bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimates of Methane Release From Gas Seeps at the Southern Hikurangi Margin, New Zealand
Authors: Turco Francesco , Ladroit Yoann , Watson Sally J. , Seabrook Sarah , Law Cliff S. , Crutchley Gareth J. , Mountjoy Joshu , Pecher Ingo A. , Hillman Jess I. T. , Woelz Susi , Gorman Andrew R. 
Published: March 2022

The highest concentration of cold seep sites worldwide has been observed along convergent margins, where fluid migration through sedimentary sequences is enhanced by tectonic deformation and dewatering of marine sediments. In these regions, gas seeps support thriving chemosynthetic ecosystems increasing productivity and biodiversity along the margin. In this paper, we combine seismic reflection, multibeam and split-beam hydroacoustic data to identify, map and characterize five known sites of active gas seepage. The study area, on the southern Hikurangi Margin off the North Island of Aotearoa/New Zealand, is a well-established gas hydrate province and has widespread evidence for methane seepage. The combination of seismic and hydroacoustic data enable us to investigate the geological structures underlying the seep sites, the origin of the gas in the subsurface and the associated distribution of gas flares emanating from the seabed. Using multi-frequency split-beam echosounder (EK60) data we constrain the volume of gas released at the targeted seep sites that lie between 1,110 and 2,060 m deep. We estimate the total deep-water seeps in the study area emission between 8.66 and 27.21 × 106 kg of methane gas per year. Moreover, we extrpolate methane fluxes for the whole Hikurangi Margin based on an existing gas seep database, that range between 2.77 × 108 and 9.32 × 108 kg of methane released each year. These estimates can result in a potential decrease of regional pH of 0.015–0.166 relative to the background value of 7.962. This study provides the most quantitative assessment to date of total methane release on the Hikurangi Margin. The results have implications for understanding what drives variation in seafloor biological communities and ocean biogeochemistry in subduction margin cold seep sites.
Numerical Simulations of Combined Brine Flooding With Electrical Heating–Assisted Depressurization for Exploitation of Natural Gas Hydrate in the Shenhu Area of the South China Sea
Authors: Zhang Qi , Wang Yanfei 
Published: March 2022

The Shenhu area of the South China Sea (SCS) is one of the most promising fields for natural gas hydrate (NGH) exploitation. However, previous studies conclude that using only depressurization is inefficient for this challenging hydrate deposits surrounded by permeable water zones, which requires assistance by thermal stimulation to promote hydrate decomposition and methane recovery. However, traditional thermal stimulation methods with hot water or steam injection induce massive heat loss along the wellbore. In addition, in situ electrical heating only results in a limited high temperature region due to low thermal conductivity of hydrate deposits. Therefore, we numerically investigate the performance of combined brine flooding with electrical heating–assisted depressurization in horizontal wells for exploitation of natural gas hydrate in the SCS, which simultaneously possesses the merits of low heat loss and enhanced heat transfer by convection. Our simulation results show that thermal stimulation by combined brine flooding with electrical heating can significantly enhance hydrate dissociation and methane recovery. After 20 years of production, the cumulative methane production of combined brine flooding with electrical heating–assisted depressurization is 1.41 times of that conducted by the only depressurization method. Moreover, the energy efficiency can be improved by reducing electrical heating time, and terminating electrical heating with 70% hydrate dissociation achieves the highest net energy gain. In addition, methane recovery and net energy gain increases with electrical heating power and brine injection pressure but with a decreasing rate. Therefore, the selection of electrical heating power and brine injection pressure should be performed carefully and comprehensively considering both the efficiency of gas production and risks of geological hazard. It is hoped that our research results will provide reference and guidance for the development of a similar NGH reservoir in order to promote the industrial development process of NGH.
KCNJ5 Somatic Mutation Is Associated With Higher Aortic Wall Thickness and Less Calcification in Patients With Aldosterone-Producing Adenoma
Authors: Lee Bo-Ching , Kang Victor Jing-Wei , Pan Chien-Ting , Huang Jia-Zheng , Lin Yu-Li , Chang Yi-Yao , Tsai Cheng-Hsuan , Chou Chia-Hung , Chen Zheng-Wei , Liao Che-Wei , Chiu Yu-Wei , Wu Vin-Cent , Hung Chi-Sheng , Chang Chin-Chen , Lin Yen-Hung 
Published: March 2022

ObjectivePrimary aldosteronism (PA) is the most common type of secondary hypertension, and it is associated with a higher rate of cardiovascular complications. KCNJ5 somatic mutations have recently been identified in aldosterone-producing adenoma (APA), however their influence on vascular remodeling and injury is still unclear. The aim of this study was to investigate the association between KCNJ5 somatic mutation status and vascular status.MethodsWe enrolled 179 APA patients who had undergone adrenalectomy from a prospectively maintained database, of whom 99 had KCNJ5 somatic mutations. Preoperative clinical, biochemical and imaging data of abdominal CT, including abdominal aortic calcification (AAC) score, aortic diameter and wall thickness at levels of superior (SMA) and inferior (IMA) mesenteric arteries were analyzed.ResultsAfter propensity score matching for age, sex, body mass index, triglycerides and low-density lipoprotein, there were 48 patients in each KCNJ5 (+) and KCNJ5 (-) group. Mutation carriers had a lower AAC score (217.3 ± 562.2 vs. 605.6 ± 1359.1, P=0.018), higher aortic wall thickness (SMA level: 2.2 ± 0.6 mm vs. 1.8 ± 0.6 mm, P=0.006; IMA level: 2.4 ± 0.6 mm vs. 1.8 ± 0.7 mm, P&lt;0.001) than non-carriers. In multivariate analysis, KCNJ5 mutations were independently associated with AAC score (P=0.014) and aortic wall thickness (SMA level: P&lt;0.001; IMA level: P=0.004). After adrenalectomy, mutation carriers had less aortic wall thickness progression than non-carriers (Δthickness SMA: -0.1 ± 0.8 mm vs. 0.9 ± 0.6 mm, P=0.024; IMA: -0.1 ± 0.6 mm vs. 0.8 ± 0.7 mm, P=0.04).ConclusionKCNJ5 mutation carriers had less calcification burden of the aorta, thickened aortic wall, and less wall thickness progression than non-carriers.
Copy Number Variations in Genetic Diagnosis of Congenital Adrenal Hyperplasia Children
Authors: Tolba Aisha , Mandour Iman , Musa Noha , Elmougy Fatma , Hafez Mona , Abdelatty Sahar , Ibrahim Amany , Soliman Hend , Labib Bahaaeldin , Elshiwy Yasmine , Ramzy Tarek , Elsharkawy Marwa 
Published: March 2022

Background: Congenital adrenal hyperplasia (CAH) is a monogenic disorder caused by genetic diversity in the CYP21A2 gene, with 21-hydroxylase deficiency (21-OHD) as the most common type. Early sex assignment and early diagnosis of different genetic variations with a proper technique are important to reduce mortality and morbidity. Proper early sex identification reduces emotional, social, and psychological stress.Aim: Detection of a spectrum of aberrations in the CYP21A2 gene, including copy number variations, gene conversion, chimeric genes, and point variations.Methods: The CYP21A2 gene was screened using MLPA assay in 112 unrelated Egyptian children with 21-OHD CAH (33 males and 79 females).Results: In the studied group, 79.5% were diagnosed within the first month of life. 46.8% of the genetic females were misdiagnosed as males. Among the copy number variation results, large deletions in 15.4% and three types of chimeric genes in 9% (CH-1, CH-7, and CAH-X CH-1) were detected. Regarding gene dosage, one copy of CYP21A2 was found in 5 cases (4.5%), three copies were detected in 7 cases (6.3%), and one case (0.9%) showed four copies. Eight common genetic variants were identified, I2G, large deletions, large gene conversion (LGC), I172N, F306 + T, -113 SNP, 8bp Del, and exon 6 cluster (V237E and M239K) with an allelic frequency of 32.62%, 15.45%, 7.30%, 3.00%, 2.58%, 2.15%, 0.86%, and 0.86%, respectively.Conclusion: High prevalence of copy number variations highlights the added value of using MLPA in routine laboratory diagnosis of CAH patients.
The Spring Festival Is Associated With Increased Mortality Risk in China: A Study Based on 285 Chinese Locations
Authors: He Guanhao , Cai Min , Meng Ruilin , Hu Jianxiong , Peng Ke , Hou Zhulin , Zhou Chunliang , Xu Xiaojun , Xiao Yize , Yu Min , Huang Biao , Lin Lifeng , Liu Tao , Xiao Jianpeng , Gong Weiwei , Hu Ruying , Li Junhua , Jin Donghui , Qin Mingfang , Zhao Qinglong , Xu Yiqing , Zeng Weilin , Li Xing , Huang Cunrui , Si Lei , Yang Xingfen , Ma Wenjun 
Published: March 2022

BackgroundThe Spring Festival is one of the most important traditional festivals in China. This study aimed to estimate the mortality risk attributable to the Spring Festival.MethodsBetween 2013 and 2017, daily meteorological, air pollution, and mortality data were collected from 285 locations in China. The Spring Festival was divided into three periods: pre-Spring Festival (16 days before Lunar New Year's Eve), mid-Spring Festival (16 days from Lunar New Year's Eve to Lantern Festival), and post-Spring Festival (16 days after Lantern Festival). The mortality risk attributed to the Spring Festival in each location was first evaluated using a distributed lag nonlinear model (DLNM), and then it was pooled using a meta-analysis model.ResultsWe observed a dip/rise mortality pattern during the Spring Festival. Pre-Spring Festival was significantly associated with decreased mortality risk (ER: −1.58%, 95%CI: −3.09% to −0.05%), and mid-Spring Festival was unrelated to mortality risks, while post-Spring Festival was significantly associated with increased mortality risk (ER: 3.63%, 95%CI: 2.15–5.12%). Overall, a 48-day Spring Festival period was associated with a 2.11% (95%CI: 0.91–3.33%) increased mortality. We also found that the elderly aged over 64 years old, women, people with cardiovascular disease (CVD), and people living in urban areas were more vulnerable to the Spring Festival.ConclusionOur study found that the Spring Festival significantly increased the mortality risk in China. These findings suggest that it is necessary to develop clinical and public health policies to alleviate the mortality burden associated with the Spring Festival.
Changes of Dry Eye Parameters Especially Meibomian Gland Functions After Punctal Plugs Insertion in Aqueous-Deficient Dry Eye Patients
Authors: Liu Tingting , Liu Shulin , Gan Meiqi , He Yuqin , Fu Hongxue , Xu Mei 
Published: March 2022

BackgroundThe study aimed at investigating the changes of dry eye parameters, especially the meibomian gland function in dry eye patients with primary Sjögren's syndrome (SS) and non-Sjögren's syndrome (non-SS) before and after punctal plugs insertion.Material and MethodsThe SS and non-SS dry eye patients that received punctal plugs insertion were prospectively investigated. This study recruited fifty patients. The standardized patient evaluation of eye dryness (SPEED), ocular surface disease index (OSDI), tear meniscus height (TMH), non-invasive Keratographic breakup time (NIKBUT), Schirmer test without anesthesia (Schirmer I Test, SI T), corneal fluorescein staining (CFS), the meibomian gland dropout (meiboscore), meibum expressibility score (MES), meibum quality score (MQS), lid margin abnormalities and the lipid layer thickness (LLT) were analyzed at pre-obstruction, 2 weeks, 2 months and 6 months following the obstruction.ResultsOur study observed a statistically significant improvement in ocular symptom scores (SPEED and OSDI scores) after punctal plugs insertion at every visit in both SS and non-SS patients (all p &lt; 0.05). A similar pattern was observed in TMH, SI T, NIKBUT and CFS score in both groups (all p &lt; 0.05), except that NIKBUT and CFS score had no obvious change in SS group at 6 months (P &gt; 0.05). In terms of the meibomian gland evaluation, meiboscore did not change significantly, MES decreased at 2 and 6 months and MQS decreased only at 2 months in both groups. The lid margin abnormalities of the non-SS group were significantly improved at 2 and 6 months, while that of the SS group had changes only at 2 months. Interestingly, LLT in non-SS group continued to rise, reaching a higher level at 2 months (p &lt; 0.05), while LLT in SS group increased only at 2 months (p &lt; 0.05). Meanwhile, after the puntcal plugs insertion, non-SS group showed better outcomes concerning some parameters, such as lower ocular symptom scores, higher TMH and significantly greater LLT, compared with that in SS group (all p &lt; 0.05).ConclusionsOur study revealed that dry eye symptoms and signs, including meibomian gland function, improved for at least 6 months in non-SS dry eye patients as well as in SS dry eye patients after punctal plugs insertion.
J147 Reduces tPA-Induced Brain Hemorrhage in Acute Experimental Stroke in Rats
Authors: Jin Rong , Wang Min , Zhong Wei , Kissinger Charles R. , Villafranca J. Ernest , Li Guohong 
Published: March 2022

Background and purposeJ147, a novel neurotrophic compound, was originally developed to treat aging-associated neurological diseases. Based on the broad spectrum of cytoprotective effects exhibited by this compound, we investigated whether J147 has cerebroprotection for acute ischemic stroke and whether it can enhance the effectiveness of thrombolytic therapy with tissue plasminogen activator (tPA).MethodsRats were subjected to transient occlusion of the middle cerebral artery (tMCAO) by insertion of an intraluminal suture or embolic middle cerebral artery occlusion (eMCAO), and treated intravenously with J147 alone or in combination with tPA.ResultsWe found that J147 treatment significantly reduced infarct volume when administered at 2 h after stroke onset in the tMCAO model, but had no effect in eMCAO without tPA. However, combination treatment with J147 plus tPA at 4 h after stroke onset significantly reduced infarct volume and neurological deficits at 72 h after stroke compared with saline or tPA alone groups in the eMCAO model. Importantly, the combination treatment significantly reduced delayed tPA-associated brain hemorrhage and secondary microvascular thrombosis. These protective effects were associated with J147-mediated inhibition of matrix metalloproteinase-9 (MMP9), 15-lipoxygenase-1, and plasminogen activator inhibitor (PAI) expression in the ischemic hemispheres (predominantly in ischemic cerebral endothelium). Moreover, the combination treatment significantly reduced circulating platelet activation and platelet-leukocyte aggregation compared with saline or tPA alone groups at 24 h after stroke, which might also contribute to reduced microvascular thrombosis and neuroinflammation (as demonstrated by reduced neutrophil brain infiltration and microglial activation).ConclusionOur results demonstrate that J147 treatment alone exerts cerebral cytoprotective effects in a suture model of acute ischemic stroke, while in an embolic stroke model co-administration of J147 with tPA reduces delayed tPA-induced intracerebral hemorrhage and confers cerebroprotection. These findings suggest that J147-tPA combination therapy could be a promising approach to improving the treatment of ischemic stroke.
The Impact of Ischemic Stroke on Gray and White Matter Injury Correlated With Motor and Cognitive Impairments in Permanent MCAO Rats: A Multimodal MRI-Based Study
Authors: Yang Le , Li Manzhong , Zhan Yu , Feng Xuefeng , Lu Yun , Li Mingcong , Zhuang Yuming , Lei Jianfeng , Zhao Hui 
Published: March 2022

BackgroundIdentifying the alterations of the cerebral gray and white matter is an important prerequisite for developing potential pharmacological therapy for stroke. This study aimed to assess the changes of gray and white matter after permanent middle cerebral artery occlusion (pMCAO) in rats using magnetic resonance imaging (MRI), and to correlate them with the behavior performance.MethodsRats were subjected to pMCAO or sham surgery and reared for 30 days. Motor and cognitive function of the rats were examined by gait and Morris water maze (MWM) tests, respectively. Multimodal MRI was conducted to examine the functional and structural changes of the gray and white matter followed with luxol fast blue (LFB) staining.ResultsThe gait and MWM tests revealed significant motor and cognitive dysfunction in pMCAO rats, respectively. Magnetic resonance angiography presented abnormal intracranial arteries in pMCAO rats with reduced signal intensity of the anterior cerebral artery, anterior communicating cerebral artery, internal carotid artery, and increased basilar artery vessel signal compared with sham rats. Arterial spin labeling confirmed the decreased cerebral blood flow in the infarcted sensorimotor cortex and striatum. Structural T2-weighted imaging and T2 mapping showed brain atrophy and elevation of T2 value in the gray (sensorimotor cortex, striatum) and white (external capsule, internal capsule) matter of pMCAO rats. The results from diffusion tensor imaging (DTI) corresponded well with LFB staining showing reduced relative FA accompanied with increased relative AD and RD in the gray and white matter of pMCAO rats compared with sham rats. Fiber tracking derived from DTI further observed significantly reduced fiber density and length in the corresponding brain regions of pMCAO rats compared with sham rats. Specially, the DTI parameters (especially FA) in the relevant gray matter and white matter significantly correlated with the behavior performance in the gait and MWM tests.ConclusionCollectively, the gray and white matter damages could be non-invasively monitored in pMCAO rats by multimodal MRI. DTI-derived parameters, particularly the FA, might be a good imaging index to stage gray and white matter damages associated with post-stroke motor and cognitive impairments.
Endovascular Treatment of Large or Giant Basilar Artery Aneurysms Using the Pipeline Embolization Device: Complications and Outcomes
Authors: Ge Huijian , Chen Xiheng , Liu Kai , Zhao Yang , Zhang Longhui , Liu Peng , Jiang Yuhua , He Hongwei , Lv Ming , Li Youxiang 
Published: March 2022

BackgroundThis study aimed to investigate clinical and angiographic outcomes of Pipeline embolization device (PED) treatment of large or giant basilar artery (BA) aneurysms and examine associated factors.MethodsClinical and angiographic data of 29 patients (18 men, 11 women) with large or giant BA aneurysms were retrospectively examined. Mean age was 44.1 ± 21.2 years (range, 30–68). Mean aneurysm size was 22.2 ± 8.3 mm (range, 12.0–40.1).ResultsMean angiographic follow-up was 18.3 ± 3.4 months (range, 4.5–60). The rate of adequate aneurysmal occlusion (O'Kelly–Marotta grade C–D) was 87%. The overall complication rate was 44.8%; most complications (84.6%) occurred in the periprocedural period. Univariable comparison of patients who did and did not develop complications showed significant differences in aneurysm size (p &lt; 0.01), intra-aneurysmal thrombus (p = 0.03), and mean number of PEDs used (p = 0.02). Aneurysm size (odds ratio, 1.4; p = 0.04) was an independent risk factor for periprocedural complications in multivariable analysis. Mean clinical follow-up was 23.5 ± 3.2 months (range, 0.1–65). Nine patients (31%) had a poor clinical outcome (modified Rankin scale score ≥3) at last follow-up, including 7 patients who died. Univariable comparisons between patients with favorable and unfavorable clinical outcomes showed that aneurysm size (p = 0.009) and intra-aneurysmal thrombus (p = 0.04) significantly differed between the groups. Multivariable analysis showed that aneurysm size (odds ratio, 1.1; p = 0.04) was an independent risk factor for poor clinical outcome.ConclusionPED treatment of large or giant BA aneurysms is effective and can achieve a satisfactory long-term occlusion rate. However, the treatment complications are not negligible. Aneurysm size is the strongest predictor of perioperative complications and poor clinical outcome.
Prognostic Implications of Molecular Subtypes in Primary Small Cell Lung Cancer and Their Correlation With Cancer Immunity
Authors: Qi Jing , Zhang Jiaqi , Liu Ningbo , Zhao Lujun , Xu Bo 
Published: March 2022

IntroductionSmall cell lung cancer (SCLC) has recently been characterized as heterogeneous tumors due to consensus nomenclature for distinct molecular subtypes on the basis of differential expression of four transcription markers (ASCL1, NEUROD1, POU2F3, and YAP1). It is necessary to validate molecular subtype classification in primary SCLC tumors by immunohistochemical (IHC) staining and investigate its relevance to survival outcomes.MethodsUsing a large number of surgically resected primary SCLC tumors, we assessed the mRNA and protein levels of the four subtype markers (ASCL1, NEUROD1, POU2F3 and YAP1) in two independent cohorts, respectively. Next, molecular subtypes defined by the four subtype markers was conducted to identify the association with clinicopathologic characteristics, survival outcomes, the expression of classic neuroendocrine markers, and molecules related to tumor immune microenvironment.ResultsSamples were categorized into four subtypes based on the relative expression levels of the four subtype markers, yielding to ASCL1, NEUROD1, POU2F3 and YAP1 subtypes, respectively. The combined neuroendocrine differentiation features were more prevalent in either ASCL1 or NEUROD1 subtypes. Kaplan-Meier analyses found that patients with tumors of the YAP1 subtype and ASCL1 subtype obtained the best and worst prognosis on both mRNA and IHC levels, respectively. Based on multivariate Cox proportional-hazards regression model, molecular subtype classification determined by IHC was identified as an independent indicator for survival outcomes in primary SCLC tumors. Correlation analyses indicated that the four subtype markers in SCLC cancer cells were interacted with its tumor immune microenvironment. Specifically, tumors positive for YAP1 was associated with fewer CTLA4+ T cell infiltration, while more immune-inhibitory receptors (FoxP3,PD1, and CTLA4) and fewer immune-promoting receptor (CD8) were found in tumors positive for ASCL1.ConclusionsWe validated the new molecular subtype classification and clinical relevance on both mRNA and protein levels from primary SCLC tumors. The molecular subtypes determined by IHC could be a pre-selected effective biomarker significantly influenced on prognosis in patients with SCLC, which warrants further studies to provide better preventative and therapeutic options for distinct molecular subtypes.