tbuckley/cabot-search huggingface dataset:
Brown fat activation mitigates alcohol-induced liver steatosis and injury in mice
Authors: Hong Shen, Lin Jiang, Jiandie D. Lin, M. Bishr Omary, Liangyou Rui
Journal: Journal of Clinical Investigation (2019)

Chronic alcohol consumption causes liver injury, inflammation, and fibrosis, thereby increasing morbidity and mortality. Paradoxically, modest drinking is believed to confer metabolic improvement, but the underlying mechanism remains elusive. Here, we have identified a hepatoprotective brain/brown adipose tissue (BAT)/liver axis. Alcohol consumption or direct alcohol administration into the brain stimulated hypothalamic neural circuits and sympathetic nerves innervating BAT and dramatically increased BAT uncoupling protein 1 (Ucp1) expression and activity in a BAT-sympathetic nerve-dependent manner. BAT and beige fat oxidized fatty acids to fuel Ucp1-mediated thermogenesis, thereby inhibiting lipid trafficking into the liver. BAT also secreted several adipokines, including adiponectin, which suppressed hepatocyte injury and death. Genetic deletion of Ucp1 profoundly augmented alcohol-induced liver steatosis, injury, inflammation, and fibrosis in male and female mice. Conversely, activation of BAT and beige fat through cold exposure suppressed alcoholic liver disease development. Our results unravel an unrecognized brain alcohol-sensing/sympathetic nerve/BAT/liver axis that counteracts liver steatosis and injury.
Partha Kar: Dieting and body shaming
Authors: Partha Kar
Journal: BMJ (2019)

Give this a try. Walk up to someone you love or like. Pick someone who, in your eyes, looks “overweight.” And then say, “Shame on you for not eating the right things. You will die early, and you deserve to.”

Many things would stop you doing this: most importantly, common decency, but also recognition of the importance of not judging others against your own situation, economic status, or cultural background. And yet body shaming is treated by some sectors of society as if it were perfectly normal and even acceptable. Social media show that healthcare professionals are not exempt either, with quick judgments about others’ bodies not …
Hyperprogression—Immunotherapy-Related Phenomenon vs Intrinsic Natural History of Cancer
Authors: Alexander T. Pearson, Randy F. Sweis
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
BPI19-009: Late Administration of Luteinizing Hormone-Releasing Hormone (LHRH) Agonists and Testosterone Levels &gt;50NG/DL in Prostate Cancer
Authors: Stuart Atkinson, Raoul S. Concepcion, John A. McLane, Deborah Boldt-Houle, Eleni Efstathiou
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: Achieving and maintaining effective testosterone (T) suppression is key to treatment of advanced prostate cancer (PCa), for which LHRH agonists are standard of care. Increasing evidence suggests maintaining very low T levels to &lt;20 ng/dL with androgen deprivation therapy (ADT) is desirable and correlates with disease-specific survival in patients with advanced PCa. Consistent drug delivery is important in providing continuous T suppression throughout the course of treatment without T rising above castrate level (T breakthrough). However, T breakthrough may occur between administrations, especially if a subsequent dose is delayed. Contributing factors to late administrations may include scheduling challenges, shortage of available appointments, and increasing number of patients. While FDA approvals for ADT drugs are based on a 28-day month, insurers may mandate full calendar months between doses for reimbursement. This study explored timeliness of subsequent LHRH agonist administrations and its relationship with T breakthrough. Methods: A retrospective review of electronic medical records from January 1, 2007 and June 30, 2016 of 85,030 LHRH agonist administrations for PCa treatment was conducted to evaluate the percentage of late subsequent dosing and impact on frequencies of T breakthrough, defined as T&gt;50 ng/dL. Late administrations were defined as those on or after day 33, 98, 129, and 195 for 1, 3, 4, and 6 month formulations, respectively. Results: 26.9% of all subsequent LHRH agonist administrations were late: 14.4% were ≤1 week late, 3.1% were between 1–2 weeks late, and 9.4% were &gt;2 weeks late. While only 4% of T values exceeded 50 ng/dL when doses were administered early/on time, 21% of T values exceeded 50 ng/dL when administrations were late. Conclusions: Over a quarter of subsequent administrations were defined as late, leading to &gt;20% incidence of T values exceeding 50 ng/dL. Considering the clinical benefits of maintaining effective T suppression throughout a course of ADT, clinicians should administer treatments within approved dosing instructions, routinely monitor T levels, and consider prescribing treatments with proven efficacy through the dosing interval to maintain T at castrate levels.
Abstract MP66: Lipidomics Profiling and Progression of Carotid Artery Atherosclerosis in HIV-infected Individuals
Authors: Jin Choul Chai, Simin Hua, Clary B Clish, Amy A Deik, Tao Wang, David B Hanna, Sabina A Haberlen, Sanjiv J Shah, Wendy S Post, Howard N Hodis, Alan L Landay, Kathryn Anastos, Robert C Kaplan, Qibin Qi
Journal: Circulation (2018)

Background: Lipid metabolism disruption and excess cardiovascular disease (CVD) risk have been associated with HIV infection, yet plasma lipidomics profile and its relationship with CVD risk has been rarely examined in HIV-infected individuals. Methods: Using liquid chromatography tandem mass spectrometry, 211 plasma lipid species from 13 classes were profiled in 737 women and men aged 35-55 years (520 HIV+, 217 HIV-) from the Women’s Interagency HIV Study and the Multicenter AIDS Cohort Study. Repeated B-mode carotid artery ultrasound imaging was obtained in 2004-2013. Poisson regression and network analysis were used to examine associations of baseline lipids with incident carotid plaque over 7 years (112 cases, 90 HIV+ and 22 HIV-). Results: Adjusted for demographic and behavioral factors, 120 individual species from 11 lipid classes showed significant associations with incident carotid plaque (all P &lt;0.05 FDR adjusted). The risk ratios were 1.22 to 1.44 per standard deviation increment for top significant lipids from 11 classes. Further adjustment for HIV serostatus and conventional CVD risk factors did not change the results. No evidence of effect modification by HIV serostatus was observed. Network analysis identified 2 lipid modules (Blue and Pink), which included triacylglycerols (TAGs) and phosphatidylcholines of higher acyl carbon number and greater double bond content, showing the strongest associations with incident carotid plaque ( Figure ). Of note, the Blue module, but not the Pink module, also showed a strong positive association with HIV infection. Most lipids in the Blue module had higher levels in HIV+ compared to HIV- individuals, and were associated with increased risk of carotid plaque ( Figure ). Conclusions: Lipidomics profiling identified that multiple lipids, especially, TAGs, are increased in HIV infection and associated with progression of atherosclerosis. Our data provide new insights into early lipid metabolism alterations preceding the development of CVD in HIV infection.
MMP-2-Controlled Transforming Micelles for Heterogeneic Targeting and Programmable Cancer Therapy
Authors: Zihua Wang, Yuehua Wang, Xiangqian Jia, Qiuju Han, Yixia Qian, Qian Li, Junfeng Xiang, Qian Wang, Zhiyuan Hu, Weizhi Wang
Journal: Theranostics (2019)

Herein, through the active-peptide-functionalization, we developed a nanoscale micelles system (named HEKM) which consists of tumor microenvironment-regulated shape-changing with specific recognition abilities for enhanced cellular targeting, internalization and therapy of heterogeneic tumors.As a result, HEKMs could recognize and bind the tumor heterogeneity marker EGFR-HER2 complex, which led to an enhanced tumor targeting effect.In particular, HEKMs could self-assemble into nanorods under normal physiological conditions while transform into nanospheres in the tumor extracellular microenvironment by a sensitive response to matrix metalloproteinase-2 (MMP-2).The nanorods could prolong the blood circulation time while the nanospheres could accelerate tissue penetration in tumors.In vivo dual-modal targeted imaging was realized by FRET-fluorophore conjugation and gadolinium loading in HEKMs.Tumor cell apoptosis was achieved by proapoptotic element integration.The in vitro and in vivo studies both demonstrated that these rationally designed, shape-changing and targeting micelles could achieve maximized drug efficacy and minimum side effects.
Agreement Between Prospective and Retrospective Measures of Childhood Maltreatment
Authors: Jessie R. Baldwin, Aaron Reuben, Joanne B. Newbury, Andrea Danese
Journal: JAMA Psychiatry (2019)

Childhood maltreatment is associated with mental illness. Researchers, clinicians, and public health professionals use prospective or retrospective measures interchangeably to assess childhood maltreatment, assuming that the 2 measures identify the same individuals. However, this assumption has not been comprehensively tested.To meta-analyze the agreement between prospective and retrospective measures of childhood maltreatment.MEDLINE, PsycINFO, Embase, and Sociological Abstracts were searched for peer-reviewed, English-language articles from inception through January 1, 2018. Search terms included child* maltreatment, child* abuse, child* neglect, child bull*, child* trauma, child* advers*, and early life stress combined with prospective* and cohort.Studies with prospective measures of childhood maltreatment were first selected. Among the selected studies, those with corresponding retrospective measures of maltreatment were identified. Of 450 studies with prospective measures of childhood maltreatment, 16 had paired retrospective data to compute the Cohen κ coefficient.Multiple investigators independently extracted data according to PRISMA and MOOSE guidelines. Random-effects meta-analyses were used to pool the results and test predictors of heterogeneity.The primary outcome was the agreement between prospective and retrospective measures of childhood maltreatment, expressed as a κ coefficient. Moderators of agreement were selected a priori and included the measure used for prospective or retrospective assessment of childhood maltreatment, age at retrospective report, sample size, sex distribution, and study quality.Sixteen unique studies including 25 471 unique participants (52.4% female [SD, 10.6%]; mean [SD] age, 30.6 [11.6] years) contained data on the agreement between prospective and retrospective measures of childhood maltreatment. The agreement between prospective and retrospective measures of childhood maltreatment was poor, with κ = 0.19 (95% CI, 0.14-0.24; P < .001). Agreement was higher when retrospective measures of childhood maltreatment were based on interviews rather than questionnaires (Q = 4.1521; df = 1; P = .04) and in studies with smaller samples (Q = 4.2251; df = 1; P = .04). Agreement was not affected by the type of prospective measure used, age at retrospective report, sex distribution of the sample, or study quality.Prospective and retrospective measures of childhood maltreatment identify different groups of individuals. Therefore, children identified prospectively as having experienced maltreatment may have different risk pathways to mental illness than adults retrospectively reporting childhood maltreatment. Researchers, clinicians, and public health care professionals should recognize these critical measurement differences when conducting research into childhood maltreatment and developing interventions.
CLO19-041: Lymphatic Ligation Versus Conventional Axillary Lymph Node Dissection in Breast Cancer Patients: A Randomized Control Trial
Authors: Nawin Kuntaraksa
Journal: Journal of the National Comprehensive Cancer Network (2019)

Objective: The primary objective was to evaluate seroma formation in a comparison between the lymphatic ligation technique and conventional axillary lymph node dissection. The secondary objective was to evaluate the factors affecting seroma formation. Materials and Methods: A randomized control trial was conducted between January 2014 and November 2017. 68 consecutive patients undergoing mastectomy with axillary lymph node dissection by one experienced surgeon. The patients were randomly sampled and assigned to Group 1 (lymphatic ligation; n=34) and Group 2 (conventional surgery; n=35). Results: 18 patients had developed seroma (26.09%) with 8 (23.53%) patients who were in the lymphatic ligation group and 10 (28.57%) patients who were in the conventional group. No statistical significance was discovered in seroma formation ( P =.633), drain duration ( P =.238) or total drain volume ( P =.330) between the two groups. Longer operative time was statistically and significantly correlated with lymphatic ligation ( P =.002). Age, BMI, total drain volume, and drain dislodgement were significant factors influencing seroma formation ( P =.005, P =.002, P =.008, P =.015, respectively). Multivariate analysis showed age and BMI were significant factors influencing seroma formation ( P= .008, P =.025, respectively). Conclusion: The lymphatic ligation technique could not reduce the incidence of seroma formation. Age, BMI were the factors influencing seroma formation in the patients undergoing mastectomy with axillary lymph node dissection.
Adverse Events Associated With Immune Checkpoint Inhibitors—Reply
Authors: Douglas B. Johnson, Sunandana Chandra, Jeffrey A. Sosman
Journal: JAMA (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Author Correction: Invasion of white matter tracts by glioma stem cells is regulated by a NOTCH1–SOX2 positive-feedback loop
Authors: Jun Wang, Sen-Lin Xu, Jiang-Jie Duan, Liang Yi, Yu-Feng Guo, Yu Shi, Lin Li, Ze-Yu Yang, Xue-Mei Liao, Jiao Cai, Yan-Qi Zhang, Hua-Liang Xiao, Li Yin, Hao Wu, Jing-Na Zhang, Sheng-Qing Lv, Qing-Kai Yang, Xiao-Jun Yang, Tao Jiang, Xia Zhang, Xiu-Wu Bian, Shi-Cang Yu
Journal: Nature Neuroscience (2019)
CLO19-023: Induction Chemotherapy Followed by Chemoradiation and Trans-Anal Full Thickness Local Excision or Total Mesorectal Resection in Patients With T2-T3/NO-N+ Adenocarcinoma of the Rectum; Preliminary Results of Phase 2 Prospective Clinical Trial
Authors: Ahmed Abdalla, Amr Aref, Amer Alame, Mohamad Barawi, Danny Ma, Zyad Kafri
Journal: Journal of the National Comprehensive Cancer Network (2019)

Background: The National Comprehensive Cancer Network (NCCN) Guidelines recently recognized total neoadjuvant therapy (TNT) as an acceptable option in patients with T3 and any N rectal cancer. Previous studies suggested that patients who received chemotherapy prior to conventional preoperative chemoradiation (CRT) and surgery allowed patients to receive more of their planned treatment with a better toxicity profile and increase in pathological response. However, those studies used a long course of FOLFOX or used capecitabine and oxaliplatin as an induction regimen. We are conducting a phase 2 prospective clinical trial to evaluate the use of 6 cycles of FOLFOX as TNT in patients with T2-T3/N0-N+. Patients and Methods: Patients with T2-T3/N0-N+ enrolled on our phase 2 prospective trial were included for this analysis. Patients received 6 cycles of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin), which was administered every 2 weeks. After 3 weeks of recovery period, patients then received conventional CRT with 5FU or capecitabine. All patients got MRI and endorectal ultrasound (ERUS) at baseline, after completing FOLFOX 3-months regimen and after finishing conventional CRT. Patients underwent either full-thickness local excision or total mesorectal resection depending on their tumor response to neoadjuvant therapy. The time interval between completion of radiation therapy and surgery ranged between 7and 12 weeks. Results: A total of 10 patients completed the chemotherapy and CRT treatment regimen. 9 patients proceeded to surgery and the 10th patient is scheduled for surgery. Clinical downstaging by MRI or ERUS was shown in 9 of 10 patients with only 6 cycles of FOLFOX. Complete clinical response was achieved in 6 patients as evident by ERUS/MRI of the pelvis after 3 months of FOLFOX before CRT. Complete pathological response was found in 4 of 9 patients (44%). In addition, 4 other patients had significant albeit not complete pathological response. Conclusions: This study suggests that adding only 6 cycles of neoadjuvant FOLFOX before CRT improved clinical and pathological downstaging of T2-T3/N0-N+ rectal adenocarcinoma and may facilitate organ preservation surgery. This is strategy needs to be investigated in larger phase III trials to validate these findings.
NLRP12 Regulates Anti-viral RIG-I Activation via Interaction with TRIM25
Authors: Szu-Ting Chen, Liang Chen, Diego Shih-Chieh Lin, Sei-Yi Chen, Yen-Po Tsao, Haitao Guo, Fei-Ju Li, Wei-Ting Tseng, Jason W. Tam, Chih-Wei Chao, W. June Brickey, Ivan Dzhagalov, Moon-Jung Song, Hye-Ri Kang, Jae U. Jung, Jenny P.-Y. Ting
Journal: Cell Host & Microbe (2019)
CD317 Activates EGFR by Regulating Its Association with Lipid Rafts
Authors: Guizhong Zhang, Xin Li, Qian Chen, Junxin Li, Qingguo Ruan, Youhai H. Chen, Xiaolu Yang, Xiaochun Wan
Journal: Cancer Research (2019)

Abstract EGFR regulates various fundamental cellular processes, and its constitutive activation is a common driver for cancer. Anti-EGFR therapies have shown benefit in cancer patients, yet drug resistance almost inevitably develops, emphasizing the need for a better understanding of the mechanisms that govern EGFR activation. Here we report that CD317, a surface molecule with a unique topology, activated EGFR in hepatocellular carcinoma (HCC) cells by regulating its localization on the plasma membrane. CD317 was upregulated in HCC cells, promoting cell-cycle progression and enhancing tumorigenic potential in a manner dependent on EGFR. Mechanistically, CD317 associated with lipid rafts and released EGFR from these ordered membrane domains, facilitating the activation of EGFR and the initiation of downstream signaling pathways, including the Ras–Raf–MEK–ERK and JAK–STAT pathways. Moreover, in HCC mouse models and patient samples, upregulation of CD317 correlated with EGFR activation. These results reveal a previously unrecognized mode of regulation for EGFR and suggest CD317 as an alternative target for treating EGFR-driven malignancies. Significance: Activation of EGFR by CD317 in hepatocellular carcinoma cells suggests CD317 as an alternative target for treating EGFR-dependent tumors.
Familial predisposition to TP53/complex karyotype MDS and leukemia in DNA repair-deficient xeroderma pigmentosum
Authors: Alain Sarasin, Samuel Quentin, Nathalie Droin, Mourad Sahbatou, Véronique Saada, Nathalie Auger, Yannick Boursin, Philippe Dessen, Anna Raimbault, Vahid Asnafi, Jean-Luc Schmutz, Alain Taïeb, Carlos F. M. Menck, Filippo Rosselli, Laurianne Drieu La Rochelle, Caroline Robert, Flore Sicre de Fontbrune, Marie Sébert, Thierry Leblanc, Patricia Kannouche, Stéphane De Botton, Eric Solary, Jean Soulier
Journal: Blood (2019)
Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting
Authors: Jiansong Huang, Xia Li, Xiaofeng Shi, Mark Zhu, Jinghan Wang, Shujuan Huang, Xin Huang, Huafeng Wang, Ling Li, Huan Deng, Yulan Zhou, Jianhua Mao, Zhangbiao Long, Zhixin Ma, Wenle Ye, Jiajia Pan, Xiaodong Xi, Jie Jin
Journal: Journal of Hematology & Oncology (2019)

Integrins are a family of transmembrane glycoprotein signaling receptors that can transmit bioinformation bidirectionally across the plasma membrane. Integrin αIIbβ3 is expressed at a high level in platelets and their progenitors, where it plays a central role in platelet functions, hemostasis, and arterial thrombosis. Integrin αIIbβ3 also participates in cancer progression, such as tumor cell proliferation and metastasis. In resting platelets, integrin αIIbβ3 adopts an inactive conformation. Upon agonist stimulation, the transduction of inside-out signals leads integrin αIIbβ3 to switch from a low- to high-affinity state for fibrinogen and other ligands. Ligand binding causes integrin clustering and subsequently promotes outside-in signaling, which initiates and amplifies a range of cellular events to drive essential platelet functions such as spreading, aggregation, clot retraction, and thrombus consolidation. Regulation of the bidirectional signaling of integrin αIIbβ3 requires the involvement of numerous interacting proteins, which associate with the cytoplasmic tails of αIIbβ3 in particular. Integrin αIIbβ3 and its signaling pathways are considered promising targets for antithrombotic therapy. This review describes the bidirectional signal transduction of integrin αIIbβ3 in platelets, as well as the proteins responsible for its regulation and therapeutic agents that target integrin αIIbβ3 and its signaling pathways.