tbuckley/cabot-search huggingface dataset:
Human cancer germline antigen-specific cytotoxic T cell—what can we learn from patient
Authors: Megat Abd Hamid, Yanchun Peng, Tao Dong
Journal: Cellular and Molecular Immunology (2020)

Abstract In this review, we will highlight the importance of cancer germline antigen-specific cytotoxic CD8 + T lymphocytes (CTL) and the factors affecting antitumor CTL responses. In light of cancer immunotherapy, we will emphasis the need to further understand the features, characteristics, and actions of modulatory receptors of human cancer germline-specific CTLs, in order to determine the optimal conditions for antitumor CTL responses.
Exposed CendR Domain in Homing Peptide Yields Skin-Targeted Therapeutic in Epidermolysis Bullosa
Authors: Toini Pemmari, Larisa Ivanova, Ulrike May, Prakash Lingasamy, Allan Tobi, Anja Pasternack, Stuart Prince, Olli Ritvos, Shreya Makkapati, Tambet Teesalu, Mitchell S. Cairo, Tero A.H. Järvinen, Yanling Liao
Journal: Molecular Therapy (2020)

Systemic skin-selective therapeutics would be a major advancement in the treatment of diseases affecting the entire skin, such as recessive dystrophic epidermolysis bullosa (RDEB), which is caused by mutations in the COL7A1 gene and manifests in transforming growth factor-β (TGF-β)-driven fibrosis and malignant transformation. Homing peptides containing a C-terminal R/KXXR/K motif (C-end rule [CendR] sequence) activate an extravasation and tissue penetration pathway for tumor-specific drug delivery. We have previously described a homing peptide CRKDKC (CRK) that contains a cryptic CendR motif and homes to angiogenic blood vessels in wounds and tumors, but it cannot penetrate cells or tissues. In this study, we demonstrate that removal of the cysteine from CRK to expose the CendR sequence confers the peptide novel ability to home to normal skin. Fusion of the truncated CRK (tCRK) peptide to the C terminus of an extracellular matrix protein decorin (DCN), a natural TGF-β inhibitor, resulted in a skin-homing therapeutic molecule (DCN-tCRK). Systemic DCN-tCRK administration in RDEB mice led to inhibition of TGF-β signaling in the skin and significant improvement in the survival of RDEB mice. These results suggest that DCN-tCRK has the potential to be utilized as a novel therapeutic compound for the treatment of dermatological diseases such as RDEB. Systemic skin-selective therapeutics would be a major advancement in the treatment of diseases affecting the entire skin, such as recessive dystrophic epidermolysis bullosa (RDEB), which is caused by mutations in the COL7A1 gene and manifests in transforming growth factor-β (TGF-β)-driven fibrosis and malignant transformation. Homing peptides containing a C-terminal R/KXXR/K motif (C-end rule [CendR] sequence) activate an extravasation and tissue penetration pathway for tumor-specific drug delivery. We have previously described a homing peptide CRKDKC (CRK) that contains a cryptic CendR motif and homes to angiogenic blood vessels in wounds and tumors, but it cannot penetrate cells or tissues. In this study, we demonstrate that removal of the cysteine from CRK to expose the CendR sequence confers the peptide novel ability to home to normal skin. Fusion of the truncated CRK (tCRK) peptide to the C terminus of an extracellular matrix protein decorin (DCN), a natural TGF-β inhibitor, resulted in a skin-homing therapeutic molecule (DCN-tCRK). Systemic DCN-tCRK administration in RDEB mice led to inhibition of TGF-β signaling in the skin and significant improvement in the survival of RDEB mice. These results suggest that DCN-tCRK has the potential to be utilized as a novel therapeutic compound for the treatment of dermatological diseases such as RDEB.
Abstract 15311: Single Cell Coating With Surface-Anchored Nanogel Improves the Engraftment and Reparative Potency of Transplanted Mesenchymal Stem Cells in Infarcted Rat Hearts
Authors: Xin Yang Hu, Ling Zhang, Jian’an Wang, Ben Wang
Journal: Circulation (2019)

Objective: The survival and engraftment rates of stem cells in the infarcted hearts are poor and believed to limit the effectiveness of cell therapy. We developed a novel technique for applying a s...
Phenotype and Outcomes of Pulmonary Hypertension Associated with Neurofibromatosis Type 1
Authors: Etienne-Marie Jutant, Xavier Jaïs, Barbara Girerd, Laurent Savale, Maria-Rosa Ghigna, Frédéric Perros, Xavier Mignard, Mitja Jevnikar, Delphine Bourlier, Grégoire Prevot, Cécile Tromeur, Fabrice Bauer, Emmanuel Bergot, Claire Dauphin, Nicolas Favrolt, Julie Traclet, Thibaud Soumagne, Pascal De Groote, Céline Chabanne, Pascal Magro, Laurent Bertoletti, Jean-Pierre Gueffet, Ari Chaouat, François Goupil, Pamela Moceri, Raphael Borie, Elie Fadel, Pierre Wolkenstein, Pierre-Yves Brillet, Gérald Simonneau, Olivier Sitbon, Marc Humbert, David Montani
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Pulmonary hypertension (PH) associated with neurofibromatosis type 1 (NF1) is a rare and largely unknown complication of NF1.Objectives: To describe characteristics and outcomes of PH-NF1.Methods: We reported the clinical, functional, radiologic, histologic, and hemodynamic characteristics, response to pulmonary arterial hypertension (PAH)-approved drugs, and transplant-free survival of patients with PH-NF1 from the French PH registry.Measurements and Main Results: We identified 49 PH-NF1 cases, characterized by a female/male ratio of 3.9 and a median (minimum-maximum) age at diagnosis of 62 (18-82) years. At diagnosis, 92% were in New York Heart Association functional class III or IV. The 6-minute-walk distance was 211 (0-460) m. Pulmonary function tests showed low DlCO (30% [12-79%]) and severe hypoxemia (PaO2 56 [38-99] mm Hg). Right heart catheterization showed severe precapillary PH with a mean pulmonary artery pressure of 45 (10) mm Hg and a pulmonary vascular resistance of 10.7 (4.2) Wood units. High-resolution computed tomography images revealed cysts (76%), ground-glass opacities (73%), emphysema (49%), and reticulations (39%). Forty patients received PAH-approved drugs with a significant improvement in functional class and hemodynamic parameters. Transplant-free survival at 1, 3, and 5 years was 87%, 54%, and 42%, respectively, and four patients were transplanted. Pathologic assessment showed nonspecific interstitial pneumonia and major pulmonary vascular remodeling.Conclusions: PH-NF1 is characterized by a female predominance, a low DlCO, and severe functional and hemodynamic impairment. Despite a potential benefit of PAH treatment, prognosis remains poor, and double-lung transplantation is an option for eligible patients.
Abstract 114: Myocardin-Related Transcription Factors Are Required for Compensatory Signaling in Maladaptive Cardiac Remodeling
Authors: Michael A Trembley, Deanne M Mickelson, Ronald Dirkx, Jeffrey D Alexis, Christine Moravec, Eric M Small
Journal: Circulation Research (2017)

Intercellular communication is essential for coordinating the contraction of cardiomyocytes. This synchrony is established by coupling electrical activity and force transmission at specialized junctions called intercalated discs (ICDs). We have recently found that myocardin-related transcription factor A (MRTF-A) and –B (MRTFs) accumulate at ICDs of healthy mouse and human hearts, but are redistributed in cardiac pathology. MRTFs are mechanosensitive transcriptional co-activators of serum response factor (SRF) that regulate the actin cytoskeleton; however, the role of MRTFs in cardiomyocyte homeostasis remains unclear. We conditionally deleted Mrtfb in cardiomyocytes of mice harboring a homozygous null allele of Mrtfa (called MRTF cmdKO ). MRTF cmdKO mice exhibit no changes in cardiac function for up to a year; however, MRTF depletion results in conspicuous gap junction remodeling at ICDs and reduced cardiomyocyte communication. This phenotype stems from a significant reduction in genes important for trafficking gap junction proteins, including RP/EB family member 1 ( Mapre1 ), which we show is a direct transcriptional target of SRF/MRTFs. The absence of a functional phenotype amid gap junction displacement prompted us to model heart failure and mechanical stress at ICDs by subjecting MRTF cmdKO mice to transaortic constriction (TAC) surgery. Unexpectedly, MRTF cmdKO mice display partially penetrant sudden cardiac death within 2 weeks post-TAC surgery. MRTF cmdKO survivors undergo accelerated heart failure with a reduced adaptive gene response compared to controls. Future investigations are underway to determine the mechanisms governing accentuated heart failure in MRTF cmdKO mice. Taken together, the subcellular localization of MRTFs to ICDs creates a paradigm in which potent transcription factors are anchored to regions of electromechanical stress, which may represent a signaling circuit for ICD maintenance and remodeling in disease.
181TiP Xentuzumab (Xe) in combination with everolimus (Ev) and exemestane (Ex) in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) and non-visceral involvement (XENERA™-1)
Authors: P. Schmid, H.S. Rugo, J. Cortés, P. Blum, K. Crossley, D. Massey, H.A. Burris
Journal: Annals of Oncology (2020)
Leukocyte Heterogeneity in Adipose Tissue, Including in Obesity
Authors: Ada Weinstock, Hernandez Moura Silva, Kathryn J. Moore, Ann Marie Schmidt, Edward A. Fisher
Journal: Circulation Research (2020)

Adipose tissue (AT) plays a central role in both metabolic health and pathophysiology. Its expansion in obesity results in increased mortality and morbidity, with contributions to cardiovascular disease, diabetes mellitus, fatty liver disease, and cancer. Obesity prevalence is at an all-time high and is projected to be 50% in the United States by 2030. AT is home to a large variety of immune cells, which are critical to maintain normal tissue functions. For example, γδ T cells are fundamental for AT innervation and thermogenesis, and macrophages are required for recycling of lipids released by adipocytes. The expansion of visceral white AT promotes dysregulation of its immune cell composition and likely promotes low-grade chronic inflammation, which has been proposed to be the underlying cause for the complications of obesity. Interestingly, weight loss after obesity alters the AT immune compartment, which may account for the decreased risk of developing these complications. Recent technological advancements that allow molecular investigation on a single-cell level have led to the discovery of previously unappreciated heterogeneity in many organs and tissues. In this review, we will explore the heterogeneity of immune cells within the visceral white AT and their contributions to homeostasis and pathology.
2O ERBB3 mRNA expression in breast cancer (BC): A SOLTI biomarker discovery analysis
Authors: T. Pascual, M. Oliveira, E.M. Ciruelos, M. Bellet Ezquerra, C. Saura, J. Gavila Gregori, S. Pernas Simon, M. Muñoz, M.J. Vidal, M. Margeli Vila, J.M. Cejalvo, B. González-Farré, M. Espinosa-Bravo, J.M. Ferrero-Cafiero, P. Villagrasa, A. Prat
Journal: Annals of Oncology (2020)
Case 16-2020: A 47-Year-Old Woman with Recurrent Melanoma and Pulmonary Nodules
Authors: Katrina A. Armstrong, Justine V. Cohen, Jo-Anne O. Shepard, Erik E. Folch, Michael K. Mansour, Jonathan A. Stefely
Journal: New England Journal of Medicine (2020)

An asymptomatic 47-year-old woman with a history of recurrent melanoma presented to the hospital after routine quarterly surveillance imaging, performed after resection of right axillary melanoma, radiation therapy, and pembrolizumab therapy, had revealed new hilar and mediastinal lymphadenopathy and new pulmonary nodules. Diagnostic tests were performed.
134TiP A phase III trial of nivolumab with neoadjuvant chemotherapy and adjuvant endocrine therapy in ER+/HER2− primary breast cancer: CheckMate 7FL
Authors: G. Curigliano, H. McArthur, N. Harbeck, L. Pusztai, S. Delaloge, K. Letrent, T. Chen, B. Li, K. Tatsuoka, D. Zardavas, S. Loi
Journal: Annals of Oncology (2020)
Accuracy of penicillin allergy diagnostic tests: A systematic review and meta-analysis
Authors: Bernardo Sousa-Pinto, Isabel Tarrio, Kimberly G. Blumenthal, Luís Araújo, Luís Filipe Azevedo, Luís Delgado, João Almeida Fonseca
Journal: Journal of Allergy and Clinical Immunology (2020)
SOME PUBLIC HEALTH ASPECTS OF UNDULANT FEVER
Authors: HAROLD G.  NEWMAN
Journal: Annals of Internal Medicine (1938)

Article1 May 1938SOME PUBLIC HEALTH ASPECTS OF UNDULANT FEVERHAROLD G. NEWMAN, B.S., A.M., M.D.HAROLD G. NEWMAN, B.S., A.M., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-11-1973 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIn this brief discussion undulant fever is treated as a public health problem in order to bring out a few points concerning the diseases in lower animals from which the human being derives his infection. It is felt that to many medical men more information concerning the manifestations of this disease in domestic animals will be of interest.Considerable confusion exists over the terminology. Malta fever, undulant fever, brucellosis, brucelliasis, Mediterranean fever, Bang's disease and many other terms are employed. Similarly there has existed among bacteriologists considerable controversy over the classification and relationship of the bacteria present in the lower...Bibliography1. BRUCE D: Note on the discovery of a microörganism in Malta fever, Practitioner, London, 1887, xxxix, 161-170. Google Scholar2. WRIGHT AE: On the application of the serum test to the differential diagnosis of typhoid and Malta fever, and on the further application of the method of serum diagnosis to the elucidation of certain problems in connection with the duration of immunity and the geographical distribution of disease, Lancet, 1897, i. Google Scholar3. EVANS AC: Further studies on Bacterium abortus and related bacteria, Jr. Infect. Dis., 1918, xxii, 580-593. CrossrefGoogle Scholar4. BANG B: The etiology of epizoötic abortion, Jr. Comp. Path. and Therap., 1897, x, 125. CrossrefGoogle Scholar5. GILTNER W: Brucellosis, a public health problem, Memoir 1, March 1934. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: St. Louis, Missouri*Received for publication May 25, 1937.From the Medical Service of St. Luke's Hospital, St. Louis, Missouri. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1938Volume 11, Issue 11Page: 1973-1978KeywordsBacteriaBrucellosisFeversInfectious diseasesMedical servicesPrevention, policy, and public health ePublished: 1 December 2008 Issue Published: 1 May 1938 PDF downloadLoading ...
Prevalence of Sexual Activity and Associated Factors in Men Aged 75 to 95 Years
Authors: Zoë Hyde, Leon Flicker, Graeme J. Hankey, Osvaldo P. Almeida, Kieran A. McCaul, S.A. Paul Chubb, Bu B. Yeap
Journal: Annals of Internal Medicine (2010)

Data on sexuality and aging are scarce. This survey gathered data from Australian men aged 75 to 95 years about social and medical factors, hormone levels, and self-reports of sexual activity over ...
Infantile Cortical Hyperostosis
Authors: James B. Sidbury, J. Buren Sidbury
Journal: New England Journal of Medicine (1954)

THE syndrome that has become known as infantile cortical hyperostosis, after the suggestion of Caffey and Silverman,1 is characterized by the usually sudden onset of swelling of the face, thorax or extremities, hyperirritability, fever, fluctuating course and roentgenographic evidence of periosteal new-bone formation. Probably the first case was described by Roske,2 but the syndrome was not appreciated until the publication of the descriptions of the clinical and roentgenologic picture.1 , 3 , 4 There are now over 60 cases in the literature. Sherman and Hellyer5 reviewed their x-ray films taken of infants during the preceding twenty years and found no case of infantile cortical . . .
Phase I dose-escalation trial of tucatinib in combination with trastuzumab in patients with HER2-positive breast cancer brain metastases
Authors: O. Metzger Filho, J.P. Leone, T. Li, Z. Tan-Wasielewski, L. Trippa, W.T. Barry, J. Younger, E. Lawler, L. Walker, R.A. Freedman, S.M. Tolaney, I. Krop, E.P. Winer, N.U. Lin
Journal: Annals of Oncology (2020)

Brain metastases are frequent in HER2-positive breast cancer. ONT-380 (tucatinib) is a potent selective inhibitor of HER2 with intracranial activity in preclinical models.This was a phase I study of tucatinib with trastuzumab, without chemotherapy, in patients with progressive, measurable HER2-positive brain metastases. The study tested two schedules of tucatinib: cohort A was twice daily and cohort B was once daily. The primary objective was determination of the maximum tolerated dose (MTD). Secondary end points included objective response (intracranial and extracranial) using modified RECIST and clinical benefit rate (CBR).Overall, 41 patients were enrolled (cohort A, n = 22; cohort B, n = 19). Patients had a median of two prior treatments for metastatic breast cancer and 83% had progressed after prior brain radiation. The MTD of tucatinib for cohort A was 300 mg twice daily and for cohort B was 750 mg once daily. The most common dose-limiting toxicities included thrombocytopenia and aspartate transaminase/alanine aminotransferase elevation. Grade 3/4 aspartate transaminase/alanine aminotransferase elevation occurred in nine of 41 patients (22%). Intracranial responses were observed in two of 17 (12%) patients in cohort A and one of 17 (6%) patients in cohort B treated at the MTD. In cohort A, CBR at 16 weeks was 35% (n = 6). In cohort B, CBR at 16 weeks was 53% (n = 9). Of 15 patients overall who experienced clinical benefit, 12 (80%) had received prior neratinib and/or lapatinib. Median progression-free survival for cohorts A and B was 3.4 and 4.1 months, respectively.The combination of tucatinib and trastuzumab is tolerable and demonstrated preliminary evidence of efficacy in patients with HER2-positive brain metastases.NCT01921335.
Imaging-based vascular-related biomarkers for early detection of acetaminophen-induced liver injury
Authors: Haolu Wang, Leslie J. Burke, Jatin Patel, Brian WC. Tse, Kim R. Bridle, Victoria C. Cogger, Xinxing Li, Xin Liu, Haotian Yang, Darrell H. G. Crawford, Michael S. Roberts, Wenchao Gao, Xiaowen Liang
Journal: Theranostics (2020)

Acetaminophen (APAP) is the foremost cause of drug-induced liver injury in the Western world.Most studies of APAP hepatotoxicity have focused on the hepatocellular injury, but current hepatocyte-related biomarkers have delayed presentation time and a lack of sensitivity.APAP overdose can induce hepatic microvascular congestion, which importantly precedes the injury of hepatocytes.However, the underlying molecular mechanisms remain unclear.It is imperative to discover and validate sensitive and specific translational biomarkers of APAP-induced liver injury.Methods: In this study, we assessed APAP toxicity in sinusoidal endothelial cells and hepatocytes in mice treated with overdose APAP at different time points.The underlying mechanisms of APAP overdose induced sinusoidal endothelial cell injury were investigated by RT 2 Profiler PCR arrays.The impact of APAP overdose on endothelial cell function was assessed by pseudovessel formation of endothelial cells in 2D Matrigel and in vivo hepatic vascular integrity using multiphoton microscopy.Finally, the effects of APAP overdose on oxygen levels in the liver and hepatic microcirculation were evaluated by contrast enhanced ultrasonography.Potential imaging-based vascular-related markers for early detection of APAP induced liver injury were assessed.Results: Our study confirmed that hepatic endothelial cells are an early and direct target for APAP hepatotoxicity.ICAM1-related cellular adhesion pathways played a prominent role in APAP-induced endothelial cell injury, which was further validated in primary human sinusoidal endothelial cells and human livers after APAP overdose.APAP overdose impacted pseudovessel formation of endothelial cells and in vivo hepatic vascular integrity.Use of ultrasound to detect APAP-induced liver injury demonstrated that mean transit time, an imaging-based vascular-related biomarker, was more sensitive and precise for early detection of APAP hepatotoxicity and monitoring the treatment response in comparison with a conventional blood-based biomarker. Conclusion:Imaging-based vascular-related biomarkers can identify early and mild liver injury induced by APAP overdose.With further development, such biomarkers may improve the assessment of liver injury and the efficacy of clinical decision-making, which can be extended to other microvascular dysfunction of deep organs.
Smoking behavior and secondhand smoke exposure among university students in northern Portugal: Relations with knowledge on tobacco use and attitudes toward smoking
Authors: R.F. Alves, J. Precioso, E. Becoña
Journal: Pulmonology (2020)

To assess the prevalence of active smoking and secondhand smoke (SHS) exposure among college students in the north of Portugal, and analyze the relationship between knowledge about tobacco use and attitudes toward smoking.This a cross-sectional study with a representative sample of college students (n=840) in one university in Portugal. A validated self-reported questionnaire was administered to a proportional stratified random sample during the academic year of 2018/2019. We evaluated associations between smoking status, SHS exposure, smokers peers, knowledge and attitudes toward smoking and sociodemographic variables.The results showed that 20.1% of the students surveyed were current smokers (7.3% occasional smokers, 2.9% regular smokers and 9.9% daily smokers). Most current smokers started smoking before the age of 17 (61.4%) and reported never having tried to quit smoking (59.7%). Only 34.4% of students reported (almost) not having been in enclosed spaces with smokers in the past 7 days. Exposure to SHS and having smoker friends contributes to the prevalence of tobacco use. In general, students showed favorable attitudes toward smoking, especially those who are smokers, have smoking friends and are more exposed to SHS. The level of knowledge about tobacco was moderate, with a higher number of correct responses by former smokers.These results suggests an urgent need for socio-educational programs for counseling on smoking cessation. In addition, is also strongly recommended that, throughout academic training, students develop personal and social skills for dealing with the tobacco epidemic.