were men, 71 (75.53%) identified as White, and 90 (95.74%) were of non-Hispanic ethnicity. Fifty-five patients (58.51%) were retained in treatment by 3 months (90 days) after baseline. Opioid use was reduced by 32.84% at 3 months, compared with baseline, and was negatively associated with treatment duration (<i>F</i> = 12.69;<i>P</i> = .001). In addition, compared with the nearest brick-and-mortar treatment location, TM-MTU treatment was a mean of 6.52 miles (range, 0.10-58.70 miles) (10.43 km; range, 0.16-93.92 km) and a mean of 10 minutes (range, 1-49 minutes) closer for patients. <h3>Conclusions and Relevance</h3> These data demonstrate the feasibility of combining TM with mobile treatment, with outcomes (retention and opioid use) similar to those obtained from office-based TM MOUD programs. By implementing a traveling virtual platform, this clinical paradigm not only helps fill the void of rural MOUD practitioners but also facilitates access to underserved populations who are less likely to reach traditional medical settings, with critical relevance in the context of the COVID-19 pandemic.
Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19
Authors: Morris J Brown, William Alazawi, Stavroula Kanoni
Journal: New England Journal of Medicine (2021)

To the Editor: The variable efficacy of the interleukin-6 receptor antagonist tocilizumab against Covid-19, as shown most recently in the results of REMAP-CAP reported by Gordon et al. 1 and the results of the COVACTA trial reported by Rosas et al. 2 (April 22 issue), may reflect the fact that interleukin-6 has a dual role.Interleukin-6 stimulates desirable antibody production by immune cells that express membranous interleukin-6 receptors and also stimulates undesirable proinflammatory effects by cells that lack interleukin-6 receptors.Interleukin-6 trans-signaling to cells that lack interleukin-6 receptors requires dimerization of shed soluble interleukin-6 receptors with another membrane protein, glycoprotein 130 (gp130). 3 Since tocilizumab blocks both desirable and undesirable actions of interleukin-6, selective blockade of the undesirable actions by soluble recombinant gp130 could provide a greater net benefit than tocilizumab. 3,4 A related explanation for the variable efficacy of tocilizumab between trials -and indeed variable susceptibility to Covid-19 in generalis suggested by two variants of IL6ST (the gene encoding gp130) that are predicted to be deleterious: p.Ile454Thr (rs2228046) and p.Gly148Arg (rs2228044).The minor-allele frequencies of these variants are 30 to 40% higher in the African genome than in other genomes.According to data from UK Biobank, the minor (risk) alleles of both variants are associated with a higher mortality from Covid-19 in Black patients than the major (reference) alleles (Table 1); the proportion of Black patients in REMAP-CAP was 4.0% and in the COVACTA trial 15.1%.The minor allele of rs2228046 has previously been associated with an antibody response to measles vaccine that is 3 times as high as the response in its absence. 5
Abstract 3819: Mechanical Stretch Activates β-arrestin-mediated Signaling of the AT1 Receptor
Authors: ByungSu Yoo, Kriti Rakesh, Lan Mao, Howard A. Rockman
Journal: Circulation (2009)

In the heart, mechanical stretch is an important stimulus for activation of hypertrophic signaling. Here, we identify a mechanism by which mechanical stretch induces angiotensin II type I receptor ...
Preintervention Clinical Determinants and Measured β-Cell Function as Predictors of Type 2 Diabetes Remission After Roux-en-Y Gastric Bypass Surgery
Authors: Chanel Ligon, Ankit Shah, Malini Prasad, Blandine Laferrère
Journal: Diabetes Care (2021)

OBJECTIVE Bariatric surgery results in improved glycemic control in individuals with type 2 diabetes. Single and clusters of clinical determinants have been identified as presurgery predictors of postsurgery diabetes remission. Our goal was to assess whether the addition of measured preoperative β-cell function would improve established clinical models of prediction of diabetes remission. RESEARCH DESIGN AND METHODS Presurgery clinical characteristics, metabolic markers, and β-cell function after oral and intravenous (IV) glucose challenges were assessed in 73 individuals with severe obesity and type 2 diabetes and again 1 year after gastric bypass surgery. Single and multivariate analyses were conducted with preoperative variables to determine the best predictive models of remission. RESULTS Presurgery β-cell glucose sensitivity, a surrogate of β-cell function, was negatively correlated with known diabetes duration, HbA1c, insulin use, and the diabetes remission scores DiaRem and advanced (Ad)-DiaRem (all P &amp;lt; 0.001). Measured β-cell function after oral glucose was 1.6-fold greater than after the IV glucose challenge and more strongly correlated with preoperative clinical and metabolic characteristics. The addition of preoperative β-cell function to clinical models containing well-defined diabetes remission scores did not improve the model’s ability to predict diabetes remission after Roux-en-Y gastric bypass. CONCLUSIONS The addition of measured β-cell function does not add predictive value to defined clinical models of diabetes remission 1 year after surgical weight loss.
Biocompatibility pathways and mechanisms for bioactive materials: The bioactivity zone
Authors: David F. Williams
Journal: Bioactive Materials (2021)

This essay analyzes the scientific evidence that forms the basis of bioactive materials, covering the fundamental understanding of bioactivity phenomena and correlation with the mechanisms of biocompatibility of biomaterials. This is a detailed assessment of performance in areas such as bone-induction, cell adhesion, immunomodulation, thrombogenicity and antimicrobial behavior. Bioactivity is the modulation of biological activity by characteristics of the interfacial region that incorporates the material surface and the immediate local host tissue. Although the term 'bioactive material' is widely used and has a well understood general meaning, it would be useful now to concentrate on this interfacial region, considered as 'the bioactivity zone'. Bioactivity phenomena are either due to topographical/micromechanical characteristics, or to biologically active species that are presented in the bioactivity zone. Examples of topographical/micromechanical effects are the modulation of the osteoblast - osteoclast balance, nanotopographical regulation of cell adhesion, and bactericidal nanostructures. Regulation of bioactivity by biologically active species include their influence, especially of metal ions, on signaling pathways in bone formation, the role of cell adhesion molecules and bioactive peptides in cell attachment, macrophage polarization by immunoregulatory molecules and antimicrobial peptides. While much experimental data exists to demonstrate the potential of such phenomena, there are considerable barriers to their effective clinical translation. This essay shows that there is solid scientific evidence of the existence of bioactivity mechanisms that are associated with some types of biomaterials, especially when the material is modified in a manner designed to specifically induce that activity.
Brain and other central nervous system tumor statistics, 2021
Authors: Kimberly D. Miller, Quinn T. Ostrom, Carol Kruchko, Nirav Patil, Tarik Tihan, Gino Cioffi, Hannah E. Fuchs, Kristin A. Waite, Ahmedin Jemal, Rebecca L. Siegel, Jill S. Barnholtz‐Sloan
Journal: CA A Cancer Journal for Clinicians (2021)

Abstract Brain and other central nervous system (CNS) tumors are among the most fatal cancers and account for substantial morbidity and mortality in the United States. Population‐based data from the Central Brain Tumor Registry of the United States (a combined data set of the National Program of Cancer Registries [NPCR] and Surveillance, Epidemiology, and End Results [SEER] registries), NPCR, National Vital Statistics System and SEER program were analyzed to assess the contemporary burden of malignant and nonmalignant brain and other CNS tumors (hereafter brain) by histology, anatomic site, age, sex, and race/ethnicity. Malignant brain tumor incidence rates declined by 0.8% annually from 2008 to 2017 for all ages combined but increased 0.5% to 0.7% per year among children and adolescents. Malignant brain tumor incidence is highest in males and non‐Hispanic White individuals, whereas the rates for nonmalignant tumors are highest in females and non‐Hispanic Black individuals. Five‐year relative survival for all malignant brain tumors combined increased between 1975 to 1977 and 2009 to 2015 from 23% to 36%, with larger gains among younger age groups. Less improvement among older age groups largely reflects a higher burden of glioblastoma, for which there have been few major advances in prevention, early detection, and treatment the past 4 decades. Specifically, 5‐year glioblastoma survival only increased from 4% to 7% during the same time period. In addition, important survival disparities by race/ethnicity remain for childhood tumors, with the largest Black‐White disparities for diffuse astrocytomas (75% vs 86% for patients diagnosed during 2009‐2015) and embryonal tumors (59% vs 67%). Increased resources for the collection and reporting of timely consistent data are critical for advancing research to elucidate the causes of sex, age, and racial/ethnic differences in brain tumor occurrence, especially for rarer subtypes and among understudied populations.
Esthesioneuroblastoma
Authors: J. P. Shah, J. Feghali
Journal: CA A Cancer Journal for Clinicians (1983)

A retrospective review of the clinical records of 31 patients with esthesioneuroblastoma is presented. A bimodal age distribution was noted. The tumor is extremely rare among blacks. Most patients presented with locally advanced disease. However, regional and distant metastases at the time of initial diagnosis are uncommon. Local recurrence at the primary site was very common, and this reflects either the conservative initial surgical treatment employed or the multicentric nature of the tumor. Cervical lymph node metastasis is present in less than 10 percent of patients at the time of diagnosis. The survival rates were better in patients with early stages of disease. From this study, we conclude that the current management of these tumors should consist of a combination of radiation therapy and surgery. Radical resection followed by postoperative radiation therapy appears to be the treatment combination of choice. The five-year survival rate in our series was 52 percent.
Association of Antineoplastic Therapy With Decreased SARS-CoV-2 Infection Rates in Patients With Cancer
Authors: Michael B. Foote, James Robert White, Justin Jee, Guillem Argilés, Jonathan C. M. Wan, Benoit Rousseau, Melissa S. Pessin, Luis A. Diaz
Journal: JAMA Oncology (2021)

Novel therapies for SARS-CoV-2 infection are urgently needed. Antineoplastic compounds that target cellular machinery used by SARS-CoV-2 for entry and replication, including angiotensin-converting enzyme 2 (ACE2), may disrupt SARS-CoV-2 activity.To determine whether patients with cancer treated with potential ACE2-lowering antineoplastic compounds exhibit lower SARS-CoV-2 infection rates.We used the Library of Integrated Network-Based Cellular Signatures database to identify antineoplastic compounds associated with decreased ACE2 gene expression across cell lines. We then evaluated a retrospective cohort of 1701 patients who were undergoing antineoplastic therapy at Memorial Sloan Kettering Cancer Center in New York, New York, during the COVID-19 pandemic to determine if treatment with an ACE2-lowering antineoplastic was associated with a decreased odds ratio (OR) of SARS-CoV-2 infection. Patients included in the analysis underwent active treatment for cancer and received a SARS-CoV-2 test between March 10 and May 28, 2020.The association between potential ACE2-lowering antineoplastic treatment and a positive SARS-CoV-2 test.In the cohort of 1701 patients, SARS-CoV-2 infection rates were determined for 949 (55.8%) female and 752 (44.2%) male patients (mean [SD] age, 63.1 [13.1] years) with diverse cancers receiving antineoplastic therapy. In silico analysis of gene expression signatures after drug treatment identified 91 compounds associated with downregulation of ACE2 across cell lines. Of the total cohort, 215 (12.6%) patients were treated with 8 of these compounds, including 3 mTOR/PI3K inhibitors and 2 antimetabolites. In a multivariable analysis of patients who received an ACE2-lowering antineoplastic adjusting for confounders, 15 of 215 (7.0%) patients had a positive SARS-CoV-2 test compared with 191 of 1486 (12.9%) patients who received other antineoplastic therapies (OR, 0.53; 95% CI, 0.29-0.88). Findings were confirmed in additional sensitivity analyses including cancer type, steroid use, and a propensity-matched subcohort. Gemcitabine treatment was associated with reduced SARS-CoV-2 infection (OR, 0.42; 95% CI, 0.17-0.87).In this cohort study, in silico analysis of drug-associated gene expression signatures identified potential ACE2-lowering antineoplastic compounds, including mTOR/PI3K inhibitors and antimetabolites. Patients who received these compounds exhibited statistically significantly lower rates of SARS-CoV-2 infection compared with patients given other antineoplastics. Further evaluation of the biological and clinical anti-SARS-CoV-2 properties of identified antineoplastic compounds is warranted.
CD4+ T cells in the lungs of acute sarcoidosis patients recognize an <i>Aspergillus nidulans</i> epitope
Authors: Sarah A. Greaves, Avinash Ravindran, Radleigh G. Santos, Lan Chen, Michael T. Falta, Yang Wang, Angela M. Mitchell, Shaikh M. Atif, Douglas G. Mack, Alex N. Tinega, Lisa A. Maier, Shaodong Dai, Clemencia Pinilla, Johan Grunewald, Andrew P. Fontenot
Journal: The Journal of Experimental Medicine (2021)

Löfgren’s syndrome (LS) is an acute form of sarcoidosis characterized by a genetic association with HLA-DRB1*03 (HLA-DR3) and an accumulation of CD4+ T cells of unknown specificity in the bronchoalveolar lavage (BAL). Here, we screened related LS-specific TCRs for antigen specificity and identified a peptide derived from NAD-dependent histone deacetylase hst4 (NDPD) of Aspergillus nidulans that stimulated these CD4+ T cells in an HLA-DR3–restricted manner. Using ELISPOT analysis, a greater number of IFN-γ– and IL-2–secreting T cells in the BAL of DR3+ LS subjects compared with DR3+ control subjects was observed in response to the NDPD peptide. Finally, increased IgG antibody responses to A. nidulans NDPD were detected in the serum of DR3+ LS subjects. Thus, our findings identify a ligand for CD4+ T cells derived from the lungs of LS patients and suggest a role of A. nidulans in the etiology of LS.
Keeping your lab together in the COVID-19 era
Authors: Timothy R. Sands
Journal: Genome biology (2021)

The COVID-19 pandemic has had a dramatic effect on lives around the world, with scientists and the conduct of their research being no exception.With restrictions in many parts of the world being gradually relieved, we canvassed members of our Editorial Board for their experiences, advice and lessons learned on keeping your lab going, and getting your research up and running again.We expected to see a difference between groups conducting purely computational work and those with predominantly wet labs, with the former intuitively seeming more amenable to remote working.While one fortunate respondent indicated that their computational lab functioning had continued without major issues arising from home working, this was an exception.Computational researchers found themselves just as vulnerable to the effects of isolation and difficulties from lack of face-to-face collaboration as their wet-lab colleagues.Indeed, a common theme emphasized in the majority of all responses was the importance of helping colleagues with their mental wellbeing, maintaining lab morale, and facilitating return to the lab in person.Ross Fitzgerald said, "Many people suffered psychologically from the enforced isolation allied to concern regarding lack of progress in their science, particularly those working towards post-graduate degree.My computational scientists have been less affected with regard to progress but of course they have had similar mental challenges to the others-they've kept pretty positive though… the biggest challenge has been managing my group/keeping spirits up from afar-I put aside all of Monday for lab meeting and one-to-one catch-ups with everyone in my group."Sam Aparicio raised similar points: "We found that careful attention to regular interactions, not all based around work matters, was important to keep cohesion and a sense of community and purpose."… "The general assumption has been that dry lab working is less affected, but this is not entirely the case.Some persons don't have conducive home environments, others have found that the complete absence of social contact in the environment to lead to a loss of structure.We allowed part time work by informaticians and admin staff from last quarter of 2020, because it was important for social cohesion."
26191 Time to onset of creatine kinase elevation in patients with advanced basal cell carcinoma receiving sonidegib 200 mg daily: Results from the 42-month BOLT study
Authors: Aaron S. Farberg, Karl Lewis, Meenal Kheterpal, Kurt Gebauer, Alexander Guminski, Carmen Loquai, Nicholas Squittieri, Ralf Gutzmer
Journal: Journal of the American Academy of Dermatology (2021)
Effectiveness of COVID-19 Vaccines in Preventing SARS-CoV-2 Infection Among Frontline Workers Before and During B.1.617.2 (Delta) Variant Predominance — Eight U.S. Locations, December 2020–August 2021
Authors: Ashley Fowlkes, Manjusha Gaglani, Kimberly Groover, Matthew S. Thiese, Harmony Tyner, Katherine Ellingson
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

During December 14, 2020-April 10, 2021, data from the HEROES-RECOVER Cohorts,* a network of prospective cohorts among frontline workers, showed that the Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines were approximately 90% effective in preventing symptomatic and asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19, in real-world conditions (1,2). This report updates vaccine effectiveness (VE) estimates including all COVID-19 vaccines available through August 14, 2021, and examines whether VE differs for adults with increasing time since completion of all recommended vaccine doses. VE before and during SARS-CoV-2 B.1.617.2 (Delta) variant predominance, which coincided with an increase in reported COVID-19 vaccine breakthrough infections, were compared (3,4).
ナブメトン ヒトにおいて活性代謝物6-MNAが腸肝循環しない証拠
Authors: Brett M A, Buscher G, Ellrich E, Greb W H, Kurth H J, Ruelander G, Schmerenbeck B, Haddock R E, Thawley A R
Journal: Drugs (1990)
circMRPS35 promotes malignant progression and cisplatin resistance in hepatocellular carcinoma
Authors: Peng Li, Runjie Song, Fan Yin, Mei Liu, Huijiao Liu, Shuoqian Ma, Xiaomeng Jia, Xiaohui Lu, Yuting Zhong, Lei Yu, Xiru Li, Xiangdong Li
Journal: Molecular Therapy (2021)

Hepatocellular carcinoma (HCC) is one of the major causes of cancer-related death worldwide. Circular RNAs (circRNAs), a novel class of non-coding RNA, have been reported to be involved in the etiology of various malignancies. However, the underlying cellular mechanisms of circRNAs implicated in the pathogenesis of HCC remain unknown. In this study, we identified a functional RNA, hsa_circ_0000384 (circMRPS35), from public tumor databases using a set of computational analyses, and we further identified that circMRPS35 was highly expressed in 35 pairs of HCC from patients. Moreover, knockdown of the expression of circMRPS35 in Huh-7 and HCC-LM3 cells suppressed their proliferation, migration, invasion, clone formation, and cell cycle in vitro, and it suppressed tumor growth in vivo as well. Mechanically, circMRPS35 sponged microRNA-148a-3p (miR-148a), regulating the expression of Syntaxin 3 (STX3), which modulated the ubiquitination and degradation of phosphatase and tensin homolog (PTEN). Unexpectedly, we detected a peptide encoded by circMRPS35 (circMRPS35-168aa), which was significantly induced by chemotherapeutic drugs and promoted cisplatin resistance in HCC. These results demonstrated that circMRPS35 might be a novel mediator in HCC progress, and they raise the potential of a new biomarker for HCC diagnosis and prognosis, as well as a novel therapeutic target for HCC patients.
27457 Secukinumab helps achieving clear/almost clear skin and improve quality of life in psoriasis over 36 months of treatment: PURE study
Authors: Kim Papp, Melinda Gooderham, Michael Robern, Michael Shaffelburg, Dusan Sajic, Juan C. Garcia-Rodriguez, Carmen Taveras, Simon Nigen, Victoria Taraska, Antonio Vieira, Lenka Rihakova
Journal: Journal of the American Academy of Dermatology (2021)