tbuckley/cabot-search huggingface dataset:
Loss of Soluble (Pro)renin Receptor Attenuates Angiotensin-II Induced Hypertension and Renal Injury
Authors: Nirupama Ramkumar, Deborah Stuart, Caitlin S. Peterson, Chunyan Hu, William Wheatley, Jae Min Cho, J David Symons, Donald E. Kohan
Journal: Circulation Research (2021)

[Figure: see text].
원저 : 간이식 대기 중인 간경변 환자에서 의미 있는 폐내 단락의 빈도와 이와 연관된 인자에 관한 연구
Authors: 이지민(Ji Min Lee), 최문석(Moon Seok Choi), 이상철(Sang Chol Lee), 박승우(Seung Woo Park), 배문희(Mun Hee Bae), 이준혁(Joon Hyeok Lee), 고광철(Kwang Cheol Koh), 백승운(Seung Woon Paik), 이풍렬(Poong Lyul Rhee), 김재준(Jae Jun Kim), 이종철(Jong Chul Rhee)
Journal: Clinical and Molecular Hepatology (2002)

목적: 간폐증후군은 간질환이 있는 환자에서 저산소증이 유발되는 상태로서, 폐내 단락이 그 주된 기전으로 알려져있다. 간이식은 간폐증후군의 유일한 치료 방법으로 알려져 있고, 이식 후에 폐내 단락의 정상화가 일어날 수 있다. 그러나 간이식을 시행할 경우 가역성을 미리 예측할 수 없는 것이 문제이다. 국내에서는 이식 대기중인 간경변증 환자에서의 폐내 단락의 유병률에 관한 연구가 아직 없는 실정이다. 저자 등은 간이식 대기중인 간경변증 환자에서 의미 있는 폐내 단락의 유병률과 폐내 단락과 연관된 위험 인자를 알아보고자 하였다. 대상과 방법: 1999년 11월부터 2001년 2월까지 삼성서울병원 에서 간경변증이나 이에 동반된 간암으로 간이식 대기 중인 환자 57명 (남 : 여 = 38 : 19, 연령 18∼71 세, 중앙값 49세)을 대상으로 하였다. 간경변증의 원인은 B형 간염이 47명, C형 간염이 4명, 그 외 알코올과 윌슨병, 원발성 담도성 간경변증 등이 6명이었고, 전체 환자 중에 간암이 동반된 환자는 13명이었다. 이들에게 조영 증강 심초음파를 시행하여 폐내 단락의 유무 및 정도를 평가하였으며, Ⅱ등급 이상의 단락을 의미 있는 단락으로 보았다. 대상 환자를 의미 있는 단락을 가진 군과 그렇지 않은 군으로 나누어, 양 군 간의 간기능, 식도 정맥류 유무, 위 정맥류 유무, 복수, 간성 뇌증 유무를 비교하였다. 결과: 총 57명의 환자 중 의미 있는 폐내 단락을 가진 군 은 30명(52.6%)이었다. 의미 있는 폐내 단락은 Child- Pugh분류 C군에서 38명 중 24명(63.2%), A, B군에서 19명 중 6명(31.6%)으로 관찰되었다(p< 0.05). 의미 있는 폐내 단락이 있는 군과 없는 군 간의 성별, 나이, 간경변증 원인, 식도 정맥류 유무, 위 정맥류 유무, 복수, 간성 뇌증 유무 등에는 유의한 차이가 없었다. 결론: 이상의 결과로 폐내 단락은 간이식 대기중인 간경변증 환자에서 흔히 관찰되는 소견이며, Child-Pugh 분류 C군은 의미 있는 폐내 단락의 위험 인자임을 알 수 있었다.
Feeding-induced hepatokine, Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway
Authors: Tong Wu, Qinhui Liu, Yanping Li, Hong Li, Lei Chen, Xuping Yang, Qin Tang, Shiyun Pu, Jiangying Kuang, Rui Li, Ya Huang, Jinhang Zhang, Zijing Zhang, Jian Zhou, Cuiyuan Huang, Guorong Zhang, Yingnan Zhao, Min Zou, Wei Jiang, Li Mo, Jinhan He
Journal: The Journal of Experimental Medicine (2021)

Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy to combat obesity. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) is a feeding-induced hepatokine. Liver-specific Manf overexpression protected mice against high-fat diet-induced obesity and promoted browning of inguinal subcutaneous WAT (iWAT). Manf overexpression in liver was also associated with decreased adipose inflammation and improved insulin sensitivity and hepatic steatosis. Mechanistically, Manf could directly promote browning of white adipocytes via the p38 MAPK pathway. Blockade of p38 MAPK abolished Manf-induced browning. Consistently, liver-specific Manf knockout mice showed impaired iWAT browning and exacerbated diet-induced obesity, insulin resistance, and hepatic steatosis. Recombinant Manf reduced obesity and improved insulin resistance in both diet-induced and genetic obese mouse models. Finally, we showed that circulating Manf level was positively correlated with BMI in humans. This study reveals the crucial role of Manf in regulating thermogenesis in adipose tissue, representing a potential therapeutic target for obesity and related metabolic disorders.
Racial disparities in patients diagnosed with light chain (AL) amyloidosis
Authors: Anita D’Souza, Liliana Pezzin, Purushottam Laud, Ashima Singh
Journal: Blood Cancer Journal (2021)

Dear Editor,Light chain (AL) amyloidosis arises from a precursor plasma cell neoplasm that produces clonal free light chains that form insoluble fibril deposits leading to organ dysfunction 1 .Because the disease is rare, heterogeneous, and multi-systemic, it can take several months to years for the symptoms to show in patients before a diagnosis is made 2 .Knowledge of the pre-existing clinical characteristics of patients eventually diagnosed with AL amyloidosis is critical as it may inform early diagnosis of the disease.Evidence suggests that early diagnosis of AL amyloidosis leads to improved outcomes, including superior survival, as the disease can be modulated with recently available therapies 3,4 .Among diagnosed amyloidosis patients, Black men and women have the highest mortality rate 5 .Although existing literature has documented a racial predisposition in plasma cell disorders, such as monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma 6,7 , racial differences in the incidence of the multiple other potential clinical precursor diagnoses associated with AL amyloidosis remain unknown.In this report, we use nationally representative electronic health records (EHR) data to document and contrast the clinical characteristics of patients diagnosed with AL amyloidosis by self-reported race.We also compare the clinical characteristics between patients with AL amyloidosis and matched individuals without amyloidosis by race.We hypothesized that differences in AL-associated, preexisting diagnoses will be evident in patients prior to their diagnosis of AL amyloidosis and that these differences will vary by the patients' race.
Clinical utility of 30% relative decline in MRI-PDFF in predicting fibrosis regression in non-alcoholic fatty liver disease
Authors: Nobuharu Tamaki, Nagambika Munaganuru, Jinho Jung, Aed Qas Yonan, Rohan R Loomba, Richele Bettencourt, Veeral Ajmera, Mark A Valasek, Cynthia Behling, Claude B Sirlin, Rohit Loomba
Journal: Gut (2021)

Emerging data suggest that a 30% relative decline in liver fat, as assessed by MRI-proton density fat fraction (MRI-PDFF), may be associated with Non-Alcoholic Fatty Liver Disease Activity Score improvement, but the association between decline in MRI-PDFF and fibrosis regression is not known. Therefore, we aimed to examine the association between ≥30% relative decline in MRI-PDFF and fibrosis regression in non-alcoholic fatty liver disease (NAFLD).
A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency
Authors: Wendell Jones, Binsheng Gong, Natalia Novoradovskaya, Dan Li, Rebecca Kusko, Todd A. Richmond, Donald J. Johann, Halil Bisgin, Sayed Mohammad Ebrahim Sahraeian, Pierre R. Bushel, Mehdi Pirooznia, Katherine Wilkins, Marco Chierici, Wenjun Bao, Lee Scott Basehore, Anne Bergstrom Lucas, Daniel Burgess, Daniel J. Butler, Simon Cawley, Chia-Jung Chang, Guangchun Chen, Tao Chen, Yun-Ching Chen, Daniel J. Craig, Angela del Pozo, Jonathan Foox, Margherita Francescatto, Yutao Fu, Cesare Furlanello, Kristina Giorda, Kira P. Grist, Meijian Guan, Yingyi Hao, Scott Happe, Gunjan Hariani, Nathan Haseley, Jeff Jasper, Giuseppe Jurman, David Philip Kreil, Paweł Łabaj, Kevin Lai, Jianying Li, Quan-Zhen Li, Yulong Li, Zhiguang Li, Zhichao Liu, Mario Solís López, Kelci Miclaus, Raymond Miller, Vinay K. Mittal, Marghoob Mohiyuddin, Carlos Pabón-Peña, Barbara L. Parsons, Fujun Qiu, Andreas Scherer, Tieliu Shi, Suzy Stiegelmeyer, Chen Suo, Nikola Tom, Dong Wang, Zhining Wen, Leihong Wu, Wenzhong Xiao, Chang Xu, Ying Yu, Jiyang Zhang, Yifan Zhang, Zhihong Zhang, Yuanting Zheng, Christopher E. Mason, James C. Willey, Weida Tong, Leming Shi, Joshua Xu
Journal: Genome biology (2021)

Abstract Background Oncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance. Results In reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5–100× more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels. Conclusion These new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.
Genetic therapies for the first molecular disease
Authors: Phillip A. Doerfler, Akshay Sharma, Jerlym S. Porter, Yan Zheng, John F. Tisdale, Mitchell J. Weiss
Journal: Journal of Clinical Investigation (2021)

Sickle cell disease (SCD) is a monogenic disorder characterized by recurrent episodes of severe bone pain, multi-organ failure, and early mortality. Although medical progress over the past several decades has improved clinical outcomes and offered cures for many affected individuals living in high-income countries, most SCD patients still experience substantial morbidity and premature death. Emerging technologies to manipulate somatic cell genomes and insights into the mechanisms of developmental globin gene regulation are generating potentially transformative approaches to cure SCD by autologous hematopoietic stem cell (HSC) transplantation. Key components of current approaches include ethical informed consent, isolation of patient HSCs, in vitro genetic modification of HSCs to correct the SCD mutation or circumvent its damaging effects, and reinfusion of the modified HSCs following myelotoxic bone marrow conditioning. Successful integration of these components into effective therapies requires interdisciplinary collaborations between laboratory researchers, clinical caregivers, and patients. Here we summarize current knowledge and research challenges for each key component, emphasizing that the best approaches have yet to be developed.
May the force be with you: will artificial intelligence take over traditional endoscopy?
Authors: Torsten Beyna
Journal: Endoscopy (2021)

Since the introduction of the first fully flexible fiberoptic endoscope by Hirschowitz in 1957 and the advent of digital video endoscopy developed by Welch Allyn in 1984, the gross design and mechanical buildup of flexible endoscopes have not been altered fundamentally. In principle, further improvements have been achieved mainly in the field of image quality, such as resolution, illumination, field of view, magnification, and (virtual) image-enhancement technologies. However, the primary aim of diagnostic procedures is the detection of pathological findings, namely precancerous or early cancerous lesions in the gastrointestinal tract, which is still mainly determined by the ability of the endoscopist to first detect then to correctly characterize a lesion. In this context, we have to admit that seeing a lesion is not equal to recognizing it. Nowadays, clear quality indicators have been established for diagnostic and therapeutic procedures in the gastrointestinal tract, for example, the adenoma detection rate (ADR) in the setting of a screening colonoscopy [1]. We also divide endoscopists examining the lower gastrointestinal tract into high and low detectors. However, quality of diagnostic as well as therapeutic endoscopy is still widely related to the skills of the individual endoscopist. In this context, computer-assisted diagnostic (CAD) systems could be the key to achieving a consistently high(er) level of quality.
Bimekizumab versus Secukinumab in Plaque Psoriasis
Authors: Kristian Reich, Richard B. Warren, Mark Lebwohl, Melinda Gooderham, Bruce Strober, Richard G. Langley, Carle Paul, Dirk De Cuyper, Veerle Vanvoorden, Cynthia Madden, Christopher Cioffi, Luke Peterson, Andrew Blauvelt
Journal: New England Journal of Medicine (2021)

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits both interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with secukinumab, which selectively inhibits interleukin-17A alone, in patients with moderate-to-severe plaque psoriasis have not been extensively examined.
NPM1c Alters FLT3-D835Y Localization and Signaling Thereby Inducing a Fulminant Myeloproliferative Disorder in Mice
Authors: Alina Rudorf, Tony Andreas Müller, Cathrin Klingeberg, George S. Vassiliou, Allan Bradley, Robert Zeiser, Justus Duyster, Anna Lena Illert
Journal: Blood (2017)
The natriuretic peptide system in heart failure: Diagnostic and therapeutic implications
Authors: Koichiro Kuwahara
Journal: Pharmacology & Therapeutics (2021)

Natriuretic peptides, which are activated in heart failure, play an important cardioprotective role. The most notable of the cardioprotective natriuretic peptides are atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which are abundantly expressed and secreted in the atrium and ventricles, respectively, and C-type natriuretic peptide (CNP), which is expressed mainly in the vasculature, central nervous system, and bone. ANP and BNP exhibit antagonistic effects against angiotensin II via diuretic/natriuretic actions, vasodilatory actions, and inhibition of aldosterone secretion, whereas CNP is involved in the regulation of vascular tone and blood pressure, among other roles. ANP and BNP are of particular interest with respect to heart failure, as their levels, most notably BNP and N-terminal proBNP—a cleavage product produced when proBNP is processed to mature BNP—are increased in patients with heart failure. Furthermore, the identification of natriuretic peptides as sensitive markers of cardiac load has driven significant research into their physiological roles in cardiovascular homeostasis and disease, as well as their potential use as both biomarkers and therapeutics. In this review, I discuss the physiological functions of the natriuretic peptide family, with a particular focus on the basic research that has led to our current understanding of its roles in maintaining cardiovascular homeostasis, and the pathophysiological implications for the onset and progression of heart failure. The clinical significance and potential of natriuretic peptides as diagnostic and/or therapeutic agents are also discussed.
Postoperative In-Hospital Morbidity and Mortality of Patients With COVID-19 Infection Compared With Patients Without COVID-19 Infection
Authors: Max R. Haffner, Hai V. Le, Augustine M. Saiz, Gloria Han, Jeffrey Fine, Philip Wolinsky, Eric O. Klineberg
Journal: JAMA Network Open (2021)

This cohort study uses the Vizient Clinical Data Base to compare the postoperative in-hospital morbidity and mortality of surgical patients with COVID-19 infection with patients without COVID-19 infection.
Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial
Authors: Ben M. Eyck, J. Jan B. van Lanschot, Maarten C. C. M. Hulshof, Berend J. van der Wilk, Joel Shapiro, Pieter van Hagen, Mark I. van Berge Henegouwen, Bas P. L. Wijnhoven, Hanneke W. M. van Laarhoven, Grard A. P. Nieuwenhuijzen, Geke A. P. Hospers, Johannes J. Bonenkamp, Miguel A. Cuesta, Reinoud J. B. Blaisse, Olivier R. Busch, Geert-Jan M. Creemers, Cornelis J. A. Punt, John Th. M. Plukker, Henk M. W. Verheul, Ernst J. Spillenaar Bilgen, Maurice J. C. van der Sangen, Tom Rozema, Fiebo J. W. ten Kate, Jannet C. Beukema, Anna H. M. Piet, Caroline M. van Rij, Janny G. Reinders, Hugo W. Tilanus, Ewout W. Steyerberg, Ate van der Gaast
Journal: Journal of Clinical Oncology (2021)

PURPOSE Preoperative chemoradiotherapy according to the chemoradiotherapy for esophageal cancer followed by surgery study (CROSS) has become a standard of care for patients with locally advanced resectable esophageal or junctional cancer. We aimed to assess long-term outcome of this regimen. METHODS From 2004 through 2008, we randomly assigned 366 patients to either five weekly cycles of carboplatin and paclitaxel with concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone. Follow-up data were collected through 2018. Cox regression analyses were performed to compare overall survival, cause-specific survival, and risks of locoregional and distant relapse. The effect of neoadjuvant chemoradiotherapy beyond 5 years of follow-up was tested with time-dependent Cox regression and landmark analyses. RESULTS The median follow-up was 147 months (interquartile range, 134-157). Patients receiving neoadjuvant chemoradiotherapy had better overall survival (hazard ratio [HR], 0.70; 95% CI, 0.55 to 0.89). The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent ( P value for interaction, P = .73), and landmark analyses suggested a stable effect on overall survival up to 10 years of follow-up. The absolute 10-year overall survival benefit was 13% (38% v 25%). Neoadjuvant chemoradiotherapy reduced risk of death from esophageal cancer (HR, 0.60; 95% CI, 0.46 to 0.80). Death from other causes was similar between study arms (HR, 1.17; 95% CI, 0.68 to 1.99). Although a clear effect on isolated locoregional (HR, 0.40; 95% CI, 0.21 to 0.72) and synchronous locoregional plus distant relapse (HR, 0.43; 95% CI, 0.26 to 0.72) persisted, isolated distant relapse was comparable (HR, 0.76; 95% CI, 0.52 to 1.13). CONCLUSION The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.
Tissue-resident-like CD4+ T cells secreting IL-17 control Mycobacterium tuberculosis in the human lung
Authors: Paul Ogongo, Liku B. Tezera, Amanda Ardain, Shepherd Nhamoyebonde, Duran Ramsuran, Alveera Singh, Abigail Ng’oepe, Farina Karim, Taryn Naidoo, Khadija Khan, Kaylesh J. Dullabh, Michael Fehlings, Boon Heng Lee, Alessandra Nardin, Cecilia S. Lindestam Arlehamn, Alessandro Sette, Samuel M. Behar, Adrie J.C. Steyn, Rajhmun Madansein, Henrik N. Kløverpris, Paul T. Elkington, Alasdair Leslie
Journal: Journal of Clinical Investigation (2021)

T cell immunity is essential for the control of tuberculosis (TB), an important disease of the lung, and is generally studied in humans using peripheral blood cells. Mounting evidence, however, indicates that tissue-resident memory T cells (Trms) are superior at controlling many pathogens, including Mycobacterium tuberculosis (M. tuberculosis), and can be quite different from those in circulation. Using freshly resected lung tissue, from individuals with active or previous TB, we identified distinct CD4+ and CD8+ Trm-like clusters within TB-diseased lung tissue that were functional and enriched for IL-17–producing cells. M. tuberculosis–specific CD4+ T cells producing TNF-α, IL-2, and IL-17 were highly expanded in the lung compared with matched blood samples, in which IL-17+ cells were largely absent. Strikingly, the frequency of M. tuberculosis–specific lung T cells making IL-17, but not other cytokines, inversely correlated with the plasma IL-1β levels, suggesting a potential link with disease severity. Using a human granuloma model, we showed the addition of either exogenous IL-17 or IL-2 enhanced immune control of M. tuberculosis and was associated with increased NO production. Taken together, these data support an important role for M. tuberculosis–specific Trm-like, IL-17–producing cells in the immune control of M. tuberculosis in the human lung.
A Charge to Academic Chairs—Reply
Authors: Bismarck C. Odei, Fumiko Chino, Darrion Mitchell
Journal: JAMA Internal Medicine (2021)

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A Correction to the Research Article Titled: "Adducin- and Ouabain-Related Gene Variants Predict the Antihypertensive Activity of Rostafuroxin. Part 1: Experimental Studies" by Mara Ferrandi, Isabella Molinari, Lucia Torielli, Gloria Padoani, Sergio Salardi, Maria Pia Rastaldi, Patrizia Ferrari, Giuseppe Bianchi
Journal: Science Translational Medicine (2010)
Abstract 2330: Relationship Between Coronary Calcification, Myocardial Ischemia, and Outcomes in Patients With Intermediate Likelihood of Coronary Artery Disease
Authors: Matthew P Schenker, Sharmila Dorbala, Eric C Hong, Frank J Rybicki, Rory Hachamovitch, Raymond Y Kwong, Marcelo F Di Carli
Journal: Circulation (2007)

Background - Although the value of coronary artery calcium (CAC) for atherosclerosis screening is gaining acceptance, its efficacy in predicting flow-limiting CAD remains controversial and its incremental prognostic value over myocardial perfusion is not well established. Methods and Results - We evaluated 621 consecutive patients undergoing combined rest-stress Rubidium-82 PET perfusion imaging and CAC scanning on a hybrid PET-CT scanner. The frequency of abnormal scans among patients with CAC ≥400 was higher than that in patients with CAC 1–399 (53.3% vs 30.0%, p&lt;0.001). Multivariate logistic regression analysis supported the concept of a CAC ≥400 threshold value governing this relationship (OR 2.74, p&lt;0.001). However, the frequency of ischemia among patients with no CAC was 24.4%, and its absence only afforded a negative predictive value of 75.6%. Risk adjusted survival analysis demonstrated a stepwise increase in event rates with increasing CAC scores in patients with and without ischemia on PET. Among patients with normal PET, the annualized event rate in patients with CAC score=zero was lower than in those with a CAC ≥1,000 (2.4% vs 13.6%, respectively). Likewise, in patients with ischemia on PET the annualized event rate in those with CAC score=zero was lower than among patients with a CAC ≥1,000 (6.9% vs 19.4%). Conclusions - Although increasing CAC scores are generally predictive of a higher likelihood of ischemia, its absence does not eliminate the possibility of flow-limiting CAD. Importantly, there is a stepwise increase in the risk of adverse events with increasing CAC scores in patients with and without ischemia on PET.