tbuckley/cabot-search huggingface dataset:
An innovative approach to manage cancer patient information for care coordination and monitoring using a digital health platform for a nonprofit tertiary cancer care institute in India.
Authors: Sharon Hensley Alford, Rishi Kumar Gupta, Nayan Sonawane, Srishti Mahatma, Shilpa Mahatma, Tarun Kumar
Journal: Journal of Clinical Oncology (2020)

e14102 Background: In India, most patients maintain a personal copy of their medical record in paper form which is hard to manage and collate. Newly diagnosed cancer patients and their doctors have an insurmountable task of consuming and using that information. Making this information available in an easy to consume format as well as recording a patient’s cancer experience is a technical challenge. We piloted an innovative mobile application to address this pain point. Methods: A pilot engagement was performed with 100+ cancer patients visiting a non-profit oncology center between March 2019 and January 2020 in a suburb of New Delhi, India. Systematic medical information was captured on stage, TNM, molecular markers, tumor size, tests, and treatments. We assessed the utility of a digital health application for the purpose of cancer information management and ease of use by the medical team. Results: Data for a total of 65 patients with a single cancer and diagnosis and treatment information was captured. Patients were between the ages of 23 and 78, mean age 49. Of these patients, there were 21 (32%) early stage cases ( &lt; Stage 3), 23 (35%) late stage cases ( &gt; Stage 2), and 21 (32%) cases with missing stage. Overall, 39 (60%) received a chemotherapy only regimen, 2 (3%) radiation only, 6 (9%) surgery only, 6 (9%) received chemotherapy and radiation, 11 (17%) received surgery and chemotherapy, and 1 (1%) patient received surgery, chemotherapy, and radiation. Clinic staff reported that the application was easy to use and helpful. We continue to enhance the application with staff feedback. Conclusions: We demonstrate the feasibility and value of moving to a next generation digitized mobile platform circumventing the need for a traditional EMR system at a busy non-profit oncology clinic in the suburbs of New Delhi, India. Using the pilot, we make a case that this type of technology has the ability to transform cancer care for rural and low-resource cancer centers. We also demonstrate that it is easy to capture patient longitudinal data using this innovative platform.
慢性左心衰的治疗--由病例看治疗原则
Authors: 吴学思
Journal: BMJ (2004)

心力衰竭(心衰)是一种复杂的临床症候群,是各种心脏病的严重阶段,也是心脏病的最后大战场.随着人口老龄化、心肌梗死(AMI)生存率的增加和患者寿命的延长,充血性心力衰竭患者逐渐增加.著名的Framingham研究显示,男性心衰患者2年死亡率为37%,6年死亡率高达82%.近50年来,对充血性心力衰竭机制的认识逐步深入,现在认为导致心衰发生发展的基本机制是心室重塑。
Genome-Wide DNA Methylation in Peripheral Blood and Long-Term Exposure to Source-Specific Transportation Noise and Air Pollution: The SAPALDIA Study
Authors: Ikenna C. Eze, Ayoung Jeong, Emmanuel Schaffner, Faisal I. Rezwan, Akram Ghantous, Maria Foraster, Danielle Vienneau, Florian Kronenberg, Zdenko Herceg, Paolo Vineis, Mark Brink, Jean-Marc Wunderli, Christian Schindler, Christian Cajochen, Martin Röösli, John W. Holloway, Medea Imboden, Nicole Probst-Hensch
Journal: Environmental Health Perspectives (2020)

Background: Few epigenome-wide association studies (EWAS) on air pollutants exist, and none have been done on transportation noise exposures, which also contribute to environmental burden of disease. Objective: We performed mutually independent EWAS on transportation noise and air pollution exposures. Methods: We used data from two time points of the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA) from 1,389 participants contributing 2,542 observations. We applied multiexposure linear mixed-effects regressions with participant-level random intercept to identify significant Cytosine-phosphate-Guanine (CpG) sites and differentially methylated regions (DMRs) in relation to 1-y average aircraft, railway, and road traffic day-evening-night noise (Lden); nitrogen dioxide (NO2); and particulate matter (PM) with aerodynamic diameter &lt;2.5μm (PM2.5). We performed candidate (CpG-based; cross-systemic phenotypes, combined into “allostatic load”) and agnostic (DMR-based) pathway enrichment tests, and replicated previously reported air pollution EWAS signals. Results: We found no statistically significant CpGs at false discovery rate &lt;0.05. However, 14, 48, 183, 8, and 71 DMRs independently associated with aircraft, railway, and road traffic Lden; NO2; and PM2.5, respectively, with minimally overlapping signals. Transportation Lden and air pollutants tendentially associated with decreased and increased methylation, respectively. We observed significant enrichment of candidate DNA methylation related to C-reactive protein and body mass index (aircraft, road traffic Lden, and PM2.5), renal function and “allostatic load” (all exposures). Agnostic functional networks related to cellular immunity, gene expression, cell growth/proliferation, cardiovascular, auditory, embryonic, and neurological systems development were enriched. We replicated increased methylation in cg08500171 (NO2) and decreased methylation in cg17629796 (PM2.5). Conclusions: Mutually independent DNA methylation was associated with source-specific transportation noise and air pollution exposures, with distinct and shared enrichments for pathways related to inflammation, cellular development, and immune responses. These findings contribute in clarifying the pathways linking these exposures and age-related diseases but need further confirmation in the context of mediation analyses. https://doi.org/10.1289/EHP6174
Efficacy and safety of <sup>177</sup>Lu-PSMA radionuclide treatment in patients with diffuse bone marrow involvement: A multicenter retrospective study.
Authors: Andrei Gafita, Wolfgang Peter Fendler, Hui Wang, Shahneen Kaur Sandhu, Manuel Weber, Rouzbeh Esfandiari, Johannes Czernin, Hendrik Rathke, Isabel Rauscher, Robert Tauber, Ebrahim Delpassand, Wolfgang A Weber, Ken Herrmann, Jeremie Calais, Matthias Eiber, Michael S Hofman
Journal: Journal of Clinical Oncology (2020)

e17543 Background: 177 Lu-labelled prostate-specific membrane antigen (LuPSMA) radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC) is currently under investigation in phase III trial (VISION). However, patients with diffuse bone involvement, diagnosed with a superscan by bone scintigraphy at baseline, were excluded due to lack of efficacy and safety data. We therefore aimed to investigate the feasibility of LuPSMA in patients with diffuse bone marrow involvement on baseline PSMA-targeted PET/CT. Methods: Patients with progressive mCRPC treated with LuPSMA at six centers in Germany, USA and Australia were considered for inclusion.Eligible patients had 50% or greater bone involvement of the axial skeleton on the baseline PSMA PET. The primary endpoints were PSA response (PCWG3), toxicity (CTCAE v4.02), and overall survival (OS). Secondary endpoints included quality of life (assessed with Brief Pain Inventory-Short Form questionnaires) and radiological response (as measured by CT using RECIST 1.1). Results: 43 of 352 (12%) screened patients met inclusion criteria and were retrospectively analyzed. Median baseline PSA was 1000 (IQR 431-2151) ng/ml. PSA decline ≥50% was achieved in 26/43 (65%) patients, while median PSA progression-free survival was 4.8 (95%CI 2.4–7.1) mo. 15/42 (36%) evaluable patients exhibited pain progression with a median time-to-pain progression of 8.3 (95%CI 5.4–11.3) mo. After a median follow-up of 18.9 mo, median OS was 11.6 (95%CI 8.8-14.3) mo. Objective response in nodal or visceral disease was reported in 7/18 (39%) patients with evaluable target lesions on CT. Grade 3/4 anemia, thrombocytopenia and neutropenia occurred in 9/43 (21%), 10/43 (23%) and 3/43 (8%) patients, respectively. Of note, all patients had grade 1 anemia at baseline, with a median hemoglobin of 9.6 g/dl. 2/43 (5%) patients experienced an adverse event that required a reduction to the LuPSMA activity beginning with the third cycle. Conclusions: Patients with diffuse bone marrow involvement demonstrate similar LuPSMA efficacy and safety when compared to phase II evidence. Acceptable safety outcomes do not support exclusion of patients with a superscan from future LuPSMA treatment protocols.
光コヒーレンストモグラフィーにより評価されたベアメタルステント及びシロリムス溶出ステント留置術後の新生内膜の晩期臨床的イベント病変の出現 | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Ino Yasushi, Kubo Takashi, Kitabata Hironori, Ishibashi Kohei, Tanimoto Takashi, Yamaguchi Tomoyuki, Yamano Takashi, Shiono Yasutsugu, Shimamura Kunihiro, Orii Makoto, Ota Shingo, Ozaki Yuuichi, Hirata Kumiko, Tanaka Atsushi, Imanishi Toshio, Akasaka Takashi
Journal: Circulation (2013)
造血干细胞移植在自身免疫病中的应用
Authors: 冷晓梅
Journal: BMJ (2006)

自身免疫病如系统性红斑狼疮(SLE)、类风湿关节炎(RA)、系统性硬化(SSc)等具有较高的致残率和致死率.这些疾病不仅造成患者本身的极大负担和伤害,而且使家庭和社会负担明显增加.因此,近十年来人们更趋于早期和更积极地给予治疗以防止或延缓患者内脏器官出现明显的不可逆损伤.大剂量免疫抑制剂并造血干细胞移植(hematopoietic stem cell transplantation,HSCT)治疗自身免疫病是这一领域的重要进展[1]。
Acute Hyperglycemia and Spatial Working Memory in Adolescents With Type 1 Diabetes
Authors: Jasna Šuput Omladič, Anka Slana Ozimič, Andrej Vovk, Dušan Šuput, Grega Repovš, Klemen Dovc, Nataša Bratina, Magdalena Avbelj Stefanija, Tadej Battelino
Journal: Diabetes Care (2020)

OBJECTIVE To investigate the effect of acute hyperglycemia on brain function in adolescents with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS Twenty participants with T1D (aged 14.64 ± 1.78 years) and 20 age-matched healthy control subjects (aged 14.40 ± 2.82 years) performed two functional MRI sessions. Participants with T1D performed the first scanning session under euglycemic and the second under hyperglycemic clamp (20 mmol/L [360 mg/dL]). RESULTS Lower spatial working memory (sWM) capacity during acute hyperglycemia and significant differences in activation of regions of interest during different stages of the sWM task (P = 0.014) were observed. CONCLUSIONS Acute hyperglycemia negatively affected sWM capacity in adolescents with T1D, which is relevant for daily functioning and academic performance.
溃疡型胃癌癌组织分布在胃镜检查中的意义
Authors: 姚海山, 姚中秀, 李亚琼
Journal: BMJ (2005)

纤维胃镜是目前诊断胃癌的一个重要手段,但在胃镜取材过程中,时常出现漏取现象,给胃癌的病理诊断带来一定困难.我们对160例溃疡型胃癌标本的癌组织分布进行了研究,旨在探讨如何提高胃镜对胃癌的检出率[1],报告如下。
T lymphocyte sub-populations in malignant and tuberculous pleural effusion or ascites
Authors: Bao-xin Su, Qing Li, Jia-feng Niu, Jin-ling Wang, Shu-cui Li, Tian-ling Zhang
Journal: BMJ (2010)

Objective To determine counts of T lymphocyte sub-populations in malignant and tuberculous pleural effusion or ascites and evaluate its significance in difierential diagnosis.Methods T lymphocyte sub-populations in pleural effusion or ascites and peripheral blood were determined in 30 patients with tuberculosis and 31 patients with cancer by flow cytometry.Concentrations of cytokines Th1 and Th2,γ-interferon(IFN-γ),interleukin-12(IL-12)and IL-4 in pleural effusion or ascites were measured by enzyme-linked immunosorbent assay(ELISA).Results Compared to that in peripheral blood,percentage of CD3+ and CD4+ T-celI counts were all higher in both malignant and tuberculous pleural effusion or ascites [(73±6)%and(67±20)%vs.(51±19)%and(48±14)%,P＜0.05].Although CD3+T-cells count was higher in tuberculous pleural effusions or ascites,no difference in ratio of CD3+ and CD4+/CD3+ and CD8+ T-cell counts was found between malignant and tuberculous pleural effusions or ascites.However,ratios of IFN-γ and IL-12 to IL-4 were higher in tuberculous pleural effusion or ascites(54±24 and 82±19vs.8±6 and 19±10,t=10.34 and 16.28,respectively,P＜0.01).Conclusions CD3+ and CD4+ Tcells can be aggregated in both malignant and tuberculous pleural effusions or ascites,80 nature (tuberculosis or malignancy)of pleural effusion or ascites can not be differentiated by CD4+ and/or CD8+ T-cell counts only,and determination of cytokines Th1 and Th2 can help their differentiation.

Key words: 
Hydrothorax;  Ascites; Tuberculosis;  Neoplasm; T-lymphocyte sub-population
Preclinical evaluation of KZR-261, a novel small molecule inhibitor of Sec61.
Authors: Eric Lowe, R. Andrea Fan, Jing Jiang, Henry W. B. Johnson, Christopher J. Kirk, Dustin McMinn, Beatriz Millare, Tony Muchamuel, Yu Qian, Brian Benjamin Tuch, Jennifer A. Whang, Patricia Zuno
Journal: Journal of Clinical Oncology (2020)

3582 Background: Secreted and transmembrane proteins play key roles in malignant transformation and growth, including in autocrine growth factor expression, receptor oncogene signaling, and immune system evasion. Biogenesis of these proteins involves translocation of the nascent polypeptides into the endoplasmic reticulum (ER) through the Sec61 channel, providing an untapped therapeutic target for a broad spectrum of malignancies. Here we describe preclinical activity of KZR-261 and related inhibitors of Sec61-dependent protein secretion. Methods: Sec61 inhibition with KZR-261 and related analog KZR-834 were evaluated using cell lines overexpressing proteins of interest tagged with luciferase. In vitro anti-tumor activity was assessed against a panel of 346 cell lines across 25 tumor types. Quantitative proteomic profiling by mass spec and gene expression profiling by RNAseq were conducted following treatment in multiple solid and heme tumor cell lines. Anti-tumor efficacy was evaluated in athymic nude mice implanted with the cancer cell lines H82 (SCLC), HT29 (CRC), BxPC3 (Pancreatic), 22RV1 (Prostate), H929 (Myeloma) and RL (NHL). Activity was also evaluated in a MC38 syngeneic colon tumor model. Results: KZR-261 and KZR-834 exhibited nanomolar potency against many therapeutic targets, including immune checkpoints, VEGF-A, VEGFR and EGFR. Broad in vitro anti-cancer activity was observed with KZR-834, which potently decreased cell viability across both solid and heme tumor types including CRC, Pancreatic, HNSCC, HCC, Lymphoma and Myeloma. Global proteomic analysis observed more than 1.5 fold downregulation of &lt; 10% of detected Sec61 client proteins following treatment, while gene expression profiling revealed upregulation of ER stress response genes in sensitive versus resistant cell lines. Analysis of the TCGA database also found these genes upregulated in a number of different tumor types. In vivo, weekly IV administration was well tolerated and induced a dose dependent anti-tumor response at doses below the MTD in solid and heme xenograft models. In the syngeneic MC38 model, administration of KZR-834 in combination with anti-PD1 antibody resulted in greater anti-tumor activity than either single agent. Conclusions: Novel Sec61 inhibitors potently block expression of secreted and membrane proteins, translating into anti-tumor activity against many tumor types in vitro and in vivo, suggesting broad therapeutic potential. Clinical trials are being planned with KZR-261 to understand safety and early efficacy of this novel compound and therapeutic target.
Toxicity analysis of capecitabine/temozolomide in NETs.
Authors: Taymeyah E. Al-Toubah, Eleonora Pelle, Mintallah Haider, Jonathan R. Strosberg
Journal: Journal of Clinical Oncology (2020)

4614 Background: The capecitabine/temozolomide regimen has significant activity in advanced NETs. Concerns exist regarding risk of opportunistic infections and long-term myelotoxicity. Analysis of large patient cohorts is needed for evaluation of rare toxicities and for assessment of risk factors. Methods: Retrospective study of all patients with advanced neuroendocrine neoplasms seen at the Moffitt Cancer Center between 1/2008 and 6/2019 who received treatment with CAPTEM. Patients who initiated treatment at outside institutions were included if they were prescribed treatment at appropriate doses and if complete records were available. Results: 462 patients met eligibility criteria for evaluation: 210 (45%) females and 252 (55%) males with a median age of 59. Median starting doses of CAP and TEM were 658mg/m 2 and 180mg/m 2 respectively. Median duration on treatment was 8 months. 25% of patients required a dose reduction and 16% discontinued due to toxicity of any grade. Incidence of grade 4 thrombocytopenia was 7%: 10% in females and 5% in males (p = 0.02). 4 cases were complicated by bleeding (0.8%). Incidence of grade 4 neutropenia was 3%: 5% in females and 1% in males (p = 0.004). Incidence of grade 4 lymphopenia was 2%. Only one case (0.2%) of suspected PCP was observed in a patient taking corticosteroids. There were 5 cases of herpes zoster and no other opportunistic infections. 3 patients developed myelodysplastic or myeloproliferative disease, all of whom had also received prior PRRT with Lutetium-Dotatate. There were no acute treatment related deaths, although one patient died 2 months after a thrombocytopenic bleed. Conclusions: Severe myelotoxicity is rare, but risks of grade 4 thrombocytopenia and neutropenia are significantly increased in females compared to males. Gender-based dosing should be considered. While alkylating agents are often associated with MDS, there were no cases except among patients who also had received PRRT, a known risk factor. PCP is not a significant risk with this regimen in patients not concurrently on corticosteroids.
Quality of life in patients with polycystic ovary syndrome
Authors: Ya-qin Wang, Jing Yang, Wang-ming Xu, Tai-lang Yin, Ai-bin Li, Jing Hu
Journal: BMJ (2009)

A cross-sectional study in 116 patients with polycystic ovary syndrome (PCOS) was carried out by using the short-form-36 health survey (SF-36), serf-rating anxiety scale ( SAS), and self-rating depression scale (SDS) from January 2008 to April 2008 in our reproduction center. In comparison with the healthy controls, the PCOS patients showed decreased quality of life (QOL) for all items of SF-36 (P<0.05) except for body pain or role-physical scales. The differences in SAS and SDS between the PCOS and the healthy controls were statistically significant (P<0.05). Our study results confirm the negative impacts of PCOS over the quality of life;subfertility, obesity, hirsutism, acne, complications, menstrual irregularity and educational levels might contribute to the reduced QOL.

Key words: 
Polycystic ovary syndrome; Quality of life
A single institution experience with droplet digital polymerase chain reaction (dd-PCR) liquid biopsy (LB) for therapeutic decision in advanced solid tumors.
Authors: Andre Marcio Murad, José Claudio Casali-da-Rocha, Juliana Garcia Carneiro
Journal: Journal of Clinical Oncology (2020)

e15562 Background: Droplet digital polymerase chain reaction (ddPCR) is a promising method for analyzing minor amounts of cell-free circulating free nucleic acid (DNA and RNA) due to its high sensitivity, low cost, and fast reading, since it dispenses bioinformatics, making it an appropriate alternative to new generation sequencing (NGS) for the detection of biomarkers to guide molecularly targeted cancer therapy. The assay covers main actionable hotspot alterations across many actionable genes: EGF(mutations), ALK (fusion, mutations), ROS1(fusion), BRAF(mutations), KRAS (mutations), NRAS(mutations), PIK3CA (mutations), ERBB2(CNV- copy number variation), ESR1(mutations), KIT(CNV) and PDGFRA(CNV). Therefore, our genes can be used in panels, both in therapeutically applied genotyping and in detecting molecular responses as well as in secondary resistance to tumors such as NSCLC, breast, cervix. rectal, GIST, melanoma and pancreas. Methods: dd-PCR was performed using the QX200 system (BIO-RAD, Hercules). The extraction of DNA and RNA was done using the magnetic beads technique of Thermofisher's MagMAX Kit. All samples were tested in duplicate. Up to now, 54 metastatic cancer patients were tested: NSCLC - 14 (26%), breast - 11 (20%), colorectal - 11 (20%), melanoma - 9(17%), pancreas - 4(7%), ovarian - 3(6%) and salivary glands - 2 (4%). Results: Significant genomic alterations were detected in 19 (35%) patients: 5 (9%) mutations in the KRAS G12V gene (all in colorectal cancer), 5 (9%) ERBB2 amplification (breast cancer), 2 (3.65%) EGFR L858R mutations (NSCLC), 2 (3.5%) EGFR del19 mutations (NSLC), 2 (3.5%) EGFR T790M mutations (NSCLC), 2 (3.5%) BRAF-V600E mutations (colon and melanoma), 1 (1.8%) ALK-EML4 fusion (NSCLC). The MAF (Mutant Allele Fraction) ranged from 0.9% to 24%. In all cases, the results were decisive for the indication or change of a targeted therapy. Median turnaround time was 36 hours and the average cost of the panels was around 500 USD (median of 4 genes per panel). Conclusions: Our results suggest that dd-PCR is a highly sensitive method and could be used for a routine laboratory detection of the important genomic variations to determine the targeted therapy in patients with varied advanced solid tumors.
Extracurricular activities in general practice teaching for medical students
Authors: 齐殿君, 王爽, 杜改燕, 何旖旎, 吴彬, 张联红, 施萍, 于晓松
Journal: BMJ (2011)

One hundred and forty-four medical students were enrolled in the study, the participants were randomly divided into experimental group and control group with 72 in each. All students attended the theoretical lecture of general medicine. Students in experimental group took part in the extracurricular teaching activities including the nutritional course and practice, the clinical case study and problem based learning ( PBL), students in control group did not have the extracurricular activities. The results showed that although there was no difference in general testing scores between two groups, the problem solving ability and assay-writing ability of experimental group were significantly higher than those of control group.

Key words: 
Family practice ;  Education,medical,undergraduate ;