tbuckley/cabot-search huggingface dataset:
2021 update on clinical trials in β‐thalassemia
Authors: Khaled M. Musallam, Rayan Bou‐Fakhredin, Maria Domenica Cappellini, Ali T. Taher
Journal: American Journal of Hematology (2021)

The treatment landscape for patients with β-thalassemia is witnessing a swift evolution, yet several unmet needs continue to persist. Patients with transfusion-dependent β-thalassemia (TDT) primarily rely on regular transfusion and iron chelation therapy, which can be associated with considerable treatment burden and cost. Patients with non-transfusion-dependent β-thalassemia (NTDT) are also at risk of significant morbidity due to the underlying anemia and iron overload, but treatment options in this patient subgroup are limited. In this review, we provide updates on clinical trials of novel therapies targeting the underlying pathology in β-thalassemia, including the α/non-α-globin chain imbalance, ineffective erythropoiesis, and iron dysregulation.
Perioperative Opioids—Reclaiming Lost Ground
Authors: William J. Fawcett, Olle Ljungqvist, Dileep N. Lobo
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
Abstract 15920: Thyroid Hormones Maintain Functional T-Tubule Networks in Cardiomyocytes
Authors: Nimra Gilani, Kaihao Zhang, Youhua Zhang, A. M Gerdes, Kaie M Ojamaa
Journal: Circulation (2019)

In patients with pre-existing heart failure, subclinical hypothyroidism or low T3 syndrome are associated with poor outcomes, and several studies have reported improved prognosis with T3 treatment....
2020年に焦点を当てた,僧帽弁閉鎖不全症の管理についての2017 ACC専門家コンセンサス決定経路の最新情報 米国心臓病学会ソリューションセットオーバービジョン委員会の報告【JST・京大機械翻訳】
Authors: O Bonow Robert, T O’Gara Patrick, H Adams David, Badhwar Vinay, E Bavaria Joseph, Elmariah Sammy, W Hung Judy, Lindenfeld JoAnn, A Morris Alanna, Satpathy Ruby, Whisenant Brian, Woo Y. Joseph
Journal: Journal of the American College of Cardiology (2020)
Enhanced cGAS-STING–dependent interferon signaling associated with mutations in ATAD3A
Authors: Alice Lepelley, Erika Della Mina, Erika Van Nieuwenhove, Lise Waumans, Sylvie Fraitag, Gillian I. Rice, Ashish Dhir, Marie-Louise Frémond, Mathieu P. Rodero, Luis Seabra, Edwin Carter, Christine Bodemer, Daniela Buhas, Bert Callewaert, Pascale de Lonlay, Lien De Somer, David A. Dyment, Fran Faes, Lucy Grove, Simon Holden, Marie Hully, Manju A. Kurian, Hugh J. McMillan, Kristin Suetens, Henna Tyynismaa, Stéphanie Chhun, Timothy Wai, Carine Wouters, Brigitte Bader-Meunier, Yanick J. Crow
Journal: The Journal of Experimental Medicine (2021)

Mitochondrial DNA (mtDNA) has been suggested to drive immune system activation, but the induction of interferon signaling by mtDNA has not been demonstrated in a Mendelian mitochondrial disease. We initially ascertained two patients, one with a purely neurological phenotype and one with features suggestive of systemic sclerosis in a syndromic context, and found them both to demonstrate enhanced interferon-stimulated gene (ISG) expression in blood. We determined each to harbor a previously described de novo dominant-negative heterozygous mutation in ATAD3A, encoding ATPase family AAA domain-containing protein 3A (ATAD3A). We identified five further patients with mutations in ATAD3A and recorded up-regulated ISG expression and interferon α protein in four of them. Knockdown of ATAD3A in THP-1 cells resulted in increased interferon signaling, mediated by cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING). Enhanced interferon signaling was abrogated in THP-1 cells and patient fibroblasts depleted of mtDNA. Thus, mutations in the mitochondrial membrane protein ATAD3A define a novel type I interferonopathy.
Interpreting the Complex Landscape of Immune–Tumor Interface
Authors: W. Fraser Symmans
Journal: Clinical Cancer Research (2021)

Abstract Predictive biomarkers for immune therapy must address a complex interface between the immune system and triple-negative breast cancer and still be technically reliable for diagnostic use. Two recent articles describe the assessment of spatial heterogeneity using digital methods that promise to improve the quantification of immune infiltrate or molecular targets. See related articles by Bai et al., p. 5557 and Carter et al., p. 5628
Primary Chemoradiotherapy for Older Patients With Esophageal Cancer
Authors: Jennifer R. Eads, Daniel G. Haller
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
ラット実験的な糖尿病ネフロパシーにおけるスーパーオキシドの主要源であるNAD(P)Hオキシダーゼと脱共役一酸化窒素シンターゼ
Authors: Satoh M, Kashihara N, Fujimoto S, Haruna Y, Arakawa S, Kobayashi S, Ozeki M, Sasaki T, Makino H
Journal: Journal of the American Society of Nephrology (2003)
Hypersensitivity pneumonitis
Authors: M. Girard, Y. Lacasse, Y. Cormier
Journal: Allergy (2009)

The first few cases of hypersensitivity pneumonitis (HP) were described in the early 20th century in farmers exposed to moldy hay or straw. As then, HP has been ascribed to multiple inhaled antigens found in a large variety of environmental settings. Hypersensitivity pneumonitis results from an exaggerated immune response, which gives rise to acute infection-like symptoms or to progressive, sometimes irreversible lung damage. The diagnosis is based on a combination of clinical characteristics of the disease. Clinical diagnostic criteria have recently been published. The immune mechanisms leading to HP are still incompletely understood. Initially, believed to be a classes III and IV immune response, we now have a clearer understanding of the complex inflammatory events involved. These include the release of pro inflammatory cytokines and a decrease in the immune control mechanisms via surfactant, dendritic and T-regulatory cells. Despite the improved understanding, the treatment and outcome of HP have not changed. Oral corticosteroids remain the only effective drugs and contact withdrawal constitutes the ideal solution. If unchecked, HP can lead to irreversible lung damage in the form of fibrosis or emphysema, respiratory insufficiency and even death.
Variable Patterns of Remission From ADHD in the Multimodal Treatment Study of ADHD
Authors: Margaret H. Sibley, L. Eugene Arnold, James M. Swanson, Lily T. Hechtman, Traci M. Kennedy, Elizabeth Owens, Brooke S.G. Molina, Peter S. Jensen, Stephen P. Hinshaw, Arunima Roy, Andrea Chronis-Tuscano, Jeffrey H. Newcorn, Luis A. Rohde
Journal: American Journal of Psychiatry (2021)

It is estimated that childhood attention deficit hyperactivity disorder (ADHD) remits by adulthood in approximately 50% of cases; however, this conclusion is typically based on single endpoints, failing to consider longitudinal patterns of ADHD expression. The authors investigated the extent to which children with ADHD experience recovery and variable patterns of remission by adulthood.Children with ADHD (N=558) in the Multimodal Treatment Study of ADHD (MTA) underwent eight assessments over follow-ups ranging from 2 years (mean age, 10.44 years) to 16 years (mean age, 25.12 years) after baseline. The authors identified participants with fully remitted, partially remitted, and persistent ADHD at each time point on the basis of parent, teacher, and self-reports of ADHD symptoms and impairment, treatment utilization, and substance use and mental disorders. Longitudinal patterns of remission and persistence were identified that considered context and timing.Approximately 30% of children with ADHD experienced full remission at some point during the follow-up period; however, a majority of them (60%) experienced recurrence of ADHD after the initial period of remission. Only 9.1% of the sample demonstrated recovery (sustained remission) by study endpoint, and only 10.8% demonstrated stable ADHD persistence across study time points. Most participants with ADHD (63.8%) had fluctuating periods of remission and recurrence over time.The MTA findings challenge the notion that approximately 50% of children with ADHD outgrow the disorder by adulthood. Most cases demonstrated fluctuating symptoms between childhood and young adulthood. Although intermittent periods of remission can be expected in most cases, 90% of children with ADHD in MTA continued to experience residual symptoms into young adulthood.
Current knowledge about biomarkers of acute kidney injury in liver cirrhosis
Authors: Han Ah Lee, Yeon Seok Seo
Journal: Clinical and Molecular Hepatology (2021)

Acute kidney injury (AKI) is common in advanced cirrhosis. Prerenal azotemia, hepatorenal syndrome, and acute tubular necrosis are the main causes of AKI in patients with cirrhosis. Evaluation of renal function and differentiation between functional and structural kidney injury are important issues in the management of cirrhosis. However, AKI in cirrhosis exists as a complex clinical spectrum rather than concrete clinical entity. Based on current evidence, changes in serum creatinine (Cr) levels remain the most appropriate standard for defining AKI in cirrhosis. However, serum Cr has a limited role in assessing renal function in this population. This review examines previous studies that investigated the ability of recent biomarkers for AKI in cirrhosis from the perspective of earlier and accurate diagnosis, classification of AKI phenotype, and prediction of clinical outcomes. Serum cystatin C and urine neutrophil gelatinase-associated lipocalin have been extensively studied in cirrhosis, and have facilitated improved diagnosis and prognosis prediction in patients with AKI. In addition, urine N-acetyl-β-D-glucosaminidase, interleukin 18, and kidney injury molecule 1 are other promising biomarkers for advanced cirrhosis. However, the clinical significance of these markers remains unclear because there are no cut-off values defining the normal range and differentiating phenotypes of AKI. In addition, AKI has been defined in terms of serum Cr, and renal biopsy—the gold standard—has not been carried out in most studies. Further discovery of innovate biomarkers and incorporation of various markers could improve the diagnosis and prognosis prediction of AKI, and will translate into meaningful improvements in patient outcomes.
Abstract 14899: 4D Flow Magnetic Resonance Imaging Evaluation Of Double-decker Technique For Partial Anomalous Pulmonary Venous Return
Authors: Hisayuki Hongu, Masaaki Yamagishi, Takako Miyazaki, Yoshinobu Maeda, Satoshi Taniguchi, Shuhei Fujita, Hiroki Nakatsuji, Rina Makino, Keiichi Itatani, Hitoshi Yaku
Journal: Circulation (2017)

Introduction: Conventional procedures for partial anomalous pulmonary venous return (PAPVR) to the superior vena cava (SVC) still have problems such as late SVC obstruction, supraventricular arrhyt...
Low-cost modified endoscopic vacuum therapy using a triple-lumen tube allows nutrition and drainage for treatment of an early post–bariatric surgery leak
Authors: Diogo Turiani Hourneaux de Moura, Bruno Salomão Hirsch, Mateus Bond Boghossian, Flaubert Sena de Medeiros, Thomas R. McCarty, Christopher C. Thompson, Eduardo Guimarães Hourneaux de Moura
Journal: Endoscopy (2021)

Leaks after laparoscopic sleeve gastrectomy (LSG) occur in up to 5 % of patients, with mortality rates approaching 4 % [1]. Among available therapies for leaks after bariatric surgery, endoscopic approaches have been shown to be safe and effective. Tissue sealants, cap-mounted clips, suturing, stents, a cardiac septal defect occluder, septotomy, endoscopic internal drainage with double pigtails, and endoscopic vacuum therapy (EVT) are the forefront of the therapeutic endoscopic arsenal [2] [3]. However, an individualized approach is needed to determine the best endoscopic treatment strategy for a given patient. In this video, we describe the successful treatment of a LSG leak using low-cost modified EVT.
Somatic reversion impacts myelodysplastic syndromes and acute myeloid leukemia evolution in the short telomere disorders
Authors: Kristen E. Schratz, Valeriya Gaysinskaya, Zoe L. Cosner, Emily A. DeBoy, Zhimin Xiang, Laura Kasch-Semenza, Liliana Florea, Pali D. Shah, Mary Armanios
Journal: Journal of Clinical Investigation (2021)

BACKGROUND. Germline mutations in telomerase and other telomere maintenance genes manifest in the premature aging short telomere syndromes. Myelodysplastic syndromes and acute myeloid leukemia (MDS/AML) account for 75% of associated malignancies, but how these cancers overcome the inherited telomere defect is unknown.
Prevalence, Causes, and Health Care Burden of Pleural Effusions Among Hospitalized Adults in China
Authors: Panwen Tian, Rong Qiu, Meifang Wang, Shufeng Xu, Liming Cao, Ping Yang, Weimin Li
Journal: JAMA Network Open (2021)

This cross-sectional study investigates the estimated prevalence, common causes, and health care burden of pleural effusions among hospitalized adults in China.
Usefulness of endoscopic band ligation with gel immersion endoscopy for colonic diverticular bleeding and hemorrhoidal bleeding
Authors: Yu Kobayashi, Katsuyoshi Ando, Takahiro Sasaki, Nobuhiro Ueno, Shin Kashima, Kentaro Moriichi, Mikihiro Fujiya
Journal: Endoscopy (2021)

Endoscopic band ligation (EBL) has been recently reported as a useful hemostatic method for colonic diverticular and hemorrhoid bleeding, because of the low rate of rebleeding and high safety. However, the entry of blood into the ligation device attached to the colonoscope disturbs the visual field [1] [2]. Gel immersion endoscopy (GIE) has been recently reported to be useful for clearing the visual field when bleeding occurs during endoscopic resection [3] [4]. We report two cases in which EBL with GIE was effective for achieving endoscopic hemostasis of bleeding from diverticula and hemorrhoids.
A SARS-CoV-2 antibody broadly neutralizes SARS-related coronaviruses and variants by coordinated recognition of a virus-vulnerable site
Authors: Taishi Onodera, Shunsuke Kita, Yu Adachi, Saya Moriyama, Akihiko Sato, Takao Nomura, Shuhei Sakakibara, Takeshi Inoue, Takashi Tadokoro, Yuki Anraku, Kohei Yumoto, Cong Tian, Hideo Fukuhara, Michihito Sasaki, Yasuko Orba, Nozomi Shiwa, Naoko Iwata, Noriyo Nagata, Tateki Suzuki, Jiei Sasaki, Tsuyoshi Sekizuka, Keisuke Tonouchi, Lin Sun, Shuetsu Fukushi, Hiroyuki Satofuka, Yasuhiro Kazuki, Mitsuo Oshimura, Tomohiro Kurosaki, Makoto Kuroda, Yoshiharu Matsuura, Tadaki Suzuki, Hirofumi Sawa, Takao Hashiguchi, Katsumi Maenaka, Yoshimasa Takahashi
Journal: Immunity (2021)

Potent neutralizing SARS-CoV-2 antibodies often target the spike protein receptor-binding site (RBS), but the variability of RBS epitopes hampers broad neutralization of multiple sarbecoviruses and drifted viruses. Here, using humanized mice, we identified an RBS antibody with a germline VH gene that potently neutralized SARS-related coronaviruses, including SARS-CoV and SARS-CoV-2 variants. X-ray crystallography revealed coordinated recognition by the heavy chain of non-RBS conserved sites and the light chain of RBS with a binding angle mimicking the angiotensin-converting enzyme 2 (ACE2) receptor. The minimum footprints in the hypervariable region of RBS contributed to the breadth of neutralization, which was enhanced by immunoglobulin G3 (IgG3) class switching. The coordinated binding resulted in broad neutralization of SARS-CoV and emerging SARS-CoV-2 variants of concern. Low-dose therapeutic antibody treatment in hamsters reduced the virus titers and morbidity during SARS-CoV-2 challenge. The structural basis for broad neutralizing activity may inform the design of a broad spectrum of therapeutics and vaccines.
Allogeneic CAR Invariant Natural Killer T Cells Exert Potent Antitumor Effects through Host CD8 T-Cell Cross-Priming
Authors: Federico Simonetta, Juliane K. Lohmeyer, Toshihito Hirai, Kristina Maas-Bauer, Maite Alvarez, Arielle S. Wenokur, Jeanette Baker, Amin Aalipour, Xuhuai Ji, Samuel Haile, Crystal L. Mackall, Robert S. Negrin
Journal: Clinical Cancer Research (2021)

Abstract Purpose: The development of allogeneic chimeric antigen receptor (CAR) T-cell therapies for off-the-shelf use is a major goal that faces two main immunologic challenges, namely the risk of graft-versus-host disease (GvHD) induction by the transferred cells and the rejection by the host immune system limiting their persistence. In this work we assessed the direct and indirect antitumor effect of allogeneic CAR-engineered invariant natural killer T (iNKT) cells, a cell population without GvHD-induction potential that displays immunomodulatory properties. Experimental Design: After assessing murine CAR iNKT cells direct antitumor effects in vitro and in vivo, we employed an immunocompetent mouse model of B-cell lymphoma to assess the interaction between allogeneic CAR iNKT cells and endogenous immune cells. Results: We demonstrate that allogeneic CAR iNKT cells exerted potent direct and indirect antitumor activity when administered across major MHC barriers by inducing tumor-specific antitumor immunity through host CD8 T-cell cross-priming. Conclusions: In addition to their known direct cytotoxic effect, allogeneic CAR iNKT cells induce host CD8 T-cell antitumor responses, resulting in a potent antitumor effect lasting longer than the physical persistence of the allogeneic cells. The utilization of off-the-shelf allogeneic CAR iNKT cells could meet significant unmet needs in the clinic.
Abstract 13411: Worse Exercise Capacity With Age in VSD Patients?
Authors: Marie Maagaard, Filip Eckerstrom, Nicolai Boutrup, Vibeke Hjortdal
Journal: Circulation (2019)

Young patients in their twenties operated for a simple ventricular septal defect (VSD) in early childhood and patients with a small open VSD (QpQs<1.5) have 20% lower peak exercise capacity compare...
27489 Depth of response to abrocitinib in adults with moderate-to-severe atopic dermatitis (AD): Pooled analysis of monotherapy studies
Authors: Sonja Ständer, Neal Bhatia, Melinda J. Gooderham, Jonathan I. Silverberg, Jacob P. Thyssen, Pinaki Biswas, Marco DiBonaventura, William Romero, Saleem A. Farooqui
Journal: Journal of the American Academy of Dermatology (2021)
PD-5 Retrospective comparative analysis of K-ras G12C vs other K-ras mutations in metastatic colorectal cancer patients treated with first-line chemotherapy doublet + bevacizumab
Authors: R. Giampieri, A. Lupi, P. Ziranu, F. Pecci, A. Pretta, M. Persano, S. Crocetti, E. Giglio, A. Bittoni, A. Mandolesi, M. Scartozzi, R. Berardi
Journal: Annals of Oncology (2021)
P-187 Watch-and-wait strategy for DNA mismatch repair-deficient/microsatellite instability-high rectal cancer with a clinical complete response after neoadjuvant immunotherapy: An observational cohort study
Authors: Q. Wang, B. Xiao, W. Jiang, S. Steele, J. Cai, Z. Pan, X. Zhang, P. Ding
Journal: Annals of Oncology (2021)
Identification of TBX15 as an adipose master trans regulator of abdominal obesity genes
Authors: David Z. Pan, Zong Miao, Caroline Comenho, Sandhya Rajkumar, Amogha Koka, Seung Hyuk T. Lee, Marcus Alvarez, Dorota Kaminska, Arthur Ko, Janet S. Sinsheimer, Karen L. Mohlke, Nicholas Mancuso, Linda Liliana Muñoz-Hernandez, Miguel Herrera-Hernandez, Maria Teresa Tusié-Luna, Carlos Aguilar-Salinas, Kirsi H. Pietiläinen, Jussi Pihlajamäki, Markku Laakso, Kristina M. Garske, Päivi Pajukanta
Journal: Genome Medicine (2021)

Obesity predisposes individuals to multiple cardiometabolic disorders, including type 2 diabetes (T2D). As body mass index (BMI) cannot reliably differentiate fat from lean mass, the metabolically detrimental abdominal obesity has been estimated using waist-hip ratio (WHR). Waist-hip ratio adjusted for body mass index (WHRadjBMI) in turn is a well-established sex-specific marker for abdominal fat and adiposity, and a predictor of adverse metabolic outcomes, such as T2D. However, the underlying genes and regulatory mechanisms orchestrating the sex differences in obesity and body fat distribution in humans are not well understood.We searched for genetic master regulators of WHRadjBMI by employing integrative genomics approaches on human subcutaneous adipose RNA sequencing (RNA-seq) data (n ~ 1400) and WHRadjBMI GWAS data (n ~ 700,000) from the WHRadjBMI GWAS cohorts and the UK Biobank (UKB), using co-expression network, transcriptome-wide association study (TWAS), and polygenic risk score (PRS) approaches. Finally, we functionally verified our genomic results using gene knockdown experiments in a human primary cell type that is critical for adipose tissue function.Here, we identified an adipose gene co-expression network that contains 35 obesity GWAS genes and explains a significant amount of polygenic risk for abdominal obesity and T2D in the UKB (n = 392,551) in a sex-dependent way. We showed that this network is preserved in the adipose tissue data from the Finnish Kuopio Obesity Study and Mexican Obesity Study. The network is controlled by a novel adipose master transcription factor (TF), TBX15, a WHRadjBMI GWAS gene that regulates the network in trans. Knockdown of TBX15 in human primary preadipocytes resulted in changes in expression of 130 network genes, including the key adipose TFs, PPARG and KLF15, which were significantly impacted (FDR < 0.05), thus functionally verifying the trans regulatory effect of TBX15 on the WHRadjBMI co-expression network.Our study discovers a novel key function for the TBX15 TF in trans regulating an adipose co-expression network of 347 adipose, mitochondrial, and metabolically important genes, including PPARG, KLF15, PPARA, ADIPOQ, and 35 obesity GWAS genes. Thus, based on our converging genomic, transcriptional, and functional evidence, we interpret the role of TBX15 to be a main transcriptional regulator in the adipose tissue and discover its importance in human abdominal obesity.