tbuckley/cabot-search huggingface dataset:
Development of thermosensitive hydrogels carrying drugs and contrast agents for preventing the post-operative recurrence of brain tumor
Authors: Chiungyin Haung, Kuochen Wei
Journal: Neuro-Oncology (2018)

Brain tumor is one of the most deadly tumors for adults. The standard treatment is surgical resection followed by adjuvant chemo/radiotherapy. Due to the blockage of blood brain barrier (BBB) that protects normal brain from harmful agents, the chemotherapeutic agent is hardly achieving the target area. Thus, tumor may recur and result in poor prognosis. Therefore, if there is a material that can be sprayed and attached on the residual tumor tissues after tumor resection and sustained release drug locally to inhibit the residual tumor cells, it would be helpful for preventing the post-operative recurrence of brain tumor. In the present study, we developed a new highly thermosensitive hydrogels with low lower critical solution temperature which could simultaneously deliver hydrophilic epirubicin (EPI) and hydrophobic paclitaxel (PTX) with bovine serum albumin nanoparticles (BSA NPs) incorporation. Besides, the developed hydrogel also exhibits excellent magnetic resonance (MR) T1 contrast ability real-time monitor the distribution and degradation of hydrogel. Our results show this highly thermosensitive hydrogel could be congealed in 4 sec at 28°C, exhibit strong MR T1 contrast ability same as commercial contrast agent. The use of this hydrogel containing EPI and PTX can significantly and long-termly inhibit tumor growth over 63 days without the phenomenon of tumor recurrence in a mouse glioma xenograft model. Importantly, average survival was significantly improved in mice receiving BSA/PTX NPs-incorporated hydrogelGd/EPI treatment to outclass 63 days of median survival, compared to average survival spans of only about 18 days for control group, 21 days for BSA incorporated hydrogelGd treated group, and 32 days for free EPI treated group. The promising results reveal a conceptually new approach to the development of locally and long-termly drug release system against brain tumor recurrence used for post-operation.
SPECT/CT MIBG Imaging Is Crucial in the Follow-up of the Patients With High-Risk Neuroblastoma
Authors: Bin Liu, Sabah Servaes, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2018)

Planar whole-body imaging with I-radiolabeled metaiodobenzylguanidine (I-MIBG) is routinely used in the follow-up evaluation of neuroblastoma. In recent years, SPECT with integrated low-dose CT (SPECT/CT) has become more accessible. We investigated how much SPECT/CT can have additional diagnostic value over planar imaging in detection of residual and recurrent neuroblastoma.A total of 170 planar I-MIBG imaging scans with SPECT/CT follow-up scans performed in 147 patients with known high-risk neuroblastoma were retrospectively analyzed. Regions of increased I-MIBG uptake on planar images and the findings on SPECT/CT were compared.In 61% of the studies, the whole-body planar images and SPECT/CT images yielded the same result. In 39% of the time, however, SPECT/CT images provided additional information.In the follow-up of patients with high-risk neuroblastoma, SPECT/CT can significantly improve planar imaging interpretation and impact patient management.
Germline Mutations in the Mitochondrial 2-Oxoglutarate/Malate Carrier <i>SLC25A11</i> Gene Confer a Predisposition to Metastatic Paragangliomas
Authors: Alexandre Buffet, Aurélie Morin, Luis-Jaime Castro-Vega, Florence Habarou, Charlotte Lussey-Lepoutre, Eric Letouzé, Hervé Lefebvre, Isabelle Guilhem, Magalie Haissaguerre, Isabelle Raingeard, Mathilde Padilla-Girola, Thi Tran, Lucien Tchara, Jérôme Bertherat, Laurence Amar, Chris Ottolenghi, Nelly Burnichon, Anne-Paule Gimenez-Roqueplo, Judith Favier
Journal: Cancer Research (2018)

Abstract Comprehensive genetic analyses have identified germline SDHB and FH gene mutations as predominant causes of metastatic paraganglioma and pheochromocytoma. However, some suspicious cases remain unexplained. In this study, we performed whole-exome sequencing of a paraganglioma exhibiting an SDHx-like molecular profile in the absence of SDHx or FH mutations and identified a germline mutation in the SLC25A11 gene, which encodes the mitochondrial 2-oxoglutarate/malate carrier. Germline SLC25A11 mutations were identified in six other patients, five of whom had metastatic disease. These mutations were associated with loss of heterozygosity, suggesting that SLC25A11 acts as a tumor-suppressor gene. Pseudohypoxic and hypermethylator phenotypes comparable with those described in SDHx- and FH-related tumors were observed both in tumors with mutated SLC25A11 and in Slc25a11Δ/Δ immortalized mouse chromaffin knockout cells generated by CRISPR-Cas9 technology. These data show that SLC25A11 is a novel paraganglioma susceptibility gene for which loss of function correlates with metastatic presentation. Significance: A gene encoding a mitochondrial carrier is implicated in a hereditary cancer predisposition syndrome, expanding the role of mitochondrial dysfunction in paraganglioma. Cancer Res; 78(8); 1914–22. ©2018 AACR.
Coronary Computed Tomographic Angiography and Potential for Overtreatment—Reply
Authors: Andrew J. Foy, John M. Mandrola
Journal: JAMA Internal Medicine (2018)

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 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 Internal Medicine journal
Demonstrating Your Competence
Authors: Patrick Hutt
Journal: BMJ (2005)

Demonstrating Your Competence 4: Respiratory Disease, Mental Health, Diabetes, Dermatology 

Ruth Chambers, Gill Wakely, Alistair Pullan

Radcliffe Medical Press, 2004, £21.95, pp 256 ISBN 1 85775 6134

Rating: ⋆⋆⋆⋆/5





Demonstrating Your Competence 5: Substance Abuse, Palliative Care, Musculoskeletal Conditions, Prescribing Practice 

Gill Wakely, Ruth Chambers, Clare Gerada

Radcliffe Medical Press, 2004, £21.95, pp 240 ISBN 1 85775 6142

Rating: ⋆⋆⋆⋆/5



Appraisal and revalidation are the mottos of the new millennium. General practitioners, like it or not, need to show that they are up to speed with current clinical practice. How does one do this? No formal exam is required for revalidation (yet), but doctors are expected to produce …
More Extensive Lymph Node Dissection at Radical Prostatectomy is Associated with Improved Outcomes with Salvage Radiotherapy for Rising Prostate-specific Antigen After Surgery: A Long-term, Multi-institutional Analysis
Authors: Nicola Fossati, William P. Parker, R. Jeffrey Karnes, Michele Colicchia, Alberto Bossi, Thomas Seisen, Nadia Di Muzio, Cesare Cozzarini, Barbara Noris Chiorda, Claudio Fiorino, Giorgio Gandaglia, Detlef Bartkowiak, Thomas Wiegel, Shahrokh Shariat, Gregor Goldner, Antonino Battaglia, Steven Joniau, Karin Haustermans, Gert De Meerleer, Valérie Fonteyne, Piet Ost, Hein Van Poppel, Francesco Montorsi, Alberto Briganti, Stephen A. Boorjian
Journal: European Urology (2018)
Abstract P6-08-21: Early breast cancer-specific mortality in women with early stage breast cancer: Epidemiological and clinical characteristics
Authors: HM Johnson, JH Wong, NA Vohra, M Muzaffar
Journal: Cancer Research (2018)

Abstract Background and Aim: The five-year survival for women with stage I-II breast cancer is 93-100%. Despite standard of care treatment, a small subset of these women suffer early breast cancer-specific mortality and die within 12 months of diagnosis. This subset of women has not been previously described. The aim of this study is to characterize the incidence, demographics, and clinical characteristics of women with early stage breast cancer who suffer early breast cancer-specific mortality. Methods: Retrospective population study of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry of women diagnosed with stage I, IIA, or IIB breast cancer between 2004 and 2010. Data were filtered to histology codes 8500-8543 and 8575. Patient demographics (age, race, ethnicity) and clinical characteristics (stage, T stage, N stage, grade, ER status, PR status) of women in the early mortality subset were compared with those of women who survived &amp;gt; 12 months via the Chi-square test and the student t-test. Results: 259,380 women formed the basis of our analysis. 4,572 women (0.018%) died within 12 months of diagnosis. Compared with those who survived &amp;gt; 12 months, women who suffered early breast cancer-specific mortality were on average older (mean age 65.7 years versus 60.3 years, p&amp;lt;0.00001) and more likely to be Hispanic (14.3% versus 8.9%, p&amp;lt;0.00001) or black (11.0% versus 9.1%, p&amp;lt;0.00001). Clinical characteristics associated with early mortality included higher stage (stage IIA 34.2% versus 29.4%, stage IIB 21.8% versus 12.9%, p&amp;lt;0.00001), higher T stage (T2 40.5% versus 28.1%, T3 3.1% versus 1.6%, p&amp;lt;0.00001), higher N stage (N1 29.7% versus 23.2%, N2 0.8% versus 0.4%, N3 0.4% versus 0.1%, p&amp;lt;0.00001), higher grade (moderate 39.3% versus 42.5%, high 40.0% versus 31.5%, p&amp;lt;0.00001), higher rates of ER negativity (27.2% versus 19.0%, p&amp;lt;0.00001), and higher rates of PR negativity (38.5% versus 30.2%, p&amp;lt;0.00001). Conclusions: Breast cancer-specific mortality within 12 months of diagnosis of stage I-II breast cancer is a rare phenomenon which has not been previously characterized. There are several demographic and clinical features associated with early mortality, however further research is needed to identify specific prognostic factors that will allow identification of women at risk for early mortality at the time of diagnosis. Citation Format: Johnson HM, Wong JH, Vohra NA, Muzaffar M. Early breast cancer-specific mortality in women with early stage breast cancer: Epidemiological and clinical characteristics [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-08-21.
The prognostic significance of PDL1 expression in locally advanced non-small-cell lung cancer (LA-NSCLC) treated with definitive intent.
Authors: Devarati Mitra, Vishesh Agarwal, Yu-Hui Chen, Elizabeth H. Baldini, David Allen Barbie, Aileen B. Chen, Benjamin Glass, Gretchen Herman, David E. Kozono, Jonathan Daniel Schoenfeld, Raymond H. Mak
Journal: Journal of Clinical Oncology (2018)

150 Background: The PACIFIC trial showed an 11-month (mo) improved median (med) progression-free survival after definitive chemoradiation in LA-NSCLC using the PDL1 inhibitor, durvalumab. This study will likely change practice and puts further emphasis on understanding the significance of immune marker expression in this poor-prognosis disease. Methods: From 1999-2012, pathology specimens from 126 patients (pts) with LA-NSCLC who received combined modality therapy at our institution and had sufficient tissue available were selected for tissue microarrays. Immunohistochemistry for PDL1 (E1L3N), PDL2 (9E5), PD1 (NAT105) and CD3 (F7.2.38) was performed and tumor cells and infiltrating immune cells with moderate or high staining intensity were quantified using Definiens Tissue Studio image analysis software. Univariate and multivariate analyses (MVA) were performed using a Cox proportional hazards model. Results: Distribution by stage was: IIA-3%, IIB-3%, IIIA-65%, IIIB-29%. Sixty-three percent of pts had surgery. All patients received fractionated radiation and chemotherapy with 81% receiving concurrent chemoradiation. Med follow-up from start of therapy was 20 mo (rg 2-168 mo). Median overall survival (OS) was 21 mo (2-yr OS 43%). Median progression-free survival (PFS) was 11 mo (2-yr PFS 26%). Immune marker expression was: PDL1-med 3% (rg 0-58%), PDL2-med 0.03% (rg 0-0.5%), PD1-med 0% (rg 0-76%) and CD3-med 21% (rg 0-78%). PDL2, PD1 and CD3 were not associated with outcomes. However, PDL1 &gt; 8% (chosen as the 75 th -percentile) was associated with lower risk of distant metastases (DM) (HR 0.57, 95% CI 0.31-0.98, p = 0.04) and a trend towards longer time to disease progression (HR 0.63, 95% CI 0.37-1.02, p = 0.06). There was no association with local-regional recurrence or OS. On MVA including disease stage, PDL1 &gt; 8% was associated with lower risk of DM (HR 0.59, 95% CI 0.35-0.96, p = 0.03) and overall disease progression (HR 0.53, 95% CI 0.29-0.93), p = 0.02). Conclusions: PDL1 &gt; 8% is associated with lower risk of DM and better PFS in LA-NSCLC. This data suggests that even with traditional cancer therapies, the best outcomes may be seen in patients with higher PDL1 expression.
Consultants “robbed of place at heart of commissioning”
Authors: Caroline White
Journal: BMJ (2013)

Consultants say that they are being “robbed of a place at the heart of commissioning” because commissioning groups in England are only going through the motions of appointing secondary care clinicians to their boards.

Speaking at the BMA’s annual UK consultants conference in London on 6 March, Shanu Datta said that after starting well, the appointments process had “unravelled.” The goalposts had changed, he said, with priority given to potential conflicts of interest rather than to local knowledge and expertise. He also accused boards of adopting a “heavy handed” approach to the process.

Datta said that boards were appointing consultants who were either retired or who had no knowledge of the local health economy in a bid to comply with “token targets.” …
Prognostic impact of DNA repair germline variants in hormone sensitive prostate cancer stage.
Authors: Manish Kohli, Steven Hart, Jenna Lilyquist, Chunling Hu, David W. Hillman, Kun Lee, Rohan David Gnanaolivu, Eric Polley, Fergus Couch
Journal: Journal of Clinical Oncology (2018)

262 Background: Inherited and somatic aberrations in DNA repair genes in castrate resistant prostate cancer (CRPC) are associated with poor prognosis, but respond well to poly ADP ribose polymerase (PARP) inhibitors. We evaluated the prevalence and prognostic impact of harboring germline DNA repair variants in hormone sensitive prostate cancer (HSPC). Methods: Germline DNA from buffy coat was sequenced on HiSeq4000 with a median coverage of 200X for DNA repair variants in 20 genes in HSPC and CRPC patients (pts) enrolled in a hospital registry. Pts were divided into two groups; Group A: pts enrolled at the time of CRPC stage; Group B: treatment naïve HSPC stage pts. The primary endpoints were to determine any impact of harboring DNA repair variants on time to progression from HSPC to CRPC and, from CRPC to death. Group A pts were retrospectively analyzed for time to progression from HSPC to CRPC while Group B patients were followed prospectively for outcomes. Statistical analysis included Cox proportional hazard models and Wilcoxon Rank sum test with significance at p≤0.05. Results: In Group A, 51/562 CRPC pts (9.07%) had variants in the 20 genes (most frequently in BRCA2; n = 15). 44/51 pts with variants and 399/511 without variants had died. Median time of progression from HSPC to CRPC with/without variants was 22.1 vs. 25.1 months (mths); p-value = 0.679. Median time from CRPC to death with/without variants was 32.2 Vs. 27.7 mths (p = 0.6). In HSPC Group B, 14/100 pts were identified with germline variants in ATM (n = 5), CHEK2 (n = 3), BRCA1 (n = 2), BRCA2 (n = 2), RAD50 (n = 1), and MSH2 (n = 1). 31/100 have died and median time to progression from HSPC to CRPC with/without variants was 15.6 vs.11.8 mths, p-value = 0.76. Conclusions: Pts with germline DNA repair variants detected in HSPC stage were not associated with poor prognosis. Presence of additional somatic DNA repair gene aberrations in cell-free DNA, not investigated in this cohort may add to the prevalence of DNA repair gene variations in HSPC and together impact prognosis adversely so as to provide a rationale for PARP inhibitor therapy in select HSPC stage pts.
CV and interview skills
Authors: Peter Cross
Journal: BMJ (2005)

There are plenty of commercial companies out in cyberspace wishing to flog services for curriculum vitae (CV) writing and interview skills. Many offer tasters or titbits which they hope will lure you into getting out your plastic and parting with a few pounds. CV Masterclass (http://cv-masterclass.com) is typical of the breed—a few nibbles about what makes a good or bad CV, a service offering to look over your CV and help you write a covering letter, and an inspired section warning browsers about the cowboys in this field. There are four archetypal bad CVs: the …
Investigating the role of nuclear sphingosine kinase 1 (SphK1) in lung cancer
Authors: F. Napolitano, R. Rosa, V. D'Amato, R.C. Orsini, P. Ciciola, C. Di Mauro, A. Santaniello, R. Marciano, S. De Placido, R. Bianco
Journal: Annals of Oncology (2018)
Chronic breathlessness: re-thinking the symptom
Authors: Jane Macnaughton, Rebecca Oxley, Arthur Rose, Andrew Russell, James W. Dodd, Havi Carel
Journal: European Respiratory Journal (2018)

We wholly applaud the move by Johnson et al. [1] to improve awareness of breathlessness and to raise its profile as a subject for focussed clinical research. We consider their research and the ensuing proposal to recognise breathlessness via a new medical term, "chronic breathlessness syndrome", as important and justified. We share their goal, which is to direct attention to this neglected, undertreated and under-researched symptom. People with breathlessness should be involved in renaming their condition as their experience can be influenced by clinical language <http://ow.ly/ZKNj30hzUUM>
Febrile illness in Asia: gaps in epidemiology, diagnosis and management for informing health policy
Authors: P. Shrestha, T. Roberts, A. Homsana, T.O. Myat, J.A. Crump, Y. Lubell, P.N. Newton
Journal: Clinical Microbiology and Infection (2018)

Increasing evidence is becoming available on the aetiology and management of fevers in Asia; the importance of these fevers has increased with the decline in the incidence of malaria.To conduct a narrative review of the epidemiology and management of fevers in South and South-East Asia and to highlight gaps in our knowledge that impair evidence-based health policy decisions.A narrative review of papers published since 2012 on developments in fever epidemiology, diagnosis and treatment in South and South-East Asia. The papers that the authors felt were pivotal, from their personal perspectives, are discussed.We identified 100 studies. Among the 30 studies (30%)-including both children and adults-that investigated three or more pathogens, the most frequently reported fever aetiology was dengue (reported by 15, 50%), followed by leptospirosis (eight, 27%), scrub typhus (seven, 23%) and Salmonella serovar Typhi (six, 20%). Among four studies investigating three or more pathogens in children, dengue and Staphylococcus aureus were the most frequent, followed by non-typhoidal Salmonella spp, Streptococcus pneumoniae, Salmonella serovar Typhi, and Orientia tsutsugamushi. Increased awareness is needed that rickettsial pathogens are common but do not respond to cephalosporins, and that alternative therapies, such as tetracyclines, are required.Many key gaps remain, and consensus guidelines for study design are needed to aid comparative understanding of the epidemiology of fevers. More investment in developing accurate and affordable diagnostic tests for rural Asia and independent evaluation of those already on the market are needed. Treatment algorithms, including simple biomarker assays, appropriate for empirical therapy of fevers in different areas of rural Asia should be a major aim of fever research. Enhanced antimicrobial resistance (AMR) surveillance and openly accessible databases of geography-specific AMR data would inform policy on empirical and specific therapy. More investment in innovative strategies facilitating infectious disease surveillance in remote rural communities would be an important component of poverty reduction and improving public health.
Rapid Repigmentation of Vitiligo Using Tofacitinib Plus Low-Dose, Narrowband UV-B Phototherapy
Authors: Sa Rang Kim, Henry Heaton, Lucy Y. Liu, Brett A. King
Journal: JAMA Dermatology (2018)

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 Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast 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 Dermatology journal
INCREASED RISK OF THE PROGRESSION OF CORONARY ARTERY CALCIFICATION ACCORDING TO TRADITIONAL CARDIOVASCULAR RISK BURDEN IN ASYMPTOMATIC SUBJECTS: RESULTS FROM THE KOREA INITIATIVES ON CORONARY ARTERY CALCIFICATION (KOICA) REGISTRY
Authors: Ji Hyun Lee, David Sung, Kisang Yoo, Donghee Han, Hyeonju Jung, Hyo Eun Park, Su-Yeon Choi, Eun Ju Chun, Jidong Sung, Sung Hak Park, Hae-Won Han, Ji Min Sung, Hyuk-Jae Chang
Journal: Journal of the American College of Cardiology (2018)