tbuckley/cabot-search huggingface dataset:
A facile approach to functionalizing cell membrane-coated nanoparticles with neurotoxin-derived peptide for brain-targeted drug delivery
Authors: Zhilan Chai, Xuefeng Hu, Xiaoli Wei, Changyou Zhan, Linwei Lu, Kuan Jiang, Bingxia Su, Huitong Ruan, Danni Ran, Ronnie H. Fang, Liangfang Zhang, Weiyue Lu
Journal: Journal of Controlled Release (2017)
Biosynthesis of antibiotic chuangxinmycin from Actinoplanes tsinanensis
Authors: Yuanyuan Shi, Zhibo Jiang, Xingxing Li, Lijie Zuo, Xuan Lei, Liyan Yu, Linzhuan Wu, Jiandong Jiang, Bin Hong
Journal: Acta Pharmaceutica Sinica B (2017)

Chuangxinmycin is an antibiotic isolated from Actinoplanes tsinanensis CPCC 200056 in the 1970s with a novel indole-dihydrothiopyran heterocyclic skeleton. Chuangxinmycin showed in vitro antibacterial activity and in vivo efficacy in mouse infection models as well as preliminary clinical trials. But the biosynthetic pathway of chuangxinmycin has been obscure since its discovery. Herein, we report the identification of a stretch of DNA from the genome of A. tsinanensis CPCC 200056 that encodes genes for biosynthesis of chuangxinmycin by bioinformatics analysis. The designated cxn cluster was then confirmed to be responsible for chuangxinmycin biosynthesis by direct cloning and heterologous expressing in Streptomyces coelicolor M1146. The cytochrome P450 CxnD was verified to be involved in the dihydrothiopyran ring closure reaction by the identification of seco-chuangxinmycin in S. coelicolor M1146 harboring the cxn gene cluster with an inactivated cxnD. Based on these results, a plausible biosynthetic pathway for chuangxinmycin biosynthesis was proposed, by hijacking the primary sulfur transfer system for sulfur incorporation. The identification of the biosynthetic gene cluster of chuangxinmycin paves the way for elucidating the detail biochemical machinery for chuangxinmycin biosynthesis, and provides the basis for the generation of novel chuangxinmycin derivatives by means of combinatorial biosynthesis and synthetic biology.
Riboflavin Content of Tumor Tissues
Authors: William v. B. Robertson, Herbert Kahler
Journal: JNCI Journal of the National Cancer Institute (1942)

Riboflavin Content of Tumor Tissues Get access William v. B. Robertson, William v. B. Robertson research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Herbert Kahler Herbert Kahler senior biophysicist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 2, Issue 6, June 1942, Pages 595–600, https://doi.org/10.1093/jnci/2.6.595 Published: 01 June 1942
An Elderly Man With a Pacemaker and a Recent Fall
Authors: A. Carolina Morales-Lara, Juan C. Leoni, Fred M. Kusumoto
Journal: JAMA Cardiology (2017)

A man in his 80s with a pacemaker presents to the emergency department after falling in his bathroom; there was no associated loss of consciousness, chest pain, dyspnea, or palpitations. What would you do next?
Image Gallery: A case of cutaneous giant angiosarcoma treated successfully with electrochemotherapy
Authors: M. Guida, E. Ruggieri, L. Fucci, M. Ressa, L. D'Aluisio, G. Fanelli, S. Strippoli
Journal: British Journal of Dermatology (2017)

Funding sources: S.S. is supported by a grant from the 'Maria Ruggieri No Profit Association for research on angiosarcoma and rare tumors'. Conflicts of interest: none declared. Dear Editor, We report the case of a 52‐year‐old woman with a giant angiosarcoma of about 30 cm in diameter involving her left supraclavicular and shoulder region (a–c). Due to the absence of metastases and the unsuitability of a surgical approach, we treated the patient with electrochemotherapy (ECT) according to standardized procedures (d).1 Following two sessions of ECT the patient obtained a progressive complete regression of the lesion, ongoing after 17 months (e, f). The patient did not have other treatment for angiosarcoma. Our experience depicts ECT as a new, elective therapeutic option for superficial giant lesions when a surgical approach is not feasible.2
Polymeric nanoparticles of siRNA prepared by a double-emulsion solvent-diffusion technique: Physicochemical properties, toxicity, biodistribution and efficacy in a mammary carcinoma mice model
Authors: Meital Ben David-Naim, Etty Grad, Gil Aizik, Mirjam M. Nordling-David, Ofra Moshel, Zvi Granot, Gershon Golomb
Journal: Biomaterials (2017)
マクロファージインテグリンは超高分子量ポリエチレン粒子に対する応答と直接粒子誘導骨溶解を調節する【Powered by NICT】
Authors: D Zaveri Toral, V Dolgova Natalia, S Lewis Jamal, Hamaker Kiri, J Clare-Salzler Michael, G Keselowsky Benjamin
Journal: Biomaterials (2017)
Late outcomes among adult survivors of childhood non-Hodgkin lymphoma (NHL): A report from the St. Jude Lifetime Cohort Study.
Authors: Matthew J. Ehrhardt, John T. Sandlund, Nan Zhang, Kirsten K. Ness, Wassim Chemaitilly, Kevin R. Krull, Tara M. Brinkman, Deborah B. Crom, Larry E. Kun, Sue C. Kaste, Gregory T. Armstrong, Daniel M. Green, Deo Kumar Srivastava, Leslie L. Robison, Melissa M. Hudson, Daniel A. Mulrooney
Journal: Journal of Clinical Oncology (2015)

10064 Background: Adult survivors of childhood NHL are at risk for chronic conditions likely underestimated by patient reported outcomes. Prevalence and severity based on direct clinical assessment are lacking. Methods: Clinical, laboratory, and performance-based evaluations were obtained on 200 adult survivors of pediatric NHL at St. Jude Children’s Research Hospital. Chronic conditions were graded per CTCAE criteria. Impaired physical function was defined as performance below the 10th percentile of normative data. Multivariable Poisson regression models were used to investigate associations [relative risk (RR), 95% confidence intervals (CI)] between patient characteristics, therapies, and clinical outcomes. Results: Survivors (66% male, 87% white) were a median age of 10 years (range 1-19) at diagnosis and 34 years (20-58) at evaluation. Forty-six (23%) received radiation to the brain, 69(35%) high dose methotrexate, and 161(81%) steroids. Most (93%) had ≥ 1 chronic condition, 77% ≥ 2 chronic conditions, and 50% a severe/life-threatening (grade 3-4) condition. Most prevalent were overweight/obesity (65%), cognitive impairment (46%), dyslipidemia (41%), and impaired fasting glucose (37%). Most prevalent grade 3-4 conditions were obesity (35%), hypertension (15%), and cognitive impairment (13%). Risk-based screening detected cardiomyopathy in 14(8.5%); 50% grades 3-4. There were 27 second cancers (61% grades 3-4) in 23(12%) survivors. Prevalence of abnormal body composition, measured by waist to height ratio and percent fat on dual-energy x-ray absorptiometry was 72%. Many had impaired aerobic (22%), strength (48%), muscular endurance (36%), flexibility (39%), and mobility (36%) assessments. Adjusting for ages at diagnosis and evaluation, race, and methotrexate, male sex (RR 1.2, CI 1.1-1.5), anthracycline ≥ 250mg/m2 (RR 1.3, CI 1.1-1.6), and radiation (RR 1.3, CI 1.1-1.6) were associated with having ≥ 2 chronic conditions. Non-white race (RR 1.6, CI 1.2-2.1) was associated with a grade 3-4 condition. Conclusions: Prospective systematic evaluation identified significant chronic conditions and performance limitations in adult survivors of childhood NHL.
Using a Next Generation Sequencing Panel to Discover the Obscure Causes of Hereditary Hemolytic Anemias
Authors: Archana M Agarwal, N. Scott Reading, Kimberly Frizzell, Wei Shen, Shelly Sorrells, Mohamed E Salama, Josef T. Prchal, Hassan M. Yaish, Jay L Patel, Robert D. Christensen
Journal: Blood (2016)
Underprivilege as Privilege
Authors: Stephanie Y. Zhou
Journal: JAMA (2017)

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
Histone methyltransferase SETD2 modulates alternative splicing to inhibit intestinal tumorigenesis
Authors: Huairui Yuan, Ni Li, Da Fu, Jiale Ren, Jingyi Hui, Junjie Peng, Yongfeng Liu, Tong Qiu, Min Jiang, Qiang Pan, Ying Han, Xiaoming Wang, Qintong Li, Jun Qin
Journal: Journal of Clinical Investigation (2017)

The histone H3K36 methyltransferase SETD2 is frequently mutated or deleted in a variety of human tumors. Nevertheless, the role of SETD2 loss in oncogenesis remains largely undefined. Here, we found that SETD2 counteracts Wnt signaling and its inactivation promotes intestinal tumorigenesis in mouse models of colorectal cancer (CRC). SETD2 was not required for intestinal homeostasis under steady state; however, upon irradiation, genetic inactivation of Setd2 in mouse intestinal epithelium facilitated the self-renewal of intestinal stem/progenitor cells as well as tissue regeneration. Furthermore, depletion of SETD2 enhanced the susceptibility to tumorigenesis in the context of dysregulated Wnt signaling. Mechanistic characterizations indicated that SETD2 downregulation affects the alternative splicing of a subset of genes implicated in tumorigenesis. Importantly, we uncovered that SETD2 ablation reduces intron retention of dishevelled segment polarity protein 2 (DVL2) pre-mRNA, which would otherwise be degraded by nonsense-mediated decay, thereby augmenting Wnt signaling. The signaling cascades mediated by SETD2 were further substantiated by a CRC patient cohort analysis. Together, our studies highlight SETD2 as an integral regulator of Wnt signaling through epigenetic regulation of RNA processing during tissue regeneration and tumorigenesis.
Cognitive Function in a Randomized Trial of Evolocumab
Authors: Robert P. Giugliano, François Mach, Kenton Zavitz, Christopher Kurtz, Kyungah Im, Estella Kanevsky, Jingjing Schneider, Huei Wang, Anthony Keech, Terje R. Pedersen, Marc S. Sabatine, Peter S. Sever, Jennifer G. Robinson, Narimon Honarpour, Scott M. Wasserman, Brian R. Ott
Journal: New England Journal of Medicine (2017)

Background Findings from clinical trials of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors have led to concern that these drugs or the low levels of low-density lipoprotein (LDL) cholesterol that result from their use are associated with cognitive deficits. Methods In a subgroup of patients from a randomized, placebo-controlled trial of evolocumab added to statin therapy, we prospectively assessed cognitive function using the Cambridge Neuropsychological Test Automated Battery. The primary end point was the score on the spatial working memory strategy index of executive function (scores range from 4 to 28, with lower scores indicating a more efficient use of strategy and planning). Secondary end points were the scores for working memory (scores range from 0 to 279, with lower scores indicating fewer errors), episodic memory (scores range from 0 to 70, with lower scores indicating fewer errors), and psychomotor speed (scores range from 100 to 5100 msec, with faster times representing better performance). Assessments of cognitive function were performed at baseline, week 24, yearly, and at the end of the trial. The primary analysis was a noninferiority comparison of the mean change from baseline in the score on the spatial working memory strategy index of executive function between the patients who received evolocumab and those who received placebo; the noninferiority margin was set at 20% of the standard deviation of the score in the placebo group. Results A total of 1204 patients were followed for a median of 19 months; the mean (±SD) change from baseline over time in the raw score for the spatial working memory strategy index of executive function (primary end point) was -0.21±2.62 in the evolocumab group and -0.29±2.81 in the placebo group (P<0.001 for noninferiority; P=0.85 for superiority). There were no significant between-group differences in the secondary end points of scores for working memory (change in raw score, -0.52 in the evolocumab group and -0.93 in the placebo group), episodic memory (change in raw score, -1.53 and -1.53, respectively), or psychomotor speed (change in raw score, 5.2 msec and 0.9 msec, respectively). In an exploratory analysis, there were no associations between LDL cholesterol levels and cognitive changes. Conclusions In a randomized trial involving patients who received either evolocumab or placebo in addition to statin therapy, no significant between-group difference in cognitive function was observed over a median of 19 months. (Funded by Amgen; EBBINGHAUS ClinicalTrials.gov number, NCT02207634 .).
Phosphorylation of SOS1 on tyrosine 1196 promotes its RAC GEF activity and contributes to BCR-ABL leukemogenesis
Authors: S Gerboth, E Frittoli, A Palamidessi, F C Baltanas, M Salek, J Rappsilber, C Giuliani, F Troglio, Y Rolland, G Pruneri, S Kreutmair, I Pallavicini, M Zobel, M Cinquanta, S Minucci, C Gomez, E Santos, A L Illert, G Scita
Journal: Leukemia (2017)

Son of Sevenless 1 (SOS1) is a dual guanine nucleotide exchange factor (GEF) that activates the small GTPases RAC and RAS. Although the molecular mechanisms of RAS GEF catalysis have been unveiled, how SOS1 acquires RAC GEF activity and what is the physio-pathological relevance of this activity is much less understood. Here we show that SOS1 is tyrosine phosphorylated on Y1196 by ABL. Phosphorylation of Y1196 controls SOS1 inter-molecular interaction, is required to promote the exchange of nucleotides on RAC in vitro and for platelet-derived growth factor (PDGF) activation of RAC- and RAC-dependent actin remodeling and cell migration. SOS1 is also phosphorylated on Y1196 by BCR-ABL in chronic myelogenous leukemic cells. Importantly, in these cells, SOS1 is required for BCR-ABL-mediated activation of RAC, cell proliferation and transformation in vitro and in a xenograft mouse model. Finally, genetic removal of Sos1 in the bone marrow-derived cells (BMDCs) from Sos1fl/fl mice and infected with BCR-ABL causes a significant delay in the onset of leukemogenesis once BMDCs are injected into recipient, lethally irradiated mice. Thus, SOS1 is required for full transformation and critically contribute to the leukemogenic potential of BCR-ABL.
Medicines, excipients, and dietary intolerances
Journal: BMJ (2017)

#### What you need to know

Medicinal products contain not only active drugs but also other ingredients included for a variety of purposes and collectively known as excipients.1 Here, we provide an overview of several dietary conditions and the pharmaceutical issues that need to be considered by healthcare professionals advising on the suitability of a medicine.

A food allergy is an adverse immune response and a food intolerance is a non-immunological reaction that can be caused by enzyme deficiencies, pharmacological agents and naturally occurring substances.2 It is estimated that between 1% and 10% of adults and children have some form of food allergy or intolerance. The reason why a person has intolerance to a certain type of food is often not clear. However, as many as 20% of the population experience reactions to foods which make them believe that they have a food intolerance or hypersensitivity.3 For children, the most common food allergens include cows’ milk, chicken eggs, shellfish, fish, soy, peanuts, wheat and tree nuts. The most common type of enzymatic food intolerance is lactose intolerance.3 Excipients in medicines may not be suitable for some people with a dietary intolerance …
Mylan settles for overcharging in suit brought by EpiPen competitor
Authors: Owen Dyer
Journal: BMJ (2017)

The drug company Mylan NV has agreed to pay $465m (£360m; €395m) to settle claims that it overcharged the US social healthcare program Medicaid for its anaphylaxis treatment EpiPen, a portable, single use syringe carried by patients who are at risk of life threatening allergic reactions.

Although Mylan marketed and priced EpiPen as a branded device, it classified it as a generic for state Medicaid programs, allowing the company to reduce the rebates it was obliged to pay to those programs.

Mylan, which is based in the US but registered …
Response to Comment by Ayubi and Safiri. Insulin Resistance Predicts Cognitive Decline: An 11-Year Follow-up of a Nationally Representative Adult Population Sample. Diabetes Care 2017;40:751–758
Authors: Laura L. Ekblad, Juha O. Rinne, Pauli Puukka, Hanna Laine, Satu Ahtiluoto, Raimo Sulkava, Matti Viitanen, Antti Jula
Journal: Diabetes Care (2017)

We thank Drs. Ayubi and Safiri for their comments (1) on our article (2). First, they pointed out that because baseline measurements, instead of repeated measurements, of insulin resistance (IR), insulin, and glucose were used to evaluate associations between these risk factors and cognitive decline, the results might not be accurate because of regression dilution bias and collinearity. It is true that we did not have access to repeated measurements of IR, insulin, and glucose during the follow-up time, which is why we could not account for within-person variability in our analyses nor answer the question asked by Ayubi and Safiri (1): “Is there an …
The Role of Environmental Factors in the Pathogenesis of Inflammatory Bowel Diseases
Authors: Dror S. Shouval, Paul A. Rufo
Journal: JAMA Pediatrics (2017)

Inflammatory bowel diseases (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing conditions that affect a growing number of children worldwide. The pathogenesis of these disorders is complex and thought to be mediated by the interplay between genetic susceptibility, microbial dysbiosis, and environmental factors that result in a dysregulated immune system. This dysregulation ultimately mediates intestinal inflammation and clinical symptoms typically observed in patients with IBD including abdominal pain, diarrhea, and poor growth. A dramatic increase in the incidence of IBD has been observed in the past 2 decades, mainly in developed countries but also in developing regions. This increased incidence has paralleled changes in diet, sanitation conditions, and lifestyle habits.The increased incidence of IBD can likely be attributed to more than evolving genetic diversity alone and strongly suggests that environmental factors are playing an increasingly critical role in the development of these disorders and in the modulation of IBD clinical phenotypes over time. Here, we review the data suggesting how different environmental factors may modulate the risk of developing IBD including diets, smoking, lifestyle choices, enteric infections, appendectomy, air pollution, and the use of medications, with an emphasis on antibiotics. We will also discuss how early-life events can influence the subsequent likelihood of developing one of these diseases and suggest directions that can help decrease the risk of IBD in particularly high-risk populations.Dramatic lifestyle changes in the last century have substantially improved the quality of life but are also associated with increased risk of various diseases. Pediatricians should be aware of the changing epidemiology of IBD and environmental factors that modulate the risk of developing these conditions.
A distinctive histidine residue is essential for in vivo glycation-inactivation of human CD59 transgenically expressed in mice erythrocytes: Implications for human diabetes complications
Authors: Rupam Sahoo, Pamela Ghosh, Michael Chorev, Jose A. Halperin
Journal: American Journal of Hematology (2017)

Clinical and experimental evidences support a link between the complement system and the pathogenesis of diabetes complications. CD59, an extracellular cell membrane-anchored protein, inhibits formation of the membrane attack complex (MAC), the main effector of complement-mediated tissue damage. This complement regulatory activity of human CD59 (hCD59) is inhibited by hyperglycemia-induced ɛ-amino glycation of Lys41 . Biochemical and structural analyses of glycated proteins with known three-dimensional structure revealed that glycation of ɛ-amino lysyl residues occurs predominantly at "glycation motives" that include lysyl/lysyl pairs or proximity of a histidyl residue, in which the imidazolyl moiety is ≈ 5Å from the ɛ-amino group. hCD59 contains a distinctive Lys41 /His44 putative glycation motif within its active site. In a model of transgenic diabetic mice expressing in erythrocytes either the wild type or a H44Q mutant form of hCD59, we demonstrate in vivo that the His44 is required for Lys41 glycation and consequent functional inactivation of hCD59, as evidenced using a mouse erythrocytes hemolytic assay. Since (1) the His44 residue is not present in CD59 from other animal species and (2) humans are particularly prone to develop complications of diabetes, our results indicate that the Lys41 /His44 glycation motif in human CD59 may confer humans a higher risk of developing vascular disease in response to hyperglycemia.