tbuckley/cabot-search huggingface dataset:
Is cancer pain associated with employment and cost concerns for individuals with cancer?
Authors: Michael T. Halpern, Janet S. de Moor, K Robin Yabroff
Journal: Journal of Clinical Oncology (2019)

94 Background: Pain is frequently reported by individuals with cancer. While the adverse effects of pain on quality of life are well-established, it is unknown if pain is associated with patients’ concerns about employment and cancer costs. Methods: We used data from the Medical Expenditure Panel Survey (MEPS) 2016 Experiences with Cancer Supplement including cancer diagnosis, pain level over the past 7 days, employment changes, and cost concerns. Respondents diagnosed with cancer at age &gt; 18 (excluding non-melanoma skin cancer) with non-missing pain information were included. Sampling weights were used in analysis to provide nationally representative estimates. Results: Among 875 eligible respondents with cancer (weighted total of 1.3 million individuals), pain was reported by 57% (severe pain by 12%). The likelihood of pain was significantly associated with age, gender, race/ethnicity, education, cancer site, insurance, and time since treatment. Controlling for these factors, individuals reporting pain were significantly more likely to take time off from work (odds ratio [OR] 1.76); change to a less demanding or part time job (OR 1.91); not pursue promotions (OR 1.39); retire early (OR 3.06); and feel less productive (OR 2.35). Individuals with pain were significantly more likely to have uncovered medical expenses (OR 1.28); be in debt (OR 2.68); and be unable to cover medical bills (OR 1.46). These individuals were significantly more likely to worry about paying medical bills (OR 1.94); to delay medical treatment (OR 4.30), follow-up care (OR 2.20), and mental health care (OR 4.11); and were less likely to receive necessary medical care (OR 0.50). Despite these, concerns, they were significantly less likely to discuss out-of-pocket costs for cancer care (OR 0.86) or cancer treatments (OR 0.96) with a healthcare provider. Conclusions: Cancer pain is associated with increased cost and employment concerns but with a lower likelihood of discussing costs with healthcare provider. Interventions are needed to address financial hardship among this high-risk population.
Helen Salisbury: Why I resist giving up home visits
Authors: Helen Salisbury
Journal: BMJ (2019)

GPs no longer have time to visit patients in their own homes, so the requirement to do so should be removed from their contract. This was the outcome of a motion debated on 22 November by the Local Medical Committee conference (England): 54% voted for the motion to remove home visits from core contract work.1

It’s true that we’re too busy. Many partners work 12 hour days routinely, with an unmanageable workload. Travel time makes home visits inefficient, as it may take 40 minutes to do a visit that would have been a 10 minute consultation in the surgery. However, …
MECHANISMS OF ACTION OF BISPHOSPHONATES
Authors: Gideon A. Rodan
Journal: The Annual Review of Pharmacology and Toxicology (1998)

▪ Abstract Bisphosphonates (BPs) are pyrophosphate analogs in which the oxygen bridge has been replaced by carbon and diverse carbon side chains have generated a large family of compounds. Several are potent inhibitors of bone destruction (resorption) and are in clinical use for the treatment and prevention of osteoporosis, Paget's disease, hypercalcemia caused by malignancy, tumor metastases in bone, and other bone ailments. Selective action on bone is based on the binding of the BP moiety to the bone mineral. The molecular mode of action of BPs, which may differ from compound to compound, is unknown. However, at the tissue level, all BPs inhibit bone destruction and lead to an increase in bone mineral density by decreasing bone resorption and bone turnover. At the cellular level, the ultimate target of BP action is the osteoclast, the bone resorbing cell. In vitro evidence shows BP inhibition of osteoclast formation, via action on osteoblasts, and there is in vitro and in vivo evidence for BP inhibition of osteoclast activity. There is in vivo and in vitro evidence for increased apoptosis. The relative contribution of these various effects on the therapeutic action of BPs remains to be established. At the molecular level, it is not known if BPs act on a single or multiple targets. Enzymes in the cholesterol biosynthesis pathway and protein tyrosine phosphatases were shown to be inhibited by BPs.
Superior Intellectual Outcomes After Proton Radiotherapy Compared With Photon Radiotherapy for Pediatric Medulloblastoma
Authors: Lisa S. Kahalley, Rachel Peterson, M. Douglas Ris, Laura Janzen, M. Fatih Okcu, David R. Grosshans, Vijay Ramaswamy, Arnold C. Paulino, David Hodgson, Anita Mahajan, Derek S. Tsang, Normand Laperriere, William E. Whitehead, Robert C. Dauser, Michael D. Taylor, Heather M. Conklin, Murali Chintagumpala, Eric Bouffet, Donald Mabbott
Journal: Journal of Clinical Oncology (2019)

Proton radiotherapy (PRT) may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy (XRT). We examined the change in intellectual scores over time in patients with pediatric medulloblastoma treated with craniospinal PRT versus XRT.Intelligence test scores were obtained for a sample of pediatric patients treated between 2007 and 2018 on the same medulloblastoma protocols that differed only in radiotherapy modality (PRT v XRT). Growth curve analyses compared change in scores over time since diagnosis between groups.Longitudinal intelligence data from 79 patients (37 PRT, 42 XRT) were examined. Groups were similar on most demographic/clinical variables, including sex (67.1% male), age at diagnosis (mean, 8.6 years), craniospinal irradiation dose (median, 23.4 Gy), length of follow-up (mean, 4.3 years), and parental education (mean, 14.3 years). Boost dose (P < .001) and boost margin (P = .001) differed between groups. Adjusting for covariates, the PRT group exhibited superior long-term outcomes in global intelligence quotient (IQ), perceptual reasoning, and working memory compared with the XRT group (all P < .05). The XRT group exhibited a significant decline in global IQ, working memory, and processing speed (all P < .05). The PRT group exhibited stable scores over time in all domains with the exception of processing speed (P = .003).To our knowledge, this is the first study to compare intellectual trajectories between pediatric patients treated for medulloblastoma with PRT versus those treated with XRT on comparable, contemporary protocols. PRT was associated with more favorable intellectual outcomes in most domains compared with XRT, although processing speed emerged as a vulnerable domain for both groups. This study provides the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.
Central Sfrp5 regulates hepatic glucose flux and VLDL-triglyceride secretion
Authors: Yang Li, Mingyuan Tian, Mengliu Yang, Gangyi Yang, Jianrong Chen, Han Wang, Dongfang Liu, Hongyan Wang, Wuquan Deng, Zhiming Zhu, Hongting Zheng, Ling Li
Journal: Metabolism (2019)

Secreted frizzled-related protein 5 (Sfrp5) has been shown to be associated with energy homeostasis and insulin resistance in mouse models of obesity and diabetes. However, its central role in glucose and lipid metabolism is unknown.HFD-fed rats received ICV infusions of vehicle or Sfrp5 during a pancreatic euglycemic clamp procedure. To delineate the pathway(s) by which ICV Sfrp5 modulates HGP and VLDL-TG secretion, we inhibited the hypothalamic KATP channel using glibenclamide, the DVC NMDA receptor with MK801, and selectively transected the hepatic branch of the vagal nerve while centrally infusing Sfrp5.ICV Sfrp5 in HFD-fed rats significantly increased the glucose infusion required to maintain euglycemia due to HGP inhibition during the clamp procedure; moreover, hepatic PEPCK and G6Pase expression was decreased, and InsR and Akt phosphorylation was increased in the liver. ICV Sfrp5 also decreased circulating triglyceride levels via inhibiting hepatic VLDL-TG secretion. These changes were accompanied by the inhibition of enzymes related to lipogenesis in the liver. ICV Sfrp5 significantly increased insulin-stimulated phosphorylation of InsR and Akt in the hypothalamus of HFD-fed rats, and insulin-stimulated immunodetectable PIP3 levels were higher in Sfrp5 group than in control group both in vitro and vivo. The glucose- and lipid-lowering effects of ICV Sfrp5 were eliminated by NMDA receptor or DVC KATP channel inhibition or HVAG.The present study demonstrates that central Sfrp5 signaling activates a previously unappreciated InsR-Akt-PI3k-KATP channel pathway in the hypothalamus and brain-hepatic vagus neurocircuitry to decrease HGP and VLDL-TG secretion.
Reorienting health systems to care for people with HIV beyond viral suppression
Authors: Kelly Safreed-Harmon, Jane Anderson, Natasha Azzopardi-Muscat, Georg M N Behrens, Antonella d'Arminio Monforte, Udi Davidovich, Julia del Amo, Meaghan Kall, Teymur Noori, Kholoud Porter, Jeffrey V Lazarus
Journal: The Lancet HIV (2019)
The von Willebrand Factor Facilitates Model for End‐Stage Liver Disease–Independent Risk Stratification on the Waiting List for Liver Transplantation
Authors: Georg P. Györi, David Pereyra, Benedikt Rumpf, Hubert Hackl, Christoph Köditz, Gregor Ortmayr, Thomas Reiberger, Michael Trauner, Gabriela A. Berlakovich, Patrick Starlinger
Journal: Hepatology (2019)

Background and Aims The Model for End‐Stage Liver Disease (MELD) is used for clinical decision‐making and organ allocation for orthotopic liver transplantation (OLT) and was previously upgraded through inclusion of serum sodium (Na) concentrations (MELD‐Na). However, MELD‐Na may underestimate complications arising from portal hypertension or infection. The von Willebrand factor (vWF) antigen (vWF‐Ag) correlates with portal pressure and seems capable of predicting complications in patients with cirrhosis. Accordingly, this study aimed to evaluate vWF‐Ag as an adjunct surrogate marker for risk stratification on the waiting list for OLT. Approach and Results Hence, WF‐Ag at time of listing was assessed in patients listed for OLT. Clinical characteristics, MELD‐Na, and mortality on the waiting list were recorded. Prediction of 3‐month waiting‐list survival was assessed by receiver operating characteristics and net reclassification improvement. Interestingly, patients dying within 3 months on the waiting list displayed elevated levels of vWF‐Ag ( P &lt; 0.001). MELD‐Na and vWF‐Ag were comparable and independent in their predictive potential for 3‐month mortality on the waiting list (area under the curve [AUC], vWF‐Ag = 0.739; MELD‐Na = 0.764). Importantly, a vWF‐Ag cutoff at 413% identified patients at risk for death within 3 months of listing with a higher odds ratio (OR) than the previously published cutoff at a MELD‐Na of 20 points (vWF‐Ag, OR = 10.873, 95% confidence interval [CI], 3.160, 36.084; MELD‐Na, OR = 7.594, 95% CI, 2.578, 22.372; P &lt; 0.001, respectively). Ultimately, inclusion of vWF‐Ag into the MELD‐Na equation significantly improved prediction of 3‐month waiting‐list mortality (AUC, MELD‐Na–vWF = 0.804). Conclusions A single measurement of vWF‐Ag at listing for OLT predicts early mortality. Combining vWF‐Ag levels with MELD‐Na improves risk stratification and may help to prioritize organ allocation to decrease waiting‐list mortality.
The importance of being not significant: Blood eosinophils and clinical responses do not correlate in severe asthma patients treated with mepolizumab in real life
Authors: Diego Bagnasco, Alessandro Massolo, Marco Bonavia, Luisa Brussino, Caterina Bucca, Marco Caminati, Giorgio Walter Canonica, Cristiano Caruso, Maria D’Amato, Laura De Ferrari, Giuseppe Guida, Enrico Heffler, Carlo Lombardi, Francesco Menzella, Manlio Milanese, Giovanni Paoletti, Anna Maria Riccio, Giovanni Rolla, Gianenrico Senna, Elisa Testino, Giovanni Passalacqua
Journal: Allergy (2019)

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Real-World Outcome for Newly Diagnosed Patients with Functional High-Risk Myeloma - a Myeloma and Related Diseases Registry Analysis
Authors: Andrew Spencer, Peter Mollee, Hilary Anne Blacklock, Simon Harrison, Hang Quach, P. Joy Ho, Ruth Spearing, Jay Hocking, Bradley Augustson, H. Miles Prince, Elizabeth M. Moore, Zoe McQuilten, Erica M. Wood, Cameron Wellard
Journal: Blood (2019)
A Single Ketamine Infusion Combined With Motivational Enhancement Therapy for Alcohol Use Disorder: A Randomized Midazolam-Controlled Pilot Trial
Authors: Elias Dakwar, Frances Levin, Carl L. Hart, Cale Basaraba, Jean Choi, Martina Pavlicova, Edward V. Nunes
Journal: American Journal of Psychiatry (2019)

Pharmacotherapy and behavioral treatments for alcohol use disorder are limited in their effectiveness, and new treatments with innovative mechanisms would be valuable. In this pilot study, the authors tested whether a single subanesthetic infusion of ketamine administered to adults with alcohol dependence and engaged in motivational enhancement therapy affects drinking outcomes.Participants were randomly assigned to a 52-minute intravenous administration of ketamine (0.71 mg/kg, N=17) or the active control midazolam (0.025 mg/kg, N=23), provided during the second week of a 5-week outpatient regimen of motivational enhancement therapy. Alcohol use following the infusion was assessed with timeline followback method, with abstinence confirmed by urine ethyl glucuronide testing. A longitudinal logistic mixed-effects model was used to model daily abstinence from alcohol over the 21 days after ketamine infusion.Participants (N=40) were mostly middle-aged (mean age=53 years [SD=9.8]), predominantly white (70.3%), and largely employed (71.8%) and consumed an average of five drinks per day prior to entering the study. Ketamine significantly increased the likelihood of abstinence, delayed the time to relapse, and reduced the likelihood of heavy drinking days compared with midazolam. Infusions were well tolerated, with no participants removed from the study as a result of adverse events.A single ketamine infusion was found to improve measures of drinking in persons with alcohol dependence engaged in motivational enhancement therapy. These preliminary data suggest new directions in integrated pharmacotherapy-behavioral treatments for alcohol use disorder. Further research is needed to replicate these promising results in a larger sample.
Discovering Precise Temporal Patterns in Large-Scale Neural Recordings through Robust and Interpretable Time Warping
Authors: Alex H. Williams, Ben Poole, Niru Maheswaranathan, Ashesh K. Dhawale, Tucker Fisher, Christopher D. Wilson, David H. Brann, Eric M. Trautmann, Stephen Ryu, Roman Shusterman, Dmitry Rinberg, Bence P. Ölveczky, Krishna V. Shenoy, Surya Ganguli
Journal: Neuron (2019)
Affluence boosted intelligence? How the interaction between cognition and environment may have produced an eighteenth-century Flynn effect during the Industrial Revolution
Authors: Max van der Linden, Denny Borsboom
Journal: Behavioral and Brain Sciences (2019)

Abstract Cognition played a pivotal role in the acceleration of technological innovation during the Industrial Revolution. Growing affluence may have provided favourable environmental conditions for a boost in cognition, enabling individuals to tackle more complex (industrial) problems. Dynamical systems thinking may provide useful tools to describe sudden transitions like the Industrial Revolution, by modelling the recursive feedback between psychology and environment.
Different Prevalence of Drug Metabolism Gene Polymorphisms (GSTP and GSTT) in FA Patients Compared to a Normal Population.
Authors: Moema Nene Santos, Vanderson Rocha, Dalila Zanette, Raphael Porcher, Irina Ionescu, Marli Tavela, Jean Soulier, Thierry Leblanc, Gustavo Fisher, André Baruchel, Marco Antonio Zago, Eliane Gluckman
Journal: Blood (2005)
Non-visible haematuria for the Detection of Bladder, Upper Tract, and Kidney Cancer: An Updated Systematic Review and Meta-analysis
Authors: Ibrahim Jubber, Shahrokh F. Shariat, Samantha Conroy, Wei Shen Tan, Patrick C. Gordon, Yair Lotan, Edward M. Messing, Arnulf Stenzl, Bas van Rhijn, John D. Kelly, James W.F. Catto, Marcus G. Cumberbatch
Journal: European Urology (2019)
Initial results of lung cancer genomic screening project for individualized medicine in Asia: LC-SCRUM-Asia
Authors: C.-H.S. Kuo, K. Yoh, C.-T. Yang, C.-C. Wang, T.-C. Yen, K.-J. Lin, T. Ikeda, Y. Zenke, S. Matsumoto, K. Goto
Journal: Annals of Oncology (2019)
Routine Edmonton Symptom Assessment System (ESAS) scores in epithelioid malignant pleural mesothelioma (eMPM) patients undergoing palliative systemic therapy.
Authors: Kristen Dietrich, Luna Jia Zhan, Michael Herman, Subiksha Nagaratnam, Kathryn Corbett, Devalben Patel, Katrina Hueniken, Wei Xu, M. Catherine Brown, Marc de Perrot, John Cho, Natasha B. Leighl, Penelope Ann Bradbury, Geoffrey Liu
Journal: Journal of Clinical Oncology (2019)

96 Background: Palliative chemotherapy, the mainstay for incurable eMPM, is offered to patients with good standing performance status (ECOG 0-1). We determined the proportion of eMPM patients experiencing moderate (Mod) to severe (Sev) symptoms while on palliative chemotherapy using ESAS symptom scores at diagnosis and during first and subsequent lines of systemic therapy. Methods: ESAS scores (0=no symptom; 10=worst symptom) were routinely captured in eMPM patients at Princess Margaret (Toronto, Canada). Retrospective chart review collected ESAS, clinical, treatment and outcome data. ESAS scores and proportions were summarized within baseline, firstline, and subsequent lines of therapy. Mod symptom was defined as ESAS scores of 4-6, and Sev as 7-10. ESAS scores between treatment lines were analyzed by Mann-Whitney U tests. Locally weighted smoothing (LOESS) plots assessed ESAS scores over treatment duration. Results: Of 37 palliative eMPM patients, the most frequent baseline symptoms were fatigue (33% Mod, 25% Sev), dyspnea (27% Mod; 17% Sev), anxiety (21% Mod; 21% Sev) and depression (34% Mod; 4% Sev). Overall well-being was poor in 45% of patients (31% Mod; 14% Sev). Compared to baseline, patients on firstline therapy reported increased pain ( p = 0.002), poor appetite ( p = 0.005) and nausea ( p = 0.02); decreased depression ( p = 0.03) and anxiety ( p = 0.006); and stable well-being ( p = 0.27). In patients well enough for subsequent therapy, patients reported reduced drowsiness ( p = 0.01) and improved overall well-being ( p = 0.04) compared to firstline therapy. LOESS plot patterns were similar between firstline and subsequent lines of treatment. Conclusions: eMPM patients had high symptom scores at the time of diagnosis. However, patients’ depression and anxiety decreased when starting initial treatment, and general well-being was stable. Of patients fit enough for subsequent lines of therapy, there were improvements in drowsiness and overall well-being. When selectively used, palliative systemic therapy of all lines are associated with some improved symptoms, but pain, poor appetite, and nausea need to be monitored and managed more effectively.
Genetically Engineered Hematopoietic Progenitors Derived from Human Induced Pluripotent Stem Cells Achieve the Feeder-Free and Robust Production of Neutrophils with the Functional Capacity In Vivo
Authors: Masashi Miyauchi, Yusuke ITO, Fumio Nakahara, Fumi Nakamura, Yuki Iwasaki, Taiki Kawagoshi, Yuki Kagoya, Shunya Arai, Mineo Kurokawa
Journal: Blood (2019)
Improvement in Pediatric Cardiac Surgical Outcomes Through Interhospital Collaboration
Authors: Michael Gaies, Sara K. Pasquali, Mousumi Banerjee, Justin B. Dimick, John D. Birkmeyer, Wenying Zhang, Jeffrey A. Alten, Nikhil Chanani, David S. Cooper, John M. Costello, J. William Gaynor, Nancy Ghanayem, Jeffrey P. Jacobs, John E. Mayer, Richard G. Ohye, Mark A. Scheurer, Steven M. Schwartz, Sarah Tabbutt, John R. Charpie
Journal: Journal of the American College of Cardiology (2019)
Precision Medicine Treatment in Older AML: Results of Beat AML Master Trial
Authors: Amy Burd, Ross L. Levine, Amy S. Ruppert, Alice S. Mims, Uma Borate, Eytan M. Stein, Prapti A. Patel, Maria R. Baer, Wendy Stock, Michael W. Deininger, William Blum, Gary J. Schiller, Rebecca L. Olin, Mark Litzow, James M. Foran, Tara L. Lin, Brian J Ball, Michael Boyiadzis, Elie Traer, Olatoyosi Odenike, Martha L. Arellano, Alison R. Walker, Vu H. Duong, Robert H. Collins, Nyla A. Heerema, Jo-Anne Vergilio, TIm Brennan, Christine Vietz, Molly Vittorio, Leonard Rosenberg, Sonja Marcus, Ashley Owen Yocum, Mona Stefanos, Brian J. Druker, John C. Byrd
Journal: Blood (2019)
Launching the Antibiotic Era: Personal Accounts of the Discovery and Use of the First Antibiotics
Journal: Annals of Internal Medicine (1992)

Interest in the nature and functioning of research groups is, of course, not new.Gerald Geison's account of Michael Foster's Cambridge Physiology School remains the most accomplished elaboration, to date, of J. B. Morrell's earlier attempt to construct a model to explain the success or failure of individual "schools".Like Morrell, Fruton begins here with Liebig's group at Giessen, before going on to analyse other prominent German chemical and biochemical research groups in the period 1830-1914.Particular attention is focused on the groups of Felix Hoppe-Seyler, Willy Kiihne, and Franz Hofmeister in biochemistry, and on Adolf von Baeyer and Emil Fischer in chemistry.Biographical details of each leader's 'scientific progeny" fill seven appendices.Together with a bibliography
B Cell Synovitis and Clinical Phenotypes in Rheumatoid Arthritis: Relationship to Disease Stages and Drug Exposure
Authors: F. Rivellese, F. Humby, S. Bugatti, L. Fossati‐Jimack, H. Rizvi, D. Lucchesi, G. Lliso‐Ribera, A. Nerviani, R. E. Hands, G. Giorli, B. Frias, G. Thorborn, E. Jaworska, C. John, K. Goldmann, M. J. Lewis, A. Manzo, M. Bombardieri, C. Pitzalis
Journal: Arthritis & Rheumatology (2019)

Objective To define the relationship of synovial B cells to clinical phenotypes at different stages of disease evolution and drug exposure in rheumatoid arthritis ( RA ). Methods Synovial biopsy specimens and demographic and clinical data were collected from 2 RA cohorts (n = 329), one of patients with untreated early RA (n = 165) and one of patients with established RA with an inadequate response to tumor necrosis factor inhibitors ( TNF i‐ IR ; n = 164). Synovial tissue was subjected to hematoxylin and eosin and immunohistochemical staining and semiquantitative assessment for the degree of synovitis (on a scale of 0–9) and of CD 20+ B cell infiltrate (on a scale of 0–4). B cell scores were validated by digital image analysis and B cell lineage–specific transcript analysis ( RNA ‐Seq) in the early RA (n = 91) and TNF i‐ IR (n = 127) cohorts. Semiquantitative CD 20 scores were used to classify patients as B cell rich (≥2) or B cell poor (&lt;2). Results Semiquantitative B cell scores correlated with digital image analysis quantitative measurements and B cell lineage–specific transcripts. B cell–rich synovitis was present in 35% of patients in the early RA cohort and 47.7% of patients in the TNF i‐ IR cohort ( P = 0.025). B cell–rich patients showed higher levels of disease activity and seropositivity for rheumatoid factor and anti–citrullinated protein antibody in early RA but not in established RA , while significantly higher histologic synovitis scores in B cell–rich patients were demonstrated in both cohorts. Conclusion We describe a robust semiquantitative histologic B cell score that closely replicates the quantification of B cells by digital or molecular analyses. Our findings indicate an ongoing B cell–rich synovitis, which does not seem to be captured by standard clinimetric assessment, in a larger proportion of patients with established RA than early RA .