tbuckley/cabot-search huggingface dataset:
PDSS1-Mediated Activation of CAMK2A-STAT3 Signaling Promotes Metastasis in Triple-Negative Breast Cancer
Authors: Tian-Jian Yu, Ying-Ying Liu, Xiao-Guang Li, Bi Lian, Xun-Xi Lu, Xi Jin, Zhi-Ming Shao, Xin Hu, Gen-Hong Di, Yi-Zhou Jiang
Journal: Cancer Research (2021)

Abstract Genomic alterations are crucial for the development and progression of human cancers. Copy-number gains found in genes encoding metabolic enzymes may induce triple-negative breast cancer (TNBC) adaptation. However, little is known about how metabolic enzymes regulate TNBC metastasis. Using our previously constructed multiomic profiling of a TNBC cohort, we identified decaprenyl diphosphate synthase subunit 1 (PDSS1) as an essential gene for TNBC metastasis. PDSS1 expression was significantly upregulated in TNBC tissues compared with adjacent normal tissues and was positively associated with poor survival among patients with TNBC. PDSS1 knockdown inhibited TNBC cell migration, invasion, and distant metastasis. Mechanistically, PDSS1, but not a catalytically inactive mutant, positively regulated the cellular level of coenzyme Q10 (CoQ10) and intracellular calcium levels, thereby inducing CAMK2A phosphorylation, which is essential for STAT3 phosphorylation in the cytoplasm. Phosphorylated STAT3 entered the nucleus, promoting oncogenic STAT3 signaling and TNBC metastasis. STAT3 phosphorylation inhibitors (e.g., Stattic) effectively blocked PDSS1-induced cell migration and invasion in vitro and tumor metastasis in vivo. Taken together, our study highlights the importance of targeting the previously uncharacterized PDSS1/CAMK2A/STAT3 oncogenic signaling axis, expanding the repertoire of precision medicine in TNBC. Significance: A novel metabolic gene PDSS1 is highly expressed in triple-negative breast cancer tissues and contributes to metastasis, serving as a potential therapeutic target for combating metastatic disease.
Opportunities and challenges of macrogenetic studies
Authors: Deborah M. Leigh, Charles B. van Rees, Katie L. Millette, Martin F. Breed, Chloé Schmidt, Laura D. Bertola, Brian K. Hand, Margaret E. Hunter, Evelyn L. Jensen, Francine Kershaw, Libby Liggins, Gordon Luikart, Stéphanie Manel, Joachim Mergeay, Joshua M. Miller, Gernot Segelbacher, Sean Hoban, Ivan Paz-Vinas
Journal: Nature Reviews Genetics (2021)
27464 Bimekizumab vs adalimumab in plaque psoriasis: Higher efficacy translates into improvements in quality of life in the BE SURE multicenter, randomized, double-blinded phase 3 trial
Authors: Andrew Blauvelt, Diamant Thaçi, Kim A. Papp, Joseph F. Merola, Eva Cullen, Veerle Vanvoorden, Valerie Ciaravino, Luke Peterson, Kenneth Gordon
Journal: Journal of the American Academy of Dermatology (2021)
Abstract 1005: Tamoxifen treatment induces the epigenetic changes in breast cancer stem cells
Authors: Kanagarj Palaniyandi, Dhanavathy Gnasampandapandian, Ilangovan Ramachandran, Yuvaraj Sambandam, Parthasarathy Chandrakesan
Journal: Cancer Research (2019)

Abstract Purpose: Breast cancer is diagnosed in younger women population and is the leading cause of cancer-related deaths in India. Tamoxifen (TOM) is one of the most effective and widely used first-line endocrine therapy for ER+ breast cancer. However, breast cancer patients often develop TOM resistance and enhanced with caner stem cell (CSC)-like phenotypes. These TOM-resistance (TR) breast cancer phenotypes are highly aggressive and they do not respond to most of the chemotherapies. It is therefore essential to understand the mechanism that resulted in the development of TR in breast cancer. The current study was designed to investigate the epigenetic changes associated mechanism that induces the development of hormone-resistance in breast CSCs. Experimental Procedure: In this study, we used ALDEFLOUR assay, flow cytometry, mammosphere culture, western blot, Chromatin-immunoprecipitation, and RT-PCR analyses. Results: Our study showed that breast CSC-like population possesses higher TR cancer cell phenotypes than non-CSCs. We generated MCF7-derived mammospheres (CSCs) utilizing MammoCult media. However, when treated with TOM (1µM)-we observed an increased number of mammospheres (CSCs) than vehicle control. We found a strong interplay between TR and epigenetic changes, in particular, the changes observed in histone demethylase, which is believed to be one of the crucial links that involved in the development of therapy resistance and enhanced CSC population. Furthermore, TR breast CSCs derived from MCF7 cells display an increased expression of the NOTCH-1 protein. Induced overexpression of NOTCH in MCF7 cells increased the number of mammosphere formation ability than control cells. Finally, overexpression of NOTCH-1 also led to transcriptional up-regulation of cyclin genes A, B, and D. Conclusion: We observed a crucial interplay between TR and breast CSCs. TR associated epigenetic alteration enhanced the expression of NOTCH1, which resulted in increased mitotic signals in the tumor cells including CSCs. Thus, these new phenotypes of breast CSCs with TR characteristics need more understanding for the development of effective combinatorial and adjuvant therapies. Note: This abstract was not presented at the meeting. Citation Format: Kanagarj Palaniyandi, Dhanavathy Gnasampandapandian, Ilangovan Ramachandran, Yuvaraj Sambandam, Parthasarathy Chandrakesan. Tamoxifen treatment induces the epigenetic changes in breast cancer stem cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1005.
Prevalence of Osteoporosis and Fracture in China
Authors: Linhong Wang, Wei Yu, Xiangjun Yin, Lijia Cui, Shunyu Tang, Ning Jiang, Lu Cui, Nan Zhao, Qiang Lin, Lin Chen, Hua Lin, Xiaolan Jin, Zhong Dong, Zeping Ren, Zhulin Hou, Yongqing Zhang, Jieming Zhong, Shunxiang Cai, Yuan Liu, Ruilin Meng, Ying Deng, Xianbin Ding, Jingang Ma, Zhongjian Xie, Lin Shen, Wen Wu, Mengmeng Zhang, Qifeng Ying, Yuhong Zeng, Jin Dong, Steven R. Cummings, Zhixin Li, Weibo Xia
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known. <h3>Objective</h3> To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China. <h3>Design, Setting. and Participants</h3> This cross-sectional study, the China Osteoporosis Prevalence Study, was conducted from December 2017 to August 2018. A random sample of individuals aged 20 years or older who represented urban and rural areas of China were enrolled, with a 99% participation rate. <h3>Main Outcomes and Measures</h3> Weighted prevalence of osteoporosis, clinical fracture, and vertebral fracture by age, sex, and urban vs rural residence as determined by x-ray absorptiometry, questionnaire, and radiography. <h3>Results</h3> A total of 20 416 participants were included in this study; 20 164 (98.8%; 11 443 women [56.7%]; mean [SD] age, 53 [13] years) had a qualified x-ray absorptiometry image and completed the questionnaire, and 8423 of 8800 (95.7%) had a qualified spine radiograph. The prevalence of osteoporosis among those aged 40 years or older was 5.0% (95% CI, 4.2%-5.8%) among men and 20.6% (95% CI, 19.3%-22.0%) among women. The prevalence of vertebral fracture was 10.5% (95% CI, 9.0%-12.0%) among men and 9.7% (95% CI, 8.2%-11.1%) among women. The prevalence of clinical fracture in the past 5 years was 4.1% (95% CI, 3.3%-4.9%) among men and 4.2% (95% CI, 3.6%-4.7%) among women. Among men and women, 0.3% (95% CI, 0.0%-0.7%) and 1.4% (95% CI, 0.8%-2.0%), respectively, with osteoporosis diagnosed on the basis of bone mineral density or with fracture were receiving antiosteoporosis treatment to prevent fracture. <h3>Conclusions and Relevance</h3> In this cross-sectional study of an adult population in mainland China, the prevalence of osteoporosis and vertebral fracture were high and the prevalence of vertebral fracture and clinical fracture was similarly high in men and women. These findings suggest that current guidelines for screening and treatment of fractures among patients in China should focus equally on men and women and should emphasize the prevention of vertebral fractures.
25444 Ligelizumab further reduced sleep impairment in patients with chronic spontaneous urticaria previously treated with omalizumab
Authors: Marcus Maurer, Karl Sitz, Gordon Sussman, Martin Metz, Michihiro Hide, Ana Giménez-Arnau, Nathalie Barbier, Eva Hua, Reinhold Janocha, Maria-Magdalena Balp, Thomas Severin
Journal: Journal of the American Academy of Dermatology (2021)
Formulation strategies to improve the efficacy of intestinal permeation enhancers,
Authors: Sam Maher, David J. Brayden
Journal: Advanced Drug Delivery Reviews (2021)

The use of chemical permeation enhancers (PEs) is the most widely tested approach to improve oral absorption of low permeability active agents, as represented by peptides. Several hundred PEs increase intestinal permeability in preclinical bioassays, yet few have progressed to clinical testing and, of those, only incremental increases in oral bioavailability (BA) have been observed. Still, average BA values of ~1% were sufficient for two recent FDA approvals of semaglutide and octreotide oral formulations. PEs are typically screened in static in vitro and ex-vivo models where co-presentation of active agent and PE in high concentrations allows the PE to alter barrier integrity with sufficient contact time to promote flux across the intestinal epithelium. The capacity to maintain high concentrations of co-presented agents at the epithelium is not reached by standard oral dosage forms in the upper GI tract in vivo due to dilution, interference from luminal components, fast intestinal transit, and possible absorption of the PE per se. The PE-based formulations that have been assessed in clinical trials in either immediate-release or enteric-coated solid dosage forms produce low and variable oral BA due to these uncontrollable physiological factors. For PEs to appreciably increase intestinal permeability from oral dosage forms in vivo, strategies must facilitate co-presentation of PE and active agent at the epithelium for a sustained period at the required concentrations. Focusing on peptides as examples of a macromolecule class, we review physiological impediments to optimal luminal presentation, discuss the efficacy of current PE-based oral dosage forms, and suggest strategies that might be used to improve them.
PD11: Access to phototherapy during the COVID‐19 pandemic
Authors: S Butt, A Mcmullan, R Dawe, S Ibbotson, L Finlayson, I Barnard, L Mcmillan, E Eadie, K Wood, C Brown
Journal: British Journal of Dermatology (2021)

Over the last few years, we have seen 11 patients presenting with proton pump inhibitor (PPI) photosensitivity at our tertiary referral photodiagnostic service and in our local dermatology department.Many adverse effects, including the discovery in 2020 of an almost twofold increased risk of severe COVID-19, of this widely used group of drugs have been noted (Lee SW, Ha EK, Yeniova A € O et al.Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching.Gut 2020; 70: 76-84.).Although PPI-induced phototoxicity has been described, phototest results have not been reported and all clinical presentations have not been described.We aimed to identify all patients with PPI photosensitivity who presented to our unit.We sought to better understand their clinical characteristics, blood test results and photodiagnostic results.We retrospectively reviewed all case notes and investigation results of patients who were diagnosed with PPI photosensitivity.Eleven patients were identified to have been seen between 2014 and 2019.Two patients were male and nine were female.Mean duration of disease was 3Á6 years and mean duration of PPI ingestion was 5 years.Five patients presented with a drug-induced lupus pattern [subcutaneous lupus erythematosus (SCLE; n = 2), papulosquamous SCLE and discoid (n = 1), tumid (n = 1) and acute cutaneous (n = 1)], four with drug-induced phototoxicity (sunburn-like) and two with a drug-induced solar urticaria relating to a lupus mechanism.The majority of patients reported symptoms on sun-exposed sites.The most common indication for PPI prescription was gastroesophageal reflux disease with omeprazole being the most commonly prescribed PPI.All patients underwent phototesting.Three patients were not on an PPI while undergoing phototesting and did not demonstrate photosensitivity.Of the remaining patients who underwent phototesting the most common finding was delayed sensitivity to ultraviolet A and to visible light.Drug-induced photosensitivity can be a challenging diagnostic entity owing to the varied clinical presentation and heterogeneous time to onset.We present this case series to further help clinicians in recognizing the clinical and diagnostic pattern of photosensitivity present with PPI use.
25853 Efficacy and safety of oral nalbuphine extended release in prurigo nodularis: Results of a phase 2 randomized controlled trial with an open-label extension phase
Authors: Elke Weisshaar, Jacek C. Szepietowski, Thomas R. Sciascia, Gil Yosipovitch, Sonja Ständer
Journal: Journal of the American Academy of Dermatology (2021)
Dietary fibres and IBS: translating functional characteristics to clinical value in the era of personalised medicine
Authors: Daniel So, Peter R Gibson, Jane G Muir, Chu K Yao
Journal: Gut (2021)

Clinical guidelines in the use of fibre supplementation for patients with IBS provide one-size-fits-all advice, which has limited value. This narrative review addresses data and concepts around the functional characteristics of fibre and subsequent physiological responses induced in patients with IBS with a view to exploring the application of such knowledge to the precision use of fibre supplements. The key findings are that first, individual fibres elicit highly distinct physiological responses that are associated with their functional characteristics rather than solubility. Second, the current evidence has focused on the use of fibres as a monotherapy for IBS symptoms overall without attempting to exploit these functional characteristics to elicit specific, symptom-targeted effects, or to use fibre types as adjunctive therapies. Personalisation of fibre therapies can therefore target several therapeutic goals. Proposed goals include achieving normalisation of bowel habit, modulation of gut microbiota function towards health and correction of microbial effects of other dietary therapies. To put into perspective, bulking fibres that are minimally fermented can offer utility in modulating indices of bowel habit; slowly fermented fibres may enhance the activities of the gut microbiota; and the combination of both fibres may potentially offer both benefits while optimising the activities of the microbiota throughout the different regions of the colon. In conclusion, understanding the GI responses to specific fibres, particularly in relation to the physiology of the individual, will be the future for personalising fibre therapy for enhancing the personalised management of patients with IBS.
A Systematic Review of Filtering Facepiece Respirator Reprocessing—Reply
Authors: Max A. Schumm, Melinda Maggard-Gibbons
Journal: JAMA (2021)

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
Conflicts of Interest and Authors of Commentaries in Medical Journals
Authors: Robert Steinbrook, Deborah Grady, Rita F. Redberg
Journal: JAMA Internal Medicine (2021)

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 Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Journals 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 Internal Medicine journal
25991 Application of the statistical method to convert published PASI 50/75/90/100 into absolute PASI response rate in patients with moderate-to-severe plaque psoriasis treated with tildrakizumab based on data from two pivotal phase 3 studies (reSURFACE 1/2)
Authors: Igor Dykukha, Andreu Schoenenberger, Ismail Kasujee, Ulrich Mrowietz, Reinhard Vonthein
Journal: Journal of the American Academy of Dermatology (2021)
Attenuated activation of pulmonary immune cells in mRNA-1273–vaccinated hamsters after SARS-CoV-2 infection
Authors: Michelle Meyer, Yuan Wang, Darin Edwards, Gregory R. Smith, Aliza B. Rubenstein, Palaniappan Ramanathan, Chad E. Mire, Colette Pietzsch, Xi Chen, Yongchao Ge, Wan Sze Cheng, Carole Henry, Angela Woods, LingZhi Ma, Guillaume B.E. Stewart-Jones, Kevin W. Bock, Mahnaz Minai, Bianca M. Nagata, Sivakumar Periasamy, Pei-Yong Shi, Barney S. Graham, Ian N. Moore, Irene Ramos, Olga G. Troyanskaya, Elena Zaslavsky, Andrea Carfi, Stuart C. Sealfon, Alexander Bukreyev
Journal: Journal of Clinical Investigation (2021)

The mRNA-1273 vaccine is effective against SARS-CoV-2 and was granted emergency use authorization by the FDA. Clinical studies, however, cannot provide the controlled response to infection and complex immunological insight that are only possible with preclinical studies. Hamsters are the only model that reliably exhibits severe SARS-CoV-2 disease similar to that in hospitalized patients, making them pertinent for vaccine evaluation. We demonstrate that prime or prime-boost administration of mRNA-1273 in hamsters elicited robust neutralizing antibodies, ameliorated weight loss, suppressed SARS-CoV-2 replication in the airways, and better protected against disease at the highest prime-boost dose. Unlike in mice and nonhuman primates, low-level virus replication in mRNA-1273–vaccinated hamsters coincided with an anamnestic response. Single-cell RNA sequencing of lung tissue permitted high-resolution analysis that is not possible in vaccinated humans. mRNA-1273 prevented inflammatory cell infiltration and the reduction of lymphocyte proportions, but enabled antiviral responses conducive to lung homeostasis. Surprisingly, infection triggered transcriptome programs in some types of immune cells from vaccinated hamsters that were shared, albeit attenuated, with mock-vaccinated hamsters. Our results support the use of mRNA-1273 in a 2-dose schedule and provide insight into the potential responses within the lungs of vaccinated humans who are exposed to SARS-CoV-2.
Liver function after combined selective internal radiation therapy or sorafenib monotherapy in advanced hepatocellular carcinoma
Authors: Jens Ricke, Regina Schinner, Max Seidensticker, Antonio Gasbarrini, Otto M. van Delden, Holger Amthauer, Bora Peynircioglu, Irene Bargellini, Roberto Iezzi, Enrico N. De Toni, Peter Malfertheiner, Maciej Pech, Bruno Sangro
Journal: Journal of Hepatology (2021)
28481 Risk for nonmelanoma second primary malignancy in malignant melanoma survivors: A nationwide report from the National Cancer Institute Surveillance, Epidemiology, and End Results program
Authors: Ghazal Ghafari, Yasmeen Ali, Danyal Tahseen, Walter J. Liszewski, Dennis P. West, Beatrice Nardone
Journal: Journal of the American Academy of Dermatology (2021)
27633 Efficacy and safety of ruxolitinib cream among adolescents with atopic dermatitis: Pooled Results from two phase 3 studies
Authors: Lawrence F. Eichenfield, Eric L. Simpson, Elaine C. Siegfried, Michael E. Kuligowski, May E. Venturanza, Kang Sun, Amy S. Paller
Journal: Journal of the American Academy of Dermatology (2021)
28036 Phase 2 randomized, placebo-controlled, dose-ranging study to evaluate the safety and efficacy of onabotulinumtoxina for the treatment of platysma prominence
Authors: Rodney Rohrich, David E. Bank, Vince Bertucci, Brian S. Biesman, Steven Dayan, Shannon Humphrey, Derek Jones, Joely Kaufman-Janette, Channy Y. Muhn, Jason K. Rivers, Warren Tong
Journal: Journal of the American Academy of Dermatology (2021)
EEG-based musical neurointerfaces in the correction of stress-induced states
Authors: Alexander Fedotchev, Sergey Parin, Sofia Polevaya, Anna Zemlianaia
Journal: Brain-Computer Interfaces (2021)

Chronic action of work-related and background stresses causes a disruption of coping mechanisms and may first lead to functional disorders, and then develop into serious stress-related diseases. This generates a need for timely correction of stress-induced functional disturbances. Prior research has shown promise in closed-loop EEG feedback systems to alter patients' mental states induced by stress. The present study aims to assess the effects of stress suppression using a single (music) or double (music+video) feedback from the patient's EEG. In one of three experiments, 18 stressed volunteers were presented with classical music without feedback (control). In the other two experiments, either a single feedback was used, where music loudness varied in strict accordance with the current amplitude of the patient's EEG oscillator, or a double feedback, in which the described music signals are supplemented by rhythmic light stimuli generated from the patient's EEG. A significant increase in alpha EEG power, accompanied by positive emotional reactions and shifts in the functional state of the participants were observed only in the presence of the feedback from the EEG. Doubling the feedback from human EEG leads to increased effectiveness of neurointerfaces due to resonant interaction between rhythmic sensory stimuli and bioelectric processes of the human brain.