tbuckley/cabot-search huggingface dataset:
Prior nasal delivery of antagomiR-122 prevents radiation-induced brain injury
Authors: Haihong Zhou, Furong Sun, Mingqian Ou, Yu Zhang, Meijun Lin, Liqin Song, Yangsheng Yu, Haojie Liao, Weihao Fan, Huaijie Xing, Minhua Li, Kui Zhao, Xiaolian Wu, Yuanhong Sun, Chunmei Liang, Yujie Cai, Lili Cui
Journal: Molecular Therapy (2021)

Radiation-induced brain injury is a major adverse event in head and neck tumor treatment, influencing the quality of life for the more than 50% of patients who undergo radiation therapy and experience long-term survival. However, no effective treatments are available for these patients, and preventative drugs and effective drug-delivery methods must be developed. Based on our results, miR-122-5p was upregulated in the mouse radiation-induced brain injury (RBI) model and patients with nasopharyngeal carcinoma (NPC) who received radiation therapy. Intranasal administration of a single antagomiR-122-5p dose before irradiation effectively alleviated radiation-induced cognitive impairment, neuronal injury, and neuroinflammation in the mouse RBI model. Results further indicated that miR-122-5p inhibition in microglia reduced the levels of proinflammatory cytokines and enhanced the phagocytic function to protect against radiation-induced neuronal injury in cell models. Further, we profiled transcriptome data and verified that Tensin 1 (TNS1) may be the target of miR-122-5p in RBI. In summary, our results reveal a distinct role for miR-122-5p in regulating neuroinflammation in RBI, indicating that a non-invasive strategy for intranasal miR-122-5p administration may be an attractive therapeutic target in RBI, providing new insights for clinical trials. Further systematic safety assessment, optimization of drug administration, and clarity of mechanism will accelerate the process into clinical practice.
Baseline FeNO as a prognostic biomarker for subsequent severe asthma exacerbations in patients with uncontrolled, moderate-to-severe asthma receiving placebo in the LIBERTY ASTHMA QUEST study: a post-hoc analysis
Authors: William W Busse, Sally E Wenzel, Thomas B Casale, J Mark FitzGerald, Megan S Rice, Nadia Daizadeh, Yamo Deniz, Naimish Patel, Sivan Harel, Paul J Rowe, Neil M H Graham, Thomas O'Riordan, Ian D Pavord
Journal: The Lancet Respiratory Medicine (2021)
Should we screen for type 2 diabetes: Yes
Authors: K. Khunti, M. Davies
Journal: BMJ (2012)

<b>Kamlesh Khunti</b> and <b>Melanie Davies </b>believe that screening for diabetes is feasible and cost effective, but <b>Elizabeth Goyer and colleagues</b> (doi:10.1136/bmj.e4516) think that a population approach to modifying risk factors would be better
A Phase II Study of Azacitidine and Sirolimus for the Treatment of Acute Myeloid Leukemia (AML) Refractory to or Not Eligible for Intensive Chemotherapy or High Risk Myelodysplastic Syndrome (MDS)
Authors: Neil Palmisiano, Grace Jeschke, Lindsay Wilde, Benjamin E Leiby, Onder Alpdogan, Matthew Carabasi, Joanne Filicko-O'Hara, Sameh Gaballa, Dolores Grosso, Thomas R. Klumpp, Ubaldo Martinez Outschoorn, John L Wagner, Martin Carroll, Pierluigi Porcu, Neal Flomenberg, Alexander E. Perl, Margaret Kasner
Journal: Blood (2017)
Sleep and physical activity in relation to all-cause, cardiovascular disease and cancer mortality risk
Authors: Bo-Huei Huang, Mitch J Duncan, Peter A Cistulli, Natasha Nassar, Mark Hamer, Emmanuel Stamatakis
Journal: British Journal of Sports Medicine (2021)

Although both physical inactivity and poor sleep are deleteriously associated with mortality, the joint effects of these two behaviours remain unknown. This study aimed to investigate the joint association of physical activity (PA) and sleep with all-cause and cause-specific mortality risks.380 055 participants aged 55.9 (8.1) years (55% women) from the UK Biobank were included. Baseline PA levels were categorised as high, medium, low and no moderate-to-vigorous PA (MVPA) based on current public health guidelines. We categorised sleep into healthy, intermediate and poor with an established composited sleep score of chronotype, sleep duration, insomnia, snoring and daytime sleepiness. We derived 12 PA-sleep combinations, accordingly. Mortality risks were ascertained to May 2020 for all-cause, total cardiovascular disease (CVD), CVD subtypes (coronary heart disease, haemorrhagic stroke, ischaemic stroke), as well as total cancer and lung cancer.After an average follow-up of 11.1 years, sleep scores showed dose-response associations with all-cause, total CVD and ischaemic stroke mortality. Compared with high PA-healthy sleep group (reference), the no MVPA-poor sleep group had the highest mortality risks for all-cause (HR (95% CIs), (1.57 (1.35 to 1.82)), total CVD (1.67 (1.27 to 2.19)), total cancer (1.45 (1.18 to 1.77)) and lung cancer (1.91 (1.30 to 2.81))). The deleterious associations of poor sleep with all outcomes, except for stroke, was amplified with lower PA.The detrimental associations of poor sleep with all-cause and cause-specific mortality risks are exacerbated by low PA, suggesting likely synergistic effects. Our study supports the need to target both behaviours in research and clinical practice.
冠状動脈疾患を伴う高血圧症におけるニフェジピン抑制対ACE阻害剤の長期効果 J-MIC(B)の最終報告
Authors: Yui Y, Sumiyoshi T, Kodama K, Hirayama A, Nonogi H, Kanmatsuse K, Iimura O, Ishii M, Kawai C
Journal: Circulation (2002)
α1-Acid Glycoprotein Enhances the Immunosuppressive and Protumor Functions of Tumor-Associated Macrophages
Authors: Kotaro Matsusaka, Yukio Fujiwara, Cheng Pan, Shigeyuki Esumi, Yoichi Saito, Jing Bi, Yuka Nakamura, Ayumi Mukunoki, Toru Takeo, Naomi Nakagata, Daiki Yoshii, Ryo Fukuda, Taisei Nagasaki, Ryusei Tanaka, Hisakazu Komori, Hitoshi Maeda, Hiroshi Watanabe, Koji Tamada, Yoshihiro Komohara, Toru Maruyama
Journal: Cancer Research (2021)

Blood levels of acute-phase protein α1-acid glycoprotein (AGP, orosmucoid) increase in patients with cancer. Although AGP is produced from hepatocytes following stimulation by immune cell-derived cytokines under conditions of inflammation and tumorigenesis, the functions of AGP in tumorigenesis and tumor progression remain unknown. In the present study, we revealed that AGP contributes directly to tumor development by induction of programmed death ligand 1 (PD-L1) expression and IL6 production in macrophages. Stimulation of AGP induced PD-L1 expression in both human monocyte-derived macrophages through STAT1 activation, whereas AGP had no direct effect on PD-L1 expression in tumor cells. AGP also induced IL6 production from macrophages, which stimulated proliferation in tumor cells by IL6R-mediated activation of STAT3. Furthermore, administration of AGP to AGP KO mice phenocopied effects of tumor-associated macrophages (TAM) on tumor progression. AGP decreased IFNγ secretion from T cells and enhanced STAT3 activation in subcutaneous tumor tissues. In addition, AGP regulated PD-L1 expression and IL6 production in macrophages by binding with CD14, a coreceptor for Toll-like receptor 4 (TLR4), and inducing TLR4 signaling. These results provide the first evidence that AGP is directly involved in tumorigenesis by interacting with TAMs and that AGP might be a target molecule for anticancer therapy. SIGNIFICANCE: AGP-mediated suppression of antitumor immunity contributes to tumor progression by inducing PD-L1 expression and IL6 production in TAMs.
Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response
Authors: Tong Fu, Lei-Jie Dai, Song-Yang Wu, Yi Xiao, Ding Ma, Yi-Zhou Jiang, Zhi-Ming Shao
Journal: Journal of Hematology & Oncology (2021)

Tumors are not only aggregates of malignant cells but also well-organized complex ecosystems. The immunological components within tumors, termed the tumor immune microenvironment (TIME), have long been shown to be strongly related to tumor development, recurrence and metastasis. However, conventional studies that underestimate the potential value of the spatial architecture of the TIME are unable to completely elucidate its complexity. As innovative high-flux and high-dimensional technologies emerge, researchers can more feasibly and accurately detect and depict the spatial architecture of the TIME. These findings have improved our understanding of the complexity and role of the TIME in tumor biology. In this review, we first epitomized some representative emerging technologies in the study of the spatial architecture of the TIME and categorized the description methods used to characterize these structures. Then, we determined the functions of the spatial architecture of the TIME in tumor biology and the effects of the gradient of extracellular nonspecific chemicals (ENSCs) on the TIME. We also discussed the potential clinical value of our understanding of the spatial architectures of the TIME, as well as current limitations and future prospects in this novel field. This review will bring spatial architectures of the TIME, an emerging dimension of tumor ecosystem research, to the attention of more researchers and promote its application in tumor research and clinical practice.
Correspondence on ‘Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study’
Authors: Timothée Klopfenstein, Vincent Gendrin, Thierry Conrozier, Aurélie Gerazime, Marc Puyraveau, Souheil Zayet
Journal: Annals of the Rheumatic Diseases (2021)

We have read with great interest the study conducted by Ramiro et al 1 entitled ‘Historically controlled comparison of glucocorticoids with or without tocilizumab versus supportive care only in patients with COVID-19-associated cytokine storm syndrome: results of the CHIC study’. This study was among the first publications showing benefit of tocilizumab administration in patients with severe COVID-19-associated cytokine storm syndrome, in July 2020.1 In the same way, we observed a benefit of tocilizumab administration in a cohort of 206 patients during the first wave of the pandemic, in June 2020.2

We have now more ‘evidence-based medicine’ to discuss tocilizumab’s place in COVID-19. Thus, nine randomised clinical trials (RCTs)3–11 have been published about tocilizumab administration in COVID-19; however, the effects on mortality remain heterogeneous in these trials.12 We recently made a …
Body-mass index and obesity in urban and rural China: findings from consecutive nationally representative surveys during 2004–18
Authors: Limin Wang, Bin Zhou, Zhenping Zhao, Ling Yang, Mei Zhang, Yong Jiang, Yichong Li, Maigeng Zhou, Linhong Wang, Zhengjing Huang, Xiao Zhang, Liyun Zhao, Dongmei Yu, Chun Li, Majid Ezzati, Zhengming Chen, Jing Wu, Gangqiang Ding, Xinhua Li
Journal: The Lancet (2021)
Blast Phase Myeloproliferative Neoplasm: A Mayo Agimm Study of 419 Consecutive Cases
Authors: Ayalew Tefferi, Mythri Mudireddy, Kebede H. Begna, Curtis A. Hanson, Rhett P. Ketterling, Naseema Gangat, Animesh Pardanani, Meera Yogarajah, Valerio De Stefano, Francesco Passamonti, Vittorio Rosti, Maria Chiara Finazzi, Alessandro Rambaldi, Francesco Mannelli, Paola Guglielmelli, Alessandro M. Vannucchi
Journal: Blood (2017)
ステント破砕はステントデザインまたは薬物溶出性質で引き起こされるか?シロリムス溶出ステント(SES)とBX-速度ステント(BX-BMS)との間の比較
Authors: Gohchi Tomoko, Umeda Hisashi, Hattori Kosuke, Ishikawa Makoto, Okumura Masanori, Kann Shino, Naruse Hiroyuki, Matsui Shigeru, Ishii Junichi, Hishida Hitoshi, Ozaki Yukio
Journal: Circulation (2008)
Self-tunable engineered yeast probiotics for the treatment of inflammatory bowel disease
Authors: Benjamin M. Scott, Cristina Gutiérrez-Vázquez, Liliana M. Sanmarco, Jessica A. da Silva Pereira, Zhaorong Li, Agustín Plasencia, Patrick Hewson, Laura M. Cox, Madelynn O’Brien, Steven K. Chen, Pedro M. Moraes-Vieira, Belinda S. W. Chang, Sergio G. Peisajovich, Francisco J. Quintana
Journal: Nature Medicine (2021)
A proteomic network approach resolves stage-specific molecular phenotypes in chronic traumatic encephalopathy
Authors: Laura Gutierrez-Quiceno, Eric B. Dammer, Ashlyn Grace Johnson, James A. Webster, Rhythm Shah, Duc Duong, Luming Yin, Nicholas T. Seyfried, Victor E. Alvarez, Thor D. Stein, Ann C. McKee, Chadwick M. Hales
Journal: Molecular Neurodegeneration (2021)

Abstract Background There is an association between repetitive head injury (RHI) and a pathologic diagnosis of chronic traumatic encephalopathy (CTE) characterized by the aggregation of proteins including tau. The underlying molecular events that cause these abnormal protein accumulations remain unclear. Here, we hypothesized that identifying the human brain proteome from serial CTE stages (CTE I-IV) would provide critical new insights into CTE pathogenesis. Brain samples from frontotemporal lobar degeneration due to microtubule associated protein tau (FTLD-MAPT) mutations were also included as a distinct tauopathy phenotype for comparison. Methods Isobaric tandem mass tagged labeling and mass spectrometry (TMT-MS) followed by integrated differential and co-expression analysis (i.e., weighted gene co-expression network analysis (WGCNA)) was used to define modules of highly correlated proteins associated with clinical and pathological phenotypes in control ( n = 23), CTE ( n = 43), and FTLD-MAPT ( n = 12) post-mortem cortical tissues. We also compared these findings to network analysis of AD brain. Results We identified over 6000 unique proteins across all four CTE stages which sorted into 28 WGCNA modules. Consistent with Alzheimer’s disease, specific modules demonstrated reduced neuronal protein levels, suggesting a neurodegeneration phenotype, while other modules were increased, including proteins associated with inflammation and glial cell proliferation. Notably, unique CTE-specific modules demonstrated prominent enrichment of immunoglobulins, including IGHM and IGLL5, and extracellular matrix (ECM) proteins as well as progressive protein changes with increasing CTE pathologic stage. Finally, aggregate cell subtype (i.e., neurons, microglia, astrocytes) protein abundance levels in CTE cases were similar in expression to AD, but at intermediate levels between controls and the more exaggerated phenotype of FTLD-MAPT, especially in astrocytes. Conclusions Overall, we identified thousands of protein changes in CTE postmortem brain and demonstrated that CTE has a pattern of neurodegeneration in neuronal-synaptic and inflammation modules similar to AD. We also identified unique CTE progressive changes, including the enrichment of immunoglobulins and ECM proteins even in early CTE stages. Early and sustained changes in astrocyte modules were also observed. Overall, the prominent overlap with FTLD-MAPT cases confirmed that CTE is on the tauopathy continuum and identified CTE stage specific molecular phenotypes that provide novel insights into disease pathogenesis.
The Control of the Lead Hazard in the Storage Battery Industry
Authors: Waldemar C. Dreessen, Thomas I. Edwards, Warren H. Reinhart, Richard T. Page, Stewart H. Webster, David W. Armstrong, R. R. Sayers
Journal: JAMA (1941)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Late and very late relapsed acute lymphoblastic leukemia: clinical and molecular features, and treatment outcomes
Authors: Ibrahim Aldoss, Raju Pillai, Dongyun Yang, Lixin Yang, Shukaib Arslan, Sally Mokhtari, Monzr M. Al Malki, Amandeep Salhotra, Shilpa Shahani, Haris Ali, Matthew Mei, Andrew Artz, David Snyder, Michelle Afkhami, Saro Armenian, Anthony Stein, Guido Marcucci, Stephen J. Forman, Ryotaro Nakamura, Vinod Pullarkat
Journal: Blood Cancer Journal (2021)
Abstract 313: Nonionic Acid is a Target Metabolite of Diabetic Microvasculopathy
Authors: Yasuko K Bando, Haruya Kawase, Kazuyuki Nishimura, Akio Monji, Toyoaki Murohara
Journal: Circulation Research (2016)

Aim: The purpose of this study is to screen the target metabolites of diabetic microangiopathy in heart by use of whole heart metabolome analysis. Methods: Diet-induced type 2 diabetic mouse were divided into two groups; control and those treated with diabetic remedy GLP-1 receptor agonist Ex-4 for 5 weeks. Mice were euthanized and analyzed at the age of 16 week-old. Results: The capillary density of the T2DM was reduced as compared to those non-diabetic counterparts, which was restored by Ex4 treatment. Changes in angiogenic signals detected by immunoblotting analysis revealed that the phosphorylation levels of eNOS and AMPK were elevated by Ex-4, but those Akt remained unchanged. Tube formation assay revealed that Ex-4 increased tube length and branch points in HUVECs. Consistently with the trend that was observed in vivo experiment, AMPK and eNOS phosphorylation levels were enhanced by Ex4 without affecting Akt phosphorylation. To screen the candidate metabolites that is responsible for the diabetic microvasculopathy in GLP-1-dependent fashion, we performed metabolome analysis by using the whole heart of each mouse. The hierarchical cluster analysis revealed that nonanoic acid (NNA) was the only metabolite that increased in type 2 diabetic mice with concomitant decline by Ex-4 treatment. We next examined the impact of nonanoic acid on in vitro angiogenesis and found that NNA suppressed tube length and branch points in HUVECs in a dose-dependent fashion. Interestingly, NNA canceled eNOS and AMPK phosphorylation that was enhanced by Ex4. Conclusion: GLP-1 ameliorated diabetic microvasculopathy via the AMPK and eNOS axis. NNA is presumably one of the novel anti-angiogenic metabolites that causes diabetic microangiopathy.
Prognostic accuracy of a peripheral blood transcriptome signature in chronic hypersensitivity pneumonitis
Authors: Evans R Fernández Pérez, Laura D Harmacek, Brian P O'Connor, Thomas Danhorn, Brian Vestal, Lisa A Maier, Tilman L Koelsch, Sonia M Leach
Journal: Thorax (2021)

The prognostic value of peripheral blood mononuclear cell (PBMC) expression profiles, when used in patients with chronic hypersensitivity pneumonitis (CHP), as an adjunct to traditional clinical assessment is unknown. RNA-seq analysis on PBMC from 37 patients with CHP at initial presentation determined that (1) 74 differentially expressed transcripts at a 10% false discovery rate distinguished those with (n=10) and without (n=27) disease progression, defined as absolute FVC and/or diffusing capacity of the lungs for carbon monoxide (DLCO) decline of ≥10% and increased fibrosis on chest CT images within 24 months, and (2) classification models based on gene expression and clinical factors strongly outperform models based solely on clinical factors (baseline FVC%, DLCO% and chest CT fibrosis).
Association of Clonal Hematopoiesis With Incident Heart Failure
Authors: Bing Yu, Mary B. Roberts, Laura M. Raffield, Seyedeh Maryam Zekavat, Ngoc Quynh H. Nguyen, Mary L. Biggs, Michael R. Brown, Gabriel Griffin, Pinkal Desai, Adolfo Correa, Alanna C. Morrison, Amil M. Shah, Abhishek Niroula, Md Mesbah Uddin, Michael C. Honigberg, Benjamin L. Ebert, Bruce M. Psaty, Eric A. Whitsel, JoAnn E. Manson, Charles Kooperberg, Alexander G. Bick, Christie M. Ballantyne, Alex P. Reiner, Pradeep Natarajan, Charles B. Eaton
Journal: Journal of the American College of Cardiology (2021)
Fishing for an Association With Sudden Cardiac Death—Reply
Authors: Andrew Mente, Mahshid Dehghan, Salim Yusuf
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Genomic Profiling Reveals Spatial Intra-Tumor Heterogeneity in Follicular Lymphoma
Authors: Shamzah Araf, Jun Wang, Koorosh Korfi, Celine Pangault, Eleni Kotsiou, Ana Rio-Machin, Tahrima Rahim, James Andrew Heward, Andrew James Clear, Sameena Iqbal, Jeff Davies, Peter Johnson, Maria Calaminici, Silvia Montoto, Rebecca Auer, Claude Chelala, John G. Gribben, Trevor Graham, Thierry Fest, Jude Fitzgibbon, Jessica Okosun
Journal: Blood (2017)
Is Food Addictive? A Review of the Science
Authors: Ashley N. Gearhardt, Erica M. Schulte
Journal: Annual Review of Nutrition (2021)

As ultraprocessed foods (i.e., foods composed of mostly cheap industrial sources of dietary energy and nutrients plus additives) have become more abundant in our food supply, rates of obesity and diet-related disease have increased simultaneously. Food addiction has emerged as a phenotype of significant empirical interest within the past decade, conceptualized most commonly as a substance-based addiction to ultraprocessed foods. We detail (a) how approaches used to understand substance-use disorders may be applicable for operationalizing food addiction, (b) evidence for the reinforcing potential of ingredients in ultraprocessed foods that may drive compulsive consumptions, (c) the utility of conceptualizing food addiction as a substance-use disorder versus a behavioral addiction, and (d) clinical and policy implications that may follow if ultraprocessed foods exhibit an addictive potential. Broadly, the existing literature suggests biological and behavioral parallels between food addiction and substance addictions, with ultraprocessed foods high in both added fat and refined carbohydrates being most implicated in addictive-like eating. Future research priorities are also discussed, including the need for longitudinal studies and the potential negative impact of addictive ultraprocessed foods on children.