tbuckley/cabot-search huggingface dataset:
Serum endotoxin, gut permeability and skeletal muscle metabolic adaptations following a short term high fat diet in humans
Authors: Suzanne M. Bowser, Ryan P. McMillan, Nabil E. Boutagy, Michael D. Tarpey, Andrew T. Smithson, Kristin L. Osterberg, Andrew P. Neilson, Brenda M. Davy, Kevin P. Davy, Matthew W. Hulver
Journal: Metabolism (2019)

BackgroundOur previous work demonstrated that a short-term high fat diet (HFD) increased fasting serum endotoxin, altered postprandial excursions of serum endotoxin, and led to metabolic and transcriptional responses in skeletal muscle in young, healthy male humans.PurposeThe purpose of the present study was to determine if a short-term high fat diet: 1) increases intestinal permeability and, in turn, fasting endotoxin concentrations and 2) decreases postprandial skeletal muscle fat oxidation.MethodsThirteen normal weight young adult males (BMI 23.1 ± 0.8 kg/m2, age 22.2 ± 0.4 years) were fed a control diet (55% carbohydrate, 30% fat, 9% of which was saturated, 15% protein) for two weeks, followed by 5 days of an isocaloric HFD (30% carbohydrate, 55% fat, 25% of which was saturated, 15% protein, isocaloric to the control diet). Intestinal permeability (via four sugar probe test) was assessed in the fasting state. Both before and after the HFD, a high fat meal challenge (HFM, 820 kcal, 25% carbohydrate, 63% fat, 26% of which was saturated, and 12% protein) was administered. After an overnight fast, blood samples were collected before and every hour for 4 h after the HFM to assess endotoxin, and other serum blood measures. Muscle biopsies were obtained from the vastus lateralis before and 4 h after the HFM in order to assess substrate oxidation (glucose, fatty acid and pyruvate) using radiolabeled techniques. Insulin sensitivity was assessed via intravenous glucose tolerance test. Intestinal permeability, blood samples and muscle biopsies were assessed in the same manner before and following the HFD.Main findingsIntestinal permeability was not affected by HFD (p > 0.05), but fasting endotoxin increased two fold following the HFD (p = 0.04). Glucose oxidation and fatty acid oxidation in skeletal muscle homogenates significantly increased after the HFM before the HFD (+97%, and +106% respectively) but declined after the HFM following 5 days of the HFD (−24% and +16% respectively). Fatty acid suppressibility of pyruvate oxidation increased significantly after the HFM (+32%) but this physiological effect was abolished following 5 days of the HFD (+7%). Insulin sensitivity did not change following the HFD.ConclusionThese findings demonstrate that in healthy young men, consuming an isocaloric HFD for 5 days increases fasting endotoxin, independent of changes in gut permeability. These changes in endotoxin are accompanied by a broad effect on skeletal muscle substrate metabolism including increases in postprandial fat oxidation. Importantly, the latter occurs independent of changes in body weight and whole-body insulin sensitivity.
Artificial intelligence for precision medicine in neurodevelopmental disorders
Authors: Mohammed Uddin, Yujiang Wang, Marc Woodbury-Smith
Journal: npj Digital Medicine (2019)

The ambition of precision medicine is to design and optimize the pathway for diagnosis, therapeutic intervention, and prognosis by using large multidimensional biological datasets that capture individual variability in genes, function and environment. This offers clinicians the opportunity to more carefully tailor early interventions- whether treatment or preventative in nature-to each individual patient. Taking advantage of high performance computer capabilities, artificial intelligence (AI) algorithms can now achieve reasonable success in predicting risk in certain cancers and cardiovascular disease from available multidimensional clinical and biological data. In contrast, less progress has been made with the neurodevelopmental disorders, which include intellectual disability (ID), autism spectrum disorder (ASD), epilepsy and broader neurodevelopmental disorders. Much hope is pinned on the opportunity to quantify risk from patterns of genomic variation, including the functional characterization of genes and variants, but this ambition is confounded by phenotypic and etiologic heterogeneity, along with the rare and variable penetrant nature of the underlying risk variants identified so far. Structural and functional brain imaging and neuropsychological and neurophysiological markers may provide further dimensionality, but often require more development to achieve sensitivity for diagnosis. Herein, therefore, lies a precision medicine conundrum: can artificial intelligence offer a breakthrough in predicting risks and prognosis for neurodevelopmental disorders? In this review we will examine these complexities, and consider some of the strategies whereby artificial intelligence may overcome them.
Skin barrier damage after exposure to paraphenylenediamine
Authors: Sanne S. Meisser, Can Altunbulakli, Josefine Bandier, Morten S. Opstrup, Francesc Castro-Giner, Mübeccel Akdis, Charlotte M. Bonefeld, Jeanne D. Johansen, Cezmi A. Akdis
Journal: Journal of Allergy and Clinical Immunology (2019)
Solid-pseudopapillary tumor of the pancreas and pancreatoblastoma in children: Experience over 18 years at a Pediatric Oncology Center
Authors: M. Rizzatti, E. Gatti, S. R. Brandalise, A. G. Oliveira Filho, I. A. Cardinalli, S. D. Aguiar
Journal: Journal of Clinical Oncology (2006)

9062 Background: Malignant pancreatic tumor is a rare disease in the pediatric population. Guidelines for treatment, including management in advanced disease are controversial until this moment (REBHANDL, 2001). Regarding to the pathology findings, pancreatoblastoma and solid-pseudopapillary tumor of the pancreas (Frantz’s tumor) are the more frequent pancreatic tumors in childhood. The aim of this study was a retrospective analysis of all malignant pancreatic tumors diagnosed at Boldrini’s Children Cancer Center during a period of 18 years. Methods: A retrospective analysis of eight cases of malignant pancreatic tumors, admitted at the Boldrini’s Children Cancer Center, from January 1987 to April 2005. All the data concerning age, sex, clinical presentation, stage, treatment and follow-up were collected. Results: The patient’s population refers to 8 children. There were 4 boys and 4 girls. Age ranged from 1 month to 15 years old (median age of 14 years). Main symptom was the increase of abdominal volume. None of them had metastatic disease at diagnosis. Regarding to pathology, 4 patients had pancreatoblastoma and 4 Frantz’s tumor. One patient (who had pancreatoblastoma) received chemotherapy before surgery, with a partial response, and then had a complete tumor ressection. All others (7 patients) had complete surgery as first treatment. Only one patient with Frantz’s tumor had pancreatic injury during tumor ressection and is now receiving enzimatic reposition. All the patients are alive, free of disease, from 6 months to 11 years (median follow-up of 2 years). Table I . Conclusions: Total pancreatectomy is the most important treatment in pancreatoblastoma and Frantz’s tumor. Neoadjuvant chemotherapy may be an important tool in unresectable tumors, increasing the disease-free survival. [Table: see text] No significant financial relationships to disclose.
Oncogene-Independent Adaptation of Pre-B Cell Receptor Signaling Confers Drug Resistance and Signaling Plasticity in Ph-like ALL
Authors: Christian Hurtz, Gerald Wertheim, Joseph Patrick Loftus, Daniel Blumenthal, Anne Lehman, Yong Li, Bryan Manning, Katherine D Cummins, Janis K Burkhardt, Alexander E. Perl, Martin Carroll, Sarah K. Tasian
Journal: Blood (2019)
Impact of genomic alterations and HPV genotypes on clinical outcomes of Japanese patients with locally advanced cervical cancer
Authors: I. Kuno, D. Takayanagi, H. Yoshida, S. Hirose, N. Murakami, M. Uno, M. Ishikawa, M. Matsuda, Y. Asami, Y. Shimada, K. Okuma, T. Kohno, J. Itami, K. Shiraishi, T. Kato
Journal: Annals of Oncology (2019)
Fred W. Whitehouse, MD, MACP (1926–2019)
Authors: George Grunberger
Journal: Diabetes Care (2019)

First and last of my vivid memories of Fred Whitehouse are actually tied to Davida Kruger. Shortly after I moved to Detroit in 1986 to establish a comprehensive diabetes center at Wayne State University and the Detroit Medical Center I made an appointment to see Fred to pay him homage as the giant of diabetology. Upon my entrance he stopped my compliments and said, with his usual dry humor, “Oh, I don’t really do anything here. My job is just to hold the doors open so Davida does not run into closed ones….” More sadly, it was on 1 March 2019, while flying to Houston for a meeting, when Davida, who happened to sit next to me on the plane, received the call about Fred’s passing. She was clearly shaken by that awful news. Ironically, the night before, at the meeting of the Endocrine Club of the Michigan chapter of the American Association of Clinical Endocrinologists (AACE), the past officers of AACE took a picture together to deliver it to Fred upon learning that he was in a local hospice.

Another classic “Fred” recollection: We were caught in the epic snowstorm of 2003 at the Washington, DC, Mandarin Oriental Hotel (where we were preparing educational efforts for the anticipated approval of insulin glulisine) and the nation’s capital was shut down. All airports were closed, our flights canceled, and streets became impassable with the huge amount of snow. Fred approached me and said, “Let’s go and see if the Freer Art Gallery is open.” And so we went out into the blizzard, trudging the half mile through more than a foot of snow, the only crazy ones out in the street. I had a hard time keeping up with his long strides, but we made it and were the only people …
Single-Cell Gene Expression Analyses Reveal Distinct Self-Renewing and Proliferating Subsets in the Leukemia Stem Cell Compartment in Acute Myeloid Leukemia
Authors: Karen Sachs, Aaron L. Sarver, Klara E. Noble-Orcutt, Rebecca S. LaRue, Marie Lue Antony, Daniel Chang, Yoonkyu Lee, Connor M. Navis, Alexandria L. Hillesheim, Ian R. Nykaza, Ngoc A. Ha, Conner J. Hansen, Fatma K. Karadag, Rachel J. Bergerson, Michael R. Verneris, Matthew M. Meredith, Matthew L. Schomaker, Michael A. Linden, Chad L. Myers, David A. Largaespada, Zohar Sachs
Journal: Cancer Research (2019)

Standard chemotherapy for acute myeloid leukemia (AML) targets proliferative cells and efficiently induces complete remission; however, many patients relapse and die of their disease. Relapse is caused by leukemia stem cells (LSC), the cells with self-renewal capacity. Self-renewal and proliferation are separate functions in normal hematopoietic stem cells (HSC) in steady-state conditions. If these functions are also separate functions in LSCs, then antiproliferative therapies may fail to target self-renewal, allowing for relapse. We investigated whether proliferation and self-renewal are separate functions in LSCs as they often are in HSCs. Distinct transcriptional profiles within LSCs of
Co-localized delivery of nanomedicine and nanovaccine augments the postoperative cancer immunotherapy by amplifying T-cell responses
Authors: Xiang Liu, Zujian Feng, Changrong Wang, Qi Su, Huijuan Song, Chuangnian Zhang, Pingsheng Huang, Xing-Jie Liang, Anjie Dong, Deling Kong, Weiwei Wang
Journal: Biomaterials (2019)
Primary Prevention of Strokes in Nigerian Children with Sickle Cell Disease (SPIN Trial): Final Results
Authors: Najibah Aliyu Galadanci, Shehu Umar Abdullahi, Shehi Abubakar, Aisha Amal Galadanci, Halima Bello-Manga, Musa Tabari, Binta Jibir, Lori Jordan, Adetola A. Kassim, Muktar Aliyu, Michael R. DeBaun
Journal: Blood (2019)
Nanoparticles for the Treatment of Oral Biofilms: Current State, Mechanisms, Influencing Factors, and Prospects
Authors: Chen Hu, Lin‐Lin Wang, Yu‐Qing Lin, Hui‐Min Liang, Shan‐Yu Zhou, Fen Zheng, Xiao‐Li Feng, Yong‐Yu Rui, Long‐Quan Shao
Journal: Advanced Healthcare Materials (2019)

Due to their excellent size, designability, and outstanding targeted antibacterial effects, nanoparticles have become a potential option for controlling oral biofilm-related infections. However, the formation of an oral biofilm is a dynamic process, and factors affecting the performance of antibiofilm treatments are complex. As such, when examining the existing literature on the antibiofilm effects of nanoparticles, attention should be paid to the specific mechanisms of action at different stages of oral biofilm formation, as well as relevant influencing factors, in order to achieve an objective and comprehensive evaluation. This review is intended to detail the antibacterial mechanisms of nanoparticles during the four stages of the formation of oral biofilms: 1) acquired film formation; 2) bacterial adhesion; 3) early biofilm development; and 4) biofilm maturation. In addition, factors influencing the antibiofilm properties of nanoparticles are summarized from the aspects of nanoparticles themselves, biofilm models, and host factors. The limitations of current research and possible trends for future research are also discussed. In summary, nanoparticles are a promising antioral biofilm strategy. It is hoped that this review can serve as a reference and inspire ideas for further research on the application of nanoparticles for effectively targeting and treating oral biofilms.
Patient perceptions of treatment benefit in advanced cancer.
Authors: Rushad Patell, David Johnson Einstein, Jennifer Halleck, Mary K. Buss
Journal: Journal of Clinical Oncology (2019)

e23163 Background: Informed consent assumes accurate perceptions of potential benefits and risks of treatment, yet many patients receiving palliative cancer therapies misperceive the likelihood of cure. Our study aims to further explore patient perceptions of benefits and risks of palliative treatments and to examine this in the era of novel therapeutics. Methods: We surveyed patients with advanced solid cancers and their oncologists regarding benefits/risks of palliative therapies. We serially assessed patients’ perceptions of likelihood of tumor response, survival benefit, symptom palliation and side effects, as well as information-seeking behavior pre-treatment and decisional regret at the end of treatment. We also compared patients’ perceptions of benefits/risks to that of their oncologists. Results: Across four disease groups, 52 patients have enrolled (target accrual: 120). Median age is 64 years (range 20-84), 58% are male, and 60% had prior treatment. Treatments included chemotherapy (42%), targeted therapy (31%), and immunotherapy (27%). Misperceptions (patient-assessed likelihood minus oncologist-assessed likelihood) at the beginning of treatment across different domains are shown in the table. Conclusions: Compared with their oncologists, patients overestimate not only curability but also chance of tumor response, symptom palliation, and survival benefit, yet they accurately perceive chance of toxicity. Thus, efforts at improving communication should focus on the chances of treatment benefit and multiple types of benefits rather than treatment risks. In future analyses after full accrual, we will assess differences between domains, internal consistency of misperceptions, change in misperceptions over time on treatment, decisional regret at end of treatment, and association of misperceptions with information-seeking behavior and sources of education. [Table: see text]
Venetoclax Added to Ibrutinib in High-Risk CLL Achieves a High Rate of Undetectable Minimal Residual Disease. [RTS1]
Authors: Philip A. Thompson, Michael J Keating, Nitin Jain, Alessandra Ferrajoli, Tapan M. Kadia, Prithviraj Bose, William G. Wierda
Journal: Blood (2019)
DT2216, a BCL-XL Proteolysis Targeting Chimera (PROTAC), Is a Potent Anti T-Cell Lymphoma Agent That Does Not Induce Significant Thrombocytopenia
Authors: Yonghan He, Raphael Koch, Vivekananda Budamagunta, Dongwen Lv, Sajid Khan, Xuan Zhang, Janet S Wiegand, Guangrong Zheng, David M. Weinstock, Daohong Zhou
Journal: Blood (2019)
Clinical Validity of<i>DSM-5</i>Attenuated Psychosis Syndrome
Authors: Gonzalo Salazar de Pablo, Ana Catalan, Paolo Fusar-Poli
Journal: JAMA Psychiatry (2019)

Since the release of the DSM-5 diagnosis of attenuated psychosis syndrome (DSM-5-APS) in 2013, several research studies have investigated its clinical validity. Although critical and narrative reviews have reviewed these progresses, no systematic review has comprehensively summarized the available evidence regarding the clinical validity of DSM-5-APS.To provide current evidence on the clinical validity of DSM-5-APS, focusing on recent advances in diagnosis, prognosis, and treatment.A multistep literature search using the Web of Science database, Cochrane Central Register of Reviews, Ovid/PsychINFO, conference proceedings, and trial registries from database inception to June 16, 2019, was conducted following PRISMA and MOOSE guidelines and PROSPERO protocol. Studies with original data investigating individuals diagnosed using DSM-5-APS or meeting comparable criteria were included. The results of the systematic review were summarized in tables and narratively synthesized against established evidence-based antecedent, concurrent, and prognostic validators. A quantitative meta-analysis was conducted to explore the cumulative risk of psychosis onset at 6, 12, 24, and 36 months in individuals diagnosed using DSM-5-APS criteria.The systematic review included 56 articles, which reported on 124 validators, including 15 antecedent, 55 concurrent, and 54 prognostic validators. The epidemiological prevalence of the general non-help-seeking young population meeting DSM-5-APS criteria was 0.3%; the prevalence of individuals meeting DSM-5-APS criteria was variable in clinical samples. The interrater reliability for DSM-5-APS criteria was comparable with that of other DSM-5 mental disorders and can be optimized by the use of specific psychometric instruments. DSM-5-APS criteria were associated with frequent depressive comorbid disorders, distress, suicidality, and functional impairment. The meta-analysis included 23 prospective cohort studies, including 2376 individuals. The meta-analytical risk of psychosis onset was 11% at 6 months, 15% at 12 months, 20% at 24 months, and 23% at 36 months. Research into predisposing and precipitating epidemiological factors, neurobiological correlates, and effective treatments for DSM-5-APS criteria has been limited.Over recent years, DSM-5-APS criteria have received substantial concurrent and prognostic validation, mostly driven by research into the clinical high-risk state for psychosis. Precipitating and predisposing factors, neurobiological correlates, and effective treatments are undetermined to date.
Keynote-407 China Extension study: Pembrolizumab (pembro) plus chemotherapy in Chinese patients with metastatic squamous NSCLC
Authors: Y. Cheng, L. Zhang, J. Hu, D. Wang, C. Hu, J. Zhou, L. Wu, L. Cao, J. Liu, H. Zhang, H. Sun, Z. Wang, H. Gao, J. Ge, H. Wang, Y. Tian, B. Piperdi, L. Paz-Ares
Journal: Annals of Oncology (2019)
<i>Listeria</i> Susceptibility in Patients With Multiple Myeloma Receiving Daratumumab-Based Therapy
Authors: Sahar Khan, Alon Vaisman, Susy S. Hota, Sabrina Bennett, Suzanne Trudel, Donna Reece, Rodger E. Tiedemann
Journal: JAMA Oncology (2019)

reduce treatmentassociated Listeria risk.
FDG PET Findings of Hyperprogression During Immunotherapy in a Patient With Hepatocellular Carcinoma
Authors: Jingnan Wang, Xuezhu Wang, Xu Yang, Haitao Zhao, Li Huo
Journal: Clinical Nuclear Medicine (2019)

Although immunotherapy is a successful approach in oncology, it might be detrimental to some patients. In the condition of hyperprogression, patients experience accelerated progression after immunotherapy, resulting in a worse outcome. Hyperprogression may be difficult to be identified in the early stage. Once the diagnosis is confirmed in the follow-up evaluation, the immunotherapy should be stopped immediately. In this case, we report a hyperprogression patient during combined immunotherapy toward metastatic hepatocellular carcinoma observed by serial F-FDG PET.
Cadmium exposure enhances organic cation transporter 2 trafficking to the kidney membrane and exacerbates cisplatin nephrotoxicity
Authors: Hong Yang, Jie Tang, Dong Guo, Qingqing Zhao, Jiagen Wen, Yanjuan Zhang, Obinna N. Obianom, Shiwei Zhou, Wei Zhang, Yan Shu
Journal: Kidney International (2019)
Second-line treatment after first-line vinorelbine in advanced platinum unfit NSCLC patients: An exploratory analysis of randomized Tempo-Lung trial
Authors: A. Camerini, A. Morabito, A. Montanino, R. Bernabe Caro, F. Grossi, R. Ramlau, T.-E. Ciuleanu, G.L. Ceresoli, G. Pasello, F. de Marinis, J. Bosch-Barrera, P. Landreau, S. Gautier, C. Ta Thanh Minh, D. Kowalski
Journal: Annals of Oncology (2019)
Frequency of MRI changes suggestive of axial spondyloarthritis in the axial skeleton in a large population-based cohort of individuals aged &lt;45 years
Authors: Xenofon Baraliakos, Adrian Richter, Daniel Feldmann, Anne Ott, Robin Buelow, Carsten O Schmidt, Juergen Braun
Journal: Annals of the Rheumatic Diseases (2019)

To investigate the frequency of bone marrow oedema (BME) and fatty lesions (FL) suggestive of axial spondyloarthritis (axSpA) on MRI of the spine and sacroiliac joints (SIJ) in a general population sample.As part of a community-based cohort project (Study of Health in Pomerania), volunteers underwent spinal (sagittal T1/T2) and SIJ (semicoronal short tau inversion recovery) MRI examinations. Two calibrated readers evaluated the images to detect BME in SIJ and vertebral corners (VC) and FL in VC suggestive of axSpA using Assessment of SpondyloArthritis international Society definitions.MRIs of 793 volunteers (49.4% males, mean age 37.3±6.3 years, 8.4% human leucocyte antigen-B27+) aged <45 years were evaluated. SIJ BME was seen in 136 (17.2%), VC BME in 218 (27.5%) and FL in 645 (81.4%) volunteers. SIJ BME in ≥1, ≥3 and ≥5 SIJ quadrants was seen in 136 (17.2%), 7 (0.9%) and 1 (0.1%) volunteers, respectively. In VC, BME≥1, ≥3 and ≥5 lesions were seen in 218 (27.5%), 38 (4.8%) and 6 (0.8%) volunteers, respectively, while FL≥1, ≥3 and ≥5 were seen in 645 (81.3%), 351 (44.3%) and 185 (23.3%) volunteers, respectively. Logistic regression analysis showed that BME and FL in VC were related to increasing age: OR 1.33, 95% CI 1.02 to 1.72, and OR 1.73, 95% CI 1.32 to 2.27, per decade increase, respectively.In this large population-based study, a high frequency of inflammatory and fatty MRI lesions suggestive of axSpA was found, especially in the spine. This indicates a limited value of such MRI findings for diagnosis and classification of axSpA. The increasing frequency with age suggests that mechanical factors could play a role.