tbuckley/cabot-search huggingface dataset:
Degree of Cardiometabolic Risk Factor Normalization in Individuals Receiving Bariatric Surgery: Evidence From NHANES 2015–2018
Authors: Young-Rock Hong, Aaron S. Kelly, Crystal Johnson-Mann, Dominick J. Lemas, Michelle I. Cardel
Journal: Diabetes Care (2021)

Bariatric surgery leads to clinically significant weight loss and improvements in cardiometabolic risk factors (1–3). However, population-based evidence evaluating the degree of improvements in cardiometabolic outcomes among those receiving bariatric surgery is limited. Using the National Health and Nutrition Examination Survey (NHANES) 2015–2018, we examined cardiometabolic risk factors among individuals who had undergone bariatric surgery, those eligible for but not receiving bariatric surgery, and normal-weight adults.

This study included adults aged ≥18 years who responded to bariatric surgery questions during the NHANES 2015–2018 cycles. The NHANES uses a stratified multistage probability method to sample the nationally representative U.S. population (https://www.cdc.gov/nchs/nhanes/index.htm). We analyzed six cardiometabolic measures—systolic blood pressure (SBP), diastolic blood pressure (DBP), hemoglobin A1c (HbA1c), total cholesterol (TC), HDL cholesterol (HDL-C), and hs-CRP—measured in a mobile examination center.

We used survey design–adjusted descriptive statistics to characterize the study population into three groups: 1 ) individuals with normal weight (BMI 18.5–24.9 kg/m2), 2 ) individuals reporting receipt of bariatric surgery, and 3 ) individuals medically eligible for bariatric surgery but reporting they had not received it. Surgery eligibility criteria include BMI ≥40 kg/m2 or …
Design of Electrohydrodynamic Devices with Consideration of Electrostatic Energy
Authors: Tasuku Sato, Shinya Sakuma, Masato Hijikuro, Shingo Maeda, Masayuki Anyoji, Yoko Yamanishi
Journal: Cyborg and Bionic Systems (2021)

The importance of actuators that can be integrated with flexible robot structures and mechanisms has increased in recent years with the advance of soft robotics. In particular, electrohydrodynamic (EHD) actuators, which have expandable integrability to adapt to the flexible motion of soft robots, have received much attention in the field of soft robotics. Studies have deepened the understanding of steady states of EHD phenomena but nonsteady states are not well understood. We herein observe the development process of fluid in a microchannel adopting a Schlieren technique with the aid of a high-speed camera. In addition, we analyze the behavior of fluid flow in a microchannel that is designed to have pairs of parallel plate electrodes adopting a computational fluid dynamics technique. Results indicate the importance of considering flow generated by electrostatic energy, which tends to be ignored in constructing and evaluating EHD devices, and by the body force generated by the ion-drag force. By considering these effects, we estimate the development process of EHD flow and confirm the importance of considering the generation of vortices and their interactions inside the microchannel during the development of EHD devices.
Nivolumab Plus Ipilimumab for Treatment-Naïve Metastatic Uveal Melanoma: An Open-Label, Multicenter, Phase II Trial by the Spanish Multidisciplinary Melanoma Group (GEM-1402)
Authors: José María Piulats, Enrique Espinosa, Luis de la Cruz Merino, Mar Varela, Lorenzo Alonso Carrión, Salvador Martín-Algarra, Rafael López Castro, Teresa Curiel, Delvys Rodríguez-Abreu, Miriam Redrado, Montserrat Gomà, Antonio José Rullán, Alfonso Calvo González, Alfonso Berrocal-Jaime
Journal: Journal of Clinical Oncology (2021)

This study aimed to assess the efficacy of the combination of nivolumab (nivo) plus ipilimumab (ipi) as a first-line therapy with respect to the 12-month overall survival (OS) in patients with metastatic uveal melanoma (MUM) who are not eligible for liver resection.This was a single-arm, phase II trial led by the Spanish Multidisciplinary Melanoma Group (GEM) on nivo plus ipi for systemic treatment-naïve patients of age > 18 years, with histologically confirmed MUM, Eastern Cooperative Oncology Group-PS 0/1, and confirmed progressive metastatic disease (M1). Nivo (1 mg/kg once every 3 weeks) and ipi (3 mg/kg once every 3 weeks) were administered during four inductions, followed by nivo (3 mg/kg once every 2 weeks) until progressive disease, toxicity, or withdrawal. The primary end point was 12-month OS. OS, progression-free survival (PFS), and overall response rate were evaluated every 6 weeks using RECIST (v1.1). Safety was also evaluated. Logistic regression and Cox proportional hazard models comprising relevant clinical factors were used to evaluate the potential association with response to treatment and survival. Cytokines were quantified in serum samples for their putative role in immune modulation/angiogenesis and/or earlier evidence of involvement in immunotherapy.A total of 52 patients with a median age of 59 years (range, 26-84 years) were enrolled. Overall, 78.8%, 56%, and 32% of patients had liver M1, extra-liver M1, and elevated lactate dehydrogenase. Stable disease was the most common outcome (51.9%). The primary end point was 12-month OS, which was 51.9% (95% CI, 38.3 to 65.5). The median OS and PFS were 12.7 months and 3.0 months, respectively. PFS was influenced by higher LDH values.Nivo plus ipi in the first-line setting for MUM showed a modest improvement in OS over historical benchmarks of chemotherapy, with a manageable toxicity profile.
Cell cycle stress in normal human cells: A route to “first cells” (with/without fitness gain) and cancer-like cell-shape changes
Authors: Kirsten H. Walen
Journal: Seminars in Cancer Biology (2021)

We have presented an in vitro trackable model system, atavistic induced from conservation in our genome, which strongly is applicable to tumorigenesis start and evolution. The inducing factor was death signals to proliferating normal human cells (primary cell strains), which respon-ded by a special type of tetraploidization, chromosomes with 4-chromatids (diplochromosomes, earlier described in cancer cells). The response included cell cycle stress, which prolonged S-period with result of mitotic slippage process, forming the special 4n cells by re-replication of diploid cells, which showed cell division capability to unexpected, genome reduced diploid cells which remarkably, showed fitness gain. This unique response through cell cycle stress and mitotic slippage process was further discovered to be linked to a rather special characteristic of the, 4n nucleus. The nucleus turned, self-inflicted, 90° perpendicular to the cell's cytoskeleton axis, importantly, before the special 4n-division system produced genome reduce diploid cells, we call "first cells", because of fitness gain. These 2n cells also showed the nuclear dependent 90° turn, which in both cases was associated with cells gaining cell shape changes, herein illustrated from normal fibroblastic cells changing to roundness cells, indistinguishable from todays' diagnostic cancer cell morphology. This 3-D ball-like cell shape, in metastasis, sque-ezing in and out between (?) endothelial cells in the lining of blood veins during disbursement, would be advantageous.
CRISPR/Cas9 directed to the Ube3a antisense transcript improves Angelman syndrome phenotype in mice
Authors: Ralf S. Schmid, Xuefeng Deng, Priyalakshmi Panikker, Msema Msackyi, Camilo Breton, James M. Wilson
Journal: Journal of Clinical Investigation (2021)

Gene editing holds the potential to correct mutations and cure devastating genetic disorders. The technology has not yet proven efficacious for therapeutic use in CNS diseases with ubiquitous neuronal defects. Angelman syndrome (AS), a severe neurodevelopmental disorder, is caused by a lack of maternal expression of the UBE3A gene. Because of genomic imprinting, only neurons are affected. One therapeutic approach focuses on the intact paternal UBE3A copy in patients with AS that is silenced by an antisense transcript (UBE3A-ATS). We show here that gene editing of Ube3a-ATS in the mouse brain resulted in the formation of base pair insertions/deletions (indels) in neurons and the subsequent unsilencing of the paternal Ube3a allele in neurons, which partially corrected the behavioral phenotype of a murine AS model. This study provides compelling evidence to further investigate editing of the homologous region of the human UBE3A-ATS because this may provide a lasting therapeutic effect for patients with AS.
MO01.02 Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab in the First-Line Treatment of Metastatic Non-Small Cell Lung Cancer in the United States
Authors: M. Berling, M.A. Chaudhary, Y. Yuan, N. Varol, P. Dale, E. Testa, J. Klint, A. Lee, S.J. Lubinga, J.R. Penrod
Journal: Journal of Thoracic Oncology (2021)
Empagliflozin Reduces Myocardial Extracellular Volume in Patients With Type 2 Diabetes and Coronary Artery Disease
Authors: Tamique Mason, Otavio R. Coelho-Filho, Subodh Verma, Biswajit Chowdhury, Fei Zuo, Adrian Quan, Kevin E. Thorpe, Christopher Bonneau, Hwee Teoh, Richard E. Gilbert, Lawrence A. Leiter, Peter Jüni, Bernard Zinman, Michael Jerosch-Herold, C. David Mazer, Andrew T. Yan, Kim A. Connelly
Journal: JACC. Cardiovascular imaging (2021)
Gendered movement ecology and landscape use in Hadza hunter-gatherers
Authors: Brian M. Wood, Jacob A. Harris, David A. Raichlen, Herman Pontzer, Katherine Sayre, Amelia Sancilio, Colette Berbesque, Alyssa N. Crittenden, Audax Mabulla, Richard McElreath, Elizabeth Cashdan, James Holland Jones
Journal: Nature Human Behaviour (2021)

Understanding how gendered economic roles structure space use is critical to evolutionary models of foraging behaviour, social organization and cognition. Here, we examine hunter-gatherer spatial behaviour on a very large scale, using GPS devices worn by Hadza foragers to record 2,078 person-days of movement. Theory in movement ecology suggests that the density and mobility of targeted foods should predict spatial behaviour and that strong gender differences should arise in a hunter-gatherer context. As predicted, we find that men walked further per day, explored more land, followed more sinuous paths and were more likely to be alone. These data are consistent with the ecology of male- and female-targeted foods and suggest that male landscape use is more navigationally challenging in this hunter-gatherer context. Comparisons of Hadza space use with space use data available for non-human primates suggest that the sexual division of labour likely co-evolved with increased sex differences in spatial behaviour and landscape use.
NHS Race and Health Observatory appoints global experts on inequalities to its board
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The newly created NHS Race and Health Observatory has appointed some of the world’s leading experts on health inequalities to its board of non‐executive directors.

The observatory, which is supported by NHS England and hosted by the NHS Confederation, was set up in May 2020 to investigate the effects of race and ethnicity on people’s health.1 Its creation was approved after Mala Rao and Victor Adebowale, who guest edited a special issue of The BMJ in February 2020 focused on the continuing problem of racism in medicine (bmj.com/racism-in-medicine), called for an independent “observatory” to “inform action towards the overarching NHS race equality goals.”2

Newly appointed board members include David Williams …
Incidence of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) including CNS relapse in a population-based cohort of 4243 patients in Sweden
Authors: Sara Harrysson, Sandra Eloranta, Sara Ekberg, Gunilla Enblad, Mats Jerkeman, Bjorn E. Wahlin, Per-Ola Andersson, Karin E. Smedby
Journal: Blood Cancer Journal (2021)

Abstract We performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007–2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) ( n = 3550, median age 69 years), whereas 14% did not ( n = 594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7–66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7–24.6, n = 847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5–3.6, n = 118) overall, and 8.0% (95% CI: 6.0–10.6, n = 48) among patients with high CNS-IPI (4–6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.
OA05.02 Analysis of Resistance Mmechanisms to Pralsetinib in Patients with RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC) from the ARROW Study
Authors: J. Gainor, G. Curigliano, R.C. Doebele, J.J. Lin, S.-H. Ou, S. Miller, C.D. Turner, V. Subbiah
Journal: Journal of Thoracic Oncology (2021)
Adherence to inhaled corticosteroids and clinical outcomes following a year of benralizumab therapy for severe eosinophilic asthma
Authors: Grainne d'Ancona, Joanne E. Kavanagh, Jaideep Dhariwal, Andrew P. Hearn, Cris Roxas, Mariana Fernandes, Linda Green, Louise Thomson, Alexandra M. Nanzer, David J. Jackson, Brian D. Kent
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
ATR Inhibition as an Attractive Therapeutic Resource against Cancer
Authors: Antoine Italiano
Journal: Cancer Discovery (2021)

Abstract Summary: In this issue of Cancer Discovery, Yap and colleagues demonstrate in a phase I trial enrolling 22 patients diagnosed with advanced solid tumors that BAY 1895344, a new potent and specific ATR inhibitor, is safe and able to induce durable responses in ATM-deficient tumors. This compelling clinical activity paves the way for innovative combination regimens that rely on exploitation of DNA damage response defects in cancer. See related article by Yap et al., p. 80.
Postdischarge Virtual Visits for Low-risk Surgeries
Authors: Kristen Harkey, Nicole Kaiser, Jing Zhao, Timothy Hetherington, Bella Gutnik, Brent D. Matthews, Rachel R. Kelz, Caroline E. Reinke
Journal: JAMA Surgery (2021)

Postdischarge video-based virtual visits are a growing aspect of surgical care and have dramatically increased in the setting of the coronavirus disease 2019 (COVID-19) pandemic.To evaluate the outcomes of all-cause 30-day hospital encounter proportion among patients who have a postdischarge video-based virtual visit follow-up compared with in-person follow-up.Randomized, active, controlled noninferiority trial in an urban setting, including patients from a small community hospital and a large, tertiary care hospital. Patients who underwent minimally invasive appendectomy or cholecystectomy by a group of surgeons who cover emergency general surgery at these 2 hospitals were included. Patients undergoing elective and nonelective procedures were included.Patients were randomized in a 2:1 fashion to video-based virtual visit or in-person visit.The primary outcome is the percentage of patients with 30-day hospital encounter, and we hypothesized that there would not be a significant increase in the 30-day hospital encounter proportion for patients who receive video-based virtual postdischarge care compared with patients who receive standard (in-person) care. Hospital encounter includes emergency department visit, observation, or inpatient admission.A total of 1645 patients were screened; 289 patients were randomized to the virtual group and 143 to the in-person group. Fifty-three patients crossed over to the in-person follow-up group. The percentage of patients who had a hospital encounter was noninferior for virtual visits (12.8% vs 13.3% for in-person, Δ 0.5% with 1-sided 95% CI, -∞ to 5.2%). The amount of time patients spent with the clinician (mean of 8.4 minutes virtual vs 7.8 minutes in-person; P = .30) was not different, but the median overall postoperative visit time was 27.5 minutes shorter (95% CI, -33.5 to -24.0).Postdischarge video-based virtual visits did not increase hospital encounter proportions and provided shorter overall time commitment but equal time with the surgical team member. This information will help surgeons and patients feel more confident in using video-based virtual visits.ClinicalTrials.gov Identifier: NCT03258177.
Spatiotemporal single-cell profiling reveals that invasive and tissue-resident memory donor CD8 <sup>+</sup> T cells drive gastrointestinal acute graft-versus-host disease
Authors: Victor Tkachev, James Kaminski, E. Lake Potter, Scott N. Furlan, Alison Yu, Daniel J. Hunt, Connor McGuckin, Hengqi Zheng, Lucrezia Colonna, Ulrike Gerdemann, Judith Carlson, Michelle Hoffman, Joe Olvera, Chris English, Audrey Baldessari, Angela Panoskaltsis-Mortari, Benjamin Watkins, Muna Qayed, Yvonne Suessmuth, Kayla Betz, Brandi Bratrude, Amelia Langston, John T. Horan, Jose Ordovas-Montanes, Alex K. Shalek, Bruce R. Blazar, Mario Roederer, Leslie S. Kean
Journal: Science Translational Medicine (2021)

Organ infiltration by donor T cells is critical to the development of acute graft-versus-host disease (aGVHD) in recipients after allogeneic hematopoietic stem cell transplant (allo-HCT). However, deconvoluting the transcriptional programs of newly recruited donor T cells from those of tissue-resident T cells in aGVHD target organs remains a challenge. Here, we combined the serial intravascular staining technique with single-cell RNA sequencing to dissect the tightly connected processes by which donor T cells initially infiltrate tissues and then establish a pathogenic tissue residency program in a rhesus macaque allo-HCT model that develops aGVHD. Our results enabled creation of a spatiotemporal map of the transcriptional programs controlling donor CD8+ T cell infiltration into the primary aGVHD target organ, the gastrointestinal (GI) tract. We identified the large and small intestines as the only two sites demonstrating allo-specific, rather than lymphodepletion-driven, T cell infiltration. GI-infiltrating donor CD8+ T cells demonstrated a highly activated, cytotoxic phenotype while simultaneously developing a canonical tissue-resident memory T cell (TRM) transcriptional signature driven by interleukin-15 (IL-15)/IL-21 signaling. We found expression of a cluster of genes directly associated with tissue invasiveness, including those encoding adhesion molecules (ITGB2), specific chemokines (CCL3 and CCL4L1) and chemokine receptors (CD74), as well as multiple cytoskeletal proteins. This tissue invasion transcriptional signature was validated by its ability to discriminate the CD8+ T cell transcriptome of patients with GI aGVHD from those of GVHD-free patients. These results provide insights into the mechanisms controlling tissue occupancy of target organs by pathogenic donor CD8+ TRM cells during aGVHD in primate transplant recipients.
Abstract 13276: Right Heart Morphology and Function in Elite Female Athletes: A Systematic Review and Meta-Analysis
Authors: Robyn Bryde, Abd Moain Abu Dabrh, Andres Applewhite, George Yazji, Rashid Alhusain, Brian P Shapiro
Journal: Circulation (2019)

Introduction: In elite athletes, exposure to chronic exercise forces the right ventricle (RV) to work against increasing afterloads. This exposure is known to induce physiologic structural and func...
Modular gene analysis reveals distinct molecular signatures for subsets of patients with cutaneous lupus erythematosus*
Authors: J. L. Zhu, L. T. Tran, M. Smith, F. Zheng, L. Cai, J. A. James, J. M. Guthridge, B. F. Chong
Journal: British Journal of Dermatology (2021)

Cutaneous lupus erythematosus (CLE) is a heterogeneous autoimmune disease with clinical sequelae such as itching, dyspigmentation and scarring.We applied a previously described modular analysis approach to assess the molecular heterogeneity of patients with CLE.Whole-blood transcriptomes of RNA sequencing data from a racially and ethnically diverse group of patients with CLE (n = 62) were used to calculate gene co-expression module scores. An unsupervised cluster analysis and k-means clustering based on these module scores were then performed. We used Fisher's exact tests and Kruskal-Wallis tests to compare characteristics between patient clusters.Six unique clusters of patients with CLE were identified from the cluster analysis. We observed that seven inflammation modules were elevated in two clusters of patients with CLE. Additionally, these clusters were characterized by interferon, neutrophil and cell-death signatures, suggesting that interferon-related proteins, neutrophils and cell-death processes could be driving the inflammatory response in these subgroups. Three different clusters had a predominant T-cell signature, which were supported by lymphocyte counts.Our data support a diverse molecular profile in CLE that further adds to the clinical variations of this skin disease, and may affect disease course and treatment selection. Future studies with a larger and diverse cohort of patients with CLE are warranted to confirm these findings.
Current Indications for Transcatheter Mitral Valve Replacement Using Transcatheter Aortic Valves
Authors: Marina Urena, Alec Vahanian, Eric Brochet, Gregory Ducrocq, Bernard Iung, Dominique Himbert
Journal: Circulation (2021)

Use of transcatheter mitral valve replacement (TMVR) using transcatheter aortic valves in clinical practice is limited to patients with failing bioprostheses and rings or mitral valve disease associated with severe mitral annulus calcification. Whereas the use of valve-in-valve TMVR appears to be a reasonable alternative to surgery in patients at high surgical risk, much less evidence supports valve-in-ring and valve-in-mitral annulus calcification interventions. Data on the results of TMVR in these settings are derived from small case series or voluntary registries. This review summarizes the current evidence on TMVR using transcatheter aortic valves in clinical practice from the characteristics of the TMVR candidates, screening process, performance of the procedure, and description of current results and future perspectives. TMVR using dedicated devices in native noncalcified mitral valve diseases is beyond the scope of the article.
Current results and expectations of renal transplantation
Journal: JAMA (1981)

Results of renal transplantation performed at seven centers during the years 1977 and 1978 were evaluated. One-year patient survival rates for recipients of living related and cadaver grafts were 95.1% and 88.6%, respectively. One-year graft survival rates were 78.6% and 55% for living-related and cadaver transplants. Postoperative surgical complication rates were low. These results reflect recent improvements in patient care and characterize current performance expectations of renal transplant centers.