tbuckley/cabot-search huggingface dataset:
Incidence of skeletal-related events in men with castration-resistant prostate cancer.
Authors: Alison Tse Kawai, David Martinez, Catherine W. Saltus, Zdravko Vassilev, Montse Soriano-Gabarro, James A. Kaye
Journal: Journal of Clinical Oncology (2018)

188 Background: Skeletal-related events (SREs) are common in men with bone metastases and have negative consequences for patients with castration-resistant prostate cancer (CRPC), including pain, reduced quality of life, and increased risk of death. Published data on background rates of SREs in men with CPRC in real-world practice are sparse. Methods: We included men aged ≥ 65 years in the SEER-Medicare database with a prostate cancer diagnosis in 2000-2011 if they had no prior malignancy, had surgical or medical castration, and met protocol-defined criteria for castration resistance. Castration resistance was inferred from subsequent treatment with any of these systemic therapies: abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, or sipuleucel-T. The first occurrence of an SRE was identified in Medicare claims using diagnosis or procedure codes for fracture, bone surgery, radiation therapy, or spinal cord compression. We estimated incidence rates (IRs) of SREs in all eligible person-time and stratified by person-time before and after any use of the following bone-targeted agents (BTAs): alendronate, denosumab, ibandronate, pamidronate, risedronate, or zoledronic acid. Results: Of 2,234 men with CRPC (84% white, mean age 76.6 years), 896 (40%) had an SRE during follow-up, with 74% occurring within a year after cohort entry. Overall, the IR of SREs was 3.78 (95% CI, 3.53-4.03) per 100 person-months. The IR of SREs before any BTA use was 4.16 (95% CI, 3.71-4.65) per 100 person-months, and after any use was 3.60 (95% CI, 3.32-3.91) per 100 person-months. Conclusions: In this large cohort of elderly men with CRPC in a real-world setting in the U.S., SREs were common, with most occurring within a year after cohort entry. Although a direct causal interpretation of the difference in rates before and after BTA use is not possible (since confounding by indication and other factors cannot be excluded), further analysis may address at least some potential confounders.
The Future of Complementarity: Disentangling Causes from Consequences
Authors: Kathryn E. Barry, Liesje Mommer, Jasper van Ruijven, Christian Wirth, Alexandra J. Wright, Yongfei Bai, John Connolly, Gerlinde B. De Deyn, Hans de Kroon, Forest Isbell, Alexandru Milcu, Christiane Roscher, Michael Scherer-Lorenzen, Bernhard Schmid, Alexandra Weigelt
Journal: Trends in Ecology & Evolution (2018)
Christopher Arthur Rodrigues
Authors: Mark Spring
Journal: BMJ (2018)

Christopher Arthur Rodrigues (“Chris”) studied at the Armed Forces Medical College in his native Poona, one of the top ranked institutions nationally. The college encourages extracurricular activities, and Chris became an outstanding captain of the basketball team, winning several intercollegiate tournaments. Close friends saw another side—his love of literature, poetry, music, and playing the piano. After graduating, Chris enrolled at the highly competitive postgraduate institute in …
Correlation of the refined Hurley classification for hidradenitis suppurativa with patient‐reported quality of life and objective disease severity assessment
Authors: A. Rondags, K.R. Straalen, J.R. Hasselt, I.C. Janse, C.B. Ardon, A.R.J.V. Vossen, E.P. Prens, H.H. Zee, B. Horváth
Journal: British Journal of Dermatology (2018)

Hidradenitis suppurativa (HS) is a chronic, debilitating, heterogeneous disease requiring different treatment approaches. Recently, we refined the classic Hurley classification into a seven‐stage classification in order to guide these treatment choices. This new classification subdivides Hurley stage I and II into three substages, namely mild (A), moderate (B) and severe (C) HS disease. Hurley stage III is not subcategorized and is always severe. To investigate the correlation between the given severity grades of Hurley I and Hurley II in the refined Hurley classification, and the patient‐reported quality of life and physician‐assessed objective severity score. In this cross‐sectional study, patients with HS participating in the observational cohorts of two Dutch tertiary referral centres were included before June 2017. The patient‐reported Dermatology Life Quality Index (DLQI) and physician‐assessed International HS Severity Score System (IHS4) scores were compared between the refined Hurley stages. In total, 433 patients were analysed. DLQI and IHS4 scores increased within Hurley stage I and II from A through C. There was a significant positive correlation of DLQI and IHS4 with increasing refined Hurley substages [refined Hurley stage I (A, B and C) to DLQI: rs = 0·259, P < 0·001 and refined Hurley stage II (A, B and C) to DLQI: rs = 0·185, P = 0·010; refined Hurley stage I (A, B and C) to IHS4: rs = 0·603, P < 0·001 and refined Hurley stage II (A, B and C) to IHS4: rs = 0·532, P < 0·001]. The refined Hurley classification accurately correlates with HS severity assessed by both patients and clinicians. Therefore, the refined Hurley classification is a useful tool for the quick assessment of severity in HS.
CML Hematopoietic Stem Cells Expressing IL1RAP Can Be Targeted by Chimeric Antigen Receptor–Engineered T Cells
Authors: Walid Warda, Fabrice Larosa, Mathieu Neto Da Rocha, Rim Trad, Eric Deconinck, Ziad Fajloun, Cyril Faure, Denis Caillot, Marius Moldovan, Severine Valmary-Degano, Sabeha Biichle, Etienne Daguindau, Francine Garnache-Ottou, Sebastien Tabruyn, Olivier Adotevi, Marina Deschamps, Christophe Ferrand
Journal: Cancer Research (2018)

Abstract Chronic myeloid leukemia (CML) is a chronic disease resulting in myeloid cell expansion through expression of the BCR-ABL1 fusion transcript. Tyrosine kinase inhibitors (TKI) have significantly increased survival of patients with CML, and deep responders may consider stopping the treatment. However, more than 50% of patients relapse and restart TKI, subsequently suffering unknown toxicity. Because CML is a model immune system–sensitive disease, we hypothesize that chimeric antigen receptor (CAR) T cells targeting IL1 receptor-associated protein (IL1RAP) in quiescent CML stem cells may offer an opportunity for a permanent cure. In this study, we produced and molecularly characterized a specific monoclonal anti-IL1RAP antibody from which fragment antigen-binding nucleotide coding sequences were cloned as a single chain into a lentiviral backbone and secured with the suicide gene iCASP9/rimiducid system. Our CAR T-cell therapy exhibited cytotoxicity against both leukemic stem cells and, to a lesser extent, monocytes expressing IL1RAP, with no apparent effect on the hematopoietic system, including CD34+ stem cells. This suggests IL1RAP as a tumor-associated antigen for immunotherapy cell targeting. IL1RAP CAR T cells were activated in the presence of IL1RAP+ cell lines or primary CML cells, resulting in secretion of proinflammatory cytokines and specifically killing in vitro and in a xenograft murine model. Overall, we demonstrate the proof of concept of a CAR T-cell immunotherapy approach in the context of CML that is applicable for young patients and primary TKI-resistant, intolerant, or allograft candidate patients. Significance: These findings present the first characterization and proof of concept of a chimeric antigen receptor directed against IL1RAP expressed by leukemic stem cells in the context of CML.
The Circadian Protein Period2 Suppresses mTORC1 Activity via Recruiting Tsc1 to mTORC1 Complex
Authors: Rong Wu, Fabin Dang, Peng Li, Pengfei Wang, Qian Xu, Zhengshuai Liu, Yu Li, Yuting Wu, Yaqiong Chen, Yi Liu
Journal: Cell Metabolism (2018)
Needs for patients with cancer who have young children.
Authors: Rebekah Kojima, Hiromi Takada, Tetsuhiko Yoshida, Masaki Shimizu, Daisuke Kiuchi, Hiroto Ishiki, Eriko Satomi
Journal: Journal of Clinical Oncology (2018)

150 Background: The number of cancer patients has been increasing in Japan. It is estimated that 56,143 parents with 87,017 young children (under 18 years old) are diagnosed with cancer per year in Japan (Inoue, 2015). The aim of this study is to investigate the needs of cancer patients who have young children. Methods: The survey was conducted from February to April 2018 to the cancer patients who have young children treated at the National Cancer Center Hospital with the questionnaires. It was on items about parenting concerns evaluated with the 4-point Likert scale: 1. strongly disagree, 2. slightly disagree, 3. slightly agree, and 4. strongly agree. The items included “cancer notification to their children”, “parental anxieties”, and others. The items were analyzed separately. Results: The respondents were 152 (143 cancer patients (94%) and nine spouses (6%)). Most respondents (92%) agreed the importance of psychosocial support for the children and parents in hospital. The average age of their young children (n = 237) was 9.5 (ages 0 – 17). The result showed that 148 (62%) children were told true parents’ illness. This study also revealed that parents were struggling with the conflict telling their children truth. Most parents wanted to protect children from emotional distresses and were afraid of it or don’t know how to cope with some changes during treatments. Conclusions: The study describes how cancer impacts on parents for child rearing. Almost all of the patients with minor children had been found psychologically distressed. It is necessary to improve an effective psychosocial support system in hospitals for cancer patients with young children based on their needs.
Abstract 12498: Antiplatelet Effects of Ticagrelor versus Clopidogrel in Native American Patients With Stable Coronary Artery Disease
Authors: Roger DeRaad, Lisa K Jennings, Edward Hord, James S Walder
Journal: Circulation (2015)

Introduction: Ticagrelor is a potent, reversibly binding, P2Y12 platelet inhibitor that, compared with clopidogrel, decreased the rate of myocardial infarction and vascular mortality in acute coronary syndrome. Although Native Americans have the highest death rate attributable to premature heart disease among all races, they are generally under-represented in clinical trials. Hypothesis: Native Americans with stable CAD on low dose aspirin administered with ticagrelor, compared with clopidogrel, will exhibit a faster onset and higher platelet inhibition, and maintain this difference on day 7 of the treatment. Methods: Single center, randomized, open-label, crossover study of Native Americans with stable CAD randomly allocated to either ticagrelor (180 mg loading dose [LD] and 90 mg twice daily maintenance dose [MD] for 7-9 days) or clopidogrel (600 mg LD and 75mg once daily MD for 7- 9 days), and then received the alternative P2Y 12 inhibitor after a washout period. All patients received aspirin 81 mg daily. Platelet reactivity was measured with the VerifyNow P2Y 12 assay, which reports results in P2Y 12 reaction units (PRU). Results: A total of 28 patients were evaluated. At 30 minutes after the LD, on-treatment reactivity after ticagrelor (mean ± standard error of mean) was 205 ± 53 compared with 275 ± 71 PRU after clopidogrel ( P &lt;0.001) (Figure 1). At 2 hours after the LD, on-treatment reactivity was 36 ± 52 and 225 ± 71 PRU for ticagrelor and clopidogrel, respectively ( P &lt;0.001). At 8 hours after last MD, on-treatment reactivity was 40 ± 36 with ticagrelor compared with 197 ± 78 PRU with clopidogrel ( P &lt;0.001). At 24 hours after last MD residual reactivity was 140 + 55 for ticagrelor and 192 + 58.3 PRU for clopidogrel ( P &lt;0.001). No significant adverse events were noted with either study drug. Conclusions: In Native Americans with stable CAD on low dose ASA, ticagrelor provided a significantly faster onset, greater extent of platelet inhibition and faster offset than clopidogrel.
Sequential Neuroimaging of the Fetus and Newborn With In Utero Zika Virus Exposure
Authors: Sarah B. Mulkey, Dorothy I. Bulas, Gilbert Vezina, Yamil Fourzali, Armando Morales, Margarita Arroyave-Wessel, Christopher B. Swisher, Caitlin Cristante, Stephanie M. Russo, Liliana Encinales, Nelly Pacheco, Youssef A. Kousa, Robert S. Lanciotti, Carlos Cure, Roberta L. DeBiasi, Adre J. du Plessis
Journal: JAMA Pediatrics (2018)

<h3>Importance</h3> The evolution of fetal brain injury by Zika virus (ZIKV) infection is not well described. <h3>Objectives</h3> To perform longitudinal neuroimaging of fetuses and infants exposed to in utero maternal ZIKV infection using concomitant magnetic resonance imaging (MRI) and ultrasonography (US), as well as to determine the duration of viremia in pregnant women with ZIKV infection and whether the duration of viremia correlated with fetal and/or infant brain abnormalities. <h3>Design, Setting, and Participants</h3> A cohort of 82 pregnant women with clinical criteria for probable ZIKV infection in Barranquilla, Colombia, and Washington, DC, were enrolled from June 15, 2016, through June 27, 2017, with Colombian women identified by community recruitment and physician referral and travel-related cases of American women recruited from a Congenital Zika Program. <h3>Interventions and Exposures</h3> Women received 1 or more MRI and US examinations during the second and/or third trimesters. Postnatally, infants underwent brain MRI and cranial US. Blood samples were tested for ZIKV. <h3>Main Outcomes and Measures</h3> The neuroimaging studies were evaluated for brain injury and cerebral biometry. <h3>Results</h3> Of the 82 women, 80 were from Colombia and 2 were from the United States. In 3 of 82 cases (4%), fetal MRI demonstrated abnormalities consistent with congenital ZIKV infection. Two cases had heterotopias and malformations in cortical development and 1 case had a parietal encephalocele, Chiari II malformation, and microcephaly. In 1 case, US results remained normal despite fetal abnormalities detected on MRI. Prolonged maternal polymerase chain reaction positivity was present in 1 case. Of the remaining 79 cases with normal results of prenatal imaging, postnatal brain MRI was acquired in 53 infants and demonstrated mild abnormalities in 7 (13%). Fifty-seven infants underwent postnatal cranial US, which detected changes of lenticulostriate vasculopathy, choroid plexus cysts, germinolytic/subependymal cysts, and/or calcification in 21 infants (37%). <h3>Conclusions and Relevance</h3> In a cohort of pregnant women with ZIKV infection, prenatal US examination appeared to detect all but 1 abnormal fetal case. Postnatal neuroimaging in infants who had normal prenatal imaging revealed new mild abnormalities. For most patients, prenatal and postnatal US may identify ZIKV-related brain injury.
Differences in the way patient and partner experience the metastatic disease.
Authors: Cristiane Decat Bergerot, Karen L. Clark, Paulo Gustavo Bergerot, Renata Nunes Pedras, Maria Fernanda Manhaes, Courtney Bitz, Matthew J. Loscalzo, Sumanta K. Pal
Journal: Journal of Clinical Oncology (2018)

115 Background: In Brazil, 60.5% of patients are diagnosed with an advanced stage of cancer. Patients with incurable cancer and their partners experience high rates of distress. This study aimed to assess problem-related distress among patients with stage IV cancer and their partners. Methods: A descriptive study was conducted at a large public hospital. Patients and their partners completed the 33-item SupportScreen-Couples Distress, on a five Likert scale, which contains questions related to emotional and physical symptoms, relationship issues and concerns around diagnosis, treatment, prognosis, and end-of-life. The McNemar’s test was used to compare rates of problem-related distress between patients and their partners. Results: A total of 64 patients (median 56 yrs old; 57.8% male; 51.6% white; 87.5% Eastern Cooperative Oncology Group &lt; 2) and 64 partners (median 56 yrs old; 53.1% white; 93.8% primary caregiver) were enrolled. Couples were married for a median of 27.3 yrs. Patients reported higher levels of distress related to fatigue (42.1% vs 29.7%; P = 0.02), worry about the future (28.1% vs 20.3%; P = 0.08), sleep problems (28.1% vs 20.3%; P = 0.07) and feeling depressed (26.6% vs 15.6%; P = 0.03) compared to their associated partners. Partners reported more anxiety (37.5% vs 28.1%) and financial concerns (25.1% vs 17.2%) compared to associated patients (P &lt; 0.01 for both). Patients and partners had a similar understanding that curative treatment is unlikely and that the goal of treatment was disease control (51.6% and 56.2%, respectively). Patients (versus their partners) were generally more worried about how their family was coping with their cancer diagnosis (42.2% vs 15.6%) and demonstrated hesitancy in talking about fears related to the end of life (60.9% vs 14.1%) (P &lt; 0.001 for both). Conclusions: We identify key differences in psychosocial issues experience by patients and their partners. Furthermore, patients and partners demonstrate unique concerns related to the spectrum of oncology care. Our findings can be used to tailor unique supportive care interventions for patients and partners.
Abstract 15928: miR-195 Regulates Myocardial Metabolism in Heart Failure via Alternations in SIRT3 Expression and Mitochondrial Protein Acetylation Profile
Authors: Xiaokan Zhang, Ruiping Ji, Xianghai Liao, Estibaliz Castillero, Peter Kennel, Danielle L Brunjes, Konstantinos Drosatos, Isaac George, Emily Chen, Paolo C Colombo, P. Christian Schulze
Journal: Circulation (2017)

Background: Post-translational lysine acetylation has been described as a major mechanism regulating protein activity and cardiac function. Unique cardiac miRNAs play an important role in cardiac r...
Lopinavir–ritonavir super-boosting in young HIV-infected children on rifampicin-based tuberculosis therapy compared with lopinavir–ritonavir without rifampicin: a pharmacokinetic modelling and clinical study
Authors: Helena Rabie, Paolo Denti, Janice Lee, Mhleli Masango, Ashraf Coovadia, Sandy Pillay, Afaaf Liberty, François Simon, Helen McIlleron, Mark F Cotton, Marc Lallemant
Journal: The Lancet HIV (2018)
Definition of psoriasis severity
Authors: M. Augustin, A. Langenbruch, M. Gutknecht, K. Reich, A. Körber, D. Maaßen, U. Mrowietz, D. Thaçi, R. von Kiedrowski, M.A. Radtke
Journal: British Journal of Dermatology (2018)

Measurement of the severity of a patient's psoriasis is very important, for a variety of reasons. For example, it allows doctors to select the right level of treatment, to then see how well treatments are working, and it allows researchers to compare different treatments on similar patients. Some treatments called systemic treatments, which work on the whole body rather than just the skin, are only available to patients with ‘moderate to severe’ disease. Measurement of psoriasis severity is generally based on two different scoring systems: the Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI). PASI is used to record the redness, thickness and scaling of a patient's psoriasis and to measure how well a treatment works, as a reduction in the PASI score means a reduction in these symptoms. DLQI consists of 10 questions concerning a dermatology patient's perception of the impact of their skin disease on different aspects of their quality of life (QoL) over the last week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships and the side effects of treatment. Higher scores indicate greater impairment of QoL. However, not all guidelines give the same advice on how to combine the results of DLQI and PASI; for example, some say that a score of >10 for both DLQI and PASI suggests moderate‐to‐severe psoriasis, while others say a score of >10 for DLQI or PASI suggests moderate‐to‐severe psoriasis. In this study from Germany, data from 3274 patients were analysed for disease severity based on PASI and DLQI together or separately. The proportion of patients with PASI and DLQI >10 was 14.0%, although 45.3% attained at least PASI or DLQI >10. The authors therefore propose an international standardization for the sake of more reliable treatment and healthcare planning.
Happy Birthday Concussion!
Authors: Michael Turner
Journal: British Journal of Sports Medicine (2018)

The consensus definition of concussion was only agreed in 20011 which means that concussion has just turned 18. It must, therefore, be viewed as an unruly teenager, rebellious and changing, but finally beginning to mature. Along the way, there has been a book, a film, extensive litigation and legislation, millions of words written in the media, thousands of peer-reviewed articles, more consensus meetings, more books and the threat of still more litigation. Hardly a week goes by without another story about concussion hitting the headlines and the centre of the concussion maelstrom is the USA.

In terms of global participation, volleyball leads the field with 998 million participants, followed by basketball (400 m), soccer (242 m), badminton (200 m) and tennis (60 m). Not the strongest line-up for sports involving concussion and in the USA, the list is only slightly …
A heparan sulfate-based matrix therapy reduces brain damage and enhances functional recovery following stroke
Authors: Yacine Khelif, Jérôme Toutain, Marie-Sophie Quittet, Sandrine Chantepie, Xavier Laffray, Samuel Valable, Didier Divoux, Fernando Sineriz, Emanuelle Pascolo-Rebouillat, Dulce Papy-Garcia, Denis Barritault, Omar Touzani, Myriam Bernaudin
Journal: Theranostics (2018)

Alteration of the extracellular matrix (ECM) is one of the major events in the pathogenesis of brain lesions following ischemic stroke. Heparan sulfate mimetics (HSm) are synthetic pharmacologically active polysaccharides that promote ECM remodeling and tissue regeneration in various types of lesions. HSm bind to growth factors, protect them from enzymatic degradation and increase their bioavailability, which promotes tissue repair. As the ECM is altered during stroke and HSm have been shown to restore the ECM, we investigated the potential of HSm4131 (also named RGTA-4131®) to protect brain tissue and promote regeneration and plasticity after a stroke. Methods: Ischemic stroke was induced in rats using transient (1 h) intraluminal middle cerebral artery occlusion (MCAo). Animals were assigned to the treatment (HSm4131; 0.1, 0.5, 1.5, or 5 mg/kg) or vehicle control (saline) groups at different times (1, 2.5 or 6 h) after MCAo. Brain damage was assessed by MRI for the acute (2 days) and chronic (14 days) phases post-occlusion. Functional deficits were evaluated with a battery of sensorimotor behavioral tests. HSm4131-99mTc biodistribution in the ischemic brain was analyzed between 5 min and 3 h following middle cerebral artery reperfusion. Heparan sulfate distribution and cellular reactions, including angiogenesis and neurogenesis, were evaluated by immunohistochemistry, and growth factor gene expression (VEGF-A, Ang-2) was quantified by RT-PCR. Results: HSm4131, administered intravenously after stroke induction, located and remained in the ischemic hemisphere. HSm4131 conferred long-lasting neuroprotection, and significantly reduced functional deficits with no alteration of physiological parameters. It also restored the ECM, and increased brain plasticity processes, i.e., angiogenesis and neurogenesis, in the affected brain hemisphere. Conclusion: HSm represent a promising ECM-based therapeutic strategy to protect and repair the brain after a stroke and favor functional recovery.
Single-Cell Atlas of Driver Mutations in Acute Myeloid Leukemia (AML)
Authors: Kiyomi Morita, Feng Wang, Robert Durruthy-Durruthy, Anup Parikh, Jairo Matthews, Latasha Little, Samantha Tippen, Curtis Gumbs, Jianhua Zhang, Xingzhi Song, Erika Thompson, Keyur Patel, Carlos E. Bueso-Ramos, Courtney D. DiNardo, Farhad Ravandi, Elias J. Jabbour, Michael Andreeff, Jorge E. Cortes, Marina Y. Konopleva, Guillermo Garcia-Manero, Hagop M. Kantarjian, Dennis J. Eastburn, P Andrew Futreal, Koichi Takahashi
Journal: Blood (2018)