tbuckley/cabot-search huggingface dataset:
Prognosis, biological characteristics and importance of treatment's delay of breast cancer diagnosed during pregnancy.
Authors: Wendy Munoz-Montano, Alberto Alvarado, Paula Cabrera, Fernando Lara, Porras-Reyes Fany, Victor Perez-Sanchez, Alejandro Mohar, Oscar Arrieta, Rafael Vazquez, Juan Enrique Bargallo-Rocha
Journal: Journal of Clinical Oncology (2020)

e12545 Background: Breast cancer in pregnancy is that diagnosed during pregnancy or in the first year after birth (1), is the most frequent malignant neoplasms during pregnancy, (2,3); however, only 0.2% to 2.9% of all breast cancers occur during pregnancy(4), the incidence of breast cancer during pregnancy (BCDP) has increased the last few decades probably because of the delayed childbearing and the rise of maternal age (5,6). Because of the rarity of cases and the impracticability of conducting randomized controlled studies in this setting, several studies are retrospective, whilst some studies suggest outcomes for women are similar to non-pregnant patients with breast cancer(8–11), others (12–17) have demonstrated that pregnancy in itself is an adverse prognostic factor for survival. To contribute with the existing literature, we aimed to perform a cohort to analyze if there is a difference prognosis of patients with BCDP who started treatment during pregnancy or waited for delivery. Methods: We analyzed the baseline characteristics distribution in the BCP using the chi-square test and the Fisher’s exact test for categorical variables. We considered a statistically significant association when p value was &lt; 0.05. DFS and OS analyses were conducted using the Kaplan–Meier method, and the log-rank test was used to determine if there were any differences in the survival curves by the variables of interest. We performed the statistical analysis using the SPSS 25.0 software for Windows (SPSS Inc., Chicago, IL, USA). Results: Among 8037 breast cancer patients enrolled in the database at Instituto Nacional de Cancerología, Mexico (INCan), within the social security program named “Seguro Popular”, between January 2007 and June 2018, we identified and included 61 women, median maternal age at diagnosis in our BCP group was 35 years (range 21-47), triple negative and her2 comprised 50.8% and 49.2% of BCP is comprised by luminal tumors. Conclusions: We strongly believe that the treatment of breast cancer during pregnancy should be started as soon as possible, since we have seen that its delay in childbirth translates into worse disease-free and overall survival. [Table: see text][Table: see text]
A phase I study of safety and pharmacokinetics of A166, a novel selective inhibitor of human epidermal growth factor receptor-2 in Chinese patients with advanced solid tumors.
Authors: Yongheng Liu, Wei Lian, Xi Zhao, Wei Qi, Jian Xu, Liang Xiao, Yan Qing, Tongtong Xue, Jingyi Wang
Journal: Journal of Clinical Oncology (2020)

e13007 Background: Human epidermal growth factor receptor 2 (HER2) is an effective therapeutic target for breast and gastric cancer. A166 is an antibody-drug conjugate composed of a novel cytotoxic drug (monomethyl auristatin F derivative ) site-specifically conjugated to transtuzumab sequence via a stable protease-cleavable valine citrulline linker, which has a DAR (Drug Antibody Ratio) of Better efficacy were observed in preclinical CDX and PDX studies including HER2 low expression and T-DM1 resistant models while toxicity studies demonstrated a good safety profile in cynomolgus monkey. Methods: Patients with HER2-expressing or amplified advanced solid tumors refractory to standard therapies were recruited. A modified Fibonacci 3 + 3 dose-escalation design was employed with 7 dose levels (0.1, 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg every 3 weeks). Safety analyses included all patients. PK and antitumor activity were also assessed. Primary objectives in dose escalation are safety and tolerability and determination of maximum tolerated dose (MTD) and recommended Phase 2 dose. Results: As of October 1, 2019 among 19 patients (breast cancer, colorectal cancer and gastric cancer)treated,no one experienced dose-limiting toxicity. No maximum tolerated dose was determined until 4.8mg/kg dose level. Grade≥3 adverse event was reported for 4 patient as neutropenia、anemia、Hyponatremia and Hypophosphatemia. Notably, 36.8% (n = 7) of patients experienced dry eye, as well as corneal epitheliopathy, and 2 patients withdraw from the study due to grade 2 corneal epitheliopathy. In 3.6 and 4.8 mg/kg groups, 6 patients were evaluable for tumor response, including 3 with partial response, 2 with stable disease. A166 exposure increased with the increase of dose, and extremely low exposure of free toxin and toxin-linker conjugates were observed; t 1/2 was 8.29 days at the 4.8mg/kg. Conclusions: A166 showed an acceptable safety profile and promising anti-tumor activity in patients with HER2-expressing advanced solid tumors. Clinical trial information: CTR20181301 .
Relationship between volume, angle and extent index in non-traumatic avascular osteonecrosis on the femoral head
Authors: Shao-hui Shi
Journal: BMJ (2009)

Objective To explore the relationship between the osteonecrotic volume (lesion size), angle and the index of necrotic extent on the femoral head. Methods Fifty-one hips in 39 patients with non-traumatic avascular osteonecrosis on the femoral head were divided into 12 equal segments from the head to the neck junction (a turning point of the spherical curve of the head) with whole hip displacement, each with 30 degrees on a coronal plane of weight-bearing surface. The osteonecrotic angle of the arc of each necrotic segment from the center of the femoral head was measured at the point of one- to 12-o'clock on imaging of two dimensional reconstruction of computerized tomography (CT) scans and anteroposterior and lateral radiographs. Necrotic volume on each segment of the femoral head was calculated with fluid displacement method. The index of osteonecrotic extent on the femoral head was calculated using direct anatomical measurements. Results Osteoneerotic volume on the femoral head at the point of 12- to one-o'clock on coronal plane was (74. 5 ± 7.4)% of the sphere equivalent of the whole femoral head, which was positively correlated to its necrotic angle [ (41.9±8. 3) degrees] at the point of one-o'clock on the plane, with a coefficient of correlation of 0. 843, and that at the point of one- to two-o'clock on the plane was (73.7 ±0. 4) %, which was positively correlated to its necrotic angle [ (41.9 ± 1.8) degrees] at the point of two-o'clock, with a coefficient of correlation of 0. 543. Osteonecrotic volume on the point of 11- to 12-o'cleck was (83.6±8.6)%, and the necrotic angle at the point of 12-o'clock was (44. 9±3.9) degrees, which were positively correlated each other, with a coefficient of correlation of 0. 701 (P <0. 01 ). Osteonecrotic volume on the femoral head was positively correlated to its necrotic angle , modified index of necrotic extent, index of necrotic extent and Kerboul conjugated necrotic angle, with coefficients of correlation of 0. 798, 0. 701, 0. 377 and 0. 398 ( P < 0. 01 ), respectively, at the point of one o' clock. Conclusions Measurements of osteonecrotic volume was positively correlated to the index of necrotic extent and necrotic angle on the femoral head, respectively. Necrotic angle on the plane at 30-degree of the trochanter on the femoral head can well reflect its necrotic volume.

Key words: 
Femur head necrosis; Tomography, X-ray; Severity of illness index
Resensitization of palbociclib-resistant MCF-7 cells by inhibiting TGF-β-induced epithelial-mesenchymal transition.
Authors: Minsun Chang, Sujeong Park, Byung Ha An
Journal: Journal of Clinical Oncology (2020)

e13061 Background: Inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) is the most recent therapeutic method to treat estrogen receptor (ER)-positive breast cancer. Three CDK4/6 inhibitors have been approved by the FDA. The acquired resistance to CDK4/6 inhibitors are expected to have a negative impact on success of breast cancer therapy. It is critical to understand the molecular mechanisms underlying drug resistances to devise a better regimen or overcome drug resistance. Methods: The derivative MCF-7 (MCF-7:PR) cells which exert acquired resistance to palbociclib (PCB), one of the FDA-approved CDK4/6 inhibitors, are recently established. The EMT characteristics, major mechanisms for the EMT, and inhibition of TGF-β signaling pathways are studied in MCF-7:PR cells. Results: The mesenchymal markers are increased and the epithelial ones are decreased at both mRNA and protein levels in our cell line model. Transwell migration and would healing assays also demonstrated that MCF-7:PR cells exert EMT properties. Hyperactivation of TGF-β/Smad signaling was observed in MCF-7:PR cells. Chemical inhibition of TGF-β signaling lead to diminished cell migration and resistance to PCB. Conclusions: Resistance to PCB in MCF-7 cells resulted in significant changes in cell motility and molecular markers associated with EMT. In particular, TGF-β signaling is closely related to EMT and its inhibition reversed the EMT and cellular response to PCT. Our findings suggest that the modulation of EMT via inhibition of TGF-β signaling can be one of strategies to bypass PCB resistance in ER-positive breast cancer.
Preventive and therapeutic strategies of breast cancer-related lymphedema
Authors: Binbin Tang, Xiping Zhang, Jinfeng Dai
Journal: BMJ (2017)

Breast cancer-related lymphedema (BCRL) is one of the common complications after surgery. The pathogenesis of BCRL is unclear, and there is no definitely effective treatment for it. In this article we review the pathogenesis, risk factors and treatment of BCRL, propose the comprehensive strategies for prevention and treatment of BCRL.


Key words: 
Breast cancer; Lymphedema; Treatment
Follow-up studies on patients with middle cerebral artery stenosis in cerebral infarction
Authors: 祁风, 徐恩, 陆雪芬, 陈秀梅
Journal: BMJ (2004)

目的 探讨脑梗死大脑中动脉(MCA)狭窄的转归和预后.方法采用德国DWL公司生产的经颅多普勒(TCD)检测仪,对经CT或MRI证实的脑梗死患者进行TCD检查,依据TCD血管狭窄诊断标准,筛选有MCA狭窄的脑梗死患者60例.间隔6个月后复查TCD,记录6个月内任何脑血管事件的发生,根据前后2次检查狭窄MCA血流速度的变化,判断狭窄MCA的转归.结果首次检查时有73条MCA狭窄;间隔6个月TCD复查时,73条狭窄的MCA有15条(15/73,21%)狭窄好转或恢复正常,46条(46/73,63%)狭窄稳定,12条(12/73,16%)狭窄进展或闭塞.6个月内10例患者(10/60,17%)有脑血管事件再发,在10例再发患者的10条症状性MCA中,7条狭窄进展,3条狭窄稳定,狭窄进展组患者再次发生脑血管事件的几率高于狭窄稳定组(t=17.91,P<0.01).Kendall等级相关分析显示脑血管事件的再发与血管狭窄的严重程度有关(CI=0.296,P<0.01). 结论 TCD随访检查可用于评价狭窄MCA的转归和预后,并可预示脑血管事件的发生;脑血管事件的再发与MCA狭窄进展有关,狭窄程度越高,再发脑血管事件的危险性越大。
Exosomal circular RNAs derived from serum: Promising biomarkers for therapeutic targets and prognosis of triple-negative breast cancer (TNBC).
Authors: Sujin Yang, Jinhai Tang
Journal: Journal of Clinical Oncology (2020)

3528 Background: Exosomes are well known by the "exosomal shuttle" that delivers oncogenic microRNAs (miRNAs), mRNAs, circular RNAs (circRNAs) and proteins to the recipient cells and tumor microenvironment, and may be used as promising biomarkers for disease diagnosis. This study aims to provide a theoretical basis to use stable exosomal circRNAs as new biomarkers for predicting the development, metastasis and therapeutic targets of TNBC. Methods: A strategy combining RNA-sequencing technique, bioinformatic analysis and RT-qPCR was used to determine the level of differential expressed circRNAs in serum exosomes samples (n = 43) from TNBC patients compared with non-TNBC patients. The expression of circHSDL2 were also detected in tumor tissues (n = 20) from TNBC patients and breast cancer cell lines by qRT-PCR. Cell cycle analysis, the wound healing assays and transwell assays were used to investigate the function of circHSDL2 in proliferation, invasion and metastasis of TNBC cells. FISH, dual-luciferase reporter and functional assays were performed to confirm the interaction between circHSDL2 and let-7a-2-3p in TNBC cells. Results: We profiled the circRNAs in the serum exosomes samples from TNBC patients and non-TNBC patients by RNA sequencing and detected 803 significantly differentially-expressed circRNAs. After bioinformatic analysis, circHSDL2 was chose to further study. RT-qPCR results showed that higher expression of circHSDL2 in TNBC cell lines and tumor tissues from TNBC patients. Moreover, overexpression of circHSDL2 promoted TNBC cells proliferation and invasion, while knockdown of circHSDL2 inhibited TNBC cells proliferation and invasion. Mechanistically, circHSDL2 acted as a "miRNAs sponge" to absorb let-7a-2-3p; let-7a-2-3p inhibited TNBC cell invasion and metastasis. Kaplan-Meier plots showed lower expression of let-7a-2-3p was connected to poor prognosis in TNBC metastasis patients from TCGA database. Conclusions: The expression of circHSDL2 was found significantly upregulated in serum exosomes and tumor tissues from TNBC patients. Moreover, circHSDL2 could promote cell proliferation, invasion and metastasis in TNBC cells. CircHSDL2 might be function as competing endogenous RNAs (ceRNAs) by targeting let-7a-2-3p in the progression of TNBC. Therefore, this study provides a fresh perspective on novel therapeutic targets and potential biomarkers for TNBC from exosomal circRNAs.
Mass-surveillance technologies to fight coronavirus spread: the case of Israel
Authors: Moran Amit, Heli Kimhi, Tarif Bader, Jacob Chen, Elon Glassberg, Avi Benov
Journal: Nature Medicine (2020)

As the COVID-19 pandemic escalates, teams around the world are now advocating for a new approach to monitoring transmission: tapping into cellphone location data to track infection spread and warn people who may have been exposed. Here we present data collected in Israel through this approach so far and discuss the privacy concerns, alternatives and different 'flavors' of cellphone surveillance. We also propose safeguards needed to minimize the risk for civil rights.
Perceptions of process barriers to lung cancer screening at community oncology programs.
Authors: Linda Sutton, Lisi Lotz, Eileen V. Horn, Trudy Pendergraft
Journal: Journal of Clinical Oncology (2020)

e19218 Background: Lung cancer screening (LCS) has potential to detect earlier stage cancer, favorably impacting patient outcomes, however evolving data suggest that LCS is underutilized. Because LCS is an extensive process with diverse barriers specific to each clinical setting, a multidisciplinary quality improvement (QI) initiative was undertaken to develop and test LCS processes to improve effective LCS. Baseline findings and approaches are presented. Methods: To inform the development of effective strategies to improve LCS, a survey was developed to examine perceptions and barriers to LCS across a group of community oncology programs in the Duke Cancer Network (DCN). The survey analyzed contextual, institutional, and patient factors influencing utilization of LCS. Survey results were used to support purpose-driven multidisciplinary teams to develop site-specific improvement plans for LCS with the support of QI consultants from Bite-Size QI. Results: Surveys were sent to 62 administrators and providers at 12 community oncology programs, with 36 respondents across 9 sites. LCS rates ranged between 4%-16% at participating sites. Respondents identified the lack of processes and infrastructure to support LCS as the most common challenges. Processes related to identification of LCS candidates, conduct of shared decision-making (SDM), follow up of lung nodules, and recurring screens were named specifically. Contributing factors identified were lack of robust community outreach, patient education, and protocols for providers. With regard to SDM, both administrators and providers reported systematic issues including provider time constraints and nonexistent or inconsistent identification/tracking systems, with patient compliance and health literacy as further barriers. The lack of these processes not only affected patients receiving initial LCS, but also how recurrent screenings were tracked. Conclusions: Identifying challenges in processes facilitated creation of improvement projects for participating sites. Initial improvement projects focus on patient notification of LCS results through follow up letters, integration of tracking LCS into hospital systems, development of patient education, community outreach and smoking cessation programs. Follow-up analyses will be undertaken to evaluate each approach.
Diagnosis and treatment of pyelogenic cyst
Authors: Le Che
Journal: BMJ (2011)

The clinical data of 32 patients with pyelogenic cyst were reviewed retrospectively. The diagnosis of 25 cases was confirmed by intravenous pyelography (IVP) , in which the ultrasonography and computed tomography ( CT) failed to provide accurate diagnosis. Eighteen cases were treated by surgical operations, among them 16 cases were cured, one case lost follow-up, and one case recurred in 6 months after surgery. The data indicate that the diagnosis of pyelogenic cyst mainly depends on IVP examination and the laparoscopic technique can be effectively applied for treatment of pyelogenic cyst.

Key words: 
Kidney pelvis;  Cysts
Research progress on related factors of wound healing after skin injury in diabetic patients
Authors: Lanqin Han, Chunli Zhang, Xuelian Zhao, Jie Zhang
Journal: BMJ (2017)

Diabetes is a common disease, the complications caused by hyperglycemia have a serious impact on the quality of life of patients. The wound healing after skin injury in diabetic patient is affected by many factors. This article reviews various factors related to angiogenesis and wound healing in diabetes, including insulin, endogenous hydrogen sulfide, hypoxia inducible factor-1α and tumor necrosis factor-α. These findings may provide a new theoretical basis for the treatment of diabetic wound healing, foot ulcer and other complications.


Key words: 
Diabetes mellitus; Wound healing; Insulin
成人回盲部肠系膜坏死增生性淋巴结病误诊为急性阑尾炎15例分析
Authors: 曹亮, 胡祥, 王长淼
Journal: BMJ (2006)

坏死增生性淋巴结病是一种病因不明的非肿瘤性淋巴结肿大,好发于颈部、腋下、腹股沟等表浅部位,肠系膜处淋巴结发生该病变非常少见.[1].回盲部肠系膜坏死增生性淋巴结病在临床表现上和急性阑尾炎极为相似,多数被误诊而行手术治疗.现就我院1986年以来诊治的15例误诊为急性阑尾炎而行手术治疗、病理检查证实为坏死增生性淋巴结病患者的临床资料分析如下。
Using machine learning to predict immunotherapy response in advanced melanoma.
Authors: Paul Johannet, Nicolas Coudray, Douglas M. Donnelly, George Jour, Irineu Illa-Bochaca, Yuhe Xia, Douglas Buckner Johnson, Lee E Wheless, James Randall Patrinely, Anna C. Pavlick, Jeffrey S. Weber, Hua Zhong, Aristotelis Tsirigos, Iman Osman
Journal: Journal of Clinical Oncology (2020)

10010 Background: Several predictors of response to checkpoint inhibitors show potential, but use pathological assays and/or molecular characterization, which limits their clinical utility outside of the academic setting. We aimed to develop a streamlined approach by leveraging information immediately available through standard care. Here, we present a computational method that integrates deep learning on histology specimens with clinicodemographic variables to predict treatment outcomes in advanced melanoma. Methods: We used hematoxylin and eosin (H&amp;E) sections from 72 patients ( n= 153 slides) from New York University (NYU) to build a Segmentation Classifier that distinguishes tumor, lymphocyte, and connective tissue. Using pre-treatment H&amp;E slides from 121 NYU patients ( n =302 slides), we trained a Response Classifier to predict response by selectively analyzing tumor regions. We then developed a logistic regression classifier that combines neural network output with clinicodemographic variables. The classifiers were tested on an independent cohort of 32 patients from Vanderbilt University ( n =42 slides). Area under the curve (AUC) was calculated as a measure of prediction accuracy. Results: The Segmentation Classifier distinguished tumor, lymphocyte, and connective tissue with AUCs 0.886-0.984. For the Response Classifier, optimal learning conditions were identified through training on NYU patients and testing on Vanderbilt patients (AUCs 0.685 and 0.728, respectively). The fully trained Response Classifier performed with AUC 0.711 on Vanderbilt patients. The logistic regression model performed with enhanced prediction accuracy with AUC 0.803 on NYU patients and AUC 0.793 on Vanderbilt patients. Conclusions: Histology slides and patients’ clinicodemographic characteristics are readily available through routine standard of care and have the potential to predict immunotherapy response. Our approach is time-efficient, reproducible, and requires minimal resource allocation, thus overcoming multiple common barriers to generalizability for contemporary biomarkers.
Estimates of the ongoing need for social distancing and control measures post-“lockdown” from trajectories of COVID-19 cases and mortality
Authors: Mike Lonergan, James D. Chalmers
Journal: European Respiratory Journal (2020)

By 21 May 2020, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) had caused more than 5 million cases of coronavirus 2019 (COVID-19) across more than 200 countries. Most countries with significant outbreaks have introduced social distancing or “lockdown” measures to reduce viral transmission. So the key question now is when, how and to what extent these measures can be lifted. Publicly available data on daily numbers of newly confirmed cases and mortality were used to fit regression models estimating trajectories, doubling times and the reproduction number (R 0 ) of the disease, before and under the control measures. These data ran up to 21 May 2020, and were sufficient for analysis in 89 countries. The estimates of R 0 before lockdown based on these data were broadly consistent with those previously published: between 2.0 and 3.7 in the countries with the largest number of cases available for analysis (USA, Italy, Spain, France and UK). There was little evidence to suggest that the restrictions had reduced R far below 1 in many places, with France having the most rapid reductions: R 0 0.76 (95% CI 0.72–0.82) based on cases, and 0.77 (95% CI 0.73–0.80) based on mortality. Intermittent lockdown has been proposed as a means of controlling the outbreak while allowing periods of increased freedom and economic activity. These data suggest that few countries could have even 1 week per month unrestricted without seeing resurgence of the epidemic. Similarly, restoring 20% of the activity that has been prevented by the lockdowns looks difficult to reconcile with preventing the resurgence of the disease in most countries.