tbuckley/cabot-search huggingface dataset:
Accelerating Indigenous health and wellbeing: the Lancet Commission on Arctic and Northern Health
Authors: Lisa V Adams, Dalee Sambo Dorough, Lisa V Adams, Dalee Sambo Dorough, Susan Chatwood, Willy Erasmus, Heidi Eriksen, Selma Ford, Ross A Virginia, Siila Watt-Cloutier
Journal: The Lancet (2022)
Gene Regulatory Networks of Epidermal and Neural Fate Choice in a Chordate
Authors: Anthony Leon, Lucie Subirana, Kevin Magre, Ildefonso Cases, Juan J. Tena, Manuel Irimia, Jose Luis Gomez-Skarmeta, Hector Escriva, Stéphanie Bertrand
Journal: Molecular Biology and Evolution (2022)

Neurons are a highly specialized cell type only found in metazoans. They can be scattered throughout the body or grouped together, forming ganglia or nerve cords. During embryogenesis, centralized nervous systems develop from the ectoderm, which also forms the epidermis. How pluripotent ectodermal cells are directed toward neural or epidermal fates, and to which extent this process is shared among different animal lineages, are still open questions. Here, by using micromere explants, we were able to define in silico the putative gene regulatory networks (GRNs) underlying the first steps of the epidermis and the central nervous system formation in the cephalochordate amphioxus. We propose that although the signal triggering neural induction in amphioxus (i.e., Nodal) is different from vertebrates, the main transcription factors implicated in this process are conserved. Moreover, our data reveal that transcription factors of the neural program seem to not only activate neural genes but also to potentially have direct inputs into the epidermal GRN, suggesting that the Nodal signal might also contribute to neural fate commitment by repressing the epidermal program. Our functional data on whole embryos support this result and highlight the complex interactions among the transcription factors activated by the signaling pathways that drive ectodermal cell fate choice in chordates.
FUNCTIONAL EFFECTS OF THERAPEUTIC ULTRASOUND FOR CALCIFIC DEGENERATIVE MITRAL STENOSIS
Authors: Patricia Rodriguez Lozano, Keshav Kohli, Austin Robinson, Yanjun Xie, FeiFei Zhao, Vahid Sadri, Shelley Gooden, Milad Samaee, Andrew Thim, Mohamed Morsy, Alexander Klibanov, Christopher M. Kramer, John Hossack, Ajit P. Yoganathan
Journal: Journal of the American College of Cardiology (2022)
CGE22-103: Identifying Patients at Risk for Hereditary Myeloid Malignancy Syndromes Using a Self-Administered Questionnaire as an Initial Screening Tool: A Single Center Experience
Authors: Mohammad Faizan Zahid, Courtney Dryden, Ruth Ikpefan, Kelsey Moriarty, Robert H Collins, Madhuri Vusirikala, Yazan F Madanat, Prapti A Patel
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CGE22-103: Identifying Patients at Risk for Hereditary Myeloid Malignancy Syndromes Using a Self-Administered Questionnaire as an Initial Screening Tool: A Single Center Experience" published on 31 Mar 2022 by National Comprehensive Cancer Network.
PREVALENCE AND PROGNOSTIC VALUE OF LATE GADOLINIUM ENHANCEMENT PHENOTYPES IN PATIENTS REFERRED FOR SUSPECTED INFILTRATIVE CARDIOMYOPATHY: AN ANALYSIS OF THE CIROC REGISTRY
Authors: Bradley Sarak, Dina Labib, Steven Dykstra, Jackie Flewitt, Alessandro Satriano, Sandra Rivest, Andrew G. Howarth, Carmen P. Lydell, Robert H. Miller, Nowell M. Fine, James White
Journal: Journal of the American College of Cardiology (2022)
Erratum. Circulating Palmitoyl Sphingomyelin Is Associated With Cardiovascular Disease in Individuals With Type 2 Diabetes: Findings From the China Da Qing Diabetes Study. Diabetes Care 2022;45:666–673
Authors: Yanyan Chen, Hongmei Jia, Xin Qian, Jinping Wang, Meng Yu, Qiuhong Gong, Yali An, Hui Li, Sidong Li, Na Shi, Zhongmei Zou, Guangwei Li
Journal: Diabetes Care (2022)
Abstract P1-05-06: Establishment of novel BRCA1ness score to quantify BRCAness in breast cancer
Authors: Masanori Oshi, Rongrong Wu, Akimitsu Yamada, Li Yan, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe
Journal: Cancer Research (2022)

Abstract Germline mutations in the loci of BRCA1 or BRCA2 genes with loss of heterozygosity or additional somatic truncation at the WT allele in breast cancer result in characteristic clinicopathological features of homologous recombination deficiency, also known as “BRCAness.”. Although clinical genetic testing for mutations of BRCA1 and BRCA2 has increased the chances of identifying pathogenic variants, we speculated that there may be a difference in cancer biology by the degree of BRCAness. To address this question, we sought to develop a means to estimate the amount of BRCAness using a score consists of BRCA1-mutation-related genes. Thirty-four BRCA1-mutation related genes were selected by high area under the curve (AUC) levels in receiver operating characteristic (ROC) curve between BRCA1 mutation and non-mutation breast cancer, consistently in two large breast cancer cohorts, TCGA and METABRIC. The score was established by using gene set variation analysis (GSVA) algorithm on 34 genes. We found that the BRCA1ness score was the highest in triple negative breast cancer (TNBC) among subtypes consistently in both cohorts (both p &amp;lt; 0.001). Although BRCA1ness score did not correlate with mRNA expression of BRCA1 nor BRCA2 at all (spearman’s rank correlation coefficient (r) = 0.191 and 0.093, respectively), high BRCA1ness score was significantly associated with high rate of BRCA1 mutation (AUC = 0.735 and 0.709, respectively) in both cohorts. This level of AUC for BRCA1ness mutation score was highest compared to other factors, including BRCA1 expression (AUC = 0.323), DNA repair gene set score (AUC = 0.553 and 0.543), nor homologous recombination deficient (HRD) (AUC = 0.659), which are known as the characteristics of BRCAness. Furthermore, the score was significantly correlated with DNA repair gene set score (r = 0.593 and 0.323, both p &amp;lt; 0.01) as well as MKI67 expression (r = 0.655 and 0.626, both p &amp;lt; 0.01) in both cohorts. HRD score was also strongly correlated with BRCA1ness score in the TCGA cohort (r = 0.633). Interestingly, high BRCA1ness was significantly associated with worse disease-free survival (DFS) (p = 0.037 and p &amp;lt; 0.001, respectively) and disease-specific survival (DSS) (p = 0.012 and p &amp;lt; 0.001, respectively) in both cohorts. In conclusion, we established novel BRCA1ness score using mRNA expression of BRCA1-mutation-related genes, and found that it associate with DNA repair and worse survival. Citation Format: Masanori Oshi, Rongrong Wu, Akimitsu Yamada, Li Yan, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. Establishment of novel BRCA1ness score to quantify BRCAness in breast cancer [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 P1-05-06.
Endopeptidase Cleavage of Anti-Glomerular Basement Membrane Antibodies in vivo in Severe Kidney Disease: An Open-Label Phase 2a Study
Authors: Fredrik Uhlin, Wladimir Szpirt, Andreas Kronbichler, Annette Bruchfeld, Inga Soveri, Lionel Rostaing, Eric Daugas, Arnaud Lionet, Nassim Kamar, Cédric Rafat, Marek Mysliveček, Vladimír Tesař, Anders Fernström, Christian Kjellman, Charlotte Elfving, Stephen McAdoo, Johan Mölne, Ingeborg Bajema, Elisabeth Sonesson, Mårten Segelmark
Journal: Journal of the American Society of Nephrology (2022)

The prognosis for kidney survival is poor in patients presenting with circulating anti-glomerular basement membrane (GBM) antibodies and severe kidney injury. It is unknown if treatment with an endopeptidase that cleaves circulating and kidney bound IgG can alter the prognosis.An investigator-driven phase 2a one-arm study (EudraCT 2016-004082-39) was performed in 17 hospitals in five European countries. A single dose of 0.25 mg/kg of imlifidase was given to 15 adults with circulating anti-GBM antibodies and an eGFR <15 ml/min per 1.73m2. All patients received standard treatment with cyclophosphamide and corticosteroids, but plasma exchange only if autoantibodies rebounded. The primary outcomes were safety and dialysis independency at 6 months.At inclusion, ten patients were dialysis dependent and the other five had eGFR levels between 7 and 14 ml/min per 1.73m2. The median age was 61 years (range 19-77), six were women, and six were also positive for anti-neutrophil cytoplasmic antibodies. Then 6 hours after imlifidase infusion, all patients had anti-GBM antibodies levels below the reference range of a prespecified assay. At 6 months 67% (ten out of 15) were dialysis independent. This is significantly higher compared with 18% (nine out of 50) in a historical control cohort (P<0.001, Fisher's exact test). Eight serious adverse events (including one death) were reported, none assessed as probably or possibly related to the study drug.In this pilot study, the use of imlifidase was associated with a better outcome compared with earlier publications, without major safety issues, but the findings need to be confirmed in a randomized controlled trial.Clinical Trial registration number: EUDRACT 2016-004082-39 https://www.clinicaltrialsregister.eu/ctr-search/trial/2007-001377-28/results.
Normalizing tumor microenvironment with nanomedicine and metronomic therapy to improve immunotherapy
Authors: Fotios Mpekris, Chrysovalantis Voutouri, Myrofora Panagi, James W. Baish, Rakesh K. Jain, Triantafyllos Stylianopoulos
Journal: Journal of Controlled Release (2022)

Nanomedicine offered hope for improving the treatment of cancer but the survival benefits of the clinically approved nanomedicines are modest in many cases when compared to conventional chemotherapy. Metronomic therapy, defined as the frequent, low dose administration of chemotherapeutics - is being tested in clinical trials as an alternative to the conventional maximum tolerated dose (MTD) chemotherapy schedule. Although metronomic chemotherapy has not been clinically approved yet, it has shown better survival than MTD in many preclinical studies. When beneficial, metronomic therapy seems to be associated with normalization of the tumor microenvironment including improvements in tumor perfusion, tissue oxygenation and drug delivery as well as activation of the immune system. Recent preclinical studies suggest that nanomedicines can cause similar changes in the tumor microenvironment. Here, by employing a mathematical framework, we show that both approaches can serve as normalization strategies to enhance treatment. Furthermore, employing murine breast and fibrosarcoma tumor models as well as ultrasound shear wave elastography and contrast-enhanced ultrasound, we provide evidence that the approved nanomedicine Doxil can induce normalization in a dose-dependent manner by improving tumor perfusion as a result of tissue softening. Finally, we show that pretreatment with a normalizing dose of Doxil can improve the efficacy of immune checkpoint inhibition.
Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor–Amplified Gastroesophageal Cancer: Retrospective Global Experience
Authors: Steven B. Maron, Stephanie Moya, Federica Morano, Matthew J. Emmett, Joanne F. Chou, Shalom Sabwa, Henry Walch, Bryan Peterson, Alexa B. Schrock, Liangliang Zhang, Yelena Y. Janjigian, Sree Chalasani, Geoffrey Y. Ku, Umut Disel, Peter Enzinger, Nataliya Uboha, Shumei Kato, Takayuki Yoshino, Kohei Shitara, Yoshiaki Nakamura, Anwaar Saeed, Pashtoon M. Kasi, Joseph Chao, Jeeyun Lee, Marinela Capanu, Zev Wainberg, Russell Petty, Filippo Pietrantonio, Samuel J. Klempner, Daniel V.T. Catenacci
Journal: Journal of Clinical Oncology (2022)

Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with EGFR-amplified GEA to date.A total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria. These criteria required histologically confirmed GEA in the metastatic or unresectable setting with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments-approved assay, and who received on- or off-protocol EGFRi. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, and/or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments approved laboratory. Treatment patterns and outcomes analysis was also performed using a deidentified clinicogenomic database (CGDB).Sixty patients with EGFR-amplified GEA received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median progression-free survival of 4.6 months (95% CI, 3.5 to 6.4). Patients receiving EGFRi in first-, second-, and third-line therapy achieved a median overall survival of 20.6 months (95% CI, 13.5 to not reached [NR]), 9 months (95% CI, 7.9 to NR), and 8.4 months (7.6 to NR), respectively. This survival far exceeded the 11.2-month (95% CI, 8.7 to 14.2) median overall survival from first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA in the CGDB. Despite this benefit, analysis of the CGDB (January 2011-December 2020) suggests that only 5% of patients with EGFR-amplified GEA received EGFRi.Patients with EGFR-amplified GEA derive significant benefit from EGFRi. Further prospective investigation of EGFRi in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR and/or MET amplified GEA.
Estimated COVID-19 Cases and Hospitalizations Averted by Case Investigation and Contact Tracing in the US
Authors: Gabriel Rainisch, Seonghye Jeon, Danielle Pappas, Kimberly D. Spencer, Leah S. Fischer, Bishwa B. Adhikari, Melanie M. Taylor, Bradford Greening, Patrick K. Moonan, John E. Oeltmann, Emily B. Kahn, Michael L. Washington, Martin I. Meltzer
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Evidence of the impact of COVID-19 case investigation and contact tracing (CICT) programs is lacking, but policy makers need this evidence to assess the value of such programs. <h3>Objective</h3> To estimate COVID-19 cases and hospitalizations averted nationwide by US states’ CICT programs. <h3>Design, Setting, and Participants</h3> This decision analytical model study used combined data from US CICT programs (eg, proportion of cases interviewed, contacts notified or monitored, and days to case and contact notification) with incidence data to model outcomes of CICT over a 60-day period (November 25, 2020, to January 23, 2021). The study estimated a range of outcomes by varying assumed compliance with isolation and quarantine recommendations. Fifty-nine state and territorial health departments that received federal funding supporting COVID-19 pandemic response activities were eligible for inclusion. Data analysis was performed from July to September 2021. <h3>Exposure</h3> Public health case investigation and contact tracing. <h3>Main Outcomes and Measures</h3> The primary outcomes were numbers of cases and hospitalizations averted and the percentage of cases averted among cases not prevented by vaccination and other nonpharmaceutical interventions. <h3>Results</h3> In total, 22 states and 1 territory reported all measures necessary for the analysis. These 23 jurisdictions covered 42.5% of the US population (approximately 140 million persons), spanned all 4 US Census regions, and reported data that reflected all 59 federally funded CICT programs. This study estimated that 1.11 million cases and 27 231 hospitalizations were averted by CICT programs under a scenario where 80% of interviewed cases and monitored contacts and 30% of notified contacts fully complied with isolation and quarantine guidance, eliminating their contributions to future transmission. As many as 1.36 million cases and 33 527 hospitalizations could have been prevented if all interviewed cases and monitored contacts had entered into and fully complied with isolation and quarantine guidelines upon being interviewed or notified. Across both scenarios and all jurisdictions, CICT averted an estimated median of 21.2% (range, 1.3%-65.8%) of the cases not prevented by vaccination and other nonpharmaceutical interventions. <h3>Conclusions and Relevance</h3> These findings suggest that CICT programs likely had a substantial role in curtailing the pandemic in most jurisdictions during the 2020 to 2021 winter peak. Differences in outcomes across jurisdictions indicate an opportunity to further improve CICT effectiveness. These estimates demonstrate the potential benefits from sustaining and improving these programs.
THE ASSOCIATION OF THORACIC FAT WITH LIPID CHANGE FROM STATIN THERAPY AND RISK OF LONG TERM ALL-CAUSE MORTALITY
Authors: Lu Chen, Jonathan Scheiner, Niloofar Fouladi Nashta, Jonathan Weber, Qingtao Zhou, Kathleen Rapejle, Damini Dey, Jie J. Cao
Journal: Journal of the American College of Cardiology (2022)
CLINICAL CHARACTERISTICS OF NEUROLOGICAL DISEASE AND COVID-19
Authors: Kajal Thakkar, Alan Goldberg, Joanne Gomez, Tisha Marie Suboc, Jeanne du Fay de Lavallaz, Athina Bouroukas, Annabelle S. Volgman, Kim Allan Williams, Neelum T. Aggarwal
Journal: Journal of the American College of Cardiology (2022)
DIFFERENTIAL CARDIOTOXICITY OF IMMUNE CHECKPOINT INHIBITORS INVOLVES DAMPS FIBRONECTIN-EDA, S100/CALGRANULIN, GALECTINE-3 AND ASSOCIATED NLRP3 INFLAMMASOMECHEMOKINE PATHWAY IN PRECLINICAL MODELS
Authors: Nicola Maurea, Claudia De Lorenzo, Margherita Passariello, Martina Iovine, Simona Buccolo, Antonio Barbieri, Domenica Rea, Annabella Di Mauro, Ciro Cipullo, Andrea Paccone, Antonietta Caronna, Vincenzo Quagliariello
Journal: Journal of the American College of Cardiology (2022)
FOSL1 promotes proneural-to-mesenchymal transition of glioblastoma stem cells via UBC9/CYLD/NF-κB axis
Authors: Zhengxin Chen, Shuai Wang, Hai-Lin Li, Hui Luo, Xiaoting Wu, Jiacheng Lu, Hong-Wei Wang, Yuanyuan Chen, Dan Chen, Wen-Ting Wu, Shuyu Zhang, Qiongqiong He, Daru Lu, Ning Liu, Yongping You, Wei Wu, Huibo Wang
Journal: Molecular Therapy (2022)

Proneural (PN) to mesenchymal (MES) transition (PMT) is a crucial phenotypic shift in glioblastoma stem cells (GSCs). However, the mechanisms driving this process remain poorly understood. Here, we report that Fos-like antigen 1 (FOSL1), a component of AP1 transcription factor complexes, is a key player in regulating PMT. FOSL1 is predominantly expressed in the MES subtype, but not PN subtype, of GSCs. Knocking down FOSL1 expression in MES GSCs leads to the loss of MES features and tumor-initiating ability, whereas ectopic expression of FOSL1 in PN GSCs is able to induce PMT and maintain MES features. Moreover, FOSL1 facilitates ionizing radiation (IR)-induced PMT and radioresistance of PN GSCs. Inhibition of FOSL1 enhances the anti-tumor effects of IR by preventing IR-induced PMT. Mechanistically, we find that FOSL1 promotes UBC9-dependent CYLD SUMOylation, thereby inducing K63-linked polyubiquitination of major nuclear factor κB (NF-κB) intermediaries and subsequent NF-κB activation, which results in PMT induction in GSCs. Our study underscores the importance of FOSL1 in the regulation of PMT and suggests that therapeutic targeting of FOSL1 holds promise to attenuate molecular subtype switching in patients with glioblastomas.
HOSPITALIZATION OUTCOMES IN PATIENTS WITH UPPER GASTROINTESTINAL BLEEDING AND ATRIAL FIBRILLATION: ANALYSIS OF NATIONAL INPATIENT SAMPLE
Authors: Raquel Soon-Shiong, Emmanuel Akuna, Iriagbonse Asemota, Muhammad Usman, Muhammad Usman Almani, Bharosa Sharma, Smriti Khanal, Dennis Danso Kumi, Prajwal Shrestha
Journal: Journal of the American College of Cardiology (2022)
DEMOGRAPHIC DISPARITIES AMONG LEADERSHIP POSITIONS WITHIN MEDICAL/SURGICAL SOCIETIES WITHIN THE UNITED STATES
Authors: Rishi Ajeet Charate, Adnan Ahmed, Jalaj Garg, Mehmet Ali Elbey, Sri Harsha Kanuri, Mehmet Akkaya, Vasvi Singh, Donita Atkins, Rakesh Gopinathannair, Dhanunjaya R. Lakkireddy, Andrea Natale
Journal: Journal of the American College of Cardiology (2022)
Hydrogels derived from decellularized liver tissue support the growth and differentiation of cholangiocyte organoids
Authors: Jorke Willemse, Gilles van Tienderen, Eline van Hengel, Ivo Schurink, Diana van der Ven, Yik Kan, Petra de Ruiter, Oskar Rosmark, Gunilla Westergren-Thorsson G, Kerstin Schneeberger, Bram van der Eerden, Henk Roest, Bart Spee, Luc van der Laan, Jeroen de Jonge, Monique Verstegen
Journal: Biomaterials (2022)

Human cholangiocyte organoids are promising for regenerative medicine applications, such as repair of damaged bile ducts. However, organoids are typically cultured in mouse tumor-derived basement membrane extracts (BME), which is poorly defined, highly variable and limits the direct clinical applications of organoids in patients. Extracellular matrix (ECM)-derived hydrogels prepared from decellularized human or porcine livers are attractive alternative culture substrates. Here, the culture and expansion of human cholangiocyte organoids in liver ECM(LECM)-derived hydrogels is described. These hydrogels support proliferation of cholangiocyte organoids and maintain the cholangiocyte-like phenotype. The use of LECM hydrogels does not significantly alter the expression of selected genes or proteins, such as the cholangiocyte marker cytokeratin-7, and no species-specific effect is found between human or porcine LECM hydrogels. Proliferation rates of organoids cultured in LECM hydrogels are lower, but the differentiation capacity of the cholangiocyte organoids towards hepatocyte-like cells is not altered by the presence of tissue-specific ECM components. Moreover, human LECM extracts support the expansion of ICO in a dynamic culture set up without the need for laborious static culture of organoids in hydrogel domes. Liver ECM hydrogels can successfully replace tumor-derived BME and can potentially unlock the full clinical potential of human cholangiocyte organoids.
THERAPEUTIC HYPOTHERMIA IS ASSOCIATED WITH A DECREASE IN ALL-CAUSE MORTALITY IN CARDIAC ARREST WITH INITIAL SHOCKABLE RHYTHM
Authors: Usama Nasir, Shivaraj Nagalli, Keerat R. Ahuja, Tayyab Waheed, Muhammad Qasim, Murtaza Sundhu, Satish K. Ahuja, Jaghat Ram, Rittu Vinoo Hingorani
Journal: Journal of the American College of Cardiology (2022)
FOXK2 promotes ovarian cancer stemness by regulating the unfolded protein response pathway
Authors: Yaqi Zhang, Yinu Wang, Guangyuan Zhao, Edward J. Tanner, Mazhar Adli, Daniela Matei
Journal: Journal of Clinical Investigation (2022)

Understanding the regulatory programs enabling cancer stem cells (CSCs) to self-renew and drive tumorigenicity could identify new treatments. Through comparative chromatin-state and gene expression analyses in ovarian CSCs versus non-CSCs, we identified FOXK2 as a highly expressed stemness-specific transcription factor in ovarian cancer. Its genetic depletion diminished stemness features and reduced tumor initiation capacity. Our mechanistic studies highlight that FOXK2 directly regulated IRE1α (encoded by ERN1) expression, a key sensor for the unfolded protein response (UPR). Chromatin immunoprecipitation and sequencing revealed that FOXK2 bound to an intronic regulatory element of ERN1. Blocking FOXK2 from binding to this enhancer by using a catalytically inactive CRISPR/Cas9 (dCas9) diminished IRE1α transcription. At the molecular level, FOXK2-driven upregulation of IRE1α led to alternative XBP1 splicing and activation of stemness pathways, while genetic or pharmacological blockade of this sensor of the UPR inhibited ovarian CSCs. Collectively, these data establish what we believe is a new function for FOXK2 as a key transcriptional regulator of CSCs and a mediator of the UPR, providing insight into potentially targetable new pathways in CSCs.