tbuckley/cabot-search huggingface dataset:
MO01.39 Liposomal Irinotecan in Adults with Small Cell Lung Cancer who Progressed on Platinum-Based Therapy: Subgroup Analyses by Platinum Sensitivity
Authors: D.R. Spigel, L.G. Paz-Ares, Y. Chen, M. Jove, O. Juan-Vidal, P. Rich, T. Hayes, V.G. Calderón, R.B. Caro, A. Navarro, A. Dowlati, B. Zhang, Y. Moore, T. Wang, N. Nazarenko, J. Kokhreidze, S. Ponce, P. Bunn
Journal: Journal of Thoracic Oncology (2021)
Aberrant splicing isoforms detected by full-length transcriptome sequencing as transcripts of potential neoantigens in non-small cell lung cancer
Authors: Miho Oka, Liu Xu, Toshihiro Suzuki, Toshiaki Yoshikawa, Hiromi Sakamoto, Hayato Uemura, Akiyasu C. Yoshizawa, Yutaka Suzuki, Tetsuya Nakatsura, Yasushi Ishihama, Ayako Suzuki, Masahide Seki
Journal: Genome biology (2021)

Abstract Background Long-read sequencing of full-length cDNAs enables the detection of structures of aberrant splicing isoforms in cancer cells. These isoforms are occasionally translated, presented by HLA molecules, and recognized as neoantigens. This study used a long-read sequencer (MinION) to construct a comprehensive catalog of aberrant splicing isoforms in non-small-cell lung cancers, by which novel isoforms and potential neoantigens are identified. Results Full-length cDNA sequencing is performed using 22 cell lines, and a total of 2021 novel splicing isoforms are identified. The protein expression of some of these isoforms is then validated by proteome analysis. Ablations of a nonsense-mediated mRNA decay (NMD) factor, UPF1, and a splicing factor, SF3B1, are found to increase the proportion of aberrant transcripts. NetMHC evaluation of the binding affinities to each type of HLA molecule reveals that some of the isoforms potentially generate neoantigen candidates. We also identify aberrant splicing isoforms in seven non-small-cell lung cancer specimens. An enzyme-linked immune absorbent spot assay indicates that approximately half the peptide candidates have the potential to activate T cell responses through their interaction with HLA molecules. Finally, we estimate the number of isoforms in The Cancer Genome Atlas (TCGA) datasets by referring to the constructed catalog and found that disruption of NMD factors is significantly correlated with the number of splicing isoforms found in the TCGA-Lung Adenocarcinoma data collection. Conclusions Our results indicate that long-read sequencing of full-length cDNAs is essential for the precise identification of aberrant transcript structures in cancer cells.
Opening of Large Institutions of Higher Education and County-Level COVID-19 Incidence — United States, July 6–September 17, 2020
Authors: Andrew J. Leidner, Vaughn Barry, Virginia B. Bowen, Rachel Silver, Trieste Musial, Gloria J. Kang, Matthew D. Ritchey, Kelly Fletcher, Lisa Barrios, Eric Pevzner
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Instructional format was assigned based on the advertised method of instruction for the first day of fall 2020 classes."Remote" format was defined as an instructional format that appeared to minimize in-person classwork on campus.This definition did allow in-person instruction for a very select number of students, including those in laboratory courses, studio courses, or courses for small groups of students with specific
Abstract 12885: Mid-Term Outcomes After Percutaneous Coronary Intervention in Cancer Patients
Authors: Raymundo A Quintana Quezada, Dominique Monlezun, Giovanni E Davogustto, Humberto R Saenz, Francisco Lozano-Ruiz, Daisuke Sueta, Kenichi Tsujita, Uri Landes, Ali E Denktas, Mahboob Alam, Daniel Addison, David Paniagua, Hani Jneid
Journal: Circulation (2019)

Introduction: Randomized clinical trials demonstrated the benefits of percutaneous coronary interventions (PCI) in diverse clinical settings. Patients with cancer were not included in these studies...
LncRNA CRNDE attenuates chemoresistance in gastric cancer via SRSF6-regulated alternative splicing of PICALM
Authors: Feifei Zhang, Hui Wang, Jiang Yu, Xueqing Yao, Shibin Yang, Weidong Li, Lijun Xu, Liang Zhao
Journal: Molecular Cancer (2021)

De novo and acquired resistance, which are mainly mediated by genetic alterations, are barriers to effective routine chemotherapy. However, the mechanisms underlying gastric cancer (GC) resistance to chemotherapy are still unclear. We showed that the long noncoding RNA CRNDE was related to the chemosensitivity of GC in clinical samples and a PDX model. CRNDE was decreased and inhibited autophagy flux in chemoresistant GC cells. CRNDE directly bound to splicing protein SRSF6 to reduce its protein stability and thus regulate alternative splicing (AS) events. We determined that SRSF6 regulated the PICALM exon 14 skip splice variant and triggered a significant S-to-L isoform switch, which contributed to the expression of the long isoform of PICALM (encoding PICALML). Collectively, our findings reveal the key role of CRNDE in autophagy regulation, highlighting the significance of CRNDE as a potential prognostic marker and therapeutic target against chemoresistance in GC.
OFP01.03 Systemic and Intracranial Efficacy of Brigatinib vs.Crizotinib: Updated Results from the ALTA-1L Trial
Authors: S. Popat, H.R. Kim, M.-J. Ahn, James CH. Yang, J.-Y. Han, M. Hochmair, K.H. Lee, A. Delmonte, M.R. Garcia Campelo, D.-W. Kim, F. Griesinger, E. Felip, R. Califano, A. Spira, S. Gettinger, M. Tiseo, H. Lin, Y. Liu, P. Zhang, D.R. Camidge
Journal: Journal of Thoracic Oncology (2021)
Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy
Authors: Kailin Li, Jieqiong You, Qian Wu, Wen Meng, Qiaojun He, Bo Yang, Chengliang Zhu, Ji Cao
Journal: Acta Pharmaceutica Sinica B (2021)

Synthetic lethality is a proven effective antitumor strategy that has attracted great attention. Large-scale screening has revealed many synthetic lethal genetic phenotypes, and relevant small-molecule drugs have also been implemented in clinical practice. Increasing evidence suggests that CDKs, constituting a kinase family predominantly involved in cell cycle control, are synthetic lethal factors when combined with certain oncogenes, such as MYC, TP53, and RAS, which facilitate numerous antitumor treatment options based on CDK-related synthetic lethality. In this review, we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future.
Assessment of Duplicate Evidence in Systematic Reviews of Imaging Findings of Children With COVID-19
Authors: Giordano Pérez-Gaxiola, Francisca Verdugo-Paiva, Gabriel Rada, Iván D. Flórez
Journal: JAMA Network Open (2021)

included.Four studies (21%) were probably missed during the review process, and the other 15 (79%) were published after their search. DiscussionThis study presents a particular case in which, in less than 6 months, the literature was flooded with more systematic reviews than primary studies trying to answer a very specific clinical question, such as the imaging findings in children with COVID-19.Replication of systematic reviews may be appropriate to verify their findings or to extend or narrow the question they are trying to answer. 1 However, needless repetition is wasteful.Initiatives like the PROSPERO database were created so authors could identify ongoing systematic reviews and perhaps stop the development of a new, unnecessary study. 3,4plication at a massive level, which has happened with COVID-19, is unjustified and may be unethical. 1,5,6None of the systematic reviews included the totality of primary studies, which may be partly explained by the rapid rate of reporting of new studies but also by limitations of search strategies.This also highlights how quickly published reviews can become obsolete if they are not continuously updated.This study has limitations.Our analysis cannot provide clinical guidance regarding the imaging findings of children with COVID-19.The findings are also limited to the date of our search.
Rodney Douglas Antcliffe
Authors: Andy Webster
Journal: BMJ (2021)

Rodney Douglas Antcliffe (“Rod”) graduated from the Middlesex Hospital Medical School in 1970. He decided that further exams were not for him, went into general practice training, and after three years started his first post as a full time partner in Kettering, where he worked from 1974 to 2002. He also developed an …
Rates of COVID-19 Among Residents and Staff Members in Nursing Homes — United States, May 25–November 22, 2020
Authors: Suparna Bagchi, Josephine Mak, Qunna Li, Edward Sheriff, Elisabeth Mungai, Angela Anttila, Minn Minn Soe, Jonathan R. Edwards, Andrea L. Benin, Daniel A. Pollock, Evan Shulman, Shari Ling, Jean Moody-Williams, Lee A. Fleisher, Arjun Srinivasan, Jeneita M. Bell
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

During the beginning of the coronavirus disease 2019 (COVID-19) pandemic, nursing homes were identified as congregate settings at high risk for outbreaks of COVID-19 (1,2). Their residents also are at higher risk than the general population for morbidity and mortality associated with infection with SARS-CoV-2, the virus that causes COVID-19, in light of the association of severe outcomes with older age and certain underlying medical conditions (1,3). CDC's National Healthcare Safety Network (NHSN) launched nationwide, facility-level COVID-19 nursing home surveillance on April 26, 2020. A federal mandate issued by the Centers for Medicare & Medicaid Services (CMS), required nursing homes to commence enrollment and routine reporting of COVID-19 cases among residents and staff members by May 25, 2020. This report uses the NHSN nursing home COVID-19 data reported during May 25-November 22, 2020, to describe COVID-19 rates among nursing home residents and staff members and compares these with rates in surrounding communities by corresponding U.S. Department of Health and Human Services (HHS) region.* COVID-19 cases among nursing home residents increased during June and July 2020, reaching 11.5 cases per 1,000 resident-weeks (calculated as the total number of occupied beds on the day that weekly data were reported) (week of July 26). By mid-September, rates had declined to 6.3 per 1,000 resident-weeks (week of September 13) before increasing again, reaching 23.2 cases per 1,000 resident-weeks by late November (week of November 22). COVID-19 cases among nursing home staff members also increased during June and July (week of July 26 = 10.9 cases per 1,000 resident-weeks) before declining during August-September (week of September 13 = 6.3 per 1,000 resident-weeks); rates increased by late November (week of November 22 = 21.3 cases per 1,000 resident-weeks). Rates of COVID-19 in the surrounding communities followed similar trends. Increases in community rates might be associated with increases in nursing home COVID-19 incidence, and nursing home mitigation strategies need to include a comprehensive plan to monitor local SARS-CoV-2 transmission and minimize high-risk exposures within facilities.
Towards safe drinking water and clean cooking for all
Authors: Isha Ray, Kirk R Smith
Journal: The Lancet Global Health (2021)

The public health community has tried for decades to show, through evidence-based research, that safe water, sanitation, and hygiene (WASH) and clean cooking fuels that reduce household air pollution are essential to safeguard health and save lives in low-income and middle-income countries. In the past 40 decades, there have been many innovations in the development of low-cost and efficacious technologies for WASH and household air pollution, but many of these technologies have been associated with disappointing health outcomes, often because low-income households have either not adopted, or inconsistently adopted, these technologies. In this Viewpoint, we argue that public health researchers (ourselves included) have had an oversimplified understanding of poverty; our work has not focused on insights into the lived experience of poverty, with its uncertainties, stresses from constant scarcity, and attendant fears. Such insights are central to understanding why technologies for safe water or clean cooking are unused by so many households that could benefit from them. We argue that, rather than improved versions of household-scale delivery models, transformative investments in safe water and clean cooking for all require utility-scale service models. Until then, research should focus on interim safe water and clean cooking options that are directed towards the utility-scale service model.
Ewing’s Sarcoma
Authors: Nicolò Riggi, Mario L. Suvà, Ivan Stamenkovic
Journal: New England Journal of Medicine (2021)

Ewing's sarcoma, an aggressive cancer of bone and soft tissue, primarily affects children and young adults. A t(11;22) translocation is noted in 85 to 90% of cases. Management includes surgery, radiotherapy, and chemotherapy. The 5-year survival is about 70%.
Abstract 10277: The Branched-chain Amino Acids Valine and Leucine Predict All-cause Mortality in Cardiovascular Disease Patients Independently From the Presence of Type 2 Diabetes Mellitus
Authors: Axel Muendlein, Andreas Leiherer, Christoph H Saely, Alexander Vonbank, Marc Schindewolf, Joern F Dopheide, Iris Baumgartner, Arthur Mader, Peter Fraunberger, Heinz Drexel
Journal: Circulation (2019)

Introduction: Circulating branched-chain amino acids (BCAAs) are linked with mortality in population-based studies. Hypothesis: We hypothesize that BCAAs have the power to predict mortality in pati...
Impact of Axillary Dissection Among Patients With Sentinel Node–Positive Breast Cancer Undergoing Mastectomy
Authors: James Sun, Brittany J. Mathias, Christine Laronga, Weihong Sun, Jun-Min Zhou, William J. Fulp, John V. Kiluk, M. Catherine Lee
Journal: Journal of the National Comprehensive Cancer Network (2021)

Background: Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. Materials and Methods: A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). Results: Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46–62 years). The median number of SLNs sampled was 3 (IQR, 2–4), and the median number of positive SLNs was 1 (IQR, 1–2). Patients receiving CLND had higher tumor grades ( P =.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P =.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29–83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS ( P =.04). Conclusions: CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.
Inhibition of LIM kinase reduces contraction and proliferation in bladder smooth muscle
Authors: Qingfeng Yu, Chengjie Wu, Yeda Chen, Bingsheng Li, Ruixiao Wang, Ru Huang, Xuechun Li, Di Gu, Xiaolong Wang, Xiaolu Duan, Shujue Li, Yang Liu, Wenqi Wu, Martin Hennenberg, Guohua Zeng
Journal: Acta Pharmaceutica Sinica B (2021)

Overactive bladder (OAB) is the most bothersome symptom in lower urinary tract symptoms (LUTS). Current pharmacologic treatment aims to inhibit detrusor contraction; however, shows unsatisfied efficacy and high discontinuation rate. LIM kinases (LIMKs) promote smooth muscle contraction in the prostate; however, their function in the bladder smooth muscle remains unclear. Here, we studied effects of the LIMK inhibitors on bladder smooth muscle contraction and proliferation both in vitro and in vivo experiments. Bladder expressions of LIMKs are elevated in OAB rat detrusor tissues. Two LIMK inhibitors, SR7826 and LIMKi3, inhibit contraction of human detrusor strip, and cause actin filament breakdown, as well as cell proliferation reduction in cultured human bladder smooth muscle cells (HBSMCs), paralleled by reduced cofilin phosphorylation. Silencing of LIMK1 and LIMK2 in HBSMCs resulted in breakdown of actin filaments and decreased cell proliferation. Treatment with SR7826 or LIMKi3 decreased micturition frequency and bladder detrusor hypertrophy in rats with bladder outlet obstruction. Our study suggests that LIMKs may promote contraction and proliferation in the bladder smooth muscle, which could be inhibited by small molecule LIMK inhibitors. LIMK inhibitors could be a potential therapeutic strategy for OAB- related LUTS.
Duration of Adjuvant Doublet Chemotherapy (3 or 6 months) in Patients With High-Risk Stage II Colorectal Cancer
Authors: Timothy J. Iveson, Alberto F. Sobrero, Takayuki Yoshino, Ioannis Souglakos, Fang-Shu Ou, Jeffrey P. Meyers, Qian Shi, Axel Grothey, Mark P. Saunders, Roberto Labianca, Takeharu Yamanaka, Ioannis Boukovinas, Niels H. Hollander, Fabio Galli, Kentaro Yamazaki, Vassilis Georgoulias, Rachel Kerr, Eiji Oki, Sara Lonardi, Andrea Harkin, Gerardo Rosati, James Paul
Journal: Journal of Clinical Oncology (2021)

As oxaliplatin results in cumulative neurotoxicity, reducing treatment duration without loss of efficacy would benefit patients and healthcare providers.
Cellulose fibers-reinforced self-expanding porous composite with multiple hemostatic efficacy and shape adaptability for uncontrollable massive hemorrhage treatment
Authors: Yansen Wang, Yifan Zhao, Longxue Qiao, Faxing Zou, Yajie Xie, Yudong Zheng, Yong Chao, Ying Yang, Wei He, Siming Yang
Journal: Bioactive Materials (2021)

Uncontrollable hemorrhage leads to high mortality and thus effective bleeding control becomes increasingly important in the military field and civilian trauma arena. However, current hemostats not only present limitation when treating major bleeding, but also have various side effects. Here we report a self-expanding porous composites (CMCP) based on novel carboxymethyl cellulose (CMC) fibers and acetalized polyvinyl alcohol (PVA) for lethal hemorrhage control. The CMC fibers with uniform fibrous structure, high liquid absorption and procoagulant ability, are evenly interspersed inside the composite matrix. The obtained composites possess unique fiber-porous network, excellent absorption capacity, fast liquid-triggered self-expanding ability and robust fatigue resistance, and their physicochemical performance can be fine-tuned through varying the CMC content. In vitro tests show that the porous composite exhibits strong blood clotting ability, high adhesion to blood cells and protein, and the ability to activate platelet and the coagulation system. In vivo hemostatic evaluation further confirms that the CMCP presents high hemostatic efficacy and multiple hemostatic effects in swine femoral artery major hemorrhage model. Additionally, the CMCP will not fall off from the injury site, and is also easy to surgically remove from the wound cavity after the hemostasis. Importantly, results of CT tomography and 3D reconstruction indicate that CMCP can achieve shape adaptation to the surrounding tissues and the wound cavities with different depths and shapes, to accelerate hemostasis while protecting wound tissue and preventing infection.
TT01.01 Real-World Outcomes in Patients with EGFR/ALK-Positive NSCLC Treated with Chemotherapy Following 1 or 2 Lines of TKI Therapy
Authors: P. Cheema, T. Ton, P. Lambert, D. Merritt, S. Morris, G. Shankar, A.K. Ganti
Journal: Journal of Thoracic Oncology (2021)
Excess body weight is an independent risk factor for severe forms of COVID-19
Authors: Léa Pietri, Roch Giorgi, Audrey Bégu, Manon Lojou, Marie Koubi, Raphael Cauchois, Rachel Grangeot, Noémie Dubois, Gilles Kaplanski, René Valéro, Sophie Béliard
Journal: Metabolism (2021)
Abstract 10763: Resting Heart Rate as an Indicator of Ideal Cardiovascular Health: The Multi-Ethnic Study of Atherosclerosis
Authors: Olatokunbo Osibogun, Oluseye Ogunmoroti, Erica S Spatz, Oluwaseun E Fashanu, Erin D Michos
Journal: Circulation (2018)

Background: Resting heart rate (RHR) is an inexpensive clinical marker associated with increased cardiovascular disease (CVD) risk. Epidemiological studies show that elevated RHR is associated with...
Praegnatio Perturbatio—Impact of Endocrine-Disrupting Chemicals
Authors: Vasantha Padmanabhan, Wenhui Song, Muraly Puttabyatappa
Journal: Endocrine Reviews (2021)

Abstract The burden of adverse pregnancy outcomes such as preterm birth and low birth weight is considerable across the world. Several risk factors for adverse pregnancy outcomes have been identified. One risk factor for adverse pregnancy outcomes receiving considerable attention in recent years is gestational exposure to endocrine-disrupting chemicals (EDCs). Humans are exposed to a multitude of environmental chemicals with known endocrine-disrupting properties, and evidence suggests exposure to these EDCs have the potential to disrupt the maternal-fetal environment culminating in adverse pregnancy and birth outcomes. This review addresses the impact of maternal and fetal exposure to environmental EDCs of natural and man-made chemicals in disrupting the maternal-fetal milieu in human leading to adverse pregnancy and birth outcomes—a risk factor for adult-onset noncommunicable diseases, the role lifestyle and environmental factors play in mitigating or amplifying the effects of EDCs, the underlying mechanisms and mediators involved, and the research directions on which to focus future investigations to help alleviate the adverse effects of EDC exposure.
Stem cell origins of JMML
Authors: Sriram Sundaravel, Ulrich Steidl
Journal: The Journal of Experimental Medicine (2021)

In this issue of JEM, Louka et al. (https://doi.org/10.1084/jem.20180853) report that leukemia stem cells lie within the phenotypic hematopoietic stem cell and progenitor cell compartments in juvenile myelomonocytic leukemia (JMML). Furthermore, they identify several candidate biomarker/therapeutic targets, such as CD96 and SLC2A1, that are of translational significance in JMML.