tbuckley/cabot-search huggingface dataset:
From the Exposome to the Socioexposome in COVID-19 Research—A Call for More Multidisciplinary Research
Authors: Sarah Koch, Liv Yoon, Bieke Gils
Journal: JAMA Network Open (2020)

Lauren A. Eberly, MD, MPH; Michael J. Kallan, MS; Howard M. Julien, MD, MPH, ML; Norrisa Haynes, MD, MPH; Sameed Ahmed M. Khatana, MD, MPH; Ashwin S. Nathan, MD; Christopher Snider, MPH; Neel P. Chokshi, MD, MBA; Nwamaka D. Eneanya, MD, MPH; Samuel U. Takvorian, MD, MS; Rebecca Anastos-Wallen, MD; Krisda Chaiyachati, MD, MPH, MS; Marietta Ambrose, MD, MPH, MSEd; Rupal O'Quinn, MD; Matthew Seigerman, MD; Lee R. Goldberg, MD, MPH; Damien Leri, MSEd, MPH; Katherine Choi, MD; Yevginiy Gitelman, MD; Daniel M. Kolansky, MD; Thomas P. Cappola, MD, ScM; Victor A. Ferrari, MD; C. William Hanson, MD; Mary Elizabeth Deleener, MBA, BSN, RN; Srinath Adusumalli, MD, MSc
Association of the Leukocyte Immunoglobulin‐like Receptor A3 Gene With Neutrophil Activation and Disease Susceptibility in Adult‐Onset Still’s Disease
Authors: Mengyan Wang, Mengru Liu, Jinchao Jia, Hui Shi, Jialin Teng, Honglei Liu, Yue Sun, Xiaobing Cheng, Junna Ye, Yutong Su, Huihui Chi, Tingting Liu, Zhihong Wang, Liyan Wan, Jianfen Meng, Yuning Ma, Chengde Yang, Qiongyi Hu
Journal: Arthritis & Rheumatology (2020)

Objective Adult‐onset Still’s disease (AOSD) is a severe autoinflammatory disease. Neutrophil activation with enhanced neutrophil extracellular trap (NET) formation is involved in the pathogenesis of AOSD. Functional leukocyte immunoglobulin‐like receptor A3 (LIR‐A3; gene name LILRA3 ) has been reported to be associated with many autoimmune diseases. We aimed to investigate the association of LILRA3 with disease susceptibility and neutrophil activation in AOSD. Methods The LILRA3 deletion polymorphism and its tagging single‐nucleotide polymorphism rs103294 were genotyped in 164 patients with AOSD and 305 healthy controls. The impact of LILRA3 on clinical features and messenger RNA expression was evaluated. Plasma levels of LIR‐A3 were detected using enzyme‐linked immunosorbent assay (ELISA), and the correlation between LIR‐A3 plasma levels and disease activity and levels of circulating NET‐DNA was investigated. LIR‐A3–induced NETs were determined using PicoGreen double‐stranded DNA dye and immunofluorescence analysis in human neutrophils and a neutrophil‐like differentiated NB4 cell line transfected with LIR‐B2 small interfering RNA. Results The findings from genotyping demonstrated that functional LILRA3 was a risk factor for AOSD (11% in AOSD patients versus 5.6% in healthy controls; odds ratio 2.089 [95% confidence interval 1.030–4.291], P = 0.034), and associated with leukocytosis ( P = 0.039) and increased levels of circulating neutrophils ( P = 0.027). Functional LILRA3 messenger RNA expression was higher in the peripheral blood mononuclear cells ( P &lt; 0.0001) and neutrophils ( P &lt; 0.001) of LILRA3 +/+ patients. Plasma levels of LIR‐A3 were elevated in patients with AOSD ( P &lt; 0.0001) and correlated with disease activity indicators and levels of circulating NET–DNA complexes. Finally, enhanced NET formation was identified in neutrophils from healthy controls and patients with inactive AOSD after stimulation of the neutrophils with LIR‐A3. Moreover, NET formation was impaired in NB4 cells after knockdown of LILRB2 gene expression. Conclusion Our study provides the first evidence that functional LILRA3 is a novel genetic risk factor for the development of AOSD and that functional LIR‐A3 may play a pathogenic role by inducing formation of NETs.
Combinatorial Normalization of Liver-Derived Cytokine Pathways Alleviates Hepatic Tumor-Associated Cachexia in Zebrafish
Authors: Fei Fei, Shaoyang Sun, Qiang Li, Zhou Pei, Lei Wang, Ranran Zhang, Feihong Luo, Min Yu, Xu Wang
Journal: Cancer Research (2020)

The role and significance of liver-derived cytokines in cancer-associated cachexia syndrome remain elusive. Here we report that combinatorial counterbalances of the leptin and Igf1 signaling pathways in hepatocellular carcinoma (HCC) models significantly relieves cachexia. Double transgenic zebrafish models of HCC that stably displayed focal lesions, anorexia, and wasting of adipose and muscle tissues were first generated. Knockout of lepr or mc4r from these zebrafish partially restored appetite and exerted moderate or no effect on tissue wasting. However, genetic replenishment of Igf1 in a lepr-mutant background effectively relieved the cachexia-like phenotype without affecting tumor growth. Similarly, administration of napabucasin, a Stat3/Socs3 inhibitor, on the zebrafish HCC model, mammalian cell lines with exogenous IGF1, and two mouse xenograft models restored insulin sensitivity and rescued the wasting of nontumor tissues. Together, these results describe the synergistic impact of leptin and Igf1 normalization in treating certain HCC-associated cachexia as a practical strategy. SIGNIFICANCE: Disruption of leptin signaling with normalized Igf1 expression significantly rescues anorexia, muscle wasting, and adipose wasting in Ras- and Myc-driven zebrafish models of HCC.
The role of metabolism in chondrocyte dysfunction and the progression of osteoarthritis
Authors: Linli Zheng, Ziji Zhang, Puyi Sheng, Ali Mobasheri
Journal: Ageing Research Reviews (2020)

Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and high levels of clinical heterogeneity. Aberrant chondrocyte metabolism is a response to changes in the inflammatory microenvironment and may play a key role in cartilage degeneration and OA progression. Under conditions of environmental stress, chondrocytes tend to adapt their metabolism to microenvironmental changes by shifting from one metabolic pathway to another, for example from oxidative phosphorylation to glycolysis. Similar changes occur in other joint cells, including synoviocytes. Switching between these pathways is implicated in metabolic alterations that involve mitochondrial dysfunction, enhanced anaerobic glycolysis, and altered lipid and amino acid metabolism. The shift between oxidative phosphorylation and glycolysis is mainly regulated by the AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) pathways. Chondrocyte metabolic changes are likely to be a feature of different OA phenotypes. Determining the role of chondrocyte metabolism in OA has revealed key features of disease pathogenesis. Future research should place greater emphasis on immunometabolism and altered metabolic pathways as a means to understand the pathophysiology of age-related OA. This knowledge will advance the development of new drugs against therapeutic targets of metabolic significance.
Randomized comparison of long-term carvedilol and propranolol administration in the treatment of portal hypertension in cirrhosis
Authors: Rafael Bañares, Eduardo Moitinho, Ana Matilla, Juan Carlos García-Pagán, José Luis Lampreave, Carlos Piera, Juan G. Abraldes, Alejandro De Diego, Agustín Albillos, Jaime Bosch
Journal: Hepatology (2002)

Short-term carvedilol administration is more powerful than propranolol in decreasing hepatic venous pressure gradient (HVPG) in cirrhotic patients, but induces arterial hypotension that may prevent its long-term use in portal hypertensive patients. This study compared the HVPG reduction and safety of long-term carvedilol and propranolol. Fifty-one cirrhotic patients were randomly assigned to receive carvedilol (n = 26) and propranolol (n = 25). Hemodynamic measurements and renal function were assessed at baseline and after 11.1 ± 4.1 weeks. Carvedilol caused a greater decrease in HVPG than popranolol (− 19 ± 2% vs. − 12 ± 2%; P &lt; 0.001). The proportion of patients achieving an HVPG reduction ≥20% or ≤ 20 mm Hg was greater after carvedilol (54% vs. 23%; P &lt; 0.05). Carvedilol, but not propranolol caused a significant decrease in mean arterial pressure (MAP) (- 11 ± 1% vs. - 5 ± 3%; P = 0.05) and a significant increase in plasma volume (PV) and body weight (11 ± 5% and 2 ± 1%, respectively; P &lt; 0.05). Glomerular filtration rate (GFR) was unchanged with either drug, but the dose of diuretics was increased more frequently after carvedilol (27% vs. 8% P = 0.07). Adverse events requiring discontinuation of treatment occurred in 2 patients receiving carvedilol and in 3 receiving propranolol. In conclusion, carvedilol has a greater portal hypotensive effect than propranolol in patients with cirrhosis. However, its clinical applicability may be limited by its systemic hypotensive effects. Further trials are needed to confirm the therapeutic potential of carvedilol. (Hepatology2002;36:1367-1373).
Postoperative Radiotherapy for Cutaneous Squamous Cell Carcinoma in Patients With Microscopic Residual Disease
Authors: Alet J. G. Leus, Estelle F. D. Perrels, Gyorgy B. Halmos, Jorrit B. Terra, Roel J. H. M. Steenbakkers, Marloes S. van Kester, Emöke Rácz
Journal: JAMA Dermatology (2020)

31 of 988 (3.1%) after MHT, with 27 of 984 (2.7%) patients developing AGA after starting MHT.The median duration of MHT prior to AGA diagnosis was 1035 days (IQR, 781-1153 days), or 2.8 years.The incidence of AGA diagnosis was 2 of 984 (0.2%) in the first year of MHT, and 4 of 982 (0.4%) in the second, 10 of 978 (1.0%) in the third, 8 of 760 (1.1%) in the fourth, 2 of 455 (0.4%) in the fifth, and 1 of 206 (0.5%) in the sixth year of MHT, respectively.Among the 31 AGA patients, 22 (71%) were prescribed finasteride for treatment, 3 (9.7%)were prescribed topical minoxidil, and 6 (19.4%) were not prescribed medication.The median age of all patients diagnosed with post-MHT AGA was 26 years (IQR, 23.7-30.0)(Table ).Discussion | The proportion of patients with AGA increased from 4 (0.4%) to 31 (3.1%) after MHT initiation, with the highest incidence in the fourth year of MHT and the median duration of MHT prior to diagnosis 2.8 years.This is consistent with prior studies showing a delayed development of AGA in transgender patients receiving MHT.However, the proportion of patients affected in this study was lower than prospective studies 2,3 of MHT patients in which 5% to 17%% of patients developed AGA.This was most likely due to the ascertainment of AGA being limited to ICD-10 diagnoses in the electronic medical record, patients not mentioning mild cases of hair loss to clinicians, or the relatively young age of patients in this study.Limitations of this study include the fact that median duration of follow-up was only 3.4 years and did not capture the prevalence of AGA for long-term use of MHT.The patient cohort examined was overwhelmingly White and may not reflect AGA prevalence among a diverse racial and ethnic population.Finally, treatment success for AGA could not be assessed due to lack of follow-up information in the electronic health records.
Mortality of AKI in Human Immunodeficiency Virus with and Without Co-Infection with COVID-19
Authors: Jie Ouyang, Siddhartha D. Bajracharya, Ernie Yap, Mary C. Mallappallil
Journal: Journal of the American Society of Nephrology (2020)

Background: Acute kidney injury (AKI) is a manifestation of COVID-19 (CoVAKI)  However, there is paucity of data from United States, particularly in a predominantly African American (AA) population  We report the phenotype and outcomes of AKI at an academic hospital in New Orleans  Methods: We conducted an observational study in patients hospitalized at Ochsner Medical Center over 1-month period with COVID-19 and diagnosis of AKI by KDIGO  We examined the rates of renal replacement therapy (RRT) and in-hospital mortality as outcome measures  Adjudication of cause of AKI was independently performed via manual chart review by 3 study team members  Results: Of 644 admissions with COVID-19, 69 were excluded due to ESRD or kidney transplant  Thus, 575 patients entered the cohort [173 (28%) to an intensive care unit (ICU)]  Patients were predominantly AA (71%)  AKI was diagnosed in 161 patients (28% overall, 61% of ICU admissions), median age 65 (34 - 96), predominantly male (62%) and hypertensive (83%)  Median follow up was 25 (1 - 45) days  Vasopressors and/or mechanical ventilation was required in 105 (65%) of them  In-hospital mortality rate for those with AKI was 50% (80/181)  De novo AKI was diagnosed in 65%, whereas AKI over preexisting chronic kidney disease occurred in 35% of the cohort  Ninetyone (57%) patients arrived with AKI, whereas the remaining 43% acquired AKI during the hospitalization [median hospital day of AKI onset: 4 (2 - 10)]  RRT was required in 89/161 (55%) and 77/105 (73%) patients for all AKI cases and the ICU subset, respectively  The mortality rate for those with AKI-RRT was 72% (64/89)  Hemodynamic instability leading to ischemic acute tubular injury (ATI) and rhabdomyolysis accounted for 66% and 7% of the etiology, respectively  Reversible prerenal azotemia occurred in 9%  In 13%, no obvious cause of AKI was identified aside from the COVID-19 diagnosis  Three (1 8%) patients had De novo collapsing glomerulopathy  Conclusions: CoV-AKI is associated with high rates of RRT, ICU care and death  Hemodynamic instability leading to ischemic ATI is the predominant cause of AKI in this setting, but other etiologies contribute to the overall AKI burden
Microvascular maturation by mesenchymal stem cells in vitro improves blood perfusion in implanted tissue constructs
Authors: Yoann Atlas, Caroline Gorin, Anita Novais, Marion F. Marchand, Eirini Chatzopoulou, Julie Lesieur, Rumeyza Bascetin, Clément Binet-Moussy, Jeremy Sadoine, Matthieu Lesage, Sibylle Opsal-Vital, Bruno Péault, Catherine Monnot, Anne Poliard, Philippe Girard, Stéphane Germain, Catherine Chaussain, Laurent Muller
Journal: Biomaterials (2020)
Reduction in Revascularization With Icosapent Ethyl
Authors: Benjamin E. Peterson, Deepak L. Bhatt, Ph. Gabriel Steg, Michael Miller, Eliot A. Brinton, Terry A. Jacobson, Steven B. Ketchum, Rebecca A. Juliano, Lixia Jiao, Ralph T. Doyle, Craig Granowitz, C. Michael Gibson, Duane Pinto, Robert P. Giugliano, Matthew J. Budoff, Jean-Claude Tardif, Subodh Verma, Christie M. Ballantyne
Journal: Circulation (2020)

Patients with elevated triglycerides despite statin therapy have increased risk for ischemic events, including coronary revascularizations.
Correction to: Role of non-coding RNA networks in leukemia progression, metastasis and drug resistance
Authors: Ajaz A. Bhat, Salma N. Younes, Syed Shadab Raza, Lubna Zarif, Sabah Nisar, Ikhlak Ahmed, Rashid Mir, Sachin Kumar, Surender K. Sharawat, Sheema Hashem, Imadeldin Elfaki, Michal Kulinski, Shilpa Kuttikrishnan, Kirti S. Prabhu, Abdul Q. Khan, Santosh K. Yadav, Wael El-Rifai, Mohammad A. Zargar, Hatem Zayed, Mohammad Haris, Shahab Uddin
Journal: Molecular Cancer (2020)

An amendment to this paper has been published and can be accessed via the original article.
Weighted gene co-expression network analysis revealed host transcriptional response to H1N1 influenza A virus infection
Authors: Jinyue Guo, Hai Yu, Jing Yang, Yong Li, Xuelian Zhang, Kun Mei, Shihong Chi, Sheng Yuan, Hao Liu, Saeed El-Ashram, Shujian Huang, Feng Wen
Journal: Journal of Infection (2020)
IL8, Neutrophils, and NETs in a Collusion against Cancer Immunity and Immunotherapy
Authors: Alvaro Teijeira, Saray Garasa, Maria C. Ochoa, Maria Villalba, Irene Olivera, Assunta Cirella, Iñaki Eguren-Santamaria, Pedro Berraondo, Kurt A. Schalper, Carlos E. de Andrea, Miguel F. Sanmamed, Ignacio Melero
Journal: Clinical Cancer Research (2020)

Abstract One of the most important mechanisms by which cancer fosters its own development is the generation of an immune microenvironment that inhibits or impairs antitumor immune responses. A cancer permissive immune microenvironment is present in a large proportion of the patients with cancer who do not respond to immunotherapy approaches intended to trigger preexisting antitumor immune responses, for instance, immune checkpoint blockade. High circulating levels of IL8 in patients with cancer quite accurately predict those who will not benefit from checkpoint-based immunotherapy. IL8 has been reported to favor cancer progression and metastases via different mechanisms, including proangiogenesis and the maintenance of cancer stem cells, but its ability to attract and functionally modulate neutrophils and macrophages is arguably one of the most important factors. IL8 does not only recruit neutrophils to tumor lesions, but also triggers the extrusion of neutrophil extracellular traps (NET). The relevance and mechanisms underlying the contribution of both neutrophils and NETs to cancer development and progression are starting to be uncovered and include both direct effects on cancer cells and changes in the tumor microenvironment, such as facilitating metastasis, awakening micrometastases from dormancy, and facilitating escape from cytotoxic immune cells. Blockade of IL8 or its receptors (CXCR1 and CXCR2) is being pursued in drug development, and clinical trials alone or in combination with anti-PD-L1 checkpoint inhibitors are already ongoing.
Air Quality in Africa: Public Health Implications
Authors: Asmamaw Abera, Johan Friberg, Christina Isaxon, Michael Jerrett, Ebba Malmqvist, Cheryl Sjöström, Tahir Taj, Ana Maria Vargas
Journal: Annual Review of Public Health (2020)

This review highlights the importance of air quality in the African urban development process. We address connections between air pollution and (a) rapid urbanization, (b) social problems, (c) health impacts, (d) climate change, (e) policies, and (f) new innovations. We acknowledge that air pollution levels in Africa can be extremely high and a serious health threat. The toxic content of the pollution could relate to region-specific sources such as low standards for vehicles and fuels, cooking with solid fuels, and burning household waste. We implore the pursuit of interdisciplinary research to create new approaches with relevant stakeholders. Moreover, successful air pollution research must regard conflicts, tensions, and synergies inherent to development processes in African municipalities, regions, and countries. This includes global relationships regarding climate change, trade, urban planning, and transportation. Incorporating aspects of local political situations (e.g., democracy) can also enhance greater political accountability and awareness about air pollution.
Re: Umang Swami, Pedro Isaacsson Velho, Roberto Nussenzveig, et al. Association of SPOP Mutations with Outcomes in Men with De Novo Metastatic Castration-sensitive Prostate Cancer. Eur Urol 2020;78:652–6
Authors: Salma Kaochar, Nicholas Mitsiades
Journal: European Urology (2020)
Clinical Decision-making About Neoadjuvant Nivolumab Plus Ipilimumab
Authors: Manuel David Gil-Sierra, Marina Sánchez-Hidalgo, Catalina Alarcón de la Lastra-Romero
Journal: JAMA Oncology (2020)

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The Centrality of Relational Autonomy and Compassion Fatigue in the COVID-19 Era
Authors: Kellie R. Lang, D. Micah Hester
Journal: The American Journal of Bioethics (2020)

Click to increase image sizeClick to decrease image sizeThis article refers to:Relational Autonomy in an Era of Limited Visitation: What’s a Son, Mother, and Medical Team to Do?
Vismodegib
Authors: Charles M. Rudin
Journal: Clinical Cancer Research (2012)

Vismodegib (GDC-0449), an orally bioavailable small-molecule inhibitor of Hedgehog signaling, was recently approved by the U.S. Food and Drug Administration for the treatment of basal cell carcinoma that is either metastatic or locally advanced in patients who are not candidates for surgical resection or radiation. Given the absence of previously defined effective drug therapy for this disease, approval was granted primarily on the basis of outcome of a nonrandomized parallel cohort phase II study of 99 patients with advanced basal cell carcinoma, with a primary endpoint of objective response rate. Response rates of 30.3% and 42.9% were observed in metastatic and locally advanced cohorts in this study, respectively, associated with median progression-free survival in both cohorts of 9.5 months. Ongoing clinical investigations include evaluation of the potential efficacy of vismodegib in a variety of diseases and in combination with other agents. The mechanism of action, preclinical and clinical data, and potential utility in other disease contexts are reviewed here.
In situ-gelling starch nanoparticle (SNP)/O-carboxymethyl chitosan (CMCh) nanoparticle network hydrogels for the intranasal delivery of an antipsychotic peptide
Authors: Michael J. Majcher, Ali Babar, Andrew Lofts, Ashlyn Leung, Xiaoyun Li, Fahed Abu-Hijleh, Niels M.B. Smeets, Ram K. Mishra, Todd Hoare
Journal: Journal of Controlled Release (2020)
Leveraging Frailty to Mitigate Sex-Based Disparities in Access to Liver Transplant
Authors: Saulat S. Sheikh, Jayme E. Locke
Journal: JAMA Surgery (2020)

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B-cell acute lymphoblastic leukemia in patients with chronic lymphocytic leukemia treated with lenalidomide
Authors: Moritz Fürstenau, Anna Maria Fink, Anke Schilhabel, Jonathan Weiss, Sandra Robrecht, Robert Eckert, Javier de la Serna, Marta Crespo, Marta Coscia, Candida Vitale, Sebastian Böttcher, Gesche Weppner, Matthias Ritgen, Stephan Stilgenbauer, Eugen Tausch, Kirsten Fischer, Michael Hallek, Barbara Eichhorst, Monika Brüggemann, Carmen D. Herling
Journal: Blood (2020)