tbuckley/cabot-search huggingface dataset:
Arthroscopic Partial Meniscectomy vs Physical Therapy for Nonobstructive Meniscal Tears
Authors: Thoralf R. Liebs
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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Metastatic Insulinoma Controlled by Targeted Radionuclide Therapy With 177Lu-DOTATATE in a Patient With Solitary Kidney and MEN-1 Syndrome
Authors: Fuad Novruzov, Leyla Mehmetbeyli, Jamil A. Aliyev, Bahadur Abbasov, Elnur Mehdi
Journal: Clinical Nuclear Medicine (2019)

A 54-year-old man with multiple endocrine neoplasia type 1 had previous history of parathyroid surgery and left thyroid lobectomy 5 years earlier, and was referred for recurrent hypoglycemic episodes. Ga-DOTATATE PET/CT had showed multiple lesions in the right lung, liver, and pancreas. Biopsy from pancreas revealed low-grade neuroendocrine neoplasia. After 2 fractions of Lu-DOTATATE therapy, the size of lesions and its activity reduced on the Ga-DOTATATE scan and the hypoglycemic episodes manifested every day have scaled down to 1 time over 1-year follow-up. Herein, we report a case of malignant insulinoma successfully treated with radiolabeled somatostatin receptor therapy using Lu-DOTATATE.
P056 Important role of CD11C+ dendritic cells in inflammatory arthritis
Authors: A Puchner, V Saferding, R Pfeifle, G Krönke, K Redlich, J Smolen, S Blüml
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> The main function of dendritic cells (DCs) is to present antigen to T-cells and therefore they play an important role in bridging the innate and the adaptive immune response. However, DCs can be divided in different subsets, which have intrinsic differences that lead to functional specialisation in the generation and maintenance of autoimmunity. Therefore the aim of our study was to investigate the role of CD11c<sup>+</sup> conventional DCs and monocytes dervived DCs in inflammatory arthritis. <h3>Methods</h3> We analysed histological sections of K/BxN serum transfer arthritis as well as hTNFtg arthritis for the presence of CD11c<sup>+</sup> cells by immunohistochemistry. We also performed synovial biopsies and analysed the cellular composition of the inflammatory infiltrate with respect to DCs. We used CD11c-diphteria toxin receptor (DTR) transgenic mice, which express the human diphtheria-toxin receptor under the CD11c promoter, allowing for specific depletion of CD11c<sup>+</sup> cells by administration of diphtheria toxin (DT). K/BxN serum transfer arthritis was induced, and mice were given either DT or PBS or in wt and BARF3 deficient mice. In addition CD11c DTR mice were crossed into hTNFtg animals and also received either DT or PBS. The severity of arthritis was determined clinically and histologically. <h3>Results</h3> We show that Cd11c<sup>+</sup> cells are present in significant numbers in the synovia of K/BxN and TNF driven arthritis. Both CD8<sup>+</sup>CD11c<sup>+</sup> and CD11b<sup>+</sup>CD11c<sup>+</sup>, can be found in synovial tissue. In K/BxN serum transfer arthritis, clinical scores showed that CD11c-DTR transgenic mice that received DT had significantly reduced paw swelling and loss of grip strength compared to PBS treated animals. Histological analysis found reduced inflammation after the depletion of CD11c<sup>+</sup> cells in K/BxN arthritis. In addition local bone destruction and the number of osteoclasts was significantly reduced. Analysis of K/BxN arthritis in wt mice and BATF3<sup>-/-</sup> mice, which lack CD8<sup>+</sup>CD11<sup>+</sup> DCs revealed no difference in arthritis severity between the two groups. In addition to K/BxN arthritis, we found that also in TNF-driven arthritis depletion of CD11c<sup>+</sup> cells led to a significant reduction of synovial inflammation and a complete depletion of osteoclasts. <h3>Conclusions</h3> These data show that in addition to initiating an adaptive immune response, CD11c<sup>+</sup>dendritic cells, are also involved in innate effector mechanisms of inflammatory arthritis. Especially CD11b<sup>+</sup>CD11c<sup>+</sup> and monocyte derived inflammatory seem to play a role in inflammatory arthritis, suggesting that they could be an important therapeutic target for patients suffering from inflammatory arthritis. <h3>Disclosure of interest</h3> None declared
High incidence of injuries at the Pyeongchang 2018 Paralympic Winter Games: a prospective cohort study of 6804 athlete days
Authors: Wayne Derman, Phoebe Runciman, Esme Jordaan, Martin Schwellnus, Cheri Blauwet, Nick Webborn, Jan Lexell, Peter van de Vliet, James Kissick, Jaap Stomphorst, Young-Hee Lee, Keun-Suh Kim
Journal: British Journal of Sports Medicine (2019)

To describe the epidemiology of sports injury at the Pyeongchang 2018 Paralympic Winter Games.567 athletes from 49 countries were monitored daily for 12 days over the Pyeongchang 2018 Paralympic Winter Games (6804 athlete days). Injury data were obtained daily from teams with their own medical support (41 teams and 557 athletes) and teams without their own medical support (8 teams and 10 athletes) through two electronic data capturing systems.112 of 567 athletes (19.8%) reported a total of 142 injuries, with an injury incidence rate (IR) of 20.9 per 1000 athlete days (95% CI 17.4 to 25.0). The highest IR was reported for para snowboard (IR of 40.5 per 1000 athlete days [95% CI 28.5 to 57.5]; p<0.02), particularly in the lower limb and head/face/neck anatomical areas. Across all sports at the Games, acute traumatic injuries (IR of 16.2 per 1000 athlete days [95% CI 13.2 to 19.8]) and injuries to the shoulder/arm/elbow complex (IR of 5.7 per 1000 athlete days [95% CI 4.2 to 7.8]) were most common. However, most injuries (78.9%) did not require time loss.The new Paralympic Winter Games sport of Para snowboard requires attention to implement actions that will reduce injury risk. The shoulder was the most injured single joint-a consistent finding in elite para sport.
NHS staff survey: just 29% of organisations take health and wellbeing seriously
Authors: Jacqui Thornton
Journal: BMJ (2019)

Doctors and other NHS employees are increasingly experiencing workforce stress, but the number who say that their organisation is taking positive action on health and wellbeing is falling, the latest NHS staff survey has found.1

The 2018 staff survey of NHS trusts and foundation trusts reported that 39.8% of staff had felt unwell in the past 12 months as a result of work related stress—the worst result in five years.

Only 28.6% said that their organisation took positive action on health and wellbeing, down from 31.8% in 2017, which the BMA describes as “worrying.”

Nearly one in five staff reported harassment, bullying, or abuse at work from colleagues (19.1%, up from 18.0%), and abuse by managers was lower but still …
Update in Cystic Fibrosis 2006
Authors: Frank J. Accurso
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Cystic fibrosis (CF) is a complex inherited condition resulting from abnormalities in the gene that codes for the cystic fibrosis transmembrane conductance regulator (CFTR).CFTR, a membrane glycoprotein present in certain epithelia, contributes to regulation of ion flux across the cell surface in a number of ways, including direct chloride channel activity.The clinical picture of CF includes variable, but often severe, injury to the primary organs involved (exocrine pancreas, lung, sinus, liver, intestine) as well as a staggering array of secondary complications (including polymicrobial infection, malnutrition in many forms, hypoelectrolytemia, diabetes, vasculitis, nasal polyps, and pulmonary hypertension).Chronic, progressive lung disease results in most of the morbidity and mortality in CF and is therefore the main focus of clinical care and research.Care and research in CF have developed in parallel since the first clear definition of this condition in the 1930s (1).The curious elevation of sweat electrolytes seen in CF, first described in the 1950s, resulted in a robust diagnostic test.Comprehensive care centers soon followed and have evolved to include newer quality improvement and evidence-based approaches.The discovery and characterization of the abnormal gene in 1989 opened up many paths to research in model systems and in patients.It is now appreciated that CF airway disease involves intricate interrelationships among airway surface liquid, mucus clearance, infection, inflammation, repair, and fibrosis. CELL BIOLOGY Intracellular TraffickingIntracellular trafficking of wild-type and mutant CFTR has been the subject of dozens of reports in the past year.This is because the most common mutation in CF, ⌬F508, results in almost complete degradation of CFTR during endoplasmic reticulum processing.Treatment of this mutation is a central goal of research in CF because approximately 90% of all individuals in the United States with CF have at least one copy of the ⌬F508 mutation.Wang and colleagues, through an elegant proteomic approach, described the CFTR interactome, the complement of intracellular proteins that interact with CFTR (2).More than 200 proteins were identified, providing a foundation for more detailed study of individual protein complexes.Using small interfering (si)RNA, they further showed a special role for Aha1,
Inhibition of PDE4 sensitizes drug resistant NSCLC to TKI therapy
Authors: S. Mukherjee, D. Suresh, A. Upendran, R. Kannan
Journal: Annals of Oncology (2019)

Background: NSCLC patients undergoing tyrosine kinase inhibitor (TKI) therapy often develop resistance (9-12 months) resulting in low median survival (10-14 months) among stage IV patients. Studies showed that, in some cases, the resistance can be attributed to upregulation of pro-survival PI3K-Akt pathway. Indeed, EGFR-mutant patients with elevated levels of phospho-Akt have shown poor therapeutic response and the levels of p-Akt are increased upon prolonged EGFR TK treatment. In addition, several mechanistic studies attribute increased phospho-Akt (p-Akt) levels in tumor as one of the reasons for drug resistance. In an independent study, researchers have shown that suppression of phosphorylation of Akt can be achieved by inhibition of Phosphodiesterase- 4(PDE4) and in turn activate luminal apoptosis. Therefore, we hypothesized that PDE4 inhibition would sensitize drug resistant NSCLC to tyrosine kinase inhibitor therapy by abrogating the PI3K-Akt pathway. Methods: TK resistant cell lines along with controls were used for the study. First generation TKIs, Dasatinib, Erlotinib and Gefitinib were used to study the efficacy of TKI. Roflumilast, a drug already used in chronic obstructive pulmonary disorder (COPD), was used as the PDE4 inhibitor. Results: Inhibition of PDE4 followed by treatment with TKIs showed remarkable decrease in IC50values, compared to either PDE4 inhibition or TK inhibition. Upon PDE4 inhibition, efficacy of TKIs is found to be increased several folds compared to individual inhibitors. Cells showed no signs toxicity to the PDE4 inhibitor at the dose levels used, thus making the inhibitor itself absolutely nontoxic at this treatment dose. Conclusions: Our results suggest that PDE4 inhibition is a potential way to reverse TKI resistance and also to improve TKI therapy in patients with high levels of p-Akt. Legal entity responsible for the study: University of Missouri - Columbia, Missouri, USA. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
Effects of Oral N -Acetylcysteine on Oxidative Stress in Patients with Sickle Cell Disease
Authors: Joep W.R. Sins, Xiaoyun Fu, Karin Fijnvandraat, Melissa Dominguez, A. W. Rijneveld, Jean-Louis Kerkhoffs, A van Meurs, M. R. De Groot, H Heijboer, Erfan Nur, Brenda M Luken, Sacha S Zeerleder, Marie-Françoise Dresse, Phu-Quoc Le, Philippe Hermans, Anna Vanderfaeillie, Eric Van Den Neste, Fleur Samantha Benghiat, Rachel Kesse-Adu, Andre Delannoy, Andre Efira, Marie-Agnes Azerad, C A de Borgie, Junmei Chen, Jose A. Lopez, Bart J. Biemond
Journal: Blood (2017)
Giant bilateral pulmonary arteriovenous malformations with refractory hypoxaemia
Authors: Saad Emhmed Ali, Leanne Lin, Steven Krohmer, Wesam Frandah
Journal: BMJ (2019)

A 63 year old woman with alcoholic cirrhosis presented with a 2 week history of platypnoea (dyspnoea worse on sitting up). She had a history of upper gastrointestinal bleeding …
Adenine base editing in an adult mouse model of tyrosinaemia
Authors: Chun-Qing Song, Tingting Jiang, Michelle Richter, Luke H. Rhym, Luke W. Koblan, Maria Paz Zafra, Emma M. Schatoff, Jordan L. Doman, Yueying Cao, Lukas E. Dow, Lihua Julie Zhu, Daniel G Anderson, David R. Liu, Hao Yin, Wen Xue
Journal: Nature Biomedical Engineering (2019)
Brain metabolism modulates neuronal excitability in a mouse model of pyruvate dehydrogenase deficiency
Authors: Vikram Jakkamsetti, Isaac Marin-Valencia, Qian Ma, Levi B. Good, Tyler Terrill, Karthik Rajasekaran, Kumar Pichumani, Chalermchai Khemtong, M. Ali Hooshyar, Chandrasekhar Sundarrajan, Mulchand S. Patel, Robert M. Bachoo, Craig R. Malloy, Juan M. Pascual
Journal: Science Translational Medicine (2019)

Decreased metabolic flux due to deficient mitochondrial pyruvate dehydrogenase causes excitability dysfunction that can be modulated by acetate.
Long term conditions in young people: UK is third worst of 15 countries
Authors: Nigel Hawkes
Journal: BMJ (2019)

Young people in the UK are more likely than those in almost all comparable countries to have had a long term condition diagnosed, says a report from the Nuffield Trust and the Association for Young People’s Health.1

The proportion of 16-24 year olds in the UK with a longstanding condition such as asthma or diabetes was the third highest of 15 countries, the report found, using data taken principally from the European statistical office, Eurostat. The two countries with an even higher proportion were Sweden and Finland.

The report did not suggest that this may reflect the degree of ascertainment of disease in different countries …
Abstract 2030: A novel role for the 185delAG BRCA1 mutant protein, BRAT, in ovarian cancer pathology
Authors: Kamisha T. Woolery, Rebecca J. Linger, Patricia A. Kruk
Journal: Cancer Research (2011)

Abstract Objective: Familial history is the strongest risk factor for developing ovarian cancer (OC) and is associated with BRCA1 truncation mutations, such as the founder mutation 185delAG. Studying these risk-associated mutations may reveal signaling pathways important in OC etiology. Normal human ovarian surface epithelial (HOSE) cells expressing the 185delAG mutant, BRAT, exhibit phenotypic changes due, in part, to up-regulation of maspin, a tumor suppressor important in apoptosis, invasion, and metastasis that exhibits unique up-regulation in some cancer types. In the current study, we determined BRAT's impact on expression of Interleukin-1beta (IL1β), another key player in invasion and metastasis. Methods: HOSE cells transiently and stably expressing the 185delAG mutation and HOSE cells with endogenous 185delAG were analyzed for differential target gene expression by semi-quantitative, real time PCR, western blot; as well as, IL1β bioactivity. Western blot was used to identify cell signaling targets of BRAT mediated IL1β expression via MAPK pathways. Breast epithelial and breast cancer cells transiently and stably expressing BRAT were evaluated by real time PCR to determine whether BRAT induced IL1β is tissue specific. Results: BRAT-expressing HOSE cells exhibited enhanced IL1β mRNA expression. Higher levels of pro-IL1β protein were detected by Western blotting of cell lysate and conditioned media. Increased phosphorylation of MAPK pathway constituents were seen in BRAT-expressing HOSE cells as detected by Western blotting of cell lysate. However, expression of BRAT in normal breast and breast cancer cell lines failed to significantly alter IL1β expression levels. Conclusion: Normal HOSE cells expressing the BRAT mutation exhibit increased expression of IL1β. Further investigation is warranted to elucidate the mechanism of tissue-specific BRAT-mediated IL1β expression since increased IL1β expression may represent an early step of malignant transformation contributing to ovarian cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2030. doi:10.1158/1538-7445.AM2011-2030
Butein inhibits solid tumors cell viability, colony, and tumor growth via STAT3 signaling pathway and enhance the anti-cancer effects of Frondoside-A and camptothecin
Authors: S. Attoub, S. Sulaiman, K. Arafat
Journal: Annals of Oncology (2019)

Background: Despite the major recent advances in cancer management, cure of cancer remains a serious challenge. Methods: In the current study, we investigated the impact of butein, a biologically active flavonoid, on the human cancer cell survival and colony growth in vitro, and on tumor growth in vivo, alone and in combination with Frondoside-A, a triterpenoid glycoside isolated from an Atlantic sea cucumber, and camptothecin. Results: We demonstrate that butein causes a concentration- and time-dependent decrease in the viability of the lung cancer cells (A549 and LNM35), the breast cancer cells (MDA-MB-231 and T47D), and a decrease in their related colonies growth in vitro. Similarly, treatment with butein significantly decreased the growth of A549 and MDA-MB-231 xenografts in the chick embryo model in vivo (P < 0.01) without significant toxicity. To determine whether the inhibition of cell viability and tumor growth by butein is due to growth arrest or to cell death, we assessed the induction of apoptosis by measuring caspase-3 activity and PARP cleavage. The treatment of lung and breast cancer cells with butein induce caspase-3 activation leading to PARP inactivation in a concentration and time-dependent manner. More than 50% of lung cancers and 40% of breast cancers show constitutive activation of STAT3. The role of this transcription factor in cancer progression is now well established and its targeting in cancer therapy is a very promising and challenging option. We observed that butein treatment induce a concentration and time-dependent inhibition of STAT3 phosphorylation without any impact on total STAT3. We finally demonstrate that butein at the IC25 and IC50 concentration enhances the anti-cancer effect of Frondoside-A as well as the effect of camptothecin on lung and breast cancer cells in vitro. Conclusions: These findings increase our confidence of the potential benefit of using butein as an anticancer agent for the treatment of solid tumors either alone, and/or in combination with Frondoside-A and camptothecin. Legal entity responsible for the study: Samir Attoub. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
A Prognostic Nomogram and Survival Analysis in Relapsed or Refractory Diffuse Large B-Cell Lymphoma Patients
Authors: Shiyu Jiang, Yan Qin, Peng Liu, Jiangliang Yang, Sheng Yang, Xiaohui He, Shengyu Zhou, Lin Gui, Changgong Zhang, Liqiang Zhou, Ming-Zhe Han, Yan Sun, Yuankai Shi
Journal: Blood (2018)
Abstract 16907: Modification of Hemeoxygenase-1 Expression Enhances the Therapeutic Potency of CD34+ Cells in Ischemic Tissue Repair
Authors: Jorn Tongers, Kentaro Jujo, Jerome G Roncalli, Marie-Ange Renault, Christine E Kamide, Ekaterina Klyachko, Tina Thorne, Johann Bauersachs, David L Amrani, Delara Motlagh, Douglas W Losordo
Journal: Circulation (2011)

The potency of cell-based therapy in ischemic tissue repair is limited by low viability and retention of transplanted cells. The hemeoxygenase system catabolizes heme cleavage and has been shown to...
Cancer of the Head and Neck
Authors: Philip Rubin
Journal: JAMA (1972)

The expectation behind combining two successful modalities of cancer treatment is that the cure rate will increase. The use of radical surgery and radiation therapy has been avidly explored in different sequence, with the use of various schedules and with assorted modifications. Agreement as to their value or the manner of executing the combination remains debatable. Application to the complete spectrum of malignant neoplasms and in innumerable schemata has not been sufficient to create a distinct approach or "school." This is not surprising, since the modalities are effective via distinct and separate mechanisms, and it is unlikely that the same population of tumors is interchangeably curable by either method in the same manner. In the past, the most common reason for combining these approaches has been to correct or rectify the other's mistakes. When the surgeon had failed in effecting a cure for head and neck cancer, it became the
Impact of Procedure Time on Outcomes of Thrombectomy for Stroke
Authors: Ali Alawieh, Jan Vargas, Kyle M. Fargen, E. Farris Langley, Robert M. Starke, Reade De Leacy, Rano Chatterjee, Ansaar Rai, Travis Dumont, Peter Kan, David McCarthy, Fábio A. Nascimento, Jasmeet Singh, Lukas Vilella, Aquilla Turk, Alejandro M. Spiotta
Journal: Journal of the American College of Cardiology (2019)