tbuckley/cabot-search huggingface dataset:
True, True, and Unrelated—Complications and Survival After Hybrid Minimally Invasive Esophagectomy
Authors: Katherine D. Gray, Daniela Molena
Journal: JAMA Surgery (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Surgery HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Surgery journal
Pathology in Relationships
Authors: Susan C. South
Journal: Annual Review of Clinical Psychology (2021)

Committed, long-term romantic relationships are ubiquitous among modern society. They are one of the most important contexts for the development, maintenance, and treatment of psychopathology. In this review, I first place psychopathology within the most commonly cited theoretical model of marital satisfaction and stability and then discuss how relationship satisfaction is conceptualized and assessed in this literature. In the second half of the review, I describe the theories regarding how romantic relationships may be connected to psychopathology. Relationship distress is easily incorporated into a diathesis–stress model as an important trigger for psychopathology. Next, I review cross-sectional research, longitudinal research, and treatment efficacy research linking relationship quality and psychopathology. I provide evidence for the robustness of these effects and areas where research must expand. I finish with a summary section that synthesizes what is known about the mechanisms linking relationship distress and psychopathology.
Proof of concept for a rapidly switchable universal CAR-T platform with UniCAR-T-CD123 in relapsed/refractory AML
Authors: Martin Wermke, Sabrina Kraus, Armin Ehninger, Ralf C. Bargou, Maria-Elisabeth Goebeler, Jan Moritz Middeke, Carla Kreissig, Malte von Bonin, Jan Koedam, Michael Pehl, Martin Bornhäuser, Hermann Einsele, Gerhard Ehninger, Marc Cartellieri
Journal: Blood (2021)
Paclitaxel mitigates structural alterations and cardiac conduction system defects in a mouse model of Hutchinson–Gilford progeria syndrome
Authors: Álvaro Macías, J Jaime Díaz-Larrosa, Yaazan Blanco, Víctor Fanjul, Cristina González-Gómez, Pilar Gonzalo, María Jesús Andrés-Manzano, Andre Monteiro da Rocha, Daniela Ponce-Balbuena, Andrew Allan, David Filgueiras-Rama, José Jalife, Vicente Andrés
Journal: Cardiovascular Research (2021)

Abstract Aims Hutchinson–Gilford progeria syndrome (HGPS) is an ultrarare laminopathy caused by expression of progerin, a lamin A variant, also present at low levels in non-HGPS individuals. HGPS patients age and die prematurely, predominantly from cardiovascular complications. Progerin-induced cardiac repolarization defects have been described previously, although the underlying mechanisms are unknown. Methods and results We conducted studies in heart tissue from progerin-expressing LmnaG609G/G609G (G609G) mice, including microscopy, intracellular calcium dynamics, patch-clamping, in vivo magnetic resonance imaging, and electrocardiography. G609G mouse cardiomyocytes showed tubulin-cytoskeleton disorganization, t-tubular system disruption, sarcomere shortening, altered excitation–contraction coupling, and reductions in ventricular thickening and cardiac index. G609G mice exhibited severe bradycardia, and significant alterations of atrio-ventricular conduction and repolarization. Most importantly, 50% of G609G mice had altered heart rate variability, and sinoatrial block, both significant signs of premature cardiac aging. G609G cardiomyocytes had electrophysiological alterations, which resulted in an elevated action potential plateau and early afterdepolarization bursting, reflecting slower sodium current inactivation and long Ca+2 transient duration, which may also help explain the mild QT prolongation in some HGPS patients. Chronic treatment with low-dose paclitaxel ameliorated structural and functional alterations in G609G hearts. Conclusions Our results demonstrate that tubulin-cytoskeleton disorganization in progerin-expressing cardiomyocytes causes structural, cardiac conduction, and excitation–contraction coupling defects, all of which can be partially corrected by chronic treatment with low dose paclitaxel.
Abstract 10878: Global Longitudinal Strain or Ejection Fraction as a Marker of LV Function in a Multicentre Trial: Stability Over Time in the SUCCOUR Trial
Authors: Tomoko Negishi, Paaladinesh Thavendiranathan, Martin Penicka, Jonathan Deblois, Svend Aakhus, Sakiko Miyazaki, Dragos Vinereanu, Mitra Shirazi, Goo-Yeong Cho, Krassimira Hristova, Bogdan A Popescu, Maurizio Galderisi, Kazuaki Negishi, Thomas H Marwick
Journal: Circulation (2018)

Introduction: Ejection fraction (EF) has been widely used in the assessment of LV function but global longitudinal strain (GLS) is more reproducible and has been adopted in cardio-oncology recommen...
Endothelium-derived semaphorin 3G attenuates ischemic retinopathy by coordinating β-catenin–dependent vascular remodeling
Authors: Dan-Yang Chen, Ning-He Sun, Xiang Chen, Jun-Jie Gong, Song-Tao Yuan, Zi-Zhong Hu, Nan-Nan Lu, Jakob Körbelin, Kohji Fukunaga, Qing-Huai Liu, Ying-Mei Lu, Feng Han
Journal: Journal of Clinical Investigation (2021)

Abnormal angiogenesis and regression of the diseased retinal vasculature are key processes associated with ischemic retinopathies, but the underlying mechanisms that regulate vascular remodeling remain poorly understood. Here, we confirmed the specific expression of semaphorin 3G (Sema3G) in retinal endothelial cells (ECs), which was required for vascular remodeling and the amelioration of ischemic retinopathy. We found that Sema3G was elevated in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and in the neovascularization regression phase of oxygen-induced retinopathy (OIR). Endothelial-specific Sema3G knockout mice exhibited decreased vessel density and excessive matrix deposition in the retinal vasculature. Moreover, loss of Sema3G aggravated pathological angiogenesis in mice with OIR. Mechanistically, we demonstrated that HIF-2α directly regulated Sema3G transcription in ECs under hypoxia. Sema3G coordinated the functional interaction between β-catenin and VE-cadherin by increasing β-catenin stability in the endothelium through the neuropilin-2 (Nrp2)/PlexinD1 receptor. Furthermore, Sema3G supplementation enhanced healthy vascular network formation and promoted diseased vasculature regression during blood vessel remodeling. Overall, we deciphered the endothelium-derived Sema3G-dependent events involved in modulating physiological vascular remodeling and regression of pathological blood vessels for reparative vascular regeneration. Our findings shed light on the protective effect of Sema3G in ischemic retinopathies.
Immunomodulatory therapies for SARS-CoV-2 infection: a systematic literature review to inform EULAR points to consider
Authors: Alessia Alunno, Aurélie Najm, Xavier Mariette, Gabriele De Marco, Jenny Emmel, Laura Mason, Dennis G McGonagle, Pedro M Machado
Journal: Annals of the Rheumatic Diseases (2021)

To summarise the available information on efficacy and safety of immunomodulatory agents in SARS-CoV-2 infection.
ZAP-70 constitutively regulates gene expression and protein synthesis in chronic lymphocytic leukemia
Authors: Jingyu Chen, Vijitha Sathiaseelan, Andrew Moore, Shengjiang Tan, Chandra Sekkar Reddy Chilamakuri, Valar Nila Roamio Franklin, Arash Shahsavari, Constanze A. Jakwerth, Sandra B. Hake, Alan J. Warren, Irina Mohorianu, Clive D’Santos, Ingo Ringshausen
Journal: Blood (2021)
Molecular Features of Cancer-associated Fibroblast Subtypes and their Implication on Cancer Pathogenesis, Prognosis, and Immunotherapy Resistance
Authors: Phillip M. Galbo, Xingxing Zang, Deyou Zheng
Journal: Clinical Cancer Research (2021)

Cancer-associated fibroblasts (CAFs) are an important component of the tumor microenvironment, but a systematic investigation of their molecular characteristics and clinical relevance are lacking. Here, we sought to compare CAFs across multiple cancer types to identify critical molecular pathways activated in CAF subtypes, which may contribute to clinical outcome, disease progression, and immunotherapy resistance.We performed integrated analysis of CAFs from melanoma, head and neck squamous cell carcinoma, and lung cancer, and identified the molecular characteristics that are distinctly active in each CAF subtype. Gene signatures for individual CAF subtypes were identified and used to study the association of subtype abundance with clinical outcome and immunotherapy resistance.We identified six CAF subtypes (pan-CAF) shared across cancer types and uncovered the molecular characteristics and genetic pathways distinguishing them. Interestingly, these CAF subtypes express distinct immunosuppressive factors, such as CXCL12 and CXLC14, and stem cell-promoting factor IL6. In addition, we identified novel transcriptional drivers (MEF2C, TWIST1, NR1H3, RELB, and FOXM1) key to CAF heterogeneity. Furthermore, we showed that CAF subtypes were associated with different clinical outcomes and uncovered key molecular pathways that could activate or suppress cancer progression or were involved in resistance to anti-PD1 or anti-PD-L1 immunotherapy.Our study identifies the molecular characteristics of CAF subtypes shared across several cancer types, implicates cancer types that may benefit from CAF subtype targeted therapies, and identifies specific CAF subtypes associated with immunotherapy resistance.
Polyglutamic acid-based crosslinked doxorubicin nanogels as an anti-metastatic treatment for triple negative breast cancer
Authors: Aroa Duro-Castano, Ana Sousa-Herves, Ana Armiñán, David Charbonnier, Juan José Arroyo-Crespo, Stefanie Wedepohl, Marcelo Calderón, María J. Vicent
Journal: Journal of Controlled Release (2021)
From the origin of NASH to the future of metabolic fatty liver disease
Authors: Andreas Geier, Dina Tiniakos, Helmut Denk, Michael Trauner
Journal: Gut (2021)

Non-alcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide. Understanding the pathological and molecular hallmarks from its first description to definitions of disease entities, classifications and molecular phenotypes is crucial for both appropriate clinical management and research in this complex disease. We provide an overview through almost two hundred years of clinical research from the beginnings as a nebulous disease entity of unknown origin in the 19th century to the most frequent and vigorously investigated liver disease today. The clinical discrimination between alcohol-related liver disease and NAFLD was uncommon until the 1950s and likely contributed to the late acceptance of NAFLD as a metabolic disease entity for long time. Although the term ‘fatty liver hepatitis’ first appeared in 1962, it was in 1980 that the term ‘non-alcoholic steatohepatitis’ (NASH) was coined and the histopathological hallmarks that are still valid today were defined. The 2005 NASH Clinical Research Network scoring was the first globally accepted grading and staging system for the full spectrum of NAFLD and is still used to semiquantify main histological features. In 2021, liver biopsy remains the only diagnostic procedure that can reliably assess the presence of NASH and early fibrosis but increasing efforts are made towards non-invasive testing and molecular classification of NAFLD subtypes.
Irvin Alexander Lampert
Authors: Jo Boxer
Journal: BMJ (2021)

Irvin Alexander Lampert was born in Johannesburg to fairly orthodox Jewish parents. After qualifying he did house jobs at Johannesburg General Hospital and Baragwanath Hospital, Soweto, during a famine before entering pathology in 1966 at the South African Institute for Medical Research. In 1969 he moved to the UK and became an assistant lecturer at the University of Nottingham with K Weinbren. In 1970 he began his long association with the Royal Postgraduate Medical School, first spending a year on the DCP Course, then as registrar and senior registrar at Hammersmith Hospital, before being appointed a senior lecture and honorary …
ATP citrate lyase is a potential therapeutic target for suppression of aberrant metabolic adaptation in glycolytic brain tumors
Authors: Marie Beckner, Naomi Agostino, Wendy Fellows-Mayle, Jeffrey Kant, Ian Pollack
Journal: Cancer Research (2008)

1208  ATP citrate lyase (ACLY) cleaves citric acid, a tricarboxylic acid that is released from inactive mitochondria, thus moderating cytosolic levels of citric acid. Although ACLY is better known for its role in production of lipids, its control of metabolic acid levels may permit liberation of glycolytic cells from vascular dependence during invasion. The lack of vascular dependence for glycolytic tumor cells is proposed as a malignant feature that is a consequence of ACLYs increased expression and activity. Levels of ACLY expression were increased at least 2-fold in 51 of 163 brain tumors and were associated with significantly decreased survival of the patients, p = 0.0062. Expression of ACLY was increased in 37 of the 87 glioblastomas included in the same group. In glioblastomas there were concordantly increased expressions of one or more growth factors (epidermal growth factor (EGF), hepatocyte growth factor (HGF), insulin like growth factor 2 (IGF2), platelet derived growth factor (PDGF) A, and PDGFB) in 32 (86.5%) of 37 cases (Respository of Molecular Brain Neoplasia Database (REMBRANDT), NCI, NINDS, NIH). In cell culture, a competitive inhibitor of ACLY, hydroxycitrate, suppressed glycolytic migration of U87 and LN229 glioblastoma cells. When combined with SU11274, an inhibitor of the HGF receptor, Met, hydroxycitrate lowered the IC50 of SU11274 by 48%, a significant (p
Evaluation of Deviation From Planned Cohort Size and Operating Characteristics of Phase 1 Trials
Authors: Minjeong Park, Suyu Liu, Timothy Anthony Yap, Ying Yuan
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The cohort size of phase 1 clinical trials and thus the timing of the interim decisions are typically prespecified in the trial protocol. During trial implementation, however, the cohort size often deviates from the planned one, which shifts the schedule of the interims. Despite its pervasiveness in phase 1 trials, the association of cohort size deviation with the operating characteristics of these trials is not clear. <h3>Objective</h3> To explore the association between cohort size deviation and the operating characteristics of phase 1 clinical trials. <h3>Design, Setting, and Participants</h3> In this cross-sectional simulation study, a review was conducted of 102 phase 1 dose-escalation trials published between January 2017 and May 2018 in 3 peer-reviewed journals (<i>Journal of Clinical Oncology</i>,<i>Clinical Cancer Research</i>, and<i>Cancer</i>). After exclusion of studies that did not report the cohort size, 45 trials remained for analysis. Based on the analysis results, a simulation study was performed to systematically investigate the association of cohort size deviation with the operating characteristics of the trials. <h3>Main Outcomes and Measures</h3> The prevalence of cohort size deviation and the percentage of correct selection of the maximum tolerated dose. <h3>Results</h3> Of the 45 reviewed trials, 10 (22.2%) adhered strictly to the planned cohort size. The simulation study showed that when cohort size deviation was random, it had little association with the performance of novel model-based and model-assisted designs (mean reduction in the percentage of correct selection of the maximum tolerated dose was 0.87 percentage point for the continual reassessment method and 0.84 percentage point for the bayesian optimal interval design). When the cohort size deviation was informative and made based on the observed data on toxicity (eg, if dose-limiting toxicity was observed, the size of the next or current cohort was reduced or expanded), the variation of the design performance increased. The range of the change in the percentage of correct selection was −3.7 to 1.3 percentage points for the continual reassessment method and −4.5 to 0 percentage points for the bayesian optimal interval design. <h3>Conclusions and Relevance</h3> The findings suggest that when novel phase 1 clinical trial designs are used, some cohort size deviation is acceptable and has little association with the performance of the designs. These deviations may be used by expert investigators to properly interpret the data, ensure safety, and leverage flexibility in the protocol.
Importance of non-pharmaceutical interventions in lowering the viral inoculum to reduce susceptibility to infection by SARS-CoV-2 and potentially disease severity
Authors: Matthew A Spinelli, David V Glidden, Efstathios D Gennatas, Michel Bielecki, Chris Beyrer, George Rutherford, Henry Chambers, Eric Goosby, Monica Gandhi
Journal: The Lancet Infectious Diseases (2021)

Adherence to non-pharmaceutical interventions to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been highly variable across settings, particularly in the USA. In this Personal View, we review data supporting the importance of the viral inoculum (the dose of viral particles from an infected source over time) in increasing the probability of infection in respiratory, gastrointestinal, and sexually transmitted viral infections in humans. We also review the available evidence linking the relationship of the viral inoculum to disease severity. Non-pharmaceutical interventions might reduce the susceptibility to SARS-CoV-2 infection by reducing the viral inoculum when there is exposure to an infectious source. Data from physical sciences research suggest that masks protect the wearer by filtering virus from external sources, and others by reducing expulsion of virus by the wearer. Social distancing, handwashing, and improved ventilation also reduce the exposure amount of viral particles from an infectious source. Maintaining and increasing non-pharmaceutical interventions can help to quell SARS-CoV-2 as we enter the second year of the pandemic. Finally, we argue that even as safe and effective vaccines are being rolled out, non-pharmaceutical interventions will continue to play an essential role in suppressing SARS-CoV-2 transmission until equitable and widespread vaccine administration has been completed.
Effect of dapagliflozin on anaemia in <scp>DAPA‐HF</scp>
Authors: Kieran F. Docherty, James P. Curtain, Inder S. Anand, Olof Bengtsson, Silvio E. Inzucchi, Lars Køber, Mikhail N. Kosiborod, Anna Maria Langkilde, Felipe A. Martinez, Piotr Ponikowski, Marc S. Sabatine, Morten Schou, Mikaela Sjöstrand, Scott D. Solomon, Pardeep S. Jhund, John J.V. McMurray
Journal: European Journal of Heart Failure (2021)

Anaemia is common in heart failure and associated with worse outcomes. We examined the effect of dapagliflozin on correction of anaemia in patients with heart failure (HF) and reduced ejection fraction in DAPA-HF. We also analysed the effect of dapagliflozin on outcomes, according to anaemia status at baseline.
Letter to the editor: Excess all-cause mortality during second wave of COVID-19 – the Polish perspective
Authors: Jakub Grabowski, Natalia Witkowska, Leszek Bidzan
Journal: Eurosurveillance (2021)

Preview this article: Letter to the editor: Excess all-cause mortality during second wave of COVID-19 – the Polish perspective, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/26/7/eurosurv-26-7-3-1.gif
Abstract 17043: Enhanced Na <sup>+</sup> Influx Alters Myocyte Mechanics and Diastolic Function
Authors: Alejandro Andrade-Vicenty, Chaoyu Sun, Daniel Cervantes, Saketh Anand, Dong Sun, Heather O’Malley, Lori Isom, Thomas H Hintze, Marcello Rota
Journal: Circulation (2018)

The late Na + current has emerged as a therapeutic target for conditions characterized by depressed diastolic function, but whether enhanced Na + fluxes in cardiomyocytes interfere with cellular and myocardial relaxation remain to be clarified. For this purpose, we employed mice with inducible, cardiac restricted deletion of the non-pore forming beta1 subunit of the Na + channel ( Scn1b -KO), a rodent model associated with enhanced Na + influx in cardiomyocytes. Two-dimensional and Doppler echocardiography and ECGs were employed to evaluate cardiac function in Scn1b -KO and control (Ctrl) animals. Properties of Ca 2+ transient and contractility were established in isolated left ventricular (LV) myocytes obtained by enzymatic digestion. Deletion of the Scn1b gene had no consequences on ejection fraction, whereas LV filling pattern was altered, isovolumic relaxation time prolonged (+30%), and electrical recovery, measured by the QT interval, was protracted (+14%). In a subgroup of animals, acute administration of GS967 (0.5 mg/kg body weight), a specific inhibitor of the late Na + current, partly ameliorated diastolic indices and shortened the QT interval. At the cellular level, kinetics of cell shortening and Ca 2+ transients were delayed in Scn1b -KO myocytes (n=609-693), with respect to Ctrl cells (369-298). Specifically, time to peak Ca 2+ and time to 50% decay of the Ca 2+ transient were increased in Scn1b -KO cells by 5% and 17%, respectively. Similarly, time to peak contraction and time to 50% relaxation were enhanced by 6% and 7% in Scn1b -KO. Interestingly, GS967 (300 nM) accelerated temporal parameters of contraction in Scn1b -KO myocytes by ~8% and led to an attenuation of fractional shortening. These effects were not observed in Ctrl cells. Thus, enhanced Na + influx modulates electromechanical coupling in cardiomyocytes and delays kinetics of contraction and relaxation with consequences on diastolic properties of the heart.
Caution With Routine Use of Daratumumab for Newly Diagnosed High-Risk Multiple Myeloma
Authors: Ghulam Rehman Mohyuddin, Al-Ola Abdallah, Brian McClune
Journal: JAMA Oncology (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal