tbuckley/cabot-search huggingface dataset:
Crosstalk between the MSI status and tumor microenvironment in colorectal cancer.
Authors: Peng Luo, Anqi Lin, Jian Zhang
Journal: Journal of Clinical Oncology (2020)

e15236 Background: In recent years, cancer immunotherapy has been extensively studied, and colorectal cancer (CRC) patients have also derived clinical benefits from immunotherapy, especially CRC patients with mismatch repair deficiency (dMMR)/microsatellite instability-high (MSI-H), whose sensitivity to immune checkpoint inhibitors (ICIs) is significantly higher than that of patients with microsatellite-stable (MSS)/microsatellite instability-low (MSI-L) disease. This study suggests that patients with MSI-H CRC have a higher mutational burden and more immune cell infiltration than those with MSS/MSI-L disease. However, most studies have not systematically evaluated the immune characteristics and immune microenvironments of MSI-H and MSS/MSI-L CRC. Methods: A published CRC cohort with mutation and immunotherapy-related prognostic data was collected. We analyzed the relationship between the MSI status and prognosis of ICI treatment in an immunotherapy cohort. We then further used mutation data for the immunotherapy and The Cancer Genome Atlas (TCGA)-CRC (colon adenocarcinoma (COAD) + rectum adenocarcinoma (READ) cohorts. For mRNA expression, mutation data analysis of the immune microenvironment and immunogenicity under different MSI status was performed. Results: Compared with MSS/MSI-L CRC patients, patients with MSI-H CRC significantly benefited from ICI treatment. We found that MSI-H CRC had more immune cell infiltration, higher expression of immune-related genes and higher immunogenicity than MSS/MSI-L disease. The MANTIS score used to predict the MSI status was positively correlated with immune cells, immune-related genes, and immunogenicity. In addition, subtype analysis showed that COAD and READ might have different tumor immune microenvironments. Conclusions: MSI-H CRC may have an inflammatory tumor microenvironment and increased sensitivity to ICIs. Unlike those of MSI-H READ, the immune characteristics of MSI-H COAD may be consistent with those of MSI-H CRC. Furthermore, the possible mechanism underlying the prognostic differences among CRC patients receiving ICIs in relation to the immune microenvironment were elucidated to provide theoretical guidance for further improving the curative effect of ICIs treatment on MSI-H CRC patients in the future and solve the problems underlying why MSS/MSI-L CRC patients do not benefit from ICIs treatment.
Successful tumor-infiltrating lymphocyte (TIL) growth from uveal melanoma (UM) using a three-signal (3.0) method.
Authors: Meredith Pelster, Marie-Andree Forget, Stephen K. Gruschkus, Cara L. Haymaker, Chantale Bernatchez, Patrick Hwu, Rodabe Navroze Amaria, Dan S. Gombos, Sapna Pradyuman Patel
Journal: Journal of Clinical Oncology (2020)

3027 Background: Metastatic UM is a rare cancer with poor response rates to systemic therapy. Adoptive transfer of patient-specific TIL may represent the best strategy for treatment. TIL are harvested from primary or metastatic tumors and initially expanded in culture with high dose IL-2 prior to undergoing rapid expansion protocol and therapeutic administration. Here, we report improved rates of initial expansion using a previously described TIL 3.0 method which utilizes dual agonistic antibodies to TCR and 4-1BB (Urelumab) for stimulation, respectively, with high dose IL-2, compared to the traditional method. Methods: Between 2006 and 2019, patients were consented for TIL harvest from either primary or metastatic UM tumors. Demographics, clinical features, and outcomes of the TIL initial expansion were collected. Success rates, number of cells expanded, and days in culture for the two methods were analyzed using partially overlapping samples t-tests and z-tests. Results: There were 85 harvests and expansions from 76 patients using the traditional method and 32 expansions from 30 patients using TIL 3.0. Initial TIL expansion was successful in 97% of TIL 3.0 harvests compared to 35% for the traditional method (p &lt; 0.001). More TIL were expanded with TIL 3.0 compared to the traditional method (291.3 million cells vs. 88.6 million cells, p &lt; 0.001), and fewer days were required in culture (18.5 vs. 29.0, p &lt; 0.001). Both primary UM harvests and metastatic harvests were more successful with TIL 3.0 (90% vs. 12% for primary, p &lt; 0.001, and 100% vs. 42% for metastatic, p &lt; 0.001). Conclusions: Expansion of UM tumors via the TIL 3.0 method led to successful growth in 97% of harvests. Therapeutic administration to patients with TIL 3.0 is under active investigation. [Table: see text]
Effects of comprehensive and integrated therapy on recovery of facial nerve damage after stroke
Authors: Chun-xiao Wan
Journal: BMJ (2011)

To investigate the effects of comprehensive and integrated therapy on the recovery of facial nerve function,60 patients with post-stroke facial nerve injury were divided into two groups:Group A (control group) was administered a simple conventional medication,and Group B underwent acupuncture by total considered therapy and was administered a simple conventional medication.Thirty patients were enrolled in each group.The Portmann modified clinical symptom score,intracranial hemodynamics,and electrophysiological parameters were analyzed before and after treatment.Thirty days later,the clinical symptom score in Group B increased significantly compared with that in the control group ( Group B,17.0 ±2.5 ; Group A,13.0 ±2.0; P ＜0.01 ).Group B showed significant improvements in middle cerebral artery blood flow [ Group B,(90 ± 17 ) cm/s; Group A,( 52 ± 15 ) cm/s ; P ＜ 0.01 ],facial nerve conductivity [Group B,latency of the ipsilateral orbicularis muscle,(3.35 ± 0.67) ms; Group A (3.95 ±0.58) ms;P ＜ 0.01 ].These results indicate that the total considered therapy improved the recovery of post-stroke facial nerve function and that this improvement was related to the increase in intracranial blood supply.

Key words: 
Facial nerve;  Acupuncture therapy
Visual acuity test for children under 5 years of age
Authors: Li-hong Li, Jian-hua Peng, Yong Wen, An-hui Zhu, Ai-lan Zhao
Journal: BMJ (2009)

The visual acuity testa were performed in 8219 children(16 438 eyes)under 5 years of age with sound and light toys,electric torch and a retinoscope.The general ocular examination and mydriatic optometry were also performed for the ametropia.In 8219 children 61 were found to have dominant strabismus,including 59 cases of concomitant strabismus and 2 paralytic strabismus.AbnormaJ refraction was detected in 404 children(739 eye)accounting for 4.92%,including 68 cases of anisometropia (0.83%).In 16 438 eyes 621(3.78%)were moderate or hyper-presbyopia;53(0.32%)were myopia;65 (0.40%)were mixed astigmatism.The vision acuity test described above is a simple and convenient method suitable for children under 5 who are not able to read the conventional test chart.

Key words: 
Optometry;  Child health services
Present situation and development direction of home healthcare
Authors: Wenjie Yan, Lingbo Sun, Jing Li
Journal: BMJ (2017)

With the population ageing, increasing health needs and demands, changing family structure and the transformation of general hospital service model, home care as an important part of primary care, has been brought more and more attention. Home healthcare would relieve the pressure caused by increasing needs of elderly care and transformation of hospital functions, so it should have greater development in the future. This article reviews the present situation and the future development direction of home healthcare in China.


Key words: 
Home nursing; Home-based care for the aged
Venom Systems as Models for Studying the Origin and Regulation of Evolutionary Novelties
Authors: Giulia Zancolli, Nicholas R Casewell
Journal: Molecular Biology and Evolution (2020)

Abstract A central goal in biology is to determine the ways in which evolution repeats itself. One of the most remarkable examples in nature of convergent evolutionary novelty is animal venom. Across diverse animal phyla, various specialized organs and anatomical structures have evolved from disparate developmental tissues to perform the same function, that is, produce and deliver a cocktail of potent molecules to subdue prey or predators. Venomous organisms therefore offer unique opportunities to investigate the evolutionary processes of convergence of key adaptive traits, and the molecular mechanisms underlying the emergence of novel genes, cells, and tissues. Indeed, some venomous species have already proven to be highly amenable as models for developmental studies, and recent work with venom gland organoids provides manipulatable systems for directly testing important evolutionary questions. Here, we provide a synthesis of the current knowledge that could serve as a starting point for the establishment of venom systems as new models for evolutionary and molecular biology. In particular, we highlight the potential of various venomous species for the study of cell differentiation and cell identity, and the regulatory dynamics of rapidly evolving, highly expressed, tissue-specific, gene paralogs. We hope that this review will encourage researchers to look beyond traditional study organisms and consider venom systems as useful tools to explore evolutionary novelties.
Quality of life assessment for elderly residents in Shanghai communities and relevant influence factors
Authors: Haitang Wang, Juan Shou, Yao Liu, Limin Ren
Journal: BMJ (2019)

Objective
To assess quality of life in elderly in Shanghai communities and to analyze relevant influence factors.


Methods
The quality of life and relevant influence factors of 4 395 residents aged 60 years or older who were registered in the health records of three community healthcare centers in Shanghai were investigated through questionnaire survey.


Results
Total 4 350 valid questionnaire were retrieved with a response rate of 99.0%. The mean physical component summary scale (PCS) score was (50.1±10.1) and the mean mental component summary scale (MCS) score was (47.3±7.9). Factors influencing the quality of life in order of importance were depressive symptom(B=-8.41), self-care ability(B=7.45), disease score(B=-1.91), participating in outdoor activities(B=1.89), proportion of medical expenses over income(B=-1.72), social intercourse score(B=-1.48), gender(B=-1.37), education level(B=-1.03) and age(B=-0.93).


Conclusion
The quality of life in elderly residents of Shanghai is relatively high, but the mental components of quality of life need to be further improved.


Key words: 
The elder; Life quality; Relevant influence factors
FAM120A-PTPN3 variations in neuroblastoma: Implications for poor prognosis and relapse.
Authors: Lan Sun, Andres Stucky, Lingli Tu, Xuelian Chen, Jun Luo, Jiang F. Zhong
Journal: Journal of Clinical Oncology (2020)

e22512 Background: Neuroblastoma (NB), the most common tumor in infants, presents clinical unpredictability of relapse and treatment response. Staging and risk stratification depending on clinical examinations are often undertaken while molecular risk factors are less known. Relapse of high-risk NB remains the greatest clinical challenge. Thus, we conduct this study to investigate the molecular mechanism of NB relapse. Methods: Six patients with neuroblastoma who had both primary tumor and relapse samples were studied to identify key mutations in relapse. A cohort analysis of genetic profiles was then performed in order to find out gene mutations associated with the relapse samples. Mutation distribution and expression profiling in 127 patients from the national cancer institute database were used to identify relapse related gene networks. Kaplan-Meier analysis was performed for Overall survival (OS) on each mutation and Ingenuity pathway analysis (IPA) was consulted for their possible interactions. Gene manipulation in two neuroblastoma cell lines were used for verification. Results: We identified 40 potential mutations that associated with the relapse samples, including FAM120A and PTPN3. Mutation distribution in a larger NB population with 127 patients showed FAM120A mutation rate was 32.3% (41/127) and PTPN3 was 52.8% (67/127). Both had significant impact on OS. The median OS (mOS) with or without FAM120A mutation was 1527±214 days and 2300±139 days, respectively (p = 0.000). mOS with or without PTPN3 mutation was 1822±163 days and 2285±179 days, respectively (p = 0.037). Additionally, mOS in group lacking both mutations (42/127) was 2555±196 days, much higher than 1857±153 days, in those who had only one (62/127), or 1391±266 days, in those who had both (23/127). Furthermore, the prevalence of FAM120A mutation was at Chr.9:93543407 (61.0%, 25/41) and PTPN3 at Chr.9: 109457194 (61.2%, 41/67). Variant at Chr.9:93543407 had more significant impact on OS compared to other sites in FAM120A-mutation subgroup (p = 0.01). Expression of FAM120A was significantly down-regulated in the FAM120A-mutation subgroup compared to non-mutated (p = 0.01). IPA and in vitro assay showed these factors may have an additive effect possibly interacting through TRIM25, MYC and VIRMA. Conclusions: Our results suggest that variations in FAM120A and PTPN3 interact in neuroblastoma resulting in poor prognosis and cancer relapse, and may be a potential target for improvement of current treatment.
Is burn-out-syndrome a problem among oncology workers? Incidence and effective tools to achieve improvement.
Authors: Alberto Jacobo Cunquero Tomas, Inmaculada Ortega, Ana Gomez, Miriam Lobo De Mena, María del Rocío Ramirez Belloch, Mireia Gil Raga, Vega Iranzo, Amaya Belen Fernandez Diaz, Ihsan Shaheen, Marina Meri Abad, Martin Núñez Abad, Milagros Franco de la Rosa, Francisco Aparisi, Maria Jose Safont Aguilera, Maria Jose Godes, Alfonso Berrocal, Cristina Caballero, Ana Blasco, Carlos Camps
Journal: Journal of Clinical Oncology (2020)

11016 Background: Burn-Out Syndrome (BOS) is defined by (1) emotional and physical exhaustion; (2) cynicism and depersonalization; and (3) no personal nor professional fulfillment. It affects up to 78% of oncology-related workers (doctors, nurses and nurse-assistants, among others). This may decrease quality in both patient assistance and institutional processes. However, there is lack of resources for its diagnosis and management. Our objective is to: (1) determine the incidence of BOS in our team; (2) analyze potential causes; and (3) decrease in 20% the percentage of BOS affected workers. Methods: From October 2018 to November 2019, 20 nurses and nurse-assistants participated. Process map and Ishikawa fish-bone diagram were design to analyze BOS potential causes and to design appropriate interventions after Priority/pay-off matrix description. To do so, participants were asked to fulfill a personal detail questionnaire at the beginning, and adapted versions for the GHQ-12 and Maslach Index questionnaires after each intervention. To track the improvement process, a PDSA cycle was fulfilled and re-evaluated overtime. Project developed through the ASCO Quality Training Program and the Fundación ECO support. Results: Population main characteristics: 87% women, 47-year-old median age. 12 nurses, 6 working in the clinic. 90% with more than 5 years of experience in Oncology. At baseline, 75% healthy (GHQ-12), BOS cause risk: exhaustion 70%, depersonalization 45%, fulfillment 55%. Two interventions developed to improve exhaustion BOS risk: (1) ergonomy tips; and (2) self-assessment and self-help tools. 9 subjects lost after 2nd intervention. After interventions, 34% exhaustion risk reduction and 100% healthy workers (GHQ-12). Conclusions: After two interventions, we have achieved an improvement of 34% lowering the risk of suffering BOS among our workers. Health perception improved to 100%. The loss of 9 subjects after the 2nd intervention may be a bias when interpreting the final results. Giving the appropriate tools to medical oncology workers helps reduce BOS risk significantly
Clinical manifestations and pulmonary radiological findings of primary anti-neutrophil cytoplasmic antibody-associated vasculitis
Authors: Youchao Yu, Haijin Yu, Xiaoxia Hou, Yingmeng Ni, Hong Chen, Guochao Shi
Journal: BMJ (2016)

Objective
To analyze the clinical features and pulmonary radiological findings of primary anti-neutrophil cytoplasmic antibody(ANCA)-associated vasculitis (AAV).


Methods
Clinical data of 271 ANCA positive primary AAV patients admitted in Shanghai Ruijin Hospital from January 2003 to November 2015 were retrospectively analyzed. Among 271 patients, there were 211 myeloperoxidase (MPO)-ANCA positive cases (MPO subgroup), 52 proteinase 3 (PR3)-ANCA positive cases (PR3 subgroup), and 8 dual positive cases (dual subgroup) according to ANCA classification. The demography, clinical characteristics, pulmonary radiological manifestation and renal function were compared among three subgroups.


Results
MPO subgroup had more renal (χ2=4.968, P=0.026) and constitutional symptoms (χ2=8.901, P=0.003) than PR3 group, while PR3 group had more ENT symptoms (χ2=19.843, P<0.001), cough (χ2=6.623, P=0.010), hemoptysis (χ2=8.656, P=0.003), dyspnea (χ2=5.127, P=0.024) , buccal and ocular mucosal symptoms (χ2=4.818, P=0.028) than MPO group. In lung radiology, interstitial manifestations were displayed more frequently in MPO than PR3 group (χ2=4.237, P=0.040), while pulmonary nodules was more frequent in PR3 than MPO group (χ2=4.503, P=0.034). Dual subgroup tended to have more nervous, respiratory and renal impairment. Renal function showed that MPO subgroup had higher creatinine (Z=-5.529, P<0.001), urea (Z=-4.646, P<0.001) and uric acid levels (Z=-2.331, P=0.020) than PR3 subgroup. Dual subgroup had higher creatinine (Z=-3.251, P=0.001) and urea (Z=-2.882, P=0.004) levels than PR3 subgroup, but there was no difference with MPO subgroup.


Conclusion
There are significant differences in both clinical and pulmonary radiological manifestations between the MPO and PR3-ANCA subgroup of primary AAV.


Key words: 
Anti-neutrophil cytoplasmic antibody-associated vasculitis; Peroxidase; Proteinase 3; Clinical characteristics; Pulmonary computed tomography
Randomised controlled trial of transanal endoscopic microsurgery versus endoscopic mucosal resection for large rectal adenomas (TREND Study)
Authors: Barendse Renée M, Musters Gijsbert D, de Graaf Eelco J R, van den Broek Frank J C, Consten Esther C J, Doornebosch Pascal G, Hardwick James C, de Hingh Ignace H J T, Hoff Chrisiaan, Jansen Jeroen M, van Milligen de Wit A W Marc, van der Schelling George P, Schoon Erik J, Schwartz Matthijs P, Weusten Bas L A M, Dijkgraaf Marcel G, Fockens Paul, Bemelman Willem A, Dekker Evelien, TREND研究小组, 李佳宁, 吴东
Journal: BMJ (2018)

目的
非随机研究表明内镜下黏膜切除术（endoscopic mucosal resection，EMR）在切除直肠较大腺瘤时与经肛门内镜显微手术（transanal endoscopic microsurgery，TEM）同样有效，但EMR可能更具成本效益且相对安全。本试验旨在对比摘除较大直肠腺瘤时EMR与TEM的临床结局与成本效益。


研究设计
研究人员将无恶性病变特征的、直肠腺瘤直径达到或超过3 cm的患者在EMR及TEM组中随机分配（1∶1），3个月内采用内镜切除残留腺瘤。对随机化分组后发现的意外恶性病变患者予以排除。该研究的主要结局为患者24个月内复发率（旨在证明EMR的非劣效性，上限为10%）及出院后无复发的存活天数。


结果
18所大学教学医院及社区医院收治的共204名患者被纳入研究。27例患者（13%）被诊断意外癌，该部分数据在进一步分析中被剔除。EMR治疗后的总复发率为15%，TEM中这一数据为11%，未达具统计学意义的非劣效性标准。2组间出院后无复发的存活天数基本相似[EMR为（609±209）天，TEM为（652±188）天，P=0.16]。并发症发生率分别为18%（EMR组）及26%（TEM组）（P=0.23），这一组数据对于严重并发症发生率分别为1%及8%（P=0.064）。基于质量调整后生命年限2组相当。相较TEM，EMR可节省费用约3 000欧元，因此更具成本效益。


结论
在该研究的统计假设下，无法证实EMR的非劣性效应。但基于更低的并发症发生率及更佳的成本效益，EMR有可能成为主要的选择方法。未来研究中应进一步关注意外癌症的高发生率。
Prognostic significance of adipose tissue distribution and metabolic activity in PET-CT images of patients with metastatic colorectal cancer.
Authors: Tuba Karacelik, Bugra Kaya, Mustafa Karaagac, Murat Araz, Melek Karakurt Eryılmaz, Hakan Sat Bozcuk, Mehmet Artac
Journal: Journal of Clinical Oncology (2020)

e16038 Background: The metabolic activity in visceral and subcutaneous adipose tissue have different metabolic risk profiles for colorectal cancer. The aim of this study was to investigate the prognostic significance of adipose tıssue distribution and metabolic activity in PET-CT and predict the overall survival in patients with metastatic colorectal cancer (mCRC). Methods: A total of 83 patients diagnosed with mCRC between 2010-2018 were evaluated retrospectively. Pretreatment PET-CT images were reevaluated to determine adipose tissue distribution and metabolic activity. Volume and metabolic activity of subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) on FDG PET-CT images were measured. SAT volume, SAT density (HU), SAT ratio (SAT volume/ SAT density) were calculated. The maximum standardized uptake (SUV) of tumor tissue was measured. The relationship between adipose tissue and overall survival was examined. Results: 53 patients died during follow-up and the median overall survival was 33.76 months (95% CI: 28.185-39.349). According to univariate analysis results, tumor location (HR:2.5; 95% CI 1.27-4.98, p = 0.008) and SAT ratio (HR:0.5; 95% CI 0.34-1.00, p = 0.053) were the significant parameters for the OAS. VAT volume (p = 0.774), VAT density (p = 0.899), VAT suv mean (p = 0.831) and SAT volume (p = 0.423), SAT density (p = 0.353), SAT suv mean (p = 0.575), tumor suv max (p = 0.589) values were not correlated with OAS. In the multivariate analysis, SAT ratio (p = 0.011) and tumor location (p = 0.001) were correlated significantly with OAS. The median OAS for the patients with SAT ratio value &lt; -1.1 and -1.1 were 38.5 (95% CI 31.54-45.58) and 24.5 (95% CI 14.13-34.93) months, respectively (p = 0.05). Conclusions: This study showed that SAT ratio was an independent prognostic factor for OAS in patients with mCRC. We need prospective studies for to observe the relationship between adipose tissue distribution and response to treatment in mCRC.