bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of NR0B1&nbsp;Gene Mutation and Analysis of Bone Damages and Drug Treatment Effect in a Big Family With X-linked Adrenal Hypoplasia Congenita: a Case Report
Authors: TAO XIAOHUI , LIU LI , LIN XIAOYUN , XU TIAN , YUE HUA , ZHANG ZHENLIN 
Published: April 2021

Abstract
Background: X-linked congenital adrenocortical hypoplasia (XL-AHC) is a rare disorder, which is characterized by primary adrenal insufficiency and hypogonadotropic hypogonadism. However, the skeletal complications caused by the disease were rarely reported, not to mention the treatment.Case presentation: The patient from a big family with XL-AHC was identified carrying a homozygous insertion mutation（p.Thr193GlyfsX13）in DAX-1 gene. The diagnosis of secondary osteoporosis was made after imaging, laboratory and bone mass density examinations. However, he showed a suboptimal response to bisphosphonates during 2 years of follow-up, even suffered from atypical femoral fracture (AFF). Now it had been replaced by menatetrenone, bone healing was satisfactory. Conclusions: We harbored the idea that clinicians should not only focus on typical clinical manifestations of XL-AHC, but also pay attention to the skeletal complications in clinical practice. Conventional anti-osteoporosis drugs may cause side effects such as AFF and osteonecrosis of the jaw (ONJ), which was rare in general osteoporosis patients. In other words, anabolic agent may be a better choice.
Resilience-based Seismic Design Optimization of typical Highway RC Bridges by Response Surface Method and NSGA-II Algorithm
Authors: Hu Sicong , Chen Baokui , Song Guquan , Wang Lianhua 
Published: April 2021

Abstract
To maximize the seismic performance and minimize the material cost of the typical highway reinforced concrete (RC) bridges, a resilience-based multi-objective optimal seismic design method is proposed in this study. The size of elastomeric bearings and the cross-section arrangement of RC piers are chosen as the design parameters. To improve the accuracy and efficiency, the nonlinear time history analysis (NTHA) based cloud analysis approach is associated with the response surface method (RSM) to obtain the seismic resilience during the seismic optimization process. Moreover, the optimization problem is solved through an improved version of non-dominated sorting genetic algorithm (NSGA-II) algorithm. Following, the proposed method is applied to a typical highway RC bridge, and the optimal design schemes are determined from the Pareto optimal solutions. The results show that the resilience response surface model can be used to accurately predict the seismic resilience of bridges. The proposed method can adjust the damage grades of various components by considering the contribution of various components, entailing the minimization of material cost and the maximization of seismic resilience.
Association of MIR17HG&nbsp;and MIR155HG&nbsp;gene variants with steroid-induced osteonecrosis of the femoral head in the population of northern&nbsp;China
Authors: Liu Tingting , Cao Yuju , Han Changxu , An Feimeng , Wang Tiantian , Sun Menghu , Ma Chao , Dong Qiumei , Wang Jianzhong 
Published: April 2021

Abstract
IntroductionSteroid-induced osteonecrosis of the femoral head (ONFH ) is a disease of bone metabolism, and genetic factors are generally considered to play an important role. The purpose of this study was to investigate the relationship between single nucleotide polymorphisms (SNPs) in MIR17HG and MIR155HG and the risk of steroid-induced ONFH in the population of northern China.MethodsA total of 199 steroid-induced ONFH patients and 506 healthy controls were recruited for the study. Four SNPs of MIR17HG and seven SNPs of MIR155HG were genotyped by Sequenom MassARRAY. ORs and 95% CIs were used to evaluate the relationship between these SNPs and steroid-induced ONFH.ResultsIn the codominant model, patients with the MIR17HG SNPs(rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.79, p = 0.039), in the recessive model, patients with the MIR17HG SNP(rs7318578) AA genotype had an increased risk of steroid-induced ONFH (OR = 1.78, p = 0.032). Stratified analysis showed that a MIR17HG SNP (rs7318578) and MIR155HG SNPs(rs77218221, rs11911469, rs34904192 and rs4143370) were closely related to different unornamented phenotypes of steroid-induced ONFH. Analysis of the clinical indicators revealed significant differences in high-density lipoprotein (HDL-C) levels between the ONFH group and the control group (p = 0.005). MIR17HG SNP(rs75267932) and MIR155HG SNPs(rs77699734, rs1893650 and rs34904192) were correlated with different lipid indexes.ConclusionOur results confirm that MIR17HG and MIR155HG gene mutations are associated with steroid-induced ONFH susceptibility in the population of northern China, providing new evidence for the early detection and prevention of ONFH.
Bi-directional Coupling of an Unstructured Triangular Meshes-based Integrated Hydrodynamic Model for Heterogeneous Feature-based Urban Flood Simulation
Authors: Peng Guoqiang , Zhang Zhuo , Zhang Tian , Song Zhiyao , Masrur Arif 
Published: April 2021

Abstract
Urban pluvial flash floods have become a matter of widespread concern, as they severely impact people’s lives in urban areas. Hydrological and hydraulic models have been widely used for urban flood management and urban planning. Traditionally, to reduce the complexity of urban flood modelling and simulations, simplification or generalization methods have been used; for example, some models focus on the simulation of overland water flow, and some models focus on the simulation of the water flow in sewer systems. However, the water flow of urban floods includes both overland flow and sewer system flow. The overland flow processes are impacted by many different geographical features in what is an extremely spatially heterogeneous environment. Therefore, this article is based on two widely used models (SWMM and ANUGA) that are coupled to develop a bi-directional method of simulating water flow processes in urban areas. The open source overland flow model uses the unstructured triangular as the spatial discretization scheme. The unstructured triangular-based hydraulic model can be better used to capture the spatial heterogeneity of the urban surfaces. So, the unstructured triangular-based model is an essential condition for heterogeneous feature-based urban flood simulation. The experiments indicate that the proposed coupled model in this article can accurately depict surface waterlogged areas and that the heterogeneous feature-based urban flood model can be used to determine different types of urban flow processes.
On the Relationship between Inhibition and Receptor Occupancy by Nondepolarizing Neuromuscular Blocking Drugs
Authors: Hoshino Hikaru , Furutani Eiko 
Published: April 2021

Abstract
Background: Nondepolarizing neuromuscular blocking drugs (NDNBs) are clinically used to produce muscle relaxation during general anesthesia. To better understand clinical properties of NDNBs, comparative in vitro pharmacologic studies have been performed. In these studies, a receptor binding model, which relies on the assumption that the inhibition, i.e., the e ect of an NDNB, is proportional to the receptor occupancy by the drug, has been effectively used to describe obtained experimental data. However, it has not been studied in literature under which conditions the above assumption can be justified nor the assumption still holds in vivo. The purpose of this study is to explore the in vivo relationship between the inhibition and the receptor occupancy by an NDNB and to draw implications on how in vitro experimental results can be used to discuss the in vivo properties of NDNBs. Methods: An ordinary di erential equation model is employed to simulate physiologic processes of the activation of receptors by acetylcholine (ACh) as well as inhibition by an NDNB. With this model, the degree of inhibition is quantified by the fractional amount of receptors that are not activated by ACh due to the presence of an NDNB. The results are visualized by plotting the fractional amounts of the activated receptors as a function of the receptor occupancy. Results: Numerical investigations reflecting in vivo conditions show that the degree of inhibition is not proportional to the receptor occupancy, i.e., there is a nonlinear relationship between the inhibition and the receptor occupancy. However, under a setting of high concentration of ACh reflecting a typical situation of in vitro experiments, the relationship between the inhibition and the receptor occupancy becomes linear, suggesting the validity of the receptor binding model. Also, it is found that the extent of nonlinearity depends on the selectivity of NDNBs for the two binding sites of the receptors. Conclusions: While the receptor binding model may be effective for estimating affinity of an NDNB through in vitro experiments, these models do not directly describe in vivo properties of NDNBs, because the nonlinearity between the inhibition and the receptor occupancy causes the modulation of the resultant concentration-effect relationships of NDNBs.
Urban mosquitoes and filamentous green algae: their biomonitoring role in heavy metal pollution in open wastewater channels in Nairobi, Kenya
Authors: Kinuthia Geoffrey Kariuki , Ngure Veronica , Kamau Luna 
Published: April 2021

Abstract
Background

Levels of Mercury (Hg), Lead (Pb), Chromium (Cr), Cadmium (Cd), Thallium (Tl), and Nickel (Ni) in samples of wastewater, filamentous green algae (spirogyra) and urban mosquitoes obtained from open wastewater channels in Nairobi industrial area, Kenya, was established. Industrial wastewater may contain hazardous heavy metals upon exposure. Aquatic organisms in wastewater may accumulate the toxic elements with time. Therefore, human population living in informal settlements in Nairobi industrial area risk exposure to such toxic elements. Biomonitoring using aquatic organisms can be key in metal exposure assessment.
Results

Pb, Cr, & Ni levels ranged from 3.08 to 15.31 µg/L while Tl, Hg, & Cd levels ranged from 0.05 to 0.12 µg/L in wastewater. Pb, Cr, Ni, & Cd levels were above WHO, Kenya & US EPA limits for wastewater but Hg was not. Metals in tap water (control) which ranged from 0.01 to 0.2 µg/L was below WHO, US EPA, & Kenya standard limits. Pb, Cr, Tl, & Ni levels in assorted field mosquitoes were 1.3 to 2.4 times higher than in assorted laboratory-reared mosquitoes. Hg & Cd concentrations in laboratory-reared mosquitoes (0.26 mg/L & 1.8 mg/L respectively) was higher than in field mosquitoes (0.048 mg/L & 0.12 mg/L respectively). Pb, Cr, Ni, & Cd levels in green filamentous algae were 110.62, 29.75, 14.45, & 0.44 mg/L respectively and above WHO limits for vegetable plants. Hg level in algae samples (0.057 mg/L) was below WHO standard limits but above Kenya & US EPA limits in vegetables. Correlations for Pb & Hg (r = 0.957; P < 0.05); Cd & Cr (r = 0.985; P < 0.05) in algae samples were noted. The metal concentrations in the samples were in the order, wastewater < mosquitoes < filamentous green algae.
Conclusion

Samples of wastewater, mosquitoes and filamentous green algae from open wastewater channels and immediate vicinity, in Nairobi industrial area (Kenya) contained Hg, Pb, Cr, Cd, Tl, and Ni. Urban mosquitoes and filamentous green algae can play a role of metal biomonitoring in wastewater. The possibility of urban mosquitoes transferring the heavy metals to their hosts when sucking blood should be investigated.
Challenges in treatment of a patient suffering from neuroendocrine tumor G1 of the hilar bile duct: a case report
Authors: Zhang Biao , Sun Zhen , Chen Xu , Qi Bing , Zhang Qingkai , Zhang Guixin , Li Shuang , Shang Dong 
Published: April 2021

Abstract
Background Neuroendocrine tumors (NETs) arise from neuroendocrine cells and are extremely rare located in the biliary tract. Currently, there are no guidelines for the diagnosis and treatment of biliary NETs. We present a case with NETs G1 of the hilar bile duct and the challenges for her treatment.Case presentation A 24-year-old woman was presented to our department with painless jaundice and pruritus, and the preoperative diagnosis was the perihilar bile duct cholangiocarcinoma. She underwent Roux-en-Y hepaticojejunostomy with excision of the extrahepatic biliary tree and radical lymphadenectomy. Unexpectedly, postoperative pathology showed a perihilar bile duct NETs G1 and microscopic invasion of the resected right hepatic duct. Then the patient received 3 cycles of adjuvant chemotherapy (Gemcitabine and tegafur-gimeracil-oteracil potassium capsule). At present, this patient has been following up for 20 months without recurrence or disease progression.Conclusions NETs of the biliary tract are difficult to diagnose preoperatively. The treatment for NETs G1 with R1 resection is still controversial yet may offer potential positive adjuvant chemotherapy. The diagnosis of NETs should be kept in mind by the surgeon for proper time management and more information about biliary NETs should be registered.
Resolution of Inflammation is Disturbed in Macrophages of Diabetic Patients with Acute Ischemic Stroke
Authors: Tang Xin , Miao Zhijuan , Liu Lan , Zhang Jiawei , Cai Xiaolong , Zhao Bing-Qiao , Schultzberg Marianne , Zhao Yuwu , Wang Xiuzhe 
Published: April 2021

Abstract
Background: Inflammation plays an important role in diabetes mellitus (DM) and its related complications, including atherosclerosis and acute ischemic stroke (AIS). The mechanisms of excessive inflammation in DM are not fully understood. Specialized pro-resolving mediators (SPMs) are key regulators that promote resolution of inflammation. Unbalance of pro-resolving and pro-inflammatory signals may be the key pathogenesis in DM and DM-related diseases. We examined the resolution function in macrophages of DM patients with AIS.Methods: Macrophages were derived from peripheral blood mononuclear cells of AIS and none-AIS patients with or without DM. The cultured macrophages were treated with oxidized low-density lipoprotein. Resolution and inflammatory pathway markers were analyzed in the culture medium and cells. Results: In AIS patients, the ratios of SPMs to leukotriene B4 (LTB4) released by macrophages were decreased in those with DM compared to those without DM. Oxidized low-density lipoprotein treatment further reduced the ratios of SPMs/LTB4 in DM patients with AIS, but such a reduction was not observed in none-DM AIS patients. Analysis of M2/M1 polarization and MAPK/NFkB pathway markers also demonstrated un-resolved inflammation in macrophages of AIS patients with DM. Treatment with one of the SPMs, resolvin D2, rescued the resolution function and ameliorated inflammation in macrophages from these patients.Conclusions: Our data demonstrated that resolution of inflammation is disturbed by DM in macrophages of AIS patients, implicating a novel mechanism of un-resolved inflammation in DM-related vascular disorder. Exogenous SPMs treatment can rescue resolution and downregulate inflammatory signals, and may thus be beneficial in DM-related AIS.
Somatic Mutations in Collagens are Associated with a Distinct Tumor Environment and Overall Survival in Gastric Cancer
Authors: BRODSKY ALEXANDER , Khurana Jay , Guo Kevin S , Wu Elizabeth Y. , Yang Dongfang , Wong Ian Y. , Uzun Ece D. Gamsiz , Resnick Murray B. 
Published: April 2021

Abstract
Background
Gastric cancer is a heterogeneous disease with poorly understood genetic and microenvironmental factors. Mutations in collagen genes are associated with genetic diseases that compromise tissue integrity, but their role in tumor progression has not been extensively reported. In contrast, aberrant collagen expression has been long associated with malignant tumor growth, invasion, chemoresistance, and patient outcomes. We hypothesized that somatic mutations in collagens could functionally alter the tumor microenvironment, including the extracellular matrix.
Methods
We used publicly available datasets including the Tumor Cancer Genome Atlas (TCGA) to interrogate somatic mutations in collagens in stomach adenocarcinomas. To demonstrate that collagens were significantly mutated above background mutation rates, we used a moderated Kolmogorov-Smirnov test along with combination analysis with a bootstrap approach to define the background. Association between mutations and clinicopathological features was evaluated by Fisher or chi-squared tests. Association with overall survival was assessed by Kaplan-Meier and the Cox-Proportional Hazards Model. Gene Set Enrichment Analysis was used to interrogate pathways. Immunohistochemistry and in situ hybridization tested expression of COL7A1 in stomach tumors.
Results
In stomach adenocarcinomas, we identified individual collagen genes and sets of collagen genes harboring somatic mutations at a high frequency compared to background in both microsatellite stable, and microsatellite instable tumors in The Cancer Genome Atlas (TCGA). Many of the missense mutations resemble the same types of loss of function mutations in collagenopathies that disrupt tissue formation and destabilize cells providing guidance to interpret the somatic mutations. We identified combinations of somatic mutations in collagens associated with overall survival, with a distinctive tumor microenvironment marked by lower matrisome expression and immune cell signatures. Truncation mutations were strongly associated with improved outcomes suggesting that loss of expression of tumor cell secreted collagens have large impacts on tumor progression and treatment response.
Conclusions
These observations highlight that many minor collagens, expressed in non-physiologically relevant conditions in tumors, secreted from tumor cells, harbor impactful somatic mutations in tumors, suggesting new approaches for classification and therapy development in stomach cancer. In sum, these findings demonstrate how classification of tumors by collagen mutations identified strong links between specific genotypes and the tumor environment.
Breast-Conserving Therapy is Associated with Better Survival than Mastectomy in Early-Stage Breast Cancer: A Propensity Score Analysis
Authors: Ji Jiali , Yuan Shushu , He Jiawei , Liu Hong , Yang Lei , He xuexin 
Published: April 2021

Abstract
Background: Recent retrospective studies have reported that breast-conserving therapy (BCT) led to improved overall survival (OS) than mastectomy in some populations. We aimed to compare the efficacy of BCT and mastectomy using the SEER database. Methods: Between 2010 and 2015, 99,790 eligible patients were identified. We included early-stage breast cancer patients with 5cm or smaller tumors and three or fewer positive lymph nodes in our study. We compared the OS results among patients with BCT and mastectomy. Kaplan-Meier plots, Cox proportional hazard regressions were used to evaluate the outcomes. Propensity-score matching was used to assemble a cohort of patients with similar baseline characteristics. Results: In our study, 77,452 (77.6%) patients underwent BCT and 22,338 (22.4%) underwent mastectomy. The 5-year OS rate was 94.7% in the BCT group and 87.6% in the mastectomy group (P <0.001). After matching, multivariate analysis in the matched cohort showed that women underwent mastectomy was associated with worse OS results compared with those with BCT (Hazard ratio (HR) = 1.628; 95% confidence intervals (CIs) = 1.445- 1.834, P<0.001). Patients with different subtypes and age group (>50 years old; ≤50 years old) received BCT all showed significantly better OS than those received mastectomy. The effect of surgery choice on survival was the same in matched and all cohorts. Conclusions: Our study showed that BCT was associated with improved survival compared with mastectomy in early-stage breast cancer patients. It seems advisable to encourage patients to receive BCT rather than mastectomy in early-stage patients when feasible and appropriate.
Giant Pulmonary Bulla Underlying Bronchopulmonary Dysplasia in a Very Low-birth-weight Infant: a Case Report
Authors: Shinohara Tamao , Hasebe Yohei , Watanabe Daisuke , Numano Fuminori , Saito Tomohiro , Koizumi Keiichi , Nemoto Atsushi , Tandou Tomoko , Oyama Toshio , Oyachi Noboru , Hoshiai Minako , Naito Atsushi 
Published: April 2021

Abstract
Background: Acquired cystic lung disease is a serious respiratory complication of bronchopulmonary dysplasia in premature infants. Most cases of acquired cystic lung disease underlying bronchopulmonary dysplasia involve pulmonary interstitial emphysema. Although this is a reversible condition, there are a few instances where surgery might be necessary. An accurate diagnosis is important to decide the therapeutic strategy for acquired cystic lung disease. Here, we report a rare case of a giant pulmonary bulla in an infant treated with bullectomy. Case presentation: A male infant born at 23 weeks of gestation with a birth weight of 524 g was initially diagnosed with respiratory distress syndrome. During mechanical ventilatory support, he presented with recurrent pneumothorax and a gradually expanding pulmonary cyst in the right lung. Chest CT at 5 months of age revealed a large cyst located in the subpleural area adjacent to the multiple cystic air spaces. These findings are consistent with the diagnosis of giant pulmonary bulla with pulmonary interstitial emphysema underlying bronchopulmonary dysplasia . At 9 months of age, the giant pulmonary bulla expanded further due to acute bronchitis for which he developed respiratory failure and obstructive shock. This warranted a bullectomy for the giant pulmonary bulla. After the operation, the unresected pulmonary interstitial emphysema lesion did not expand further. He is currently three years old and has no respiratory problems. Conclusions: This case demonstrated that chest CT is useful for providing valuable anatomical information necessary in deciding the treatment strategy for acquired cystic lung disease in infants.
The Role of Osteocalcin in Placenta Function in Gestational Diabetes Mellitus
Authors: Song Liang , Huang Yiming , Long Junqing , Li Yuanfan , Pan Zongqin , Fang Fang , Long Yu , Huang Cheng , Qi Nana , Guo Yajie , Xia Hongwei , jiang yonghua 
Published: April 2021

Abstract
Background: Evidence for osteocalcin role in glucose and energy metabolism is increasing. However, little is known about osteocalcin function in gestational diabetes mellitus. The aim of this study is to examine the associations between osteocalcin and gestational diabetes mellitus. Method: 36 patients with gestational diabetes mellitus and 40 normal glucose tolerance controls were recruited in the Maternal and Child Health Hospital Guangxi Zhuang Autonomous Region from May to August 2018. Total osteocalcin and biochemical indexes of maternal serum and umbilical vein serum were analyzed. Transcriptome of placenta were sequenced. Human trophoblast JAR cells were used for evaluated the affection of osteocalcin on trophoblast In vitro. There were no significant differences with maternal serum total osteocalcin levels between gestational diabetes mellitus and normal glucose tolerance groups. The gestational diabetes mellitus group has lower umbilical vein serum total osteocalcin (51.46 ng/mL ± 24.29 Vs 67.00 ng/mL ± 25.33, P = 0.008 ), lower adiponectin (1099.72 μg/L ± 102.65 Vs 1235.85 μg/L ± 94.63, P < 0.001), higher leptin (7.41 μg/L ± 0.28 Vs 6.02 μg/L ± 0.31, P ＜ 0.001). A significant relationship existed between umbilical vein serum total osteocalcin levels and leptin (r = -0.456, P = 0.007). Osteocalcin promote JAR trophoblast cells proliferation and HCG synthesis. 36 correlated gene modules of placental transcriptome were identified through weighted gene co-expression network analysis, 2 of them were associated with osteocalcin. Conclusion: lower osteocalcin in umbilical vein serum is associated with gestational diabetes mellitus, osteocalcin may regulate placenta function via adiponectin.