tbuckley/cabot-search huggingface dataset:
Analysis of mutation detection of POLD1/pole in pan-cancer.
Authors: Gao Yang, Jian'An Huang, Yukun Zu, Yan Zhang, Pingping Dai, Yaqian Han, Guojun Geng, Xiaolei Zhu, Ruimin Chang, Jiaojiao Huan, Chen Chen, Yan-Fang Guan, Ling Yang, Xin Yi, Xuefeng Xia
Journal: Journal of Clinical Oncology (2020)

3142 Background: Previous studies proved that mutation of POLD1 and POLE elevates base-substitution mutations and lead to the elevation of tumor mutation burden (TMB). Other signature needs to explore to identify driver mutations in these two genes. Methods: Using gene-panel target-capture next generation sequencing, we analyzed the TMB and POLD1/POLE mutation in 17383 tumor tissue or plasma ctDNA samples from different patients. Results: Tumor mutation burdens were calculated of all the 17383 samples. According to the present research and our panel, we use 10 and 100 Mut/Mb to define hypermutation and ultra-hypermutation. Samples with hypermutation possessed 18.8% (n = 3268) and ultra-hypermutation possessed 0.3% (n = 58). In unselected, hypermutation and ultra-hypermutation group, POLD1 or/and POLE mutations were identified in 3.5% (n = 625), 56.1% (n = 32) and 87.9%(n = 372) samples. There were 0.5% (n = 81), 17.0% (n = 73) and 87.7%(n = 51) identified more than one mutation. These results showed that POLD1 or/and POLE mutations were enriched in samples with high TMB. We screened every known POLE and POLD1 driver mutations. There were 22 ultra-hypermutation samples identified these mutations, including A456P(3), P286R(10), V411L(6), M444K(1), S459F(1) in POLE and R1016H(1) in POLD1. Interestingly, all of them were identified in microsatellite stable (MSS) samples, which suggest that driver mutation may enriched in MSS samples. These already known driver mutation was not detect in 24 high-level microsatellite instability (MSI-H) and ultra-hypermutation samples. We further analyzed 10 POLD1/POLE mutations in other 5 MSS and ultra-hypermutation samples. POLE L424V was a pathogenic germline mutation but not defined as a driver mutation clearly before. POLE P286C had not been biochemically characterized but had different residue with P286R in the same position. Others had not been biochemically characterized (R232H, A234T, V945M, S1064I, Y467H in POLD1, D462N and R749Q, E1956D in POLE). These mutations were potential driver mutations and further research need to be support. Conclusions: We found that not only POLD1 or/and POLE mutations were enriched in samples with high TMB, but also driver mutations were enriched in microsatellite stable tumors. Further researches need to continue to identify more driver mutations of POLD1 and POLE.
A phase III, open-label, randomized study of atezolizumab in combination with carboplatin + paclitaxel + bevacizumab compared with pemetrexed + cisplatin or carboplatin with stage IV non-squamous non-small cell lung cancer (NSCLC) with activating EGFR mutation or ALK translocation (ATLAS Trial).
Authors: Sehhoon Park, Yun-Gyoo Lee, Ji Hyun Park, Gyeong-Won Lee, Eun Joo Kang, Yoon Ji Choi, SeongHoon Shin, Ji-Youn Han, Suee Lee, YuJung Kim, Tae Min Kim, Sang-We Kim, Byoung Yong Shim, Jinhyun Cho, Hye Sook Kim, Sang Gon Park, Ki Hyeong Lee, Ilhwan Kim, Myung-Ju Ahn
Journal: Journal of Clinical Oncology (2020)

TPS9636 Background: In patients with activating EGFR mutations and ALK fusion, target specific tyrosine kinase inhibitor (TKI) showed significant survival improvement compared to the cytotoxic chemotherapy. However, the questions remain which combination strategy will be the best option for the patients who have failed from TKI. Especially, the role of an immune checkpoint inhibitor (ICI) in this population is still unclear. This study is designed and conducted based on the recent subgroup analyses from the IMpower 150 study which showed the positive clinical outcomes of atezolizumab combined with VEGF inhibitor and conventional cytotoxic chemotherapy in EGFR mutation and ALK translocation. Methods: This study is the phase III, open-label, multicenter study of atezolizumab in combination with bevacizumab + carboplatin + paclitaxel (ABCP, Arm A) compared with pemetrexed + cisplatin or carboplatin (Arm B). The study population will be randomized to either Arm A (n = 152) or Arm B (n = 72) based on two stratification factors, EGFR vs. ALK and presence of brain metastases. In Arm A, patients will be treated with 4 or 6 cycles of ABCP followed by maintenance atezolizumab and bevacizumab every three weeks. In Arm B, pemetrexed maintenance therapy will be applied every three weeks after 4 or 6 cycles of pemetrexed + cisplatin or carboplatin. As key inclusion criteria, the patients must be diagnosed with stage IV non-squamous non-small cell lung cancer with either activating EGFR mutation or ALK translocation. All the patients need to be cytotoxic chemotherapy naïve and must have experienced disease progression to treatment with at least one EGFR or ALK TKI. If the patients have T790M mutation after 1 st or 2 nd generation EGFR TKI, second line 3 rd generation EGFR TKI treatment is mandatory. The number of T790M positive patients is restricted to under 30% of the entire study population. The primary endpoint is progression-free survival and the major secondary endpoints are overall survival, objective response rate and duration of response. A total of 228 subjects will be enrolled to detect a hazard ratio of 0.67. The first subject received treatment in Aug. 2019 and 19 patients receive the treatment. This study is opened in 3 sites and expected to be opened at 18 sites in South Korea. The time point for the primary analyses is Q3. 2022. Clinical trial information: NCT03991403 .
Association of chronic hepatitis C virus infection with an increased risk of lung cancer: A systematic review and meta-analysis.
Authors: Ben Ponvilawan, Nipith Charoenngam, Pongprueth Rujirachun, Phuuwadith Wattanachayakul, Surapa Tornsatitkul, Thanitsara Rittiphairoj, Patompong Ungprasert
Journal: Journal of Clinical Oncology (2020)

e13562 Background: Chronic hepatitis C virus (HCV) infection is associated with increased risk of multiple types of extrahepatic cancer, such as lymphomas, thyroid cancer and renal cancer. However, whether HCV infection also increases the risk of lung cancer is still inconclusive. This systematic review and meta-analysis was performed in order to determine the relationship between chronic HCV infection and lung cancer. Methods: A systematic review was performed using EMBASE and MEDLINE databases from inception to November 2019 with search strategy that represents “hepatitis C virus” and “cancer”. Eligible studies must be cohort studies which include patients with chronic HCV infection and comparators without HCV infection, then follow them for incident lung cancer. Relative risk, incidence rate ratio (IRR), standardized incidence ratio, or hazard risk ratio of this association along with associated 95% confidence interval (CI) from each study were extracted and combined for the calculation of the pooled effect estimate using the random effect, generic inverse variance. Results: 20,459 articles were discovered using the aforementioned search strategy. After two rounds of review, eight studies fulfilled the inclusion criteria and were included into the meta-analysis. Chronic HCV infection was significantly associated with increased risk of lung cancer with the pooled relative risk of 1.94 (95% CI, 1.56 – 2.42; I 2 = 87%). Funnel plot was fairly symmetric and not suggestive of presence of publication bias. Conclusions: Chronic HCV infection is significantly associated with a 1.94-fold increased risk in the development of lung cancer compared to no infection.
Real-world outcomes among patients with epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors versus immunotherapy or chemotherapy in first-line setting.
Authors: Daniel Simmons, Maral DerSarkissian, Rahul Shenolikar, Min-Jung Wang, Angela Lax, Aruna Muthukumar, François Laliberté, Mei Sheng Duh
Journal: Journal of Clinical Oncology (2020)

281 Background: While EGFR tyrosine kinase inhibitors (TKIs) are the NCCN-recommended first-line (1L) therapy for non-small cell lung cancer (NSCLC) patients (pts) with EGFR mutation (EGFRm), many pts initiate immunotherapy (IO) + chemotherapy (chemo) prior to receiving EGFRm test results. This study assessed clinical outcomes associated with initiating EGFR-TKI vs other therapies in stage IV EGFRm NSCLC. Methods: A retrospective study was conducted in adults with stage IV EGFRm NSCLC who initiated 1L EGFR-TKI, IO (+ chemo), or chemo alone from 5/2017-12/2018, using Flatiron Health Electronic Health Record data. Treatment patterns were characterized with respect to timing of EGFRm test results. Kaplan-Meier analysis and log-rank tests were used to evaluate the median duration of therapy (DoT) and time to next therapy (TTNT), as proxies for progression-free survival. Adjusted hazards ratios (HR) and 95% confidence intervals (CI) representing the effect of 1L therapy on the risk of discontinuing treatment or death (DoT) and the risk of initiating second-line therapy or death (TTNT) were reported from multivariable Cox proportional hazards models controlling for differences in demographics, smoking history, histology, cancer stage, ECOG score, NCI index, time from diagnosis to 1L initiation, and year of 1L initiation, across treatment arms. Results: Among 593 study pts, mean age was 67.5 years and 65.4% were female. EGFR-TKI was used as 1L therapy for 77.2% of pts (n=458), IO in 13.3% (n=79) and chemo in 9.4% (n=56). 7.2% of EGFR-TKI pts, 54.4% of IO pts, and 57.1% of chemo pts initiated 1L before receiving EGFRm test results. Compared to pts on IO and chemo, pts on EGFR-TKI had longer median DoT (EGFR-TKI: 8.7 months [mo]; IO: 4.8 mo; chemo: 3.0 mo, p&lt;0.01) and median TTNT (EGFR-TKI: 12.3 mo; IO: 6.5 mo; chemo: 4.0 mo, p&lt;0.01). Adjusted analyses showed that compared to pts on IO or chemo, pts on EGFR-TKI had significantly lower risk of discontinuing therapy or death (DoT) and initiating second-line therapy or death (TTNT) (Table). Conclusions: Substantial numbers of pts initiated IO + chemo in 1L and EGFR-TKI was associated with better clinical outcomes than IO + chemo, suggesting the importance of adhering to NCCN-recommended therapy for stage IV EGFRm NSCLC pts. [Table: see text]
Patients with bullous skin disease in a high‐epidemic COVID‐19 area, Bergamo, Italy
Authors: A. Carugno, P. Sena, F. Raponi, E. Robustelli Test, P. Vezzoli
Journal: British Journal of Dermatology (2020)

for one individual who had to discontinue sirolimus treatment due to painful oral ulcers (grade 3).Oral ulceration was experienced by the majority of patients in our study and has been frequently reported in prior prospective trials.mTOR inhibitor-associated stomatitis appears similar to aphthous ulceration and distinct from oral mucositis caused by chemotherapy. 2Acneiform eruptions have been reported in about one-quarter of patients taking mTOR inhibitors; 3 our findings suggest that this may be more common than previously considered.Previous trials have also reported infections, particularly of the respiratory tract, 1,2 and our results indicate that skin and soft tissue infections may occur.Remarkably, 20 (67%) experienced changes relating to the pilosebaceous unit, including changes in hair growth.This may result directly from mTOR inhibition through effects on hair follicle stem cells and hair follicle cycling, 4 or indirectly through inhibition of signalling through epidermal growth factor (EGF). 5 Several hair-related side-effects, including acne, 6 trichomegaly 7 and scalp hair changes, 7 have been associated with EGF inhibitors.A potential limitation of our study is partial reliance on patient history for documenting side-effects.Furthermore, the retrospective nature of the study limited our ability to assess the timing and dose-dependence of side-effects.Dermatological side-effects of oral mTOR inhibitors are common but generally do not necessitate treatment discontinuation.For side-effects that are particularly bothersome or complicated, routine monitoring by dermatologists can be vital for optimizing quality of life during therapy.Painful mouth ulcers that hinder oral intake may lead to poor nutrition.Patients may benefit from avoidance of foods that may traumatize the oral mucosa as well as from topical corticosteroids or analgesics. 8Acneiform eruptions, which may be painful and cause psychological distress, may be managed with conventional acne therapies. 5Patients should be cautioned prior to undergoing skin biopsies regarding the risks of poor wound healing and cutaneous infections.For individuals who are refractory to direct management of dermatological side-effects, dosage reduction or transient discontinuation of treatment may be pursued, especially if the risks of stopping therapy outweigh the benefits.
Efficacy and safety of short-term sensor-augmented insulin-pump therapy for poorly controlled patients with type 1 diabetes mellitus
Authors: Chunhong Shi, Lisha Zhang, Ran Bai, Dan Liu, Yongbo Wang, Hao Wang, Yu Yang, Xueyang Zhang, Yangyang Ji
Journal: BMJ (2016)

Objective
To evaluate the efficacy and safety of short-term sensor-augmented insulin-pump (SAP) therapy for poorly controlled patients with type 1 diabetes mellitus (T1DM).


Methods
Sixty T1DM patients with glycosylated hemoglobin (HbA1c)>9.0% were randomly assigned to 2 groups treated with SAP or multiple daily insulin injection (MDI) for 6 days, then all patients converted to MDI therapy.


Results
Compared with MDI group and before therapy, the mean blood glucose concentration (MBG), SD of blood glucose, mean amplitude of glycemic excursion (MAGE) and 24-h area under curve at 10.0 (AUC10.0) levels in SAP group significantly decreased after 6-day therapy (compared with MDI group: t=1.761, P=0.028, t=2.569, P=0.037, t=2.712, P=0.020, t=2.985, P=0.014, compared with before therapy: t=3.128, P=0.006, t=2.689, P=0.024, t=2.966, P=0.013, t=3.076, P=0.009); while there was no difference in 24-h area under curve at 3.9 (AUC3.9) between groups (P>0.05). After 1 month follow-up HbA1c levels decreased in SAP group (t=2.344, P=0.023) and were significantly lower than those in MDI group (t=1.844, P=0.035). There was no difference in daily insulin dosage, fasting C peptide (FCP) and postprandial 2 h C peptide (2 hCP) between two groups (P>0.05). Age (t=2.125, P=0.012) and SAP therapy (t=3.376, P=0.009) were independently correlated with the HbA1c after 1 month.


Conclusion
Short-term SAP therapy is effective and safe for poorly controlled T1DM patients with rapid glucose lowering and glycemic excursions reduction.


Key words: 
Diabetes mellitus, type 1; Insulin infusion systems; Continuous glucose monitoring; Treatment outcome
Abstract 12766: Perinatal Hypoxia Aggravates Occlusive Pulmonary Vasculopathy in the Adolescent Rats: Establishment of a Fatal Sugen/hypoxia Model and Its Molecular Basis
Authors: Hironori Oshita, Hirofumi Sawada, Yoshihide Mitani, Jane Kabwe, Noriko Yodoya, Naoki Tsuboya, Kazunobu Ohya, Hiroyuki Ohashi, Kazuo Maruyama, Masahiro Hirayama
Journal: Circulation (2019)

Hypothesis: We tested the hypothesis that perinatal hypoxia, simulating fetal and neonatal distress, aggravates occlusive pulmonary vascular disease (PVD) in SUGEN/hypoxia (SuHx) rats. Methods: Per...
Hormones as indicator of relapse-free period in breast cancer (BC).
Authors: Natalia Yu. Samaneva, Elena M. Frantsiyants, Liubov Yu Vladimirova, Anna E. Storozhakova, Elena A. Sheiko, Valeria A. Bandovkina, Natalia D. Cheryarina, Natalia M. Tikhanovskaya, Oleg I. Kit, Aleksandr E. Lisutin, Iuliana S. Shatova, Larisa N. Vashchenko
Journal: Journal of Clinical Oncology (2020)

e12550 Background: BC is still one of the main causes of death in women due to the tumor recurrence and/or resistance to anticancer therapy. The criteria to assess the effectiveness of BC treatment are important. The purpose of the study was to analyze blood levels of steroid and pituitary hormones in BC patients after two chemotherapy cycles. Methods: The study included 42 patients with various biological BC subtypes: luminal A, luminal B and triple-negative BC (TNBC). Levels of estradiol, testosterone, progesterone, prolactin, LH, FSH and cortisol were measured by RIA in the blood of all patients before and after two neoadjuvant chemotherapy cycles. Significance of differences was evaluated by the Student’s t-test. Results: Levels of many hormones were high before the treatment in patients with all BC subtypes. After two chemotherapy cycles, unidirectional changes in the values were found in patients with subsequent remission for more than three years. Levels of estradiol decreased in luminal A BC by 1.7 times (p˂0.05), in luminal B BC – by 11.6 times (p˂0.05), cortisol decreased by 2.4 and 1.7 times (p˂0.05) respectively, and prolactin – on average by three times (p˂0.05). LH levels increased in luminal A and luminal B BC by 1.65 times (p˂0.05). In patients with TNBC, levels of estradiol decreased by 1.8 times, and cortisol – by two times (p˂0.05). Patients with subsequent remission regardless of BC subtypes had unchanged levels of testosterone, progesterone and FSH. Patients with luminal B and TNBC subtypes with progression in 6-12 months did not show significant changes in prolactin and cortisol levels after two chemotherapy cycles, compared with the values before treatment. Conclusions: A decrease in blood levels of prolactin and cortisol after two chemotherapy cycles is an indicator of a long-term remission in patients with breast cancer.
合并睾丸炎的布氏杆菌感染一例
Authors: 陈恕平, 刘玉兰
Journal: BMJ (2008)

患者男,21岁,未婚,汉族.因发热3个月,畏寒、寒战1个月于2006年5月10日人院.入院前3个月患者无明显诱因出现低热,体温约37.5℃,伴流涕、喷嚏、轻咳、咳少量白色泡沫样痰,无畏寒、寒战、咽痛,无尿频、尿急、尿痛,无腹痛、腹泻,无关节肿痛.自服阿莫西林、APC、维C银翘片等药物后体温降至正常,咳嗽、咳痰、流涕症状好转,3～4 d后体温复升。
Efficacy and safety of dezocine and flurbiprofen axetil as combination therapy for the pain after skin grafting
Authors: Gang Xu, Zhongyin Zhufu, Yi Luo, Jie Zhou, Huibin Lian
Journal: BMJ (2017)

将40例烧伤行植皮术患者随机分为观察组和对照组，各20例，观察组术后给予地佐辛肌肉注射联合氟比洛芬酯静脉滴注，对照组为氟比洛芬酯静脉滴注。术后2、4及8 h两组患者疼痛的数字评分法(NRS)评分差异有统计学意义(均P 0.05)，不良反应发生情况差异无统计学意义(χ2＝0.914，P＝0.34)。提示地佐辛与氟比洛芬酯联合治疗烧伤植皮术后疼痛能较快达到满意的镇痛效果，未增加不良反应的发生。
Research progress of apical ballooning syndrome
Authors: 刘立新, 武云涛, 何冰鹃, 周书明
Journal: BMJ (2009)

心尖球形综合征(apical ballooning syndrome)1991年由日本学者Dote等[1]首先报道,2008年欧洲心脏病学会将其归为未分类性心肌病.这类患者左室造影心尖部收缩期呈气球样隆起,形态类似日本捕章鱼的坛子(tako tsubo),故又称Tako-tsubo心肌病,此外也叫做伤心综合征、应激心肌病、amphora或ampulla心肌病.由于临床表现与急性冠脉综合征(ACS)相似,初诊时极易误诊。
Differential diagnosis of food allergy and food intolerance
Authors: Junge Wang, Hong Zhang
Journal: BMJ (2016)

The mechanisms of food allergy include IgE-mediated and non IgE-mediated immune responses. Food intolerance is the reaction of defected digestive function caused by many factors in which the immune system is not involved. Clinically, the cases of food intolerance are increasing and the symptoms of the disease are usually complicated. Clinicians are facing the problem of differential diagnosis of food allergy and food intolerance, this article reviews the mechanisms of these two diseases to provide the reference for differential diagnosis.


Key words: 
Food hypersensitivity; Food intolerance; Diagnosis, differential
Effect of FAmily CEntered (FACE) advance care planning (ACP) on families’ appraisals of caregiving for their teens with cancer.
Authors: Justin N. Baker, Jessica Thompkins, Sarah Friebert, Jennifer Needle, Jichuan Wang, Yao Cheng, Maureen Lyon
Journal: Journal of Clinical Oncology (2020)

e22533 Background: Little is known about how well family caregivers respond to participating in pACP. The research objective was to understand the effect of FAmily CEntered pediatric Advance Care Planning (FACE pACP) for teens with cancer (FACE-TC) on families’ appraisals of caregiving for their child over time. Methods: 126 adolescent/family dyads were randomized to either FACE-TC intervention or treatment as usual control. FACE-TC is three weekly, 60-minute pACP sessions with a trained/certified facilitator. Family Appraisal of Caregiving Questionnaire subscales assessed outcomes. Generalized Estimating equations (GEE) model was used to examine outcome change over time. The effect of intervention on the change was examined by the interaction between time and intervention. Results: 126 adolescent/family dyads completed baseline assessments. 102 dyads completed the 3-month assessment. Adolescents were mean age of 17 years (range 14-20); 57% female; 79% Caucasian. Family participants were mean age 46 (range 19-67); 83% female; 82% Caucasian. Positive caregiving appraisals subscale items are “Caring for __ is satisfying; It is a privilege to care for __; Caring for __ has made me feel closer to him/her; I am able to comfort __ when he/she needs it; I feel confident I can handle most problems in caring for __; I feel useful in my relationship with __; I am committed to caring for __”. FACE pACP significantly increased positive caregiving appraisals at 3 months post-intervention, compared to controls, (β = 0.20, Confidence Interval = 0.03-0.37, p = 0.0189). No significant differences were found between groups for the subscales: burden, distress or family well-being. Conclusions: FACE pACP significantly increased positive caregiver appraisals compared to controls. The family caregiver’s role is critical for the well-being of teens with cancer. Findings identified positive aspects of caregiving in the context of pACP without increasing caregiver burden or distress. Clinical trial information: NCT02693665.
Understanding trends in blood pressure and their associations with body mass index in Chinese children, from 1985 to 2010: a cross-sectional observational study
Authors: 董彬, 王志强, 宋逸, 王海俊, 马军
Journal: BMJ (2016)

目的
了解儿童期血压水平变化趋势对预测及降低日后成年期高血压及其相关死亡率具有重要意义。鉴于中国儿童肥胖患病率不断增加，本研究探讨了该人群血压变化趋势，并就体质指数(BMI)对其的影响进行了分析。


研究数据和参与人群
本研究使用了1985—2010年中国学生体质和健康调研数据库。该调研为一系列的全国性大样本横断面研究。共有1 010 153名8~17岁儿童纳入到本研究。


主要结果变量
血压测量依据国家高血压教育项目工作组(National High Blood Pressure Education Program Working Group)推荐标准操作。血压偏高(elevated blood pressure)依照该标准性别-年龄-身高别第95百分位数判定。


结果
1985—2005年男、女儿童调整后收缩压均值较基线值分别下降了3.9 mmHg和5.6 mmHg，2005—2010年分别上升了1.3 mmHg和1.0 mmHg。男、女童调整后血压偏高检出率分别由1985年的5.1％和5.5％降至2005年的3.5％和2.5%，继而于2010年升至4.9％和3.5%。2010年男、女童调整后BMI均值较1985年分别增加了2.0 kg/m2和1.2 kg/m2。男、女童肥胖检出率由1985年的均为0％，分别增至3.4％和0.9%。进一步控制BMI后没有改变收缩压变化趋势。在舒张压亦观察到相似结果。


结论
中国儿童血压水平在下降了20年后出现增高。该趋势无法由BMI进行解释。亟需对其他高血压相关风险因素进行研究，遏制儿童血压出现的上升趋势。
Human papillomavirus and cervical intraepithelial neoplasia
Authors: 史景丽, 郭丽娜
Journal: BMJ (2008)

人乳头瘤病毒(human papillomavirus,HPV)感染是常见的性传播疾病之一,在易感女性主要累及生殖道,其次为肛门及呼吸道.所引发的生殖道疾病主要有无症状性或亚临床型HPV感染、湿疣、官颈和外阴的上皮内肿瘤及浸润性癌。