tbuckley/cabot-search huggingface dataset:
Multifunctional STING‐Activating Mn<sub>3</sub>O<sub>4</sub>@Au‐dsDNA/DOX Nanoparticle for Antitumor Immunotherapy
Authors: Min Zhou, Xiaoyu Wang, Shichao Lin, Yuan Cheng, Sheng Zhao, Junshu Lin, Zhuoyao Fang, Zhangping Lou, Li Qin, Hui Wei
Journal: Advanced Healthcare Materials (2020)

Abstract The promise of immunotherapy for cancer therapy has not been fully fulfilled because portions of tumors are immunosuppressive. To tackle this challenge, the initiation of immune system by stimulator of interferon genes (STING) pathway is explored and multifunctional STING‐activating nanoparticles are rationally designed for synergistic antitumor therapy. The STING‐activating nanoparticles have a formulation of Mn 3 O 4 @Au‐dsDNA/DOX, where dsDNA is used to activate STING for immunotherapy and doxorubicin (DOX) is chosen as a model drug for chemotherapy. The STING‐mediated immunity is activated, inducing interferon‐β (IFN‐β) production, increasing T cell priming, and enhancing effector T cell infiltration. Combined with chemotherapy, STING‐mediated immunotherapy shows good antitumor efficacy by inhibiting tumor growth and prolonging survival rate in vivo. The promise of cancer immunotherapy can be fulfilled by combining novel antitumor immunity with innovative nanotechnology, and chemotherapy and targeted therapies.
Characterization of ERBB2 alterations in non-small cell lung cancer.
Authors: Vijendra Singh, Rebecca Feldman, Ammar Sukari, Chul Kim, Hirva Mamdani, Alexander I. Spira, Gerold Bepler, Edward S. Kim, Luis E. Raez, Sachin Gopalkrishna Pai, Chukwuemeka Ikpeazu, Ari M. Vanderwalde, Joanne Xiu, Antoinette J. Wozniak, Hossein Borghaei, Stephen V. Liu, Misako Nagasaka
Journal: Journal of Clinical Oncology (2020)

e21553 Background: ERBB2 alteration (mutation and/or amplification) is associated with poor survival in non-small cell lung cancer (NSCLC) and is commonly reported as a resistance mechanism to EGFR tyrosine kinase inhibitors. Several clinical trials are ongoing for the management of ERBB2-altered NSCLC. Here we report the prevalence of different ERBB2 alterations in NSCLC. Methods: We retrospectively analyzed ERBB2 alterations in NSCLC tumors that underwent next-generation sequencing (NGS) with Caris Life Sciences. De-identified pathological and molecular information was collected. ERBB2 copy number of greater than 6 was defined as amplification; mutations were classified among 7 groups based on their mechanism of action. Results: A total of 12946 NSCLC tumors with ERBB2 NGS results were available. Among them, 12492 had ERBB2 copy number alteration (CNA) data available. 321 tumors (2.5%) had ERBB2 alteration (mutation or amplification). Among them, ERBB2 was mutated in 197 tumors (1.5%) and amplified in 134 (1.1%) tumors. Type of ERBB2 mutation, respective median age and distribution among sex is in the table. 10 tumors with ERBB2 mutation (7.46%) also showed ERBB2 amplification. Six percent of tumors (8/135) with ERBB2 exon 20 insertion mutations had co-occurring ERBB2 amplification. One tumor for each extracellular domain (ECD) and transmembrane group had co-occurring ERBB2 amplification. Eight tumors with ERBB2 mutation had an overlapping EGFR L858R or exon19del mutation. Seven of these 8 tumors were from the ECD group (7/21) and all had mutations in the S310 locus. One tumor was from the transmembrane group. Conclusions: Exon 20 insertion mutation is the most commonly found ERBB2 mutation among NSCLC, a few of them had co-occurring ERBB2 amplification. One third of tumors with extracellular domain ERBB2 mutation had EGFR mutation. Tarloxitinib (NCT03805841), trastuzumab deruxtucan (NCT03505719), pyrotinib (NCT02500199), poziotinib (NCT03318939) are just a few of the novel ERBB2 inhibitors available in clinical trials. It will be critical to utilize next generation sequencing to effectively capture uncommon mutations and amplifications in ERBB2 so that patients may be offered therapy directly targeted to their genomic alterations. [Table: see text]
Genomic profiling and mutation burden of Chinese prostate patients with microsatellite instability.
Authors: Ning Zhang, Baoan Hong, Xiaochen Zhao, Yuezong Bai
Journal: Journal of Clinical Oncology (2020)

e17531 Background: Prostate cancer with microsatellite instability-high (MSI-H) is identified as a distinct genotype that potentially benefit from immune checkpoint inhibitors. But the incidence and genomic profiling of microsatellite instability haven’t been well characterized in Chinese prostate cancer patients. Methods: Tumor tissue and matched blood sample from 241 Chinese prostate cancer patients were analyzed with targeted next-generation sequencing covering whole exon of 381 or 90 genes and 100 microsatellite loci. Tumor mutation burden (TMB), defined by non-silent somatic mutation counts in coding region per megabase (Mb), was calculated in tumors sequenced by 381-gene panel with coding region of 1.12Mb. Results: 7 patients (2.90%) were identified as MSI-H in overall population. Somatic or germline alterations of mismatch repair genes were detected in 5 of the 7 patients, including 2 MSH2 germline mutations, 2 MSH6 somatic mutations, 1 MSH2 somatic mutation, 1 PMS2 somatic mutation and 1 MLH3 somatic mutation. In MSI-H tumors, alterations in KMT2C (6/7), EGFR (5/7), KMT2D (5/7), JAK1 (5/7), PTEN (4/7), TP53 (3/7), ZFHX3 (3/7) and SPOP (3/7) were common. AR ligand binding domain was mutated in 3 of 7 patients, while no AR amplification was detected in MSI-H tumors. In 121 tumors sequenced by 381-gene panel, median TMB was 3.23 mutations/Mb. Median TMB was significantly higher in MSI-H tumors compared with MSS tumors (median TMB, 13.71 mutations/Mb versus 2.93 mutations/Mb, P &lt; 0.001). Median counts of single nucleotide variants (SNVs) and insertion-deletions (Indels) were 13 and 10 in MSI-H tumors that were also higher than that of MSS tumors with median SNVs and Indels of 2 (P = 0.004) and 1 (P &lt; 0.001), respectively. Conclusions: 2.9% patients were identified as MSI-H in Chinese prostate patients. MSI-H was associated with higher TMB, SNVs and Indels. Targeted next-generation sequencing is a practical tool for prostate cancer genotyping and treatment decision-making.
Application of automated segmentation and classification of PD-L1 immunohistochemistry images in cancer treatment prediction.
Authors: Xinrui Zhou, Xiaochen Zhang, Jinwang Wei, Jun Liu, Chun Dai, Guan Wang, Qiang Xu
Journal: Journal of Clinical Oncology (2020)

e15572 Background: Therapies targeting immune checkpoints, such as the programmed cell death-1 (PD-1) / programmed cell death ligand 1 (PD-L1) pathway, have become successful in treating several cancer types, particularly those with high PD-L1 expression. Patient response rates, however, are variable, demanding a more sensitive companion diagnostic test than the current method of manual scoring of PD-L1 immunohistochemistry images. The low predictive value of manual PD-L1 scoring is at least partially compounded by the pathologist-to-pathologist or hospital-to-hospital variation. To eliminate the variation caused by human factors, we developed an alternative PD-L1 scoring method based on automated image analysis and assessed its predictive and prognostic values. Methods: Archival or fresh tumor biopsies were analyzed for PD-L1 expression by immunohistochemistry. Digital images were automatically scored as PD-L1 positive or negative using a custom algorithm implemented in Python and Tensorflow, which uses a fine-tuned, ImageNet pre-trained, Inception-ResNet-V2 model as the binary classifier along with a modified U-net image segmentation model to determine the final prediction. Supervised machine learning was used to control for heterogeneity introduced by PD-L1 positive inflammatory cells in the tumor microenvironment. Samples from 256 patients were collected and used in algorithm training and verification by random assignment with an 8:2 split ratio. Results: In total, 10,000 images with balanced PD-L1 positive and negative distributions were obtained. A highly significant correlation of PD-L1 scores was found between pathologist-based consensus reading and automated analysis using our custom algorithm (R = 0.97, p &lt; 0.0001). The automated analysis reached 0.94 sensitivity and 0.96 specificity. Additionally, it showed excellent reproducibility (R = 1.0, p &lt; 0.0001) in independent trials executed on different workstations, which is far superior to the manual scoring performed by human examiners. Conclusions: Our automated PD-L1 evaluation algorithm significantly reduces scoring variability. It may help to identify cancer patients who can have optimal response to PD-1/PD-L1 related immune therapy and therefore facilitate patient stratification in clinical practice.
Underscoring the Importance of Allopurinol in Treating Gout: Results of a Food and Drug Administration–Mandated Safety Trial
Authors: Nikolay P. Nikolov, Sally Seymour, Rosemarie Neuner, Ya‐Hui Hsueh, Eugenio Andraca‐Carrera, Kusum Mistry
Journal: Arthritis & Rheumatology (2020)
Application of standardized patients in teaching of communication skills for medical students
Authors: Li-min Lao, Xiang-jie Zhang, Rong Zhou, Sun-fang Jiang, Shan-zhu Zhu
Journal: BMJ (2009)

The case design,standardized patients(SPs)training and training communication skills for medical students with SPs were illustrated in this paper.And our experiences of SPs using Were summarized.

Key words: 
Teaching; Standardized patients
One-year follow-up of health-related quality of life in the Swedish PREDIX HER 2 trial, evaluating docetaxel, trastuzumab sc, pertuzumab versus trastuzumab emtansine as neoadjuvant treatment of HER2 positive breast cancer.
Authors: Yvonne Brandberg, Theodoros Foukakis, Anne Andersson, Judith Bjohle, Ana Bosch, Lena Carlsson, Zakaria Einbeigi, Hanna Fredholm, Erika Isaksson-Friman, Mats Hellstrom, Hemming Johansson, Tobias Lekberg, Henrik Lindman, Jonas C. S. Bergh, Thomas Hatschek
Journal: Journal of Clinical Oncology (2020)

590 Background: Neoadjuvant therapy combining docetaxel, trastuzumab and pertuzumab (DTP) was compared to trastuzumab emtansine (T-DM1) in the randomised phase II PREDIX HER2 trial. Patients, ≥18 years with HER2 positive breast cancer, ≥20mm or with verified lymph node metastases, were randomised to six courses of DTP (Standard group) or T-DM1 (Experimental group) before surgery. After operation patients in the Standard arm received two, and those in the Experimental arm four courses of EC. Since there were no differences in proportions of complete response at surgery and in the event-free survival between the groups, health-related quality of life (HRQoL) is of special interest. Methods: HRQoL was measured, using European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 + EORTC QLQ-BR23, before randomisation, after six courses before surgery, at three months and one year after surgery. Results: Response rate for the questionnaires varied between 87% and 99% for the 198 included patients. There were no between-group differences at baseline. Results after six courses revealed statistically significant differences (p≤0.01), favouring the Experimental group on 12 out of 21 of the EORTC QLQ-C30 and BR23 variables (Physical-, Role-, and Social- functioning, Global quality of Life, Fatigue, Dyspnea, and Diarrhea, Body image, Sexual functioning, Sexual enjoyment, Systemic therapy side effects and Upset by hair loss). Three months after surgery, however, statistically significant differences in favour of the Standard group were found for six variables (Physical functioning, Nausea/vomiting, Dyspnea, Constipation, Systemic therapy side effects, Upset by hair loss). No other between group differences were found with one exception: lower levels of Breast symptoms in the Experimental group. One possible explanation is that patients in the Experimental group were still on chemotherapy at that assessment point, whereas the majority in the Standard group had terminated their treatment. No differences were found between the groups at the one-year after surgery follow-up, where the levels on most variables had returned to baseline values. Conclusions: HRQoL was better in the Experimental group during neoadjuvant treatment. Three months after surgery, however, HRQoL was in favour or the Standard arm. HRQoL returned to baseline levels for most variables at the one-year follow-up and no between-group differences were found. Clinical trial information: NCT02568839 .
Explaining or redefining mindreading?
Authors: Krzysztof Dołęga, Tobias Schlicht, Daniel C. Dennett
Journal: Behavioral and Brain Sciences (2020)

Abstract Veissière et al. disrupt current debates over the nature of mindreading by bringing multiple positions under the umbrella of free-energy. However, it is not clear whether integrating the opposing sides under a common formal framework will yield new insights into how mindreading is achieved, rather than offering a mere redescription of the target phenomenon.
Epidermal growth factor receptor tyrosine kinase inhibitor in treatment of elderly patients with nonsmall-cell lung cancer
Authors: Jing-ying Nong, Jing-hui Wang, Xin-jie Yang, Yi-fen Sun, Xin-yong Zhang, Yu-hua Wu, Xi Li, Hui Zhang, Na Qin, Quan Zhang, Shu-cai Zhang
Journal: BMJ (2012)

Seventy patients with advanced non-small-cell lung cancer (NSCLC) aged 65 or above were treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) erlotinib or gefitinib from February 2006 to September 2010. The efficacy and toxicities of treatment were retrospectively analyzed.The overall response rate and disease control rate were 31.4％ and 84.3％,respectively. Themedian progression-free survival time and median survival time were 8.0 months and 13.5 months,respectively(P ＜ 0.05 ). One-year survival rate was 54.3％. Response rate ( CR + PR) ( 42.9％ ) anddisease control rate (94.3％ )in female patients were superior to males (20.0％ and 74.3％ ) (P ＜ 0.05 ).Non-smoking and PS score ＜ 2 were good predictors for survival.The side effects were generally mild and mainly were skin rash and diarrhea.

Key words: 
Carcinoma non-small-cell lung;  Receptor, epidermal growth factor
The clinical application of ultravidet-blood irradiation of oxygenation in China
Authors: 王春艳, 童庭辉, 冯志强, 唐显玲
Journal: BMJ (2005)

紫外线照射充氧自血回输(ultraviolet-blood irradiation of oxygenation, UBIO)是一种将患者自身少量静脉血(3～5 ml/kg)在体外经UBIO治疗仪抗凝、紫外线照射和充氧等处理后回输的技术.这样处理过的血液在体内能引发一系列生化反应,已观察到具有提高血氧饱和度、增加组织供氧、改善微循环、纠正代谢紊乱、消炎抗病原微生物、调节免疫等非特异性功能.此法产生于20世纪20年代,起初用于感染性疾病的治疗研究.自80年代在我国临床开始应用以来,由于制备简单、疗效显著,已广泛用于神经系统、呼吸系统、心血管系统、糖尿病的微血管病变、自身免疫性疾病及免疫异常、精神病等多种疾病的治疗之中。
Deimplementation of the Choosing Wisely Recommendations for Low-Value Breast Cancer Surgery
Authors: Ton Wang, Alison S. Baskin, Lesly A. Dossett
Journal: JAMA Surgery (2020)

<h3>Importance</h3> Overtreatment of early-stage breast cancer results in increased morbidity and cost without improving survival. Major surgical organizations participating in the Choosing Wisely campaign identified 4 breast cancer operations as low value: (1) axillary lymph node dissection for limited nodal disease in patients receiving lumpectomy and radiation, (2) re-excision for close but negative lumpectomy margins for invasive cancer, (3) contralateral prophylactic mastectomy in patients at average risk with unilateral cancer, and (4) sentinel lymph node biopsy in women 70 years or older with hormone receptor–positive cancer. <h3>Objective</h3> To evaluate the extent to which these procedures have been deimplemented, determine the implications of decreased use, and recognize possible barriers and facilitators to deimplementation. <h3>Evidence Review</h3> A systematic review of published literature on use trends in breast surgery was performed in accordance with PRISMA guidelines. The Ovid, Embase, Cumulative Index to Nursing and Allied Health Literature, and Cochrane databases were searched for original research with relevance to the Choosing Wisely recommendations of interest. Eligible studies were examined for data about use, and any patient-level, clinician-level, or system-level factors associated with use. <h3>Findings</h3> Concordant with recommendations, national rates of axillary lymph node dissection for patients with limited nodal disease have decreased by approximately 50% (from 44% in 2011 to 30% to 34% in 2012 and 25% to 28% in 2013), and national rates of lumpectomy margin re-excision have decreased by nearly 40% (from 16% to 34% before to 14% to 18% after publication of a consensus statement). Conversely, national rates of contralateral prophylactic mastectomy continue to rise each year, accounting for up to 30% of all mastectomies for breast cancer (range in all mastectomy cases: 2010-2012, 28%-30%; 1998, &lt;2%), and rates of sentinel lymph node biopsy in women 70 years or older with low-risk breast cancer are persistently greater than 80% (range, 80%-88%). Factors associated with high rates of contralateral prophylactic mastectomy use are younger age, white race, increased socioeconomic status, and the availability of breast reconstruction; limited data exist on factors associated with high rates of sentinel lymph node biopsy in women 70 years or older. Successful deimplementation of axillary lymph node dissection and lumpectomy margin re-excision were associated with decreased costs and improved patient-centered outcomes. <h3>Conclusions and Relevance</h3> This review demonstrates variable deimplementation of 4 low-value surgical procedures in patients with breast cancer. Addressing specific patient-level, clinician-level, and system-level barriers to deimplementation is necessary to encourage shared decision-making and reduce overtreatment.
Serum testosterone level and overall survival in first-line abiraterone and enzalutamide for metastatic castration-resistant prostate cancer patients.
Authors: Maysa Tamara Silveira Vilbert, Marcelle Goldner Cesca, Natasha Carvalho Pandolfi, Vinicius Fernando Calsavara, Bruno Cezar de Mendonça Uchôa, Poliana de Andrade, Ricardo Lima Coelho, Marcelo Corassa, Jose A. Rinck, Aldo A. Dettino, Thiago Bueno Oliveira
Journal: Journal of Clinical Oncology (2020)

e17545 Background: Androgen receptor-targeted agents Abiraterone and Enzalutamide (Abi/Ez) prolonged overall survival in metastatic castration resistant prostate cancer (mCRPC). Patients with very-low serum testosterone levels seem to have less benefit from these therapies as well as more aggressive prostate cancer. Methods: A retrospective observational cohort study was conducted to evaluate whether a serum testosterone measured at time of start first-line therapy with Abi/Ez is related to overall survival (OS) and time-to-treatment failure (TTF) in mCRPC patients. Kaplan-Meier survival estimates and Cox-regression models were used for time-to-event analyses. The best cut-off for testosterone was defined using Log-rank statistics (Lausen and Schumacher). X² test and Mann-Whitney U-test were applied to compare categorical and continuous variables, respectively. Logistic regression was used to assess characteristics related to serum testosterone levels. Statistical significance was fixed at 0.05. Results: From May 2012 to February 2017, 100 patients were assessed. Median follow-up was 27.8 months (range 2.23 to 68.26). Pts with a high testosterone level ( &gt; 28.2; n = 20) achieved a significantly higher OS (median 66.0 vs 31.9 mo, testosterone &gt; 28.2 HR: 0.206, 95% CI 0.074 to 0.571, p = 0.002) and TTF (median 30.6 vs 11.8 mo, testosterone &gt; 28.2 HR: 0.408, 95%CI 0.219 to 0.762, p = 0.005) than pts with a low serum testosterone level ( &lt; 28.2; n = 80), regardless of receiving therapy with either Abi (n = 69) or Ez (n = 31). Pts with a higher testosterone level were younger (median 67.7 vs 73.6 years; p = 0.026), had a higher body mass index (BMI) (28.5 vs 25.9, p = 0.023) and a lower PSA at start Abi/Ez (12 vs 26, p = 0.031) than pts with lower values. Age (OR 0.93, 95%CI 0.8 to 0.9, p = 0.021), BMI (OR 1.21, 95%CI 1.1 to 1.4, p = 0.006) and baseline PSA (OR 1.2, 95%CI 1.03 to 1.4, p = 0.020) were significantly associated with testosterone &gt; 28.2. After 4 months of Abi/Ez treatment, PSA decrease &gt; 50% of baseline was seen more frequently in high testosterone levels group than in low testosterone levels pts (90% vs 57.5% of pts, respectively, p = 0.007). Conclusions: Pts with high levels of testosterone ( &gt; 28.2) achieved a better OS and TTF when treated with Abi/Ez in first-line mCRPC than those with low levels. Testosterone can be considered a prognostic and predictive biomarker in this scenario, and could be used in treatment decision for this population.
Questionnaire survey on requirements of vascular dementia-related knowledge among outpatients
Authors: Qianlu Zhao, Qin Xiao, Longxi Ren, Deyuan Liu, Xiaojuan Ru, Ning Zhuang, Ju Yang, Baoen Zhang
Journal: BMJ (2016)

Objective
To survey the requirements of the vascular dementia(VaD)-related knowledge among outpatients.


Methods
Total 1 286 outpatients from Chaoyang district south medical alliance participated in a questionnaire survey on July 2015. There were 562 men and 724 women with an average age of (59.4±13.0) years; and 84.4% (1 085/1 286) of subjects had junior high school education and over. There were 4 topics with 32 items in the questionnaire, including the common knowledge of dementia (10 items), the etiology and risk factors of VaD (8 items), the requirements of health education (6 items) and its mode of knowledge delivery (8 items).


Results
Participants had a higher requirements for the common knowledge about dementia, centering in basic concept, common etiology and risk factor, and early clinical symptom. The groups had a higher demand on common etiology and risk factor of VaD, centering in cerebral infarction, hypertension, and diabetes. All groups intended to increase individual health-related knowledge and lecture of health education in the community was selected as the main mode of knowledge delivery.


Concludsions
Outpatients from Beijing Chaoyang district south medical Alliance have higher demands of the VaD related-knowledge and lecture shall be the main channel for delivery of healthy education in the community.


Key words: 
Dementia, vascular; Healthy knowledge, attitudes, practice; Community health services; Community-institutional relations