tbuckley/cabot-search huggingface dataset:
失去亲人的 CTCL 患者的家庭照护者经历
Authors: D. Orlowska, L.E. Selman, T. Beynon, E. Radcliffe, S. Whittaker, F. Child, R. Harding
Journal: British Journal of Dermatology (2018)

皮肤 T‐细胞淋巴瘤 (CTCL) 是一种罕见的皮肤癌类型。皮肤可能会发生肿瘤或溃疡。有时这些肿瘤或溃疡可能会覆盖相当大的区域并让人感到发痒或不舒服。在更晚期的疾病中, 内部身体部位可能会受到影响。每年只有少数人得到诊断(每百万人中有 8 人), 因此大多数全科医生 (GP) 都不会遇到患有这种疾病的人。这项来自英国的研究旨在了解因此疾病死亡者的家人或亲密朋友的经历(并非所有患有这种疾病的人都死于此疾病)。11 例死亡的 CTCL 患者的亲属接受了访谈, 访谈是在患者死亡后 4 个月或更长时间以后进行的。对他们所说的主题进行了叙述。家庭成员生动地描述了疾病如何改变了他们亲属的外表。他们谈到了照顾皮肤受损的人是多么困难。他们描述了他们在医院和家中照顾亲人时必须做的许多不同的事情。一些患者经常进出医院。有的照护者期望他们每次都能回家,所以当他们的亲戚去世时他们感到毫无准备。一些照护者描述, 看到他们的亲属去世前疾病对其造成的影响是多么令人沮丧。作者认为,应该将家庭照护者视为照顾病人的护理团队的一部分。他们建议, 在每位患者患病期间, 应考虑照护者对实际和情感支持以及信息的需求。在亲属去世后也应提供对照护者的支持。
Abstract P176: Moderate Physical Activity and Sleep Duration as Predictors of Cognitive Function in Older Adults With Hypertension: NHANES 2011-2014
Authors: Nicole Hoffmann, Megan E Petrov
Journal: Circulation (2018)

Introduction: Hypertension is associated with increased risk for cognitive decline. Lifestyle behaviors such as moderate physical activity (MPA) and adequate sleep duration may mitigate this decline, though limited research exists. The aim of the study was to examine the joint association of MPA and sleep duration on cognitive function by hypertension status. Methods: Adults (n=2976, ≥60yrs) from the 2011-2014 National Health and Nutrition Examination Survey (NHANES) were assessed for their habitual sleep duration (&lt;7, 7-8.9, ≥9hr) , self-reported participation in regular MPA (yes/no), reported physician-diagnosed hypertension (yes/no), and cognitive function (Digit Symbol Substitution Test [DSST]; Animal Fluency test). Weighted linear regression analyses were conducted to assess joint association of sleep duration and MPA on cognitive function, and test the modifying effect of hypertension status (alpha level set at 0.1) after adjustment for demographics. Results: See Table. There were significant main effects for combined MPA and sleep duration on DSST (Wald F (5,28)=5.33, p =.001) and Animal Fluency (Wald F (5,28)=2.58, p =.05). Participants who did not engage in MPA regardless of sleep duration had significantly worse cognitive function compared to participants who engaged in MPA and obtained 7-8.9hr sleep. There was a significant interaction between MPA-sleep duration groups and hypertension status on DSST (Wald F (5,28)=2.42, p =.06), but not on Animal Fluency. Stratified analyses indicated among individuals with hypertension the buffering effect of MPA regardless of sleep duration was maintained, but not for individuals without hypertension. Conclusions: In a sample of adults, regular MPA predicted better cognitive outcomes regardless of sleep duration. Among individuals with hypertension regular MPA regardless of sleep duration was significantly associated with better executive function, but no such association was found among individuals without hypertension.
A severe case of neuro-Sjögren’s syndrome induced by pembrolizumab
Authors: Jaqueline Ghosn, Alex Vicino, Olivier Michielin, George Coukos, Thierry Kuntzer, Michel Obeid
Journal: Journal for ImmunoTherapy of Cancer (2018)

<h3>Background</h3> The prevalence of connective tissue disease (CTD) induced by immune checkpoint inhibitors (CPIs) in the absence of pre-existing autoimmunity is unknown. <h3>Case presentation</h3> We report the case of a melanoma patient treated for 8&nbsp;months with pembrolizumab who developed a subacute ataxic sensory neuronopathy (SNN), including a right trigeminal neuropathy. Salivary gland biopsy showed inflammatory changes suggestive of Sjögren's syndrome, while brain MRI revealed enhancement of the right trigeminal ganglia. A high level of protein and pleocytosis was found in the cerebrospinal fluid, with negative cultures. Nerve conduction studies revealed the absence of sensory nerve action potentials in the upper and lower limbs and reduced motor responses in the upper limbs, fulfilling criteria for SNN. Blood tests revealed an important inflammatory syndrome, hemolytic anemia, elevation of total IgG levels and the presence of ANA autoantibodies specific to anti-SSA (52 and 60 kd). All these elements were absent before the initiation of the treatment with pembrolizumab. Initially, there was a clinical response following intravenous frontline methylprednisone, but the subacute relapse required the introduction of second-line treatment with intravenous immunoglobulins and then rituximab, which led to a quick clinical improvement. <h3>Conclusions</h3> Herein, we describe the first case of a patient who developed a typical SNN as a complication of severe neuro-Sjögren's syndrome induced by pembrolizumab treatment.
The Big Picture: Outrunning child obesity trends
Authors: Rebecca Coombes
Journal: BMJ (2018)

Neil Hall/EPA-EFE/Shutterstock

London’s mayor, Sadiq Khan, and the Olympic champion Mo Farah took to the track with schoolchildren in east London this week to promote an anti-obesity programme that is gaining in popularity across Europe. Children from Cubitt Town Junior School are pictured taking part in the Daily Mile, a 15 minute session to get pupils walking or …
Preoperative nivolumab in patients(pts) with locally advanced colon cancer (T3 or T4): A window-of-opportunity study (NICOLE)
Authors: A. Avallone, P. Delrio, G. Nasti, A. Cassata, L. Silvestro, A. De Stefano, S. Lastoria, R. Casaretti, C. Romano, A. Ottaiano, E. Di gennaro, A. Nappi, P. Maiolino, E. Cavalcanti, A. Petrillo, F. Tatangelo, D. Giannarelli, J. Galon, P.A. Ascierto, A. Budillon
Journal: Annals of Oncology (2018)
Engaging the Uncertainties of Ebola Outbreaks: An Anthropo-Ecological Perspective
Authors: Michael O. S. Afolabi, Ikeolu O. Afolabi
Journal: The American Journal of Bioethics (2018)

Annamarie Sehovic (2017) recently observed that it is important to come to grips with the permanence of uncertainty in dealing with public health emergencies. A context of local and global signific...
First-Line Treatment of Widely Metastatic <i>BRAF</i>-Mutated Salivary Duct Carcinoma With Combined BRAF and MEK Inhibition
Authors: Victor T.G. Lin, Lisle M. Nabell, Sharon A. Spencer, William R. Carroll, Shuko Harada, Eddy S. Yang
Journal: Journal of the National Comprehensive Cancer Network (2018)

Salivary duct carcinoma (SDC) is a rare and aggressive malignancy for which limited data exist to guide treatment decisions. With the advent of advanced molecular testing and tumor genomic profiling, clinicians now have the ability to identify potential therapeutic targets in difficult-to-treat cancers such as SDC. This report presents a male patient with widely metastatic SDC found on targeted next-generation sequencing to have a BRAF p.V600E mutation. He experienced a prolonged and robust response to first-line systemic chemotherapy with dabrafenib and trametinib. During his response interval, new data emerged to justify subsequent treatment with both an immune checkpoint inhibitor and androgen blockade after his disease progressed. To our knowledge, this is the first report of frontline BRAF-directed therapy eliciting a response in metastatic SDC.
Intraoperative detection of resection margin by inhalation of ICG in lung cancer preclinical study
Authors: Y.H. Quan, C.H. Oh, D. Jung, J.-Y. Lim, B.H. Choi, J. Rho, Y. Choi, K.N. Han, J.-H. Park, H.K. Kim, Y.H. Choi
Journal: Annals of Oncology (2018)
Efficacy of metastasectomy on survival in patients with metachronous soft tissue sarcoma-metastasis: Results of a bi-centre study including 135 patients
Authors: A. Leithner, V. van Praag, F. Posch, M. Bergovec, L. Leitner, J. Friesenbichler, R. Heregger, F.-M. Smolle-Jüttner, M. Fiocco, M. van de Sande, J. Riedl, M. Pichler, A. Gerger, J. Szkandera, H. Stöger, B. Liegl-Atzwanger, M.A. Smolle
Journal: Annals of Oncology (2018)
Deletion of Macrophage Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Accelerates Atherosclerosis Regression and Increases C-C Chemokine Receptor Type 7 (CCR7) Expression in Plaque Macrophages
Authors: Paul A. Mueller, Lin Zhu, Hagai Tavori, Katherine Huynh, Ilaria Giunzioni, John M. Stafford, MacRae F. Linton, Sergio Fazio
Journal: Circulation (2018)

We previously showed that mice lacking MΦLRP1-/- (low-density lipoprotein receptor-related protein 1 in macrophages) undergo accelerated atherosclerotic plaque formation due to changes in macrophages including increased apoptosis, decreased efferocytosis, and exaggerated transition to the inflammatory M1 phenotype. Here we sought to explore the role of macrophage low-density lipoprotein receptor-related protein 1 during regression of atherosclerosis since regressing plaques are characterized by transitioning of macrophages to M2 status as inflammation resolves.Apolipoprotein E-/- mice on a high-fat diet for 12 weeks were reconstituted with bone marrow from apolipoprotein E-producing wild-type or MΦLRP1-/- mice, and then placed on a chow diet for 10 weeks (n=9 to 11 mice/group). A cohort of apolipoprotein E-/- mice reconstituted with apolipoprotein E-/- bone marrow served as baseline controls (n=9).Plaques of both wild-type and MΦLRP1-/- bone marrow recipients regressed compared with controls (11% and 22%, respectively; P<0.05), and plaques of MΦLRP1-/- recipients were 13% smaller than those of wild-type recipients ( P<0.05). Recipients of MΦLRP1-/- marrow had 36% fewer M1 macrophages ( P<0.01) and 2.5-fold more CCR7 (C-C chemokine receptor type 7)-positive macrophages in the plaque relative to wild-type mice ( P<0.01). Additionally, in vivo studies of cellular egress showed a 4.6-fold increase in 5-ethynyl-2´-deoxyuridine-labeled CCR7+ macrophages in mediastinal lymph nodes. Finally, in vivo studies of reverse cholesterol transport showed a 1.4-fold higher reverse cholesterol transport in MΦLRP1-/- recipient mice ( P<0.01).Absence of macrophage low-density lipoprotein receptor-related protein 1 unexpectedly accelerates atherosclerosis regression, enhances reverse cholesterol transport, and increases expression of the motility receptor CCR7, which drives macrophage egress from lesions.
Validation of the maximum symptom day among children with asthma
Authors: Tianshi David Wu, Matthew Perzanowski, Roger D. Peng, Robert A. Wise, Susan Balcer-Whaley, Michelle Newman, Amparito Cunningham, Wanda Phipatanakul, Elizabeth C. Matsui, Meredith C. McCormack
Journal: Journal of Allergy and Clinical Immunology (2018)
Transcription Factor Myeloid Zinc-Finger 1 Suppresses Human Gastric Carcinogenesis by Interacting with Metallothionein 2A
Authors: Shuye Lin, Xiaoyue Wang, Yuanming Pan, Rongmeng Tian, Bonan Lin, Guosheng Jiang, Keqiang Chen, Yuqi He, Lulu Zhang, Wanli Zhai, Peng Jin, Lang Yang, Guoqiang Li, Yun Wu, Jiang Hu, Wanghua Gong, Zhijie Chang, Jian-qiu Sheng, Youyong Lu, Ji Ming Wang, Jiaqiang Huang
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Metallothionein 2A (MT2A) suppresses the progression of human gastric cancer potentially through an “MT2A–NF-κB pathway” with unclear mechanisms. This study explored the role of a transcription factor, myeloid zinc-finger 1 (MZF1), in MT2A-NF-κB pathway and its clinical significance in gastric cancer. Experimental Design: MZF1 expression and function in gastric cancer were investigated in vitro and in vivo. The relationship between MZF1 and MT2A was determined by gain-of-function and loss-of-function assays in gastric cancer cells and an immortalized gastric cell line GES-1. The prognostic value of MZF1 expression in association with MT2A was evaluated using IHC in two cohorts. Results: MZF1 was epigenetically silenced in human gastric cancer cell lines and primary tumors. Overexpression of MZF1 in gastric cancer cells suppressed cell proliferation and migration, as well as the growth of xenograft tumors in nude mice. Knocking-down of MZF1 transformed GES-1 cells into a malignant phenotype characterized by increased cell growth and migration. Mechanistically, MZF1 was upregulated in both GC and GES-1 cells by MT2A ectopically expressed or induced upon treatment with a garlic-derived compound, diallyl trisulfide (DATS). MZF1 associated with MT2A was colocalized in the nuclei of GES-1 cells to target the promoter of NF-κB inhibitor alpha (NFKBIA). Clinically, MT2A and MZF1 were progressively downregulated in clinical specimens undergoing gastric malignant transformation. Downregulation of MT2A and MZF1 was significantly correlated with poorer patient prognosis. Conclusions: MT2A exerts its anti-gastric cancer effects by complexing with MZF1 to target NFKBIA. MT2A/MZF1 may serve as a valuable prognostic marker and a novel therapeutic target for human gastric cancer.
TGFβ-Activated USP27X Deubiquitinase Regulates Cell Migration and Chemoresistance via Stabilization of Snail1
Authors: Guillem Lambies, Martina Miceli, Catalina Martínez-Guillamon, Rubén Olivera-Salguero, Raúl Peña, Carolina-Paola Frías, Irene Calderón, Boyko S. Atanassov, Sharon Y. R. Dent, Joaquín Arribas, Antonio García de Herreros, Víctor M. Díaz
Journal: Cancer Research (2018)

In cancer cells, epithelial-to-mesenchymal transition (EMT) is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAF). Snail1 is short-lived in normal epithelial cells as a consequence of its coordinated and continuous ubiquitination by several F-box-specific E3 ligases, but its degradation is prevented in cancer cells and in activated fibroblasts. Here, we performed an siRNA screen and identified USP27X as a deubiquitinase that increases Snail1 stability. Expression of USP27X in breast and pancreatic cancer cell lines and tumors positively correlated with Snail1 expression levels. Accordingly, downregulation of USP27X decreased Snail1 protein in several tumor cell lines. USP27X depletion impaired Snail1-dependent cell migration and invasion and metastasis formation and increased cellular sensitivity to cisplatin. USP27X was upregulated by TGFβ during EMT and was required for TGFβ-induced expression of Snail1 and other mesenchymal markers in epithelial cells and CAF. In agreement with this, depletion of USP27X prevented TGFβ-induced EMT and fibroblast activation. Collectively, these results indicate that USP27X is an essential protein controlling Snail1 expression and function and may serve as a target for inhibition of Snail1-dependent tumoral invasion and chemoresistance. SIGNIFICANCE: These findings show that inhibition of USP27X destabilizes Snail1 to impair EMT and renders tumor cells sensitive to chemotherapy, thus opening new strategies for the inhibition of Snail1 expression and its protumoral actions.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/79/1/33/F1.large.jpg.
OVARIO: A single-arm, open-label phase II study of maintenance therapy with niraparib + bevacizumab (bev) in patients (pts) with advanced ovarian cancer (OC) after response to frontline platinum-based chemotherapy (chemo)
Authors: M. Hardesty, J.M. Hope, T. Krivak, J. Chen, M. Wainszelbaum, D. Gupta, D. Richardson
Journal: Annals of Oncology (2018)
Targeting Cancer Cells and Tumor Microenvironment in Preclinical and Clinical Models of Hodgkin Lymphoma Using the Dual PI3Kδ/γ Inhibitor RP6530
Authors: Silvia L. Locatelli, Giuseppa Careddu, Simone Serio, Francesca M. Consonni, Akihiro Maeda, Srikant Viswanadha, Swaroop Vakkalanka, Luca Castagna, Armando Santoro, Paola Allavena, Antonio Sica, Carmelo Carlo-Stella
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Tumor-associated macrophages (TAMs) and the hyperactivation of the PI3K/AKT pathway are involved in the pathogenesis of Hodgkin lymphoma and affect disease outcome. Because the δ and γ isoforms of PI3K are overexpressed in Hodgkin/Reed–Sternberg (HRS) cells and the tumor microenvironment (TME), we propose that the PI3Kδ/γ inhibitor RP6530 might affect both HRS cells and TME, ultimately leading to an enhanced antitumor response. Experimental Design: Hodgkin lymphoma cell lines (L-540, KM-H2, and L-428) and primary human macrophages were used to investigate the activity of RP6530 in vitro and in vivo in Hodgkin lymphoma cell line xenografts. Results: In vitro, RP6530 besides killing and inhibiting the proliferation of Hodgkin lymphoma cells, downregulated lactic acid metabolism, switching the activation of macrophages from an immunosuppressive M2-like phenotype to a more inflammatory M1-like state. By RNA sequencing, we define tumor glycolysis as a specific PI3Kδ/γ-dependent pathway implicated in the metabolic reprogramming of cancer cells. We identify the metabolic regulator pyruvate kinase M2 as the main mediator of tumor-induced immunosuppressive phenotype of macrophages. Furthermore, we show in human tumor xenografts that RP6530 repolarizes TAMs into proinflammatory macrophages and inhibits tumor vasculature, leading to tumor regression. Interestingly, patients with Hodgkin lymphoma experiencing objective responses (complete response and partial response) in a phase I trial using RP6530 showed a significant inhibition of circulating myeloid-derived suppressor cells and an average mean reduction in serum thymus and activation-regulated chemokine levels of 40% (range, 4%–76%). Conclusions: Our results support PI3Kδ/γ inhibition as a novel therapeutic strategy that targets both malignant cells and the TME to treat patients with Hodgkin lymphoma.
Is 30 Newtons of Prevention Worth a Pound of a Cure?—Cricoid Pressure
Authors: Samuel A. Tisherman, Megan G. Anders, Samuel M. Galvagno
Journal: JAMA Surgery (2018)

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Inhibition of monoacylglycerol lipase, an anti-inflammatory and antifibrogenic strategy in the liver
Authors: Aida Habib, Dina Chokr, JingHong Wan, Pushpa Hegde, Morgane Mabire, Matthieu Siebert, Lara Ribeiro-Parenti, Maude Le Gall, Philippe Lettéron, Nathalie Pilard, Abdellah Mansouri, Arthur Brouillet, Matteo Tardelli, Emmanuel Weiss, Pauline Le Faouder, Hervé Guillou, Benjamin F Cravatt, Richard Moreau, Michael Trauner, Sophie Lotersztajn
Journal: Gut (2018)

Objective Sustained inflammation originating from macrophages is a driving force of fibrosis progression and resolution. Monoacylglycerol lipase (MAGL) is the rate-limiting enzyme in the degradation of monoacylglycerols. It is a proinflammatory enzyme that metabolises 2-arachidonoylglycerol, an endocannabinoid receptor ligand, into arachidonic acid. Here, we investigated the impact of MAGL on inflammation and fibrosis during chronic liver injury. Design C57BL/6J mice and mice with global invalidation of MAGL (MAGL -/- ), or myeloid-specific deletion of either MAGL (MAGL Mye-/- ), ATG5 (ATG Mye-/- ) or CB2 (CB2 Mye-/- ), were used. Fibrosis was induced by repeated carbon tetrachloride (CCl 4 ) injections or bile duct ligation (BDL). Studies were performed on peritoneal or bone marrow-derived macrophages and Kupffer cells. Results MAGL -/- or MAGL Mye-/- mice exposed to CCl 4 or subjected to BDL were more resistant to inflammation and fibrosis than wild-type counterparts. Therapeutic intervention with MJN110, an MAGL inhibitor, reduced hepatic macrophage number and inflammatory gene expression and slowed down fibrosis progression. MAGL inhibitors also accelerated fibrosis regression and increased Ly-6C low macrophage number. Antifibrogenic effects exclusively relied on MAGL inhibition in macrophages, since MJN110 treatment of MAGL Mye-/- BDL mice did not further decrease liver fibrosis. Cultured macrophages exposed to MJN110 or from MAGL Mye-/- mice displayed reduced cytokine secretion. These effects were independent of the cannabinoid receptor 2, as they were preserved in CB2 Mye-/- mice. They relied on macrophage autophagy, since anti-inflammatory and antifibrogenic effects of MJN110 were lost in ATG5 Mye-/- BDL mice, and were associated with increased autophagic flux and autophagosome biosynthesis in macrophages when MAGL was pharmacologically or genetically inhibited. Conclusion MAGL is an immunometabolic target in the liver. MAGL inhibitors may show promising antifibrogenic effects during chronic liver injury.
Health concerns of veterans with high-level lower extremity amputations
Authors: Elahe Faraji, Mostafa Allami, Nafiseh Feizollahi, Amir Karimi, Amir Yavari, Mohammadreza Soroush, Majid Moudi
Journal: Military Medical Research (2018)

The aim of the study was to identify health concerns of veterans with high-level lower extremity amputations.Through a cross-sectional study, general practitioners, an orthopedic specialist, psychologists, psychiatrists, physiotherapist and prosthetists examined 100 veterans using a short-form health-related quality of life questionnaire (SF-36) that assessed their ability to perform activities of daily living (ADL), instrumental activities of daily living (IADL) and life satisfaction (SWLS) after hip disarticulation or hemi-pelvectomy amputations. The assessment tool was designed to gather statistically useful information about their health needs.The means of the Physical Component Summary (PCS), Mental Component Summary (MCS), SWLS, ADL and IADL were 48.58 ± 29.6, 33.33 ± 22.0, 19.30 ± 7.7, 48.10 ± 10.5 and 5.08 ± 1.8, respectively. Somatization, depression, and anxiety were the most prevalent disorders; among the veterans who were visited by psychiatrists, 11.6% had a history of hospitalization in a psychiatry section, and 53.2% had a psychiatric visit. Regardless of their injury in battle, 34% of veterans were hospitalized. Hearing problems were common, and about four-fifths of the participants suffered from at least one orthopedic condition. Neuroma (49%) was the most common stump-related complication during orthopedic evaluations, though the prevalence of phantom pain was 81% during the pain assessment. A total of 87% of the participants had a history of wearing a prosthesis, but only 29% wore a prosthesis at the time of the present study. The Canadian-type of prosthesis was uncomfortable and not useful (27%) and excessively heavy (10%) according to the amputees.Understanding veterans' characteristics and special needs are important to make sure that enough facilities and services are afforded to them. These findings emphasize the importance of paying close attention to different dimensions of health in veterans and can help health providers identify health needs and make regular assessments.
GW29-e0122 Low-Intensity Ultrasound-Induced Anti-inflammatory Effects Are Mediated by Several New Mechanisms Including Gene Induction, Immunosuppressor Cell Promotion, and Enhancement of Exosome Biogenesis and Docking
Authors: Qian Yang, Liwen Liu, Shuping Ge, Hong Wang, Xiaofeng Yang, Xiaodong Zhou
Journal: Journal of the American College of Cardiology (2018)
P3.09-09 “Prevalence of Epidermal Growth Factor Receptor Mutation in Non-Small Cell Carcinoma Lungs at a Cancer Center in Nepal”
Authors: B. Gurung, R. Shrestha, S. Shrestha, M. Singh, A. Koirala, S. Chataut, S. Tuladhar, S. Shrestha, B. Ghimire, M. Shrestha, M. Gautam, H. Dhakal
Journal: Journal of Thoracic Oncology (2018)