tbuckley/cabot-search huggingface dataset:
A phase I/II study of HB-201, an arenavirus-based cancer immunotherapy, alone, or in combination with anti-PD-1 in patients with HPV16+ cancers.
Authors: Bharat Burman, Jiaxin Niu, Rom S. Leidner, Ding Wang, Debra L. Richardson, Corinne Iacobucci, Andy Hwang, Xiaoping Qing, Igor Matushansky, Dmitriy Zamarin, Alan Loh Ho, David G. Pfister, Marshall R. Posner
Journal: Journal of Clinical Oncology (2020)

TPS3171 Background: Human Papillomavirus 16 (HPV16) is linked to several cancer types; treatment options are limited for patients with HPV16+ recurrent or metastatic cancers. The generation and maintenance of the HPV16+ malignant state requires the stable expression of HPV16-specific E7 and E6 oncogenes, which can also serve as immunogenic tumor-associated antigens. HB-201 is a replication-competent live-attenuated vector based on the arenavirus LCMV encoding a non-oncogenic E7 and E6 fusion protein. In preclinical models, both intravenously (IV) and intratumorally (IT) administered HB-201 demonstrate potent immunogenicity by induction of HPV16-specific cytotoxic T cells and associated efficacy. Methods: This is a first in human, Phase I/II study of HB-201 monotherapy or in combination with PD-1 immune checkpoint inhibitor (anti-PD-1) in HPV16+ confirmed recurrent/metastatic cancers. Phase I consists of 2 treatment groups, each conducted with a 3+3 dose escalation design. Group 1 is enrolling patients with HPV16+ head and neck squamous cell carcinoma who will receive HB-201 IV only. Group 2 is enrolling HPV16+ cancer patients with a safely accessible tumor site who will receive HB-201 IT for the first dose, followed by HB-201 IV for subsequent doses (IT-IV). HB-201 will be administered every 21 days. The Phase II component will be conducted with the recommended Phase II doses (RP2Ds) defined in Phase I and will consist of 3 groups: Group A (HB-201 IV only), Group B (HB-201 IV plus anti-PD-1), and Group C (HB-201 IT-IV). Key eligibility criteria include age &gt; 18, ECOG performance status 0-1, confirmed HPV16+ recurrent or metastatic cancer, disease progression from at least 1 systemic standard of care therapy, and measurable disease per RECIST v1.1. The Phase I primary objective is to determine RP2Ds for IV and IT HB-201. The Phase II primary objective is to assess antitumor activity. Secondary endpoints for both phases include safety, tolerability, overall survival, progression-free survival, and duration of response. Exploratory objectives include characterization of immunogenicity of HB-201 and biomarkers associated with immune or antitumor response. Enrollment to Groups 1 and 2 began in December 2019. Clinical trial information: NCT04180215 .
Role of miR-122-5P, miR-107, miR-22-3P, and miR-330-3P microRNAs in regulation of HIF1A expression in high-grade gliomas.
Authors: Anton A. Pushkin, Ilya A. Alliluev, Eduard E. Rostorguev, Sergey E. Kavitskiy, Natalya S. Kuznetsova, Natalya N. Timoshkina, Oleg I. Kit
Journal: Journal of Clinical Oncology (2020)

e14550 Background: HIF1-alfa is a powerful regulator of angiogenesis and cell invasion activating a wide range of oncogenes. Control of the HIF1-alpha transcription is strictly regulated by many molecular pathways, including miRNAs which can become targets for gene therapy of cancer. Methods: The study included 30 patients with histologically verified high-grade gliomas. RNAs were isolated from 30 paired (tumor and control) samples using the TRIzol reagent (Thermo Fisher, USA). The cDNA synthesis was performed using the Reverta MMLV kit (Sintol, Russia). Expression of miRNAs and HIF1A was evaluated by RT-PCR using the CFX96 system (Bio-Rad, USA). The 2 −ΔΔ Сt method was used to analyze the qPCR data. Statisical processing of the results was performed with the Statistica 10 program (StatSoft Inc., USA). Results: Using analysis of TargetScan and miRTarBase databases and appropriate literature, miRNAs (miR-122-5p, miR-107, miR-22-5p and miR-330-3p) able to regulate HIF1A expression were selected. The HIF1A expression in the tumor was 1.8 times higher, compared to normal tissue (p = 0.0031). The 2 −ΔΔ Сt value for miR-122-5p, miR-107, miR-22-3p and miR-330-3p decreased by 40%, 45%, 36%, and 91.5%, respectively, in tumor samples relative to the control point (p &lt; 0.05 in all cases). A correlation was found between the expression of miRNA 122-5p and HIF1A (Spearman’s r = -0.46 at p &lt; 0.05). Conclusions: An increase in the HIF1A miRNA level was found, together with a decrease in the expression of four potentially targeting miRNAs in high-grade gliomas. A negative correlation between the expression of miR-122-5p and HIF1A in high-grade gliomas was revealed, which can be used for the development of new therapy options.
Evaluation of Medicaid Expansion Under the Affordable Care Act and Contraceptive Care in US Community Health Centers
Authors: Blair G. Darney, R. Lorie Jacob, Megan Hoopes, Maria I. Rodriguez, Brigit Hatch, Miguel Marino, Anna Templeton, Jee Oakley, Erika K. Cottrell
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Use of effective contraception decreases unintended pregnancy. It is not known whether Medicaid expansion under the Affordable Care Act increased use of contraception for women who are underserved in the US health care safety net. <h3>Objective</h3> To evaluate the association of Medicaid expansion under the Affordable Care Act with changes in use of contraception among patients at risk of pregnancy at US community health centers, with the hypothesis that Medicaid expansion would be associated with increases in use of the most effective contraceptive methods (long-acting reversible contraception). <h3>Design, Setting, and Participants</h3> This was a participant-level retrospective cross-sectional study comparing receipt of contraception before (2013) vs immediately after (2014) and a longer time after (2016) Medicaid expansion. Electronic health record data from a clinical research network of community health centers across 24 states were included. The sample included all female patients ages 15 to 44 years at risk for pregnancy, with an ambulatory care visit at a participating community health center during the study period (315 clinics in expansion states and 165 clinics in nonexpansion states). <h3>Exposures</h3> Medicaid expansion status (by state). <h3>Main Outcomes and Measures</h3> Two National Quality Forum–endorsed contraception quality metrics, calculated annually: the proportion of women at risk of pregnancy who received (1) either a moderately effective or most effective method (hormonal and long-acting reversible contraception) methods and (2) the most effective method (long-acting reversible contraception). <h3>Results</h3> The sample included 310 132 women from expansion states and 235 408 women from nonexpansion states. The absolute adjusted increase in use of long-acting reversible contraceptive methods was 0.58 (95% CI, 0.13-1.05) percentage points greater among women in expansion states compared with nonexpansion states in 2014 and 1.19 (95% CI, 0.41-1.96) percentage points larger in 2016. Among adolescents, the association was larger, particularly in the longer term (2014 vs 2013: absolute difference-in-difference, 0.80 [95% CI, 0.30-1.30] percentage points; 2016 vs 2013: absolute difference, 1.79 [95% CI, 0.88-2.70] percentage points). Women from expansion states who received care at a Title X clinic had the highest percentage of women receiving most effective contraceptive methods compared with non–Title X clinics and nonexpansion states. <h3>Conclusions and Relevance</h3> In this study, Medicaid expansion was associated with an increase in use of long-acting reversible contraceptive methods among women at risk of pregnancy seeking care in the US safety net system, and gains were greatest among adolescents.
Perioperative chemotherapy versus adjuvant chemoradiation in resectable gastric cancer: A national cancer database analysis.
Authors: Sindhu Janarthanam Malapati, Sunny R K Singh, Rohit Kumar, Ahmed Abdalla, Tarik H. Hadid
Journal: Journal of Clinical Oncology (2020)

7066 Background: In patients with resectable gastric cancer, the use of either perioperative chemotherapy (POC) or adjuvant chemoradiotherapy (CRT) are acceptable treatment options in addition to surgical resection. Both approaches improved overall survival (OS) compared to surgery alone. Randomized controlled trials comparing these two modalities are lacking. This study uses real-world data to compare the clinical outcomes of these two approaches. Methods: We identified gastric cancer patients in the NCDB who had definitive surgery between years 2004 and 2015. They were divided into two cohorts: POC and adjuvant CRT. We compared the OS and surgical outcomes in both groups. Kaplan-Meier method and multivariable Cox regression model were used to estimate survival. Results: Of 75,654 patients who underwent definitive surgical resection, 1,920 had POC and 9,161 had adjuvant CRT. Median OS was 56 months with POC and 38.5 months with CRT. After adjusting for age, gender, race, insurance status, comorbidity index, and treatment facility, patients who received POC had an 18% reduction in all-cause mortality compared to those who received adjuvant CRT (p &lt;0.0001, 95% confidence interval 0.74- 0.88). Although, 30- and 90-day mortality was slightly higher with POC compared to CRT (0.047 vs. 0.03%, p&lt;0.0001 and 1.46 vs. 0.45%, p&lt;0.0001 for 30 and 90 day mortality, respectively). Length of hospital stay for primary tumor resection was similar between the two groups; but the 30 day readmission rate after surgery was higher with CRT compared to POC (12.74 vs. 8.33%, p&lt;0.0001). Conclusions: Among patients undergoing definitive surgical resection for gastric cancer, our study shows an association between the use of POC (vs. adjuvant CRT) and improvement in OS. In the POC cohort, while there was a slight increase in postoperative mortality, this was surpassed by the benefit derived from use of POC, resulting in net improvement of survival. These interesting observations warrant confirmation in randomized clinical trials. [Table: see text]
血尿的常见原因与诊治
Authors: 隋准, 董葆
Journal: BMJ (2011)

血尿是指尿沉渣镜检发现红细胞>3爪/高倍镜视野或爱迪(Addis)计数时,12 h尿沉渣红细胞计数>50万个[1].因此,血尿的诊断一定要求有显微镜对于尿沉渣的检测,如果仅仅尿色发红或尿常规显示潜血阳性,是不能诊断为血尿的.近年来,血尿的发生率呈持续上升的趋势,根据北京大学第一医院Xu等[2]分析,北京市大于18岁的成人中,血尿的发生率超过4%。
Health-related quality of life (HRQL) in patients with advanced cutaneous squamous cell carcinoma (CSCC) treated with cemiplimab: Post hoc exploratory analyses of a phase II clinical trial.
Authors: Michael Robert Migden, Danny Rischin, Medha Sasane, Vera Mastey, Anna Pavlick, Chrysalyne D. Schmults, Zhen Chen, Alexander David Guminski, Axel Hauschild, Denise Bury, Anne Lynn S. Chang, Guilherme Rabinowits, Sherrif F. Ibrahim, Israel Lowy, Matthew G. Fury, Siyu Li, Chieh-I Chen
Journal: Journal of Clinical Oncology (2020)

10033 Background: Cemiplimab-rwlc (cemiplimab), a PD-1 Inhibitor, showed a robust clinical response in patients (pts) with metastatic (mCSCC) or locally advanced (laCSCC) CSCC not eligible for curative surgery/radiation. This post hoc exploratory analysis examined data from the EORTC cancer specific 30-item HRQL questionnaire (QLQ-C30) for pts participating in a cemiplimab phase 2 clinical trial (clinicaltrials.gov NCT02760498). Methods: Adults (N = 193) with invasive CSCC, ≥1 lesion and ECOG performance status ≤1 received IV cemiplimab 3mg/kg q2w (mCSCC n = 59; laCSCC n = 78) or 350mg q3w (mCSCC n = 56). At baseline (BL) and day 1 of each treatment cycle, pts were administered the QLQ-C30. Mixed effects repeated measures (MMRM) models were used to estimate mean change from BL to cycle 5 (C5) for domains/items of the QLQ-C30. For pts with data from BL to C5, the proportion who reported clinically meaningful improvement or worsening (≥10 points) or maintenance (those who did not have ≥10 point change) on each domain was determined for combined and individual treatment groups. Results: BL scores indicated moderate to high levels of functioning and low symptom burden. From BL to C5, a clinically meaningful improvement in pain score was observed (least squares [LS] mean [standard error] change -12.1 [2.1]; P&lt; .0001); other domains/items remained stable or showed a trend towards improvement (LS mean changes &lt; 10 points). By C5, the majority of pts experienced clinically meaningful improvement or remained stable across key domains (Table). Similar findings were observed on individual symptoms (85%-94% for dyspnea, nausea/vomiting, diarrhea, constipation, appetite loss) and in each treatment group. Conclusions: Cemiplimab-treated patients achieved a clinically meaningful reduction in pain and most pts either improved or maintained their HRQL, function with low symptom burden. Clinical trial information: NCT02760498. [Table: see text]
Depression in cancer: An evaluation of patient education resources.
Authors: Jim (Zhang Hao) Li, Mingyang Wang, Paris-Ann Ingledew
Journal: Journal of Clinical Oncology (2020)

e24194 Background: In recent years, there has been increasing awareness surrounding mental health and depression among cancer patients. Concurrently, the internet has cemented its role as a mainstay source of health information for the general public. However, little is known about the quality of online resources addressing depression specifically in cancer patients. Therefore, we aim to systematically evaluate the quality of such information. Methods: The term "depression in cancer patients" was searched online using the search engine Google and the meta-search engines Dogpile and Yippy. A set of predetermined inclusion and exclusion criteria was applied to all search results, which yielded 48 websites for inclusion. An evidence-based rating tool was then used to score the websites based on the six domains of Affiliation, Accountability, Interactivity, Structure &amp; Organization, Readability, and Content Quality. The results were analyzed using descriptive statistics. Results: Of the 48 websites evaluated, 50% were commercial. In terms of accountability measures, 63% of websites disclosed authorship, 54% cited one or more reliable sources, and 38% were updated within the last two years. Although in-site search engines and video support were found in 94% and 52% of websites respectively, the presence of other interactive features were considerably lower. The average readability was at a grade 12.3 level using the Flesch-Kincaid scale and 11.3 using the SMOG Index, both of which were significantly higher than the traditionally recommended grade-six level ( p &lt; 0.0001 for both). The most commonly covered topics were symptoms and treatment – found on 87% and 83% of websites respectively. Prevention and prognosis were not covered by any of the websites. Content accuracy was generally high among covered topics. Conclusions: Many websites addressing depression in cancer have poor authorship disclosure, attribution, and currency. Additional interactive features should be encouraged to facilitate user-friendliness. Poor readability may pose a barrier for patient comprehension, indicating a need for health care providers to proactively guide patients to suitable resources. Despite high content accuracy in other topics, prevention and prognosis are seldom covered. Our results could help guide the development of new patient education materials and better inform health care providers about the limitations of available online resources. Future research should aim to elucidate reasons contributing to difficult readability levels and identify topics that patients need additional information in.
深圳市福田区全科医学学科建设现状与发展策略
Authors: 赖光强
Journal: BMJ (2010)

近几年来,我区临床医疗急救体系和公共卫生体系建设取得了重大进步,基础设施明显改善,但全科医学学科作为新的临床二级学科未得到足够关注,学科建设滞后,已经明显影响到我区社区卫生服务体系建设的速度和质量。
Assembly and annotation of an Ashkenazi human reference genome
Authors: Alaina Shumate, Aleksey V. Zimin, Rachel M. Sherman, Daniela Puiu, Justin M. Wagner, Nathan D. Olson, Mihaela Pertea, Marc L. Salit, Justin M. Zook, Steven L. Salzberg
Journal: Genome biology (2020)

Abstract Background Thousands of experiments and studies use the human reference genome as a resource each year. This single reference genome, GRCh38, is a mosaic created from a small number of individuals, representing a very small sample of the human population. There is a need for reference genomes from multiple human populations to avoid potential biases. Results Here, we describe the assembly and annotation of the genome of an Ashkenazi individual and the creation of a new, population-specific human reference genome. This genome is more contiguous and more complete than GRCh38, the latest version of the human reference genome, and is annotated with highly similar gene content. The Ashkenazi reference genome, Ash1, contains 2,973,118,650 nucleotides as compared to 2,937,639,212 in GRCh38. Annotation identified 20,157 protein-coding genes, of which 19,563 are &gt; 99% identical to their counterparts on GRCh38. Most of the remaining genes have small differences. Forty of the protein-coding genes in GRCh38 are missing from Ash1; however, all of these genes are members of multi-gene families for which Ash1 contains other copies. Eleven genes appear on different chromosomes from their homologs in GRCh38. Alignment of DNA sequences from an unrelated Ashkenazi individual to Ash1 identified ~ 1 million fewer homozygous SNPs than alignment of those same sequences to the more-distant GRCh38 genome, illustrating one of the benefits of population-specific reference genomes. Conclusions The Ash1 genome is presented as a reference for any genetic studies involving Ashkenazi Jewish individuals.
Does age contribute to distress in new geriatric oncology patients?
Authors: Harish Saiganesh, Humera Khurshid, Sakeena Raza, Don S. Dizon
Journal: Journal of Clinical Oncology (2020)

e24023 Background: As part of routine practice at the Lifespan Cancer Institute (LCI), all new patients are screened with the NCCN Distress Thermometer (DT). There is little to no data comparing initial distress levels among patients 65 and older recently diagnosed with cancer and how this might change with increasing age. This study sought to describe distress at initial presentation among two cohorts: patients 65 to 74 years and those 75 years and over. Methods: We have retrospectively reviewed 1800 patients at Lifespan Cancer Institute so far, all of whom were initially seen between the years 2014-2017. Data related to demographics, tumor type, initial distress score, and sources of distress were gathered using our electronic medical records. Categorical data were analyzed using Fisher’s Exact Test or Chi-Square. Multinomial logistic regression was performed for multivariate analysis. All analyses were performed in STATA 15.0. Results: At time of diagnosis, 898 (49.9%) patients were over 65 years. Of those, 577 (64%) had distress thermometers and were included in this analysis. The median age was 72 (range 65 to 92), 66.9% were female, and 42.5% were married or partnered; 393 (68.1%) were under 75 years and 184 (31.9%) were 75 or older. The major cancers represented included breast (44%), lung (19.6%), and prostate (17%) cancers. The presence of severe distress (DT score of 4 or higher) did not significantly differ by age cohort (45.3 versus 45.7%, respectively, p &gt; 0.5) but differed by tumor group (p &lt; 0.001). Compared to people under 75 years, more of those 75 and older reported sadness (27 versus 20%, respectively, p &lt; 0.05), issues with memory and concentration (12 versus 7.6%, p &lt; 0.1) and trouble with getting around (14.7 versus 8.4%, p &lt; 0.05). On multinomial logistic regression, only tumor group and reporting sadness on the DT remained significant factors for severe distress, whereas age did not. Conclusions: There is no significant difference in distress reporting among geriatric patients with cancer who are under 75 compared to those 75 and older. Tumor type and sadness at the initial presentation were associated with severe distress in this group of people.
Verticalization of frontal P axis on electrocardiography in patients with acute exacerbation of chronic obstructive pulmonary disease and asthma
Authors: Weihao Li, Huifang Cao, Ying Feng, Yuting Pan, Huili Zhu
Journal: BMJ (2020)

Objective
To investigate the clinical significance of verticalization of frontal P axis on electrocardiagraphy (ECG) in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) and asthma.


Methods
Thirty five COPD patients and 20 asthma patients with acute exacerbation admitted in Jing′an District Central Hospital were enrolled and 20 health subjects served as a control group. The 12 lead ECG examination, pulmonary function test and high resolution CT (HRCT) scan of lung were performed. The P axis in ECG, pulmonary function and CT emphysema score were compared among three groups. The correlation of P axis verticalization with pulmonary function and CT emphysema score was analyzed.


Results
There were significant differences in P axis(F=24.36), FEV1/FVC(F=39.36), FEV1(F=28.82), FEV1%(F=30.64), FVC%(F=3.45), PEF%(F=13.22), RV/TLC(F=10.46) and total emphysema score (F=50.60) among the three groups (all P 60 ° as cut-off value for screening COPD, the sensitivity was 0.933, specificity was 0.667, positive predictive value was 0.833 and negative predictive value was 0.857.


Conclusion
The verticalization of frontal P axis on ECG is significantly associated with obstructive ventilation disorder and CT emphysema score, which can be used as a preliminary screening index for COPD.


Key words: 
Pulmonary disease, chronic obstructive; Respiratory function test; Electrocardiography; Vectorcardiography; Pulmonary emphysema