tbuckley/cabot-search huggingface dataset:
Blueprint for Restructuring a Department of Surgery in Concert With the Health Care System During a Pandemic
Authors: Ben L. Zarzaur, Christopher C. Stahl, Jacob A. Greenberg, Stephanie A. Savage, Rebecca M. Minter
Journal: JAMA Surgery (2020)

The current health care environment is complex. Systems often cross US state boundaries to provide care to patients with a wide variety of medical needs. The coronavirus disease 2019 pandemic is challenging health care systems across the globe. Systems face varying levels of complexity as they adapt to the new reality. This pandemic continues to escalate in hot spots nationally and internationally, and the worst strain on health care systems may be yet to come. The purpose of this article is to provide a road map developed from lessons learned from the experience in the Department of Surgery at the University of Wisconsin School of Medicine and Public Health and University of Wisconsin Health, based on past experience with incident command structures in military combat operations and Federal Emergency Management Agency responses. We will discuss administrative restructuring leveraging a team-of-teams approach, provide a framework for deploying the workforce needed to deliver all necessary urgent health care and critical care to patients in the system, and consider implications for the future.
Systemic Biomarkers Show Elevated Oxidative Stress and Chronic Inflammation in Two Disorders of Neurodegeneration with Brain Iron Accumulation (NBIA)
Authors: Michael Minkley, Nancy Sweeters, Shiva Kasravi, Jennifer Ferguson, Annie Higa, Angela Jackson, Derek Smith, Christoph Borchers, Raad Nashmi, Patrick Macleod, Lynne D. Neumayr, Elliott Vichinsky, Patrick B Walter
Journal: Blood (2017)
Heritable modifiers of the tumor microenvironment influence nanoparticle uptake, distribution and response to photothermal therapy
Authors: Gayatri Sharma, Jaidip M. Jagtap, Abdul K. Parchur, Venkateswara R. Gogineni, Sophia Ran, Carmen Bergom, Sarah B. White, Michael J. Flister, Amit Joshi
Journal: Theranostics (2020)

We report the impact of notch-DLL4-based hereditary vascular heterogeneities on the enhanced permeation and retention (EPR) effect and plasmonic photothermal therapy response in tumors.Methods: We generated two consomic rat strains with differing DLL4 expression on 3 rd chromosome.These strains were based on immunocompromised Salt-sensitive or SS IL2Rγ- (DLL4-high) and SS.BN3 IL2Rγ-(DLL4-low) rats with 3rd chromosome substituted from Brown Norway rat.We further constructed three novel SS.BN3 IL2Rγ-congenic strains by introgressing varying segments of BN chromosome 3 into the parental SS IL2Rγ-strain to localize the role of SS IL2Rγ- DLL4 on tumor EPR effect with precision.We synthesized multimodal theranostic nanoparticles (TNPs) based on Au-nanorods which provide magnetic resonance imaging (MRI), X-ray, and optical contrasts to assess image guided PTT response and quantify host specific therapy response differences in tumors orthotopically xenografted in DLL4-high and -low strains.We tested recovery of therapy sensitivity of PTT resistant strains by employing anti-DLL4 conjugated TNPs in two triple negative breast cancer tumor xenografts.Results: Host strains with high DLL4 allele demonstrated slightly increased tumor nanoparticle uptake but consistently developed photothermal therapy resistance compared to tumors in host strains with low DLL4 allele.Tumor micro-environment with low DLL4 expression altered the geographic distribution of nanoparticles towards closer proximity with vasculature which improved efficacy of PTT in spite of lower overall TNP uptake.Targeting TNPs to tumor endothelium via anti-DLL4 antibody conjugation improved therapy sensitivity in high DLL4 allele hosts for two triple negative human breast cancer xenografts.Conclusions: Inherited DLL4 expression modulates EPR effects in tumors, and molecular targeting of endothelial DLL4 via nanoparticles is an effective personalized nanomedicine strategy.
The Affordable Care Act’s Medicaid Expansion and Impact Along the Cancer-Care Continuum: A Systematic Review
Authors: Haley A Moss, Jenny Wu, Samantha J Kaplan, S Yousuf Zafar
Journal: JNCI Journal of the National Cancer Institute (2020)

Health reform and the merits of Medicaid expansion remain at the top of the legislative agenda, with growing evidence suggesting an impact on cancer care and outcomes. A systematic review was undertaken to assess the association between Medicaid expansion and the goals of the Patient Protection and Affordable Care Act in the context of cancer care. The purpose of this article is to summarize the currently published literature and to determine the effects of Medicaid expansion on outcomes during points along the cancer care continuum.A systematic search for relevant studies was performed in the PubMed/MEDLINE, EMBASE, Scopus, and Cochrane databases. Three independent observers used an abstraction form to code outcomes and perform a quality and risk of bias assessment using predefined criteria.A total of 48 studies were identified. The most common outcomes assessed were the impact of Medicaid expansion on insurance coverage (23.4% of studies), followed by evaluation of racial and/or socioeconomic disparities (17.4%) and access to screening (14.5%). Medicaid expansion was associated with increases in coverage for cancer patients and survivors as well as reduced racial- and income-related disparities.Medicaid expansion has led to improved access to insurance coverage among cancer patients and survivors, particularly among low-income and minority populations. This review highlights important gaps in the existing oncology literature, including a lack of studies evaluating changes in treatment and access to end-of-life care following implementation of expansion.
Letting rationalizations out of the box
Authors: Philip Pärnamets, Petter Johansson, Lars Hall
Journal: Behavioral and Brain Sciences (2020)

We are very happy that someone has finally tried to make sense of rationalization. But we are worried about the representational structure assumed by Cushman, particularly the "boxology" belief-desire model depicting the rational planner, and it seems to us he fails to accommodate many of the interpersonal aspects of representational exchange.
Novel coronavirus infection in newborn babies aged &lt;28 days in China
Authors: Zhi-Jiang Zhang, Xue-Jie Yu, Tao Fu, Yu Liu, Yan Jiang, Bing Xiang Yang, Yongyi Bi
Journal: European Respiratory Journal (2020)

<b>Neonates are susceptible to SARS-CoV-2 infection. The symptoms in neonates were milder and outcomes were less severe compared to adults. Intrauterine vertical transmission is not impossible but direct evidence is still lacking.</b>https://bit.ly/342jGK9
Covid-19: why we need a national health and social care service
Authors: Allyson M Pollock, Luke Clements, Louisa Harding-Edgar
Journal: BMJ (2020)

Covid-19 outbreaks in care homes expose serious inadequacies in social care services across the UK.Data from across the world show that deaths from covid-19 mainly occur among older people, particularly those over 80. 1 By 12 April 10 612 deaths had been reported in the UK 2 -40% of deaths have occurred in those aged 60-79 and 52% in those 80 years or over. 3 Close to 1.5 million vulnerable people are currently self-isolating indoors for 12 weeks. 4 These include many older people and people with disabilities and chronic illnesses.Many are essentially in solitary confinement.Many residents in care homes are trapped in their rooms, with no visits from relatives and minimal interactions with staff.The decision to exclude relatives means that care homes have become closed institutions, increasing the risk that people are inappropriately denied hospital admission as well as the risk of neglect and abuse. 5 6Of equal concern are plans to transfer patients recovering from covid-19 from the NHS into empty nursing home beds.
A COX-2/sEH dual inhibitor PTUPB alleviates lipopolysaccharide-induced acute lung injury in mice by inhibiting NLRP3 inflammasome activation
Authors: Hui-Hui Yang, Jia-Xi Duan, Shao-Kun Liu, Jian-Bing Xiong, Xin-Xin Guan, Wen-Jing Zhong, Chen-Chen Sun, Chen-Yu Zhang, Xiao-Qin Luo, Yan-Feng Zhang, Ping Chen, Bruce D. Hammock, Sung Hee Hwang, Jian-Xin Jiang, Yong Zhou, Cha-Xiang Guan
Journal: Theranostics (2020)

Rationale: Dysregulation of arachidonic acid (ARA) metabolism results in inflammation; however, its role in acute lung injury (ALI) remains elusive.In this study, we addressed the role of dysregulated ARA metabolism in cytochromes P450 (CYPs) /cyclooxygenase-2 (COX-2) pathways in the pathogenesis of lipopolysaccharide (LPS)-induced ALI in mice.Methods: The metabolism of CYPs/COX-2-derived ARA in the lungs of LPS-induced ALI was investigated in C57BL/6 mice.The COX-2/sEH dual inhibitor PTUPB was used to establish the function of CYPs/COX-2 dysregulation in ALI.Primary murine macrophages were used to evaluate the underlying mechanism of PTUPB involved in the activation of NLRP3 inflammasome in vitro.Results: Dysregulation of CYPs/COX-2 metabolism of ARA occurred in the lungs and in primary macrophages under the LPS challenge.Decrease mRNA expression of Cyp2j9, Cyp2j6, and Cyp2j5 was observed, which metabolize ARA into epoxyeicosatrienoic acids (EETs).The expressions of COX-2 and soluble epoxide hydrolase (sEH), on the other hand, was significantly upregulated.Pre-treatment with the dual COX-2 and sEH inhibitor, PTUPB, attenuated the pathological injury of lung tissues and reduced the infiltration of inflammatory cells.Furthermore, PTUPB decreased the pro-inflammatory factors, oxidative stress, and activation of NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome in LPS-induced ALI mice.PTUPB pre-treatment remarkably reduced the activation of macrophages and NLRP3 inflammasome in vitro.Significantly, both preventive and therapeutic treatment with PTUPB improved the survival rate of mice receiving a lethal dose of LPS. Conclusion:The dysregulation of CYPs/COX-2 metabolized ARA contributes to the uncontrolled inflammatory response in ALI.The dual COX-2 and sEH inhibitor PTUPB exerts anti-inflammatory effects in treating ALI by inhibiting the NLRP3 inflammasome activation.
Universal Screening for SARS-CoV-2 in Women Admitted for Delivery
Authors: Desmond Sutton, Karin Fuchs, Mary D'Alton, Dena Goffman
Journal: New England Journal of Medicine (2020)

SARS-CoV-2 Testing in Obstetrical Patients Among 215 pregnant women who were admitted to a New York hospital for delivery and who underwent universal testing for SARS-CoV-2, more than one in eight ...
A Strategy for Improving U.S. Health Care Delivery — Conducting More Randomized, Controlled Trials
Authors: Amy Finkelstein
Journal: New England Journal of Medicine (2020)

Interview with Dr. Amy Finkelstein on the use of evidence from randomized, controlled trials to answer questions about health care policy. (10:56)Download Despite the prominence of randomized, controlled trials in medical research, they have rarely been used to evaluate health care delivery. But researchers, practitioners, and policymakers are starting to find ways to overcome barriers to the widespread use of such trials.
Circular RNA SAMD4A controls adipogenesis in obesity through the miR-138-5p/EZH2 axis
Authors: Yanjun Liu, Hongtao Liu, Yi Li, Rui Mao, Huawu Yang, Yuanchuan Zhang, Yu Zhang, Pengsen Guo, Dafang Zhan, Tongtong Zhang
Journal: Theranostics (2020)

A growing body of evidence has suggested that circular RNAs (circRNAs) are crucial for the regulation of gene expression and their dysregulation is implicated in several diseases.However, the function of circRNAs in obesity remains largely unexplored.Methods: Global changes in the circRNA expression patterns were detected in adipose tissues derived from obese and lean individuals.In particular, circSAMD4A was identified as significantly differentially upregulated and was functionally analyzed, both in vitro and in vivo, using various approaches.Results: CircSAMD4A overexpression was correlated with a poor prognosis in obese patients.By contrast, circSAMD4A knockdown inhibited differentiation in isolated preadipocytes.In high-fat diet (HFD) -induced obese mice, circSAMD4A knockdown reversed the associated weight gain, reduced food intake, lower body fat, and increased energy expenditure.These mice also exhibited increased insulin sensitivity and glucose tolerance.Furthermore, in vitro experiments indicated that circSAMD4A affected differentiation by binding to miR-138-5p and regulating EZH2 expression.Conclusions: CircSAMD4A regulated preadipocyte differentiation by acting as a miR-138-5p sponge, and thus increasing EZH2 expression.These results suggested that circSAMD4A can serve as a potential target for obesity treatments and/or as a potential prognostic marker for obese patients following bariatric surgery.
Nondestructive analysis of tumor-associated membrane protein MUC1 in living cells based on dual-terminal amplification of a DNA ternary complex
Authors: Xiaohao Liu, Dongsheng Mao, Guoli Deng, Yuchen Song, Fan Zhang, Shiqi Yang, Genxi Li, Feng Liu, Wei Cao, Xiaoli Zhu
Journal: Theranostics (2020)

Non-destructive analysis of cells at the molecular level is of critical importance for cell research. At present, immunoassay-based and aptamer-based methods can achieve non-structural destructive cell analysis, but still lead to changes in cells at the molecular level. Here, we have proposed a dual-terminal amplification (DTA) strategy, which enables nondestructive analysis of membrane protein MUC1 without the effect on protein expression and cell viability in living cells.
Pregnancy and Risk of Intracerebral Hemorrhage
Authors: Kazuyoshi Aoyama, Joel G. Ray
Journal: JAMA Network Open (2020)

Jennifer R. Meeks, MS; Arvind B. Bambhroliya, MBBS, MS, MPH; Katie M. Alex, BS; Sunil A. Sheth, MD; Sean I. Savitz, MD; Eliza C. Miller, MD; Louise D. McCullough, MD, PhD; Farhaan S. Vahidy, PhD, MBBS, MPH
Retrograde nerve growth factor signaling abnormalities in familial dysautonomia
Authors: Lin Li, Katherine Gruner, Warren G. Tourtellotte
Journal: Journal of Clinical Investigation (2020)

Familial dysautonomia (FD) is the most prevalent form of hereditary sensory and autonomic neuropathy (HSAN). In FD, a germline mutation in the Elp1 gene leads to Elp1 protein decrease that causes sympathetic neuron death and sympathetic nervous system dysfunction (dysautonomia). Elp1 is best known as a scaffolding protein within the nuclear hetero-hexameric transcriptional Elongator protein complex, but how it functions in sympathetic neuron survival is very poorly understood. Here, we identified a cytoplasmic function for Elp1 in sympathetic neurons that was essential for retrograde nerve growth factor (NGF) signaling and neuron target tissue innervation and survival. Elp1 was found to bind to internalized TrkA receptors in an NGF-dependent manner, where it was essential for maintaining TrkA receptor phosphorylation (activation) by regulating PTPN6 (Shp1) phosphatase activity within the signaling complex. In the absence of Elp1, Shp1 was hyperactivated, leading to premature TrkA receptor dephosphorylation, which resulted in retrograde signaling failure and neuron death. Inhibiting Shp1 phosphatase activity in the absence of Elp1 rescued NGF-dependent retrograde signaling, and in an animal model of FD it rescued abnormal sympathetic target tissue innervation. These results suggest that regulation of retrograde NGF signaling in sympathetic neurons by Elp1 may explain sympathetic neuron loss and physiologic dysautonomia in patients with FD.
A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications
Authors: George W. Wright, Da Wei Huang, James D. Phelan, Zana A. Coulibaly, Sandrine Roulland, Ryan M. Young, James Q. Wang, Roland Schmitz, Ryan D. Morin, Jeffrey Tang, Aixiang Jiang, Aleksander Bagaev, Olga Plotnikova, Nikita Kotlov, Calvin A. Johnson, Wyndham H. Wilson, David W. Scott, Louis M. Staudt
Journal: Cancer Cell (2020)
AI for the Eye — Automated Assistance for Clinicians Screening for Papilledema
Authors: Isaac Kohane
Journal: New England Journal of Medicine (2020)

Accurate assessment of the optic-nerve head, the optic disk, by funduscopy is an important, cost-effective, and noninvasive diagnostic tool for a variety of ocular, neurologic, and inflammatory conditions. Unfortunately, reliable funduscopic assessment is challenging for clinicians working with undilated pupils1; even after mydriatic dilation, nonophthalmologists have considerably lower accuracy2 than neuro-ophthalmologists in detecting optic-disk disorders, including papilledema. Could computer programs examining digital funduscopic images perform at the level of neuro-ophthalmologists in classifying disorders of the optic disk? The authors of the study now published in the Journal3 were encouraged by previous studies for the detection of diabetic retinopathy4 to undertake . . .
Clinical spectrum, genetic complexity and therapeutic approaches for retinal disease caused by ABCA4 mutations
Authors: Frans P.M. Cremers, Winston Lee, Rob W.J. Collin, Rando Allikmets
Journal: Progress in Retinal and Eye Research (2020)

The ABCA4 protein (then called a "rim protein") was first identified in 1978 in the rims and incisures of rod photoreceptors. The corresponding gene, ABCA4, was cloned in 1997, and variants were identified as the cause of autosomal recessive Stargardt disease (STGD1). Over the next two decades, variation in ABCA4 has been attributed to phenotypes other than the classically defined STGD1 or fundus flavimaculatus, ranging from early onset and fast progressing cone-rod dystrophy and retinitis pigmentosa-like phenotypes to very late onset cases of mostly mild disease sometimes resembling, and confused with, age-related macular degeneration. Similarly, analysis of the ABCA4 locus uncovered a trove of genetic information, including >1200 disease-causing mutations of varying severity, and of all types - missense, nonsense, small deletions/insertions, and splicing affecting variants, of which many are located deep-intronic. Altogether, this has greatly expanded our understanding of complexity not only of the diseases caused by ABCA4 mutations, but of all Mendelian diseases in general. This review provides an in depth assessment of the cumulative knowledge of ABCA4-associated retinopathy - clinical manifestations, genetic complexity, pathophysiology as well as current and proposed therapeutic approaches.
A toxic palmitoylation of Cdc42 enhances NF-κB signaling and drives a severe autoinflammatory syndrome
Authors: Bahia Bekhouche, Aurore Tourville, Yamini Ravichandran, Rachida Tacine, Laurence Abrami, Michael Dussiot, Andrea Khau-Dancasius, Olivia Boccara, Meriem Khirat, Marianne Mangeney, Florent Dingli, Damarys Loew, Batiste Boëda, Pénélope Jordan, Thierry Jo Molina, Nathalia Bellon, Sylvie Fraitag, Smail Hadj-Rabia, Stéphane Blanche, Anne Puel, Sandrine Etienne-Manneville, F. Gisou van der Goot, Jacqueline Cherfils, Olivier Hermine, Jean-Laurent Casanova, Christine Bodemer, Asma Smahi, Jérôme Delon
Journal: Journal of Allergy and Clinical Immunology (2020)
Abstract 11112: Rationale and Design of Ch Strong: Congenital Heart Survey to Recognize Outcomes, Needs, and Well-beinG
Authors: Sherry L Farr, Scott E Klewer, Wendy N Nembhard, Caroline Alter, Karrie F Downing, Jennifer G Andrews, R T Collins, Jill Glidewell, Argelia Benavides, Anthony Goudie, Tiffany Riehle-Colarusso, Lindsey Overman, Aspen Riser, Matthew E Oster
Journal: Circulation (2019)

Introduction: Studies of long-term outcomes among adults with congenital heart defects (CHD) have typically focused on those receiving care at specialty centers, limiting generalizability. The obje...
Predicting the diagnosis of HIV and sexually transmitted infections among men who have sex with men using machine learning approaches
Authors: Yining Bao, Nicholas A. Medland, Christopher K. Fairley, Jinrong Wu, Xianwen Shang, Eric P.F. Chow, Xianglong Xu, Zongyuan Ge, Xun Zhuang, Lei Zhang
Journal: Journal of Infection (2020)
Targeted lipidomics reveals extensive changes in circulating lipid mediators in patients with acutely decompensated cirrhosis
Authors: Cristina López-Vicario, Antonio Checa, Arantxa Urdangarin, Ferran Aguilar, José Alcaraz-Quiles, Paolo Caraceni, Alex Amorós, Marco Pavesi, David Gómez-Cabrero, Jonel Trebicka, Karl Oettl, Richard Moreau, Núria Planell, Vicente Arroyo, Craig E. Wheelock, Joan Clària
Journal: Journal of Hepatology (2020)
Low-dose interleukin-2 alleviates dextran sodium sulfate-induced colitis in mice by recovering intestinal integrity and inhibiting AKT-dependent pathways
Authors: Hana Lee, Ye Seul Son, Mi-Ok Lee, Jea-Woon Ryu, Kunhyang Park, Ohman Kwon, Kwang Bo Jung, Kwangho Kim, Tae Young Ryu, Aruem Baek, Janghwan Kim, Cho-Rok Jung, Choong-Min Ryu, Young-Jun Park, Tae-Su Han, Dae-Soo Kim, Hyun-Soo Cho, Mi-Young Son
Journal: Theranostics (2020)

Several phase 1/2 clinical trials showed that low-dose interleukin-2 (IL-2) treatment is a safe and effective strategy for the treatment of chronic graft-versus-host disease, hepatitis C virus-induced vasculitis, and type 1 diabetes. Ulcerative colitis (UC) is a chronic inflammatory condition of the colon that lacks satisfactory treatment. In this study, we aimed to determine the effects of low-dose IL-2 as a therapeutic for UC on dextran sulfate sodium (DSS)-induced colitis. Methods: Mice with DSS-induced colitis were intraperitoneally injected with low-dose IL-2. Survival, body weight, disease activity index, colon length, histopathological score, myeloperoxidase activity and inflammatory cytokine levels as well as intestinal barrier integrity were examined. Differential gene expression after low-dose IL-2 treatment was analyzed by RNA-sequencing. Results: Low-dose IL-2 significantly improved the symptoms of DSS-induced colitis in mice and attenuated pro-inflammatory cytokine production and immune cell infiltration. The most effective dose range of IL-2 was 16K-32K IU/day. Importantly, low-dose IL-2 was effective in ameliorating the disruption of epithelial barrier integrity in DSS-induced colitis tissues by restoring tight junction proteins and mucin production and suppressing apoptosis. The colon tissue of DSS-induced mice exposed to low-dose IL-2 mimic gene expression patterns in the colons of control mice. Furthermore, we identified the crucial role of the PI3K-AKT pathway in exerting the therapeutic effect of low-dose IL-2. Conclusions: The results of our study suggest that low-dose IL-2 has therapeutic effects on DSS-induced colitis and potential clinical value in treating UC.