tbuckley/cabot-search huggingface dataset:
Abstract 93: The Role of the Stretch-responsive Genes Mlf1 and Rnd1 for Cardiac Physiology and Pathophysiology
Authors: Annika Kluge, Jost Pott, Ashraf Y Rangrez, Alexander Bernt, Katharina Stiebeling, Norbert Frey, Derk Frank
Journal: Circulation Research (2016)

Cardiac remodeling is a typical change in function and morphology of the heart in response to pathological biomechanical stress. Despite substantial research in this area several underlying mechanisms remain unclear. We thus devised a screening experiment of dynamic stretch of neonatal cardiomyocytes (NRVCM) which revealed several genes which have not yet been implicated in cardiac remodeling before. In further analyses we focused on Mlf1 and Rnd1 , both showing significant expression in heart as well as in skeletal and liver. Conformational qRT-PCR revealed upregulation of Rnd1 mRNA (5.94x) after 24 h of stretch. Mlf1 mRNA was significantly downregulated (qRT-PCR 0.34x). Stimulation with phenylephrine (PE) induced Rnd1 mRNA (3.98x), while Mlf1 mRNA levels remained unchanged. Furthermore, in line with the in vitro results we found upregulation of Rnd1 (2.1x, p&lt;0.001) and downregulation of the cardiac Mlf1 expression (var. 1 0.45x, var. 2 0.36x, both p&lt;0.001) in mice after transverse aortic constriction. Adenoviral overexpression of Mlf1 in NRVCM induced the fetal gene program (e.g., nppa , nppb ). However, a significant decrease in cell size was found. We noticed the consistent findings after stretch or PE-stimulation. Rnd1 overexpression also led to induction of nppa , nppb and Rcan1.4, but caused an increase in cell size. To analyze whether Mlf1 and Rnd1 also influenced cell proliferation, we analyzed Mlf1/Rnd1-infected cells for the expression of proliferation markers Ki67 and phosphohistone H3 (PHH3). Mlf1 overexpression led to an increase in Ki67+ cells of about 5.92 fold, and in PHH3+ cells of 2.48 fold (p&lt;0.001), Rnd1 overexpression showed an increase in Ki67+ cells of about 6.9 fold and in PHH3+ cells of 5,25 fold (p&lt;0.001). Taken together, we could identify two stretch-sensitive genes which influence the process of cardiac hypertrophy and cell proliferation. Current work focuses on a knockdown of both genes in vivo and on the identification of potential protein-protein interactions to complete the characterization of Mlf1 and Rnd1.
Обоснование выбора метода операции в хирургическом лечении осложненных форм хронического панкреатита
Authors: V.M. Ratchik, Yu.A. Gaydar
Journal: GASTROENTEROLOGY (2013)

В клинике института за период 2010–2012 гг. оперировано 43 пациента по поводу осложненных форм хронического панкреатита. На основании данных компьютерной томографии и эндоскопической ретроградной панкреатохолангиографии выделялись значимые для выбора метода операции варианты патологии поджелудочной железы. Оценка интраоперационных биопсий показала, что основным проявлением хронического панкреатита во всех случаях выступал выраженный фиброз ткани железы. При этом, если у больных с III степенью фиброза фиброзная ткань составляла 68,2–76,4 % площади поджелудочной железы, а экзокринная — 16,2–24,8 %, у больных с IV степенью фиброза соответственно 79,5–95,5 и 2,3–10,8 %. Выделены показания для выполнения органосохраняющих резекционных, резекционно-дренирующих вмешательств и изолированных, дренирующих протоковую систему поджелудочной железы операций. Удельный вес комбинированных резекционно-дренирующих вмешательств с сохранением двенадцатиперстной кишки составил 30,2 %, общая летальность — 2,3 %, количество послеоперационных койко-дней — (9,1 ± 0,8).
高齢女性における尿路マイクロバイオームは宿主の遺伝的および環境的影響を示す【JST・京大機械翻訳】
Authors: A S Adebayo, G Ackermann, Bowyer R.C.E., P M Wells, G Humphreys, R Knight, T D Spector, C J Steves
Journal: Cell Host & Microbe (2020)
Retraction notice to “Amelioration of imiquimod-induced psoriasis-like dermatitis in mice by DSW therapy inspired hydrogel” [BIOMAT 6 (2021) 299–311]
Authors: Xiang He, Bing Zhu, WeiJia Xie, Yu He, Jian Song, Yi Zhang, Chi Sun, Hao Li, Qi Yu Tang, XinXin Sun, Yanni Tan, Yong Liu
Journal: Bioactive Materials (2021)

[This retracts the article DOI: 10.1016/j.bioactmat.2020.08.007.].
Presence and Determinants of Cardiovascular Disease and Mortality in Individuals With Type 1 Diabetes of Long Duration: The FinnDiane 50 Years of Diabetes Study
Authors: Valma Harjutsalo, Drazenka Pongrac Barlovic, Daniel Gordin, Carol Forsblom, George King, Per-Henrik Groop
Journal: Diabetes Care (2021)

The aim of this study was to determine the incidence of cardiovascular disease (CVD) and mortality as well as their risk factors in type 1 diabetes (T1D) of >50 years' duration.From 5,396 individuals included in the Finnish Diabetic Nephropathy Study (FinnDiane), 729 diagnosed in 1967 or earlier survived with T1D for >50 years. In this FinnDiane 50-year cohort, cumulative incidence of CVD events was assessed from the diagnosis of diabetes, and the excess CVD risk, compared with 12,710 matched individuals without diabetes. In addition, risk factors for different types of CVD (both nonfatal and fatal) and mortality were analyzed, and cause-specific hazard ratios were estimated during a median follow-up of 16.6 years from the baseline visit (median duration of diabetes 39 years at baseline).In individuals with diabetes duration of >50 years, the 60-year cumulative incidence of CVD from the diagnosis of diabetes was 64.3% (95% CI 62.5-66.0). Compared with individuals without diabetes, the standardized incidence ratio for CVD was 7.4 (6.5-8.3); in those with normoalbuminuria, it was 4.9 (4.0-5.9). Mean HbA1c and HbA1c variability, dyslipidemia, BMI, kidney disease, age, and diabetes duration were the variables associated with incident CVD. In particular, HbA1c was associated with peripheral artery disease (PAD). The standardized mortality ratio compared with the Finnish background population was 3.2 (2.8-3.7). The factors associated with mortality were diabetes duration, increased HbA1c variability, inflammation, insulin resistance, kidney disease, and PAD.Individuals with T1D of very long duration are at a high risk of CVD. In addition, throughout the lifespan, optimal glycemic control remains central to CVD and excess mortality prevention.
Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis
Authors: Efstathios Kastritis, Giovanni Palladini, Monique C. Minnema, Ashutosh D. Wechalekar, Arnaud Jaccard, Hans C. Lee, Vaishali Sanchorawala, Simon Gibbs, Peter Mollee, Christopher P. Venner, Jin Lu, Stefan Schönland, Moshe E. Gatt, Kenshi Suzuki, Kihyun Kim, M. Teresa Cibeira, Meral Beksac, Edward Libby, Jason Valent, Vania Hungria, Sandy W. Wong, Michael Rosenzweig, Naresh Bumma, Antoine Huart, Meletios A. Dimopoulos, Divaya Bhutani, Adam J. Waxman, Stacey A. Goodman, Jeffrey A. Zonder, Selay Lam, Kevin Song, Timon Hansen, Salomon Manier, Wilfried Roeloffzen, Krzysztof Jamroziak, Fiona Kwok, Chihiro Shimazaki, Jin-Seok Kim, Edvan Crusoe, Tahamtan Ahmadi, NamPhuong Tran, Xiang Qin, Sandra Y. Vasey, Brenda Tromp, Jordan M. Schecter, Brendan M. Weiss, Sen H. Zhuang, Jessica Vermeulen, Giampaolo Merlini, Raymond L. Comenzo
Journal: New England Journal of Medicine (2021)

Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease. We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response. A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy. Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).
Quantifying the Compressive Force of 3D Cardiac Tissues via Calculating the Volumetric Deformation of Built‐In Elastic Gelatin Microspheres
Authors: Chuanjiang He, Xinwei Wei, Tao Liang, Mengxue Liu, Deming Jiang, Liujing Zhuang, Ping Wang
Journal: Advanced Healthcare Materials (2021)

Abstract Quantifying cardiac contractile force is of paramount important in studying mechanical heart failure and screening therapeutic drugs. However, most existing methods can only measure the in‐plane component of twitch force of cardiomyocytes, such that mismatching the centripetal compressive stress of heart beating in physiology. Here, a non‐destructive method is developed for quantifying the compressive stress and mapping the distribution of the local stress within the 3D cardiac tissues. In detail, elastic gelatin microspheres labeled with fluorescence beads are fabricated by microfluidic chips with high throughput, and they serve as built‐in pressure sensors which are wrapped by cardiomyocytes in 3D tissues. The deformation of microspheres and the displacements of fluorescent beads induced by the contraction of cardiomyocytes are demonstrated to characterize the amount and distribution of the centripetal compressive stress. Further, the method shows a potent capability to locally quantify contractile force variation of 3D cardiac tissues, which is induced by agonist (norepinephrine) and inhibitor (blebbistatin). On the whole, the method significantly improves the 3D measurement of mechanical force in vitro and provides a solution for locally quantifying the compressive stress within engineered cardiac tissues.
Obstructive Sleep Apnea and Cardiovascular Disease: A Scientific Statement From the American Heart Association
Authors: Yerem Yeghiazarians, Hani Jneid, Jeremy R. Tietjens, Susan Redline, Devin L. Brown, Nabil El-Sherif, Reena Mehra, Biykem Bozkurt, Chiadi Ericson Ndumele, Virend K. Somers
Journal: Circulation (2021)

Obstructive sleep apnea (OSA) is characterized by recurrent complete and partial upper airway obstructive events, resulting in intermittent hypoxemia, autonomic fluctuation, and sleep fragmentation. Approximately 34% and 17% of middle-aged men and women, respectively, meet the diagnostic criteria for OSA. Sleep disturbances are common and underdiagnosed among middle-aged and older adults, and the prevalence varies by race/ethnicity, sex, and obesity status. OSA prevalence is as high as 40% to 80% in patients with hypertension, heart failure, coronary artery disease, pulmonary hypertension, atrial fibrillation, and stroke. Despite its high prevalence in patients with heart disease and the vulnerability of cardiac patients to OSA-related stressors and adverse cardiovascular outcomes, OSA is often underrecognized and undertreated in cardiovascular practice. We recommend screening for OSA in patients with resistant/poorly controlled hypertension, pulmonary hypertension, and recurrent atrial fibrillation after either cardioversion or ablation. In patients with New York Heart Association class II to IV heart failure and suspicion of sleep-disordered breathing or excessive daytime sleepiness, a formal sleep assessment is reasonable. In patients with tachy-brady syndrome or ventricular tachycardia or survivors of sudden cardiac death in whom sleep apnea is suspected after a comprehensive sleep assessment, evaluation for sleep apnea should be considered. After stroke, clinical equipoise exists with respect to screening and treatment. Patients with nocturnally occurring angina, myocardial infarction, arrhythmias, or appropriate shocks from implanted cardioverter-defibrillators may be especially likely to have comorbid sleep apnea. All patients with OSA should be considered for treatment, including behavioral modifications and weight loss as indicated. Continuous positive airway pressure should be offered to patients with severe OSA, whereas oral appliances can be considered for those with mild to moderate OSA or for continuous positive airway pressure-intolerant patients. Follow-up sleep testing should be performed to assess the effectiveness of treatment.
Covid-19: “Life on hold” for NHS patients needing musculoskeletal care
Authors: Kathy Oxtoby
Journal: BMJ (2021)

Conditions such as back pain and arthritis are the biggest cause of morbidity in the UK. But the pandemic has seen primary and secondary care appointments cancelled or held virtually. In the first of a new series on the "new normal" in medicine, <b>Kathy Oxtoby</b> reports on the backlogs
Hiv Specific T Cells Generated from HIV Naive Adult and Cord Blood Donors Target a Range of Novel Viral Epitopes: Implications for a Cure Strategy after Allogeneic HSCT and CBT
Authors: Shabnum Patel, Shuroug Albihani, Elizabeth Williams, Julia Sung, Conrad Russell Young Cruz, R. Brad Jones, Elizabeth J Shpall, David Margolis, Richard F Ambinder, Catherine M. Bollard
Journal: Blood (2017)
Xpo-1 Inhibition Synergizes with BCR Inhibition, Blocks Tumor Growth and Tumor-Associated Macrophages Infiltration and Prolongs Survival in a Bioluminescent Animal Model of Primary Central Nervous System Lymphoma
Authors: Marta Crespo, Júlia Carabia, Isabel Jiménez, Sabela Bobillo, Pau Abrisqueta, Carles Palacio, Juan C Nieto, Joan Boix, Cecilia Carpio, Josep Castellvi, Joan Seoane, Francesc Bosch
Journal: Blood (2017)
Society for Immunotherapy of Cancer (SITC) clinical practice guideline on immune checkpoint inhibitor-related adverse events
Authors: Julie R Brahmer, Hamzah Abu-Sbeih, Paolo Antonio Ascierto, Jill Brufsky, Laura C Cappelli, Frank B Cortazar, David E Gerber, Lamya Hamad, Eric Hansen, Douglas B Johnson, Mario E Lacouture, Gregory A Masters, Jarushka Naidoo, Michele Nanni, Miguel-Angel Perales, Igor Puzanov, Bianca D Santomasso, Satish P Shanbhag, Rajeev Sharma, Dimitra Skondra, Jeffrey A Sosman, Michelle Turner, Marc S Ernstoff
Journal: Journal for ImmunoTherapy of Cancer (2021)

Immune checkpoint inhibitors (ICIs) are the standard of care for the treatment of several cancers. While these immunotherapies have improved patient outcomes in many clinical settings, they bring accompanying risks of toxicity, specifically immune-related adverse events (irAEs). There is a need for clear, effective guidelines for the management of irAEs during ICI treatment, motivating the Society for Immunotherapy of Cancer (SITC) to convene an expert panel to develop a clinical practice guideline. The panel discussed the recognition and management of single and combination ICI irAEs and ultimately developed evidence- and consensus-based recommendations to assist medical professionals in clinical decision-making and to improve outcomes for patients.
Snail1 expression in endothelial cells controls growth, angiogenesis and differentiation of breast tumors
Authors: David Cabrerizo-Granados, Raúl Peña, Laura Palacios, Laura Carrillo-Bosch, Josep Lloreta-Trull, Laura Comerma, Mar Iglesias, Antonio García de Herreros
Journal: Theranostics (2021)

Snail1 is a transcriptional factor required for epithelial to mesenchymal transition and activation of cancer-associated fibroblasts (CAF). Apart from that, tumor endothelial cells also express Snail1. Here, we have unraveled the role of Snail1 in this tissue in a tumorigenic context. Methods: We generated transgenic mice with an endothelial-specific and inducible Snail1 depletion. This murine line was crossed with MMTV-PyMT mice that develop mammary gland tumors and the consequence of Snail1 depletion in the endothelium were investigated. We also interfere Snail1 expression in cultured endothelial cells. Results: Specific Snail1 depletion in the endothelium of adult mice does not promote an overt phenotype; however, it delays the formation of mammary gland tumors in MMTV-PyMT mice. These effects are associated to the inability of Snail1-deficient endothelial cells to undergo angiogenesis and to enhance CAF activation in a paracrine manner. Moreover, tumors generated in mice with endothelium-specific Snail1 depletion are less advanced and show a papillary phenotype. Similar changes on onset and tumor morphology are observed by pretreatment of MMTV-PyMT mice with the angiogenic inhibitor Bevacizumab. Human breast papillary carcinomas exhibit a lower angiogenesis and present lower staining of Snail1, both in endothelial and stromal cells, compared with other breast neoplasms. Furthermore, human breast tumors datasets show a strong correlation between Snail1 expression and high angiogenesis. Conclusion: These findings show a novel role for Snail1 in endothelial cell activation and demonstrate that these cells impact not only on angiogenesis, but also on tumor onset and phenotype.
Mammalian/mechanistic target of rapamycin (mTOR) complexes in neurodegeneration
Authors: Henry Querfurth, Han-Kyu Lee
Journal: Molecular Neurodegeneration (2021)

Abstract Novel targets to arrest neurodegeneration in several dementing conditions involving misfolded protein accumulations may be found in the diverse signaling pathways of the Mammalian/mechanistic target of rapamycin (mTOR). As a nutrient sensor, mTOR has important homeostatic functions to regulate energy metabolism and support neuronal growth and plasticity. However, in Alzheimer’s disease (AD), mTOR alternately plays important pathogenic roles by inhibiting both insulin signaling and autophagic removal of β-amyloid (Aβ) and phospho-tau (ptau) aggregates. It also plays a role in the cerebrovascular dysfunction of AD. mTOR is a serine/threonine kinase residing at the core in either of two multiprotein complexes termed mTORC1 and mTORC2. Recent data suggest that their balanced actions also have implications for Parkinson's disease (PD) and Huntington's disease (HD), Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). Beyond rapamycin; an mTOR inhibitor, there are rapalogs having greater tolerability and micro delivery modes, that hold promise in arresting these age dependent conditions.
Selectins impair regulatory T cell function and contribute to systemic lupus erythematosus pathogenesis
Authors: Marc Scherlinger, Vivien Guillotin, Isabelle Douchet, Pierre Vacher, Andréa Boizard-Moracchini, Jean-Philippe Guegan, Anne Garreau, Nathalie Merillon, Agathe Vermorel, Emmanuel Ribeiro, Irène Machelart, Estibaliz Lazaro, Lionel Couzi, Pierre Duffau, Thomas Barnetche, Jean-Luc Pellegrin, Jean-François Viallard, Maya Saleh, Thierry Schaeverbeke, Patrick Legembre, Marie-Elise Truchetet, Hélène Dumortier, Cécile Contin-Bordes, Vanja Sisirak, Christophe Richez, Patrick Blanco
Journal: Science Translational Medicine (2021)

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (T reg ) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted with T reg cells via the P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction with PSGL-1 blocked the regulatory and suppressive properties of T reg cells and particularly follicular T reg cells by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on T reg cells induced a down-regulation of the transforming growth factor–β axis, altering the phenotype of T reg cells and limiting their immunosuppressive responses. In patients with SLE, we found an up-regulation of P- and E-selectin both on microparticles and in their soluble forms that correlated with disease activity. Last, blocking P-selectin in a mouse model of SLE improved cardinal features of the disease, such as anti-dsDNA antibody concentrations and kidney pathology. Overall, our results identify a P-selectin–dependent pathway that is active in patients with SLE and validate it as a potential therapeutic avenue.
Targeting Pyruvate Kinase M2 Phosphorylation Reverses Aggressive Cancer Phenotypes
Authors: Maria Apostolidi, Ioannis A. Vathiotis, Viswanathan Muthusamy, Patricia Gaule, Brandon M. Gassaway, David L. Rimm, Jesse Rinehart
Journal: Cancer Research (2021)

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with low survival rate and a lack of biomarkers and targeted treatments. Here, we target pyruvate kinase M2 (PKM2), a key metabolic component of oncogenesis. In patients with TNBC, PKM2pS37 was identified as a prominent phosphoprotein corresponding to the aggressive breast cancer phenotype that showed a characteristic nuclear staining pattern and prognostic value. Phosphorylation of PKM2 at S37 was connected with a cyclin-dependent kinase (CDK) pathway in TNBC cells. In parallel, pyruvate kinase activator TEPP-46 bound PKM2pS37 and reduced its nuclear localization. In a TNBC mouse xenograft model, treatment with either TEPP-46 or the potent CDK inhibitor dinaciclib reduced tumor growth and diminished PKM2pS37. Combinations of dinaciclib with TEPP-46 reduced cell invasion, impaired redox balance, and triggered cancer cell death. Collectively, these data support an approach to identify PKM2pS37-positive TNBC and target the PKM2 regulatory axis as a potential treatment. SIGNIFICANCE: PKM2 phosphorylation marks aggressive breast cancer cell phenotypes and targeting PKM2pS37 could be an effective therapeutic approach for treating triple-negative breast cancer.
Biodegradable magnesium combined with distraction osteogenesis synergistically stimulates bone tissue regeneration via CGRP-FAK-VEGF signaling axis
Authors: None Ye Li, Jiankun Xu, Jie Mi, Xuan He, Qi Pan, Lizhen Zheng, Haiyue Zu, Ziyi Chen, Bingyang Dai, Xu Li, Qianqian Pang, Li Zou, Liangbin Zhou, Le Huang, Wenxue Tong, Gang Li, Ling Qin
Journal: Biomaterials (2021)