tbuckley/cabot-search huggingface dataset:
Abstract P2-04-01: Overexpressed cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors
Authors: Qiang Liu, Zijie Cai, Jingru Wang, Yudong Li, Lok Lam Wong
Journal: Cancer Research (2022)

Abstract CDK4/6 inhibitors are now the standard treatment in advanced HR+/HER2- breast cancer patients. Nevertheless, the resistance to CDK4/6 inhibitors is inevitable, limiting its use and efficacy. The mechanisms and the strategies to overcome resistance are of great interest. Here, we show that the palbociclib-resistant breast cancer cells express significantly higher levels of Cyclin D1 and CDK4 proteins because of upregulated protein synthesis. Silencing Cyclin D1 or CDK4 directly led to cell cycle arrest while silencing Cyclin E1 or CDK2 restored the sensitivity to palbociclib in palbociclib-resistant cells. Furthermore, PI3K/mTOR pathway was hyper-activated in palbociclib-resistant cells, leading to more phosphorylated 4E-BP1 and higher levels of Cyclin D1 and CDK4 translation. Targeting PI3K/mTOR pathway with a specific PI3Kα inhibitor (BYL719) or an mTOR inhibitor (everolimus) reduced the protein levels of Cyclin D1 and CDK4, and restored the sensitivity to palbociclib in resistant cells both in vitro and in vivo. The tumors from breast cancer patients who progressed after palbociclib treatment had significantly higher protein expression of Cyclin D1, CDK4, p-AKT and p-4E-BP1 than the paired samples before palbociclib treatment. In conclusion, our findings suggest that overexpressed Cyclin D1 and CDK4 proteins lead to the resistance to CDK4/6 inhibitor and PI3K/mTOR inhibitors are able to restore the sensitivity to CDK4/6 inhibitors, which provides the biomarker and rationale for the combinational use of CDK4/6 inhibitors and PI3K/mTOR inhibitors after CDK4/6 inhibitor resistance in breast cancer. Citation Format: Qiang Liu, Zijie Cai, Jingru Wang, Yudong Li, Lok Lam Wong. Overexpressed cyclin D1 and CDK4 proteins are responsible for the resistance to CDK4/6 inhibitor in breast cancer that can be reversed by PI3K/mTOR inhibitors [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-04-01.
1 Year HIIT and Omega-3 Fatty Acids to Improve Cardiometabolic Risk in Stage-A Heart Failure
Authors: Christopher M. Hearon, Katrin A. Dias, James P. MacNamara, Michinari Hieda, Yogamaya Mantha, Rakushumimarika Harada, Mitchel Samels, Margot Morris, Lidia S. Szczepaniak, Benjamin D. Levine, Satyam Sarma
Journal: JACC Heart Failure (2022)
Mortality after admission with pneumonia is higher than after admission with an exacerbation of COPD
Authors: Jørgen Vestbo, Grant Waterer, David Leather, Courtney Crim, Nawar Diar Bakerly, Lucy Frith, Loretta Jacques, Catherine Harvey, Imran Satia, Ashley Woodcock
Journal: European Respiratory Journal (2022)

<b>Mortality after an admission for pneumonia is considerably higher than for an admission for an exacerbation in COPD patients recruited from usual clinical practice. A proper diagnosis in acute worsenings of symptoms in COPD is therefore important.</b>https://bit.ly/3LyhnnC
Chimeric antigen receptors containing the OX40 signalling domain enhance the persistence of T cells even under repeated stimulation with multiple myeloma target cells
Authors: Jingwen Tan, Yujie Jia, Meixia Zhou, Chengcheng Fu, Israth Jahan Tuhin, Jing Ye, Masuma Akter Monty, Nan Xu, Liqing Kang, Minghao Li, Jiaqi Shao, Xiaoyan Fang, Hongjia Zhu, Lingzhi Yan, Changju Qu, Shengli Xue, Zhengming Jin, Suning Chen, Haiwen Huang, Yang Xu, Jia Chen, Miao Miao, Xiaowen Tang, Caixia Li, Zhiqiang Yan, Depei Wu, Lei Yu
Journal: Journal of Hematology & Oncology (2022)

Abstract Persistence of CAR-T cell function is associated with relapse rate after CAR-T therapy, while co-stimulatory agents are highly concerned with the persistence of CAR-T cells. In this study, we designed and constructed a series of BCMA-targeting second-generation CAR constructs containing CD28, 41BB, and OX40 molecules, respectively, to identify the costimulatory domains most favorable for persistence. The results of routine in vitro studies showed that OX40-CAR-T and 41BB-CAR-T had similar antitumor effects and were superior to CD28-CAR-T in terms of proliferation and cytotoxicity. Although difficult to distinguish by conventional functional assays, OX40-CAR-T cells exhibited greater proliferation and enhanced immune memory than 41BB-CAR-T cells with the repeated stimulation assay by BCMA-expressing target cells. In vivo studies further demonstrated that OX40-CAR-T cells had stronger proliferative activity than 41BB-CAR-T cells, which was highly consistent with the in vitro antitumor activity and proliferation results. Our study provides for the first time a scientific basis for designing OX40-CAR-T cell therapy to improve relapse in patients with MM after CAR-T treatment.
An Antisense Oligonucleotide for Hereditary Angioedema
Authors: Hilary J. Longhurst, Rohan Ameratunga
Journal: New England Journal of Medicine (2022)

Hereditary angioedema with C1 esterase inhibitor deficiency is an autosomal dominant disorder of high penetrance. It manifests as unpredictable episodes of disabling, disfiguring, and painful angioedema. The associated psychological and economic detriment is proportional to the severity and frequency of angioedema attacks. In the absence of specialist treatment, mortality can be as high as 40%.1-3 The disorder is caused by heterozygous mutations in SERPING1, which cause a loss of function of C1 inhibitor and inadequate control of several inflammatory pathways (
Clinical relevance of lung transplantation for COVID-19 ARDS: a nationwide study
Authors: Christian Lang, Valentin Ritschl, Florian Augustin, Gyoergy Lang, Bernhard Moser, Shahrokh Taghavi, Gabriella Murakoezy, Christopher Lambers, Holger Flick, Markus Koestenberger, Roxane Brooks, Tina Muhr, Johann Knotzer, Daniel Mydza, Marc Kaufmann, Thomas Staudinger, Christian Zauner, Claus Krenn, Eva Schaden, Andreas Bacher, Bernhard Rössler, Peter Faybik, Edda Tschernko, Maria Anwar, Klaus Markstaller, Daniel Hoefer, Tanja Stamm, Peter Jaksch, Konrad Hoetzenecker
Journal: European Respiratory Journal (2022)

Background Although the number of lung transplantations (LTx) performed worldwide for coronavirus disease 2019 (COVID-19)-induced acute respiratory distress syndrome (ARDS) is still low, there is general agreement that this treatment can save a subgroup of the most severely ill patients with irreversible lung damage. However, the true proportion of patients eligible for LTx, the overall outcome and the impact of LTx on the pandemic are unknown. Methods A retrospective analysis was performed using a nationwide registry of hospitalised patients with confirmed severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection admitted between 1 January 2020 and 30 May 2021 in Austria. Patients referred to one of the two Austrian LTx centres were analysed, and grouped into patients accepted and rejected for LTx. Detailed outcome analysis was performed for all patients who received a LTx for post-COVID-19 ARDS and compared with patients who underwent LTx for other indications. Results Between 1 January 2020 and 30 May 2021, 39 485 patients were hospitalised for COVID-19 in Austria. 2323 required mechanical ventilation and 183 received extracorporeal membrane oxygenation (ECMO) support. 106 patients with severe COVID-19 ARDS were referred for LTx. Of these, 19 (18%) underwent LTx. 30-day mortality after LTx was 0% for COVID-19 ARDS transplant recipients. At a median follow-up of 134 (47–450) days, 14 out of 19 patients were alive. Conclusions Early referral of ECMO patients to a LTx centre is pivotal in order to select patients eligible for LTx. Transplantation offers excellent midterm outcomes and should be incorporated in the treatment algorithm of post-COVID-19 ARDS.
Abstract ES7-1: Harnessing Lifestyle Interventions via Diet and Exercise for Cancer Risk Reduction
Authors: NM Iyengar
Journal: Cancer Research (2022)

Abstract A growing body of evidence indicates the importance of maintaining optimal metabolic health to reduce the risk of developing cancer and to improve outcomes after cancer diagnosis. Classical and normal weight obesity are states of metabolic dysfunction, and highly prevalent risk factors for the development and growth of several cancers. Classical obesity (defined as a body mass index (BMI) ≥ 30) is a risk factor for at least 13 different types of cancer. Recent data indicate that up to one third of normal weight individuals have metabolic obesity and, subsequently, increased risk for several cancers including breast and colon. Methods to risk-stratify metabolic health and subsequent cancer risk beyond traditional anthropometric metrics such as BMI could improve the efficacy of lifestyle interventions aimed at reducing cancer risk and improving cancer outcomes. In this educational session, the molecular mechanisms linking classical and normal weight obesity to cancer growth will be presented. Obesity-related dysfunction can contribute to cancer pathogenesis and treatment resistance through various mechanisms, including those mediated by insulin, leptin, adiponectin, pro-inflammatory mediators, and hormone signaling pathways, particularly in women. Furthermore, adiposity-related changes can influence tumor vascularity and inflammation in the tumor microenvironment, which can support tumor development and growth. Building upon these mechanistic findings, several clinical trials testing “precision lifestyle” interventions targeted at specific biologic pathways are ongoing. Several randomized control trials testing diet, exercise, and weight loss interventions in cancer populations have demonstrated the feasibility of such interventions. Here, the next generation of lifestyle interventions, such as digital interventions, that target specific pathway dysregulation will be presented. Additionally, pharmacologic interventions that target host metabolism are under study as adjuncts to standard cancer therapy. As rates of classical and normal weight obesity continue to increase, the development of individualized and biologically rational lifestyle interventions could represent an impactful strategy to reduce the worldwide cancer burden. Citation Format: NM Iyengar. Harnessing Lifestyle Interventions via Diet and Exercise for Cancer Risk Reduction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES7-1.
Errors in Figure and Table
Journal: JAMA Network Open (2022)

Yujie Liu, MBBS; Tingting Geng, PhD; Zhenzhen Wan, MPH; Qi Lu, MBBS; Xuena Zhang, MBBS; Zixin Qiu, MBBS; Lin Li, MBBS; Kai Zhu, MBBS; Liegang Liu, PhD; An Pan, PhD; Gang Liu, PhD
PROGNOSTIC IMPACT OF PRE-PROCEDURAL PULMONARY HYPERTENSION ON LATE ALL-CAUSE MORTALITY OF TRANSCATHETER MITRAL VALVE REPAIR USING MITRACLIP: SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Olayinka Adebolu, Israel Safiriyu, Nicole Lao, Joseph Lim, Abiodun Idowu, Oseiwe Eromosele
Journal: Journal of the American College of Cardiology (2022)
A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti–PD-L1 mAb Combination to Enhance the Antitumor Effect
Authors: Xuejun Wen, Changrong Shi, Xinying Zeng, Liang Zhao, Lanlin Yao, Zhida Liu, Lixia Feng, Deliang Zhang, Jinxiong Huang, Yesen Li, Qin Lin, Haojun Chen, Rongqiang Zhuang, Xiaoyuan Chen, Xianzhong Zhang, Zhide Guo
Journal: Clinical Cancer Research (2022)

Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[18F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[18F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy.We designed a series of assays to verify PD-L1 upregulation, and tested immunotherapy regimens based on 2-[18F]FDG and anti-PD-L1 mAb, as monotherapy and in combination, in fully immunocompetent mice of MC38 and CT26 models. PD-L1 expression and tumor microenvironment (TME) changes were analyzed by Western blot, transcriptomics study, and flow-cytometric analysis.PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 2-[18F]FDG. The activation of NF-κB/IRF3 pathway and STAT1/3-IRF1 pathway play crucial parts in modulating PD-L1 expression after DNA damage and repair. Improved αPD-L1 mAb utilization rate and significant tumor growth delay were observed when the personalized therapeutic alliance of 2-[18F]FDG stimulation and ICB was used. In addition, combination of 2-[18F]FDG with αPD-L1 mAb could reprogram a TME from "cold" to "hot," to make low immunoactivity tumors sensitive to ICB therapy.In summary, this promising paradigm has the potential to expand the traditional tumor theranostics. 2-[18F]FDG-based ICB immunotherapy is highly significant in enhancing antitumor effect. A research of 2-[18F]FDG-based ICB immunotherapy has been proposed to enhance the antitumor effect.
THE EARLY DIAGNOSTIC VALUE OF CHEST X-RAY SCANNING BY THE HELP OF ARTIFICIAL INTELLIGENCE IN HEART FAILURE (ART-IN-HF) : THE FIRST OUTCOMES
Authors: Ahmet Celik, Ali O. Surmeli, Mustafa Demir, Kaan Esen, Oguzhan Fural, Ahmet Camsari
Journal: Journal of the American College of Cardiology (2022)
Recurrent Ovarian Cancer Presenting as a Solitary Chest Wall Metastasis Revealed by FDG PET/CT
Authors: Guohua Shen, Anren Kuang
Journal: Clinical Nuclear Medicine (2021)

A 55-year-old woman who was diagnosed with ovarian cancer 4 years ago complained of back pain for 1 month, and the CA-125 level was elevated. FDG PET/CT was then performed for restaging, and the images revealed a hypermetabolic mass in the right posterior chest wall. Postsurgical pathology confirmed metastasis from ovarian cancer.
Expanding Efforts and Support to Respond to the HIV and COVID-19 Intersecting Pandemics
Authors: Lawrence Corey, Russell Corbett-Detig, Chris Beyrer
Journal: JAMA (2022)

This Viewpoint discusses the generation of SARS-CoV-2 variants of concern globally and the need for increased access to COVID-19 vaccination in Africa, particularly for people living with HIV and for households and people living in densely populated communities.
BIO22-031: Potential Implications in Immunotherapy and Prognostic Outcomes of Non-Small Cell Lung Cancer for Computational Recognition of lncRNA Signature of Tumor-Associated Neutrophils
Authors: Zhuoran Tang, Chunyu Li, Peixin Chen, Haoyue Guo, Jinpeng Shi, Yingying Pan, Qi Wang, Caicun Zhou
Journal: Journal of the National Comprehensive Cancer Network (2022)

"BIO22-031: Potential Implications in Immunotherapy and Prognostic Outcomes of Non-Small Cell Lung Cancer for Computational Recognition of lncRNA Signature of Tumor-Associated Neutrophils" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Immune responses against SARS-CoV-2 variants after two and three doses of vaccine in B-cell malignancies: UK PROSECO study
Authors: Sean H. Lim, Beth Stuart, Debora Joseph-Pietras, Marina Johnson, Nicola Campbell, Adam Kelly, Danielle Jeffrey, Anna H. Turaj, Kate Rolfvondenbaumen, Celine Galloway, Thomas Wynn, Adam R. Coleman, Benjamin Ward, Karen Long, Helen Coleman, Carina Mundy, Andrew T. Bates, Diana Ayres, Robert Lown, Janlyn Falconer, Oliver Brake, James Batchelor, Victoria Willimott, Anna Bowzyk Al-Naeeb, Lisa Robinson, Ann O’Callaghan, Graham P. Collins, Tobias Menne, Saul N. Faust, Christopher P. Fox, Matthew Ahearne, Peter W. M. Johnson, Andrew J. Davies, David Goldblatt
Journal: Nature Cancer (2022)

Abstract Patients with hematological malignancies are at increased risk of severe COVID-19 outcomes due to compromised immune responses, but the insights of these studies have been compromised due to intrinsic limitations in study design. Here we present the PROSECO prospective observational study ( NCT04858568 ) on 457 patients with lymphoma that received two or three COVID-19 vaccine doses. We show undetectable humoral responses following two vaccine doses in 52% of patients undergoing active anticancer treatment. Moreover, 60% of patients on anti-CD20 therapy had undetectable antibodies following full vaccination within 12 months of receiving their anticancer therapy. However, 70% of individuals with indolent B-cell lymphoma displayed improved antibody responses following booster vaccination. Notably, 63% of all patients displayed antigen-specific T-cell responses, which increased after a third dose irrespective of their cancer treatment status. Our results emphasize the urgency of careful monitoring of COVID-19-specific immune responses to guide vaccination schemes in these vulnerable populations.
Understanding One Health through biological and behavioral risk surveillance in Liberia: a cross-sectional study
Authors: Sandra Samuels, Nenneh Kamara-Chieyoe, Jallah Arku, Amos G. Kollie, Nyamah Jallah Carl, Kortu Ndebe, Emily Hagan, Stephanie Martinez, Catherine Machalaba, James Desmond, Leilani Francisco, Maureen Miller, William Karesh, Kelly Rose Nunziata, Peter Daszak, Jonathan Epstein
Journal: The Lancet Global Health (2022)

The 2014 Ebola crisis in West Africa mainly affected Guinea, Liberia, and Sierra Leone, claiming the lives of over 11 000 people, including health-care workers. Following this crisis, the Ebola Host Project worked to identify the wildlife reservoir for the virus that started the epidemic, to detect other related filoviruses, and to better understand ecological and human behavioral dynamics that could inform future risk reduction and prevention strategies. Here, we report key ecological and behavioral results for Liberia.In Liberia, this cross-sectional study was conducted in 13 sites throughout eight counties. The project used a One Health biological-behavioral surveillance approach that included catch-and-release wildlife sampling and behavioral risk surveys. These sites were chosen from counties with forested areas inhabited by bats and rodents and included counties that were both severely and minimally impacted by the Ebola crisis. The analysis included 5000 bat and rodent biological samples, and the behavioural risk survey included 585 enrolled human participants from eight counties. Participants were selected from villages within a 5 km range of the 18 sampling sites, and they provided writteninformed consent. In addition to US based approvals, the Liberian National Ethical and Review Board, the Liberian Forest Development Authority and local government authorities approved the study and community work.This sampling effort led to the first-time discovery of an Ebolavirus in a west African bat (Miniopterus inflatus) in January 2019. Across five of the eight counties, including Nimba County where the infected Miniopterus inflatus was sampled, mosquitos and tsetse flies were also identified as present vectors. Respondents reported the ways in which they interfaced with taxa of interest such as rodents. These interactions included wildlife consumption and proximity to human dwellings-interactions that present the risk of zoonotic infections that may go misdiagnosed as fevers of unknown origin. Respondents additionally described gaps in knowledge around topics such as the aetiology of Ebola in Liberia, as well as changes in the level of concern towards Ebola risk, which rose during the crisis but later returned to pre-crisis levels.Our results highlight how, against the backdrop of human-wildlife interactions in these Liberian communities that present spillover risk, there exist opportunities to bridge knowledge gaps and create cues to encourage continued vigilance against transmission.This project was funded by USAID, and analysis with regard to the risk of acute febrile illnesses continues with funding from the US Defense Threat Reduction Agency.
Positive Selection during Niche Adaptation Results in Large-Scale and Irreversible Rearrangement of Chromosomal Gene Order in Bacteria
Authors: Sha Cao, Gerrit Brandis, Douglas L. Huseby, Diarmaid Hughes
Journal: Molecular Biology and Evolution (2022)

Analysis of bacterial genomes shows that, whereas diverse species share many genes in common, their linear order on the chromosome is often not conserved. Whereas rearrangements in gene order could occur by genetic drift, an alternative hypothesis is rearrangement driven by positive selection during niche adaptation (SNAP). Here, we provide the first experimental support for the SNAP hypothesis. We evolved Salmonella to adapt to growth on malate as the sole carbon source and followed the evolutionary trajectories. The initial adaptation to growth in the new environment involved the duplication of 1.66 Mb, corresponding to one-third of the Salmonella chromosome. This duplication is selected to increase the copy number of a single gene, dctA, involved in the uptake of malate. Continuing selection led to the rapid loss or mutation of duplicate genes from either copy of the duplicated region. After 2000 generations, only 31% of the originally duplicated genes remained intact and the gene order within the Salmonella chromosome has been significantly and irreversibly altered. These results experientially validate predictions made by the SNAP hypothesis and show that SNAP can be a strong driving force for rearrangements in chromosomal gene order.
Nirsevimab for Prevention of RSV in Healthy Late-Preterm and Term Infants
Authors: Laura L. Hammitt, Ron Dagan, Yuan Yuan, Manuel Baca Cots, Miroslava Bosheva, Shabir A. Madhi, William J. Muller, Heather J. Zar, Dennis Brooks, Amy Grenham, Ulrika Wählby Hamrén, Vaishali S. Mankad, Pin Ren, Therese Takas, Michael E. Abram, Amanda Leach, M. Pamela Griffin, Tonya Villafana
Journal: New England Journal of Medicine (2022)

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection and hospitalization in infants. Nirsevimab is a monoclonal antibody to the RSV fusion protein that has an extended half-life. The efficacy and safety of nirsevimab in healthy late-preterm and term infants are uncertain.