bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of combination therapy with ezetimibe and statins versus a double dose of statin monotherapy in participants with hypercholesterolemia: a meta-analysis of literature
Authors: Yu Min , Liang Chunshui , Kong Qianran , Wang Yihan , Li Minmin 
Published: January 2020

Abstract
Background
The aim of this study was to compare and summarize the lipid-altering effects of combination therapy with ezetimibe and statins (E/S) and a double dose of statin (D/S) monotherapy on patients with hypercholesterolemia.

Methods
We conducted search on 2 medical databases, PubMed and EMBASE to identify all relevant studies. A meta-analysis was performed to clarify the efficacy in the two groups. Only double-blind Randomized controlled study (RCTs) of efficacy evaluation in the two groups with ezetimibe and statins and a double dose of statin in participants with hypercholesterolemia that examined low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and high-density lipoprotein (HDL) were included. Two reviewers extracted data from all primary studies independently. The primary data were the level of LDL-C, TC and HDL-C concentrations at the end point and are expressed as mean and standard deviation (SD).

Results
A total of 11 double-blind, active or placebo-controlled studies with 1926 hypercholesterolemia adults randomized to ezetimibe 10 mg added to ongoing statins (N = 994) or statin titration (doubling) (N = 932) were pooled for the global meta-analysis. The effect size between treatment groups within individual studies was assessed by weighted mean difference (MD) using a random- or fixed-effect model. The result showed that the participants in E/S group get obvious lower LDL-C [MD = -13.14 mg/dL, 95%CI (−16.83, -9.44), p = 0.00001] and TC concentration [MD = -23.79 mg/dL, 95%CI (−38.65, -8.93), p = 0.002] from baseline to follow-up, comparing to the D/S group. Besides, no significant between-group differences were observed for concentrations of HDL-C [MD = 0.46 mg/dL, 95%CI (− 1.14, 2.06), p = 0.57]. According to subgroup analysis, the combination of ezetimibe and atorvastatin (10 mg) [MD = -16.98 mg/dL, p < 0 .0001] or simvastatin (20 mg) [MD = -17.35 mg/dL, p < 0 .0001] showed stronger ability of reducing LDL-C than combination of ezetimibe and rosuvastatin (10 mg) [MD = -9.29 mg/dL, p = 0.05]. The efficacy of short-term (endpoint time between 6 to 16 week) and long-term (52 week) treatment in the LDL-C between two groups did not show significant differences. Besides, only participants from Asia treated with combination therapy were associated with a significant lower LDL-C concentration [MD = -14.7 mg/dL, p < 0 .0001].

Conclusions
The addition of ezetimibe to statin appears to be more effective on reducing LDL-C and TC concentrations than doubling the statin dose. Moreover, the ability to reduce cholesterol levels of combinations therapy with ezetimibe and different statins or to participants from different geographic location may vary, based on this meta-analysis, while more samples are needed to verify.
Beneficial effect of ezetimibe-atorvastatin combination therapy in patients with a mutation in ABCG5 or ABCG8 gene
Authors: Tada Hayato , Okada Hirofumi , Nomura Akihiro , Takamura Masayuki , Kawashiri Masa-aki 
Published: January 2020

Abstract
Background
Use of ezetimibe on top of statin therapy has been shown to be effective to reduce LDL cholesterol level in hypercholesterolemic patients. However, little is known regarding the individual variety of the effectiveness of ezetimibe. We hypothesized that hypercholesterolemic patients with a mutation in ABCG5 or ABCG8 gene exhibit better response to ezetimibe than those without, based on the fact that ezetimibe is hyper-effective for in patients with sitosterolemia caused by ABCG5 or ABCG8 genetic mutations.

Methods
Electronical medical record were reviewed in a total of 321 hypercholesterolemic patients (baseline LDL cholesterol = 192 ± 46 mg/dl) prescribed ezetimibe 10 mg daily on top of atorvastatin 10 mg daily who had undergone genetic analysis of ABCG5 or ABCG8 gene in our institute since 2006 to 2017. Pathogenicity of the variants were determined using standard variant filtering schema, including minor allele frequency, in silico annotation tools. Patients were divided into 2 groups based on the presence of ABCG5 or ABCG8 mutation. We compared the percent reduction of LDL cholesterol as well as the achieved LDL cholesterol levels between these 2 groups.

Results
We found 26 (8%) individuals who exhibit deleterious mutations in ABCG5 or ABCG8 gene. Baseline characteristics under the atorvastatin 10 mg therapy were comparable in age, gender, and LDL cholesterol level between 2 groups. Under these conditions, percent reduction of LDL cholesterol in mutation positive group was significantly larger than that of mutation negative group (28 ± 16% vs. 39 ± 21%, p < 0.05). As a result, the achieved LDL cholesterol level in mutation positive group was significantly lower than that of mutation negative group (87 ± 29 mg/dl vs. 72 ± 26% mg/dl, p < 0.05).

Conclusion
These results suggest that ezetimibe-atorvastatin combination therapy might be more beneficial in hypercholesterolemic patients with a mutation in ABCG5 or ABCG8 gene.
Time-varying pattern of recurrence risk for localized melanoma in China
Authors: Wen Xizhi , Li Dandan , Zhao Jingjing , Li Jingjing , Yang Tao , Ding Ya , Peng Ruiqing , Zhu Baoyan , Huang Fuxue , Zhang Xiaoshi 
Published: January 2020

Abstract
Background
Acral and mucosal melanomas are rarely seen in Caucasians but common in China. There are limited data on the recurrence characteristics for these patients. This study aimed to identify the recurrence pattern for localized melanoma in China, especially acral and mucosal subtypes.

Methods
Patients with localized melanoma who underwent radical resection between January 1999 and December 2014 in southern China were retrospectively reviewed. Survival and annual recurrence hazard were analyzed by Kaplan–Meier method and hazard function, respectively.

Results
Totally, 1012 patients were included (acral melanoma 400; chronic sun-induced damage (CSD)/non-CSD melanoma 314; mucosal melanoma 298). Recurrence was recorded in 808 patients (localized 14.1%; regional 29.6%, and distant 56.3%). Mucosal melanoma had local and M1c stage recurrence more frequently than cutaneous melanoma, but less frequent regional node relapse. There was no difference in recurrent site distribution between acral and CSD/non-CSD melanoma. The annual recurrence hazard curve for the entire cohort showed a double-peaked pattern with the first major peak in the second year after surgery and the second peak near the seventh year. Mucosal melanoma had a higher recurrence risk than cutaneous melanoma. Acral melanoma had a lower flat recurrence peak than CSD/non-CSD melanoma. Tumor thickness > 4.0 mm, ulceration, positive regional nodes, and wound infection were associated with a higher recurrence risk in cutaneous melanoma. Adjuvant therapy reduced the recurrence risk of cutaneous melanoma but not of mucosal melanoma.

Conclusions
This is a large cohort about the rule of recurrence risk in acral and mucosal melanoma and will provide an initial framework for development of surveillance and adjuvant strategy for Chinese melanoma patients.
Safety and efficacy of en bloc transurethral resection versus conventional transurethral resection for primary nonmuscle-invasive bladder cancer: a meta-analysis
Authors: Zhang Dong , Yao Lifeng , Yu Sui , Cheng Yue , Jiang Junhui , Ma Qi , Yan Zejun 
Published: January 2020

Abstract
Background
The purpose of this meta-analysis is to compare the safety and efficacy of en bloc transurethral resection of bladder tumor (EBRT) versus conventional transurethral resection of bladder tumor (CTURBT).

Methods
We performed a meta-analysis of relevant articles through November 2019 using PubMed, Embase, and Cochrane Central Register to compare the safety and efficacy of EBRT versus CTURBT. The main endpoint included the operation time (OT), hospitalization time (HT), catheterization time (AT), perioperative period complications, bladder detrusor muscle found in the specimen, the residual tumor on the base, the ratio of the same site recurrence, and 12/24/36-month recurrence rate. Cochrane Collaboration’s Revman software, version 5.3, was used for statistical analysis.

Results
A total of 19 studies with 2651 patients were included, 1369 underwent EBRT and 1282 underwent CTURBT. Patients treated with EBRT had a significantly lower AT, HT, obturator nerve reflex, bladder perforation, bladder irritation, postoperative complications, and 24-month recurrence rate than those who underwent CTURBT. While no significant difference was found in terms of OT, the ratio of bladder detrusor muscle found in the specimen, the residual tumor on the base, 12-month recurrence rate, 36-month recurrence rate, and the ratio of the same site recurrence. In mitomycin subgroup, EBRT was superior to CTURBT in terms of 12/24-month recurrence rate. Similarly, in the prospective subgroup and retrospective subgroup, EBRT had a lower 24-month recurrence rate than CTURBT. However, no significant difference was found in the low, intermediate, and high-risk group in the light of 12–36-month recurrence rate.

Conclusions
Based on the included 19 articles, EBRT had a significantly lower AT, HT, intraoperative and postoperative complications, and 24-month recurrence rate than those treated with CTURBT. Well-designed randomized controlled trials were needed to reevaluate these outcomes.

Trial registration
This meta-analysis was reported in agreement with the PRISMA statement and was registered on PROSPERO 2019 CRD42019121673.
The choice of dissection or preservation of the inferior pulmonary ligament after an upper lobectomy: a systematic review and meta-analysis
Authors: Lv Hao , Zhou Rui , Zhan Xianghong , Di Dongmei , Qian Yongxian , Zhang Xiaoying 
Published: January 2020

Abstract
Background
The necessity of the inferior pulmonary ligament (IPL) dissection after an upper lobectomy remains controversial. This meta-analysis aimed to evaluate whether this accessional procedure could reduce the postoperative complications and improve outcomes.

Methods
PubMed, Embase, Ovid, Cochrane Library, CBM, and CNKI databases were searched for the relevant studies which compared the dissection with preservation of IPL during the upper lobectomy. The Review Manager 5.3 software was used for this meta-analysis.

Results
Three RCTs and five CCTs were included in this meta-analysis. These studies contained a total of 610 patients, in which 315 patients received a pulmonary ligament dissection (group D) after the upper lobectomy, while the other 295 patients preserved the pulmonary ligament (group P). No significant difference was demonstrated between the group D and group P in terms of drainage time after surgery (MD 0.14, 95%CI − 0.05 to 0.33, P = 0.15), rate of postoperative dead space (OR 1.33, 95%CI 0.72 to 2.46, P = 0.36), rate of postoperative complications (OR 1.20, 95%CI 0.66 to 2.19, P = 0.56). However, the pooled comparison revealed a greater change of the right main bronchial angle (MD 5.00, 95%CI 1.68 to 8.33, P = 0.003) in group D compared with group P, indicated that the dissection of IPL may lead to a greater distortion of bronchus.

Conclusions
This meta-analysis confirmed that the dissection of IPL do not effectively reduce the postoperative complications and improve the prognosis. Therefore, it is not necessary to dissect the IPL after an upper lobectomy.
Right-side versus left-side hepatectomy for the treatment of hilar cholangiocarcinoma: a comparative study
Authors: Jo Hye-Sung , Kim Dong-Sik , Yu Young-Dong , Kang Woo-Hyoung , Yoon Kyung Chul 
Published: January 2020

Abstract
Background
Radical resection is the only curative treatment for patients with hilar cholangiocarcinoma. While left-side hepatectomy (LH) may have an oncological disadvantage over right-side hepatectomy (RH) owing to the contiguous anatomical relationship between right hepatic inflow and biliary confluence, a small future liver remnant after RH could cause worse surgical morbidity and mortality. We retrospectively compared surgical morbidity and long-term outcome between RH and LH to determine the optimal surgical strategy for the treatment of hilar cholangiocarcinoma.

Methods
This study considered 83 patients who underwent surgical resection for hilar cholangiocarcinoma between 2010 and 2017. Among them, 57 patients undergoing curative-intent surgery including liver resection were enrolled for analysis—33 in the RH group and 27 in the LH group. Prospectively collected clinicopathologic characteristics, perioperative outcomes, and long-term survival were evaluated.

Results
Portal vein embolization was more frequently performed in the RH group than in the LH group (18.2% vs. 0%, P = 0.034). The proportion of R0 resection was comparable in both groups (75.8% vs. 75.0%, P = 0.948). The 5-year overall and recurrence-free survival rates did not differ between the groups (37.7% vs. 41.9%, P = 0.500, and 26.3% vs. 33.9%, P = 0.580, respectively). The side of liver resection did not affect long-term survival. In multivariate analysis, transfusion (odds ratio, 3.12 [1.42–6.87], P = 0.005) and post-hepatectomy liver failure (≥ grade B, 4.62 [1.86–11.49], P = 0.001) were independent risk factors for overall survival.

Conclusions
We recommend deciding the side of liver resection according to the possibility of achieving radical resection considering the anatomical differences between RH and LH.
Neuroinflammation trajectories precede cognitive impairment after experimental meningitis—evidence from an in vivo PET study
Authors: Giridharan Vijayasree V. , Collodel Allan , Generoso Jaqueline S. , Scaini Giselli , Wassather Rico , Selvaraj Sudhakar , Hasbun Rodrigo , Dal-Pizzol Felipe , Petronilho Fabricia , Barichello Tatiana 
Published: January 2020

AbstractBackgroundBacterial meningitis is a devastating central nervous system (CNS) infection with acute and long-term neurological consequences, including cognitive impairment. The aim of this study was to understand the association between activated microglia-induced neuroinflammation and post-meningitis cognitive impairment.MethodMeningitis was induced in male Wistar rats by injectingStreptococcus pneumoniaeinto the brain through the cisterna magna, and rats were then treated with ceftriaxone. Twenty-four hours and 10 days after meningitis induction, rats were imaged with positron emission tomography (PET) using [11C]PBR28, a specific translocator protein (TSPO) radiotracer, to determine in vivo microglial activation. Following imaging, the expression of TSPO, cardiolipin, and cytochromec, inflammatory mediators, oxidative stress markers, and glial activation markers were evaluated in the prefrontal cortex and hippocampus. Ten days after meningitis induction, animals were subjected to behavioral tests, such as the open-field, step-down inhibitory avoidance, and novel object recognition tests.ResultsBoth 24-h (acute) and 10-day (long-term) groups of rats demonstrated increased [11C]PBR28 uptake and microglial activation in the whole brain compared to levels in the control group. Although free from infection, 10-day group rats exhibited increased expression levels of cytokines and markers of oxidative stress, microglial activation (IBA-1), and astrocyte activation (GFAP) similar to those seen in the 24-h group. Acute meningitis induction also elevated TSPO, cytochromec, and caspase-3 levels with no change in caspase-9 levels. Furthermore, upregulated levels of TSPO, cytochromec, and caspase-3 and caspase-9 were observed in the rat hippocampus 10 days after meningitis induction with a simultaneous reduction in cardiolipin levels. Animals showed a cognitive decline in all tasks compared with the control group, and this impairment may be at least partially mediated by activating a glia-mediated immune response and upregulating TSPO.ConclusionsTSPO-PET could potentially be used as an imaging biomarker for microglial activation and long-term cognitive impairment post-meningitis. Additionally, this study opens a new avenue for the potential use of TSPO ligands after infection-induced neurological sequelae.
Immune cell extracellular vesicles and their mitochondrial content decline with ageing
Authors: Zhang Xin , Hubal Monica Jeanne , Kraus Virginia Byers 
Published: January 2020

AbstractBackgroundAlthough the mechanisms of action are not fully understood, extracellular vesicles (EVs) have emerged as key indicators and effectors of immune function. Characterizing circulating EVs associated with stem and immune cells across the lifespan of healthy individuals could aid an understanding of immunosenescence, a process of age-related decline of cells in both adaptive and innate immune systems.ResultsUsing high resolution multicolor flow cytometry, we identified three major subsets of EVs of varying sizes in healthy control (HC) plasma. Multiple plasma EVs associated with immune cells declined with ageing in HCs. In addition, we observed age-associated declines of respiring mitochondria cargo in EVs of several types of immune cells, suggesting that these parent cells may experience a decline in mitophagy or a mitochondrial dysfunction-induced immunosenescence. By contrast, the number of CD34+hematopoietic stem cell-associated EVs were high and carried respiring mitochondria, which did not decline with age.ConclusionAs demonstrated here, multicolor flow cytometry simultaneously measures plasma EV size, surface markers and cargo that reflect biological processes of specific cell types. The distinct surface markers and cytokine cargo of plasma EVs suggest that they may carry different bio-messages and originate by different biogenesis pathways.
Sexual dimorphism in cognitive disorders in a murine model of neuropathic pain
Authors: Won Soonmi , Park Keebum , Lim Hyoungsub , Lee Sung Joong 
Published: January 2020

AbstractBackgroundA sex-difference in susceptibility to chronic pain is well-known. Although recent studies have begun to reveal the sex-dependent mechanisms of nerve injury-induced pain sensitization, sex differences in the affective and cognitive brain dysfunctions associated with chronic pain have not been investigated. Therefore, we tested whether chronic pain leads to affective and cognitive disorders in a mouse neuropathic pain model and whether those disorders are sexually dimorphic.MethodsChronic neuropathic pain was induced in male and female mice by L5 spinal nerve transection (SNT) injury. Pain sensitivity was measured with the von Frey test. Affective behaviors such as depression and anxiety were assessed by the forced swim, tail suspension, and open field tests. Cognitive brain function was assessed with the Morris water maze and the novel object location and novel object recognition tests.ResultsMechanical allodynia was induced and maintained for up to 8 weeks after SNT in both male and female mice. Depressive- and anxiety-like behaviors were observed 8 weeks post-SNT injury regardless of sex. Chronic pain-induced cognitive deficits measured with the Morris water maze and novel object location test were seen only in male mice, not in female mice.ConclusionsChronic neuropathic pain is accompanied by anxiety- and depressive-like behaviors in a mouse model regardless of sex, and male mice are more vulnerable than female mice to chronic pain-associated cognitive deficits.
Orbital involvement by NUT midline carcinoma: new presentation and encouraging outcome managed by radiotherapy combined with tyrosine kinase inhibitor: a case report
Authors: Chai Peiwei , Zhou Chuandi , Jia Renbing , Wang Yefei 
Published: January 2020

Abstract
Background
NUT midline carcinoma (NMC) is a poorly differentiated squamous cancer with a median survival at less than 7 months. NMC is resistant to conventional chemotherapies and characterized by rearrangement of the NUT gene.

Case presentation
Here, we described a patient who initially presented with epiphora, and an orbit involved NMC. In addition, we for the first time demonstrated that local radiotherapy combined with tyrosine kinase inhibitor (TKI) could significantly inhibit tumor progression in orbital involvement by NMC.

Conclusions
Our study for the first time described an orbit involved NMC patient initially presented with epiphora. In addition, we provided an alternative to the management of orbit involved NMC.
Large scale genome skimming from herbarium material for accurate plant identification and phylogenomics
Authors: Nevill Paul G. , Zhong Xiao , Tonti-Filippini Julian , Byrne Margaret , Hislop Michael , Thiele Kevin , van Leeuwen Stephen , Boykin Laura M. , Small Ian 
Published: January 2020

AbstractBackgroundHerbaria are valuable sources of extensive curated plant material that are now accessible to genetic studies because of advances in high-throughput, next-generation sequencing methods. As an applied assessment of large-scale recovery of plastid and ribosomal genome sequences from herbarium material for plant identification and phylogenomics, we sequenced 672 samples covering 21 families, 142 genera and 530 named and proposed named species. We explored the impact of parameters such as sample age, DNA concentration and quality, read depth and fragment length on plastid assembly error. We also tested the efficacy of DNA sequence information for identifying plant samples using 45 specimens recently collected in the Pilbara.ResultsGenome skimming was effective at producing genomic information at large scale. Substantial sequence information on the chloroplast genome was obtained from 96.1% of samples, and complete or near-complete sequences of the nuclear ribosomal RNA gene repeat were obtained from 93.3% of samples. We were able to extract sequences for the core DNA barcode regionsrbcLandmatKfrom 96 to 93.3% of samples, respectively. Read quality and DNA fragment length had significant effects on sequencing outcomes and error correction of reads proved essential. Assembly problems were specific to certain taxa with low GC and high repeat content (Goodenia,Scaevola,Cyperus,Bulbostylis,Fimbristylis) suggesting biological rather than technical explanations. The structure of related genomes was needed to guide the assembly of repeats that exceeded the read length. DNA-based matching proved highly effective and showed that the efficacy for species identification declined in the order cpDNA >> rDNA > matK >> rbcL.ConclusionsWe showed that a large-scale approach to genome sequencing using herbarium specimens produces high-quality complete cpDNA and rDNA sequences as a source of data for DNA barcoding and phylogenomics.