tbuckley/cabot-search huggingface dataset:
Translational randomized phase II trial of cabozantinib in combination with nivolumab in advanced, recurrent, or metastatic endometrial cancer
Authors: Stephanie Lheureux, Daniela E Matei, Panagiotis A Konstantinopoulos, Ben X Wang, Ramy Gadalla, Matthew S Block, Andrea Jewell, Stephanie L Gaillard, Michael McHale, Carolyn McCourt, Sarah Temkin, Eugenia Girda, Floor J Backes, Theresa L Werner, Linda Duska, Siobhan Kehoe, Ilaria Colombo, Lisa Wang, Xuan Li, Rachel Wildman, Shirin Soleimani, Scott Lien, John Wright, Trevor Pugh, Pamela S Ohashi, David G Brooks, Gini F Fleming
Journal: Journal for ImmunoTherapy of Cancer (2022)

Combining immunotherapy and antiangiogenic agents is a promising treatment strategy in endometrial cancer. To date, no biomarkers for response have been identified and data on post-immunotherapy progression are lacking. We explored the combination of a checkpoint inhibitor (nivolumab) and an antiangiogenic agent (cabozantinib) in immunotherapy-naïve endometrial cancer and in patients whose disease progressed on previous immunotherapy with baseline biopsy for immune profiling.In this phase II trial (ClinicalTrials.gov NCT03367741, registered December 11, 2017), women with recurrent endometrial cancer were randomized 2:1 to nivolumab with cabozantinib (Arm A) or nivolumab alone (Arm B). The primary endpoint was Response Evaluation Criteria in Solid Tumors-defined progression-free survival (PFS). Patients with carcinosarcoma or prior immune checkpoint inhibitor received combination treatment (Arm C). Baseline biopsy and serial peripheral blood mononuclear cell (PBMC) samples were analyzed and associations between patient outcome and immune data from cytometry by time of flight (CyTOF) and PBMCs were explored.Median PFS was 5.3 (90% CI 3.5 to 9.2) months in Arm A (n=36) and 1.9 (90% CI 1.6 to 3.4) months in Arm B (n=18) (HR=0.59, 90% CI 0.35 to 0.98; log-rank p=0.09, meeting the prespecified statistical significance criteria). The most common treatment-related adverse events in Arm A were diarrhea (50%) and elevated liver enzymes (aspartate aminotransferase 47%, alanine aminotransferase 42%). In-depth baseline CyTOF analysis across treatment arms (n=40) identified 35 immune-cell subsets. Among immunotherapy-pretreated patients in Arm C, non-progressors had significantly higher proportions of activated tissue-resident (CD103+CD69+) ɣδ T cells than progressors (adjusted p=0.009).Adding cabozantinib to nivolumab significantly improved outcomes in heavily pretreated endometrial cancer. A subgroup of immunotherapy-pretreated patients identified by baseline immune profile and potentially benefiting from combination with antiangiogenics requires further investigation.
Use of Early Intrathecal Therapy to Manage High-Grade Immune Effector Cell-Associated Neurotoxicity Syndrome
Authors: Joanna C. Zurko, Bryon D. Johnson, Emilie Aschenbrenner, Timothy S. Fenske, Mehdi Hamadani, Parameswaran Hari, Nirav N. Shah
Journal: JAMA Oncology (2022)

This case series describes the use of early intrathecal steroid administration to manage high-grade and steroid-refractory immune effector cell-associated neurotoxicity syndrome among patients with B-cell non-Hodgkin lymphoma.
HIGHER BODY MASS INDEX IN EARLY ADULTHOOD AND SUBSEQUENT RISK OF HEART FAILURE
Authors: Ebad Ur Rahman, Fatima Farah, Muchi Ditah Chobufo, Ebubechukwu Ezeh, Kanaan Mansoor, Olusola Olubowale, Mohamed Tashani, Gregg C. Fonarow, Mark A. Studeny, Ellen A. Thompson, Carlos Alberto Rueda Rios
Journal: Journal of the American College of Cardiology (2022)
Subclonal heterogeneity sheds light on the transformation trajectory in IGLV3-21R110 chronic lymphocytic leukemia
Authors: Lisa Paschold, Donjete Simnica, Ramon Benitez Brito, Tianjiao Zhang, Christoph Schultheiß, Christine Dierks, Mascha Binder
Journal: Blood Cancer Journal (2022)

In chronic lymphocytic leukemia (CLL), a specific G-to-R replacement at the boundary of variable and constant region of the B cell receptor (BCR) light chain IGLV3-21 (IGLV3-21 R110 ) facilitates homotypic BCR-BCR interactions [1-7].While virtually all CLL BCR are prone to autonomous signaling induced by such contacts, the IGLV3-21 R110 molecular interaction defines a distinct clinical subset of patients that show a very aggressive clinical course [8].While we currently lack an exact mechanistic understanding of how the CLL-promoting R110 residue is generated, its localization at the boundary of variable and constant regions suggests that it may be a product of errors in double strand break repair in the process of the V-J rearrangement of the light chain.This is especially interesting since mutations in SF3B1 and ATM have been found overrepresented in IGLV3-21 R110 expressing CLL [9, 10].Both genes are involved in DNA damage response and repair of DNA double strand breaks that do occur in the V-J recombination process [11,12].This could open up the intriguing possibility that these mutations are acquired first and may subsequently prevent the repair of point mutations such as the one resulting in IGLV3-21 R110 .If indeed IGLV3-21 R110 was generated through dysfunctional V-J recombination that is facilitated through mutations in genes involved in DNA repair, this would require acquisition of such mutations before light chain V-J recombination e.g. at the pre-B cell stage or earlier.The error permissive environment created by such mutations would be supported by the finding of different CLL clones that undergo independent G to R exchanges in the process of V-J recombination.To investigate this hypothesis and thereby gain insight into the transformation trajectory of IGLV3-21 R110 CLL, we screened a cohort of 127 CLL by flow cytometry for IGLV3-21 R110 using an IGLV3-21 R110 specific antibody (Fig. 1A).Twelve IGLV3-21 R110 expressing CLL cases were identified making up 9.4% of the overall CLL cohort.These were studied in greater detail using nextgeneration sequencing (NGS) of immunoglobulin gene rearrangements on flow cytometry sorted and unsorted cells, evolutionary reconstruction of the CLL clone by analysis of V(D)J rearrangements and somatic hypermutation as well as genetic typing for driver gene mutations and chromosomal deletions as described in the Detailed Methods Section.Indeed, genetic alterations in ATM and SF3B1 that are associated with the DNA damage response and repair of DNA double strand breaks that do occur in the V-J recombination process were found overrepresented in our IGLV3-21 R110 CLL cases thereby confirming prior evidence: [9, 10] 42% (5 of 12) of the
GUIDELINE BASED RISK STRATIFICATION AND SELECTION OF AORTIC VALVE INTERVENTION: A REPORT FROM THE NORTHERN NEW ENGLAND CARDIOVASCULAR DISEASE STUDY GROUP
Authors: Althea Jem Tapales, Toishi Sharma, Cathy S. Ross, David J. Malenka, James M. Flynn, David W. Butzel, Michael A. Ferguson, Michael N. Young, Samip Vasaiwala, Robert S. Kramer, Alexander Iribarne, Harold L. Dauerman
Journal: Journal of the American College of Cardiology (2022)
David Oliver: Is Sajid Javid putting political ideology before prevention?
Authors: David Oliver
Journal: BMJ (2022)

Politicians and their parties obviously embrace ideology, but problems as serious as preventable disease and health inequalities require proper solutions based on expertise and evidence, not on political biases.On 8 March the secretary of state for health and social care, Sajid Javid, set out his vision for NHS reform. 1 His three stated priorities were prevention, personalisation, and performance.
A Smart Hydrogel with Anti‐Biofilm and Anti‐Virulence Activities to Treat <i>Pseudomonas aeruginosa</i> Infections
Authors: Jingjing Hu, Sijia Chen, Yongxin Yang, Lin Li, Xuejing Cheng, Yiyun Cheng, Quan Huang
Journal: Advanced Healthcare Materials (2022)

Biofilm is the main culprit of refractory infections and seriously threaten to the human health. Here, a smart hydrogel consisted of norspermidine, aminoglycosides, and oxidized polysaccharide is prepared via the formation of acid-labile imine linkage to treat Pseudomonas aeruginosa biofilm infections in several animal models. The increased acidity caused by bacterial infection triggers the release of norspermidine and aminoglycosides covalently bound with the polymer scaffold. The released norspermidine inhibits biofilm formation and virulence production by regulating the quorum sensing of P. aeruginosa, while the aminoglycoside antibiotics effectively kill the released bacteria. The gel thoroughly inhibits biofilm formation on various medical devices and decreases bacteria pathogenicity. It efficiently inhibits implantation-associated biofilm infections and chronic wound infections, and shows great promise to prevent and treat biofilm-induced refractory infection in clinics.
Longitudinal Changes in Structural Connectivity in Young People at High Genetic Risk for Bipolar Disorder
Authors: Gloria Roberts, Alistair Perry, Kate Ridgway, Vivian Leung, Megan Campbell, Rhoshel Lenroot, Philip B. Mitchell, Michael Breakspear
Journal: American Journal of Psychiatry (2022)

Objective: Recent studies of patients with bipolar disorder or at high genetic risk reveal structural dysconnections among key brain networks supporting cognitive and affective processes. Understanding the longitudinal trajectories of these networks across the peak age range of bipolar disorder onset could inform mechanisms of illness onset or resilience. Methods: Longitudinal diffusion-weighted MRI and phenotypic data were acquired at baseline and after 2 years in 183 individuals ages 12–30 years in two cohorts: 97 unaffected individuals with a first-degree relative with bipolar disorder (the high-risk group) and 86 individuals with no family history of mental illness (the control group). Whole-brain structural networks were derived using tractography, and longitudinal changes in these networks were studied using network-based statistics and mixed linear models. Results: Both groups showed widespread longitudinal changes, comprising both increases and decreases in structural connectivity, consistent with a shared neurodevelopmental process. On top of these shared changes, high-risk participants showed weakening of connectivity in a network encompassing the left inferior and middle frontal areas, left striatal and thalamic structures, the left fusiform, and right parietal and occipital regions. Connections among these regions strengthened in the control group, whereas they weakened in the high-risk group, shifting toward a cohort with established bipolar disorder. There was marginal evidence for even greater network weakening in those who had their first manic or hypomanic episode before follow-up. Conclusions: Neurodevelopment from adolescence into early adulthood is associated with a substantial reorganization of structural brain networks. Differences in these maturational processes occur in a multisystem network in individuals at high genetic risk of bipolar disorder. This may represent a novel candidate to understand resilience and predict conversion to bipolar disorder.
Archbishop Desmond Tutu and the universality of health and human rights
Authors: Chris Beyrer, Chris Beyrer, Pascale Allotey, Joseph J Amon, Stefan D Baral, Mary T Bassett, Harriet Deacon, Lorraine T Dean, Lilianne Fan, Rita Giacaman, Carolyn Gomes, Sofia Gruskin, Samer Jabbour, Michel Kazatchkine, Lucy Stackpool-Moore, Allan Maleche, Martin McKee, Sandra Hsu Hnin Mon, Vera Paiva, Alena Peryskina, Dainius Pūras, Leonard Rubenstein, Adeeba Kamarulzaman, Gergon Smoger, Javier Cepeda
Journal: The Lancet (2022)
Species Persistence with Hybridization in Toad-Headed Lizards Driven by Divergent Selection and Low Recombination
Authors: Wei Gao, Chuan-Xin Yu, Wei-Wei Zhou, Bao-Lin Zhang, E. Anne Chambers, Hollis A. Dahn, Jie-Qiong Jin, Robert W. Murphy, Ya-Ping Zhang, Jing Che
Journal: Molecular Biology and Evolution (2022)

Speciation plays a central role in evolutionary studies, and particularly how reproductive isolation (RI) evolves. The origins and persistence of RI are distinct processes that require separate evaluations. Treating them separately clarifies the drivers of speciation and then it is possible to link the processes to understand large-scale patterns of diversity. Recent genomic studies have focused predominantly on how species or RI originate. However, we know little about how species persist in face of gene flow. Here, we evaluate a contact zone of two closely related toad-headed lizards (Phrynocephalus) using a chromosome-level genome assembly and population genomics. To some extent, recent asymmetric introgression from Phrynocephalus putjatai to P. vlangalii reduces their genomic differences. However, their highly divergent regions (HDRs) have heterogeneous distributions across the genomes. Functional gene annotation indicates that many genes within HDRs are involved in reproduction and RI. Compared with allopatric populations, contact areas exhibit recent divergent selection on the HDRs and a lower population recombination rate. Taken together, this implies that divergent selection and low genetic recombination help maintain RI. This study provides insights into the genomic mechanisms that drive RI and two species persistence in the face of gene flow during the late stage of speciation.
Alloyed nanostructures integrated metal-phenolic nanoplatform for synergistic wound disinfection and revascularization
Authors: Yi Xie, Shengqiu Chen, Xu Peng, Xiaoling Wang, Zhiwei Wei, Joseph J. Richardson, Kang Liang, Hirotaka Ejima, Junling Guo, Changsheng Zhao
Journal: Bioactive Materials (2022)

New materials for combating bacteria-caused infection and promoting the formation of microvascular networks during wound healing are of vital importance. Although antibiotics can be used to prevent infection, treatments that can disinfect and accelerate wound healing are scarce. Herein, we engineer a coating that is both highly compatible with current wound dressing substrates and capable of simultaneously disinfecting and revascularizing wounds using a metal-phenolic nanoplatform containing an alloyed nanostructured architecture (Ag@Cu-MPNNC). The alloyed nanostructure is formed by the spontaneous co-reduction and catalytic disproportionation reaction of multiple metal ions on a foundation metal-phenolic supramolecular layer. This synergistic presence of metals greatly improves the antibacterial activity against both Gram-negative and Gram-positive pathogenic bacteria, while demonstrating negligible cytotoxicity to normal tissue. In infected rat models, the Ag@Cu-MPNNC could kill bacteria efficiently, promoting revascularization and accelerate wound closure with no adverse side effects in infected in vivo models. In other words, this material acts as a combination therapy by inhibiting bacterial invasion and modulating bio-nano interactions in the wound.
Health app policy: international comparison of nine countries’ approaches
Authors: Anna Essén, Ariel D. Stern, Christoffer Bjerre Haase, Josip Car, Felix Greaves, Dragana Paparova, Steven Vandeput, Rik Wehrens, David W. Bates
Journal: npj Digital Medicine (2022)

An abundant and growing supply of digital health applications (apps) exists in the commercial tech-sector, which can be bewildering for clinicians, patients, and payers. A growing challenge for the health care system is therefore to facilitate the identification of safe and effective apps for health care practitioners and patients to generate the most health benefit as well as guide payer coverage decisions. Nearly all developed countries are attempting to define policy frameworks to improve decision-making, patient care, and health outcomes in this context. This study compares the national policy approaches currently in development/use for health apps in nine countries. We used secondary data, combined with a detailed review of policy and regulatory documents, and interviews with key individuals and experts in the field of digital health policy to collect data about implemented and planned policies and initiatives. We found that most approaches aim for centralized pipelines for health app approvals, although some countries are adding decentralized elements. While the countries studied are taking diverse paths, there is nevertheless broad, international convergence in terms of requirements in the areas of transparency, health content, interoperability, and privacy and security. The sheer number of apps on the market in most countries represents a challenge for clinicians and patients. Our analyses of the relevant policies identified challenges in areas such as reimbursement, safety, and privacy and suggest that more regulatory work is needed in the areas of operationalization, implementation and international transferability of approvals. Cross-national efforts are needed around regulation and for countries to realize the benefits of these technologies.
Polysaccharide utilization loci in Bacteroides determine population fitness and community-level interactions
Authors: Jun Feng, Yili Qian, Zhichao Zhou, Sarah Ertmer, Eugenio I. Vivas, Freeman Lan, Joshua J. Hamilton, Federico E. Rey, Karthik Anantharaman, Ophelia S. Venturelli
Journal: Cell Host & Microbe (2022)
YIA22-001: Development of hKIT Chimeric Antigen Receptor T-Cells as Dual Hematopoietic Stem Cell Transplantation Conditioning and Immunotherapeutic Agents for Cure of Pediatric Acute Myeloid Leukemia
Authors: Quenton Rashawn Bubb, Corey Cheung, Gabriel Eduardo Seir, Leah Swartzrock, Rebecca Richards, Crystal Mackall, Agnieszka Czechowicz
Journal: Journal of the National Comprehensive Cancer Network (2022)

"YIA22-001: Development of hKIT Chimeric Antigen Receptor T-Cells as Dual Hematopoietic Stem Cell Transplantation Conditioning and Immunotherapeutic Agents for Cure of Pediatric Acute Myeloid Leukemia" published on 31 Mar 2022 by National Comprehensive Cancer Network.
CLO22-051: Influence of Environmental Temperature on Pathological Complete Response and Overall Survival in Breast Cancer: A National Cancer Database Population-Based Study
Authors: Ashish Gupta, Kristopher Attwood, Kush Gupta, Asha Gandhi, Stephen Edge, Kazuaki Takabe, Shipra Gandhi
Journal: Journal of the National Comprehensive Cancer Network (2022)

"CLO22-051: Influence of Environmental Temperature on Pathological Complete Response and Overall Survival in Breast Cancer: A National Cancer Database Population-Based Study" published on 31 Mar 2022 by National Comprehensive Cancer Network.
Automatic scan range for dose-reduced multiphase CT imaging of the liver utilizing CNNs and Gaussian models
Authors: Manh Ha Luu, Theo van Walsum, Hong Son Mai, Daniel Franklin, Thi Thu Thao Nguyen, Thi My Le, Adriaan Moelker, Van Khang Le, Dang Luu Vu, Ngoc Ha Le, Quoc Long Tran, Duc Trinh Chu, Nguyen Linh Trung
Journal: Medical Image Analysis (2022)
Sleep Positional Therapy for Nocturnal Gastroesophageal Reflux: A Double-Blind, Randomized, Sham-Controlled Trial
Authors: Jeroen M Schuitenmaker, Thijs Kuipers, Renske A B Oude Nijhuis, Marlies P Schijven, André J P M Smout, Paul Fockens, Albert J Bredenoord
Journal: Clinical Gastroenterology and Hepatology (2022)
Simultaneously enhancing the photocatalytic and photothermal effect of NH2-MIL-125-GO-Pt ternary heterojunction for rapid therapy of bacteria-infected wounds
Authors: Yue Luo, Bo Li, Xiangmei Liu, Yufeng Zheng, Erjing Wang, Zhaoyang Li, Zhenduo Cui, Yanqin Liang, Shengli Zhu, Shuilin Wu
Journal: Bioactive Materials (2022)
TICAGRELOR DOES NOT MEDIATE ITS EARLY BENEFICIAL EFFECTS IN ST-ELEVATION MYOCARDIAL INFARCTION BY IMPROVING CORONARY MICROVASCULAR DYSFUNCTION – THE TIMES DOUBLE-BLIND RANDOMISED CONTROLLED TRIAL
Authors: Stephen P. Hoole, Muhammad Aetesam-ur-Rahman, Yi-Da Chiu, Tian Zhao, Kitty Paques, Joana Oliveira, Jo Steele, Melissa Duckworth, Sarah Fielding, Nick E. West
Journal: Journal of the American College of Cardiology (2022)
MATERNAL AND FOETAL OUTCOME IN EISENMENGER PREGNANCIES: A PROSPECTIVE OBSERVATIONAL STUDY
Authors: Justin Paul Gnanaraj, Anne Princy, Thirumal Gnanaprakasam, Karthikeyan Balu, Anju Surendran, Elavarasi Manimegalai, Venkatesan S, Ravishankar G, Manohar G, Swaminathan Nagarajan, Vijaya S, Meena S, Meena Suresh, Gomathi K, Kanmani K
Journal: Journal of the American College of Cardiology (2022)
Synchronously boosting type-I photodynamic and photothermal efficacies via molecular manipulation for pancreatic cancer theranostics in the NIR-II window
Authors: Dan Li, Xiaohui Chen, Deliang Wang, Hongzhuo Wu, Haifei Wen, Lei Wang, Qiao Jin, Dong Wang, Jian Ji, Ben Zhong Tang
Journal: Biomaterials (2022)
CHARACTERISTICS AND OUTCOMES OF IN-HOSPITAL BLEEDING EVENTS IN WOMEN WITH STEMI TREATED WITH RADIAL ACCESS PCI
Authors: Neha Gupta, Raunak Nair, Anirudh Kumar, Chetan Prakash Huded, Kathleen Kravitz, Grant W. Reed, Amar Krishnaswamy, Venu Menon, Michael Johnson, A. Michael Lincoff, Samir R. Kapadia, Umesh Khot
Journal: Journal of the American College of Cardiology (2022)
NOT SO CRYPTOGENIC AFTER ALL: LEFT VENTRICULAR NONCOMPACTION CARDIOMYOPATHY PRESENTING AS ORGANIZING PNEUMONIA IN A YOUNG FEMALE TRAVELER
Authors: Amanda Doval, Paola C. Mercado Millan, Jonathan Cordero, Carla Colón, Hillarie Rios, Steven Alfonso Garcia Santiago, Juan Nieves
Journal: Journal of the American College of Cardiology (2022)
Gambling disorder in the UK: key research priorities and the urgent need for independent research funding
Authors: Henrietta Bowden-Jones, Roxanne W Hook, Jon E Grant, Konstantinos Ioannidis, Ornella Corazza, Naomi A Fineberg, Bryan F Singer, Amanda Roberts, Richard Bethlehem, Simon Dymond, Rafa Romero-Garcia, Trevor W Robbins, Samuele Cortese, Shane A Thomas, Barbara J Sahakian, Nicki A Dowling, Samuel R Chamberlain
Journal: The Lancet Psychiatry (2022)
DIFFERENCES IN OUTCOME AMONG PATIENTS ADMITTED ON THE WEEKEND WITH ACUTE NON-ST ELEVATION MYOCARDIAL INFARCTION AND INTERMEDIATE TIMI SCORE
Authors: Rezwan F. Munshi, James Pellegrini, Narois Nehru, Aditya Iyer, Kashyap Shah, Samarthkumar Thakkar, Ofek Hai, Roman Zeltser, Amgad N. Makaryus
Journal: Journal of the American College of Cardiology (2022)
Evolution of the Coronary Microcirculation After Restoration of Epicardial Blood Flow in STEMI
Authors: Christopher C.Y. Wong, Andy S.C. Yong, Anthony Keech, Cuneyt Ada, Kaivan Vaidya, Rachel O’Connell, BMath, Jamie Layland, Harvey White, William F. Fearon, Martin K.C. Ng
Journal: Journal of the American College of Cardiology (2022)
High-throughput characterization of the role of non-B DNA motifs on promoter function
Authors: Ilias Georgakopoulos-Soares, Jesus Victorino, Guillermo E. Parada, Vikram Agarwal, Jingjing Zhao, Hei Yuen Wong, Mubarak Ishaq Umar, Orry Elor, Allan Muhwezi, Joon-Yong An, Stephan J. Sanders, Chun Kit Kwok, Fumitaka Inoue, Martin Hemberg, Nadav Ahituv
Journal: Cell Genomics (2022)

lternative DNA conformations, termed non-B DNA structures, can affect transcription, but the underlying mechanisms and their functional impact have not been systematically characterized. Here, we used computational genomic analyses coupled with massively parallel reporter assays (MPRAs) to show that certain non-B DNA structures have a substantial effect on gene expression. Genomic analyses found that non-B DNA structures at promoters harbor an excess of germline variants. Analysis of multiple MPRAs, including a promoter library specifically designed to perturb non-B DNA structures, functionally validated that Z-DNA can significantly affect promoter activity. We also observed that biophysical properties of non-B DNA motifs, such as the length of Z-DNA motifs and the orientation of G-quadruplex structures relative to transcriptional direction, have a significant effect on promoter activity. Combined, their higher mutation rate and functional effect on transcription implicate a subset of non-B DNA motifs as major drivers of human gene-expression-associated phenotypes.
LEFT ATRIAL VOLUME INDEX AS A PREDICTOR OF ATRIAL FIBRILLATION RECURRENCE AFTER ELECTRICAL CARDIOVERSION
Authors: Sittinun Thangjui, Ratdanai Yodsuwan, Harshith Thyagaturu, Angkawipa Trongtorsak, Jerel M. Zoltick
Journal: Journal of the American College of Cardiology (2022)