tbuckley/cabot-search huggingface dataset:
Inherited cardiomyopathies
Authors: Chris Miles, Zephryn Fanton, Maite Tome, Elijah R Behr
Journal: BMJ (2019)

Cardiomyopathies are structural and functional disorders of the heart muscle.They are common, often 3 inherited, and an important cause of sudden cardiac death.Herein, we provide an overview of 4 diagnosis, genetic evaluation, and management of inherited cardiomyopathies for non-specialists.We 5 focus on the key role of the general practitioner in recognising symptoms and clues from the family 6 history.Further specialist evaluation is discussed alongside updated guidance from national and 7 international bodies.8 9 WHAT ARE THE CAUSES? 10 11 Cardiomyopathies are broadly divided into genetic and non-genetic causes, the former being inherited 12 cardiomyopathies.Non-genetic causes are classified as idiopathic or may be acquired, resulting from 13 metabolic, endocrinological, or inflammatory disorders, pregnancy, amyloidosis, infections, and toxic 14 agents including drugs and alcohol.Most inherited cardiomyopathies are single gene (monogenic) 15 disorders with an autosomal dominant pattern and a 50% risk of transmission to a child.The main 16 inherited cardiomyopathies are: Hypertrophic Cardiomyopathy (HCM), Dilated Cardiomyopathy (DCM), 17 and Arrhythmogenic Cardiomyopathy (ACM )(Figure 1).DCM may be considered genetic or acquired.18 19 HOW COMMON ARE THEY? 20 21 Inherited cardiomyopathies are found among all ethnicities and populations.HCM is the most common What you need to know  Inherited cardiomyopathies are common and a major cause of heart disease across all age groups. Asymptomatic individuals may still be at risk from sudden cardiac death. The ECG and echocardiogram will detect the majority of cardiomyopathies, but further evaluation may include additional ECG testing, specialist imaging, and genetic testing. Assessment of family members should be considered at an early stage with involvement of specialist centres.
Letter: Fetal activity and fetal wellbeing.
Journal: BMJ (1976)

phenomenon of inter-laboratory variation in MICs, there is no published evidence which suggests that yeasts isolated in the late 1950s are more sensitive than those isolated in the 1970s.Thus, there seems to be no firm indication that the basic premise involved here, that polyene-resistant fungi have not emerged, is false, and indeed there seems every reason to suppose it to be true."From a clinical point of view Stieritz et a16 found that no resistance occurred when amphotericin was given systemically.Witb this lack of evidence that resistance occurs we made available oral and topical amphotericin in 1970.Since at that time amphotericin was the only drug available for systemic use we would clearly not have developed other forms if we had known that resistant strains could develop.I would be grateful therefore if you could let us have the substantiated evidence that resistance occurs to amphotericin.While it is known that resistance may occur to 5 fluorocytosine (another systemic antifungal agent in use), to our knowledge this has not been the case with amphotericin.
Endemic Cardiovascular Diseases of the Poorest Billion
Authors: Gene F. Kwan, Bongani M. Mayosi, Ana O. Mocumbi, J. Jaime Miranda, Majid Ezzati, Yogesh Jain, Gisela Robles, Emelia J. Benjamin, S. V. Subramanian, Gene Bukhman
Journal: Circulation (2016)

The poorest billion people are distributed throughout the world, though most are concentrated in rural sub-Saharan Africa and South Asia. Cardiovascular disease (CVD) data can be sparse in low- and middle-income countries beyond urban centers. Despite this urban bias, CVD registries from the poorest countries have long revealed a predominance of nonatherosclerotic stroke, hypertensive heart disease, nonischemic and Chagas cardiomyopathies, rheumatic heart disease, and congenital heart anomalies, among others. Ischemic heart disease has been relatively uncommon. Here, we summarize what is known about the epidemiology of CVDs among the world's poorest people and evaluate the relevance of global targets for CVD control in this population. We assessed both primary data sources, and the 2013 Global Burden of Disease Study modeled estimates in the world's 16 poorest countries where 62% of the population are among the poorest billion. We found that ischemic heart disease accounted for only 12% of the combined CVD and congenital heart anomaly disability-adjusted life years (DALYs) in the poorest countries, compared with 51% of DALYs in high-income countries. We found that as little as 53% of the combined CVD and congenital heart anomaly burden (1629/3049 DALYs per 100 000) was attributed to behavioral or metabolic risk factors in the poorest countries (eg, in Niger, 82% of the population among the poorest billion) compared with 85% of the combined CVD and congenital heart anomaly burden (4439/5199 DALYs) in high-income countries. Further, of the combined CVD and congenital heart anomaly burden, 34% was accrued in people under age 30 years in the poorest countries, while only 3% is accrued under age 30 years in high-income countries. We conclude although the current global targets for noncommunicable disease and CVD control will help diminish premature CVD death in the poorest populations, they are not sufficient. Specifically, the current framework (1) excludes deaths of people <30 years of age and deaths attributable to congenital heart anomalies, and (2) emphasizes interventions to prevent and treat conditions attributed to behavioral and metabolic risks factors. We recommend a complementary strategy for the poorest populations that targets premature death at younger ages, addresses environmental and infectious risks, and introduces broader integrated health system interventions, including cardiac surgery for congenital and rheumatic heart disease.
Virus Like Particle (VLP) Based Peanut Allergen Immunotherapy Candidate Display A Decreased Activation And Histamine Release From CRTH2+ Basophils: A Proof of Concept Study
Authors: Mohamed Shamji, Janice Layhadi, Paul Turner, Nandinee Patel, Rebecca Parkin, Kemi Oluwayi, Olesya Rusyn, Murray Skinner, Matthew Heath, Matthias Kramer, Pieter-Jan de Kam
Journal: Journal of Allergy and Clinical Immunology (2022)
Immunologic aspects of endocrine diseases
Authors: G. N. Beall
Journal: JAMA (1987)

ENDOCRINE organs seem predisposed to autoimmunity. This is particularly true for the thyroid gland, in which most of the common diseases are caused by immune mechanisms.<sup>1-3</sup>The evidence for participation of immune mechanisms in endocrine diseases is based on many observations. Organspecific antibodies or cell-mediated immune processes have often been found. The affected organ often contains lymphocytes that are suspected, and in some instances proved, to have the ability to synthesize autoantibody or damage tissue. A marked overlap of diseases and serological markers has been found both in individuals and in families. This evidence of genetic predisposition has been further underscored by the tendency for certain HLA haplotypes to be overrepresented in diseased individuals. Many of the diseases are more common in women than in men. Table 15-1 contains a list of endocrine diseases or syndromes that have been defined clearly enough for discussion in this chapter. <h3>THYROID DISEASES</h3>
Targeting KDM4C enhances CD8<sup>+</sup> T cell mediated antitumor immunity by activating chemokine CXCL10 transcription in lung cancer
Authors: Xiaohua Jie, Yunshang Chen, Ye Zhao, Xijie Yang, Yingzhuo Xu, Jian Wang, Rui Meng, Sheng Zhang, Xiaorong Dong, Tao Zhang, Kunyu Yang, Shuangbing Xu, Gang Wu
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Although immune checkpoint blockade (ICB) has been proven to achieve a persistent therapeutic response in various tumor types, only 20%–40% of patients benefit from this treatment. Radiotherapy (RT) can enhance tumor immunogenicity and improve the ICB response, but the outcome achieved by combining these two modalities remains clinically unsatisfactory. We previously uncovered that lysine-specific demethylase 4C (KDM4C) is a regulator of radiosensitivity in lung cancer. However, the role of KDM4C in antitumor immunity has not yet been investigated. Methods Infiltrating immune cells in our mouse tumor model were screened by flow cytometry. An in vivo subcutaneous transplanted tumor model and in vitro conditioned culture model were constructed to detect the quantitative and functional changes in CD8 + T cells. RNA sequencing and chromatin immunoprecipitation-PCR assays were used to explore the downstream regulatory mechanism of KDM4C in antitumor immunity. A C57BL/6 mouse tumor model was developed to evaluate the efficacy and safety of a triple therapy (the KDM4C-specific inhibitor SD70 plus RT and an anti-PD-L1 antibody) in lung cancer in vivo. Results Genetical or pharmacological inhibition of KDM4C specifically increased CD8 + T cell infiltration; promoted the proliferation, migration and activation of CD8 + T cells; and alleviated CD8 + T cell exhaustion in mouse tumor tissues. Mechanistically, KDM4C inhibition increased the binding of H3K36me3 to the CXCL10 promoter region, thus inducing CXCL10 transcription and enhancing the CD8 + T cell mediated antitumor immune response. More importantly, among the tested regimens, the triple therapy achieved the best therapeutic efficacy with tolerable toxicity in lung cancer. Conclusions Our data reveal a crucial role for KDM4C in antitumor immunity in lung cancer and indicate that targeting KDM4C in combination with radioimmunotherapy might be a promising synergistic strategy in lung cancer.
Delivery of CD47 blocker SIRPα-Fc by CAR-T cells enhances antitumor efficacy
Authors: Huanpeng Chen, Yuying Yang, Yuqing Deng, Fengjiao Wei, Qingyu Zhao, Yongqi Liu, Zhonghua Liu, Bolan Yu, Zhaofeng Huang
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Chimeric antigen receptor (CAR) T cell therapy has been successfully applied in treating lymphoma malignancies, but not in solid tumors. CD47 is highly expressed on tumor cells and its overexpression is believed to inhibit phagocytosis by macrophages and dendritic cells. Given the antitumor activity against preclinical model of CD47-blocking to induce the innate and adaptive immune system in the tumor microenvironment, here we developed a CAR-T cell secreting CD47 blocker signal regulatory protein α (SIRPα)-Fc fusion protein (Sirf CAR-T) to boost CAR-T cell therapeutic effect in solid tumor therapy. Methods Murine T cells were transduced to express a conventional anti-Trop2 CAR and Sirf CAR. The expression of SIRPα-Fc fusion protein in the supernatant of CAR-T cells and its effect on macrophage phagocytosis were tested in vitro. In vivo antitumor efficacy of CAR-T cells was evaluated in immunocompetent mice and analysis of the tumor microenvironment in the tumor-bearing mice was performed. Results We found that Sirf CAR-T cells dramatically decreased tumor burden and significantly prolonged survival in several syngeneic immunocompetent tumor models. Furthermore, we found that Sirf CAR-T cells induced more central memory T cells (T CM ) and improved the persistence of CAR-T cells in tumor tissue, as well as decreased PD-1 expression on the CAR-T cell surface. In addition, we demonstrated that Sirf CAR-T cells could modulate the tumor microenvironment by decreasing myeloid-derived stem cells as well as increasing CD11c + dendritic cells and M1-type macrophages in tumor tissue. Conclusions In summary, our findings indicate that CD47 blocker SIRPα-Fc enhances the antitumor efficacy of CAR-T cells and propose to block CD47/SIRPα signaling effect on CAR-T cells function, which could provide a new strategy for successful cancer immunotherapy by rationalizing combination of CD47 blocker and CAR-T cell therapy.
Canadian Medical Association Journal, Toronto
Journal: JAMA (1962)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Hyperelastic Membrane Actuators: Analysis of Toroidal and Helical Multifunctional Configurations
Authors: Eduardo Perez-Guagnelli, Joanna Jones, Dana D. Damian
Journal: Cyborg and Bionic Systems (2022)

Technologies that provide mechanical assistance are required in the medical field, such as implants that regenerate tissue through elongation and stimulation. One of the challenges is to develop actuators that combine the benefits of high axial extension at low pressures, modularity, multifunction, and load-bearing capabilities into one design while maintaining their shape and softness. Overcoming such a challenge will provide implants with enhanced capacity for mechanical assistance to induce tissue regeneration. We introduce two novel actuators (M2H) built of stacked Hyperelastic Ballooning Membrane Actuators (HBMAs) that can be realized using helical and toroidal configurations. By restraining the HBMA expansion deterministically using a semisoft exoskeleton, the actuators are endowed with axial extension and radial expansion capabilities. These actuators are thus built of modules that can be configured to different therapeutical needs and multifunctionality, to provide anatomically congruent stimulation. We present the design, fabrication, testing, and numerical and experimental validation of the M2H-HBMAs. They can axially extend up to 41% and 32% in their helical and toroidal configurations at input pressures as low as 26 and 24 kPa, respectively. If the axial extension module is used separately, its extension capacity reaches >170%. The M2H-HBMAs can perform independent and simultaneous expansion and extension motions with negligible intraluminal deformation as well as stand at least 1 kg of axial force without collapsing. The M2H-HBMAs overcome the limitations of hyperexpanding machines that show low resistance to load. We envisage M2H-HBMAs as promising tools to perform tissue regeneration procedures.
Platelet-mimicking procoagulant nanoparticles augment hemostasis in animal models of bleeding
Authors: Ujjal Didar Singh Sekhon, Kelsey Swingle, Aditya Girish, Norman Luc, Maria de la Fuente, Jurgis Alvikas, Shannon Haldeman, Adnan Hassoune, Kaisal Shah, Youjoung Kim, Steven Eppell, Jeffrey Capadona, Andrew Shoffstall, Matthew D. Neal, Wei Li, Marvin Nieman, Anirban Sen Gupta
Journal: Science Translational Medicine (2022)

Treatment of bleeding disorders using transfusion of donor-derived platelets faces logistical challenges due to their limited availability, high risk of contamination, and short (5 to 7 days) shelf life. These challenges could be potentially addressed by designing platelet mimetics that emulate the adhesion, aggregation, and procoagulant functions of platelets. To this end, we created liposome-based platelet-mimicking procoagulant nanoparticles (PPNs) that can expose the phospholipid phosphatidylserine on their surface in response to plasmin. First, we tested PPNs in vitro using human plasma and demonstrated plasmin-triggered exposure of phosphatidylserine and the resultant assembly of coagulation factors on the PPN surface. We also showed that this phosphatidylserine exposed on the PPN surface could restore and enhance thrombin generation and fibrin formation in human plasma depleted of platelets. In human plasma and whole blood in vitro, PPNs improved fibrin stability and clot robustness in a fibrinolytic environment. We then tested PPNs in vivo in a mouse model of thrombocytopenia where treatment with PPNs reduced blood loss in a manner comparable to treatment with syngeneic platelets. Furthermore, in rat and mouse models of traumatic hemorrhage, treatment with PPNs substantially reduced bleeding and improved survival. No sign of systemic or off-target thrombotic risks was observed in the animal studies. These findings demonstrate the potential of PPNs as a platelet surrogate that should be further investigated for the management of bleeding.
Correction: Supported Telemonitoring and Glycemic Control in People with Type 2 Diabetes: The Telescot Diabetes Pragmatic Multicenter Randomized Controlled Trial
Authors: Sarah H. Wild, Janet Hanley, Stephanie C. Lewis, John A. McKnight, Lucy B. McCloughan, Paul L. Padfield, Richard A. Parker, Mary Paterson, Hilary Pinnock, Aziz Sheikh, Brian McKinstry
Journal: PLoS Medicine (2016)

[This corrects the article DOI: 10.1371/journal.pmed.1002098.].
Hurricane Season Public Health Preparedness, Response, and Recovery Guidance for Health Care Providers, Response and Recovery Workers, and Affected Communities — CDC, 2017
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

CDC and the Agency for Toxic Substances and Disease Registry (ATSDR) have guidance and technical materials available in both English and Spanish to help communities prepare for hurricanes and floods (Table 1). To help protect the health and safety of the public, responders, and clean-up workers during response and recovery operations from hurricanes and floods, CDC and ATSDR have developed public health guidance and other resources; many are available in both English and Spanish (Table 2).
Correspondence
Authors: David H. Spodick
Journal: JAMA (1978)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Intertwined Interests in Expanded Prenatal Genetic Testing: The State’s Role in Facilitating Equitable Access
Authors: Lisa Dive, Ainsley J Newson, Isabella Holmes, Zuzana Deans, Kathryn MacKay
Journal: The American Journal of Bioethics (2022)

This article is referred to by:Access to Expanded Prenatal Genetic Testing: Response to Open Peer Commentaries
EValuating trEatment RESponses of dupilumab versus omalizumab in Type 2 patients: the EVEREST Trial
Authors: Lucia de Prado Gomez, Asif Khan, Anju Peters, Claus Bachert, Martin Wagenmann, Enrico Heffler, Claire Hopkins, Peter Hellings, Mei Zhang, Jun Xing, Paul Rowe, Juby Jacob-Nara
Journal: Journal of Allergy and Clinical Immunology (2022)
Evaluating Prognostic Factors for Sex Differences in Lung Cancer Survival: Findings From a Large Australian Cohort
Authors: Xue Qin Yu, Mei Ling Yap, Elvin S. Cheng, Preston J. Ngo, Pavla Vaneckova, Deme Karikios, Karen Canfell, Marianne F. Weber
Journal: Journal of Thoracic Oncology (2022)

<h2>Abstract</h2><h3>Introduction</h3> Women tend to survive a lung cancer diagnosis longer than men; however potential drivers of this sex-related disparity remain largely elusive. We quantified factors related to sex differences in lung cancer survival in a large prospective cohort in Australia. <h3>Methods</h3> Participants in the 45 and Up Study (recruited 2006–2009) diagnosed with incident lung cancer were followed up to December 2015. Prognostic factors were identified from questionnaire data linked with cancer registrations, hospital inpatient records, emergency department records, and reimbursement records for government-subsidized medical services and prescription medicines. Hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer death for men versus women were estimated using Cox proportional hazard regression in relation to key prognostic factors alone and jointly. <h3>Results</h3> A total of 488 women and 642 men were diagnosed with having lung cancer. Women survived significantly longer (median 1.28 versus 0.77 y; HR for men = 1.43, 95% CI: 1.25–1.64, <i>p</i> < 0.0001). The survival disparity remained when each subgroup of major prognostic factors was evaluated separately, including histologic subtype, stage at diagnosis, treatment received, and smoking status. Multivariable analyses revealed that treatment-related factors explained half of the survival difference, followed by lifestyle and tumor characteristics (explaining 28%, 26%, respectively). After adjusting for all major known prognostic factors, the excess risk for men was reduced by more than 80% (HR = 1.06, 95% CI: 0.96–1.18, <i>p</i> = 0.26). <h3>Conclusions</h3> The sex-related lung cancer survival disparity in this Australian cohort was largely accounted for by known prognostic factors, indicating an opportunity to explore sex differences in treatment preferences, options, and access.
Ultrasound‐Induced Mechanical Compaction in Acoustically Responsive Scaffolds Promotes Spatiotemporally Modulated Signaling in Triple Negative Breast Cancer
Authors: Brock A. Humphries, Mitra Aliabouzar, Carole Quesada, Avinash Bevoor, Kenneth K. Y. Ho, Alex Farfel, Johanna M. Buschhaus, Shrila Rajendran, Mario L. Fabiilli, Gary D. Luker
Journal: Advanced Healthcare Materials (2022)

Cancer cells continually sense and respond to mechanical cues from the extracellular matrix (ECM). Interaction with the ECM can alter intracellular signaling cascades, leading to changes in processes that promote cancer cell growth, migration, and survival. The present study used a recently developed composite hydrogel composed of a fibrin matrix and phase-shift emulsion, termed an acoustically responsive scaffold (ARS), to investigate effects of local mechanical properties on breast cancer cell signaling. Treatment of ARSs with focused ultrasound drives acoustic droplet vaporization (ADV) in a spatiotemporally controlled manner, inducing local compaction and stiffening of the fibrin matrix adjacent to the matrix-bubble interface. Combining ARSs and live single cell imaging of triple-negative breast cancer cells, it is discovered that both basal and growth-factor stimulated activities of protein kinase B (also known as Akt) and extracellular signal-regulated kinase (ERK), two major kinases driving cancer progression, negatively correlate with increasing distance from the ADV-induced bubble both in vitro and in a mouse model. Together, these data demonstrate that local changes in ECM compaction regulate Akt and ERK signaling in breast cancer and support further applications of the novel ARS technology to analyze spatial and temporal effects of ECM mechanics on cell signaling and cancer biology.