tbuckley/cabot-search huggingface dataset:
Integrative Analysis of Pediatric Acute Leukemia Identifies Immature Subtypes That Span a T Lineage and Myeloid Continuum with Distinct Prognoses
Authors: Tanja A. Gruber, Jing Ma, Sanne Noort, Yu Liu, Michael P Walsh, Stephanie Nance, Yanling Liu, Yuanyuan Wang, Guangchun Song, Tamara Lamprecht, John Easton, Martina Pigazzi, Marie Jarosova, Kelaidi Charikleia, Jeffrey Rubnitz, Dirk Reinhardt, Marry M. van den Heuvel-Eibrink, Franco Locatelli, Henrik Hasle, Jeffery M. Klco, James R. Downing, Stanley Pounds, Jinghui Zhang, Christian Michel Zwaan, Maarten Fornerod
Journal: Blood (2019)
A Busulfan Following Cyclophosphamide and Constant Cell Dose Protocol Improved Results in Alternative Donor Hematologic Stem Cell Transplantation in Thalassemia Major: A Result from Long-Term Large-Size Multi-Center Study
Authors: Yuelin He, Hua Jiang, Changgang Li, Yiping Zhu, Xuedong Wu, Liu Sixi, Qu Yuhua, Jiangyu Liao, Xiaoqin Feng, Huaying Liu, Zhiyong Peng, Lan He, Chaoke Bu, Gautam Mandeen, Leung Wing, Chunfu Li
Journal: Blood (2019)
Augmentation of Positive Valence System–Focused Cognitive Behavioral Therapy by Inaudible High-Frequency Sounds for Anhedonia
Authors: Masaya Ito, Mitsuhiro Miyamae, Chika Yokoyama, Yuichi Yamashita, Osamu Ueno, Kazushi Maruo, Asami Komazawa, Madoka Niwa, Manabu Honda, Masaru Horikoshi
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Recent conceptualizations in Research Domain Criteria have indicated that anhedonia, 1 of 2 core symptoms of depression, which can be treatment resistant, is associated with deficits in the positive valence system, and inaudible high-frequency sound therapy has been shown to enhance reward-related brain circuitry. Hence, cognitive behavioral therapy focusing on the positive valence system enhanced with sound therapy could have a synergistic effect on anhedonia. <h3>Objective</h3> To test the augmentation effect of inaudible high-frequency sounds on the efficacy of positive valence system–focused cognitive behavioral therapy to treat anhedonia. <h3>Design, Setting, and Participants</h3> In this individual-level allocation, exploratory, single-center randomized superiority pilot trial, patients, therapists, and evaluators will be masked to intervention or placebo assignment. The trial will take place at a national psychiatric referral hospital in Tokyo, Japan, among 44 adult patients with clinically significant anhedonia and moderate to severe depression. Outcomes will be analyzed following the intent-to-treat principle using a repeated-measures mixed model. <h3>Intervention</h3> The intervention group will participate in 8 weekly sessions of positive valence system–focused cognitive behavioral therapy with in-session exposure to an inaudible high-frequency sound; the comparison group will undergo cognitive behavioral therapy with in-session exposure to a placebo sound. <h3>Main Outcomes and Measures</h3> The primary outcome is anhedonia assessed using the self-reported Snaith-Hamilton Pleasure Scale. The secondary outcome is anhedonia assessed using the clinician-administered version of the Snaith-Hamilton Pleasure Scale. <h3>Discussion</h3> Recruitment for this study began in May 2018, and the projected date of final allocation is January 2020. A total of 21 eligible patients were registered for participation as of May 30, 2019. To date, treatments for depression do not guarantee clinically successful outcomes. This pilot trial will provide preliminary evidence of the augmentation effect of high-frequency inaudible sounds on cognitive behavioral therapy for anhedonia. Overall, exposure to an inaudible high-frequency sounds does not require attentional or cognitive effort from either patients or therapists; therefore, results from a future confirmative trial could indicate that cognitive behavioral therapy can be augmented in an effortless manner. <h3>Trial Registration</h3> umin.ac.jp/ctr Identifier:UMIN000031948
Precision lung cancer survivorship care: Accrual to the Kentucky LEADS Collaborative Lung Cancer Survivorship Care Program.
Authors: Jamie L Studts
Journal: Journal of Clinical Oncology (2019)

144 Background: Recent innovations in lung cancer care create an urgent need to generate survivorship care interventions that target lung cancer survivors and tailor content and services to this unique community. In addition to suffering significant distress and symptom burden, individuals diagnosed with lung cancer suffer the additional burden of stigma and bias and may not receive optimal social support. The Kentucky LEADS Collaborative Lung Cancer Survivorship Care Program adopts a precision survivorship approach by combining shared decision making and motivational interviewing to address specific threats to quality of life experienced by an individual facing lung cancer. Methods: A single-arm trial was conducted at nine cancer care facilities across Kentucky to assess intervention feasibility, acceptability, and preliminary efficacy. Eligible participants included individuals diagnosed with lung cancer who did not evince acute psychiatric or substance abuse issues. Upon consent, participants completed a baseline survey (T1) and medical data was extracted from the electronic record. Participants also completed the survey following intervention completion (T2) and six months post-baseline (T3). Analyses evaluate accrual and completion rates as well as participant demographics. Results: Over an approximately 12-month accrual period, nine sites accrued 142 participants. Three sites exceeded the accrual goal of 20. Of the participants accrued, 138 (97%) completed T1, 84 (58%) completed T2, 74 (52%) completed T3, and 70 (49%) provided complete data. The majority of participants were female (64%), the mean age was 63.4 (9.3) years, and nearly all participants were white/non-Hispanic (96%). Most participants had a high school degree or less (52%), described household incomes of $35K or less, but nearly all reported carrying health insurance (98%). Conclusions: The Kentucky LEADS program offers an intriguing approach to engaging lung cancer survivors by incorporating precision care strategies that may circumvent some of the more common challenges to reaching individuals diagnosed with lung cancer. Clinical trial information: NCT02989974.
The overweight and obesity transition from the wealthy to the poor in low- and middle-income countries: A survey of household data from 103 countries
Authors: Tara Templin, Tiago Cravo Oliveira Hashiguchi, Blake Thomson, Joseph Dieleman, Eran Bendavid
Journal: PLoS Medicine (2019)

Background In high-income countries, obesity prevalence (body mass index greater than or equal to 30 kg/m2) is highest among the poor, while overweight (body mass index greater than or equal to 25 kg/m2) is prevalent across all wealth groups. In contrast, in low-income countries, the prevalence of overweight and obesity is higher among wealthier individuals than among poorer individuals. We characterize the transition of overweight and obesity from wealthier to poorer populations as countries develop, and project the burden of overweight and obesity among the poor for 103 countries. Methods and findings Our sample used 182 Demographic and Health Surveys and World Health Surveys (n = 2.24 million respondents) from 1995 to 2016. We created a standard wealth index using household assets common among all surveys and linked national wealth by country and year identifiers. We then estimated the changing probability of overweight and obesity across every wealth decile as countries’ per capita gross domestic product (GDP) rises using logistic and linear fixed-effect regression models. We found that obesity rates among the wealthiest decile were relatively stable with increasing national wealth, and the changing gradient was largely due to increasing obesity prevalence among poorer populations (3.5% [95% uncertainty interval: 0.0%–8.3%] to 14.3% [9.7%–19.0%]). Overweight prevalence among the richest (45.0% [35.6%–54.4%]) and the poorest (45.5% [35.9%–55.0%]) were roughly equal in high-income settings. At $8,000 GDP per capita, the adjusted probability of being obese was no longer highest in the richest decile, and the same was true of overweight at $10,000. Above $25,000, individuals in the richest decile were less likely than those in the poorest decile to be obese, and the same was true of overweight at $50,000. We then projected overweight and obesity rates by wealth decile to 2040 for all countries to quantify the expected rise in prevalence in the relatively poor. Our projections indicated that, if past trends continued, the number of people who are poor and overweight will increase in our study countries by a median 84.4% (range 3.54%–383.4%), most prominently in low-income countries. The main limitations of this study included the inclusion of cross-sectional, self-reported data, possible reverse causality of overweight and obesity on wealth, and the lack of physical activity and food price data. Conclusions Our findings indicate that as countries develop economically, overweight prevalence increased substantially among the poorest and stayed mostly unchanged among the wealthiest. The relative poor in upper- and lower-middle income countries may have the greatest burden, indicating important planning and targeting needs for national health programs.
The Folate Cycle Enzyme MTHFR Is a Critical Regulator of Cell Response to MYC-Targeting Therapies
Authors: Angela Su, Frank Ling, Camille Vaganay, Bryann Pardieu, Lina Benajiba, Gaetano Sodaro, Justine Pasanisi, Kevin H Lin, Justine Rutter, Christopher F. Bassil, Iléana Antony-Debre, Gabriela Alexe, Jean-François Benoist, Yana Pikman, Jun Qi, Herve Dombret, Claude Preudhomme, Nina Fenouille, Hava M. Golan, Kimberly Stegmaier, Camille Lobry, Kris C Wood, Raphael Itzykson, Alexandre Puissant
Journal: Blood (2019)
Soluble immune checkpoint-related proteins as predictors of tumor recurrence, survival, and T cell phenotypes in clear cell renal cell carcinoma patients
Authors: Qinchuan Wang, Jinhua Zhang, Huakang Tu, Dong Liang, David. W. Chang, Yuanqing Ye, Xifeng Wu
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Immune checkpoint inhibitors have achieved unprecedented success in cancer immunotherapy. With the exception of a few candidate biomarkers, the prognostic role of soluble immune checkpoint-related proteins in clear cell renal cell cancer (ccRCC) patients is largely uninvestigated. <h3>Methods</h3> We profiled the circulating levels of 14 immune checkpoint-related proteins panel (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, CD137, CD27 and CTLA-4) and their associations with the risk of recurrence and death in 182 ccRCC patients using a multiplex Luminex assay. Gene expression in tumors from a subset of participating patients (<i>n</i> = 47) and another 533 primary ccRCC from TCGA were analyzed to elucidate potential mechanisms. Our primary endpoint is overall survival; secondary endpoint is recurrence-free survival. Multivariate Cox proportional hazard model, unconditional logistic regression model, and Kaplan-Meier analysis were applied in the study. <h3>Results</h3> sTIM3 and sLAG3 were significantly associated with advanced (stage III) disease (<i>P</i> &lt; 0.05). sPD-L2 was the strongest predictor of recurrence (HR 2.51, 95%CI 1.46–4.34, <i>P</i> = 9.33E-04), whereas high sBTLA and sTIM3 was associated with decreased survival (HR 6.02, 95%CI 2.0–18.1, <i>P</i> = 1.39E-03 and HR 3.12, 95%CI 1.44–6.75, <i>P</i> = 3.94E-03, respectively). Risk scores based on sTIM3 and sBTLA indicated that the soluble immune checkpoint-related proteins jointly predicted recurrence and death risks of ccRCC (<i>P</i> = 0.01 and 4.44E-04, respectively). Moreover, sLAG3 and sCD28 were found negatively correlated with cytolytic activity of T cells in tumors (rho = −0.31 and − 0.33, respectively). <h3>Conclusions</h3> Our study provides evidence that soluble immune checkpoint-related proteins may associate with advanced disease, recurrence and survival in ccRCC patients, which highlights the prognostic values of soluble immune checkpoint-related proteins. Future independent validation in prospective studies is warranted.
ATIM-48 (LTBK-05). MULTIDIMENSIONAL PERSONALIZED RESPONSE ASSESSMENT TO MICROGLIA MODULATORS IN GLIOBLASTOMA BIOREACTORS
Authors: Tala Shekarian, Anna Theresa Wachnowicz, Julia Flammer, Chiara Paganetti, Tomas Martins, Manuele Muraro, Christian Martijn Schürch, Gregor Hutter
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Recently, strategies harnessing the non-neoplastic immune tumor microenvironment (iTME), consisting of macrophages and microglia (TAMs), as well as adaptive immune cells have been employed to treat glioblastoma (GBM). To evaluate the effect of local TAM-modulating therapies in combination with T-cell checkpoint inhibitors, we generated 3D GBM perfusion bioreactor cultures from patient-derived samples. We report patient- and tumor region specific responses to microglia modulators and checkpoint inhibitors using multidimensional fluorescent microscopy techniques, and multiplexed cytokine measurements, Subsequently, we aime at identifying responders versus non-responders as well as predictive markers of treatment response. METHODS Fresh, neuronavigated GBM biopsies from tumor center and periphery were placed into perfusion bioreactors and cultured for 7 days. Explants were treated with combinations of TAM and T-cell modulating drugs including anti-PD1 and anti-CD47 antibodies and their combination. Tissue was harvested for histology, and supernatants were processed for multiplexed cytokine analysis. Multidimensional CODEX technology analysis using a customized TAM centric 54 marker panel was implemented, and a map of individualized response criteria to specific immunotherapies developed. RESULTS Multiplex cytokine analysis showed a dominance of proinflammatory cytokines (CCL2, CCL3, CCL4 and PAI-1) in the periphery of the tumor at baseline. We further observed that the tumor periphery was more responsive to treatments confirming the efficacy of the treatment after tumor resection. Using CODEX, we identified specific cell types responding to the treatment and undergoing phenotypic changes. Moreover, dynamic shifting of T-cell checkpoint expression levels under treatment pointed to potential resistance mechanisms in a subset of tumors. Further, we identified region-specific cytokine release as a response to the treatment in a series of 8 patient-specific explant cultures. In summary, we present an in-depth profiling of the GBM-region specific iTME at baseline and document its dynamic response under innate/adaptive immune modulators using CODEX. CONCLUSION The proposed approach serves as a patient-tailored ex vivo “Clinical Trial” by stratifying the individual patient’s iTME response.
Depletion of Neoplastic CD11b Positive Cells in Jak2V617F Mutant Mice Reduced Fibrocytes in Bone Marrow and Improved Myelofibrosis
Authors: Yoshinori Ozono, Kotaro Shide, Takuro Kameda, Ayako Kamiunten, Yuki Tahira, Masaaki Sekine, Keiichi Akizuki, Kenichi Nakamura, Hisayoshi Iwakiri, Tomonori Hidaka, Yoko Kubuki, Satoru Hasuike, Fumiyo Toyoshima, Akira Sawaguchi, Kenji Nagata, Kazuya Shimoda
Journal: Blood (2019)
Functional and Structural Adaptations of Skeletal Muscle in Long‐Term Juvenile Dermatomyositis: A Controlled Cross‐Sectional Study
Authors: Kristin Schjander Berntsen, Truls Raastad, Henriette Marstein, Eva Kirkhus, Else Merckoll, Kristoffer Toldnes Cumming, Berit Flatø, Ivar Sjaastad, Helga Sanner
Journal: Arthritis & Rheumatology (2019)

Objective To compare muscle strength and endurance of the knee extensors between patients with long‐term juvenile dermatomyositis ( DM ) and controls and between patients with active disease and those with inactive disease, and to explore associations between strength/endurance and 1) clinical parameters, 2) physical activity, and 3) humoral/structural adaptation in the skeletal muscle of patients. Methods In a cross‐sectional study (44 patients and 44 age‐ and sex‐matched controls), we tested isometric muscle strength (peak torque, in Nm) and dynamic muscle endurance (total work, in Joules) of the knee extensors, physical activity (measured by accelerometer), and serum myokine levels (by enzyme‐linked immunosorbent assay). Patients were examined with validated tools (clinical muscle tests and measures of disease activity/damage and inactive disease) and using magnetic resonance imaging of the thigh muscles, which included evaluation of the quadriceps cross‐sectional area ( CSA ). Needle biopsy samples of the vastus lateralis muscle (obtained from 12 patients ages ≥18 years) were assessed by histochemistry. Results After a mean ± SD disease duration of 21.8 ± 11.8 years, peak torque was lower in patients with juvenile DM compared to controls (mean difference 29 Nm, 95% confidence interval 13–46; P = 0.001). Similarly, total work of the knee extensors was lower in patients compared to controls (median 738J [interquartile range 565–1,155] versus 1,249J [interquartile range 815–1,665]; P &lt; 0.001). Both peak torque and total work were lower in patients with active juvenile DM compared to those with inactive disease (both P &lt; 0.019); in analyses controlled for quadriceps CSA , only total work remained lower in patients with active disease. Moreover, peak torque and total work correlated with findings from clinical muscle tests in patients with active disease (r = 0.57–0.84). Muscle biopsy results indicated that the fiber type composition was different, but capillary density was similar, between patients with active disease and those with inactive disease. Conclusion In patients with long‐term juvenile DM , both muscle strength and endurance of the knee extensors were lower when compared to matched controls, and also lower in patients with active disease compared to those with inactive disease. Our results indicate a need for more sensitive muscle tests in this clinical setting. We hypothesize that impaired muscle endurance in patients with active juvenile DM may be influenced by structural/functional adaptations of muscle tissue independent of muscle size.
Intratumor Adoptive Transfer of IL-12 mRNA Transiently Engineered Antitumor CD8+ T Cells
Authors: Iñaki Etxeberria, Elixabet Bolaños, Jose I. Quetglas, Alena Gros, Alberto Villanueva, Jara Palomero, Alfonso R. Sánchez-Paulete, Jose María Piulats, Xavier Matias-Guiu, Irene Olivera, Maria C. Ochoa, Sara Labiano, Saray Garasa, Inmaculada Rodriguez, August Vidal, Uxua Mancheño, Sandra Hervás-Stubbs, Arantza Azpilikueta, Itziar Otano, M. Angela Aznar, Miguel F. Sanmamed, Susana Inogés, Pedro Berraondo, Álvaro Teijeira, Ignacio Melero
Journal: Cancer Cell (2019)
A phase I open-label, dose escalation study to determine the maximum tolerated dose and to evaluate the safety profile of lenalidomide with every three week docetaxel in subjects with androgen independent prostate cancer
Authors: R. A. Moss, G. Shelton, J. Melia, S. G. Mohile, D. P. Petrylak
Journal: Journal of Clinical Oncology (2006)

14618 Background: Based on the known efficacy of docetaxel (D) in Androgen Independent Prostate Cancer (AIPC), and demonstrated activity of the antiangiogenesis agent thalidomide in combination with docetaxel, a Phase I trial in patients (pts) with AIPC with evidence of progression by unidimensionally measurable disease or rising serum Prostate Specific Antigen (PSA) levels after antiandrogen withdrawal was designed. The study evaluates the combination of escalating doses of D and lenalidomide (Ln), a derivative of thalidomide with immunomodulatory and antiangiogenic properties. Pts were permitted to have no more than two prior chemotherapy regimens. Methods: Pts were given D and Ln on a q3 week dose-escalation schedule. Dose Levels of D (mg/m 2 ): Level (L) 1 = 60 L2-L5 =75, given IVPB over 60 minutes in combination with prednisone 5mg po bid. Decadron 20 mg was given 12, 6 hrs and 15 minutes prior to D on D#1. Dose of Ln (mg/day) on D#1–14 of 21-day cycle: L 1 = 10 mg, L2= 10 mg, L3 = 15 mg, L4–20 mg L5 = 25 mg. Patient Characteristics: L1: N = 5. Median Age 66.2 yrs. Median PSA = 101.9 (range 5.9–164.0). Prior CT: none. Prior palliative RT: none. Patients with unidimensionally measurable disease: 4, all in lymph nodes. Patients with bone metastases: 5. Pre-treatment, 1 patient required narcotic analgesics. Results: Five L1 patients are evaluable for toxicity and response. Median number of cycles administered = 4 (range 2–5). Toxicity: There have been no Grade (G) 3 or 4 toxicities. Anti-tumor activity: Two pts (40%) have had a greater than 50% decline in serum PSA on 2 consecutive measurements at least 2 weeks apart. Of 4 pts with unidimensionally measurable disease, all have stable disease by RECIST criteria. Conclusions: At L1, D + Ln has been well tolerated in AIPC. Further dose escalation to L2 and above is planned. [Table: see text]
Dangers of selective NSAID prescribing in Quality and Outcomes Framework
Authors: Sheila Jackson
Journal: BMJ (2019)

Wallace highlights that the pace of change in healthcare is rapid and the implementation of new evidence into clinical practice is suboptimal.1

I hope that GP practices do not follow all the Quality and Outcomes Framework prescribing guidance given by NHS England in the 2019-20 General Medical Services contract as I am concerned about serious adverse consequences that may result from the …
Turning negative into positives! Exploiting ‘negative’ results in Brain–Machine Interface (BMI) research
Authors: Fabien Lotte, Camille Jeunet, Ricardo Chavarriaga, Laurent Bougrain, Dave E. Thompson, Reinhold Scherer, Rakibul Mowla, Andrea Kübler, Moritz Grosse-Wentrup, Karen Dijkstra, Natalie Dayan
Journal: Brain-Computer Interfaces (2019)

Results that do not confirm expectations are generally referred to as 'negative' results. While essential for scientific progress, they are too rarely reported in the literature – Brain–Machine Interface (BMI) research is no exception. This led us to organize a workshop on BMI negative results during the 2018 International BCI meeting. The outcomes of this workshop are reported herein. First, we demonstrate why (valid) negative results are useful, and even necessary for BMIs. These results can be used to confirm or disprove current BMI knowledge, or to refine current theories. Second, we provide concrete examples of such useful negative results, including the limits in BMI-control for complete locked-in users and predictors of motor imagery BMI performances. Finally, we suggest levers to promote the diffusion of (valid) BMI negative results, e.g. promoting hypothesis-driven research using valid statistical tools, organizing special issues dedicated to BMI negative results, or convincing institutions and editors that negative results are valuable.
Phase I/II Study of Pembrolizumab in Combination with Ublituximab (TG-1101) and Umbralisib (TGR-1202) in Patients with Relapsed/Refractory CLL
Authors: Anthony R. Mato, Colleen Dorsey, Elizabeth T Chatburn, Jessica Geoghegan, Stephen J. Schuster, Jakub Svoboda, Pamela S. Becker, Elise A. Chong, Sunita Dwivedy Nasta, Daniel J. Landsburg, Kaitlin Kennard, Eline Luning-Prak, Patricia Tsao, Mitchell E. Hughes, Michelle Purdom, Dana Paskalis, Peter Sportelli, Hari P Miskin, Michael S. Weiss, Mazyar Shadman
Journal: Blood (2017)
The efficacy of eribulin methylate for patients with taxane-resistant cutaneous angiosarcoma: Final results from a multi-center, prospective, observational study
Authors: Y. Fujisawa, K. Yoshino, T. Fujimura, Y. Yamamoto, H. Uchi, H. Hata, A. Otsuka, T. Miyagi, T. Funakoshi, S. Matsushita
Journal: Annals of Oncology (2019)
Energy, transport, and consumption in the Industrial Revolution
Authors: Joseph A. Tainter, Temis G. Taylor
Journal: Behavioral and Brain Sciences (2019)

Abstract We question Baumard's underlying assumption that humans have a propensity to innovate. Affordable transportation and energy underpinned the Industrial Revolution, making mass production/consumption possible. Although we cannot accept Baumard's thesis on the Industrial Revolution, it may help explain why complexity and innovation increase rapidly in the context of abundant energy.