tbuckley/cabot-search huggingface dataset:
The impact of novel compound 2'-hydroxyflavanone on proteomic networks of <i>VHL</i>-mutant renal cell carcinoma.
Authors: Lokesh Prasad Gowda Dalasanur Nagaprashantha, Tatjana Talamantes, Jyotsana Singhal, Sanjay Awasthi, Sharad S. Singhal, Laszlo Prokai
Journal: Journal of Clinical Oncology (2012)

e13557 Background: Von Hippel-Lindau (VHL) tumor suppressor is a major genetic factor that determines hypoxic acclimatization and response to therapy in renal cell carcinoma (RCC). Our initial studies revealed that 2'-Hydroxyflavanone (2HF) effectively inhibits the survival of VHL-mutant RCC. Hence, we performed proteomic analyses to study the signaling networks of clinical significance that are regulated by 2HF in VHL-mutant RCC. Methods: The 786-O cells, an established cell line from a male Caucasian patient, were provided by William Kaelin Jr., MD, Harvard Medical School, Boston, MA. The cells were cultured either in the presence or absence of 50 μM 2HF for 48 h in RPMI medium at 37°C in 5% CO 2 and lysed in a buffer containing 6M urea. The lysate (200 µg of protein) was reduced, alkylated and digested with trypsin. Tryptic digests were desalted using a C-18 cartridge (Waters, USA) and subjected to liquid chromatography–tandem mass spectrometry (LC-MS/MS) analyses on linear ion trap–Fourier transform ion cyclotron resonance tandem mass spectrometer (LTQ-FT, Thermo) coupled to an Eksigent nano-LC system. MS/MS spectra were searched against human protein sequence database using Mascot (Matrix Science), and protein identifications were validated by Scaffold (version 3.0, Proteome Software). Quantifications were performed by extracted peptide intensities (Progenesis LC-MS, Nonlinear Dynamics). Results: 2HF treatment lead to up-regulation of 21 proteins including protein disulfide-isomerase A4 and macrophage migration inhibition factor. 2HF treatment lead to down-regulation of 23 proteins including vimentin, HSP90AB1, 14-3-3 gamma and glutaminase. The network analyses revealed that the identified proteins form critical nodes of regulation of vital tumor proteins like MAP3K14, ERK1/2, Myc and P53. Conclusions: Proteomic analyses of 2HF treated VHL-mutant RCC revealed a striking regulation of proteins of importance in RCC survival, invasion and metastases. The critical nodes of regulation as identified by the network analyses could facilitate further studies on the development of network targeting therapies using 2HF and other anti-cancer compounds for the effective management of VHL-mutant RCC.
Orofacial Granulomatosis Presenting With Acquired Lymphangiectasia
Authors: Anthony D. Honigman, Minhee Kim, C.W. Chow, Susan J. Robertson
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
Metastatic Breast Carcinoma–Associated Fibroblasts Have Enhanced Protumorigenic Properties Related to Increased IGF2 Expression
Authors: Yirui Gui, Adriana Aguilar-Mahecha, Urszula Krzemien, Abdel Hosein, Marguerite Buchanan, Josiane Lafleur, Michael Pollak, Cristiano Ferrario, Mark Basik
Journal: Clinical Cancer Research (2019)

Abstract Purpose: The microenvironment of metastatic breast cancer is incompletely characterized, despite prior evidence that it plays a key role in the biology of metastasis. A major component of the tumor stroma is the carcinoma-associated fibroblast (CAF), which has been shown to communicate with other stromal and cancer cells to create a protumorigenic milieu. Our study was designed to characterize human CAFs from different metastatic sites. Experimental Design: We collected eight carcinoma-associated fibroblasts (mCAFs) from different metastatic sites and compared them with CAFs from primary tumors (pCAFs) and with normal breast fibroblasts (NFs). Molecular profiles and effects on breast cancer cell growth, on response to doxorubicin and on T-cell proliferation were compared. Results: We observed marked differences in mCAFs compared with pCAFs and NFs with respect to in vitro proliferation and effects on breast cancer cell migration, spheroid growth, invasion, response to doxorubicin, and in vivo tumor growth. We found marked transcriptomic differences between mCAFs and pCAFs, including increased expression of IFN-related genes and IGF2 in the former. Cluster analysis revealed two groups of mCAFs, with the liver mCAFs clustering together, with increased PDGFA expression. Treatment with an antibody against insulin-like growth factors (BI836845) inhibited growth of mixed mCAF-tumor cell xenografts in vivo. Also, mCAFs had a suppressive effect on T-cell proliferation. Conclusions: This is the first comparative analysis of a set of CAFs from metastatic sites in breast cancer. It revealed a marked protumorigenic effect in these mCAFs, which occurs in part through increased expression of IGF2.
The first enhancer in an enhancer chain safeguards subsequent enhancer-promoter contacts from a distance
Authors: Wei Song, Roded Sharan, Ivan Ovcharenko
Journal: Genome biology (2019)

Abstract Background Robustness and evolutionary stability of gene expression in the human genome are established by an array of redundant enhancers. Results Using Hi-C data in multiple cell lines, we report a comprehensive map of promoters and active enhancers connected by chromatin contacts, spanning 9000 enhancer chains in 4 human cell lines associated with 2600 human genes. We find that the first enhancer in a chain that directly contacts the target promoter is commonly located at a greater genomic distance from the promoter than the second enhancer in a chain, 96 kb vs. 45 kb, respectively. The first enhancer also features higher similarity to the promoter in terms of tissue specificity and higher enrichment of loop factors, suggestive of a stable primary contact with the promoter. In contrast, a chain of enhancers which connects to the target promoter through a neutral DNA segment instead of an enhancer is associated with a significant decrease in target gene expression, suggesting an important role of the first enhancer in initiating transcription using the target promoter and bridging the promoter with other regulatory elements in the locus. Conclusions The widespread chained structure of gene enhancers in humans reveals that the primary, critical enhancer is distal, commonly located further away than other enhancers. This first, distal enhancer establishes contacts with multiple regulatory elements and safeguards a complex regulatory program of its target gene.
Internet-Delivered Cognitive-Behavioral Therapy for Insomnia in Breast Cancer Survivors: A Randomized Controlled Trial
Authors: Robert Zachariae, Ali Amidi, Malene F Damholdt, Cecilie D R Clausen, Jesper Dahlgaard, Holly Lord, Frances P Thorndike, Lee M Ritterband
Journal: JNCI Journal of the National Cancer Institute (2017)

Insomnia is two to three times more prevalent in cancer survivors than in the general population, where it is estimated to be 10% to 20%. Cognitive-behavioral therapy for insomnia (CBT-I) is the recommended treatment for chronic insomnia, but meeting survivor needs remains a challenge. Internet-delivered CBT-I (iCBT-I) has been shown efficacious in otherwise healthy adults. We tested the efficacy of iCBT-I in breast cancer survivors with clinically significant sleep disturbance. Women from a national sample of Danish breast cancer survivors who experienced clinically significant sleep disturbance were randomly allocated to iCBT-I or waitlist control (55:45). The fully automated iCBT-I program consisted of six cores. Online measures of insomnia severity, sleep quality, and fatigue were collected at baseline, postintervention (nine weeks), and follow-up (15 weeks). Online sleep diaries were completed over two-week periods pre- and postintervention. Intention-to-treat analyses (time × group interactions) were conducted with mixed linear models and corrected for multiple outcomes. All statistical tests were two-sided. A total of 255 women were randomly allocated to iCBT-I (n = 133) or waitlist control (n = 122). Statistically significant (P ≤ .02) time × group interactions were found for all sleep-related outcomes from pre- to postintervention. Effect sizes (Cohen's d) ranged from 0.33 (95% confidence interval [CI] = 0.06 to 0.61) for wake after sleep onset to 1.17 (95% CI = 0.87 to 1.47) for insomnia severity. Improvements were maintained for outcomes measured at follow-up (d = 0.66–1.10). iCBT-I appears to be effective in breast cancer survivors, with additional benefit in terms of reduced fatigue. This low-cost treatment could be incorporated in cancer rehabilitation programs.
Transplantation of induced pluripotent stem cell-derived mesenchymal stem cells improved erectile dysfunction induced by cavernous nerve injury
Authors: Zehong Chen, Xiaoyan Han, Xi Ouyang, Jiafeng Fang, Xuna Huang, Hongbo Wei
Journal: Theranostics (2019)

Erectile dysfunction (ED) is an important kind of postoperative complication of pelvic surgery that affects patients' quality of life. Transplantation of mesenchymal stem cells (MSC) has been found to alleviate ED caused by cavernous nerve injury (CNI) in rats. However, little is known about whether induced pluripotent stem cell-derived mesenchymal stem cells (iMSC) have a therapeutic effect on CNI ED. We established an ED model on rats and evaluated the effect of iMSC on it. Methods: Eight-week-old male Sprague-Dawley rats were assigned to four groups and received following operation: sham operation (sham group); bilateral CNI and phosphate-buffered saline (PBS) injections (PBS group); bilateral CNI and adipose-derived mesenchymal stem cells transplantation (adMSC group); or bilateral CNI and iMSC injection (iMSC group). After therapy, the cavernous nerve was stimulated by electricity and the intracavernous pressure (IAP)/mean arterial blood pressure (MAP) was measured. The endothelial and smooth muscle tissue in the penis was assessed histologically with Masson's trichrome stain. Immunofluorescence/immunohistochemical stains were applied for the detection of nNOS, vWF, eNOS, SMA, Desmin, S100β, and caspase-3. Nude rats CNI ED model was established for the evaluation of iMSC longevity and differentiation capacity. The paracrine factors were assessed by real-time PCR. Results: Transplantation of iMSC significantly restored the IAP/MAP in this CNI ED model and showed long-term effects. It could rescue the expression of vWF, eNOS, SMA, and Desmin, which indicated the alleviation of endothelial and smooth muscle tissues of the penis. iMSC therapy also could increase the expression of nNOS in the cavernosum and S100β in the major pelvic ganglia (MPG) which contributed to the erectile function. Moreover, the level of BAX and caspase-3 were reduced and Bcl-2 was increased, which indicated the anti-apoptosis effects of iMSC. The iMSC showed little transdifferentiation and exerted their function by activating the secretome of the host. Conclusion: Transplantation of iMSC significantly improved ED induced by CNI. The iMSC may exert their effects via paracrine factors and may be a promising therapeutic candidate for treating CNI ED in the future.
Genetic Variants Implicate Dual Oxidase-2 in Familial and Sporadic Nonmedullary Thyroid Cancer
Authors: Darrin V. Bann, Qunyan Jin, Kathryn E. Sheldon, Kenneth R. Houser, Lan Nguyen, Joshua I. Warrick, Maria J. Baker, James R. Broach, Glenn S. Gerhard, David Goldenberg
Journal: Cancer Research (2019)

Highly penetrant hereditary thyroid cancer manifests as familial nonmedullary thyroid cancer (FNMTC), whereas low-penetrance hereditary thyroid cancer manifests as sporadic disease and is associated with common polymorphisms, including rs965513[A]. Whole-exome sequencing of an FNMTC kindred identified a novel Y1203H germline dual oxidase-2 (DUOX2) mutation. DUOX2Y1203H is enzymatically active, with increased production of reactive oxygen species. Furthermore, patients with sporadic thyroid cancer homozygous for rs965513[A] demonstrated higher DUOX2 expression than heterozygous rs965513[A/G] or homozygous rs965513[A]-negative patients. These data suggest that dysregulated hydrogen peroxide metabolism is a common mechanism by which high- and low-penetrance genetic factors increase thyroid cancer risk. SIGNIFICANCE: This study provides novel insights into the genetic and molecular mechanisms underlying familial and sporadic thyroid cancers.
Could nonhuman great apes also have cultural evolutionary psychology?
Authors: Claudio Tennie
Journal: Behavioral and Brain Sciences (2019)

Attempted answers are given to (a) whether nonhuman great apes (apes) also have evolved imitation (answer: no); (b) whether humans can transmit imitation as a gadget to apes (answer: yes, partly); (c) whether human-to-ape transmission can kickstart subsequent and stable ape cultural evolutionary psychology ("CEP"; answer: unlikely); and (d) when CEP evolved in our lineage (answer: relatively late).
Long-Term Incidence of Atrial Fibrillation and Stroke Among Cross-Country Skiers
Authors: Niclas Svedberg, Johan Sundström, Stefan James, Ulf Hållmarker, Kristina Hambraeus, Kasper Andersen
Journal: Circulation (2019)

Studies have revealed a higher incidence of atrial fibrillation among well-trained athletes. We aim to investigate associations of endurance training with incidence of atrial fibrillation and stroke and to establish potential sex differences of such associations in a cohort of endurance trained athletes.All Swedish skiers (208 654) completing 1 or more races in the 30 to 90 km cross-country skiing event Vasaloppet (1989-2011) and a matched sample (n=527 448) of nonskiers were followed until first event of atrial fibrillation or stroke. Cox regression was used to investigate associations of number of completed races and finishing time with incidence of atrial fibrillation and stroke.Female skiers in Vasaloppet had a lower incidence of atrial fibrillation than did female nonskiers (hazard ratio [HR], 0.55; 95% CI, 0.48-0.64), independent of finishing time and number of races. Male skiers had a similar incidence to that of nonskiers (HR, 0.98; 95% CI, 0.93-1.03). Skiers with the highest number of races or fastest finishing times had the highest incidence. Skiers of either sex had a lower incidence of stroke than did nonskiers (HR, 0.64; 95% CI, 0.60-0.67), independent of the number of races and finishing time. Skiers with atrial fibrillation had higher incidence of stroke than did skiers and nonskiers without atrial fibrillation (men: HR, 2.28; 95% CI, 1.93-2.70; women: HR, 3.51; 95% CI, 2.17-5.68; skiers with atrial fibrillation vs. skiers without atrial fibrillation). After diagnosis of atrial fibrillation, skiers with atrial fibrillation had a lower incidence of stroke (HR, 0.73; 95% CI, 0.50-0.91) and lower mortality compared with nonskiers with atrial fibrillation (HR, 0.57; 95% CI, 0.49-0.65).Female skiers in Vasaloppet had lower incidence of atrial fibrillation and stroke. Male skiers had similar incidence of atrial fibrillation and lower risk of stroke. Men with higher number of races and faster finishing times had the highest incidence of atrial fibrillation. After diagnosis of atrial fibrillation, skiers had lower incidence of stroke and death than did nonskiers with atrial fibrillation. This indicates that although on an individual level atrial fibrillation in well-trained individuals is associated with higher incidence of stroke, on population level, risk of stroke is low and that exercise should not be avoided.
David Oliver: Publicity stunts and hospital food
Authors: David Oliver
Journal: BMJ (2019)

Boris Johnson recently announced that Prue Leith, the Great British Bake-Off judge and catering expert, would join the government’s review of hospital food. Over an al fresco breakfast photo opportunity with Leith he claimed that better food would aid recovery and “fuel patients,” extolling the virtues of “hot buttered toast.” Leith added that millions of pounds were wasted each year on “unpalatable” hospital food.12

In reality the health secretary, Matt Hancock, had already announced a “root and branch review” of hospital food back in June, before Johnson became prime minister.3 This review will be chaired by Philip Shelley, ex-head of the Hospital Caterers Association—a man with recent direct experience with the NHS. Leith is simply an adviser.

Hancock’s original plan was in response to nine confirmed cases of listeria, which caused the death of six patients. The cases were traced back to …
A Manual of Personal Hygiene.
Journal: JAMA (1913)

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
Association of obesity with breast cancer outcome in relation to cancer subtypes.
Authors: Ana Elisa Lohmann, Sara V. Soldera, Isabel Pimentel, Domen Ribnikar, Marguerite Ennis, Eitan Amir, Pamela Jean Goodwin
Journal: Journal of Clinical Oncology (2019)

11557 Background: Obesity at breast cancer (BC) diagnosis is associated with poor outcome, although the magnitude of effect in different BC subtypes is uncertain. Here we report on the association of obesity at BC diagnosis with disease-free (DFS) and overall survival (OS) in the following subtypes: (i) hormone receptor (ER/PgR) +ve, HER2-ve, (ii) HER2+ve, any ER/PgR and (iii) triple negative (TN). Methods: We searched MEDLINE, EMBASE and COCHRANE databases to December 31, 2018 and meeting presentations (past 5 years) using predefined search terms. Study eligibility, data abstraction were performed independently by two authors; those reporting hazard ratios (HR) for obesity and DFS/OS in BC subtypes were included. Using Review Manager pooled HRs were computed and weighted using generic inverse variance in fixed and random effects models (results were similar, random effects are presented). Results: Of 10,702 titles, 26 studies (108,793 patients) were included. Pooled HR for DFS for obese vs non-obese were (i) ER/PgR+ve HER2-ve 1.21 (95% Confidence interval, CI; 1.12-1.31, p &lt; 0.00001), (ii) HER2+ve, any ER/PgR 1.16 (95%CI, 1.06-1.26; p = 0.0006) and (iii) TN, 1.13 (95%CI; 1.05-1.22 p = 0.002). Pooled HRs for OS were (i) ER/PgR+ve, HER2-ve 1.45 (95%CI; 1.30-1.62 p &lt; 0.00001), (ii) HER2+ve any ER/PgR 1.21 (95%CI; 1.10-1.34 p = 0.0001) and (iii) TN 1.13 (95%CI, 1.04-1.23, p = 0.003).PooledHR for OS (but not DFS) were somewhat higher in observational vs interventional studies in (i) ER/PgR+ve, HER2-ve 1.57 vs 1.36, HER2+ve any ER/PgR (ii) 1.37 vs 1.09 but not (iii) TN 1.12 vs 1.22 (p = 0.21, 0.03 and 0.48, respectively). Conclusions: Obesity was associated with a worse outcome in all BC subtypes. Higher HR for OS in observational studies in (i) ER/PgR+ve, HER2- and (ii) HER2+ve any ER/PgR BC may reflect selection of healthier patients for intervention trials.
Effects of inhaled corticosteroids on DNA methylation in peripheral blood cells in children with asthma
Authors: Maura Kere, Olena Gruzieva, Vilhelmina Ullemar, Cilla Söderhäll, Dario Greco, Inger Kull, Anna Bergström, Göran Pershagen, Catarina Almqvist, Erik Melén
Journal: Allergy (2019)

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Association Between Power Morcellation and Mortality in Women With Unexpected Uterine Cancer Undergoing Hysterectomy or Myomectomy
Authors: Xiao Xu, Haiqun Lin, Jason D. Wright, Cary P. Gross, Francis P. Boscoe, Lindsey M. Hutchison, Peter E. Schwartz, Vrunda B. Desai
Journal: Journal of Clinical Oncology (2019)

PURPOSE Despite concerns that power morcellation may adversely affect prognosis of patients with occult uterine cancer, empirical evidence has been limited and inconclusive. In this study, we aimed to determine whether uncontained power morcellation at the time of hysterectomy or myomectomy is associated with increased mortality risk in women with occult uterine cancer. METHODS By linking statewide hospital discharge records with cancer registry data in New York, we identified 843 women with occult endometrial carcinoma and 334 women with occult uterine sarcoma who underwent a hysterectomy or myomectomy for presumed benign indications during the period October 1, 2003, through December 31, 2013. Within this cohort, we compared disease-specific and all-cause mortality of women who underwent laparoscopic supracervical hysterectomy/laparoscopic myomectomy (LSH/LM), a surrogate indicator for uncontained power morcellation, with women who underwent supracervical abdominal hysterectomy and total abdominal hysterectomy (TAH), which did not involve power morcellation. Multivariable Cox regressions and propensity score method were used to adjust for patient characteristics. RESULTS Among women with occult uterine sarcoma, LSH/LM was associated with a higher risk for disease-specific mortality than TAH (adjusted hazard ratio [aHR], 2.66, 95% CI, 1.11 to 6.37; adjusted difference in 5-year disease-specific survival, −19.4%, 95% CI, −35.8% to −3.1%). In the subset of women with leiomyosarcoma, LSH/LM was associated with an increased risk for disease-specific mortality compared with supracervical abdominal hysterectomy (aHR, 3.64, 95% CI, 1.50 to 8.86; adjusted difference in 5-year disease-specific survival, −31.2%, 95% CI, −50.0% to −12.3%) and TAH (aHR, 4.66, 95% CI, 1.97 to 11.00; adjusted difference in 5-year disease-specific survival, −37.3%, 95% CI, −54.2% to −20.3%). Among women with occult endometrial carcinoma, there was no significant association between surgical approach and disease-specific mortality. CONCLUSION Uncontained power morcellation was associated with higher mortality risk in women with occult uterine sarcoma, especially in those with occult leiomyosarcoma.