bluuebunny/crossref_metadata_2025_split huggingface dataset:
SCIMP: A Novel Targeted Gene for Postmenopausal Osteoporosis Progression
Authors: Sun Xiaolei , Tian Aixian , Li Peng , Zhao Jin , Hou Xin , Ma Xinlong , Yuan Xubo 
Published: April 2023

ObjectiveThe literature suggests that not all postmenopausal women suffer from osteoporosis, and the occurrence of postmenopausal osteoporosis is closely related to the genetic susceptibility of genes in the population and the cellular pathways of related genes. To systematically understand the functions of SCIMP gene for osteoporosis, both in vitro and in vivo experiments were analyzed in depth in this integrated study.MethodsThe significantly differentially expressed genes of postmenopausal osteoporosis (PMOP) patients from GEO database were selected. Meanwhile, the primary target gene was also confirmed in clinically recruited individuals using ELISA method; 50 postmenopausal osteoporosis patients with a T‐score of ‐2.5 were randomly enrolled; postmenopausal women with a T‐score > −2.5 were included in the non‐osteoporotic group (including osteopenia and normal bone mineral density). The associated processes and signaling pathways were deeply investigated with GO and KEGG enrichment analysis. The downstream signaling factors including Erk‐1/2, Akt, and IkB‐related signaling pathways for the potential gene were evaluated using MG‐63 cell line; the MTT, CCK‐8, and flow cytometry assays were performed to exam MG‐63 cell viability, proliferation, as well as apoptosis, respectively, under different treatments.ResultsBased on the differentially expressed gene analysis for GEO database, PMOP patients displayed 845 differentially expressed genes, including 709 down‐regulated and 136 up‐regulated ones. Ten genes including SCIMP were significantly differentially expressed (at least three‐fold difference). SCIMP was the most markedly decreased in PMOP patients’ specimens. Using clinical recruited individuals, the concentration of SCIMP was 96.6 ± 20.8 ng/μL in the PMOP group compared with 168.8 ± 23.5 ng/μL in the control group (p < 0.05). At the same time, the osteoclast differentiation signaling pathway was significantly up‐regulated while hedgehogs as well as other signaling pathways were down‐regulated based on the KEGG analysis. The phosphorylation level of Akt was markedly blocked in si‐SCIMP treatment. Up‐regulation of SCIMP increased cell proliferation, inhibited cell apoptosis, and enhanced cell viability in MG‐63 cells, which was markedly rescued by AKT phosphorylation inhibitor. Finally, in vivo experiments also confirmed that the upregulation of SCIMP enhanced the structural parameters of rat trabecular bone and the osteogenic activity of bone tissue.ConclusionSCIMP plays a critical role in the pathogenesis of postmenopausal osteoporosis in women. SCIMP influences osteoclasts function through an akt‐dependent molecular pathway, and subsequently influences the equilibrium process of bone metabolism. This provides a new insight into the pathogenesis of postmenopausal osteoporosis as well as the clinical treatment of osteoporosis.
Hip Pain after Distal Femoral Derotational Osteotomy for a Patient with Patellar Instability: A Case Report
Authors: Fu De‐Jie , Lei Kai , Liu Li‐Ming , Guo Lin 
Published: April 2023

BackgroundIncreased torsional deformity of femur is one of the most important factors in recurrent patellofemoral instability. And distal femoral derotational osteotomy is an effective treatment option in patients with increased femoral torsional deformity. However, groin pain is a rare complication after femoral derotational osteotomy.Case presentationThe patient was a 23‐year‐old female suffering from anterior knee pain and patellar instability in her left leg. Continuous CT scans of the hip, knee, and ankle were performed and the femoral anteversion was 44.99°. Considering the significant enlargement of the femoral internal torsion which may contribute most for dislocation of patella, we did a derotational osteotomy of distal femur. The anterior knee pain and patellar instability were resolved after surgery. The femoral internal torsion angle was corrected to 21.47°. But she developed left hip pain in the groin area which she had never encountered before 1 year after the surgery. We believed that the hip pain was closely related to the surgery. And the imaging and follow‐up partly confirmed this.ConclusionsThe situation of the hip joint should be carefully evaluated before doing derotational osteotomy in recurrent patellofemoral instability and patient should be informed that derotational osteotomy may cause hip pain. Clinical studies are needed to further clarify the impact of derotational osteotomy on the hip.
Genetic and phenotypic heterogeneity of multiple lentigines and precise diagnosis in four Chinese families with multiple lentigines
Authors: Guo Kexin , Liu Jia‐Wei , Zhang Rui , Wang Rongrong , Ma Dong‐Lai , Zhang Xue 
Published: April 2023

AbstractLentigines are well‐defined, small, brown macules resulting from the accumulation of melanin content in the basement membrane zone with an increase in the number of melanocytes. Hereditary multiple lentigines (ML) can be associated with multiple genes and are not commonly encountered in clinical practice. Patients can solely have skin involvement or present with multisystemic deformative phenotypes. This study aimed to describe four unrelated Chinese families presenting with ML as their first visit symptom. We performed whole‐exome sequencing (WES) and Sanger sequencing on all patients and immediate family members for precise molecular diagnosis. Two novel variants c.1548 T > A (p.Ser516Arg) and c.1811C > A (p.Thr604Lys) in SASH1, and two recurrent variants c.1403C > T (p.Thr468Met) and c.1493G > T (p.Arg498Leu) in PTPN11, were identified in these four families. We also summarized the genes associated with ML and differential diagnosis of pigment abnormality. We suggested that the molecular diagnosis of ML should be emphasized because it can help in the clinical differential diagnosis and further genetic counseling and prognosis.
Could a trade agreement strengthen the enforcement of domestic environmental laws? Envisioning the impacts of the US–Peru environmental submissions mechanism
Authors: Peña Pablo 
Published: April 2023

AbstractCould a trade agreement strengthen the enforcement of domestic environmental laws? This article explores this question in the context of the US–Peru Trade Promotion Agreement (TPA). The article examines, in particular, the potential role of the Secretariat for Submissions on Environmental Enforcement Matters (SEEM) of the TPA. The SEEM is an advisory mechanism to the parties to the TPA which allows citizens to bring direct submissions. This article considers the extent to which the SEEM can facilitate the enforcement of domestic Peruvian environmental law thus helping secure Peruvians' constitutional right to a healthy environment. Existing domestic mechanisms of administrative, civil or criminal law are already available to Peruvian citizens. These can apply to varied situations and provide a range of remedies, but often, they are also costly and lengthy. The SEEM began operating in 2018, and its first six submissions already hint at its potential to become a useful complement to domestic legal avenues. The SEEM could become increasingly used in the future due to Peru's prevalent institutional problems and its interest in maintaining good commercial relations with the United States. The mechanism also has the potential to provide a way to address the autonomous actions of the Peruvian Congress or its subnational governments that sometimes act in defiance of the environmental laws and regulations enforced by the executive branch of the national government. Importantly, however, citizens need to be aware of the limitations of the SEEM as a non‐adjudicatory mechanism and the fact that it is not a policymaking forum. Future research on the SEEM could provide a better understanding of how the process of increasingly mainstreaming the environment in international trade law is beginning to have concrete effects.
Risk management for second‐hand clothing imports in least developed countries: Legislations and perception of public‐sector corruption
Authors: Guo Shu , Choi Tsan‐Ming 
Published: April 2023

AbstractThe second‐hand clothing imports are very popular in the least developed countries (LDCs). The social health risk (SHR) associated with second‐hand clothing products and the lack of relevant legislations in LDCs, however, bring substantial challenges. This article is therefore developed to explore the sterilization legislation design for second‐hand clothing supply chains in LDCs. To address LDCs’ different import requirements of fumigation, both the extended exporter responsibility (EER) legislation scheme and the extended importer responsibility (EIR) legislation scheme are considered. We also examine whether the perception of public‐sector corruption in LDCs may affect the performance of sterilization legislation schemes. We compare the performance of sterilization legislation schemes under different public‐sector corruption cases, different sterilization legislation structures, as well as market competition. Interestingly, our analyses show that the EER and EIR legislation schemes can achieve the same performance under a per unit SHR duty, no matter whether there is public‐sector corruption or not. However, these two legislation schemes perform differently under the lump‐sum SHR duty. Besides, with the presence of the public‐sector corruption perception, the prospect of financial benefits from bribing the regulatory agency can induce the firm to choose a higher optimal sterilization level when the bribe is sufficiently small. These implications complement the extant knowledge on risk management of second‐hand clothing in LDCs, and provide an important guidance regarding the design of sterilization legislations on second‐hand clothing imports.
Uniform boundedness and eventual Hölder continuity to a cancer invasion model with remodeling of ECM and nonlinear diffusion
Authors: Jin Chunhua 
Published: April 2023

AbstractThis paper is concerned with a class of cancer invasion model with nonlinear diffusion and remodeling of ECM. The primary difficulty that arises here is that due to nonlinear diffusion, the good coupling structure between the diffusion term and haptotactic term is destroyed, rendering the effective methods used in the linear diffusion model no longer applicable. Fortunately, we have found a new effective combination between the diffusion term and the haptotactic term, which allows the diffusion term to dominate the haptotactic term, thus preliminarily improving the regularity of the weak solution. Based on these results, we can prove part of long‐time asymptotic behavior of the solution, thereby finally proving the uniform boundedness of the weak solution. Subsequently, by improving the convergence of cancer cells u from ‐norm to ‐norm, it is also proved that after a long time, the weak solution will eventually be Hölder continuous for some slow diffusion cases.
Statistical inference with semiparametric nonignorable nonresponse models
Authors: Uehara Masatoshi , Lee Danhyang , Kim Jae‐Kwang 
Published: April 2023

AbstractHow to deal with nonignorable response is often a challenging problem encountered in statistical analysis with missing data. Parametric model assumption for the response mechanism is sensitive to model misspecification. We consider a semiparametric response model that relaxes the parametric model assumption in the response mechanism. Two types of efficient estimators, profile maximum likelihood estimator and profile calibration estimator, are proposed, and their asymptotic properties are investigated. Two extensive simulation studies are used to compare with some existing methods. We present an application of our method using data from the Korean Labor and Income Panel Survey.
Regularized t$$ t $$ distribution: definition, properties, and applications
Authors: Hu Zongliang , Yang Yiping , Li Gaorong , Tong Tiejun 
Published: April 2023

AbstractFor gene expression data analysis, an important task is to identify genes that are differentially expressed between two or more groups. Nevertheless, as biological experiments are often measured with a relatively small number of samples, how to accurately estimate the variances of gene expression becomes a challenging issue. To tackle this problem, we introduce a regularized distribution and derive its statistical properties including the probability density function and the moment generating function. The noncentral regularized distribution is also introduced for computing the statistical power of hypothesis testing. For practical applications, we apply the regularized distribution to establish the null distribution of the regularized statistic, and then formulate it as a regularized ‐test for detecting the differentially expressed genes. Simulation studies and real data analysis show that our regularized ‐test performs much better than the Bayesian ‐test in the “limma” package, in particular when the sample sizes are small.
PECT1, a rate‐limiting enzyme in phosphatidylethanolamine biosynthesis, is involved in the regulation of stomatal movement in Arabidopsis
Authors: Negi Juntaro , Obata Tomoki , Nishimura Sakura , Song Boseok , Yamagaki Sho , Ono Yuhei , Okabe Makoto , Hoshino Natsumi , Fukatsu Kohei , Tabata Ryo , Yamaguchi Katsushi , Shigenobu Shuji , Yamada Masashi , Hasebe Mitsuyasu , Sawa Shinichiro , Kinoshita Toshinori , Nishida Ikuo , Iba Koh 
Published: April 2023

SUMMARYAn Arabidopsis mutant displaying impaired stomatal responses to CO2, cdi4, was isolated by a leaf thermal imaging screening. The mutated gene PECT1 encodes CTP:phosphorylethanolamine cytidylyltransferase. The cdi4 exhibited a decrease in phosphatidylethanolamine levels and a defect in light‐induced stomatal opening as well as low‐CO2‐induced stomatal opening. We created RNAi lines in which PECT1 was specifically repressed in guard cells. These lines are impaired in their stomatal responses to low‐CO2 concentrations or light. Fungal toxin fusicoccin (FC) promotes stomatal opening by activating plasma membrane H+‐ATPases in guard cells via phosphorylation. Arabidopsis H+‐ATPase1 (AHA1) has been reported to be highly expressed in guard cells, and its activation by FC induces stomatal opening. The cdi4 and PECT1 RNAi lines displayed a reduced stomatal opening response to FC. However, similar to in the wild‐type, cdi4 maintained normal levels of phosphorylation and activation of the stomatal H+‐ATPases after FC treatment. Furthermore, the cdi4 displayed normal localization of GFP‐AHA1 fusion protein and normal levels of AHA1 transcripts. Based on these results, we discuss how PECT1 could regulate CO2‐ and light‐induced stomatal movements in guard cells in a manner that is independent and downstream of the activation of H+‐ATPases. [Correction added on 15 May 2023, after first online publication: The third sentence is revised in this version.]
Current transfusion practice and need for new blood products to ensure blood supply for patients with major hemorrhage in Europe
Authors: Apelseth Torunn Oveland , Doyle Barry , Evans Ryan , George Chloe , Humbrecht Catherine , Klei Thomas , Najdovski Tome , Sigurjónsson Ólafur Eysteinn , Wiltshire Michael , de Korte Dirk 
Published: April 2023

AbstractBackgroundNew blood products are considered for treatment of patients with major hemorrhage. The aim of this report is to describe the current transfusion practices in Europe for patients with major hemorrhage and explore the need for new or modified blood products to ensure prehospital and in‐hospital blood supply.Study Design and MethodThe European Blood Alliance (EBA) Working Group on Innovation and New Blood Products' subgroup on major hemorrhage performed a survey among the EBA member states.ResultsThe response rate was 58% (17 responses from 15 of the 26 EBA member states). Of these, sixteen (94%) provide massive transfusion packages (MTPs) with balanced ratio of red blood cells and plasma. Seven of the respondents included platelets from the start of treatment. Eleven (65%) provide prehospital blood products, mainly red cell concentrates or dried and/or thawed plasma with 5 days of extended storage. Two countries provide prehospital whole blood. Twelve respondents (71%) saw a need for implementation of new or modified blood components in their institution. The top three priorities were whole blood (12 of 12, 100%), dried plasma (8 of 12, 67%), and cold‐stored platelets (7 of 12, 58%).DiscussionCurrent national guidelines for use of blood products in patients with major hemorrhage in Europe agree on the use of balanced transfusion, however the timing and source of platelets differ. Blood products for prehospital transfusion are available in several European countries. An interest in new or modified blood products for patients with major hemorrhage was observed, especially for whole blood.
Regular high‐frequency whole blood donation and risk of cardiovascular disease in middle‐aged and older blood donors in Australia
Authors: Karki Surendra , Bell Katy J. L. , Hayen Andrew , Liu Bette , Cust Anne E. , Olynyk John K. , Irving David O. 
Published: April 2023

AbstractBackgroundPrevious mixed findings on the associations between whole blood (WB) donation and risk of cardiovascular diseases (CVD) may in part reflect inadequate adjustment for the “healthy donor effect” (HDE).MethodsWe used the Sax Institute's 45 and Up Study linked with blood donation history and other health‐related databases to examine the association between regular, high‐frequency WB donation and the risk of CVD. To mitigate the impact of HDE, we used a “5‐years qualification period,” in which donors must donate at least 1 WB donation in the 1st and 5th year of “qualification period.” We then compared the risk of CVD in the years following the “qualification period” between the regular high‐frequency WB donors (≥2 WB donation in each qualification year) and others using Cox proportional‐hazards models. Analyses were adjusted for potential confounders, such as sociodemographic, lifestyle, and health‐related variables, and results are reported separately for male and female donors.ResultsA total of 2736 male and 2917 female donors were included in the analyses. The median years of follow‐up per donor was 5.84 years (Q1‐Q3, 5.47–6.23). The rate of CVD hospitalization was 11.20 and 4.50 per 1000 person‐years for males and females, respectively. In fully adjusted models, the risk (hazard ratio) of CVD in regular high‐frequency donors compared to other donors was 0.93 (95% Confidence Interval (CI), 0.68–1.29) for males and 0.79 (95% CI, 0.49–1.28) for females.ConclusionsWe did not observe a statistically significant reduction of CVD risk in regular, high‐frequency WB donors when adjusted for potential confounders.
Stretch‐induced reactive oxygen species contribute to the Frank–Starling mechanism
Authors: Kaihara Keiko , Kai Hiroaki , Chiba Yumiko , Naruse Keiji , Iribe Gentaro 
Published: April 2023

AbstractMyocardial stretch physiologically activates NADPH oxidase 2 (NOX2) to increase reactive oxygen species (ROS) production. Although physiological low‐level ROS are known to be important as signalling molecules, the role of stretch‐induced ROS in the intact myocardium remains unclear. To address this, we investigated the effects of stretch‐induced ROS on myocardial cellular contractility and calcium transients in C57BL/6J and NOX2−/− mice. Axial stretch was applied to the isolated cardiomyocytes using a pair of carbon fibres attached to both cell ends to evaluate stretch‐induced modulation in the time course of the contraction curve and calcium transient, as well as to evaluate maximum cellular elastance, an index of cellular contractility, which is obtained from the end‐systolic force–length relationship. In NOX2−/− mice, the peak calcium transient was not altered by stretch, as that in wild‐type mice, but the lack of stretch‐induced ROS delayed the rise of calcium transients and reduced contractility. Our mathematical modelling studies suggest that the augmented activation of ryanodine receptors by stretch‐induced ROS causes a rapid and large increase in the calcium release flux, resulting in a faster rise in the calcium transient. The slight increase in the magnitude of calcium transients is offset by a decrease in sarcoplasmic reticulum calcium content as a result of ROS‐induced calcium leakage, but the faster rise in calcium transients still maintains higher contractility. In conclusion, a physiological role of stretch‐induced ROS is to increase contractility to counteract a given preload, that is, it contributes to the Frank–Starling law of the heart.
imageKey points
Myocardial stretch increases the production of reactive oxygen species by NADPH oxidase 2.
We used NADPH oxidase 2 knockout mice to elucidate the physiological role of stretch‐induced reactive oxygen species in the heart.
We showed that stretch‐induced reactive oxygen species modulate the rising phase of calcium transients and increase myocardial contractility.
A mathematical model simulation study demonstrated that rapid activation of ryanodine receptors by reactive oxygen species is important for increased contractility.
This response is advantageous for the myocardium, which must contract against a given preload.
Myelin Oligodendrocyte Glycoprotein as an Autoantigen in Inflammatory Demyelinating Diseases of the Central Nervous System
Authors: Eliseeva Daria D. , Zakharova Maria N. 
Published: April 2023

Abstract
Demyelinating diseases of the central nervous system are caused by an autoimmune attack on the myelin sheath surrounding axons. Myelin structural proteins become antigenic, leading to the development of myelin lesions. The use of highly specialized laboratory diagnostic techniques for identification of specific antibodies directed against myelin components can significantly improve diagnostic approaches. Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) currently includes demyelinating syndromes with known antigens. Based on the demonstrated pathogenic role of human IgG against MOG, MOGAD was classified as a distinct nosological entity. However, generation of multiple MOG isoforms by alternative splicing hinders antigen detection even with the most advanced immunofluorescence techniques. On the other hand, MOG conformational changes ensure the structural integrity of other myelin proteins and maintain human-specific mechanisms of immune autotolerance.
CFD modeling of vertical-axis wind turbine wake interaction
Authors: Belabes Belkacem , Paraschivoiu Marius 
Published: April 2023

Since wind turbines placed in wind farms need to minimize their footprint on the ground, the effects of the wake must be considered. Placement optimization, turbine spacing, and direction of rotation are known to affect the performance of vertical-axis wind turbines (VAWTs). However, rigorous numerical modeling methodologies that investigate the influence of these characteristics are lacking, especially in the case of large wind turbines. The goal of this study is to analyze turbine configurations that might enhance the power production of VAWT farms using two-dimensional CFD models based on the Star CCM+ package. The novelty of this work is to analyze wind farm configurations for very large turbines. This is important because large turbines are much more performant than small turbines and have a high power coefficient. Results show that CFD simulations adequately capture the performance of wind turbines in farms with multiple VAWTs. In general, if a second rotor is spaced more than 10 turbine diameters downstream of the first rotor, the effect of the wake is less significant. Furthermore, a specific farm configuration with five VAWTs is investigated and shows a 20% increase in power output compared with the same number of turbines operating in isolation.