tbuckley/cabot-search huggingface dataset:
CD8<sup>+</sup>CD57<sup>+</sup> T cells exhibit distinct features in human non-small cell lung cancer
Authors: Bing Huang, Rong Liu, Peiliang Wang, Zhiwei Yuan, Jianjian Yang, Hui Xiong, Ni Zhang, Qi Huang, Xiangning Fu, Wei Sun, Lequn Li
Journal: Journal for ImmunoTherapy of Cancer (2020)

The repetitive antigen stimulation during chronic infection often leads to the accumulation of CD8+CD57+ T cells. These cells express high levels of interferon-γ, granzyme B and perforin with elevated cytolytic effect, and are considered as the most potent cells for combating chronical viral infection. The status of CD8+CD57+ T cells in non-small cell lung cancer (NSCLC) has not been well defined. We used flow cytometry and undertook a systemic approach to examine the frequency, immunophenotyping and functional properties of CD8+CD57+ T cells in the peripheral blood, tumor tissue and the corresponding normal tissue, as well as lung draining lymph nodes, of patients with NSCLC. CD57+ T cells expressed high levels of programmed cell death-1 (PD-1) in all tested compartments and were predominantly CD8+ T cells. These cells in the peripheral blood displayed a terminally differentiated phenotype as defined by loss of CD27 and CD28 while expressing KLRG1. CD8+CD57+ T cells exhibited enhanced cytotoxic potencies and impaired proliferative capability. Unlike CD57+ T cells in the peripheral blood, a significant proportion of CD57+ T cells in the primary tumors expressed CD27 and CD28. CD8+CD57+ T cells in tumors lacked cytotoxic activity. The proliferative activity of these cells was also impaired. CD8+CD57+ T cells in the corresponding normal lung tissues shared similarities with their counterparts in peripheral blood rather than their counterparts in tumors. The vast majority of CD8+CD57+ T cells in lung draining lymph nodes were positive for CD27 and CD28. These cells were unable to produce perforin and granzyme B, but their proliferative activity was preserved. CD8+CD57+ T cells in tumors displayed an inferior response to PD-1 blockade compared with their CD8+CD57- counterparts. Interleukin (IL)-15 preferentially restored the effector function of these cells. Additionally, IL-15 was able to restore the impaired proliferative activity of CD8+CD57+ T cells in tumors and peripheral blood. Our data indicate that the failure of the immune system to fight cancer progression could be a result of impaired CD8+ T-cell functional maturation into fully differentiated effector T cells within the tumor microenvironment. Boosting IL-15 activity might promote tumor-reactive CD8+ T-cell functional maturation while preserving their proliferative activity.
The BET inhibitor CPI203 promotes ex vivo expansion of cord blood long-term repopulating HSCs and megakaryocytes
Authors: Peng Hua, Joanna Hester, George Adigbli, Rong Li, Bethan Psaila, Anindita Roy, Carole J. R. Bataille, Graham M. Wynne, Thomas Jackson, Thomas A. Milne, Angela J. Russell, James Davies, Irene Roberts, Fadi Issa, Suzanne M. Watt
Journal: Blood (2020)
Multifunctional N-P-doped carbon dots for regulation of apoptosis and autophagy in B16F10 melanoma cancer cells and <i>in vitro</i> imaging applications
Authors: Vivek K. Bajpai, Imran Khan, Shruti Shukla, Sung-Min Kang, Faisal Aziz, Kumud Malika Tripathi, Deepika Saini, Hye-Jin Cho, Nam Su Heo, Sumit K. Sonkar, Lei Chen, Yun Suk Huh, Young-Kyu Han
Journal: Theranostics (2020)

Rationale: The present study reports the multifunctional anticancer activity against B16F10 melanoma cancer cells and the bioimaging ability of fluorescent nitrogen-phosphorous-doped carbon dots (NPCDs). Methods: The NPCDs were synthesized using a single-step, thermal treatment and were characterized by TEM, XPS, fluorescence and UV-Vis spectroscopy, and FTIR analysis. The anticancer efficacy of NPCDs was confirmed by using cell viability assay, morphological evaluation, fluorescent live-dead cell assay, mitochondrial potential assay, ROS production, RT-PCR, western-blot analysis, siRNA transfection, and cellular bioimaging ability. Results: The NPCDs inhibited the proliferation of B16F10 melanoma cancer cells after 24 h of treatment and induced apoptosis, as confirmed by the presence of fragmented nuclei, reduced mitochondrial membrane potential, and elevated levels of reactive oxygen species. The NPCDs treatment further elevated the levels of pro-apoptotic factors and down-regulated the level of Bcl2 (B-cell lymphoma 2) that weakened the mitochondrial membrane, and activated proteases such as caspases. Treatment with NPCDs also resulted in dose-dependent cell cycle arrest, as indicated by reduced cyclin-dependent kinase (CDK)-2, -4, and -6 protein levels and an enhanced level of p21. More importantly, the NPCDs induced the activation of autophagy by upregulating the protein expression levels of LC3-II and ATG-5 (autophagy-related-5) and by downregulating p62 level, validated by knockdown of ATG-5. Additionally, owing to their excellent luminescence property, these NPCDs were also applicable in cellular bioimaging, as evidenced by the microscopic fluorescence imaging of B16F10 melanoma cells. Conclusion: Based on these findings, we conclude that our newly synthesized NPCDs induced cell cycle arrest, autophagy, and apoptosis in B16F10 melanoma cells and presented good cellular bioimaging capability.
The spectrum of COVID-19–associated dermatologic manifestations: An international registry of 716 patients from 31 countries
Authors: Esther E. Freeman, Devon E. McMahon, Jules B. Lipoff, Misha Rosenbach, Carrie Kovarik, Seemal R. Desai, Joanna Harp, Junko Takeshita, Lars E. French, Henry W. Lim, Bruce H. Thiers, George J. Hruza, Lindy P. Fox
Journal: Journal of the American Academy of Dermatology (2020)

BackgroundCoronavirus disease 2019 (COVID-19) has associated cutaneous manifestations.ObjectiveTo characterize the diversity of cutaneous manifestations of COVID-19 and facilitate understanding of the underlying pathophysiology.MethodsCase series from an international registry from the American Academy of Dermatology and International League of Dermatological Societies.ResultsThe registry collected 716 cases of new-onset dermatologic symptoms in patients with confirmed/suspected COVID-19. Of the 171 patients in the registry with laboratory-confirmed COVID-19, the most common morphologies were morbilliform (22%), pernio-like (18%), urticarial (16%), macular erythema (13%), vesicular (11%), papulosquamous (9.9%), and retiform purpura (6.4%). Pernio-like lesions were common in patients with mild disease, whereas retiform purpura presented exclusively in ill, hospitalized patients.LimitationsWe cannot estimate incidence or prevalence. Confirmation bias is possible.ConclusionsThis study highlights the array of cutaneous manifestations associated with COVID-19. Many morphologies were nonspecific, whereas others may provide insight into potential immune or inflammatory pathways in COVID-19 pathophysiology. Coronavirus disease 2019 (COVID-19) has associated cutaneous manifestations. To characterize the diversity of cutaneous manifestations of COVID-19 and facilitate understanding of the underlying pathophysiology. Case series from an international registry from the American Academy of Dermatology and International League of Dermatological Societies. The registry collected 716 cases of new-onset dermatologic symptoms in patients with confirmed/suspected COVID-19. Of the 171 patients in the registry with laboratory-confirmed COVID-19, the most common morphologies were morbilliform (22%), pernio-like (18%), urticarial (16%), macular erythema (13%), vesicular (11%), papulosquamous (9.9%), and retiform purpura (6.4%). Pernio-like lesions were common in patients with mild disease, whereas retiform purpura presented exclusively in ill, hospitalized patients. We cannot estimate incidence or prevalence. Confirmation bias is possible. This study highlights the array of cutaneous manifestations associated with COVID-19. Many morphologies were nonspecific, whereas others may provide insight into potential immune or inflammatory pathways in COVID-19 pathophysiology.
Combating the Hidden Health Disparity of Kernicterus in Black Infants
Authors: Francesca Okolie, Jeannette E. South-Paul, Jon F. Watchko
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Kernicterus is a devastating, permanently disabling neurologic condition resulting from bilirubin neurotoxicity. Black neonates account for more than 25% of kernicterus cases in the US, despite making up only approximately 14% of all births. This is a largely overlooked health disparity. <h3>Observations</h3> The black kernicterus health disparity exists despite a lower overall incidence of clinically significant hyperbilirubinemia among black neonates, a paradox recently explained by a previously unrecognized risk for hazardous hyperbilirubinemia. Aligned with national and global health initiatives to reduce or eliminate health disparities, this review highlights the multiple biologic and nonbiologic factors contributing to kernicterus risk in black infants and approaches to reduce this health disparity. This includes both parent-level and clinician-level kernicterus prevention strategies, with an emphasis on improving parental health literacy on neonatal jaundice and acute bilirubin encephalopathy and clinician awareness of the key factors that contribute to hazardous hyperbilirubinemia risk in this vulnerable group. Parent-level prevention strategies include efforts to improve their health literacy on neonatal jaundice and acute bilirubin encephalopathy and empower care seeking for jaundice. Clinician-level prevention strategies include efforts to eliminate community and institutional barriers that impede access to care, heighten clinician awareness of the factors that contribute to kernicterus risk in this vulnerable patient group, and strengthen newborn hyperbilirubinemia management and bilirubin surveillance. <h3>Conclusions and Relevance</h3> There are multiple opportunities for intervention to reduce black kernicterus risk. Although kernicterus is a rare disorder, the incidence among black infants is not a trivial matter nor are efforts to prevent kernicterus. While the multiple interacting biologic and nonbiologic contributors to increased kernicterus risk among black infants pose a considerable challenge to clinicians, there are opportunities for intervention to reduce this risk and health disparity. Continued study is imperative to understand the current scope of kernicterus and its occurrence in black neonates.
Risk Scores for Hepatocellular Carcinoma in Chronic Hepatitis B: A Promise for Precision Medicine
Authors: George V. Papatheodoridis, Thodoris Voulgaris, Margarita Papatheodoridi, W. Ray Kim
Journal: Hepatology (2020)

Papatheodoridis, George V.; Voulgaris, Thodoris; Papatheodoridi, Margarita; Kim, W. Ray Author Information
Shock in an Octogenarian During Percutaneous Coronary Intervention
Authors: Stephen Vampola, William B. Klaustermeyer, Rushi V. Parikh
Journal: JAMA Cardiology (2020)

A man in his 80s presented with myocardial infarction. Following a percutaneous coronary intervention, he abruptly became hypotensive. Despite stenting and administration of vasopressors, his blood pressure continued to decline and he experienced a cardiac arrest. What would you do next?
Alcohol Use Disorder and Suicide Risk: A Fresh and Closer Look
Authors: Deborah S. Hasin
Journal: American Journal of Psychiatry (2020)

Suicidal acts, both fatal and nonfatal, have increased in the United States over the past several years (1-5), as have heavy drinking and alcohol use disorders (6-8), especially among women (7,8), making the topic of the article by Edwards and colleagues in this issue (9)-namely, the relationship of alcohol use disorder (AUD) with suicide-an especially timely one for American investigators and health care providers.Edwards et al. made use of Swedish national register data that include information on health care utilization, diagnoses, and various other outcomes, such as involvements with the legal system.Focusing on the cohort of Swedes born between 1950 to 1970, the authors sought to determine the relationship of AUD to the risk for suicide mortality through 2012.Using proportional hazards analysis, the study found an association between AUD and subsequent suicide.Strengths of the study include analysis of an entire population rather than a sample, ample statistical power, the ability to employ a longitudinal approach, and inclusion of a number of relevant covariates.The message that alcohol use disorder carries a risk for eventual suicide is not a new one, nor is the message that this risk is compounded by psychiatric comorbidity.However, the information is important to reiterate in a fresh look, and to convey to health care providers.Some methodological aspects of the study do merit consideration.The main predictor of the study, AUD, is indicated by a "registration," described only in supplementary materials.From a previous study referenced as providing more information about the methods and measures (10), these included a variety of medical and psychiatric conditions in which alcohol involvement was suspected, as well as records of drunk driving or drunkoperation of a maritime vessel, crime registers, and a Swedish suspicion register that includes data on individuals suspected of crime.These are all termed registrations for AUD, although these various conditions in different Swedish registries are highly heterogeneous.Further, despite the apparent inclusiveness of this definition, population rates based on the combination of these conditions are lower than those reported in survey-based studies, raising questions about which individuals were characterized by the different registrations as having AUD.While the authors posit that they may have captured the most severe AUD cases, they may actually have identified a group of individuals with multiple characteristics predisposing to
Comparison of different incremental dose regimens of narrow-band ultraviolet B in skin types III to V: A prospective, randomized, single-blind, parallel study in patients with psoriasis
Authors: Yingyuan Yu, Xuemei Yi, Yi Zhang, Ning Yu, Qian Yu, Qianlian Le, Zeyu Chen, Yangfeng Ding, Yuling Shi
Journal: Journal of the American Academy of Dermatology (2020)
Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results
Authors: Matthew J Budoff, Joseph B Muhlestein, Deepak L Bhatt, Viet T Le Pa, Heidi T May, Kashif Shaikh, Chandana Shekar, April Kinninger, Suvasini Lakshmanan, Sion K Roy, John Tayek, John R Nelson
Journal: Cardiovascular Research (2020)

Abstract Aims Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. Methods and results EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40–115 mg/dL, and persistently high triglyceride levels (135–499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (−1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. Conclusion EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial. ClinicalTrials. govIdentifier NCT029226027.
The Affordable Care Act: Effects of Insurance on Diabetes Biomarkers
Authors: Miguel Marino, Heather Angier, Rachel Springer, Steele Valenzuela, Megan Hoopes, Jean O’Malley, Andrew Suchocki, John Heintzman, Jennifer DeVoe, Nathalie Huguet
Journal: Diabetes Care (2020)

OBJECTIVE We sought to understand how Affordable Care Act (ACA) Medicaid expansion insurance coverage gains are associated with changes in diabetes-related biomarkers. RESEARCH DESIGN AND METHODS This was a retrospective observational cohort study using electronic health record data from 178 community health centers (CHCs) in the ADVANCE (Accelerating Data Value Across a National Community Health Center Network) network. We assessed changes in diabetes-related biomarkers among adult patients with diabetes in 10 Medicaid expansion states (n = 25,279), comparing newly insured with continuously insured, discontinuously insured, and continuously uninsured patients pre– to post–ACA expansion. Primary outcomes included changes from 24 months pre- to 24 months post-ACA in glycosylated hemoglobin (HbA1c), systolic (SBP) and diastolic (DBP) blood pressure, and LDL cholesterol levels. RESULTS Newly insured patients exhibited a reduction in adjusted mean HbA1c levels (8.24% [67 mmol/mol] to 8.17% [66 mmol/mol]), which was significantly different from continuously uninsured patients, whose HbA1c levels increased (8.12% [65 mmol/mol] to 8.29% [67 mmol/mol]; difference-in-differences [DID] −0.24%; P &amp;lt; 0.001). Newly insured patients showed greater reductions than continuously uninsured patients in adjusted mean SBP (DID −1.8 mmHg; P &amp;lt; 0.001), DBP (DID −1.0 mmHg; P &amp;lt; 0.001), and LDL (DID −3.3 mg/dL; P &amp;lt; 0.001). Among patients with elevated HbA1c in the 3 months prior to expansion, newly insured patients were more likely than continuously uninsured patients to have a controlled HbA1c measurement by 24 months post-ACA (hazard ratio 1.25; 95% CI 1.02–1.54]. CONCLUSIONS Post-ACA, newly insured patients had greater improvements in diabetes-related biomarkers than continuously uninsured, discontinuously insured, or continuously insured patients. Findings suggest that health insurance gain via ACA facilitates access to appropriate diabetes care, leading to improvements in diabetes-related biomarkers.
A High Serum Level of Taurocholic Acid Is Correlated With the Severity and Resolution of Drug-induced Liver Injury
Authors: Qiuju Tian, Ruiyuan Yang, Yan Wang, Jimin Liu, Aileen Wee, Romil Saxena, Lan Wang, Min Li, Liwei Liu, Shan Shan, Yuanyuan Kong, Hong Ma, Xiaojuan Ou, Hong You, Xinyan Zhao, Jidong Jia
Journal: Clinical Gastroenterology and Hepatology (2020)
Media distortion of the public's perception of recidivism and psychiatric rehabilitation
Authors: F S Berlin, H M Malin
Journal: American Journal of Psychiatry (1991)

The public's perception about the success or failure of psychiatric rehabilitation is frequently dependent upon information received through the news media. The primary objective of this report is to present an example of how the news media can distort public perceptions of treatment outcome.Verbatim quotations were presented from a television news series that alleged criminal recidivism by nine patients purportedly treated for various paraphilias at a large, community-based sexual disorders clinic. Brief case vignettes about each of the nine were then reviewed. This allowed for comparisons between what the media had alleged and what had actually occurred.Two of the nine cases were relatively minor instances of recidivism involving no genital contact, although the media presentation had either failed to report this or had suggested otherwise. A third case of alleged recidivism involved a patient who was evaluated but never actually treated by the clinic in the community. A fourth patient had refused recommended clinic treatment upon prison release, and a fifth patient had been discharged from treatment at the clinic because of noncompliance years before recidivating. Other cases presented contained additional misleading information. None of the nine cases was reported by the media in the context of a balanced approach that included treatment successes. Clinic staff were constrained from responding publicly to correct certain misinformation because of patient-psychiatrist privilege.Inaccurate media presentations about psychiatric rehabilitation that ignore treatment successes and focus only on alleged failures do a disservice to patients, mental health workers, and society at large.