tbuckley/cabot-search huggingface dataset:
Association of Medicare Spending With Subspecialty Consultation for Elderly Hospitalized Adults
Authors: Kira L. Ryskina, Yihao Yuan, Rachel M. Werner
Journal: JAMA Network Open (2019)

<h3>Importance</h3> High use of subspecialty care is an important source of health care spending. Medical subspecialty care in particular may duplicate the scope of practice of the primary attending physicians for patients hospitalized for medical conditions. Under value-based payments, which aim to control overall spending during an episode of hospitalization (including Part B physician fees), subspecialty consultations may be a target for hospitals working to reduce costs. <h3>Objectives</h3> To measure the use of subspecialty consultation for Medicare beneficiaries hospitalized for nonsurgical conditions; to compare payments for consultative and nonconsultative care, adjusted for case mix and demographics; and to measure variation in payments across hospital referral regions (HRRs). <h3>Design, Setting, and Participants</h3> This retrospective cross-sectional study included a 15% random sample of Medicare fee-for-service beneficiaries enrolled in Parts A and B and identified all discharges after acute care hospital stays for nonsurgical conditions from January 1 through December 31, 2014. A total of 735 627 discharges were included. The analyses were conducted from December 1, 2017, through February 12, 2019. Total Part B payments were extrapolated to the population of Medicare fee-for-service beneficiaries. <h3>Main Outcomes and Measures</h3> Probability of any consultation during a hospitalization was estimated using logistic regression. The number of consultations per stay and the number of consultative visits per hospital day were estimated using Poisson regression. Part B payments for consultative and nonconsultative care were estimated using generalized linear regression with gamma-log link. All models were adjusted for patient demographics and case mix. Payment models also included HRR fixed effects. <h3>Results</h3> A total of 735 627 discharges from 4534 hospitals in 2014 were included in the analysis (41.2% men and 58.8% women; mean [SD] age, 79.6 [8.9] years; 84.7% white, 10.1% black, and 5.2% other race). After adjusting for patient case mix and demographics, a 6-fold variation between the top and bottom quintiles of hospitals (relative difference, $401 [95% CI, $368-$434]) and HRRs (relative difference, $363 [95% CI, $337-$389]) was found in payments per stay for consultative care. Part B payments for consultative care by medical subspecialists accounted for 41.3% of payments for physician visits during hospitalization and totaled $1.3 billion in 2014. <h3>Conclusions and Relevance</h3> The substantial variation in the use of subspecialty consultative care suggests potential opportunities for cost savings.
Recent advances of microneedles for biomedical applications: drug delivery and beyond
Authors: Jian Yang, Xinli Liu, Yunzhi Fu, Yujun Song
Journal: Acta Pharmaceutica Sinica B (2019)

The microneedle (MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing (3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.
Immunogenomic landscape of hepatocellular carcinoma with immune cell stroma and EBV-positive tumor-infiltrating lymphocytes
Authors: Hyo Jeong Kang, Ji-Hye Oh, Sung-Min Chun, Deokhoon Kim, Yeon-Mi Ryu, Hee Sang Hwang, Sang-Yeob Kim, Jihyun An, Eun Jeong Cho, Hyeonjin Lee, Ju Hyun Shim, Chang Ohk Sung, Eunsil Yu
Journal: Journal of Hepatology (2019)
Design and evaluation of novel inhalable sildenafil citrate spray-dried microparticles for pulmonary arterial hypertension
Authors: Hend I. Shahin, Bhavani Prasad Vinjamuri, Azza A. Mahmoud, Rehab N. Shamma, Suzan M. Mansour, Hussein O. Ammar, Mahmoud M. Ghorab, Mahavir Bhupal Chougule, Lipika Chablani
Journal: Journal of Controlled Release (2019)
Probiotics in the next-generation sequencing era
Authors: Jotham Suez, Niv Zmora, Eran Elinav
Journal: Gut Microbes (2019)

Technological developments, including massively parallel DNA sequencing, gnotobiotics, metabolomics, RNA sequencing and culturomics, have markedly propelled the field of microbiome research in recent years. These methodologies can be harnessed to improve our in-depth mechanistic understanding of basic concepts related to consumption of probiotics, including their rules of engagement with the indigenous microbiome and impacts on the human host. We have recently demonstrated that even during probiotic supplementation, resident gut bacteria in a subset of individuals resist the mucosal presence of probiotic strains, limiting their modulatory effect on the microbiome and on the host gut transcriptional landscape. Resistance is partly alleviated by antibiotics treatment, which enables probiotics to interact with the host at the gut mucosal interface, although rather than promoting reconstitution of the indigenous microbiome and of the host transcriptional profile, they inhibit these components from returning to their naïve pre-antibiotic configurations. In this commentary, we discuss our findings in the context of previous and recent works, and suggest that incorporating the state-of-the-art methods currently utilized in microbiome research into the field of probiotics may lead to improved understanding of their mechanisms of activity, as well as their efficacy and long-term safety.
Compendium of skin molecular signatures identifies key pathological features associated with fibrosis in systemic sclerosis
Authors: Su-Jin Moon, Jung Min Bae, Kyung-Su Park, Ilias Tagkopoulos, Ki-Jo Kim
Journal: Annals of the Rheumatic Diseases (2019)

Objectives Treatment of patients with systemic sclerosis (SSc) can be challenging because of clinical heterogeneity. Integration of genome-scale transcriptomic profiling for patients with SSc can provide insights on patient categorisation and novel drug targets. Methods A normalised compendium was created from 344 skin samples of 173 patients with SSc, covering an intersection of 17 424 genes from eight data sets. Differentially expressed genes (DEGs) identified by three independent methods were subjected to functional network analysis, where samples were grouped using non-negative matrix factorisation. Finally, we investigated the pathways and biomarkers associated with skin fibrosis using gene-set enrichment analysis. Results We identified 1089 upregulated DEGs, including 14 known genetic risk factors and five potential drug targets. Pathway-based subgrouping revealed four distinct clusters of patients with SSc with distinct activity signatures for SSc-relevant pathways. The inflammatory subtype was related to significant improvement in skin fibrosis at follow-up. The phosphoinositide-3-kinase-protein kinase B (PI3K-Akt) signalling pathway showed both the closest correlation and temporal pattern to skin fibrosis score. COMP , THBS1 , THBS4 , FN1 , and TNC were leading-edge genes of the PI3K-Akt pathway in skin fibrogenesis. Conclusions Construction and analysis of normalised skin transcriptomic compendia can provide useful insights on pathway involvement by SSc subsets and discovering viable biomarkers for a skin fibrosis index. Particularly, the PI3K-Akt pathway and its leading players are promising therapeutic targets.
Preclinical Evaluation of Hdp-101, a Novel Anti-BCMA Antibody-Drug Conjugate, in Multiple Myeloma
Authors: Jonathan Ko, Christian Breunig, Vianiuhini Figueroa, Nicola Lehners, Anja Baumann, Aniko Pálfi, Christoph Müller, Christian Lutz, Torsten Hechler, Michael Kulke, Carsten Müller-Tidow, Hartmut Goldschmidt, Andreas Pahl, Marc S Raab
Journal: Blood (2017)
Assessment of Health Care Utilization and Cost of Targeted Drug Delivery and Conventional Medical Management vs Conventional Medical Management Alone for Patients With Cancer-Related Pain
Authors: Lisa J. Stearns, Sanjeet Narang, Robert E. Albright, Krisstin Hammond, Ying Xia, Heather Basara Richter, Gobi K. Paramanandam, Kelly K. Haagenson, Alissa H. Doth
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Targeted drug delivery (TDD) has potential for cost savings compared with conventional medical management (CMM). Despite positive clinical and economic evidence, TDD remains underused to treat cancer pain. <h3>Objective</h3> To assess the cost of TDD and CMM in treating cancer-related pain. <h3>Design, Setting, and Participants</h3> This retrospective economic evaluation using propensity score–matched analysis was conducted using MarketScan commercial claims data on beneficiaries receiving TDD and CMM or CMM only for cancer pain from January 1, 2009, to September 30, 2015. Participants were matched on age, sex, cancer type, comorbidity score, and pre-enrollment characteristics. Data analysis was performed from June 1 to September 30, 2017. <h3>Main Outcomes and Measures</h3> Total 2-, 6-, and 12-month costs, number of health care encounters, length of hospital stay, additional components of cost, and health care utilization. <h3>Results</h3> A total of 376 TDD and CMM patients (mean [SD] age, 51.88 [9.98] years; 216 [57.5%] female) and 4839 CMM only patients (mean [SD] age, 51.52 [11.16] years; 3005 [62.1%] female) were identified for study inclusion. After matching, 536 patients were included in the study: 268 patients in the TDD and CMM group and 268 in the CMM only group. Compared with CMM only, TDD and CMM was associated with mean total cost savings of $15 142 (95% CI, $3690 to $26 594;<i>P</i> = .01) at 2 months and $63 498 (95% CI, $4620 to $122 376;<i>P</i> = .03) at 12 months; cost savings at 6 months were not statistically different ($19 577; 95% CI, −$12 831 to $51 984;<i>P</i> = .24). The TDD and CMM group had fewer inpatient visits (2-month mean difference [MD], 1.0; 95% CI, 0.8-1.2;<i>P</i> &lt; .001; 6-month MD, 1.3; 95% CI, 0.8-1.7;<i>P</i> &lt; .001; 12-month MD, 2.3; 95% CI, 1.2-3.4;<i>P</i> &lt; .001) and shorter hospital stays (2-month MD, 6.8 days; 95% CI, 5.0-8.7 days;<i>P</i> &lt; .001; 6-month MD, 6.8 days; 95% CI, 3.1-10.5 days;<i>P</i> &lt; .001; 12-month MD, 10.6 days; 95% CI, 2.9-18.3 days;<i>P</i> = .007). Use of CMM only was associated with greater opioid use at 12 months (MD, 3.2; 95% CI, 0.4-6.0;<i>P</i> = .03). <h3>Conclusions and Relevance</h3> Compared with CMM alone, TDD and CMM together were associated with significantly lower cost and health care utilization. The findings suggest that TDD is a cost-saving therapy that should be considered in patients with cancer for whom oral opioids are inadequate or produce intolerable adverse effects and should be expanded as health care systems transition to value-based models.
Integrated HIV testing, prevention, and treatment intervention for key populations in India: a cluster-randomised trial
Authors: Sunil S Solomon, Suniti Solomon, Allison M McFall, Aylur K Srikrishnan, Santhanam Anand, Vinita Verma, Canjeevaram K Vasudevan, Pachamuthu Balakrishnan, Elizabeth L Ogburn, Lawrence H Moulton, Muniratnam S Kumar, Kuldeep Singh Sachdeva, Oliver Laeyendecker, David D Celentano, Gregory M Lucas, Shruti H Mehta
Journal: The Lancet HIV (2019)
Canadian-American Differences in the Management of Acute Coronary Syndromes in the GUSTO IIb Trial
Authors: Yuling Fu, Wei-Ching Chang, Dan Mark, Robert M. Califf, Brian Mackenzie, Christopher B. Granger, Eric J. Topol, Mark Hlatky, Paul W. Armstrong
Journal: Circulation (2000)

Background —Little information exists concerning practice patterns between Canada and the United States in the management of myocardial infarction (MI) patients without ST-segment elevation and unstable angina. Methods and Results —We examined the practice patterns and 1-year outcomes of 2250 US and 922 Canadian patients without ST-elevation acute coronary syndromes in the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb trial. The US hospitals more commonly had on-site facilities for angiography and revascularization. These procedures were performed more often and sooner in the United States than Canada, whereas Canadian patients were more likely to undergo noninvasive stress testing. The length of initial hospital stay was 1 day longer for Canadian than US patients. Recurrent and refractory ischemia was more common in Canada. One-year mortality was comparable between the 2 countries. However, at 6 months, even after baseline differences were accounted for, the (re)MI rate was significantly higher in Canadian than US patients with unstable angina (8.8% versus 5.8%, P =0.039), as was the composite rate of death or (re)MI (13.1% versus 9.1%, P =0.016). Conclusions —One-year mortality was comparable between Canada and the United States in both MI and unstable angina cohorts despite higher intervention rates in the United States. However, outcomes at 6 months among patients with unstable angina differed. Whereas more frequent coronary interventions were not associated with reduced recurrent MI or death among MI patients without ST elevation, they may favorably affect outcomes in patients with unstable angina.
Impact of Health Insurance on Stage at Cancer Diagnosis Among Adolescents and Young Adults
Authors: Theresa H M Keegan, Helen M Parsons, Yi Chen, Frances B Maguire, Cyllene R Morris, Arti Parikh-Patel, Kenneth W Kizer, Ted Wun
Journal: JNCI Journal of the National Cancer Institute (2019)

Abstract Background Uninsured adolescents and young adults (AYAs) and those with publicly funded health insurance are more likely to be diagnosed with cancer at later stages. However, prior population-based studies have not distinguished between AYAs who were continuously uninsured from those who gained Medicaid coverage at the time of cancer diagnosis. Methods AYA patients (ages 15–39 years) with nine common cancers diagnosed from 2005 to 2014 were identified using California Cancer Registry data. This cohort was linked to California Medicaid enrollment files to determine continuous enrollment, discontinuous enrollment, or enrollment at diagnosis, with other types of insurance determined from registry data. Multivariable logistic regression was used to evaluate factors associated with later stages at diagnosis. Results The majority of 52 774 AYA cancer patients had private or military insurance (67.6%), followed by continuous Medicaid (12.4%), Medicaid at diagnosis (8.5%), discontinuous Medicaid (3.9%), other public insurance (1.6%), no insurance (2.9%), or unknown insurance (3.1%). Of the 13 069 with Medicaid insurance, 50.1% were continuously enrolled. Compared to those who were privately insured, AYAs who enrolled in Medicaid at diagnosis were 2.2–2.5 times more likely to be diagnosed with later stage disease, whereas AYAs discontinuously enrolled were 1.7–1.9 times and AYAs continuously enrolled were 1.4–1.5 times more likely to be diagnosed with later stage disease. Males, those residing in lower socioeconomic neighborhoods, and AYAs of Hispanic or black race and ethnicity (vs non-Hispanic white) were more likely to be diagnosed at a later stage, independent of insurance. Conclusions Our findings suggest that access to continuous medical insurance is important for decreasing the likelihood of late stage cancer diagnosis.
Antisense oligonucleotide targeting CD39 improves anti-tumor T cell immunity
Authors: Abhishek S. Kashyap, Tamara Thelemann, Richard Klar, Sandra M. Kallert, Julia Festag, Melanie Buchi, Lisa Hinterwimmer, Monika Schell, Sven Michel, Frank Jaschinski, Alfred Zippelius
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Cancer cells are known to develop mechanisms to circumvent effective anti-tumor immunity. The two ectonucleotidases CD39 and CD73 are promising drug targets, as they act in concert to convert extracellular immune-stimulating ATP to adenosine. CD39 is expressed by different immune cell populations as well as cancer cells of different tumor types and supports the tumor in escaping immune recognition and destruction. Thus, increasing extracellular ATP and simultaneously reducing adenosine concentrations in the tumor can lead to effective anti-tumor immunity. <h3>Methods</h3> We designed locked nucleic acid (LNA)-modified antisense oligonucleotides (ASOs) with specificity for human or mouse CD39 that do not need a transfection reagent or delivery system for efficient target knockdown. Knockdown efficacy of ASOs on mRNA and protein level was investigated in cancer cell lines and in primary human T cells. The effect of CD39 knockdown on ATP-degrading activity was evaluated by measuring levels of ATP in tumor cell supernatants and analysis of T cell proliferation in the presence of extracellular ATP. The in vivo effects of CD39-specific ASOs on target expression, anti-tumor immune responses and on tumor growth were analyzed in syngeneic mouse tumor models using multi-color flow cytometry. <h3>Results</h3> CD39-specific ASOs suppressed expression of CD39 mRNA and protein in different murine and human cancer cell lines and in primary human T cells. Degradation of extracellular ATP was strongly reduced by CD39-specific ASOs. Strikingly, CD39&nbsp;knockdown by ASOs was associated with improved CD8<sup>+</sup> T cell proliferation. Treatment of tumor-bearing mice with CD39-specific ASOs led to dose-dependent reduction of CD39-protein expression in regulatory T cells (Tregs) and tumor-associated macrophages. Moreover, frequency of intratumoral Tregs was substantially reduced in CD39 ASO-treated mice. As a consequence, the ratio of CD8<sup>+</sup> T cells to Tregs in tumors was improved, while PD-1 expression was induced in CD39 ASO-treated intratumoral CD8<sup>+</sup> T cells. Consequently, CD39 ASO treatment demonstrated potent reduction in tumor growth in combination with anti-PD-1 treatment. <h3>Conclusion</h3> Targeting of CD39 by ASOs represents a promising state-of-the art therapeutic approach to improve immune responses against tumors.
Abstract 16820: Impact of Qrs Duration on the Time Course of Change in Left Ventricular Ejection Fraction in Patients With Aortic Stenosis
Authors: Saki Ito, Runqing Huang, Luis S Allen, Vuyisile T Nkomo, Sorin V Pislaru, Pellikka A Patricia, Lewis R Bradley, Jae K Oh
Journal: Circulation (2017)

Background: In a subset of patients with severe aortic stenosis (AS), the left ventricular ejection fraction (LVEF) is reduced. AS has been reported to induce LV dyssynchrony which may be related t...
Discontinuation of anti-PD-1 antibody therapy in the absence of disease progression or treatment limiting toxicity: clinical outcomes in advanced melanoma
Authors: Y.J.L. Jansen, E.A. Rozeman, R. Mason, S.M. Goldinger, M.H. Geukes Foppen, L. Hoejberg, H. Schmidt, J.V. van Thienen, J.B.A.G. Haanen, L. Tiainen, I.M. Svane, S. Mäkelä, T. Seremet, A. Arance, R. Dummer, L. Bastholt, M. Nyakas, O. Straume, A.M. Menzies, G.V. Long, V. Atkinson, C.U. Blank, B. Neyns
Journal: Annals of Oncology (2019)

Programmed cell death protein 1 (PD-1) blocking monoclonal antibodies improve the overall survival of patients with advanced melanoma but the optimal duration of treatment has not been established.
Prediction of Hepatic Complications after Allogeneic Haemotopoetic Stem Cell Transplantation Using Liver and Spleen Stiffness Measurement
Authors: Georg-Nikolaus Franke, Tina Weiße, David Petroff, Sebastian Beer, Christine Döhring, Gerhard Behre, Janett Fischer, Franziska Lindner, Johannes Wiegand, Volker Keim, Dietger Niederwieser, Thomas Karlas
Journal: Blood (2018)
Adverse Maternal, Fetal, and Postnatal Effects of Hexafluoropropylene Oxide Dimer Acid (GenX) from Oral Gestational Exposure in Sprague-Dawley Rats
Authors: Justin M. Conley, Christy S. Lambright, Nicola Evans, Mark J. Strynar, James McCord, Barry S. McIntyre, Gregory S. Travlos, Mary C. Cardon, Elizabeth Medlock-Kakaley, Phillip C. Hartig, Vickie S. Wilson, L. Earl Gray
Journal: Environmental Health Perspectives (2019)

Hexafluoropropylene oxide dimer acid [(HFPO-DA), GenX] is a member of the per- and polyfluoroalkyl substances (PFAS) chemical class, and elevated levels of HFPO-DA have been detected in surface water, air, and treated drinking water in the United States and Europe.We aimed to characterize the potential maternal and postnatal toxicities of oral HFPO-DA in rats during sexual differentiation. Given that some PFAS activate peroxisome proliferator-activated receptors (PPARs), we sought to assess whether HFPO-DA affects androgen-dependent development or interferes with estrogen, androgen, or glucocorticoid receptor activity.Steroid receptor activity was assessed with a suite of in vitro transactivation assays, and Sprague-Dawley rats were used to assess maternal, fetal, and postnatal effects of HFPO-DA exposure. Dams were dosed daily via oral gavage during male reproductive development (gestation days 14-18). We evaluated fetal testes, maternal and fetal livers, maternal serum clinical chemistry, and reproductive development of F1 animals.HFPO-DA exposure resulted in negligible in vitro receptor activity and did not impact testosterone production or expression of genes key to male reproductive development in the fetal testis; however, in vivo exposure during gestation resulted in higher maternal liver weights ([Formula: see text]), lower maternal serum thyroid hormone and lipid profiles ([Formula: see text]), and up-regulated gene expression related to PPAR signaling pathways in maternal and fetal livers ([Formula: see text]). Further, the pilot postnatal study indicated lower female body weight and lower weights of male reproductive tissues in F1 animals.HFPO-DA exposure produced multiple effects that were similar to prior toxicity evaluations on PFAS, such as perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), but seen as the result of higher oral doses. The mean dam serum concentration from the lowest dose group was 4-fold greater than the maximum serum concentration detected in a worker in an HFPO-DA manufacturing facility. Research is needed to examine the mechanisms and downstream events linked to the adverse effects of PFAS as are mixture-based studies evaluating multiple PFAS. https://doi.org/10.1289/EHP4372.
ERCC6L2 defines a novel entity within inherited acute myeloid leukemia
Authors: Suvi P. M. Douglas, Pihla Siipola, Panu E. Kovanen, Marja Pyörälä, Sakari Kakko, Eeva-Riitta Savolainen, Urpu Salmenniemi, Katri Orte, Soili Kytölä, Esa Pitkänen, Kimmo Porkka, Outi Kilpivaara, Ulla Wartiovaara-Kautto
Journal: Blood (2019)