tbuckley/cabot-search huggingface dataset:
OA15.03 Amivantamab in Non-small Cell Lung Cancer (NSCLC) with MET Exon 14 Skipping (METex14) Mutation: Initial Results from CHRYSALIS
Authors: A. Spira, M. Krebs, B.C. Cho, B. Besse, J. Goldman, P. Janne, C.K. Lee, Z. Ma, A. Mansfield, A. Minchom, S. Ou, R. Salgia, Z. Wang, G. Gao, J. Curtin, A. Roshak, R. Schnepp, M. Thayu, R. Knoblauch, J.M. Trigo
Journal: Journal of Thoracic Oncology (2021)
P10.10 Trends in Treatment Patterns and Survival in Advanced NSCLC Patients Treated at Frankfurt University Hospital in 2012–2018
Authors: A. Wolf, J. Stratmann, S. Shaid, N. Niklas, A. Calleja, R. Munro, D. Waldenberger, R. Carroll, M. Daumont, J. Penrod, L. Lacoin, G. Rohde
Journal: Journal of Thoracic Oncology (2021)
Burnout and Well-Being Among Cardiology Fellowship Program Directors
Authors: Michael W. Cullen, Julie B. Damp, Victor Soukoulis, Friederike K. Keating, Islam Abudayyeh, Alex Auseon, Deepak Bhakta, Atif Qasim, Audrey Seryak, Sakima A. Smith, Marty C. Tam, Paul Theriot, Gaby Weissman
Journal: Journal of the American College of Cardiology (2021)
Patient Perceptions and Knowledge of Ionizing Radiation From Medical Imaging
Authors: Luca Bastiani, Fabio Paolicchi, Lorenzo Faggioni, Massimo Martinelli, Roberta Gerasia, Chiara Martini, Patrizia Cornacchione, Matteo Ceccarelli, Dante Chiappino, Daniele Della Latta, Jacopo Negri, Donatella Pertoldi, Donato Negro, Giovanni Nuzzi, Vincenzo Rizzo, Paola Tamburrino, Chiara Pozzessere, Giacomo Aringhieri, Davide Caramella
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Although imaging has become a standard tool of modern medicine, its widespread use has been paralleled by an increasing cumulative radiation dose to patients despite technological advancements and campaigns calling for better awareness and minimization of unnecessary exposures. <h3>Objective</h3> To assess patients' knowledge about medical radiation and related risks. <h3>Design, Setting, and Participants</h3> A survey study of hospitals in Italy was conducted; all patients in waiting rooms for medical imaging procedures before undergoing imaging examinations at 16 teaching and nonteaching hospitals were approached to take the survey. The survey was performed from June 1, 2019, to May 31, 2020. <h3>Main Outcomes and Measures</h3> Survey respondents' basic knowledge of ionizing radiation levels and health risks, earlier imaging tests performed, and information and communication about radiation protection issues. <h3>Results</h3> Among 3039 patients invited to participate, the response rate was 94.3% (n = 2866). Participants included 1531 women (53.4%); mean (SD) age was 44.9 (17.3) years. Of the 2866 participants, 1529 (53.3%) were aware of the existence of natural sources of ionizing radiation. Mammography (1101 [38.4%]) and magnetic resonance imaging (1231 [43.0%]) were categorized as radiation-based imaging modalities. More than half of the 2866 patients (1579 [55.1%];<i>P</i> = .03) did not know that chest computed tomography delivers a larger dose of radiation than chest radiography, and only 1499 (52.3%) knew that radiation can be emitted after nuclear medicine examinations (<i>P</i> = .004). A total of 667 patients (23.3%) believed that radiation risks were unrelated to age, 1273 (44.4%) deemed their knowledge about radiation risks inadequate, and 2305 (80.4%) preferred to be informed about radiation risks by medical staff. A better knowledge of radiation issues was associated with receiving information from health care professionals (odds ratio [OR], 1.71; 95% CI, 1.43-2.03;<i>P</i> &lt; .001) and having a higher educational level (intermediate vs low: OR, 1.48; 95% CI, 1.17-1.88;<i>P</i> &lt; .001; high vs low: OR, 2.68; 95% CI, 2.09-3.43;<i>P</i> &lt; .001). <h3>Conclusions and Relevance</h3> The results of this survey suggest that patients undergoing medical imaging procedures have overall limited knowledge about medical radiation. Intervention to achieve better patient awareness of radiation risks related to medical exposures may be beneficial.
Current status and outlook of biodegradable metals in neuroscience and their potential applications as cerebral vascular stent materials
Authors: Ming Li, Miaowen Jiang, Yuan Gao, Yufeng Zheng, Zhi Liu, Chen Zhou, Tao Huang, Xuenan Gu, Ang Li, Jiancheng Fang, Xunming Ji
Journal: Bioactive Materials (2021)

Over the past two decades, biodegradable metals (BMs) have emerged as promising materials to fabricate temporary biomedical devices, with the purpose of avoiding potential side effects of permanent implants. In this review, we first surveyed the current status of BMs in neuroscience, and briefly summarized the representative stents for treating vascular stenosis. Then, inspired by the convincing clinical evidence on the in vivo safety of Mg alloys as cardiovascular stents, we analyzed the possibility of producing biodegradable cerebrovascular Mg alloy stents for treating ischemic stroke. For these novel applications, some key factors should also be considered in designing BM brain stents, including the anatomic features of the cerebral vasculature, hemodynamic influences, neuro-cytocompatibility and selection of alloying elements. This work may provide insights into the future design and fabrication of BM neurological devices, especially for brain stents.
Association of the methionine sulfoxide reductase A rs10903323 gene polymorphism with functional activity and oxidative modification of alpha-1-antitrypsin in COPD patients
Authors: V. Milovanovic, A. Topic, N. Milinkovic, Z. Lazic, A. Ivosevic, D. Radojkovic, A. Divac Rankov
Journal: Pulmonology (2021)

Chronic obstructive pulmonary disease (COPD) is multi–factorial disorder which results from environmental influences and genetic factors. We aimed to investigate whether methionine sulfoxide reductase A (MSRA) rs10903323 gene polymorphism is associated with COPD development and severity in Serbian adult population. The study included 155 patients with COPD and 134 healthy volunteers. Genotyping was determined performing home-made polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The difference between the inhibitory activities of normal and oxidized Alpha-1-Antitrypsin (A1AT) against elastase and trypsin was used for determination of Oxidized Alpha-1-Antitrypsin (OxyA1AT) (expressed as % and g/L). Functional activity of A1AT was presented as a specific inhibitor activity to elastase (SIA-Elastase, kU/g). Frequencies of the genotypes AA, AG and GG were 80.0%, 20.0%, 0% in COPD patients and 80.5%, 18.5% and 1.5% in the control group, and there was no significant difference in genotype or allele distributions between groups. Serum level of A1AT (g/L) and OxyA1AT was significantly higher in COPD patients than in the control group, but functional activity of A1AT (SIA-Elastase) was significantly lower in COPD patients than in the control group. In COPD group, increased level of OxyA1AT was present in G allele carriers who were smokers relative to G allele carriers who were not smokers. In the smoker group of patients with severe and very severe COPD (GOLD3+4), significant increase in OxyA1AT level was present in G allele carriers compared to AA homozygotes. These findings suggest that MSRA rs10903323 gene polymorphism is probably not a risk for COPD by itself but could represent a COPD modifier, since minor, G allele, is associated with an increased level of oxidized A1AT, indicating impaired ability of MSRA to repair oxidized A1AT in COPD-smokers, and in severe form of COPD.
P16.04 A Phase II Clinical Study Evaluating Camrelizumab Combined With Apatinib and Albumin Paclitaxel for Advanced Non-Small CellLung Cancer
Authors: L. Wu, X. Pu, B. Chen, F. Xu, J. Li, K. Li, L. Xu, Q. Wang, Y. Kong, L. Liu, Y. Xu, M. Xiao
Journal: Journal of Thoracic Oncology (2021)
Effects of implementing universal and rapid HIV treatment on initiation of antiretroviral therapy and retention in care in Zambia: a natural experiment using regression discontinuity
Authors: Aaloke Mody, Izukanji Sikazwe, Angella Sandra Namwase, Mwanza Wa Mwanza, Theodora Savory, Annie Mwila, Lloyd Mulenga, Michael E Herce, Keith Mweebo, Paul Somwe, Ingrid Eshun-Wilson, Kombatende Sikombe, Laura K Beres, Jake Pry, Charles B Holmes, Carolyn Bolton-Moore, Elvin H Geng
Journal: The Lancet HIV (2021)
P59.23 Biomarker Testing for Non-Small Cell Lung Cancer at a Tertiary Referral Hospital in Ireland: Challenges and Opportunities
Authors: P. Bredin, O. Breathnach, E. O'Brien, R. Morgan, I. Sulaiman, M. Redmond, C. Higgins, B. Doyle, J. Naidoo
Journal: Journal of Thoracic Oncology (2021)
Glucocorticoids inhibit human hematopoietic stem cell differentiation toward a common ILC precursor
Authors: Linda Quatrini, Nicola Tumino, Francesca Besi, Cecilia Ciancaglini, Federica Galaverna, Antonio Giacomo Grasso, Pietro Merli, Franco Locatelli, Paola Vacca, Lorenzo Moretta
Journal: Journal of Allergy and Clinical Immunology (2021)

Innate lymphoid cells (ILCs) comprise cytotoxic natural killer (NK) cells and helper ILCs (hILCs). Human hILC development is less characterized as compared with that of NK cells, although all ILCs are developmentally related. It has been reported that the immunosuppressive drugs glucocorticoids (GCs) regulate ILC function, but whether they control ILC differentiation from hematopoietic stem cells (HSCs) is unknown. This study sought to analyze the effect of GCs on ILC development from HSCs. This study exploited an in vitro system to generate and expand from peripheral blood HSCs a multipotent CD56+ ILC precursor able to differentiate into NK cells, ILC1s, and ILC3s. We also analyzed ex vivo, at different time points, the peripheral blood of recipients of allogeneic HSC transplantation who were or were not treated with GCs and compared ILC subset reconstitution. Invitro, GCs favor the generation of NK cells from myeloid precursors, while they strongly impair lymphoid development. In support of these data, recipients of HSC transplantation who had been treated with GCs display a lower number of circulating hILCs, including the ILC precursor (ILCP) previously identified as a systemic substrate for tissue ILC differentiation. GCs impair the development of the CD117+ ILCP from CD34+ HSCs, while they do not affect the further steps of ILCP differentiation toward NK cells and hILC subsets. This reflects an association of GC treatment with a marked reduction of circulating hILCs in the recipients of HSC transplantation.
Myeloid-Derived Suppressor Cells: A Propitious Road to Clinic
Authors: Amit Grover, Emilio Sanseviero, Elina Timosenko, Dmitry I. Gabrilovich
Journal: Cancer Discovery (2021)

Myeloid-derived suppressor cells (MDSC) are important regulators of immune responses in cancer. They represent a relatively stable form of pathologic activation of neutrophils and monocytes and are characterized by distinct transcriptional, biochemical, functional, and phenotypical features. The close association of MDSCs with clinical outcomes in cancer suggests that these cells can be an attractive target for therapeutic intervention. However, the complex nature of MDSC biology represents a substantial challenge for the development of selective therapies. Here, we discuss the mechanisms regulating MDSC development and fate and recent research advances that have demonstrated opportunities for therapeutic regulation of these cells. SIGNIFICANCE: MDSCs are attractive therapeutic targets because of their close association with negative clinical outcomes in cancer and established biology as potent immunosuppressive cells. However, the complex nature of MDSC biology presents a substantial challenge for therapeutic targeting. In this review, we discuss those challenges and possible solutions.
Targeting adipose tissue to tackle NASH: SPARCL1 as an emerging player
Authors: Robim M. Rodrigues, Yukun Guan, Bin Gao
Journal: Journal of Clinical Investigation (2021)

Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease, affecting 1.5%-6.5% of the world population. Currently, there are no FDA-approved drugs to treat this disease. Accumulating evidence suggests that metabolically hazardous visceral fat contributes to NASH progression by releasing fatty acids and proinflammatory mediators. Therefore, targeting adipose tissue to reduce adipose inflammation may provide an effective strategy to treat NASH. Another strategy is to target specific inflammatory mediators that are produced by adipose tissue and contribute to NASH progression. In this issue of the JCI, Liu, Xiang, et al. demonstrate that secreted protein acidic and rich in cysteine-like protein 1 (SPARCL1) was highly upregulated in adipose tissue and played a role in exacerbating NASH progression in a mouse model of NASH. Thus, inhibition of SPARCL1 may provide another attractive strategy to tackle NASH.
Endoscopic submucosal dissection of a small rectal submucosal lesion: a rare case of rectal liposarcoma
Authors: Lucile Héroin, Pierre Lafeuille, Thomas Lambin, Pierre Mayer, Martin Bordet, Florian Rostain, Mathieu Pioche
Journal: Endoscopy (2021)

With the broadening of indications for colonoscopy, colonic subepithelial lesions (SELs) are more frequently detected. Their incidence is about one in 300 colonoscopies. They appear as a small bulging lesion covered with normal mucosa [1]. Liposarcoma is one of the most common soft tissue sarcomas, yet it is an extremely rare disease. Less than 20 colonic liposarcomas have been described [2].
Proteomics-Enabled Deep Learning Machine Algorithms Can Enhance Prediction of Mortality
Authors: Matthias Unterhuber, Karl-Patrik Kresoja, Karl-Philipp Rommel, Christian Besler, Andrea Baragetti, Nora Klöting, Uta Ceglarek, Matthias Blüher, Markus Scholz, Alberico L. Catapano, Holger Thiele, Philipp Lurz
Journal: Journal of the American College of Cardiology (2021)
Targeting PPARα in low ambient temperature exposure-induced cardiac dysfunction and remodeling
Authors: Xi-Yao Chen, Yang Jiao, Fu-Yang Zhang
Journal: Military Medical Research (2021)

Abstract The present study demonstrates that the down-regulation of peroxisome proliferator-activated receptor-α (PPARα) results in chronic low ambient temperature (LT) exposure-induced cardiac dysfunction and remodeling, emphasizing the therapeutic potential of PPARα activation strategies (e.g. fenofibrate treatment) in LT-associated cardiac injury.
Antibody interference and response kinetics of isatuximab plus pomalidomide and dexamethasone in multiple myeloma
Authors: Cyrille Hulin, Meral Beksac, Hugh J. Goodman, Ivan Spicka, Adrian Alegre, Miles Prince, Frank Campana, Greg Finn, Solenn Le-Guennec, Sandrine Macé, Stéphane Muccio, Alexandra Tavernier, Marie-Claude Rouchon, Paul G. Richardson
Journal: Blood Cancer Journal (2021)
In defence of general practice and the NHS
Authors: Khurram Hassan
Journal: BMJ (2021)

Mahase examines the “toxic” media stories about primary care that have left many GPs feeling demoralised and browbeaten and being blamed for government failures.1

The messaging in defence of general practice and the NHS needs to be simpler. Remembering that Boris Johnson and the electorate seem to be enamoured by banal phrases (get …
Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identify European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States.
Authors: Andrea Horimoto, Diane Xue, Jainwen Cai, James Lash, Martha Daviglus, Nora Franceschini, Timothy Thornton
Journal: Journal of the American Society of Nephrology (2021)

Background Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture, such as Hispanic or Latino individuals in the United States. These individuals have an increased risk of chronic kidney disease (CKD). Methods We performed genome-wide admixture mapping for both CKD and estimated glomerular filtration rate (eGFR) in a sample of 12,601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 African American participants from the Women's Health Initiative (WHI). We also compared the findings with those from a conventional genome-wide association study. Results Three novel ancestry-of-origin loci were identified on chromosomes 2, 14, and 15 for CKD and eGFR-loci harboring genes that have been implicated in kidney function. The chromosome 2 locus comprises two European ancestry regions encompassing the FSHR and NRXN1 genes, with European ancestry at this locus associated with increased CKD risk. The chromosome 14 locus, found within the DLK1-DIO3 imprinted domain, was associated with lower eGFR and driven by European ancestry. The eGFR-associated locus on chromosome 15 included intronic variants of RYR3 and was within an African-specific genomic region associated with higher eGFR. The genomewide association study failed to identify significant associations in these regions. We validated the chromosome 14 and 15 loci associated with eGFR in the WHI African American participants. Conclusions This study provides evidence of shared ancestry-specific genomic regions influencing eGFR in Hispanic or Latino individuals and African American individuals, and illustrates the potential for leveraging genetic ancestry in recently admixed populations for the discovery of novel candidate loci for kidney phenotypes.
Automated CUT&amp;Tag profiling of chromatin heterogeneity in mixed-lineage leukemia
Authors: Derek H. Janssens, Michael P. Meers, Steven J. Wu, Ekaterina Babaeva, Soheil Meshinchi, Jay F. Sarthy, Kami Ahmad, Steven Henikoff
Journal: Nature Genetics (2021)

Abstract Acute myeloid and lymphoid leukemias often harbor chromosomal translocations involving the KMT2A gene, encoding the KMT2A lysine methyltransferase (also known as mixed-lineage leukemia-1), and produce in-frame fusions of KMT2A to other chromatin-regulatory proteins. Here we map fusion-specific targets across the genome for diverse KMT2A oncofusion proteins in cell lines and patient samples. By modifying CUT&amp;Tag chromatin profiling for full automation, we identify common and tumor-subtype-specific sites of aberrant chromatin regulation induced by KMT2A oncofusion proteins. A subset of KMT2A oncofusion-binding sites are marked by bivalent (H3K4me3 and H3K27me3) chromatin signatures, and single-cell CUT&amp;Tag profiling reveals that these sites display cell-to-cell heterogeneity suggestive of lineage plasticity. In addition, we find that aberrant enrichment of H3K4me3 in gene bodies is sensitive to Menin inhibitors, demonstrating the utility of automated chromatin profiling for identifying therapeutic vulnerabilities. Thus, integration of automated and single-cell CUT&amp;Tag can uncover epigenomic heterogeneity within patient samples and predict sensitivity to therapeutic agents.
Metabolic and Signaling Roles of Ketone Bodies in Health and Disease
Authors: Patrycja Puchalska, Peter A. Crawford
Journal: Annual Review of Nutrition (2021)

Ketone bodies play significant roles in organismal energy homeostasis, serving as oxidative fuels, modulators of redox potential, lipogenic precursors, and signals, primarily during states of low carbohydrate availability. Efforts to enhance wellness and ameliorate disease via nutritional, chronobiological, and pharmacological interventions have markedly intensified interest in ketone body metabolism. The two ketone body redox partners, acetoacetate and D-β-hydroxybutyrate, serve distinct metabolic and signaling roles in biological systems. We discuss the pleiotropic roles played by both of these ketones in health and disease. While enthusiasm is warranted, prudent procession through therapeutic applications of ketogenic and ketone therapies is also advised, as a range of metabolic and signaling consequences continue to emerge. Organ-specific and cell-type-specific effects of ketone bodies are important to consider as prospective therapeutic and wellness applications increase.
The Japan Society for Neuro-Oncology guideline on the diagnosis and treatment of central nervous system germ cell tumors
Authors: Hideo Nakamura, Hirokazu Takami, Takaaki Yanagisawa, Toshihiro Kumabe, Takamitsu Fujimaki, Yoshiki Arakawa, Katsuyuki Karasawa, Keita Terashima, Hideaki Yokoo, Kohei Fukuoka, Yukihiko Sonoda, Kaori Sakurada, Yohei Mineharu, Toshinori Soejima, Motoaki Fujii, Naoki Shinojima, Junichi Hara, Kai Yamasaki, Junya Fujimura, Fumiyuki Yamasaki, Mayu Takahashi, Tomonari Suzuki, Iori Sato, Ryo Nishikawa, Kazuhiko Sugiyama
Journal: Neuro-Oncology (2021)

Primary CNS germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. In line with the hypothesis that the primordial germ cell is the cell-of-origin, histopathological examinations for this pathology involve a diverse range of components mirroring the embryogenic developmental dimensions. Chemotherapy and radiotherapy are the mainstays of treatment, with surgery having a limited role for diagnosis and debulking of residual tissue after treatment. While better management has been achieved over recent decades by modifying radiation coverage and selecting appropriate chemotherapy, standardization of treatment remains challenging, partly due to the low volume of cases encountered in each institution. As the incidence is higher in East Asia, including Japan, the Japan Society for Neuro-Oncology established a multidisciplinary task force to create an evidence-based guideline for CNS GCTs. This guideline provides recommendations for multiple dimensions of clinical management for CNS GCTs, with particular focus on diagnostic measures including serum markers, treatment algorithms including surgery, radiotherapy, and chemotherapy, and under-investigated but important areas such as treatment for recurrent cases, long-term follow-up protocols, and long-term sequelae. This guideline serves the purpose of helping healthcare professionals keep up to date with current knowledge and standards of management for patients with this rare disease in daily clinical practice, as well as driving future translational and clinical research by recognizing unmet needs concerning this tumor.
원발성 간암에서 PIVKA-II 및 Lens Culinaris Agglutinin-A 반응성 Alpha-fetoprotein(AFP-L3)의 임상적 유용성
Authors: 변병훈(B. H. Byun), 박영민(Y. M. Park), 배시현(S. H. Bae), 최종영(J. Y. Choi), 성광용(K. Y. Sung), 조세현(S. H. Cho), 양진모(J. M. Yang), 최상욱(S. O. Choi), 차상복(S. B. Cha), 정규원(K. W. Chung), 선희식(H. S. Sun), 박두호(D. H. Park), 김부성(B. S. Kim)
Journal: Clinical and Molecular Hepatology (2000)

Background/Aims: Des-γ-carboxy prothrombin(DCP), a protein induced by vitamin K absence or antagonist-II(PIVKA-II), and Lens culinaris agglutinin-A reactive AFP-L3 have been reported to be useful markers for the diagnosis of hepatocellular carcinoma (HCC). In the present study, both the PIVKA-II and AFP-L3 were analyzed and compared with a conventional AFP to determine its usefulness, specificity and sensitivity in the diagnosis of HCC. Methods: Sera were collected from 108 patients consisting of 17 patients with chronic hepatitis, 22 patients with liver cirrhosis and 69 patients with HCC. The AFP-L3 was determined by an lectin affinity electrophoresis coupled with an antibody-affinity blotting. Level of DCP was measured by an enzyme immunoassay with an anti-DCP monoclonal antibody. Results: The sensitivity and specificity of PIVKA-II and AFP L3 were 49.3% and 89.5%, and 32.5% and 85.7%, respectively. No significant correlation was found between the PIVKA-II or AFP L3 and serum AFP. No correlation was found between the PIVKA-II or AFP L3 and the characteristics of HCC. Conclusion: The determination of plasma DCP and AFP L3 levels combined with AFP levels may be useful especially for the differential diagnosis between HCC and chronic liver diseases without HCC.(Korean J Hepatol 2000;6:205-214)
P59.11 Real-World Data of NGS Diagnostic Biomarker Testing for Lung Cancer Patients in Japan
Authors: T. Takahashi, M. Nishio, Y. Yatabe, K. Nishino, Y. Yoshiki, N. Shiraiwa, B. Emir, L. Iadeluca, K. Nishio
Journal: Journal of Thoracic Oncology (2021)