tbuckley/cabot-search huggingface dataset:
Photodynamic Therapy Induced Enhancement of Tumor Vasculature Permeability Using an Upconversion Nanoconstruct for Improved Intratumoral Nanoparticle Delivery in Deep Tissues
Authors: Weidong Gao, Zhaohui Wang, Liwei Lv, Deyan Yin, Dan Chen, Zhihao Han, Yi Ma, Min Zhang, Man Yang, Yueqing Gu
Journal: Theranostics (2016)

Photodynamic therapy (PDT) has recently emerged as an approach to enhance intratumoral accumulation of nanoparticles. However, conventional PDT is greatly limited by the inability of the excitation light to sufficiently penetrate tissue, rendering PDT ineffective in the relatively deep tumors. To address this limitation, we developed a novel PDT platform and reported for the first time the effect of deep-tissue PDT on nanoparticle uptake in tumors. This platform employed c(RGDyK)-conjugated upconversion nanoparticles (UCNPs), which facilitate active targeting of the nanoconstruct to tumor vasculature and achieve the deep-tissue photosensitizer activation by NIR light irradiation. Results indicated that our PDT system efficiently enhanced intratumoral uptake of different nanoparticles in a deep-seated tumor model. The optimal light dose for deep-tissue PDT (34 mW/cm(2)) was determined and the most robust permeability enhancement was achieved by administering the nanoparticles within 15 minutes following PDT treatment. Further, a two-step treatment strategy was developed and validated featuring the capability of improving the therapeutic efficacy of Doxil while simultaneously reducing its cardiotoxicity. This two-step treatment resulted in a tumor inhibition rate of 79% compared with 56% after Doxil treatment alone. These findings provide evidence in support of the clinical application of deep-tissue PDT for enhanced nano-drug delivery.
Pediatric Mental Health Care Dysfunction Disorder?
Authors: Ronald Pies
Journal: New England Journal of Medicine (2010)

To the Editor: The Perspective article by Parens et al. (May 20 issue)1 misleads, misinforms, and is missing relevant facts. The authors imply that the increase in the diagnosis of pediatric bipolar disorder was due to a cabal of child psychia­ trists rather than the increase in published, peer­ reviewed research. They argue that “no existing DSM [Diagnostic and Statistical Manual of Mental Disorders] diagnosis conveys the appropriate severity” of the moods and behaviors of children “who can be explo­ sively angry, irritable, frantically active, suicidal, or even homicidal.” An adult with these symp­ toms would very likely be diagnosed with bipo­ lar disorder, and 65% of adults with bipolar disorder report an early onset of the condition.2 Research from multiple sites supports the valid­ ity of pediatric bipolar disorder.3 The authors cite “sparse” evidence supporting the efficacy of medications. Large­scale pediat­ ric trials documenting safety and efficacy have led to Food and Drug Administration approval of two agents.4 They describe nonmedical treat­ ments as “first­line,” even though few studies document the usefulness of these resource­con­ suming therapies; those that do consider them adjuncts to medication, not replacements.5
The Decision-Making Process and the Outcome of Therapeutic Abortion
Authors: Cornelia Morrison Friedma, Rhoda Greenspan, Fay Mittleman
Journal: American Journal of Psychiatry (1974)

The American literature on abortion suggests that an immediate negative response to abortion is not uncommon among women undergoing this procedure and that short-term unhappiness and guilt may be part of the normal response. The proportion of women with serious psychiatric complications is probably less than 10 percent. Four case reports of postabortion psychiatric illness are presented that indicate (in agreement with the literature) that there is high risk in abortion when any of the following elements is present: strong ambivalence, coercion, medical indication, concomitant severe psychiatric illness, and the woman's feeling that the decision was not her own.
A Systematic Comparison of Linear Regression–Based Statistical Methods to Assess Exposome-Health Associations
Authors: Lydiane Agier, Lützen Portengen, Marc Chadeau-Hyam, Xavier Basagaña, Lise Giorgis-Allemand, Valérie Siroux, Oliver Robinson, Jelle Vlaanderen, Juan R. González, Mark J. Nieuwenhuijsen, Paolo Vineis, Martine Vrijheid, Rémy Slama, Roel Vermeulen
Journal: Environmental Health Perspectives (2016)

Background:The exposome constitutes a promising framework to improve understanding of the effects of environmental exposures on health by explicitly considering multiple testing and avoiding selective reporting. However, exposome studies are challenged by the simultaneous consideration of many correlated exposures.Objectives:We compared the performances of linear regression–based statistical methods in assessing exposome-health associations.Methods:In a simulation study, we generated 237 exposure covariates with a realistic correlation structure and with a health outcome linearly related to 0 to 25 of these covariates. Statistical methods were compared primarily in terms of false discovery proportion (FDP) and sensitivity.Results:On average over all simulation settings, the elastic net and sparse partial least-squares regression showed a sensitivity of 76% and an FDP of 44%; Graphical Unit Evolutionary Stochastic Search (GUESS) and the deletion/substitution/addition (DSA) algorithm revealed a sensitivity of 81% and an FDP of 34%. The environment-wide association study (EWAS) underperformed these methods in terms of FDP (average FDP, 86%) despite a higher sensitivity. Performances decreased considerably when assuming an exposome exposure matrix with high levels of correlation between covariates.Conclusions:Correlation between exposures is a challenge for exposome research, and the statistical methods investigated in this study were limited in their ability to efficiently differentiate true predictors from correlated covariates in a realistic exposome context. Although GUESS and DSA provided a marginally better balance between sensitivity and FDP, they did not outperform the other multivariate methods across all scenarios and properties examined, and computational complexity and flexibility should also be considered when choosing between these methods.Citation:Agier L, Portengen L, Chadeau-Hyam M, Basagaña X, Giorgis-Allemand L, Siroux V, Robinson O, Vlaanderen J, González JR, Nieuwenhuijsen MJ, Vineis P, Vrijheid M, Slama R, Vermeulen R. 2016. A systematic comparison of linear regression–based statistical methods to assess exposome-health associations. Environ Health Perspect 124:1848–1856; http://dx.doi.org/10.1289/EHP172
Gastric Carcinosarcoma and 18F-FDG PET/CT
Authors: Beilei Li, Yiqiu Zhang, Jun Hou, Liang Cai, Jianwei Zhou, Hongcheng Shi
Journal: Clinical Nuclear Medicine (2015)

Gastric carcinosarcoma is a rare, malignant neoplasm that simultaneously comprises mixed epithelial and mesenchymal elements. In the present study, we report a case of gastric carcinosarcoma composed of rhabdomyosarcoma and adenocarcinoma on 18F-FDG PET/CT.
Therapy for Hyperthyroidism and Graves' Ophthalmopathy
Authors: C A Gorman, K P Offord
Journal: New England Journal of Medicine (1998)

Myocardial Infarction in Women and MenTo the Editor: Malacrida et al. (Jan. 1 issue) 1 describe a hospital-based analysis of the outcome of acute myocardial infarction in women and men.They conclude that, after adjustment for various prognostic factors including age, there is a small independent association between female sex and early mortality and morbidity after suspected acute myocardial infarction.However, they do not refer to the study by Sonke et al., 2 who used community-based data in Auckland, New Zealand.They reported that the higher in-hospital case fatality rate in women after acute cardiac events was largely explained by the lower case fatality rate before admission to the hospital.Overall, the 28-day case fatality rate for all events was similar in men and in women.The authors suggested that there may be more sudden or early deaths among men, with the result that lower-risk men arrive at the hospital, whereas women may survive long enough to get to the hospital before dying.Their findings are supported by the World Health Organization's Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) study, 3 which used community registers in 38 countries.Of deaths occurring within 28 days after the onset of acute myocardial infarction, 37 percent occurred within 1 hour and 55 percent within 24 hours among the men, and 30 percent occurred within 1 hour and 48 percent within 24 hours among the women.Much effort has been expended in trying to explain dif-ferences in case fatality rates, whether on the basis of sex, ethnic group, or medical management, in hospitalized patients.The substantial proportion of sudden deaths with acute myocardial infarction that occur before hospitalization and their possible differential occurrence should remind us of the limitations of using hospital-based data alone, however large the numbers, in arriving at any firm conclusions about the overall prognosis of acute myocardial infarction.
MicroRNA-211 Enhances the Oncogenicity of Carcinogen-Induced Oral Carcinoma by Repressing TCF12 and Increasing Antioxidant Activity
Authors: Yi-Fen Chen, Cheng-Chieh Yang, Shou-Yen Kao, Chung-Ji Liu, Shu-Chun Lin, Kuo-Wei Chang
Journal: Cancer Research (2016)

miR-211 expression in human oral squamous cell carcinoma (OSCC) has been implicated in poor patient survival. To investigate the oncogenic roles of miR-211, we generated K14-EGFP-miR-211 transgenic mice tagged with GFP. Induction of oral carcinogenesis in transgenic mice using 4-nitroquinoline 1-oxide (4NQO) resulted in more extensive and severe tongue tumorigenesis compared with control animals. We found that 4NQO and arecoline upregulated miR-211 expression in OSCC cells. In silico and experimental evidence further revealed that miR-211 directly targeted transcription factor 12 (TCF12), which mediated suppressor activities in OSCC cells and was drastically downregulated in tumor tissues. We used GeneChip analysis and bioinformatic algorithms to identify transcriptional targets of TCF12 and confirmed through reporter and ChIP assays that family with sequence similarity 213, member A (FAM213A), a peroxiredoxin-like antioxidative protein, was repressed transcriptionally by TCF12. FAM213A silencing in OSCC cells diminished oncogenic activity, reduced the ALDH1-positive cell population, and increased reactive oxygen species. TCF12 and FAM213A expression was correlated inversely in head and neck carcinoma samples according to The Cancer Genome Atlas. OSCC patients bearing tumors with high FAM213A expression tended to have worse survival. Furthermore, 4NQO treatment downregulated TCF12 and upregulated FAM213A by modulating miR-211 both in vitro and in vivo Overall, our findings develop a mouse model that recapitulates the molecular and histopathologic alterations of human OSCC pathogenesis and highlight a new miRNA-mediated oncogenic mechanism. Cancer Res; 76(16); 4872-86. ©2016 AACR.
MRSA Infections
Authors: John L. Zeller, Robert M. Golub
Journal: JAMA (2011)

MRSA InfectionsS taphylococcus aureus (S aureus) is a type of bacterium.Like other kinds of bacteria, S aureus frequently lives on the skin and in the nose without causing health problems.Staphylococcus aureus becomes a problem when it is a source of infection in the skin, lungs, or blood.These bacteria can be spread from one person to another through casual contact or through sharing contaminated objects.Methicillin-resistant Staphylococcus aureus (MRSA) bacteria are resistant to commonly used antibiotics, the medicines used to treat bacterial infections.Because of this, MRSA infections are more difficult to treat than ordinary S aureus infections.MRSA that is acquired in a hospital is called hospital-associated MRSA (HA-MRSA).MRSA infections are now becoming more common in healthy, nonhospitalized persons.These infections can occur among young people with cuts or wounds who have close contact with each other, such as members of sports teams.This type of MRSA is called community-acquired MRSA (CA-MRSA).This Patient Page is based one one originally published in the October 17,
Course of depression in patients with hypertension, myocardial infarction, or insulin-dependent diabetes
Authors: K B Wells, W Rogers, M A Burnam, P Camp
Journal: American Journal of Psychiatry (1993)

The authors examined the course of depression over 2 years for outpatients with and without a history of hypertension, a history of myocardial infarction, or current insulin-dependent diabetes.Among outpatient visitors to the practices of 523 general medical clinicians and mental health specialists, 626 depressed patients were followed for 1 or 2 years with a telephone-administered interview based on the format of the National Institute of Mental Health Diagnostic Interview Schedule.Depressed patients with and without medical illness had high rates of persistent depressive symptoms and spells over 2 years. Patients with a lifetime history of myocardial infarction had significantly more spells of depression over the first follow-up year, more total symptoms of depression in the second follow-up year, and more depressive symptoms at the end of each follow-up year than depressed patients without myocardial infarction. The course of depression did not differ significantly for depressed patients with and without a lifetime history of hypertension or current insulin-dependent diabetes.Among depressed adult outpatients, a history of myocardial infarction is associated with a particularly poor clinical prognosis. A relatively high percentage of all depressed patients in this study had persistent depression regardless of the extent of medical comorbidity.
Newborn Health on the Line
Authors: Smisha Agarwal, Alain Labrique
Journal: JAMA (2014)

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
CRISPR Repair Reveals Causative Mutation in a Preclinical Model of Retinitis Pigmentosa
Authors: Wen-Hsuan Wu, Yi-Ting Tsai, Sally Justus, Ting-Ting Lee, Lijuan Zhang, Chyuan-Sheng Lin, Alexander G Bassuk, Vinit B Mahajan, Stephen H Tsang
Journal: Molecular Therapy (2016)

Massive parallel sequencing enables identification of numerous genetic variants in mutant organisms, but determining pathogenicity of any one mutation can be daunting. The most commonly studied preclinical model of retinitis pigmentosa called the "rodless" (rd1) mouse is homozygous for two mutations: a nonsense point mutation (Y347X) and an intronic insertion of a leukemia virus (Xmv-28). Distinguishing which mutation causes retinal degeneration is still under debate nearly a century after the discovery of this model organism. Here, we performed gene editing using the CRISPR/Cas9 system and demonstrated that the Y347X mutation is the causative variant of disease. Genome editing in the first generation produced animals that were mosaic for the corrected allele but still showed neurofunction preservation despite low repair frequencies. Furthermore, second-generation CRISPR-repaired mice showed an even more robust rescue and amelioration of the disease. This predicts excellent outcomes for gene editing in diseased human tissue, as Pde6b, the mutated gene in rd1 mice, has an orthologous intron-exon relationship comparable with the human PDE6B gene. Not only do these findings resolve the debate surrounding the source of neurodegeneration in the rd1 model, but they also provide the first example of homology-directed recombination-mediated gene correction in the visual system.
Abstract P3-07-48: Prediction of complete pathologic response to veliparib/carboplatin plus standard neoadjuvant therapy in HER2 negative breast cancer: Exploratory protein pathway marker results from the I-SPY 2 trial
Authors: JD Wulfkuhle, C Yau, DM Wolf, RI Gallagher, J Deng, L Brown-Swigart, G Hirst, Investigators I-SPY 2 Trial, H Rugo, OI Olopade, L Esserman, D Berry, L van't Veer, EF Petricoin
Journal: Cancer Research (2016)

Abstract Background: In the I-SPY 2 TRIAL, HER2- patients were randomized to receive standard chemotherapy or chemotherapy plus the oral PARP inhibitor veliparib in combination with carboplatin (V+C), which graduated in the HR-/HER2- arm. Exploratory analysis of protein signaling was performed to identify biomarker candidates that correlated with pCR in the HER2- population. We evaluated 110 key signaling proteins using reverse phase protein microarray (RPPA) data from pre-treatment LCM purified tumor epithelium. Methods: Of 115 patients, 97 (V+C: 61 controls: 36) had RPPA and pCR data. RPPA data was correlated to pCR in both the treated and control patients using parametric (t-test) or non-parametric (Wilcoxon) statistical analysis, depending on data distribution. Only analytes whose pre-treatment levels were associated with response in the V+C but not the control arm were identified (P&amp;lt;0.05). Markers are analyzed individually; p-values are descriptive and were not corrected for multiple comparisons. Results: 11 protein/phosphoprotein markers were significantly associated with pCR in the V+C arm but not in controls. Two were positive predictors of response: YAP S127 p= 0.03 and LC3B p=0.04. Negative predictors of response included Cyclin D1 p=0.001, and a number of phosphorylated RTKs: ROS Y2274 p=0.03, IGF1R Y1135/Y1136-IR Y1150/Y1151 p=0.03, ERBB4 Y1284 p=0.002, total HER2 p=0.04, and total IGF1R p=0.01. Moreover, a number of AKT-mTOR pathway proteins were found to be negative predictors of V+C response: ACC S79 p=0.005, p70S6K S371 p=0.01, and B-RAF S445 p=0.01. Conclusion: Our sample size is too small to draw definitive conclusions and the results are exploratory. Coordinated RTK-mTOR pathway activation appears to be a hallmark signature of lack of response to veliparib in HER2- tumors. We also found that HER2 levels were correlated paradoxically with lack of response in this HER2- population, suggesting potential added clinical value of quantitative HER2 measurement techniques. Such exploratory results merit evaluation in larger trials with HER2- breast cancer patients. Citation Format: Wulfkuhle JD, Yau C, Wolf DM, Gallagher RI, Deng J, Brown-Swigart L, Hirst G, I-SPY 2 Trial Investigators, Rugo H, Olopade OI, Esserman L, Berry D, van't Veer L, Petricoin EF. Prediction of complete pathologic response to veliparib/carboplatin plus standard neoadjuvant therapy in HER2 negative breast cancer: Exploratory protein pathway marker results from the I-SPY 2 trial. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P3-07-48.
New broom at the top? An interview with Anders Milton, the chairman of the World Medical Association's Council
Authors: D. Carnall
Journal: BMJ (1995)

EXAMPLEThe event that most worries endoscopic surgeons is intraoperative vascular injury that leads to loss of a limb or death.We selected well known international reports of series of laparoscopic appendicectomies and cholecystectomies from the literature.3'5None of them reported a major vascular injury with subsequent loss of a limb or death.We applied Hanley's rule of three to the data in the papers to calculate the upper limit of a 95% confidence interval for such an adverse event.The table shows the results of these calculations.
Effects of Various Dietary Staples on Esophageal Carcinogenesis Induced in Rats by Subcutaneously Administered &lt;italic&gt;N&lt;/italic&gt;-Nitrosomethylbenzylamine
Authors: S J van Rensburg, J M Hall, D B du Bruyn
Journal: JNCI Journal of the National Cancer Institute (1985)

Previous epidemiologic studies associated large differences of esophageal cancer risk with the nature of the staple diet. In this study, various cereals and dietary staples were fed to inbred BD IX rats for 7 months or longer. N-Nitrosomethylbenzylamine [(MBN) CAS:937-40-6] was given five times subcutaneously between the 45th and 58th day. The percentage of rats with tumors and the mean number of tumors per esophagus were similar when corn, wheat, commercial bird-resistant sorghum, bananas, and polished rice were fed but were strikingly lower when the basis of the diets was millet, red sorghum, brown rice, or potatoes. The number of esophageal tumors was significantly related to the dietary concentration of some minerals and vitamins. Supplementing marginally deficient corn or wheat diets with various combinations of nicotinic acid, riboflavin, zinc, magnesium, molybdenum, and selenium significantly reduced the numbers of esophageal tumors. When the feeding of protective cereals or nutrients was commenced only 150 days after MBN was given, a marked inhibitory effect on the progression of tumors was still observed.
Website of the Week: Doctors and the drug industry
Authors: Marcus Müllner
Journal: BMJ (2003)

There is evidence that industry sponsored research leads more often to an outcome favourable to the drug under investigation (p 1167). Studies with low methodological quality tend to overestimate an effect but the methodological quality of studies funded by drug companies is no worse than that of other studies—often it is even better.

Developing new drugs without the industry is unfortunately not realistic. Let's ignore all the preclinical research—this is regulated by good laboratory practice guidelines (www.oecd.org/env/glp). Let's jump directly to clinical research. Good clinical practice (GCP) protects research subjects and is a quality assurance tool. The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) “is a unique project that brings together the regulatory authorities of Europe, Japan, and the United States and experts from the pharmaceutical industry in the three regions to discuss scientific and technical aspects of product registration.” All the relevant guidelines are available in pdf format (www.ich.org).

GCP is here to protect the public from inappropriately investigated drugs. The European Agency for the Evaluation of Medicinal Products is the relevant regulating body in Europe (www.emea.eu.int), the equivalent of the US Food and Drug Administration (www.fda.gov).

Designing a trial according to GCP is not all that difficult but translating this into research practice is no mean feat. Even though the industry spends more on marketing than on research (www.nofreelunch.org), there is still much money going into research and development. It seems that the non-corporate research community still has a long way to go.