tbuckley/cabot-search huggingface dataset:
Responder analysis for improvement in 6‐min walk test with ferric carboxymaltose in patients with heart failure with reduced ejection fraction and iron deficiency
Authors: Stefan D. Anker, Piotr Ponikowski, Muhammad Shahzeb Khan, Tim Friede, Ewa A. Jankowska, Vincent Fabien, Udo‐Michael Goehring, Marco Metra, Ileana L. Piña, Andrew J.S. Coats, Giuseppe Rosano, Fabio Dorigotti, Josep Comin‐Colet, Dirk J. Van Veldhuisen, Gerasimos S. Filippatos, Javed Butler
Journal: European Journal of Heart Failure (2022)

Improving functional capacity is a key goal in heart failure (HF). This pooled analysis of FAIR-HF and CONFIRM-HF assessed the likelihood of improvement or deterioration in 6-min walk test (6MWT) among iron-deficient patients with chronic HF with reduced ejection fraction (HFrEF) receiving ferric carboxymaltose (FCM).Data for 760 patients (FCM: n = 454; placebo: n = 306) were analysed. The proportions of patients receiving FCM or placebo who had ≥20, ≥30, and ≥40 m improvements or ≥10 m deterioration in 6MWT at 12 and 24 weeks were assessed. Patients receiving FCM experienced a mean (standard deviation) 31.1 (62.3) m improvement in 6MWT versus 0.1 (77.1) m improvement for placebo at week 12 (difference in mean changes 26.8 [16.6-37.0]). At week 12, the odds [95% confidence interval] of 6MWT improvements of ≥20 m (odds ratio 2.16 [1.57-2.96]; p < 0.0001), ≥30 m (2.00 [1.44-2.78]; p < 0.0001), and ≥40 m (2.29 [1.60-3.27]; p < 0.0001) were greater with FCM versus placebo, while the odds of a deterioration ≥10 m were reduced with FCM versus placebo (0.55 [0.38-0.80]; p = 0.0019). Among patients who experienced 6MWT improvements of ≥20, ≥30, or ≥40 m with FCM at week 12, more than 80% sustained this improvement at week 24.Ferric carboxymaltose resulted in a significantly higher likelihood of improvement and a reduced likelihood of deterioration in 6MWT versus placebo among iron-deficient patients with HF. Of the patients experiencing clinically significant improvements at week 12, the majority sustained this improvement at week 24. These results are supportive of FCM to improve exercise capacity in HF.
The rupture of anonymity for sperm donors—a tangled web of conflicting rights
Authors: Nathan Hodson, Freddie Howell, Joshua Parker, Susan Bewley
Journal: BMJ (2022)

Between the 1970s and early 2000s, many people in the UK were conceived using anonymous donor sperm (with the practice of anonymity only stopping in 2005).As this group has reached adulthood, we've seen a concurrent explosion in the popularity of direct-to-consumer (DTC) DNA testing.This technological development has torn the veil separating social family and genetic heritage, with implications for all parties.We examine how it has brought the rights of donor conceived people to information into conflict with donors' right to privacy, and consider how the divide might be bridged.Historically, it was often common practice for medical students, who were in close proximity to fertility doctors and keen to help patients, to act as sperm donors and, anecdotally, this group do seem to be frequently represented when donors are tracked down today.As such, these scenarios will hold personal significance for some doctors.
ALL-CAUSE THIRTY-DAY READMISSION IN ACUTE MYOCARDIAL INFARCTION PATIENTS WITH END-STAGE-RENAL-DISEASE- A NATIONWIDE STUDY
Authors: Muddasir Ashraf, Sulaiman Sajed, Viviana Zlochiver, Suhail Q. Allaqaband, Tanvir K. Bajwa, M. Fuad Jan
Journal: Journal of the American College of Cardiology (2022)
GLA/DRST real-world outcome analysis of CAR-T cell therapies for large B-cell lymphoma in Germany
Authors: Wolfgang Andreas Bethge, Peter Martus, Michael Schmitt, Udo Holtick, Marion Subklewe, Bastian von Tresckow, Francis Ayuk, Eva Maria Wagner-Drouet, Gerald G Wulf, Reinhard Marks, Olaf Penack, Ulf Schnetzke, Christian Koenecke, Malte von Bonin, Matthias Stelljes, Bertram Glass, Claudia D Baldus, Vladan Vucinic, Dimitrios Mougiakakos, Max S Topp, Matthias Alexander Fante, Roland Schroers, Lale May Bayir, Peter Borchmann, Veit Buecklein, Christine Hanoun, Simone Thomas, Dietrich W. Beelen, Claudia Lengerke, Nicolaus Kroeger, Peter Dreger
Journal: Blood (2022)
RIGHT VENTRICULAR DILATION AND RV FREE WALL ENHANCEMENT ON ECHOCARDIOGRAM IN COVID-19 PATIENTS: PROGNOSTIC INDICATORS
Authors: Kanaan Mansoor, Ebad Ur Rahman, Salman Assad, Huma Nadeem Ahmed, Susan Taylor, Natalie Lemaster, Ellen A. Thompson, Rameez Sayyed
Journal: Journal of the American College of Cardiology (2022)
Pulmonary Asbestos Fiber Burden Is Related to Patient Survival in Malignant Pleural Mesothelioma
Authors: Sanna Laaksonen, Eeva Kettunen, Eva Sutinen, Ilkka Ilonen, Tapio Vehmas, Timo Törmäkangas, Jari Räsänen, Henrik Wolff, Marjukka Myllärniemi
Journal: Journal of Thoracic Oncology (2022)
MAJOR ADVERSE CARDIAC AND CEREBROVASCULAR EVENTS WITH CANNABIS USE DISORDER IN ADULT CANCER SURVIVORS HOSPITALIZED WITH PRIOR HISTORY OF MYOCARDIAL INFARCTION
Authors: Akhil Jain, Preeti Agarwala, Avilash Mondal, Ankit Vyas, Ibrahim Ahmed, Harsha Sai Sreemantula, Anisha Mulumudi, Manasee Vyas, Mimoza Isufi, Rupak Desai
Journal: Journal of the American College of Cardiology (2022)
PULMONARY HYPERTENSION AND RIGHT VENTRICULAR FAILURE IN THE SETTING OF UNILATERAL ABSENCE OF THE RIGHT PULMONARY ARTERY, CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION AND RIGHT LUNG PERFUSION VIA THE LEFT CORONARY ARTERY
Authors: Joseph Karpenos, Allen Weiss, Faisal Alkhatib Tamimi, Matthew Ian Tomey, Hooman D. Poor, Kiran Mahmood, Mount Sinai Morningside
Journal: Journal of the American College of Cardiology (2022)
Hybrid closed-loop glucose control compared with sensor augmented pump therapy in older adults with type 1 diabetes: an open-label multicentre, multinational, randomised, crossover study
Authors: Charlotte K Boughton, Sara Hartnell, Hood Thabit, Womba M Mubita, Katharine Draxlbauer, Tina Poettler, Malgorzata E Wilinska, Korey K Hood, Julia K Mader, Parth Narendran, Lalantha Leelarathna, Mark L Evans, Roman Hovorka
Journal: The Lancet Healthy Longevity (2022)
GABAA receptor agonist suppresses pediatric medulloblastoma progression by inhibiting PKA-Gli1 signaling axis
Authors: Itishree Kaushik, Sanjay K Srivastava
Journal: Molecular Therapy (2022)

The Sonic hedgehog-activated subgroup of medulloblastoma (SHH-MB) is one of the most common malignant pediatric brain tumors. Recent clinical studies and genomic databases indicate that GABAA receptor holds significant clinical relevance as a therapeutic target for pediatric MB. Herein, we report that "moxidectin," a GABAA receptor agonist, inhibits the proliferation of Daoy, UW426, UW228, ONS76, and PFSK1 SHH-MB cells by inducing apoptosis. Immunoblotting and immunofluorescence microscopy demonstrated that moxidectin significantly induced GABAA receptor expression and inhibited cyclic AMP (cAMP)-mediated protein kinase A (PKA)-cAMP response element-binding protein (CREB)-Gli1 signaling in SHH-MB. Gli1 and the downstream effector cancer stem cell (CSC) molecules such as Pax6, Oct4, Sox2, and Nanog were also inhibited by moxidectin treatment. Interestingly, moxidectin also inhibited the expression of MDR1. Mechanistic studies using pharmacological or genetic inhibitors/activators of PKA and Gli1 confirmed that the anti-proliferative and apoptotic effects of moxidectin were mediated through inhibition of PKA-Gli1 signaling. Oral administration of 2.5 mg/kg moxidectin suppressed the growth of SHH-MB tumors by 55%-80% in subcutaneous and intracranial tumor models in mice. Ex vivo analysis of excised tumors confirmed the observations made in the in vitro studies. Moxidectin is an FDA-approved drug with an established safety record, therefore any positive findings from our studies will prompt its further clinical investigation for the treatment of MB patients.
Combination inhaler is effective in mild asthma
Authors: Helen Saul, Deniz Gursul, Samantha Cassidy, Timothy Hinks
Journal: BMJ (2022)

The study Crossingham I, Turner S, Ramakrishnan S, et al. Combination fixed-dose β agonist and steroid inhaler as required for adults or children with mild asthma: a Cochrane systematic review. BMJ Evid Based Med 2021; doi: 10.1136/bmjebm-2021-111764 . To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/combination-inhaler-is-effective-in-mild-asthma/
TGFβ receptor inhibition unleashes interferon-β production by tumor-associated macrophages and enhances radiotherapy efficacy
Authors: Pauline Hamon, Marine Gerbé De Thoré, Marion Classe, Nicolas Signolle, Winchygn Liu, Olivia Bawa, Lydia Meziani, Céline Clémenson, Fabien Milliat, Eric Deutsch, Michele Mondini
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Transforming growth factor-beta (TGFβ) can limit the efficacy of cancer treatments, including radiotherapy (RT), by inducing an immunosuppressive tumor environment. The association of TGFβ with impaired T cell infiltration and antitumor immunity is known, but the mechanisms by which TGFβ participates in immune cell exclusion and limits the efficacy of antitumor therapies warrant further investigations. Methods We used the clinically relevant TGFβ receptor 2 (TGFβR2)-neutralizing antibody MT1 and the small molecule TGFβR1 inhibitor LY3200882 and evaluated their efficacy in combination with RT against murine orthotopic models of head and neck and lung cancer. Results We demonstrated that TGFβ pathway inhibition strongly increased the efficacy of RT. TGFβR2 antibody upregulated interferon beta expression in tumor-associated macrophages within the irradiated tumors and favored T cell infiltration at the periphery and within the core of the tumor lesions. We highlighted that both the antitumor efficacy and the increased lymphocyte infiltration observed with the combination of MT1 and RT were dependent on type I interferon signaling. Conclusions These data shed new light on the role of TGFβ in limiting the efficacy of RT, identifying a novel mechanism involving the inhibition of macrophage-derived type I interferon production, and fostering the use of TGFβR inhibition in combination with RT in therapeutic strategies for the management of head and neck and lung cancer.
OUTCOMES OF NEW PERMANENT PACEMAKER IMPLANTATION FOLLOWING TRANSCATHETER AND SURGICAL AORTIC VALVE REPLACEMENT
Authors: Allison Lanfear, Stephanie Beveridge, Talia Meidan, Emily Shih, Mohanad Hamandi, Imran Baig, Arthur J. Lee, Allison Aldrich, Sarah Hale, Srinivasa P. Potluri, Molly Szerlip, Katherine Harrington, Justin Michael Schaffer, William Brinkman, J Michael DiMaio, Michael J. Mack, Karim Al-Azizi
Journal: Journal of the American College of Cardiology (2022)
Abstract P2-05-01: Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas
Authors: Joseph Kern, Andrew Tilston-Lunel, Anthony Federico, Boting Ning, Grace Peppler, Eleni Stampouloglou, Marc Lenburg, Jennifer Beane, Stefano Monti, Xaralabos Varelas
Journal: Cancer Research (2022)

Abstract Basal-like breast cancers, an aggressive breast cancer subtype that has poor treatment options, are thought to arise from luminal mammary epithelial cells but undergo plasticity to a basal-like state upon transformation. Identifying cellular mechanisms underlying this luminal-basal plasticity will allow an improved understanding of the pathogenesis of basal-like breast cancers. The Hippo signaling pathway, an important cell fate regulator across many tissues, has been implicated in breast cancer development. Central to Hippo signaling are the tumor suppressor kinases LATS1 and LATS2 (LATS1/2), which function to inhibit the transcriptional regulators YAP and TAZ (YAP/TAZ). In this study, we investigated the roles of LATS1/2 in the maintenance of mammary epithelial homeostasis and tumorigenesis in vivo. Using genetic mouse models, we found that conditional co-deletion of LATS1/2 in adult luminal cells promotes rapid proliferation and acquisition of basal cell traits, leading to early development of basal-like ductal carcinoma in situ and an eventual transition to a metastatic state. Further co-deletion experiments demonstrated that these phenotypes are dependent on YAP/TAZ. Transcriptional analyses of LATS1/2-null cells sorted from mammary glands demonstrated that these cells adopt gene expression signatures that correlate with mammary basal cells and human basal-like breast cancers, and revealed an association with Sox9, a transcription factor implicated in luminal progenitor fate and basal-like carcinomas. Collectively, this study demonstrates that LATS1/2 are important mediators of luminal cell fate in mammary epithelial homeostasis and that dysregulation of Hippo signaling in vivo promotes luminal-basal cell plasticity leading to basal-like mammary carcinoma development. Citation Format: Joseph Kern, Andrew Tilston-Lunel, Anthony Federico, Boting Ning, Grace Peppler, Eleni Stampouloglou, Marc Lenburg, Jennifer Beane, Stefano Monti, Xaralabos Varelas. Inactivation of LATS1/2 drives luminal-basal plasticity to initiate basal-like mammary carcinomas [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 P2-05-01.
Single nucleus multi-omics identifies human cortical cell regulatory genome diversity
Authors: Chongyuan Luo, Hanqing Liu, Fangming Xie, Ethan J Armand, Kimberly Siletti, Trygve E Bakken, Rongxin Fang, Wayne I Doyle, Tim Stuart, Rebecca D Hodge, Lijuan Hu, Bang-An Wang, Zhuzhu Zhang, Sebastian Preissl, Dong-Sung Lee, Jingtian Zhou, Sheng-Yong Niu, Rosa Castanon, Anna Bartlett, Angeline Rivkin, Xinxin Wang, Jacinta Lucero, Joseph R Nery, David A Davis, Deborah C Mash, Rahul Satija, Jesse R Dixon, Sten Linnarsson, Ed Lein, M Margarita Behrens, Bing Ren, Eran A Mukamel, Joseph R Ecker
Journal: Cell Genomics (2022)

Single-cell technologies measure unique cellular signatures but are typically limited to a single modality. Computational approaches allow the fusion of diverse single-cell data types, but their efficacy is difficult to validate in the absence of authentic multi-omic measurements. To comprehensively assess the molecular phenotypes of single cells, we devised single-nucleus methylcytosine, chromatin accessibility, and transcriptome sequencing (snmCAT-seq) and applied it to postmortem human frontal cortex tissue. We developed a cross-validation approach using multi-modal information to validate fine-grained cell types and assessed the effectiveness of computational data fusion methods. Correlation analysis in individual cells revealed distinct relations between methylation and gene expression. Our integrative approach enabled joint analyses of the methylome, transcriptome, chromatin accessibility, and conformation for 63 human cortical cell types. We reconstructed regulatory lineages for cortical cell populations and found specific enrichment of genetic risk for neuropsychiatric traits, enabling the prediction of cell types that are associated with diseases.
URINE TROPONIN EXCRETION IN PATIENTS WITH AND WITHOUT RENAL FAILURE - THE ROLE OF THE KIDNEY IN TROPONIN ELIMINATION
Authors: Roi Westreich, Yasmin Abu Fraiha, Vladimir Fridman, Gal Tsaban, Merav Cohen, Yosef Haviv, Yigal Abramowitz
Journal: Journal of the American College of Cardiology (2022)
CARDIAC SURGICAL THERAPY IN THE CONTEMPORARY CARDIAC INTENSIVE CARE UNIT: IMPLICATIONS FOR THE HEART TEAM, FROM THE CRITICAL CARE CARDIOLOGY TRIALS NETWORK (CCCTN) REGISTRY
Authors: Thomas S. Metkus, David Berg, Erin Bohula, Jianping Guo, Sean Van Diepen, Jason Neil Katz, David A. Morrow
Journal: Journal of the American College of Cardiology (2022)
Quality of Life Is Associated With Survival in Patients With Gastric Cancer: Results From the Randomized CRITICS Trial
Authors: Romy M. van Amelsfoort, Iris Walraven, Jacobien Kieffer, Edwin P.M. Jansen, Annemieke Cats, Nicole C.T. van Grieken, Elma Meershoek-Klein Kranenbarg, Hein Putter, Johanna W. van Sandick, Karolina Sikorska, Cornelis J.H. van de Velde, Neil K. Aaronson, Marcel Verheij, _ _
Journal: Journal of the National Comprehensive Cancer Network (2022)

The evaluation of health-related quality of life (HRQoL) in clinical trials has become increasingly important because it addresses the impact of treatment from the patient's perspective. The primary aim of this study was to investigate the effect of postoperative chemotherapy and chemoradiotherapy (CRT) after neoadjuvant chemotherapy and surgery with extended (D2) lymphadenectomy on HRQoL in the CRITICS trial. Second, we investigated the potential prognostic value of pretreatment HRQoL on event-free survival (EFS) and overall survival (OS).Patients in the CRITICS trial were asked to complete HRQoL questionnaires (EORTC Quality-of-Life Questionnaire-Core 30 and Quality-of-Life Questionnaire gastric cancer-specific module) at baseline, after preoperative chemotherapy, after surgery, after postoperative chemotherapy or CRT, and at 12 months follow-up. Patients with at least 1 evaluable questionnaire (645 of 788 randomized patients) were included in the HRQoL analyses. The predefined endpoints included dysphagia, pain, physical functioning, fatigue, and Quality-of-Life Questionnaire-Core 30 summary score. Linear mixed modeling was used to assess differences over time and at each time point. Associations of baseline HRQoL with EFS and OS were investigated using multivariate Cox proportional hazards analyses.At completion of postoperative chemo(radio)therapy, the chemotherapy group had significantly better physical functioning (P=.02; Cohen's effect size = 0.42) and less dysphagia (P=.01; Cohen's effect size = 0.38) compared with the CRT group. At baseline, worse social functioning (hazard ratio [HR], 2.20; 95% CI, 1.36-3.55; P=.001), nausea (HR, 1.89; 95% CI, 1.39-2.56; P<.001), worse WHO performance status (HR, 1.55; 95% CI, 1.13-2.13; P=.007), and histologic subtype (diffuse vs intestinal: HR, 1.94; 95% CI, 1.42-2.67; P<.001; mixed vs intestinal: HR, 2.35; 95% CI, 1.35-4.12; P=.003) were significantly associated with worse EFS and OS.In the CRITICS trial, the chemotherapy group had significantly better physical functioning and less dysphagia after postoperative treatment. HRQoL scales at baseline were significantly associated with EFS and OS.
Abstract P4-11-21: Plasma cytokine levels in breast cancer-related lymphedema patients
Authors: Anna R Vang, Simona F Shaitelman, Eva M Sevick-Muraca, Chan Wen-yaw, John C Rasmussen, Sarah D DeSnyder, Melissa B Aldrich
Journal: Cancer Research (2022)

Abstract Background: Breast cancer-related lymphedema (BCRL) is encountered by approximately 40% of breast cancer survivors. BCRL drastically affects quality of life, as the arm, breast, and trunk swelling, together with pain, depression, and cellulitis risk can make everyday functions difficult or impossible. Objective: To identify plasma biomarkers that can suggest targeted pharmacological treatments for breast cancer survivors who develop lymphedema (LE). Methods: In a prospective, ongoing, longitudinal clinical study (NCT02949726), peripheral blood, perometric arm volumes, and near-infrared fluorescence lymphatic images/videos (NIRF-LI) for the first 33 enrolled advanced breast cancer patients were collected pre-mastectomy/breast-conserving surgery with ALND, four weeks postoperatively, at the end of radiation therapy (RT), and at 6 months post-RT. 29 cytokines were measured at each time point using a MILLIPLEX MAP human cytokine/chemokine magnetic bead panel from isolated blood plasma. Cytokine levels in subjects with &amp;gt;5% perometric arm swelling at 6 months post-regional nodal RT were analyzed and compared to those with &amp;lt;5% perometric arm swelling at 6 months post-regional nodal RT. Additionally, subjects who exhibited LE-associated dermal backflow, identified by cloudy fluid masses, instead of linear vessels, with NIRF-LI, at 6 months post-regional nodal RT were compared to those without backflow at 6 months post-regional nodal RT. GraphPad/Prism 9 non-parametric Mann-Whitney t-test was used to compute the p-values of each cytokine. P-values less than 0.05 were deemed significant. Results: Out of the 33 subjects, 7 developed &amp;gt;5% perometric arm swelling 6 months post-regional nodal RT and 15 developed dermal backflow 6 months post-regional nodal RT. Of the 15 subjects that developed backflow, 7 also had &amp;gt;5% perometric arm swelling. G-CSF, GM-CSF, IL-10, IL-12p40, and IL-1R-alpha were found to be significantly higher in subjects with &amp;gt;5% perometric arm swelling at 6 months post-RT than in subjects with &amp;lt;5% perometric arm swelling while IL-1beta was identified to be significantly lower in subjects with backflow at 6 months post-regional nodal RT than those without backflow at 6 months post-regional nodal RT. Conclusions: G-CSF, GM-CSF, IL-10, IL-12p40, IL-1Ralpha, and IL-1beta are candidate biomarkers for detecting and directing pharmacological treatment for lymphedema in breast cancer survivors. Citation Format: Anna R Vang, Simona F Shaitelman, Eva M Sevick-Muraca, Chan Wen-yaw, John C Rasmussen, Sarah D DeSnyder, Melissa B Aldrich. Plasma cytokine levels in breast cancer-related lymphedema patients [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 P4-11-21.
Neural Signaling in Cancer
Authors: Michael B. Keough, Michelle Monje
Journal: Annual Review of Neuroscience (2022)

Nervous system activity regulates development, homeostasis, and plasticity of the brain as well as other organs in the body. These mechanisms are subverted in cancer to propel malignant growth. In turn, cancers modulate neural structure and function to augment growth-promoting neural signaling in the tumor microenvironment. Approaching cancer biology from a neuroscience perspective will elucidate new therapeutic strategies for presently lethal forms of cancer. In this review, we highlight the neural signaling mechanisms recapitulated in primary brain tumors, brain metastases, and solid tumors throughout the body that regulate cancer progression.
Targeting extracellular matrix stiffness and mechanotransducers to improve cancer therapy
Authors: Yangfu Jiang, Hongying Zhang, Jiao Wang, Yongliang Liu, Ting Luo, Hui Hua
Journal: Journal of Hematology & Oncology (2022)

Abstract Cancer microenvironment is critical for tumorigenesis and cancer progression. The extracellular matrix (ECM) interacts with tumor and stromal cells to promote cancer cells proliferation, migration, invasion, angiogenesis and immune evasion. Both ECM itself and ECM stiffening-induced mechanical stimuli may activate cell membrane receptors and mechanosensors such as integrin, Piezo1 and TRPV4, thereby modulating the malignant phenotype of tumor and stromal cells. A better understanding of how ECM stiffness regulates tumor progression will contribute to the development of new therapeutics. The rapidly expanding evidence in this research area suggests that the regulators and effectors of ECM stiffness represent potential therapeutic targets for cancer. This review summarizes recent work on the regulation of ECM stiffness in cancer, the effects of ECM stiffness on tumor progression, cancer immunity and drug resistance. We also discuss the potential targets that may be druggable to intervene ECM stiffness and tumor progression. Based on these advances, future efforts can be made to develop more effective and safe drugs to interrupt ECM stiffness-induced oncogenic signaling, cancer progression and drug resistance.