tbuckley/cabot-search huggingface dataset:
Trends in Utilization of Transitional Care Management in the United States
Authors: Leah M. Marcotte, Ashok Reddy, Lingmei Zhou, Sophie C. Miller, Carly Hudelson, Joshua M. Liao
Journal: JAMA Network Open (2020)

Improving care transitions after hospitalization is a key opportunity to improve health care value. Recognizing the importance and complexity of coordinating care during the postdischarge period, Medicare implemented transitional care management (TCM) codes in 2013 to increase reimbursement to ambulatory clinicians treating patients after hospital discharge. Early evidence has suggested that TCM could be beneficial, as it was associated with lower costs of care and mortality and readmission rates, although uptake was low.1,2 Little is known about national trends in TCM use over an extended period, particularly amid intensifying shifts toward value-based payment and care under federal policies, such as the Medicare Access and CHIP Reauthorization Act of 2015.
Association of Pediatric Suicide With County-Level Poverty in the United States, 2007-2016
Authors: Jennifer A. Hoffmann, Caitlin A. Farrell, Michael C. Monuteaux, Eric W. Fleegler, Lois K. Lee
Journal: JAMA Pediatrics (2020)

<h3>Importance</h3> Suicide is the second leading cause of death among youths aged 10 to 19 years in the United States, with rates nearly doubling during the past decade. Youths in impoverished communities are at increased risk for negative health outcomes; however, the association between pediatric suicide and poverty is not well understood. <h3>Objective</h3> To assess the association between pediatric suicide rates and county-level poverty concentration. <h3>Design, Setting, and Participants</h3> This retrospective, cross-sectional study examined suicides among US youths aged 5 to 19 years from January 1, 2007, to December 31, 2016. Suicides were identified using<i>International Statistical Classification of Diseases, Tenth Revision, Clinical Modification</i>codes from the Centers for Disease Control and Prevention's Compressed Mortality File. Data analysis was performed from February 1, 2019, to September 10, 2019. <h3>Exposures</h3> County poverty concentration and the percentage of the population living below the federal poverty level. Counties were divided into 5 poverty concentration categories: 0% to 4.9%, 5.0% to 9.9%, 10.0% to 14.9%, 15.0% to 19.9%, and 20.0% or more of the population living below the federal poverty level. <h3>Main Outcomes and Measures</h3> The study used a multivariable negative binomial regression model to analyze the association between pediatric suicide rates and county poverty concentration, reporting adjusted incidence rate ratios (aIRRs) with 95% CIs. The study controlled for year, demographic characteristics of the children who died (age, sex, and race/ethnicity), county urbanicity, and county demographic features (age, sex, and racial composition). Subgroup analyses were stratified by method. <h3>Results</h3> From 2007 to 2016, a total of 20 982 youths aged 5 to 19 years died by suicide (17 760 [84.6%] were aged 15-19 years, 15 982 [76.2%] male, and 14 387 [68.6%] white non-Hispanic). The annual suicide rate was 3.35 per 100 000 youths aged 5 to 19 years. In the multivariable model, compared with counties with the lowest poverty concentration (0%-4.9%), counties with poverty concentrations of 10% or greater had higher suicide rates in a stepwise manner (10.0%-14.9%: aIRR, 1.25 [95% CI, 1.06-1.47]; 15.0%-19.9%: aIRR, 1.30 [95% CI, 1.10-1.54]; and 20.0% or more: aIRR, 1.37 [95% CI, 1.15-1.64]). When stratified by method, firearm suicides had the strongest association with county poverty concentration (aIRR, 1.87; 95% CI, 1.41-2.49) in counties with 20% or higher poverty concentration compared with counties with 0% to 4.9% poverty concentration. <h3>Conclusions and Relevance</h3> The findings suggest that higher county-level poverty concentration is associated with increased suicide rates among youths aged 5 to 19 years. These findings may guide research into upstream risk factors associated with pediatric suicide to inform suicide prevention efforts.
Effects of Aluminum on the Integrity of the Intestinal Epithelium: An <i>in Vitro</i> and <i>in Vivo</i> Study
Authors: Chang Hee Jeong, Hyuk Cheol Kwon, Do Hyun Kim, Wei Nee Cheng, Sukyung Kang, Dong-Min Shin, Jong Hyeok Yune, Jee Eun Yoon, You Hyun Chang, Hyejin Sohn, Sung Gu Han
Journal: Environmental Health Perspectives (2020)

Background: Aluminum (Al) is the most abundant and ubiquitous metal in the environment. The main route of human exposure to Al is through food and water intake. Although human exposure to Al is common, the influence of Al on the gastrointestinal tract remains poorly understood. Objectives: We aimed to further understand the toxic effect of Al and to elucidate the underlying cellular mechanisms in the intestinal barrier. Methods: The human intestinal epithelial cell line HT-29 and C57BL6 mice were exposed to AlCl3 at 0–16 mM (1–24h) and 5–50mg/kg body weight (13 weeks), respectively. In cell culture experiments, intracellular oxidative stress, inflammatory protein and gene expression, and intestinal epithelial permeability were measured. In animal studies, histological examination, gene expression, and myeloperoxidase (MPO) activity assays were conducted. Results: Cellular oxidative stress level (superoxide production) in AlCl3-treated cells (4 mM, 3h) was approximately 38-fold higher than that of the control. Both protein and mRNA expression of tight junction (TJ) components (occludin and claudin-1) in AlCl3-treated cells (1–4 mM, 24h) was significantly lower than that of the control. Transepithelial electrical resistance (TEER) decreased up to 67% in AlCl3-treated cells (2 mM, 24h) compared with that of the control, which decreased approximately 7%. Al activated extracellular signal-regulated kinase 1/2 and nuclear factor-kappa B (NF-κB), resulting in mRNA expression of matrix metalloproteinase-9, myosin light-chain kinase, and inflammatory cytokines [tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and IL-6] in HT-29 cells. Moreover, oral administration of AlCl3 to mice induced pathological alteration, MPO activation, and inflammatory cytokine (TNF-α, IL-1β, and IL-6) production in the colon. Conclusion: Al induced epithelial barrier dysfunction and inflammation via generation of oxidative stress, down-regulation of the TJ proteins, and production of inflammatory cytokines in HT-29 cells. In addition, Al induced toxicity in the colon by increasing the levels of inflammatory cytokines and MPO activity and induced histological damage in a mouse model. Our data suggest that Al may be a potential risk factor for human intestinal diseases. https://doi.org/10.1289/EHP5701
Charcot-Leyden crystal protein/galectin-10 interacts with cationic ribonucleases and is required for eosinophil granulogenesis
Authors: Milica M. Grozdanovic, Christine B. Doyle, Li Liu, Brian T. Maybruck, Mark A. Kwatia, Nethaji Thiyagarajan, K. Ravi Acharya, Steven J. Ackerman
Journal: Journal of Allergy and Clinical Immunology (2020)
The Alopecia Areata Investigator Global Assessment scale: a measure for evaluating clinically meaningful success in clinical trials
Authors: K.W. Wyrwich, H. Kitchen, S. Knight, N.V.J. Aldhouse, J. Macey, F.P. Nunes, Y. Dutronc, N. Mesinkovska, J.M. Ko, B.A. King
Journal: British Journal of Dermatology (2020)

Content‐valid and clinically meaningful instruments are required to evaluate outcomes of therapeutic interventions in alopecia areata (AA). To develop an Investigator's Global Assessment (IGA) to interpret treatment response in AA treatment studies. Qualitative interviews were conducted in the USA with expert dermatologists and with patients with AA who had experienced ≥ 50% scalp‐hair loss. Thematic data analysis identified critical outcomes and evaluated the content validity of the new IGA. Expert clinicians (n = 10) judged AA treatment success by the amount of scalp‐hair growth (median 80% scalp hair). Adult (n = 25) and adolescent (n = 5) patients participated. Scalp‐hair loss was the most bothersome AA sign/symptom for most patients. Perceived treatment success – short of 100% scalp hair – was the presence of ~ 70–90% scalp hair (median 80%). Using additional clinician and patient insights, the Alopecia Areata Investigator Global Assessment (AA‐IGA™) was developed. This clinician‐reported outcome assessment is an ordinal, static measure comprising five severity categories of scalp‐hair loss. Nearly all clinicians and patients in this study agreed that, for patients with ≥ 50% scalp‐hair loss, successful treatment would be hair regrowth resulting in ≤ 20% scalp‐hair loss. We recommend using the Severity of Alopecia Tool to assess the extent (0–100%) of scalp‐hair loss. The AA‐IGA is a robust ordinal measure providing distinct and clinically meaningful gradations of scalp‐hair loss that reflects patients' and expert clinicians' perspectives and treatment expectations. What is already known about this topic? The Severity of Alopecia Tool is widely used to assess the extent of scalp‐hair loss in patients with alopecia areata. Guidelines define treatment success as a 50% improvement in scalp hair, and clinical trials have used dynamic thresholds of 50% and 90%. However, there is no clinical consensus on these endpoints, and patient perspectives on treatment success are unknown. What does this study add? Through qualitative interviews with 10 expert dermatologists and 30 patients with alopecia areata who had experienced ≥ 50% scalp‐hair loss, we developed the Alopecia Areata Investigator Global Assessment (AA‐IGA™) to measure five clinically meaningful gradations of alopecia areata scalp‐hair loss that reflects patients' and clinicians' perspectives and expectations of treatment success in alopecia areata treatment studies. What are the clinical implications of this work? The AA‐IGA is a robust ordinal measure that can inform clinical evaluation of alopecia areata treatment outcomes. The AA‐IGA can be used to determine clinically meaningful treatment success for alopecia areata, with success defined by patients and clinicians as reaching ≤ 20% scalp‐hair loss. Linked Comment:Blome. Br J Dermatol 2020; 183:609.
Mechanistic insights into effect of surfactants on oral bioavailability of amorphous solid dispersions
Authors: A. Schittny, S. Philipp-Bauer, P. Detampel, J. Huwyler, M. Puchkov
Journal: Journal of Controlled Release (2020)

Drug delivery of poorly soluble drugs in form amorphous solid dispersions (ASDs) is an appealing method to increase in vivo bioavailability. For rational formulation design, a mechanistic understanding of the impact of surfactants on the performance of ASD-based formulations is therefore of importance. In this study, we used hot-melt extrusion to prepare ASDs composed of the model drug substance efavirenz with hydroxypropyl methylcellulose phthalate (HPMCP) as the base polymer, and surfactants. Molecular dynamics simulations and in vitro dissolution studies were used to investigate formation and drug release from polymer vesicles, and their ability to maintain a supersaturation state as a function of surfactant composition. It was possible to identify main factors regulating particle formation and to modify dissolution profiles with different excipient compositions. Animal studies in the rat, in combination with physiologically based pharmacokinetic modeling, demonstrated enhanced drug absorption from formed vesicles. The surfactant composition in the ASD had a direct influence on the morphology of these vesicles, as well as kinetics of drug release, and, therefore, the oral bioavailability. ASDs, prepared by hot-melt extrusion method, were optimized for dissolution and adsorption rates increase. Our findings contribute to a better understanding of dissolution behavior of ASDs with respect to the function of surfactants, aiming to facilitate a rational formulation development and an accelerated transition from in vitro systems to in vivo applications.
Evaluating single-domain antibodies as carriers for targeted vaccine delivery to the small intestinal epithelium
Authors: Shruti Bakshi, Raquel Sanz Garcia, Hans Van der Weken, Ashuwini Tharad, Shubham Pandey, Paloma Juarez, Vikram Virdi, Bert Devriendt, Eric Cox, Ann Depicker
Journal: Journal of Controlled Release (2020)
Abstract 13922: A Comparison of Bidirectional Glenn vs. Hemi-Fontan Using Data From the Single Ventricle Reconstruction Trial
Authors: Jonathan B Edelson, Chitra Ravishankar, Heather Griffis, Xuemei Zhang, Jennifer Faerber, Maryam Y Naim, Christopher E Mascio, Andrew C Glatz, David J Goldberg
Journal: Circulation (2018)

Introduction: For patients with single ventricle heart defects (SV), there are two primary surgical options for second stage palliation: bidirectional Glenn (BDG) and hemi-Fontan (HF). Limited data...
Abstract 10122: A Randomized Trial of Exercise versus Low-energy Meal Replacement Diet to Improve Cardiac Dysfunction in Working-Age Adults With Type 2 Diabetes
Authors: Gaurav S Gulsin, Daniel J Swarbrick, Lavanya Athithan, Emer M Brady, Joseph J Henson, Emma Baldry, Stavroula Argyridou, Anna-Marie Marsh, Gareth Squire, Nishal B Jaicim, John Biglands, Thomas Yates, Kamlesh Khunti, Melanie J Davies, Gerry McCann
Journal: Circulation (2019)

Introduction: Adults with type 2 diabetes (T2DM) may already have diastolic dysfunction, a precursor to heart failure. Whether weight loss or exercise improve subclinical diastolic dysfunction in T...
Reduced susceptibility and resistance to bedaquiline in clinical M. tuberculosis isolates
Authors: Irina V. Peretokina, Ludmila Yu. Krylova, Olga V. Antonova, Margarita S. Kholina, Elena V. Kulagina, Elena Yu Nosova, Svetlana G. Safonova, Sergey E. Borisov, Danila V. Zimenkov
Journal: Journal of Infection (2020)
Tumor SUVs on 18F-FDG PET/CT and Aggressive Pathological Features in Esophageal Squamous Cell Carcinoma
Authors: Chae Hong Lim, Yong-Jin Park, Muheon Shin, Young Seok Cho, Joon Young Choi, Kyung-Han Lee, Seung Hyup Hyun
Journal: Clinical Nuclear Medicine (2019)

Purpose Considerable discrepancies are observed between clinical staging and pathological staging after surgical resection in patients with esophageal squamous cell carcinoma (ESCC). In this study, we examined the relationships between tumor SUVs on FDG PET/CT and aggressive pathological features in resected ESCC patients. Methods A total of 220 patients with surgically resected clinical stage I–II ESCC without neoadjuvant treatment were retrospectively analyzed. SUVmax of the primary tumor was measured on pretreatment FDG PET/CT. Pathological features included depth of tumor invasion, lymph node metastasis, tumor differentiation, lymphatic vessel tumor embolus, perineural invasion, Ki-67 index, and p53 protein expression. Receiver operating characteristic curve analysis was used to determine an optimal cutoff of SUVmax to predict pathologically advanced disease. Differences in pathological features associated with SUVmax were examined by t test or χ 2 test. Results The number of patients upstaged from clinical stage I–II to pathological stage III–IV was 43 (19.5%). Receiver operating characteristic curve analysis showed that the optimal cutoff SUVmax of 4.0 had good performance for predicting locally advanced disease (area under the receiver operating characteristic curve = 0.844, P &lt; 0.001). Higher tumor SUVmax was significantly associated with advanced depth of tumor invasion (deeper than submucosa, P &lt; 0.001), positive lymph node metastasis ( P &lt; 0.001), presence of lymphatic vessel tumor embolus ( P &lt; 0.001), presence of perineural invasion ( P &lt; 0.001), higher Ki-67 index ( P = 0.025), and poor tumor differentiation ( P = 0.039). Conclusions SUVmax measured on pretreatment FDG PET/CT is significantly associated with aggressive pathological features and may help clinicians identify patients at risk of advanced disease.
Treatments for the Prevention and Management of Suicide
Authors: Kristen E. D'Anci, Stacey Uhl
Journal: Annals of Internal Medicine (2020)

Letters21 January 2020Treatments for the Prevention and Management of SuicideKristen E. D'Anci, PhD and Stacey Uhl, MSKristen E. D'Anci, PhDECRI Institute Center for Clinical Evidence and Guidelines, Plymouth Meeting, Pennsylvania (K.E.D., S.U.) and Stacey Uhl, MSECRI Institute Center for Clinical Evidence and Guidelines, Plymouth Meeting, Pennsylvania (K.E.D., S.U.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0707 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Clozapine is recognized and recommended as a treatment to reduce death by suicide among adults with schizophrenia or schizoaffective disorder in the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense (VA/DoD) clinical practice guideline on the assessment and management of patients at risk for suicide (1). This recommendation was carried forward from the previous VA/DoD guideline on the management of suicide published in 2013 and is based largely on the study by Meltzer and colleagues (2), which Dr. Kelly and associates cite. Because this study was included in the previous versions of the guideline, it ...References1. Sall J, Brenner L, Millikan Bell AM, et al. Assessment and management of patients at risk for suicide: synopsis of the 2019 U.S. Department of Veterans Affairs and U.S. Department of Defense clinical practice guidelines. Ann Intern Med. 2019;171:343-53. [PMID: 31450237]. doi:10.7326/M19-0687 LinkGoogle Scholar2. Meltzer HY, Alphs L, Green AI, et al; International Suicide Prevention Trial Study Group. Clozapine treatment for suicidality in schizophrenia: International Suicide Prevention Trial (InterSePT). Arch Gen Psychiatry. 2003;60:82-91. [PMID: 12511175] CrossrefMedlineGoogle Scholar Author, Article, and Disclosure InformationAffiliations: ECRI Institute Center for Clinical Evidence and Guidelines, Plymouth Meeting, Pennsylvania (K.E.D., S.U.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19-0869. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoTreatments for the Prevention and Management of Suicide Kristen E. D'Anci , Stacey Uhl , Gina Giradi , and Constance Martin Treatments for the Prevention and Management of Suicide Deanna L. Kelly , David A. Gorelick , Heidi J. Wehring , Gopal Vyas , and Robert W. Buchanan Metrics Cited byA longitudinal analysis of person‐centred therapy with suicidal clientsWhere is the social in the biopsychosocial model of suicide prevention? 21 January 2020Volume 172, Issue 2Page: 168KeywordsDisclosureSchizophreniaSuicideSystematic reviewsTreatment guidelines ePublished: 21 January 2020 Issue Published: 21 January 2020 PDF downloadLoading ...
New targeted anti CDK4/6 peptide MM-D37K.
Authors: Vladimir Konstantinovich Bozhenko, Tatyana Michailovna Kulinich, Elena Aleksandrovna Kudinova, Andrey Boldyrev, Vladimir Alekseevich Solodkij
Journal: Journal of Clinical Oncology (2013)

e13545 Background: MM-D37K is a synthetic peptide which consists of p16INK4a-specific inhibitor of complex cyclin D- CDK4 and CDK6 and cell penetrating peptide (CPP) – Antp (Penetratin). We investigated in vitro and in vivo cytotoxic, cytostatic and antitumor activity of MM-D37K. The level of cyclin A, Ki67,bax, bcl-2 and pRb phosphorylation was investigated. Full range of Toxicology tests and Pharmacokinetics experiments in mice, rats and rabbits were performed. Methods: Different cell lines (Jurcat, Raji, A549, MCF-7, Hct-116, Ht-29, HEK293) were incubated with 0.1-100 mM MM-D37K for 24-48 hrs. Proliferation (MTT), DNA-content, cell cycle (flow cytometry) and mRNA level of appropriate proteins (RT PCR) were investigated. In vivo experiments were conducted on xenograft model of HCT116, A-549 at concentration 5 and 10 mg/kg of MM-D37K. Toxicology experiments were made under RF Law and included 3 types of animals. LC-MS MMD37K method of detection in plasma was developed. Results: MM-D37K prevented pRb phosphorilation and proliferation activation in all investigated cell lines. Cell cycle was blocked in G1 phase. Cytostatic effect did not depend on p16 mutation or expression. MM-D37K induced apoptosis in 20-82% of investigated cells at 40 mM with lowest level for MCF-7. LD10 for rats was 100 mg/kg and no deaths were registered for rabbits (highest dose was 50 mg/kg). Concentration of MMD-37K in plasma after 2 min and bolus i.v. injection in dose 10 mg/kg was 72.16±5.64 mcg/ml. Concentration decreased in two phases. 1st – t1/2 = 2.39±0.39 min and for 2nd t1/2=2.39±0.39 hr. Antitumor effects in xenograft model were 53% for A-549 and 67% for HCT116. Conclusions: Our results proved cytotoxic, cytostatic and antitumor effects of MM-D37K in investigated cell lines in vitro and in vivo. Toxicological and pharmacokinetics results allow us recommend for I/IIa Phase clinical trial. (Support: MetaMax Ltd., RFFI, Minpromtorg RF.)
Feed-forward regulatory loop driven by IRF4 and NF-κB in adult T-cell leukemia/lymphoma
Authors: Regina Wan Ju Wong, Tze King Tan, Stella Amanda, Phuong Cao Thi Ngoc, Wei Zhong Leong, Shi Hao Tan, Kaori Asamitsu, Yurina Hibi, Ryuzo Ueda, Takashi Okamoto, Takashi Ishida, Shinsuke Iida, Takaomi Sanda
Journal: Blood (2020)
Prolonged Local In Vivo Delivery of Stimuli‐Responsive Nanogels That Rapidly Release Doxorubicin in Triple‐Negative Breast Cancer Cells
Authors: Yi Zhang, Pere Dosta, João Conde, Nuria Oliva, Mian Wang, Natalie Artzi
Journal: Advanced Healthcare Materials (2020)

Abstract Triple negative breast cancer patients remain with chemotherapy as their only viable therapeutic option. However, the toxicity of available anticancer drugs and their inefficient delivery have limited the development of effective chemotherapy administration protocols and combination therapies. Drug delivery devices that can properly target chemotherapy to the right cells with efficient cancer‐cell killing may play a vital role in eliminating triple‐negative breast cancer. While systemic delivery results in low drug accumulation at the tumor site and for a short period of time, local delivery enables sustained drug release. However, a system that is able to provide rapid, yet prolonged action, would enable efficient tumor elimination. Herein, the development of dual‐sensitive nanogels is described that are designed to rapidly dislodge the chemotherapy drug, doxorubicin, inside cancer cells through dual‐sensitive action—pH and redox sensitivities—enabling efficient cancer‐cell killing while eliminating systemic side effects. Their embedding within a hydrogel injected next to a tumor in a triple‐negative breast‐cancer mouse model enables prolonged release of the drug with instantaneous action when inside the cells resulting in efficacious tumor elimination compared to sustained local delivery only. This technology can be used for the delivery of combination therapies and for the treatment of other solid tumors.
Early bronchial inflammation and remodeling and airway hyperresponsiveness at school age
Authors: Leo Pekka Malmberg, Kristiina Malmström, Anne Kotaniemi‐Syrjänen, Jouko Lohi, Anna S. Pelkonen, Seppo Sarna, Mika J. Mäkelä
Journal: Allergy (2020)

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Rare Esophageal Leptomeningeal Metastases Detected on 18F-FDG PET/CT
Authors: Yang Lu, Linghua Wang, Jaffer A. Ajani
Journal: Clinical Nuclear Medicine (2020)

Abstract A 62-year-old man with a history of locally advanced poorly differentiated adenocarcinoma of the gastroesophageal junction had received induction chemotherapy and concurrent chemoradiation. A 6-month follow-up FDG PET/CT revealed nearly resolved primary malignancy, but new hypermetabolic mediastinal lymph node metastasis and abnormal hypermetabolism in the cerebellum region. Brain MRI and lumbar puncture confirmed leptomeningeal metastasis.