tbuckley/cabot-search huggingface dataset:
Evaluation of Frequency of Encounters With Primary Care Physicians vs Visits to Community Pharmacies Among Medicare Beneficiaries
Authors: Lucas A. Berenbrok, Nico Gabriel, Kim C. Coley, Inmaculada Hernandez
Journal: JAMA Network Open (2020)

The shift toward value-based care has placed emphasis on preventive care and chronic disease management services delivered by multidisciplinary health care teams. Community pharmacists are particularly well positioned to deliver these services due to their accessibility.To compare the number of patient visits to community pharmacies and the number of encounters with primary care physicians among Medicare beneficiaries who actively access health care services.This cross-sectional study analyzed a 5% random sample of 2016 Medicare beneficiaries from January 1, 2016, to December 31, 2016 (N = 2 794 078). Data were analyzed from October 23, 2019, to December 20, 2019. Medicare Part D beneficiaries who were continuously enrolled and had at least 1 pharmacy claim and 1 encounter with a primary care physician were included in the final analysis (n = 681 456). Those excluded from the study were patients who were not continuously enrolled in Part D until death, those with Part B skilled nursing claims, and those with Part D mail-order pharmacy claims.We conducted analyses for the overall sample and for subgroups defined by demographics, region of residence, and clinical characteristics.Outcomes included the number of visits to community pharmacies and encounters with primary care physicians. Unique visits to the community pharmacy were defined using a 13-day window between individual prescription drug claims. Kruskal-Wallis tests were used to compare the medians for the 2 outcomes.A total of 681 456 patients (mean [SD] age, 72.0 [12.5] years; 418 685 [61.4%] women and 262 771 [38.6%] men) were included in the analysis; 82.2% were white, 9.6% were black, 2.4% were Hispanic, and 5.7% were other races/ethnicities. Visits to the community pharmacy outnumbered encounters with primary care physicians (median [interquartile range (IQR)], 13 [9-17] vs 7 [4-14]; P < .001). The number of pharmacy visits was significantly larger than the number of primary care physician encounters for all subgroups evaluated except for those with acute myocardial infarction (median [IQR], 15 [12-19] vs 14 [7-26]; P = .60 using a 13-day window). The difference in the number of pharmacy and primary care physician encounters was larger in rural areas (median [IQR], 14 [10-17] vs 5 [2-11]; P < .001) than in metropolitan areas (median [IQR], 13 [8-17] vs 8 [4-14]; P < .001). In all 50 states and in all but 9 counties, the number of community pharmacy visits was larger than the number of encounters with primary care physicians.This cross-sectional study suggests that community pharmacists are accessible health care professionals with frequent opportunities to interact with community-dwelling patients. Primary care physicians should work collaboratively with community pharmacists, who can assist in the delivery of preventive care and chronic disease management.
Systemic rituximab for the treatment of the indolent forms of primary cutaneous B-cell lymphomas: Data from the Spanish Primary Cutaneous Lymphoma Registry
Authors: Cristina Muniesa, Eva Domingo-Domenech, Rosa Fornons-Servent, Yeray Peñate, M. Teresa Estrach, M. Dolores Ramón, Susana Medina, Ángeles Flórez, Pablo L. Ortiz-Romero, M. Prado Sánchez-Caminero, Ignacio Torres-Navarro, Elvira Acebo, Ignacio Yanguas, Ricardo Fernández-de-Misa, Mar Blanes, Ana Zayas, Miguel A. Descalzo, Ignacio Garcia-Doval, Octavio Servitje
Journal: Journal of the American Academy of Dermatology (2020)
Clinical Risk Factors Associated with Recurrent Venous Thromboembolism and Major Bleeding in Gastrointestinal Cancer Patients Receiving Doacs for Secondary Thromboprophylaxis
Authors: Alejandro Recio Boiles, Jessica Vondrak, Kristopher J. Abbate, Hani M. Babiker, Aaron J. Scott, Ali McBride, Emad Elquza
Journal: Blood (2017)
Deciphering cellular transcriptional alterations in Alzheimer’s disease brains
Authors: Xue Wang, Mariet Allen, Shaoyu Li, Zachary S. Quicksall, Tulsi A. Patel, Troy P. Carnwath, Joseph S. Reddy, Minerva M. Carrasquillo, Sarah J. Lincoln, Thuy T. Nguyen, Kimberly G. Malphrus, Dennis W. Dickson, Julia E. Crook, Yan W. Asmann, Nilüfer Ertekin-Taner
Journal: Molecular Neurodegeneration (2020)

Large-scale brain bulk-RNAseq studies identified molecular pathways implicated in Alzheimer's disease (AD), however these findings can be confounded by cellular composition changes in bulk-tissue. To identify cell intrinsic gene expression alterations of individual cell types, we designed a bioinformatics pipeline and analyzed three AD and control bulk-RNAseq datasets of temporal and dorsolateral prefrontal cortex from 685 brain samples. We detected cell-proportion changes in AD brains that are robustly replicable across the three independently assessed cohorts. We applied three different algorithms including our in-house algorithm to identify cell intrinsic differentially expressed genes in individual cell types (CI-DEGs). We assessed the performance of all algorithms by comparison to single nucleus RNAseq data. We identified consensus CI-DEGs that are common to multiple brain regions. Despite significant overlap between consensus CI-DEGs and bulk-DEGs, many CI-DEGs were absent from bulk-DEGs. Consensus CI-DEGs and their enriched GO terms include genes and pathways previously implicated in AD or neurodegeneration, as well as novel ones. We demonstrated that the detection of CI-DEGs through computational deconvolution methods is promising and highlight remaining challenges. These findings provide novel insights into cell-intrinsic transcriptional changes of individual cell types in AD and may refine discovery and modeling of molecular targets that drive this complex disease.
Evidence for Strong Mutation Bias toward, and Selection against, U Content in SARS-CoV-2: Implications for Vaccine Design
Authors: Alan M Rice, Atahualpa Castillo Morales, Alexander T Ho, Christine Mordstein, Stefanie Mühlhausen, Samir Watson, Laura Cano, Bethan Young, Grzegorz Kudla, Laurence D Hurst
Journal: Molecular Biology and Evolution (2020)

Abstract Large-scale re-engineering of synonymous sites is a promising strategy to generate vaccines either through synthesis of attenuated viruses or via codon-optimized genes in DNA vaccines. Attenuation typically relies on deoptimization of codon pairs and maximization of CpG dinucleotide frequencies. So as to formulate evolutionarily informed attenuation strategies that aim to force nucleotide usage against the direction favored by selection, here, we examine available whole-genome sequences of SARS-CoV-2 to infer patterns of mutation and selection on synonymous sites. Analysis of mutational profiles indicates a strong mutation bias toward U. In turn, analysis of observed synonymous site composition implicates selection against U. Accounting for dinucleotide effects reinforces this conclusion, observed UU content being a quarter of that expected under neutrality. Possible mechanisms of selection against U mutations include selection for higher expression, for high mRNA stability or lower immunogenicity of viral genes. Consistent with gene-specific selection against CpG dinucleotides, we observe systematic differences of CpG content between SARS-CoV-2 genes. We propose an evolutionarily informed approach to attenuation that, unusually, seeks to increase usage of the already most common synonymous codons. Comparable analysis of H1N1 and Ebola finds that GC3 deviated from neutral equilibrium is not a universal feature, cautioning against generalization of results.
Acid-sensitive PEGylated paclitaxel prodrug nanoparticles for cancer therapy: Effect of PEG length on antitumor efficacy
Authors: Jingqing Mu, Haiping Zhong, Hui Zou, Tao Liu, Na Yu, Xi Zhang, Zunkai Xu, Ziqi Chen, Shutao Guo
Journal: Journal of Controlled Release (2020)
Distinctions with a Difference: RNA Subtyping and Clinical Outcome in Pancreatic Cancer
Authors: Eric A. Collisson
Journal: Clinical Cancer Research (2020)

Abstract Pancreatic cancer patients are in desperate need of effective therapy virtually from the moment of their diagnosis. As we acquire more therapies, how best to deploy them, in what order and to which patients is emerging as an important clinical question. Pancreatic cancer subtypes, identifiable with common lab diagnostics in diagnostic biopsy samples, may be helpful in guiding therapy selection. See related article by O'Kane et al., p. 4901
The role of visceral adiposity in the severity of COVID-19: Highlights from a unicenter cross-sectional pilot study in Germany
Authors: Antonia Petersen, Keno Bressem, Jakob Albrecht, Hans-Martin Thieß, Janis Vahldiek, Bernd Hamm, Marcus R. Makowski, Alexandra Niehues, Stefan M. Niehues, Lisa C. Adams
Journal: Metabolism (2020)
Initiating Pharmacologic Treatment in Tobacco-Dependent Adults. An Official American Thoracic Society Clinical Practice Guideline
Authors: Frank T. Leone, Yuqing Zhang, Sarah Evers-Casey, A. Eden Evins, Michelle N. Eakin, Joelle Fathi, Kathleen Fennig, Patricia Folan, Panagis Galiatsatos, Hyma Gogineni, Stephen Kantrow, Hasmeena Kathuria, Thomas Lamphere, Enid Neptune, Manuel C. Pacheco, Smita Pakhale, David Prezant, David P. L. Sachs, Benjamin Toll, Dona Upson, Dan Xiao, Luciane Cruz-Lopes, Izabela Fulone, Rachael L. Murray, Kelly K. O’Brien, Sureka Pavalagantharajah, Stephanie Ross, Yuan Zhang, Meng Zhu, Harold J. Farber
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Section:ChooseTop of pageAbstract <<ContentsSummary of Recommendation...IntroductionMethodsQuestions and Recommendat...DiscussionPatient PerspectiveReferencesCITING ARTICLES
Increased Naive, Stem Cell Memory and Terminally Differentiated CD8+ T Cells in Chronic Graft Versus Host Disease
Authors: Maria V Soares, Rita I Azevedo, Inês A Ferreira, Bucar Ventura Sara, Dario Ligeiro, Ana C Ribeiro, Paulo N.G. Pereira, Ana C Alho, Eduardo L Espada, Clara Juncal, Nádia Camacho, Carlos M Martins, José A Carmo, Fernanda Lourenço, Raul Moreno, Carlos Vaz, António Campos, Fernando Campilho, Rosa Ferreira, Jerome Ritz, Joao F Lacerda
Journal: Blood (2017)
Abstract 14570: Sex-Specific Differences in Symptomatic Peripheral Artery Disease: Insights From the EUCLID Trial
Authors: Axel Haine, Sarah Kavanagh, Jeffrey S Berger, Francis G Fowkes, Connie N Hess, Lars Norgren, Brian G Katona, Kenneth Q Mahaffey, Juuso I Blomster, Mannesh R Patel, Schuyler Jones, Frank W Rockhold, William R Hiatt, Iris Baumgartner
Journal: Circulation (2019)

Introduction: While subjects with established peripheral artery disease (PAD) are at increased risk for major adverse cardiovascular events (MACE), sex-specific differences have not been well defin...
Abstract 11173: Effect of Alirocumab on Peripheral Artery and Venous Thromboembolic Events, and Relation to Lipoprotein(a) Concentration
Authors: Gregory G Schwartz, Philippe G Steg, Michael Szarek, Vera A Bittner, Rafael Diaz, Shaun G Goodman, Corinne Hanotin, Robert A Harrington, J Wouter Jukema, Alexia Letierce, Robert Pordy, Matthew T Roe, Harvey D White, Andreas M Zeiher, Deepak L Bhatt
Journal: Circulation (2019)

Background: Patients with acute coronary syndrome (ACS) are also at risk for peripheral artery disease and venous thromboembolic events (PAD + VTE). Lipoprotein [Lp](a) has atherogenic and prothrom...
CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38α/MYC/PD-L1 signaling in non-small cell lung cancer
Authors: Jian Wang, Ruiguang Zhang, Zhenyu Lin, Sheng Zhang, Yaobing Chen, Jing Tang, Jiaxin Hong, Xiaoshu Zhou, Yan Zong, Yingzhuo Xu, Rui Meng, Shuangbing Xu, Li Liu, Tao Zhang, Kunyu Yang, Xiaorong Dong, Gang Wu
Journal: Journal of Hematology & Oncology (2020)

Abstract Background The cyclin-dependent kinase 7 (CDK7) subunit of TFIIH regulates RNA polymerase-II-based transcription and promotes tumor progression. However, the mechanisms involved in CDK7-mediated immune evasion are unclear in non-small cell lung cancer (NSCLC). Methods RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance. Flow cytometry was performed to detect the status of the immune microenvironment after CDK7 inhibition and antiPD-1 therapy in vivo. CD8 depletion antibodies were used to assess the role of CD8 + T cells in combined CDK7 and PD-1 blockade. The associations among CDK7, p38α, MYC, PD-L1, infiltrating T cells, and survival outcomes were validated in two tissue microarrays and public transcriptomic data of NSCLC. Results High CDK7 mRNA and protein levels were identified to be associated with poor prognosis in NSCLC. CDK7 silencing and CDK7 inhibitor THZ1 elicited apoptosis and suppressed tumor growth. Moreover, CDK7 ablation specifically suppressed p38α/MYC-associated genes, and THZ1 inhibited MYC transcriptional activity through downregulating p38α. CDK7 inhibition sensitized NSCLC to p38α inhibitor. Further, THZ1 suppressed PD-L1 expression by inhibiting MYC activity. THZ1 boosted antitumor immunity by recruiting infiltrating CD8 + T cells and synergized with antiPD-1 therapy. The CDK7/MYC/PD-L1 signature and infiltrating T cell status collectively stratified NSCLC patients into different risk groups. Conclusion These data suggest that the combined CDK7 inhibitor THZ1 and antiPD-1 therapy can be an effective treatment in NSCLC.
冠動脈三枝病変および左主幹冠動脈疾患患者における冠動脈バイパス移植術と経皮的冠動脈形成術の比較:無作為,臨床SYNTAX試験の5年の追跡調査 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: W Mohr Friedrich, Morice Marie-Claude, Kappetein A. Pieter, W Serruys Patrick, E Feldman Ted, Stahle Elisabeth, Colombo Antonio, J Mack Michael, Holmes David R., Morel Marie-Angele, Van Dyck Nic, M Houle Vicki, D Dawkins Keith
Journal: The Lancet (2013)
Robotic versus laparoscopic ventral hernia repair: multicenter, blinded randomized controlled trial
Authors: Oscar A Olavarria, Karla Bernardi, Shinil K Shah, Todd D Wilson, Shuyan Wei, Claudia Pedroza, Elenir B Avritscher, Michele M Loor, Tien C Ko, Lillian S Kao, Mike K Liang
Journal: BMJ (2020)

Abstract Objective To determine whether robotic ventral hernia repair is associated with fewer days in the hospital 90 days after surgery compared with laparoscopic repair. Design Pragmatic, blinded randomized controlled trial. Setting Multidisciplinary hernia clinics in Houston, USA. Participants 124 patients, deemed appropriate candidates for elective minimally invasive ventral hernia repair, consecutively presenting from April 2018 to February 2019. Interventions Robotic ventral hernia repair (n=65) versus laparoscopic ventral hernia repair (n=59). Main outcome measures The primary outcome was number of days in hospital within 90 days after surgery. Secondary outcomes included emergency department visits, operating room time, wound complications, hernia recurrence, reoperation, abdominal wall quality of life, and costs from the healthcare system perspective. Outcomes were pre-specified before data collection began and analyzed as intention to treat. Results Patients from both groups were similar at baseline. Ninety day follow-up was completed in 123 (99%) patients. No evidence was seen of a difference in days in hospital between the two groups (median 0 v 0 days; relative rate 0.90, 95% confidence interval 0.37 to 2.19; P=0.82). For secondary outcomes, no differences were noted in emergency department visits, wound complications, hernia recurrence, or reoperation. However, robotic repair had longer operative duration (141 v 77 min; mean difference 62.89, 45.75 to 80.01; P≤0.001) and increased healthcare costs ($15 865 (£12 746; €14 125) v $12 955; cost ratio 1.21, 1.07 to 1.38; adjusted absolute cost difference $2767, $910 to $4626; P=0.004). Among patients with robotic ventral hernia repair, two had an enterotomy compared none with laparoscopic repair. The median one month postoperative improvement in abdominal wall quality of life was 3 with robotic ventral hernia repair compared with 15 following laparoscopic repair. Conclusion This study found no evidence of a difference in 90 day postoperative hospital days between robotic and laparoscopic ventral hernia repair. However, robotic repair increased operative duration and healthcare costs. Trial registration Clinicaltrials.gov NCT03490266 .
Outcomes of COVID-19 in patients with CLL: a multicenter international experience
Authors: Anthony R. Mato, Lindsey E. Roeker, Nicole Lamanna, John N. Allan, Lori Leslie, John M. Pagel, Krish Patel, Anders Osterborg, Daniel Wojenski, Manali Kamdar, Scott F. Huntington, Matthew S. Davids, Jennifer R. Brown, Darko Antic, Ryan Jacobs, Inhye E. Ahn, Jeffrey Pu, Krista M. Isaac, Paul M. Barr, Chaitra S. Ujjani, Mark B. Geyer, Ellin Berman, Andrew D. Zelenetz, Nikita Malakhov, Richard R. Furman, Michael Koropsak, Neil Bailey, Lotta Hanson, Guilherme F. Perini, Shuo Ma, Christine E. Ryan, Adrian Wiestner, Craig A. Portell, Mazyar Shadman, Elise A. Chong, Danielle M. Brander, Suchitra Sundaram, Amanda N. Seddon, Erlene Seymour, Meera Patel, Nicolas Martinez-Calle, Talha Munir, Renata Walewska, Angus Broom, Harriet Walter, Dima El-Sharkawi, Helen Parry, Matthew R. Wilson, Piers E. M. Patten, José-Ángel Hernández-Rivas, Fatima Miras, Noemi Fernández Escalada, Paola Ghione, Chadi Nabhan, Sonia Lebowitz, Erica Bhavsar, Javier López-Jiménez, Daniel Naya, Jose Antonio Garcia-Marco, Sigrid S. Skånland, Raul Cordoba, Toby A. Eyre
Journal: Blood (2020)
Observational studies and “the eye of the beholder”
Authors: Miriam J. Johnson, Magnus Ekström, David C. Currow
Journal: European Respiratory Journal (2020)

Nwaru et al. [1] report a dose-related association between short-acting β2-agonists (SABA) and poorer clinical outcomes (exacerbations, emergency department visits, hospital admissions and mortality) in asthma. Acknowledging that observational studies cannot establish causality, they conclude: "Regardless of whether there is a causal effect of SABA use and these adverse effects, or if they are mainly a marker for more severe asthma and/or a reflection of the frailty of the patients, increased use of SABA should alert clinicians to monitor these patients more closely." These are important conclusions that should inform clinical care and be incorporated into international guidelines. Observational studies need explanations in both directions of association to avoid interpretation bias <https://bit.ly/3d7kLnG>
Electroactive barium titanate coated titanium scaffold improves osteogenesis and osseointegration with low-intensity pulsed ultrasound for large segmental bone defects
Authors: Bo Fan, Zheng Guo, Xiaokang Li, Songkai Li, Peng Gao, Xin Xiao, Jie Wu, Chao Shen, Yilai Jiao, Wentao Hou
Journal: Bioactive Materials (2020)

For large segmental bone defects, porous titanium scaffolds have some advantages, however, they lack electrical activity which hinders their further use. In this study, a barium titanate (BaTiO3) piezoelectric ceramic was used to modify the surface of a porous Ti6Al4V scaffold (pTi), which was characterized by scanning electron microscopy, energy dispersive spectroscopy, X-ray photoelectron spectroscopy, and roughness and water contact angle analyses. Low intensity pulsed ultrasound (LIPUS) was applied in vitro and in vivo study. The activity of bone marrow mesenchymal stem cells, including adhesion, proliferation, and gene expression, was significantly superior in the BaTiO3/pTi, pTi + LIPUS, and BaTiO3/pTi + LIPUS groups than in the pTi group. The activity was also higher in the BaTiO3/pTi + LIPUS group than in the BaTiO3/pTi and pTi + LIPUS groups. Additionally, micro-computed tomography, the mineral apposition rate, histomorphology, and the peak pull-out load showed that these scaffold conditions significantly enhanced osteogenesis and osseointegration 6 and 12 weeks after implantation in large segmental bone defects in the radius of rabbits compared with those resulting from the pTi condition. Consequently, the improved osteogenesis and osseointegration make the BaTiO3/pTi + LIPUS a promising method to promote bone regeneration in large segmental bone defects for clinical application.
COVID-19 conundrum: clinical phenotyping based on pathophysiology as a promising approach to guide therapy in a novel illness
Authors: Robin Cherian, Bharatendu Chandra, Moon Ley Tung, Alain Vuylsteke
Journal: European Respiratory Journal (2020)

We read with interest the recent editorial by Bos et al. [1] on the perils of premature phenotyping in coronavirus disease 2019 (COVID-19). The authors concluded that a normal compliance variant of acute respiratory distress syndrome (ARDS) does not exist, based on two small cohort studies reporting low respiratory system compliance in COVID-19 patients [2, 3]. However, this assumption may be erroneous, as, first, the admission and intubation thresholds are highly variable across units, resulting in marked heterogeneity. Secondly, several studies demonstrate that a high proportion of mechanically ventilated COVID-19 patients exhibit near-normal lung compliance [4–6]. The current evidence of COVID-19 pathophysiology supports the idea of specific phenotypes, and clinical phenotyping may be valuable to guide therapy <https://bit.ly/2ZagmMn>
A Gene-Expression Predictor for Efficacy of Induction Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma
Authors: Yuan Lei, Ying-Qin Li, Wei Jiang, Xiao-Hong Hong, Wen-Xiu Ge, Yuan Zhang, Wei-Han Hu, Ya-Qin Wang, Ye-Lin Liang, Jun-Yan Li, William C S Cho, Jing-Ping Yun, Jing Zeng, Jie-Wei Chen, Li-Zhi Liu, Li Li, Lei Chen, Fang-Yun Xie, Wen-Fei Li, Yan-Ping Mao, Xu Liu, Yu-Pei Chen, Ling-Long Tang, Ying Sun, Na Liu, Jun Ma
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC. Methods We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided. Results We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed. Conclusions The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.