Development of clinically relevant orthotopic xenograft mouse model of metastatic lung cancer and glioblastoma through surgical tumor tissues injection with trocar

<p>Abstract</p> <p>Objective</p> <p>Orthotopic models are important in cancer research. Here we developed orthotopic xenograft mouse model of metastatic lung cancer and glioblastoma with a specially designed system.</p> <p>Methods</p> <p>Tiny fragments of surgical tumors were implanted into the mice brain with a trocar system. Immunohistochemistry was performed to detect brain tumor stem cells among glioblastoma tissues, including both the original and resulting ones with monoclonal antibody against CD133.</p> <p>Results</p> <p>Besides the constant high take rates in both models; brain transplants perfectly resembled their original tumors in biological behaviors. The brain tumor stem cells, positively stained with CD133 were found, though not frequently, in both original and resulting glioblastoma tissues.</p> <p>Conclusions</p> <p>Orthotopic model established with a trocar system is effective and injection of tumor tissues containing stem cells promise the forming of new tumor mass when grafted.</p

Effects of climate change on the potential distribution of the threatened relict Dipentodon sinicus of subtropical forests in East Asia: Recommendations for management and conservation

Dipentodon sinicus Dunn. (Dipentodonaceae) is a rare and threatened relict plant species usually found co-dominating with other relict plants in subtropical forest patches in highly fragmented habitats of southwestern China, northern Vietnam and northeastern Myanmar of East Asia. To date, its management and conservation strategies in the light of climate change have not been explored. We evaluated effects of climate change on the distribution of climatically suitable areas of D. sinicus as found prevailing during the last glacial maximum (LGM), the mid-Holocene and the present time, and predicted the distribution of climatically suitable habitats in 2070 throughout East Asia. The results as derived from ecological niche modeling (ENM) show the current distribution to be limited to the prehistoric (the mid-Holocene and LGM) refugia, and to indicate decreasing probability of presence and a reducing range of distribution for 2070. In addition, the suitable areas predicted with high probability (0.5–1) only account for on average 9.8% of the total area of potential habitats (threshold‒1) among the models for the year 2070, thereby indicating that D. sinicus is highly vulnerable. Under all the future scenarios for the year 2070, 69–74.2% of potential habitats in China would be outside protected areas. We assess and propose priorities for protected areas, and provide suggestions for conservation management strategies.This study received financial support from Science and Technology Department of Yunnan University, China (2019YNU002), the Ministry of Science and Technology of China (2015FY210200-15), Ajuts a Grups de Recerca Consolidats” (grants nos. 2014-SGR514-GREB and 2017-SGR1116) from the Generalitat de Catalunya (Spain), Applied Basic Research Foundation of Yunnan Province, China (Grant No. 2019FB058), the Environment Research and Technology Development Fund (JPMEERF15S11407) of the Environmental Restoration and Conservation Agency of Japan, and the Kakenhi Grant Number 15H02833.Highlights Abstract Keywords 1. Introduction 2. Material and methods 2.1. Species 2.2. Occurrence data and ecological niche modeling 3. Results 3.1. Model performance and present potential distribution 3.2. Projected distribution during the mid-Holocene (ca. 6000 yr BP) and LGM (ca. 21,000 yr BP) 3.3. Projected distribution under future climate (2070) 4. Discussion 4.1. Effects of climate change on spatial distribution patterns of D. sinicus 5. Recommendations for future conservation efforts and management Declaration of competing interest Acknowledgements Appendix A. Supplementary data Reference

Identifying long-term stable refugia for dominant Castanopsis species of evergreen broad-leaved forests in East Asia: A tool for ensuring their conservation

Identifying and protecting refugia is a priority for conservation management under projected anthropogenic climate change. We have two main objectives: the first is to explore the spatial (East Asia) and temporal (Last Glacial Maximum to year 2070) distribution patterns of dominant Castanopsis species of evergreen broad-leaved forests, also the relation with their niche breadths; the second is to identify long-term stable refugia for preserving these species and provide a framework of conservation strategies. We find that there is an extraordinary richness with 32 dominant Castanopsis species, and they form both a geographically and climatically almost unbroken connection from ca. 5°N to 38°N, having thus ecological significance. During the Mid-Holocene and, particularly, the Last Glacial Maximum, the predicted suitable areas of the species as a whole were larger than those in the present. By 2070, potentially suitable areas with high richness of dominant Castanopsis species will be reduced by 94.5 % on average. No correlation between species niche breadths and distribution ranges is found, which could be due to regional climate stability. Mountains of southwestern and southern Yunnan in China are identified as climatically long-term stable refugia for 7¿9 Castanopsis species. We recommend that these refugia have the highest priority of conservation to prevent their extinction. Our suggested urgent measures include improving the effectiveness of currently protected Castanopsis species and expanding the network of protected areas to cover a larger fraction of the refugia, as well as ensuring Castanopsis species natural regeneration potential in fragmented and natural secondary forest areas.This study received financial support from the Major Program for Basic Research Project of Yunnan Province, China (202101BC070002), the Science and Technology Department of Yunnan University, China (2019YNU002), the Ministry of Science and Technology of China (2015FY210200-15), the Spanish Ministry of Science and Innovation (grant PID2020-119163GB-I00 funded by MCIN/AEI/10.13039/501100011033), the Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency of Japan (JPMEERF20202002), and the Northeastern Research Institute of Petrified Wood and Mineral Resources, Nakhon Ratchasima Rajabhat University, Thailand.Keywords 1. Introduction 2. Materials and methods 2.1. Data collection and notations 2.2. Ecological niche modeling 2.3. Data analyses 3. Results 3.1. Dominant Castanopsis species in East Asia today: richness and distribution patterns 3.2. Richness of dominant Castanopsis species shaped by climate change 3.3. Niche groups and niche breadths of dominant Castanopsis species 3.4. Climatically long-term stable refugia 4. Discussion 4.1. Richness of dominant Castanopsis species shaped by climate change 4.2. Niche groups and niche breadths of dominant Castanopsis species 4.3. Long-term stable refugia and conservation strategies 5. Conclusions CRediT authorship contribution statement Declaration of competing interest Acknowledgements Appendix A. Supplementary material Reference

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Codon Optimization, Expression in Escherichia coli, and Immunogenicity of Recombinant Chinese Sacbrood Virus (CSBV) Structural Proteins VP1, VP2, and VP3.

Chinese sacbrood virus (CSBV) is a small RNA virus family belonging to the genus Iflavirus that causes larval death, and even the collapse of entire bee colonies. The virus particle is spherical, non-enveloped, and its viral capsid is composed of four proteins, although the functions of the structural proteins are unclear. In this study, we used codon recoding to express the recombinant proteins VP1, VP2, and VP3 in Escherichia coli. SDS-PAGE analysis and Western blotting revealed that the target genes were expressed at high levels. Mice were then immunized with the purified, recombinant proteins, and antibody levels and lymphocyte proliferation were analyzed by ELISA and the MTT assay, respectively. The results show that the recombinant proteins induced high antibody levels and promoted lymphocyte proliferation. Polyclonal antibodies directed against these proteins will aid future studies of the molecular pathogenesis of CSBV

Codon Optimization, Expression in Escherichia coli, and Immunogenicity of Recombinant Chinese Sacbrood Virus (CSBV) Structural Proteins VP1, VP2, and VP3.

Chinese sacbrood virus (CSBV) is a small RNA virus family belonging to the genus Iflavirus that causes larval death, and even the collapse of entire bee colonies. The virus particle is spherical, non-enveloped, and its viral capsid is composed of four proteins, although the functions of the structural proteins are unclear. In this study, we used codon recoding to express the recombinant proteins VP1, VP2, and VP3 in Escherichia coli. SDS-PAGE analysis and Western blotting revealed that the target genes were expressed at high levels. Mice were then immunized with the purified, recombinant proteins, and antibody levels and lymphocyte proliferation were analyzed by ELISA and the MTT assay, respectively. The results show that the recombinant proteins induced high antibody levels and promoted lymphocyte proliferation. Polyclonal antibodies directed against these proteins will aid future studies of the molecular pathogenesis of CSBV

Safety and feasibility of a novel chest tube placement in uniportal video‐assisted thoracoscopic surgery for non‐small cell lung cancer

Abstract Background The type and placement of chest tube for patients undergoing uniportal video‐assisted thoracoscopic lobectomy remains controversial. The aim of this study was to assess the efficacy and safety of a novel technique in which a pigtail catheter was used alone as the chest tube and placed near the incision for chest drainage after uniportal video‐assisted thoracoscopic lobectomy and extended lymphadenectomy. Methods A total of 217 patients undergoing uniportal video‐assisted thoracoscopic lobectomy were retrospectively reviewed and divided into two groups. In group A, a 12‐Fr pigtail catheter with several side ports was placed next to the uniportal wound. In group B, a conventional 20‐Fr chest tube was placed through the uniportal wound itself. Postoperative complications related to chest tube placement and patients' subjective satisfaction were compared between the two groups. Postoperative pain management effect and other clinical outcomes such as duration of chest drainage and postoperative stay were also compared. Results There were 112 patients in group A and 105 patients in group B. A significantly lower incidence of wound complications was found in group A postoperatively (p = 0.034). The pain score on coughing in group A was significantly lower than that in group B on postoperative day two (POD2) (p = 0.021). There was no significant difference of other clinical outcomes such as duration of chest drainage and postoperative stay as well as major complications between the two groups. Conclusion Placing a 12‐Fr pigtail catheter alone next to the uniportal wound for chest drainage might be effective and safe after uniportal video‐assisted thoracoscopic lobectomy and extended lymphadenectomy

C‐reactive protein to albumin ratio is a key indicator in a predictive model for anastomosis leakage after esophagectomy: Application of classification and regression tree analysis

Background Anastomotic leakage (AL), a serious complication after esophagectomy, might impair patient quality of life, prolong hospital stay, and even lead to surgery‐related death. The aim of this study was to show a novel decision model based on classification and regression tree (CART) analysis for the prediction of postoperative AL among patients who have undergone esophagectomy. Methods A total of 450 patients (training set: 356; test set: 94) with perioperative information were included. A decision tree model was established to identify the predictors of AL in the training set, which was validated in the test set. A receiver operating characteristic curve was also created to illustrate the diagnostic ability of the decision model. Results A total of 12.2% (55/450) of the 450 patients suffered AL, which was diagnosed at median postoperative day 7 (range: 6–16). The decision tree model, containing surgical duration, postoperative lymphocyte count, and postoperative C‐reactive protein to albumin ratio, was established by CART analysis. Among the three variables, the postoperative C‐reactive protein to albumin ratio was identified as the most important indicator in the CART model with normalized importance of 100%. According to the results validated in the test set, the sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy of the prediction model were 80%, 98.8%, 88.9%, 97.6%, and 96.8%, respectively. Moreover, the area under the receiver operating characteristic curve was 0.95. Conclusion The decision model based on CART analysis presented good performance for predicting AL, and might allow the early identification of patients at high risk