tbuckley/cabot-search huggingface dataset:
Nanoscintillator-Mediated X-Ray Induced Photodynamic Therapy for Deep-Seated Tumors: From Concept to Biomedical Applications
Authors: Wenjing Sun, Zijian Zhou, Guillem Pratx, Xiaoyuan Chen, Hongmin Chen
Journal: Theranostics (2020)

Photodynamic therapy (PDT) has shown great effectiveness in oncotherapy but has not been implemented in broad clinical applications because the limited penetration depth of the light used has been unable to reach deep-seated tumors. However, X-rays have been widely used in the clinical field for imaging and radiation therapy due to their excellent tissue penetration depth. Recently, X-rays have been established as an ideal excitation source for PDT, which holds great promise for breaking the depth limitation of traditional PDT for treatment of deep-seated tumors. This review aims to provide an overview of nanoscintillator-mediated X-ray induced PDT (X-PDT) including the concept, the design considerations of nanosensitizers for X-PDT, the modelling of nanosensitizer energy deposition, the putative mechanism by which X-PDT kills cells, and the prospects of future directions. We attempt to summarize the main developments that have occurred over the past decades. Possibilities and challenges for the clinical translation of X-PDT are also discussed.
Testing a possible new way to diagnose scabies
Authors: P. Delaunay, A.L. Hérisé, L. Hasseine, C. Chiaverini, A. Tran, C. Mary, P. Del Giudice, P. Marty, M. Akhoundi, T. Hubiche
Journal: British Journal of Dermatology (2020)

This study, from a group based in different centres in France, has investigated a new non‐invasive (doesn't harm the skin in any way) method of diagnosing scabies. Scabies is an infestation due to a mite, sometimes called the itch mite, which burrows into the human skin causing a highly itchy rash. It is seen in children and the elderly, but it can affect people of any age and can be spread from person to person. It is difficult to diagnose as the main methods are either to take scrapings from the skin surface, or to examine the skin closely using a dermatoscope (surface microscope); both techniques require skill and interpretation. The new test discussed in this study is based on the rapid diagnostic technique known as the polymerase chain reaction, or PCR, which is used to identify specific pieces of the genetic code or DNA of the infecting organism, in this case a parasite, in skin material. The technique is simple to apply and uses a moistened swab which is lightly brushed over the affected areas, and this is then subjected to the PCR assay. In the study, about 38% of those patients with scabies infection, which had been proven using dermoscopy, had positive responses (i.e. shown to have scabies) in the new test. None of those without scabies infections were positive on PCR testing. This is the first step in the development of a potentially useful diagnostic technique. While the accuracy needs to be improved, it may become a useful tool for starting an investigation of a potential outbreak of scabies and, in the future, in diagnosing individual patients, rapidly and accurately. This summary relates to the study: Scabies polymerase chain reaction with standardized dry swab sampling: an easy tool for cluster diagnosis of human scabies
Randomised, double-blind, multicentre, mixed-methods, dose-escalation feasibility trial of mirtazapine for better treatment of severe breathlessness in advanced lung disease (BETTER-B feasibility)
Authors: Irene J Higginson, Andrew Wilcock, Miriam J Johnson, Sabrina Bajwah, Natasha Lovell, Deokhee Yi, Simon P Hart, Vincent Crosby, Heather Poad, David Currow, Emma Best, Sarah Brown
Journal: Thorax (2020)

New treatments are required for severe breathlessness in advanced disease. We conducted a randomised feasibility trial of mirtazapine over 28 days in adults with a modified medical research council breathlessness scale score ≥3. Sixty-four patients were randomised (409 screened), achieving our primary feasibility endpoint of recruitment. Most patients had COPD or interstitial lung disease; 52 (81%) completed the trial. There were no differences between placebo and mirtazapine in tolerability or safety, and blinding was maintained. Worst breathlessness ratings at day 28 (primary clinical activity endpoint) were, 7.1 (SD 2.3, placebo) and 6.3 (SD 1.8, mirtazapine). A phase III trial of mirtazapine is indicated. Trial registration: 32236160 ; European Clinical Trials Database (EudraCT no: 2015-004064-11).
Modelling the value of risk‐stratified skin cancer screening of asymptomatic patients by dermatologists
Authors: R.I. Hartman, Y. Xue, S. Singer, T.W. Markossian, C. Joyce, A. Mostaghimi
Journal: British Journal of Dermatology (2019)

Total‐body skin examination (TBSE) by dermatologists detects incidental skin cancers, but there is insufficient evidence for screening guidelines. As a result, the decision to perform screening TBSE in patients presenting for a focused visit is left to the dermatologist's discretion. To model the financial and time tradeoffs of risk‐stratified skin cancer screening by dermatologists in patients presenting with unrelated focused complaints. We performed an economic evaluation incorporating data from a previously published prospective multicentre international study in addition to US demographic data on age and skin phototype (SPT). The mean number needed to examine (NNE) for all US adults was 105 at an additional cost of $3796 per skin cancer detected when performing TBSE on a patient who presents for a focused exam. The NNE consistently decreased with increasing age and lighter SPT for every age and SPT screening threshold. The cost per person screened increased with higher age and lighter SPT owing to the higher likelihood of incurring diagnostic biopsies. The additional face‐to‐face time required per skin cancer detected by performing TBSE in patients who present for a focused visit was 4·5 h for all adults. We used a diverse cohort of international patients that did not include Americans and because of a low event rate, we combined detection of melanoma and nonmelanoma skin cancer. Incidental skin cancers are detected by screening TBSE and its value can be enhanced through consideration of patients' age and SPT, which are established and readily identifiable skin cancer risk factors. What is already known about this topic? Risk stratification of asymptomatic individuals using age and skin phototype (SPT) can enhance the value of total‐body skin examination when performed in the clinic by a dermatologist. What does this study add? For every age and SPT screening threshold, the number needed to examine to identify one skin cancer consistently decreased with increasing age and lighter SPT. When deciding to perform a screening skin examination in patients presenting with a focused complaint, dermatologists may wish to consider a patient's risk using age and SPT to enhance the yield of this intervention. Linked Comment: Ferris. Br J Dermatol 2020; 183:417–418.
Interpretation of OCT and OCTA images from a histological approach: Clinical and experimental implications
Authors: Nicolás Cuenca, Isabel Ortuño-Lizarán, Xavier Sánchez-Sáez, Oksana Kutsyr, Henar Albertos-Arranz, Laura Fernández-Sánchez, Natalia Martínez-Gil, Agustina Noailles, José Antonio López-Garrido, Maribel López-Gálvez, Pedro Lax, Victoria Maneu, Isabel Pinilla
Journal: Progress in Retinal and Eye Research (2020)
Preoperative survivin, ERCC1, and PTEN expression in stage III non-small cell lung cancer (NSCLC) patients (pts) treated with neoadjuvant and definitive chemoradiation and association with overall survival (OS).
Authors: Marta Batus, Mary J. Fidler, Kelly Kaiser Walters, Mark Pool, Brett Mahon, Sanjib Basu, Jeffrey Allen Borgia, David Sher, Philip D. Bonomi
Journal: Journal of Clinical Oncology (2012)

7067 Background: Thoracic radiation and concurrent chemotherapy consisting of platinum based doublets has produced modest improvement in long term survival for patient with locally advanced (LA) NSCLC. There is relatively little information regarding molecular profiles and outcome in LA-NSCLC patients (pts) treated with chemoradiation. The objective of this retrospective study is to evaluate potential relationships between expression of DNA repair enzyme ERCC1 and enzymes involved in cell survival – survivin and PTEN. Methods: Stage III NSCLC pts who were treated with chest radiation (40-60Gy) and concurrently with platinum doublet and who had sufficient pretreatment tissue were included in this study. Immunohistochemistry was used to detect nuclear and cytoplasmic expression (frequency 0-4 and intensity 0-4) of survivin, and PTEN, and for nuclear expression of ERCC1. Product of intensity and frequency was calculated for all markers and correlated with overall survival (OS). Results: 97 pts had adequate tumor samples for analysis. 53 women, median age 67. 48 pts with ERCC1 prod &lt;=6 had longer OS than 41 pts with ERCC1 prod &gt;6 (19.6 vs 1.0 months, p=0.034). 16 pts with ERCC1 prod &gt;6, PETN prod &lt;=6 and survivin prod &gt;4 had significantly lower OS than 68 pts with ERCC1&lt;=6, PETN &gt;6 and survivin &lt;=4 (17.2 vs 40.2 months, p&lt;0.001). Conclusions: The association of inferior survival in LA-NSCLC pts whose tumors express high survivin, low PTEN, and high ERCC1, suggests that combining inhibitors of survivin and or of PI3KCA with chemoradiation and developing strategies to inhibit DNA repair might improve outcomes in this group of pts.
Abstract 149: Double Sequential External Defibrillation in Refractory Ventricular Fibrillation: The Dose VF Pilot Randomized Controlled Trial
Authors: Sheldon Cheskes, Paul Dorian, Shelley McLeod, Damon Scales, Ruxandra Pinto, Linda Turner, Laurie J Morrison, Ian R Drennan, Richard Verbeek
Journal: Circulation (2019)

Background: Despite significant advances in resuscitation efforts, there are some patients who remain in ventricular fibrillation (VF) after multiple defibrillation attempts during out-of-hospital cardiac arrest (OHCA). Double sequential external defibrillation (DSED) and vector change defibrillation (VC) have been proposed as alternate therapeutic strategies for OHCA patients in shock-refractory VF. Objective: To determine the feasibility, safety and sample size required for a larger, multicentered, 3-arm, cluster randomized controlled trial (RCT) with 2 crossovers comparing DSED or VC to standard defibrillation (control group) for OHCA patients presenting in shock-refractory VF. Methods: We conducted a pilot cluster randomized controlled trial with crossover including all consecutive treated adult OHCA patients who presented in VF and received a minimum of three successive shocks. In addition to standard cardiac arrest care, each EMS agency was randomly assigned to provide standard defibrillation (control), DSED, or VC, followed by crossover to an alternate defibrillation strategy after 6 months. Results: Prior to the launch of the trial, 2,500 paramedics received in-person training in the techniques of DSED and VC defibrillation using a combination of didactic, video and simulated scenarios. Between March 2018 and June 2019, 113 patients were enrolled in 4 Canadian EMS agencies, with zero missed cases. Monthly enrollment varied from 1 to 6 cases per agency. With respect to feasibility, 96% of cases were compliant with the study protocol, and only five (4.4%) cases received a defibrillation strategy that differed from the allocation schedule. There were no reported cases of defibrillator malfunction, no concerns expressed by paramedics, patients, families, or ED staff about the trial, and no reported cases of skin burns or difficulty with pad placement. Conclusions: Findings from our pilot implementation trial suggest the DOSE VF protocol is feasible and safe. The results of this internal pilot trial will allow us to calculate a sample size for a definitive multicenter cluster RCT with crossovers to determine if these alternate defibrillation strategies for OHCA shock refractory VF will impact patient-centered, clinical outcomes.
IL-17 signaling in steatotic hepatocytes and macrophages promotes hepatocellular carcinoma in alcohol-related liver disease
Authors: Hsiao-Yen Ma, Gen Yamamoto, Jun Xu, Xiao Liu, Daniel Karin, Ju Youn Kim, Ludmil B. Alexandrov, Yukinori Koyama, Takahiro Nishio, Chris Benner, Sven Heinz, Sara B. Rosenthal, Shuang Liang, Mengxi Sun, Gabriel Karin, Peng Zhao, Pnina Brodt, Iain H. Mckillop, Oswald Quehenberger, Ed Dennis, Alan Saltiel, Hidekazu Tsukamoto, Bin Gao, Michael Karin, David A. Brenner, Tatiana Kisseleva
Journal: Journal of Hepatology (2019)
A third of community-dwelling elderly with intermediate and high level of Alzheimer’s neuropathologic changes are not demented: A meta-analysis
Authors: Mahmoud Reza Azarpazhooh, Abolfazl Avan, Lauren E. Cipriano, David G. Munoz, Mahdiyeh Erfanian, Amin Amiri, Saverio Stranges, Vladimir Hachinski
Journal: Ageing Research Reviews (2019)
Cxcl8 Expands Hematopoietic Stem and Progenitor Cells and Alters Their Interaction with the Endothelial Niche
Authors: Donn L Calkins, Jami L Shaffer, Emily M Teets, Alex M Belardo, Serine Avagyan, Leonard I Zon, Bradley W Blaser
Journal: Blood (2019)
Nanoscale pathways for human tooth decay – Central planar defect, organic-rich precipitate and high-angle grain boundary
Authors: Fan Yun, Michael V. Swain, Hansheng Chen, Julie Cairney, Jiangtao Qu, Gang Sha, Hongwei Liu, Simon P. Ringer, Yu Han, Lingmei Liu, Xixiang Zhang, Rongkun Zheng
Journal: Biomaterials (2019)
Novel ESCC-related gene ZNF750 as potential Prognostic biomarker and inhibits Epithelial-Mesenchymal Transition through directly depressing SNAI1 promoter in ESCC
Authors: Pengzhou Kong, Enwei Xu, Yanghui Bi, Xiaoqin Xu, Xue Liu, Bin Song, Ling Zhang, Caixia Cheng, Ting Yan, Yu Qian, Jian Yang, Yanchun Ma, Heyang Cui, Yuanfang Zhai, Binbin Zou, Xiangchen Liu, Yikun Cheng, Shiping Guo, Xiaolong Cheng, Yongping Cui
Journal: Theranostics (2020)

Background: Cancer genomic studies have identified Zinc Finger Protein 750 (ZNF750) was a novel significantly mutated gene in esophageal squamous cell carcinoma (ESCC).This study was designed to determine the clinical value and molecular mechanisms of ZNF750 in the development of ESCC.Methods: Genomic data from 4 reported ESCC cohorts were used to analyze the mutation profile of ZNF750.Tissue microarrays were used to detect its expression in 308 ESCC samples.Furtherly, the effects of ZNF750 on proliferation, colony formation, migration and invasion were tested in ESCC cells.PCR-array, chromatin immunoprecipitation (ChIP), luciferase reporter assays, and rescue assay were used to explore the mechanism of ZNF750.Correlation of ZNF750 with its target genes was analyzed in TCGA data from various SCC types.Results: ZNF750 was frequently mutated in ESCC and the most common type was nonsense mutation.Its nucleus/cytoplasm ratio in ESCC was significantly lower than that in paired non-tumor tissues; it was an independent and potential predictor for survival in ESCC patients.Furtherly, ZNF750 knockdown significantly promoted proliferation, colony formation, migration and invasion in ESCC cells.PCR-array showed epithelial-to-mesenchymal transition (EMT) was the main biologic process affected by ZNF750.Moreover, ZNF750 directly bound to the promoter region of SNAI1 and depressed its activity.Decreased ZNF750 up-regulated SNAI1 expression and promoted EMT phenotype.SNAI1 knockdown partially reversed the malignant phenotype induced by ZNF750 knockdown.Further TCGA data analyses showed ZNF750 expression was positively correlated with E-cadherin and negatively correlated with SNAI1, N-cadherin and Vimentin in ESCC and other SCC samples.Conclusion: Our results suggest that ZNF750 may act as a tumor suppressor by directly repressing SNAI1 and inhibiting EMT process in ESCC and other types of SCC.
一项关于 dupilumab 治疗湿疹青少年患者的研究
Authors: M.J. Cork, D. Thaçi, L.F. Eichenfield, P.D. Arkwright, T. Hultsch, J.D. Davis, Y. Zhang, X. Zhu, Z. Chen, M. Li, M. Ardeleanu, A. Teper, B. Akinlade, A. Gadkari, L. Eckert, M.A. Kamal, M. Ruddy, N.M.H. Graham, G. Pirozzi, N. Stahl, A.T. DiCioccio, A. Bansal
Journal: British Journal of Dermatology (2020)

特应性皮炎 (AD) 也称为湿疹, 其表现为皮肤发红、渗液和干燥并可能发生开裂和感染。剧烈瘙痒可能非常麻烦, 而且可能导致睡眠障碍, 是 AD 患者的主要主诉。 AD 通常从儿童开始, 而且影响全世界 1/4 的青少年。对于青少年, AD 皮肤的瘙痒和外观可显著降低生活质量,但适合长期使用的中度至重度 AD 有效治疗选择很少。 Dupilumab 是一种新的药物, 其可阻断导致过敏症状(如 AD)的关键分子。研究显示, 该药物对治疗成人中度至重度 AD 是有效的, 而且长期使用相对安全。 这项研究在 40 例年龄 12 至 17 岁的接受 dupilumab 治疗最长一年的患者中进行, 涉及欧洲和加拿大多个中心。研究人员希望了解 dupilumab 是否对治疗 AD 有效以及这类患者长期使用是否安全 。他们还希望了解 dupilumab 在此年龄段 AD 患者中的身体处理方式。 他们发现, dupilumab 治疗在这些年轻患者中显著改善了皮肤和 AD 症状(包括瘙痒), 而且不会造成任何意外的副作用。他们还发现 dupilumab 在这些年轻患者中的处理方式与成人相同。在整个一年治疗期内维持了改善。 研究结果支持使用 dupilumab 持续治疗中度至重度 AD 青少年患者。 This summary relates to the study: dupilumab 用于未控制的中度至重度特应性皮炎青少年患者中:IIA 期开放标签试验和随后的 III 期开放标签扩展研究结果
FDG PET/CT of Primary Ewing Sarcoma of IVC
Authors: Akshay Sharad Bedmutha, Ameya Puranik, Nilendu Purandare, Archi Agrawal, Sneha Shah, Ritesh R. Suthar, Venkatesh Rangarajan
Journal: Clinical Nuclear Medicine (2019)

Secondary involvement of inferior vena cava is a common presentation in aggressive solid malignancies, especially arising from kidneys, adrenals, and hepatobiliary system, mostly resulting from local infiltration. Rarely, primary tumors are seen arising from vascular tissue. The Ewing family of tumors commonly arises from bone, but there is a high propensity of these tumors to originate from nonosseous sites of mesenchymal cell origin. We would herewith demonstrate a rare presentation of Ewing sarcoma, seen originating from inferior vena cava, presenting as extensive intravascular tumor thrombosis, evaluated on FDG PET/CT imaging in a 12-year-old girl.
Abstract 15123: Depression is Associated With Cardiovascular Events in Japanese Treated Hypertensive Males, and is Not Associated With Antihypertensive Medication
Authors: Tomoyuki Kabutoya, Satoshi Hoshide, Kazuomi Kario
Journal: Circulation (2017)

Introduction: Depression is associated with cardiovascular events, and the frequency of depression is higher in females than in males. However, the associations among depression, antihypertensive m...
High frequency of BCR-ABL oncogene in pediatric acute lymphoblastic leukemia (ALL) patients as revealed by RT-PCR and interphase FISH: Association with disease biology and treatment outcome.
Authors: Zafar Iqbal, Tashfin Awan, Mudassar Iqbal, Noreen Sabir, Sultan Asad, Mohammad Hasan Siddique, Sumrin Sahar, Ammara H Tahir, Aamer Aleem, Tanveer Akhtar
Journal: Journal of Clinical Oncology (2012)

6612 Background: ALL is a complex genetic disease involving many fusion oncogenes (FGs) 1 frequency of which can vary in different ethnic groups 2,3 thus having implication in differential diagnosis, prognosis and treatment. Methods: We studied FGs in 101 pediatric ALL patients using RT-PCR 1 at Day 0, Day 15 and Day 29 and Interphase FISH, and their association with clinical features and treatment outcome. Results: Five most common FGs i.e. BCRABL (t 22; 9), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (del 1p32) were found in 88.1% (89/101) patients. Frequency of BCR-ABL was 44.5% (45/101). Patients with BCR-ABL had significantly lower survival (43.733 weeks ±4.241) as compared to others except MLL-AF4 and significantly higher TLC count. Overall survival was lower (52.2±3.75) than the patients with ETV6-RUN X 1 (65.2± 9.9) which may be due to overall high frequency of poor prognostic FGs (71%) as compared to ETV6-RUNX 1 (17.1%) (p=0.01). Conclusions: This is the first study from Pakistan correlating molecular markers, disease biology and treatment response. It is the highest reported frequency of BCR-ABL in pediatric ALL and was associated with disease biology and survival. Some authors have reported BCR-ABL frequency higher than in West 2,4,5 while others reported 45% frequency of ETV6-RUNX1 6 . These and our data reflect strong interplay of genetic and environmental factors in biology of pediatric ALL and its correlation with disease biology and treatment 2,3 . Our data indicates immediate need for large clinical trials of imatinib, dasatinib and nilotinib in paediatric ALL treatment in our ethnic group. This study will lead to unravel the mechanisms of BCR-ABL Leukemogenesis and to find population-specific biomarkers and drug targets. References: 1) van Dongen JJ, et al., Leukemia. 1999 Dec; 13(12):1901-28. 2) Iqbal Z, et al. J Pediatr Hematol Oncol. 2007 Aug; 29(8):585. 3) Ariffin H, et al. J Pediatr Hematol Oncol. 2007 Jan; 29(1):27-31. 4) Ramos C, et al. 2011 Sep; 139(9):1135-42. 5) Artigas A CG, et al. Rev Med Chil. 2006 Nov; 134(11):1367-76. 6) Karrman K, et al. Br J Haematol. 2006 Nov; 135(3):352-4.
Two processes are not necessary to understand memory deficits
Authors: Adam F Osth, John C Dunn, Andrew Heathcote, Roger Ratcliff
Journal: Behavioral and Brain Sciences (2019)

Abstract Bastin et al. propose a dual-process model to understand memory deficits. However, results from state-trace analysis have suggested a single underlying variable in behavioral and neural data. We advocate the usage of unidimensional models that are supported by data and have been successful in understanding memory deficits and in linking to neural data.