tbuckley/cabot-search huggingface dataset:
Donor Hepatic Occult Collagen Deposition Predisposes to Peritransplant Stress and Impacts Human Liver Transplantation
Authors: Hirofumi Hirao, Takahiro Ito, Kentaro Kadono, Hidenobu Kojima, Bita V. Naini, Kojiro Nakamura, Shoichi Kageyama, Ronald W. Busuttil, Jerzy W. Kupiec‐Weglinski, Fady M. Kaldas
Journal: Hepatology (2021)

Environmentally triggered chronic liver inflammation can cause collagen deposits, whereas early stages of fibrosis without any specific symptoms could hardly be detectable. We hypothesized that some of the human donor grafts in clinical liver transplantation (LT) might possess unrecognizable fibrosis, affecting their susceptibility to LT-induced stress and hepatocellular damage. This retrospective study aimed to assess the impact of occult hepatic fibrosis on clinical LT outcomes.Human (194) donor liver biopsies were stained for collagen with Sirius red, and positive areas (Sirius red-positive area; SRA) were measured. The body mass index, aspartate aminotransferase/alanine aminotransferase ratio, diabetes score was calculated using 962 cases of the donor data at the procurement. LT outcomes, including ischemia-reperfusion injury (IRI), early allograft dysfunction (EAD), and survival rates, were analyzed according to SRA and BARD scores. With the median SRA in 194 grafts of 9.4%, grafts were classified into low-SRA (<15%; n = 140) and high-SRA (≥15%; n = 54) groups. Grafts with high SRA suffered from higher rates of IRI and EAD (P < 0.05) as compared to those with low SRA. Interestingly, high SRA was identified as an independent risk factor for EAD and positively correlated with the donor BARD score. When comparing low-BARD (n = 692) with high-BARD (n = 270) grafts in the same period, those with high BARD showed significantly higher post-LT transaminase levels and higher rates of IRI and EAD.These findings from the largest clinical study cohort to date document the essential role of occult collagen deposition in donor livers on LT outcomes. High-SRA and donor BARD scores correlated with an increased incidence of hepatic IRI and EAD in LT recipients. This study provides the rationale for in-depth and prospective assessment of occult fibrosis for refined personalized LT management.
Abstract 2717: Brain Mammillary Body Volumes are Diminished in Heart Failure
Authors: Mary A Woo, Rajesh Kumar, Bramley V Birrer, Paul M Macey, Gregg C Fonarow, Michelle A Hamilton, Ronald M Harper
Journal: Circulation (2008)

Emotional and cognitive abnormalities, including memory deficits, are common in heart failure (HF). Mammillary bodies in the brain play essential roles in spatial and short-term memory processing, ...
Lessons from the pandemic: taking a covid-like approach to other diseases
Authors: Dipshikha Chakravortty, K S Nandakumar
Journal: BMJ (2021)

Preparing for the next pandemic is a global public health concern, which is well voiced by Wenham and colleagues.1 But a pertinent question might be: why do we care more about pandemics than other disease epidemics that kill millions of people worldwide every year? Should we take a covid-like approach to the research of other diseases? …
Long-Term Exposure to Particulate Matter Air Pollution and Chronic Rhinosinusitis in Nonallergic Patients
Authors: Zhenyu Zhang, Rebecca J. Kamil, Nyall R. London, Stella E. Lee, Venkataramana K. Sidhaye, Shyam Biswal, Andrew P. Lane, Jayant M. Pinto, Murugappan Ramanathan,
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

"Long-Term Exposure to Particulate Matter Air Pollution and Chronic Rhinosinusitis in Nonallergic Patients." American Journal of Respiratory and Critical Care Medicine, 204(7), pp. 859–862
Translational Nanomedicine: Translational Nanotherapeutics Reprograms Immune Microenvironment in Malignant Pleural Effusion of Lung Adenocarcinoma (Adv. Healthcare Mater. 12/2021)
Authors: Zhenhuan Song, Weizhan Luo, Haichong Zheng, Yunxiang Zeng, Jinlin Wang, Tianfeng Chen
Journal: Advanced Healthcare Materials (2021)
Abstract 15513: Reverse Cholesterol Transport is Maintained Despite Knockdown of CYP27A1 in Mice
Authors: Junko Arakawa, Makoto Ayaori, Takahumi Nishida, Makoto Sasaki, Yumiko Suenaga, Reiko Nita, Katsunori Ikewaki
Journal: Circulation (2018)

Reverse cholesterol transport (RCT) is a major anti-atherogenic property of HDL by which peripheral cholesterol is transported back to the liver for secretion into bile and finally feces. Bile acid...
Integrative Oncogenomic Analysis Combining Whole Genome, Transcriptome and Epigenome Identifies Altered Chromatin Accessibility Landscape in Multiple Myeloma
Authors: Raphael Szalat, Mehmet Kemal Samur, Christopher J. Ott, Matthew Lawlor, Charles Epstein, Brian J Abraham, Charles Y Lin, Linying Zhang, Rao Prabhala, Nina Farrell, Kenneth Wes, Yu-Tzu Tai, Mariateresa Fulciniti, Giovanni Parmigiani, Richard A. Young, Kenneth C Anderson, Nikhil Munshi
Journal: Blood (2017)
Lung function and exercise capacity after severe COVID-19
Authors: G. Moreira-Hetzel, G. D. S. Viana, R. M. C. da Silva, I. G. Benedetto, M. B. Gazzana, D. C. Berton
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: COVID-19 can progress to severe disease requiring hospitalization and oxygen support in around 14% of the cases and 5% require admission in intensive care unit. The consequences of severe COVID-19 on lung function and exercise capacity remain to be determined. Methods: A multicenter prospective cohort study that aims to evaluate the early (Visit 1: 2-6 months after acute disease) and late (Visit 2: 9-15 months and Visit 3: 18- 24 months) effects of severe acute respiratory syndrome on lung function, exercise capacity, respiratory symptoms and health related quality of life in patients with confirmed diagnosis of SARS-CoV-2 infection by PCRRT from nasal swab (ClinicalTrials.gov: NCT04410107). Severe disease was defined by respiratory rate > 30breaths/min, peripheral oxygen saturation ≤93% on room air and/or by the presence of infiltrates > 50% on chest imaging in the first two days after laboratorial confirmation. This is a preliminary report of spirometry, lung volumes by body plethysmography, lung diffusion capacity for carbon monoxide (DLCO), and performance during 6-minute walk test (6MWT) after 2-6 months (early evaluation) of severe COVID-19. Results: 51 patients were included: 54% male, 55.4±12.9 yrs-old, 23 (45%) were current or former smokers. Around half (45%) were admitted to the ICU and 26 (50%) received ventilatory support (invasive or non-invasive). The most frequent comorbidities were systemic hypertension (41%), obesity (29%), and 9% reported history of previous respiratory disease. Mean lung function parameters were (% predicted): FEV1= 85±18;FVC= 82±16;total lung capacity (TLC)= 87±14;residual volume= 93±40;DLCO= 74±17;6-min walk distance= 85±20. Mean pulse oximetry values post-6MWT were= 93%. Although mean values were within the normal limits, 14 (27%) patients presented with restrictive ventilatory defect (↓TLC), 5 (9%) patients presented with obstructive ventilatory defect (↓FEV1/FVC), 21 (41%) with abnormal resting gas exchange (↓DLCO), and 12 with significant desaturation during 6MWT. 37 (69%) walked a distance below lower limit of normality. Of note, 22/31 (70%) of the patients presenting with any functional abnormality(ies) had no previous report of respiratory diseases. Conclusions: A substantial proportion of severe COVID-19 survivors (43%) presented with respiratory functional abnormalities indicative of restrictive ventilatory defect and/or with altered gas exchange at rest or during exercise after 2-6 months of acute infection, even without previous report of any lung disease. Further information regarding remission, stabilization or progression of these findings will be possible in the follow-up of this cohort.
Abstract 10647: Precipitant Factors of Heart Failure Decompensation in Patients Attended in Primary Care, the Hefestos Study
Authors: Miguel-Angel Munoz, Helene Vaillant-Roussel, Liam Glynn, Radost Assenova, Peter Torsza, Lea Gril, Heidrun Lingner, Jacopo Demurtas, Hans Thulesius, Djurdjica Lazic, Jose-Maria Verdu-Rotellar, Rosa Abellana
Journal: Circulation (2019)

Introduction: Most knowledge about the main causes of heart failure decompensation come from hospital setting. However, evidence coming from primary care is scarce. Hypothesis: It is possible to id...
全電気的Ca2+非依存性シグナル伝達は味らいにおける魅力的なナトリウム味を仲介する【JST・京大機械翻訳】
Authors: Nomura Kengo, Nakanishi Miho, Ishidate Fumiyoshi, Iwata Kazumi, Taruno Akiyuki
Journal: Neuron (2020)
Transcatheter Treatment of Valvular Heart Disease
Authors: Laura J. Davidson, Charles J. Davidson
Journal: JAMA (2021)

<h3>Importance</h3> More than 40 million people are living with either mitral or aortic valve disease worldwide, and more than 180 000 heart valve replacement surgeries are performed each year in the US. Transcatheter valve repair has emerged as an important therapeutic option for patients who are candidates for heart valve replacement. <h3>Observations</h3> All transcatheter valve therapies involve a multidisciplinary team of interventional cardiologists, cardiothoracic surgeons, radiologists, echocardiographers, nurses, and social workers, termed the<i>heart team</i>, to determine the optimal approach for managing each patient. Transcatheter aortic valve implantation (TAVI) is an aortic valve replacement procedure that is performed percutaneously and is currently approved for patients with severe, symptomatic aortic stenosis in all surgical risk categories. The TAVI procedure can be performed using a balloon-expandable or self-expanding valve. In a low-risk cohort of patients (PARTNER [Placement of Aortic Transcatheter Valves] 3 trial), the rates of death from any cause, stroke, or rehospitalization were 8.5% for patients receiving TAVI and 15.1% for patients undergoing surgical aortic valve replacement. Decision-making regarding therapy choice should be based on individual anatomy (including the number of leaflets, annular size, and peripheral arterial anatomy), comorbidities (including concomitant coronary artery disease and aortopathies), and patient preference guide. A mitral transcatheter edge-to-edge repair device is approved by the US Food and Drug Administration for high-risk patients with degenerative and functional mitral regurgitation that has excellent safety and efficacy in these populations. In the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial, the annualized rate of all hospitalizations for heart failure was 35.8% among patients who underwent transcatheter edge-to-edge repair and received medical therapy compared with 67.9% among patients in the medical therapy alone group. Transcatheter tricuspid valve repair and replacement trials are ongoing and show promise for the treatment of patients with tricuspid regurgitation, which previously had limited therapeutic options. Multimodality imaging, which includes transthoracic echocardiography, transesophageal echocardiography, computed tomography, and intracardiac echocardiography, is important for preprocedural planning, device selection, and optimal outcomes. <h3>Conclusions and Relevance</h3> Approximately 78 000 TAVI procedures and 10 000 transcatheter mitral valve repairs take place yearly in the US to treat patients with severe, symptomatic aortic stenosis and mitral regurgitation, respectively. Transcatheter valve therapies have expanded therapeutic options for patients, including for those who previously had no viable surgical options.
General practitioners' experiences of patients' complaints
Authors: P. Thomson, G. Young
Journal: BMJ (1999)

Cancellation of debt must ensure maximum benefit to vulnerableEditor-It should be difficult for any doctor to ignore Abbasi's recent article on "third world" debt. 1 The state of health care available to families in between half and two thirds of the world is unacceptable, and the great differences in quality of health care between rich and poor countries are unethical. 2However, the experiences of our aid agency in trying to develop hospital care for children in disadvantaged countries leads us to be cautious about advocating simply a cancellation of debts.We have witnessed that an input of money alone to countries which are poorly governed, and where corruption is a way of life, may fail to reach the most vulnerable and needy within the community.Our agency's view is that all debt to poor and disadvantaged countries should be cancelled but in a more sustainable way than by releasing states from their repayments.Money earmarked for debt repayment should be retrieved but ploughed back fully and immediately into the country's healthcare and education systems.We suggest that this is implemented through the appointment in each repaying country of carefully chosen advocates for women and children.Ideally, partners appointed from within the United Nations should support these local delegates.A committee formed between the UN partners and delegates from the country repaying the debt should thereby ensure that all the money that has been repaid to rich countries is used for health care and education.Such a system would be more difficult to organise than simple cancellation of debt.Care would have to be taken to ensure that existing levels of finance for health care and education are maintained in addition to money resulting from debt repayment.The repayment of debts by the "third world" to rich countries who have prospered from earlier exploitation clearly represents an evil.However, our response to this should be "street wise" and should ensure that the abolition of debt results in maximum benefit to the most vulnerable members of disadvantaged countries.
Reconstructing single-cell karyotype alterations in colorectal cancer identifies punctuated and gradual diversification patterns
Authors: Yannik Bollen, Ellen Stelloo, Petra van Leenen, Myrna van den Bos, Bas Ponsioen, Bingxin Lu, Markus J. van Roosmalen, Ana C. F. Bolhaqueiro, Christopher Kimberley, Maximilian Mossner, William C. H. Cross, Nicolle J. M. Besselink, Bastiaan van der Roest, Sander Boymans, Koen C. Oost, Sippe G. de Vries, Holger Rehmann, Edwin Cuppen, Susanne M. A. Lens, Geert J. P. L. Kops, Wigard P. Kloosterman, Leon W. M. M. Terstappen, Chris P. Barnes, Andrea Sottoriva, Trevor A. Graham, Hugo J. G. Snippert
Journal: Nature Genetics (2021)

Abstract Central to tumor evolution is the generation of genetic diversity. However, the extent and patterns by which de novo karyotype alterations emerge and propagate within human tumors are not well understood, especially at single-cell resolution. Here, we present 3D Live-Seq—a protocol that integrates live-cell imaging of tumor organoid outgrowth and whole-genome sequencing of each imaged cell to reconstruct evolving tumor cell karyotypes across consecutive cell generations. Using patient-derived colorectal cancer organoids and fresh tumor biopsies, we demonstrate that karyotype alterations of varying complexity are prevalent and can arise within a few cell generations. Sub-chromosomal acentric fragments were prone to replication and collective missegregation across consecutive cell divisions. In contrast, gross genome-wide karyotype alterations were generated in a single erroneous cell division, providing support that aneuploid tumor genomes can evolve via punctuated evolution. Mapping the temporal dynamics and patterns of karyotype diversification in cancer enables reconstructions of evolutionary paths to malignant fitness.
Virtual consultation for red eye
Authors: Charlotte Shan Ho, Anthony John Avery, Iain A T Livingstone, Darren Shu Jeng Ting
Journal: BMJ (2021)

### What you need to know

A 63 year old woman contacts her general practice, via a telephone call, reporting a left painful red eye since yesterday. Because of the covid-19 pandemic, she is booked in for a video consultation with a GP the same day. 

Face-to-face consultations remain the optimal medium for ophthalmic consultation. Virtual consultations have been implemented as an alternative in the covid-19 pandemic.123456789 In a recent London study of 854 patients, video consultations for emergency ophthalmology services in adults had similar safety to face-to-face consultations. There was a higher rate of unplanned reattendance, but most patients were satisfied with video consultations.10

Red eye is a common ophthalmic presentation in primary care, accounting for 2 to 3% of the consultations.11 Virtual consultation for red eye(s) follow the same format and principles as face-to-face consultations. Performing ocular examination remotely can be challenging. Adaptation with specific instructions to the patient and/or family member will be required.

### Telephone consultation

You may ask for history of presenting symptoms over a telephone consultation to determine the cause and severity of red eye. A telephone consultation also provides an opportunity to advise patients on any immediate measures that need to be taken while awaiting an appointment for a virtual video examination (such as not wearing contact lenses …
In vivo targeted delivery of nucleic acids and CRISPR genome editors enabled by GSH-responsive silica nanoparticles
Authors: Yuyuan Wang, Pawan K. Shahi, Xiuxiu Wang, Ruosen Xie, Yi Zhao, Min Wu, Seth Roge, Bikash R. Pattnaik, Shaoqin Gong
Journal: Journal of Controlled Release (2021)
Extracellular Vesicles as an Advanced Delivery Biomaterial for Precision Cancer Immunotherapy
Authors: Shaobo Ruan, Zachary Greenberg, Xiaoshu Pan, Pei Zhuang, Nina Erwin, Mei He
Journal: Advanced Healthcare Materials (2021)

In recent years, cancer immunotherapy has been observed in numerous preclinical and clinical studies for showing benefits. However, due to the unpredictable outcomes and low response rates, novel targeting delivery approaches and modulators are needed for being effective to more broader patient populations and cancer types. Compared to synthetic biomaterials, extracellular vesicles (EVs) specifically open a new avenue for improving the efficacy of cancer immunotherapy by offering targeted and site-specific immunity modulation. In this review, the molecular understanding of EV cargos and surface receptors, which underpin cell targeting specificity and precisely modulating immunogenicity, are discussed. Unique properties of EVs are reviewed in terms of their surface markers, intravesicular contents, intrinsic immunity modulatory functions, and pharmacodynamic behavior in vivo with tumor tissue models, highlighting key indications of improved precision cancer immunotherapy. Novel molecular engineered strategies for reprogramming and directing cancer immunotherapeutics, and their unique challenges are also discussed to illuminate EV's future potential as a cancer immunotherapeutic biomaterial.
Abstract 14112: Clinical Practice Patterns in Percutaneous Mechanical Circulatory Support (MCS) for Shock in the Critical Care Cardiology Trials Network (CCCTN) Registry
Authors: David D Berg, Erin A Bohula, Christopher F Barnett, Benjamin B Kenigsberg, Jeong-Gun Park, Sean Van Diepen, Jason N Katz, David A Morrow
Journal: Circulation (2019)

Introduction: Percutaneous mechanical circulatory support (pMCS) provides a therapeutic option for pts w/ shock refractory to pharmacologic treatment. Because most registries have focused on single...
direct conversion of mouse fibroblasts into cholangiocyte progenitor cells
Authors: Kyung Tae Lim, Jonghun Kim, Seon In Hwang, Ludi Zhang, Heonjong Han, Dasom Bae, Kee-Pyo Kim, Yi-Ping Hu, Hans R. Schöler, Insuk Lee, Lijian Hui, Dong Wook Han
Journal: Nature Reviews Gastroenterology & Hepatology (2018)
His Service Dog
Authors: Richard Bronson
Journal: JAMA (2021)

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Abstract 402: Mutation-Specific Activation of CaMK-II in Hypertrophic Cardiomyopathy
Authors: Sarah J Lehman, Lauren Tal-Grinspan, Amanda Richards, Nora Bedrossian, Mark E Anderson, Jil C Tardiff
Journal: Circulation Research (2016)

Approximately 5-10% of all Hypertrophic Cardiomyopathy (HCM) mutations reside within cardiac troponin T (cTnT). Residue Arg92 of cTnT represents a mutational hotspot, including Arg92Leu (R92L) and Arg92Trp (R92W). Interestingly, patients expressing these substitutions that differ by only a single amino acid present with distinct phenotypes and disease severity. Studying the differential effects of the R92 mutations on Ca 2+ homeostasis revealed an age-dependent increase in phospholamban (PLB) phosphorylation at Thr17 (targeted by CaMKII) only in R92W mice. Thus, we hypothesized a mutation-specific role of CaMKII in cTnT-linked HCM progression and tested this hypothesis via genetic partial inhibition of CaMKII (AC3I peptide) in both R92W and R92L transgenic mice. A progressive increase in PKA-mediated PLB-Ser16 phosphorylation was observed in the AC3I/RW mice, leading to an increase in SERCA2 activity. This improved Ca 2+ re-uptake activity was coupled with a decrease in atrial mass, indicative of a decrease in diastolic filling pressure. Thus, the R92W mutation initiates downstream pathophysiologic activation of CaMKII, leading to progressive cardiomyopathic remodeling. Partial inhibition of CaMKII in R92W mice resulted in the alteration of the natural history of HCM, indicating a potential therapeutic target for patients expressing the mutation. In contrast, AC3I/RL mice showed no change in SERCA2 activity or atrial morphology, suggesting a CaMKII-independent progression to disease for R92L-linked HCM. Finally, R92L and R92W mice were treated with diltiazem hydrochloride, an L-type Ca 2+ channel blocker, and diastolic function monitored over time. R92W mice showed improvement in diastolic function with treatment while R92L mice showed a progressive decrease in diastolic function. These findings suggest that closely related mutations, even at the same residue, can have discrete molecular effects that result in mutation-specific ventricular remodeling and these observations can be incorporated in targeted disease management.