tbuckley/cabot-search huggingface dataset:
Prostate Cancer Pulmonary Metastasis Presenting as a Ground-Glass Pulmonary Nodule on 68Ga-PSMA-11 PET/CT
Authors: David J. Lubin, Stuart B. Holden, Matthew B. Rettig, Robert E. Reiter, Christopher R. King, Jay M. Lee, Dean W. Wallace, Jeremie Calais
Journal: Clinical Nuclear Medicine (2019)

Ga-prostate-specific membrane antigen 11 (PSMA) PET/CT imaging accurately depicts metastatic prostate adenocarcinoma (PCa). Pulmonary metastases of PCa are often overlooked on follow-up imaging in patients after initial treatment and following androgen deprivation therapy. Here we present a rare case of biopsy-proven PCa pulmonary metastasis with a ground-glass appearance. The increased PSMA expression and the evolving CT features of the solid component of the ground-glass nodule detected by PSMA PET/CT imaging led to surgical resection and PET/CT-guided therapy.
A Blood-Based Multi Marker Assay Supports the Differential Diagnosis of Early-Stage Pancreatic Cancer
Authors: Andreas W. Berger, Daniel Schwerdel, Anke Reinacher-Schick, Waldemar Uhl, Hana Algül, Helmut Friess, Klaus-Peter Janssen, Alexander König, Michael Ghadimi, Eike Gallmeier, Detlef K. Bartsch, Michael Geissler, Ludger Staib, Andrea Tannapfel, Alexander Kleger, Alica Beutel, Lucas-Alexander Schulte, Marko Kornmann, Thomas J. Ettrich, Thomas Seufferlein
Journal: Theranostics (2019)

The most frequent malignancy of the pancreas is the pancreatic ductal adenocarcinoma (PDAC).Despite many efforts PDAC has still a dismal prognosis.Biomarkers for early disease stage diagnosis as a prerequisite for a potentially curative treatment are still missing.Novel blood-based markers may help to overcome this limitation.Methods: Prior to surgery plasma levels of thrombospondin-2 (THBS2), which was recently published as a novel biomarker, and CA19-9 from 52 patients with histologically proven PDAC were determined, circulating cell-free (cfDNA) was quantified.15 patients with side-branch IPMNs without worrisome features and 32 patients with chronic pancreatitis served for comparison.Logit (logistic regression) models were used to test the performance of single biomarkers and biomarker combinations.Results: CA19-9 and THBS2 alone showed comparable c-statistics of 0.80 and 0.73, respectively, improving to 0.87 when combining these two markers.The c-statistic was further increased to 0.94 when combining CA19-9 and THBS2 with cfDNA quantification.This marker combination performed best for all PDAC stages but also for PDACs grouped by stage.The greatest improvement over CA19-9 was seen in the group of stage I PDAC, from 0.69 to 0.90 for the three marker combination.Conclusion:These data establish the combination of CA19-9, THBS2 and cfDNA as a composite liquid biomarker for non-invasive diagnosis of early-stage PDAC.
Next-generation sequencing combined with routine methods to detect the pathogens of encephalitis/meningitis from a Chinese tertiary pediatric neurology center
Authors: Jian-zhao Zhang, Ping Zheng, Hong-mei Sun, Jing-jing Dong, Shao-li Li, Si-yuan Fan, Hai-tao Ren, Hong-long Wu, Hong-zhi Guan, Qian Chen
Journal: Journal of Infection (2019)
The Spectrum of Hepatic Involvement in Patients With Telomere Disease
Authors: Devika Kapuria, Gil Ben‐Yakov, Rebecca Ortolano, Min Ho Cho, Or Kalchiem‐Dekel, Varun Takyar, Shilpa Lingala, Naveen Gara, Michele Tana, Yun Ju Kim, David E. Kleiner, Neal S. Young, Danielle M. Townsley, Christopher Koh, Theo Heller
Journal: Hepatology (2019)

Loss-of-function mutations in genes that encode for components of the telomere repair complex cause accelerated telomere shortening. Hepatic involvement has been recognized as a cause of morbidity in telomere diseases, but very few studies have characterized the nature and extent of liver involvement in affected patients. We report the prevalence and characteristics of liver involvement in a large cohort of patients with telomere disease evaluated serially at the National Institutes of Health. One hundred twenty-one patients with known or suspected telomere disease were screened; 40 patients with liver involvement were included in the current study. Median follow-up was 2.4 years. Data were collected regarding their demographic information, laboratory analysis, imaging, and histopathology. Forty patients (40% of the cohort) with a median age of 42 years were found to have liver involvement. Liver enzyme elevation was cholestatic in pattern; 8 (21%) had drug-related enzyme elevations. The most common imaging finding was increased hepatic echogenicity on ultrasound in 39% (9) of patients, followed by hepatomegaly in 26% (6). Biopsies were infrequent because of risk associated with thrombocytopenia, but in 6 patients, there were varying findings: nodular regenerative hyperplasia, steatohepatitis, hemosiderosis, cholestasis, and cirrhosis with hepatic steatosis. Almost half the cohort had pulmonary diffusion abnormalities, and 25% died during the follow-up period. Conclusion: In patients with telomere disease, hepatic involvement is common and can present in diverse ways, including elevated liver enzymes as well as histopathologic and imaging abnormalities. Liver disease has important implications for morbidity and mortality in patients with telomere disease.
Abstracts
Authors: K Aljefri, M Ally, H Fassihi, F Lewis, N Attard, J Mellerio, C D'arrigo, L Igali, A Robson, M Bajwa, J Rhee, S Walsh, M Kvaskoff, N Pandeya, A Green, C Baxter, M Davis, R Mortimore, L Westacott, D Wood, J Triscott, R Williamson, D Whiteman, J.-L Bernab, E Herrera-Acosta, M Mendiola- Fern Andez, N L Opez-Navarro, E Herrera-Ceballos, C Gomes, M Martinez, J Eon, M Cintra, R Stelini, O Almeida, E Graner, K Zechinn, U Gu ¨l, S Soylu, E Benzer, I Pak
Journal: British Journal of Dermatology (2014)

Insulin-like growth factor II mRNA-binding protein 3 (IMP-3) is an oncoprotein important in cell growth and migration in fetal development.Many studies have found IMP-3 expression in malignant tumours but not in adjacent benign tissues.Lu et al. reported that IMP-3 expression in dysplastic cervical lesions is closely associated with their invasive potential, and with more aggressive clinical behaviour of cervical squamous carcinoma (Lu D, Yang X, Jiang NY et al.IMP-3, a new biomarker to predict progression of cervical intraepithelial neoplasia into invasive cancer.Am J Surg Pathol 2011; 35: 1638-45).To date, reports have been limited to cervical, renal and urothelial carcinomas and malignant melanoma.We studied the expression of IMP-3 in a series of 62 dysplastic and/or invasive squamous lesions of the skin.These included 25 dysplastic or squamous cell carcinomas (SCCs) in situ (SCCIS) of various types and 37 SCCs, 11 of which have a coexisting in situ component.Paraffin-embedded blocks were retrieved from the departmental archives, processed and stained with IMP-3 (Dako, IgG monoclonal 69Á1, dilution 1 : 100, ethylenediaminetetraacetic acid antigen retrieval pretreatment).The stained slides were then reviewed for strength and location of immunostaining.Four of 25 SCCISs had diffuse strong IMP-3 expression, and two of these had adjacent normal epidermis that was immunonegative.Four vulval lesions were negative.The five examples of psoralen-ultraviolet A-induced dysplasia were negative.Sixteen of 37 SCCs had expression of IMP-3, usually strongly and diffusely, including two of six tumours arising following renal transplantation.Five of 10 SCCs arising in epidermolysis bullosa (EB) were positive; three of the patients with EB with positive tumours have died of widespread malignancy.These findings suggest that expression of the oncoprotein IMP-3 is associated with invasive but not in situ SCCs, and therefore might play an important role in the development of invasion in some tumours.
Cabozantinib in advanced non-clear-cell renal cell carcinoma: a multicentre, retrospective, cohort study
Authors: Nieves Martínez Chanzá, Wanling Xie, Mehmet Asim Bilen, Hannah Dzimitrowicz, Jarred Burkart, Daniel M Geynisman, Archana Balakrishnan, I Alex Bowman, Rohit Jain, Walter Stadler, Yousef Zakharia, Vivek Narayan, Benoit Beuselinck, Rana R McKay, Abhishek Tripathi, Russell Pachynski, Andrew W Hahn, JoAnn Hsu, Sumit A Shah, Elaine T Lam, Tracy L Rose, Anthony E Mega, Nicholas Vogelzang, Michael R Harrison, Amir Mortazavi, Elizabeth R Plimack, Ulka Vaishampayan, Hans Hammers, Saby George, Naomi Haas, Neeraj Agarwal, Sumanta K Pal, Sandy Srinivas, Benedito A Carneiro, Daniel Y C Heng, Dominick Bosse, Toni K Choueiri, Lauren C Harshman
Journal: The Lancet Oncology (2019)
720. EGFRvIII Retargeted Oncolytic Measles Virus Strains Have Significant Antitumor Activity Against Gliomas
Journal: Molecular Therapy (2005)

Gliomas are primary CNS tumors with dismal prognosis despite use of multimodality treatment. Amplification of the epidermal growth factor receptor (EGFR) gene is present in approximately 40% of the most common glioma type, glioblastoma multiforme (GBM). EGFR amplification is often associated with gene rearrangements, the most common of which gives rise to the tumor-specific EGFRvIII, that offers significant therapeutic targeting potential. We have shown that measles virus vaccine strains have significant activity against gliomas (Phuong L et al, 2003). We have also identified mutations, that ablate recognition of the natural receptors CD46 or SLAM (Vongpunsawad et al, 2004; Nakamura et al, 2004). Our hypothesis was that EGFRvIII retargeted oncolytic measles virus strains would demonstrate a high therapeutic index against EGFRvIII expressing GBM.
The NHS in England in 2013
Authors: C. Ham
Journal: BMJ (2012)

Funding and service pressures are likely to have an impact on the quality of care

The end of 2012 saw the NHS in England facing increasing demands from patients as a result of winter pressures and the norovirus. These demands have been compounded by cuts in social care funding and support, which make it difficult to prevent hospital admissions and ensure timely discharge. Despite these pressures, the performance of the NHS is holding up well on most of the available indicators, although a growing number of providers are in deficit, and it is proving difficult to maintain short waiting times in emergency departments.1

What then are the prospects for the NHS in 2013? As it enters the third year in which its budget will grow only in line with inflation, financial and service pressures on England’s NHS seem certain to increase. A recent survey of finance directors found that, on the basis of their plans and those of other providers in their area, many thought that quality of patient care might be adversely affected in 2013.2

Providers may also find it difficult to balance their budgets when, as the National Audit Office reported recently, most of the “easy” efficiency savings have been achieved.3 The irony here is that prudent financial management over the past two years has …
Does Trial Participation Improve Outcomes for Higher-Risk Myelodysplastic Syndromes (MDS) Patients Treated at Specialty Centers?
Authors: Sudipto Mukherjee, David P. Steensma, Rami S. Komrokji, Amy E. DeZern, Gail J. Roboz, Guillermo Garcia-Manero, Aziz Nazha, Jaroslaw P. Maciejewski, Mikkael A. Sekeres, Brian P. Hobbs, Xuefei Jia
Journal: Blood (2018)
Clinical Dermatology
Authors: N. A. Soter, D. S. Wilkinson, T. B. Fitzpatrick
Journal: New England Journal of Medicine (1973)

THIS review of clinical dermatology attempts to highlight some of the recent advances. Syphilis and primary malignant melanoma, topics that fall within the scope of dermatology, are not included here because they have already been discussed in the Journal.1 , 2 Selected Skin Disorders and Skin Manifestations of Multisystem DiseasesSkin Manifestations of Internal Malignant ConditionsCertain lesions on the skin should alert the physician to the possibility of an underlying malignant condition. A large body of literature has been generated on the association of skin lesions with malignant conditions, but it is often impossible to ascertain whether the association is . . .
2017 Update on Medical Overuse
Authors: Daniel J. Morgan, Sanket S. Dhruva, Eric R. Coon, Scott M. Wright, Deborah Korenstein
Journal: JAMA Internal Medicine (2017)

Overuse of medical care is a well-recognized problem.To identify and highlight original research articles published in 2016 that are most relevant to understanding medical overuse or strategies to reduce it.A structured review of English-language articles on PubMed published in 2016 coupled with examination of tables of contents of high-impact journals to identify articles related to medical overuse in adults. These articles were appraised for their importance to medicine.This study considered 2252 articles, 1224 of which addressed medical overuse. Of these, 122 were deemed most relevant based on originality, methodologic quality, and number of patients potentially affected. The 10 most influential articles were selected by author consensus. Select findings from the studies include the lack of benefit of transesophageal echocardiography in the workup of cryptogenic stroke, increasing use of computed tomography in the emergency department from 2.2% to 9.4% from 2001 to 2010, and carotid ultrasonography and revascularization being performed for uncertain or inappropriate indications with 95% frequency. Likewise, services for which harms are likely to outweigh benefits include treatment for early-stage prostate cancer, which provides no mortality benefit but increases absolute risk of erectile dysfunction by 10% to 30%, oxygen for patients with moderate chronic obstructive pulmonary disease, surgery for meniscal tear with mechanical symptoms, and nutritional interventions for inpatients with malnutrition. This review highlights 2 methods for reducing overuse: clinician audit and feedback with peer comparison for antibiotic use (reduction in inappropriate antibiotic use from 20% to 4%) and a practical and sensible shared decision-making tool for low-risk chest pain (reduction in emergency department workup from 52% to 37%).The body of empirical work continues to expand related to medical services that are provided for inappropriate or uncertain indications. Engaging patients in conversations aimed at shared decision making and giving practitioners feedback about their performance relative to peers appear to be useful in reducing overuse.
Response to the letter: Identification of trimethylamine N-oxide (TMAO)-producer phenotype is interesting, but is it helpful?
Authors: Wei-Kai Wu, Lee-Yan Sheen, Ming-Shiang Wu
Journal: Gut (2019)

We thank Arduini et al 1 for the feedback. The importance of identifying trimethylanine N-oxide (TMAO)-producer phenotype was challenged in doubt about the significance of TMAO in cardiovascular disease (CVD).1 2 The reason we regard TMAO as a potential harmful rather than a beneficial or bystander molecule for CVD is based on a careful literature review from both affirmative and negative sides.3 4 We appreciated the opportunity to extend our discussions about the role of TMAO in CVD.

The letter mentioned a study conducted by Collins et al 5 that TMAO was inversely correlated to atherosclerosis in mice and concluded TMAO as protective for atherosclerosis. In this study, the plasma TMAO only reached 0.2ppm (2.66 µM) for the carnitine group that is far from the estimated pathological TMAO level (>10 µM). Besides, the negative …
Real-time automatic detection system increases colonoscopic polyp and adenoma detection rates: a prospective randomised controlled study
Authors: Pu Wang, Tyler M Berzin, Jeremy Romek Glissen Brown, Shishira Bharadwaj, Aymeric Becq, Xun Xiao, Peixi Liu, Liangping Li, Yan Song, Di Zhang, Yi Li, Guangre Xu, Mengtian Tu, Xiaogang Liu
Journal: Gut (2019)

Objective The effect of colonoscopy on colorectal cancer mortality is limited by several factors, among them a certain miss rate, leading to limited adenoma detection rates (ADRs). We investigated the effect of an automatic polyp detection system based on deep learning on polyp detection rate and ADR. Design In an open, non-blinded trial, consecutive patients were prospectively randomised to undergo diagnostic colonoscopy with or without assistance of a real-time automatic polyp detection system providing a simultaneous visual notice and sound alarm on polyp detection. The primary outcome was ADR. Results Of 1058 patients included, 536 were randomised to standard colonoscopy, and 522 were randomised to colonoscopy with computer-aided diagnosis. The artificial intelligence (AI) system significantly increased ADR (29.1%vs20.3%, p&lt;0.001) and the mean number of adenomas per patient (0.53vs0.31, p&lt;0.001). This was due to a higher number of diminutive adenomas found (185vs102; p&lt;0.001), while there was no statistical difference in larger adenomas (77vs58, p=0.075). In addition, the number of hyperplastic polyps was also significantly increased (114vs52, p&lt;0.001). Conclusions In a low prevalent ADR population, an automatic polyp detection system during colonoscopy resulted in a significant increase in the number of diminutive adenomas detected, as well as an increase in the rate of hyperplastic polyps. The cost–benefit ratio of such effects has to be determined further. Trial registration number ChiCTR-DDD-17012221; Results.
Association of Intake of Whole Grains and Dietary Fiber With Risk of Hepatocellular Carcinoma in US Adults
Authors: Wanshui Yang, Yanan Ma, Yue Liu, Stephanie A. Smith-Warner, Tracey G. Simon, Dawn Q. Chong, Qibin Qi, Jeffrey A. Meyerhardt, Edward L. Giovannucci, Andrew T. Chan, Xuehong Zhang
Journal: JAMA Oncology (2019)

Increased intake of whole grain and dietary fiber has been associated with lower risk of insulin resistance, hyperinsulinemia, and inflammation, which are known predisposing factors for hepatocellular carcinoma (HCC). Therefore, we hypothesized that long-term intake of whole grains and dietary fiber may be associated with lower risk of HCC.To assess the associations of whole grain and dietary fiber intake with the risk of HCC.Cohort study of the intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) in 125 455 participants from 2 cohorts from the Nurses' Health Study and the Health Professionals Follow-up Study.Intake of whole grains, their subcomponents (bran and germ), and dietary fiber (cereal, fruit, and vegetable) were collected and updated almost every 4 years using validated food frequency questionnaires.Multivariable hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression model after adjusting for most known HCC risk factors.After an average follow-up of 24.2 years, we identified 141 patients with HCC among 125 455 participants (77 241 women and 48 214 men (mean [SD] age, 63.4 [10.7] years). Increased whole grain intake was significantly associated with lower risk of HCC (the highest vs lowest tertile intake: HR, 0.63; 95% CI, 0.41-0.96; P = .04 for trend). A nonsignificant inverse HCC association was observed for total bran (HR, 0.70; 95% CI, 0.46-1.07; P = .11 for trend), but not for germ. Increased intake of cereal fiber (HR, 0.68; 95% CI, 0.45-1.03; P = .07 for trend), but not fruit or vegetable fiber, was associated with a nonsignificant reduced risk of HCC.Increased intake of whole grains and possibly cereal fiber and bran could be associated with reduced risk of HCC among adults in the United States. Future studies that carefully consider hepatitis B and C virus infections are needed to replicate our findings, to examine these associations in other racial/ethnic or high-risk populations, and to elucidate the underlying mechanisms.
The Future of Primary Care in the United States Depends on Payment Reform
Authors: Sondra Zabar, Andrew Wallach, Adina Kalet
Journal: JAMA Internal Medicine (2019)

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521 PROSPECTIVE STUDY OF HEPATITIS B VIRUS REACTIVATION IN HBSAG-NEGATIVE PATIENTS AFTER CHEMOTHERAPY WITH RITUXIMAB: HBV-DNA MONITORING AND ENTECAVIR PROPHYLAXIS
Authors: H. Kojima, H. Tsujimura, T. Sugawara, N. Mimura, M. Ise, C. Sakai, S. Yamada, T. Miyaki, K. Kumagai
Journal: Journal of Hepatology (2012)
Abstract 1461: Wnt2 Plays a Key Role in Cardiac Development Via a Non-Canonical Pathway
Authors: Takeshi Onizuka, Shinsuke Yuasa, Kenichiro Shimoji, Keiichi Fukuda, Satoshi Ogawa
Journal: Circulation (2008)

Embryonic stem (ES) cells are a promising source of cardiomyocytes, but their clinical application has been hindered by the lack of selective differentiation methods. Although several signals are involved in heart development, the precise signals that mediate cardiomyocyte differentiation remain undetermined. Wnt family has a potent effect on the various organ development. To address this issue, we investigated the expression of wnt genes in the embryonic heart. Then we applied these findings to establish an efficient protocol to induce cardiomyocytes in vitro . (1) We analyzed TOP-EGFP mice to clarify whether canonical wnt signal pathway is important in the developing heart. TOP-EGFP mice are transgenic mice in which the EGFP gene is located under the β-catenin binding site so that the EGFP protein expresses when the canonical pathway is activated. They did not reveal any GFP in early stage heart, indicating that the canonical pathway is not involved. (2) Expression of non-canonical wnt was screened. Whole mount in situ hybridization of wnt2 and nkx2.5 (positive control) was performed at mouse embryo. Wnt2 was strongly expressed in the the heart-forming area in stages from E7.5 to E9.0. (3) We applied this embryonic wnt2 expression pattern to ES cell differentiation. Using siRNA we knocked-down wnt2 protein in various phases, which inhibited formation of beating EB, and decreased cardiac muscle genes only during the primitive stage (day 2– 4). Also adding wnt2 protein to embryonic cells in the appropriate phase led to a marked induction of cardiac specific genes. But wnt2 did not affect the mesodermal gene expression, Brachyury T and Mesp1, suggesting that Wnt2 does not affect the primitive development of the mesodermal progenitor cells. However, Wnt2 critically promotes cardiac specification after mesodermal induction and increases the eventual cardiac musculature. Wnt2 was strongly expressed in the heart-forming region. We applied this finding to develop an effective protocol for obtaining cardiomyocytes from mouse ES cells by adding wnt2 protein and also to inhibit generation of cardiomyocytes by inhibition of wnt2 signaling. We concluded that wnt2 plays a key role in cardiac development via a non-canonical pathway.