bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPLEMENTATION OF PUBLIC SERVICES IN THE ERA OF THE COVID-19 ENDEMY TRANSITION AT THE REGIONAL POPULATION AND CIVIL REGISTRATION DEPARTMENT OF TOMOHON CITY
Authors: Mantiri Jeane , Siwi Cynthia Maria
Published: July 2022

This study aims to determine the general description of the implementation of public services in the era of the covid-19 endemic transition at the Tomohon City Population and Civil Registry Office in implementing the Tomohon e-Dukcapil online service application. This study uses a descriptive qualitative approach. Based on the results of the study, it can be concluded that the implementation of services in the Covid-19 endemic transition era with the application of online service applications by the Tomohon City Population and Civil Registry Office has not been good. It can be seen from 3 indicators, namely transparency, participation and efficiency, online application-based services have not been maximized in providing information on service progress to the community, community participation and service officers from the Tomohon City Population and Civil Registration Service. also not optimal in utilizing existing technology and services provided. It is hoped that it will be faster with the existence of information technology which has not been fully realized, this is also influenced by problems in the application of the Tomohon e-Dukcapil online service application, such as the mastery of technology from service officers and also the people who make online services still not able to run properly.
Integrated Management of Verticillium Wilt of Cacao
Authors: Bouchon Anne-Sophie , Hoopen Gerben Martijn ten
Published: July 2022

The vascular disease Verticillium wilt of cacao (Theobroma cacao), caused by the soilborne fungus Verticillium dahliae, is often qualified as a “minor” disease. However, it can cause severe losses locally, for example, in western Uganda and northeast of the Democratic Republic of Congo. This disease is difficult to control, notably due to an extended host range and prolonged survival in the soil. Therefore, Verticillium wilt must be addressed through an integrated disease management strategy as employed for other tree crops such as olive. Few studies, nonetheless, have focused on how to confront this disease in cacao. This paper aims to provide an overview of our knowledge on Verticillium wilt on cacao and the integrated disease management strategies for preventing and controlling it. Promising avenues based on findings in other crops that could be adapted to cacao are also explored. Good agricultural practices, genetic resistance, biological control, induced resistance, and the use of organic amendments with or without biocontrol agents are discussed. Moreover, the potential benefits of some of these solutions toward the resistance to other cacao diseases, abiotic stress, and nutrition improvement are presented.
Calcium Phosphate/Hyaluronic Acid Composite Hydrogels for Local Antiosteoporotic Drug Delivery
Authors: Svarca Alise , Grava Andra , Dubnika Arita , Ramata-Stunda Anna , Narnickis Raimonds , Aunina Kristine , Rieksta Eleonora , Boroduskis Martins , Jurgelane Inga , Locs Janis , Loca Dagnija
Published: July 2022

Despite the bone ability of self-regeneration, large bone defects require surgical intervention. Likewise, when it comes to osteoporotic bone fractures, new approaches should be considered a supportive mechanism for the surgery. In recent years, more and more attention has been attracted to advanced drug delivery systems for local osteoporosis treatment, combining appropriate biomaterials with antiosteoporotic drugs, allowing simultaneously to regenerate the bone and locally treat the osteoporosis. Within the current research, hyaluronic acid/strontium ranelate (HA/SrRan), HA/calcium phosphate nanoparticles (HA/CaP NPs), and HA/CaP NPs/SrRan hydrogels were prepared. The effect of CaP and SrRan presence in the composites on the swelling behavior, gel fraction, molecular structure, microstructure, and SrRan and Sr2+ release, as well as in vitro cell viability was evaluated. Obtained results revealed that the route of CaP nanoparticle incorporation into the HA matrix had a significant effect on the hydrogel gel fraction, rheological properties, swelling behavior, and microstructure. Nevertheless, it had a negligible effect on the release kinetics of SrRan and Sr2+. The highest cell (3T3) viability (>80%) was observed for HA hydrogels, with and without SrRan. Moreover, the positive effect of SrRan on 3T3 cells was also demonstrated, showing a significant increase (up to 50%) in cell viability if the used concentrations of SrRan were in the range of 0.05–0.2 μg/ml.
Biomechanical Comparison Between Porous Ti6Al4V Block and Tumor Prosthesis UHMWPE Block for the Treatment of Distal Femur Bone Defects
Authors: Zhang Jiangbo , Liu Yang , Han Qing , Zhang Aobo , Chen Hao , Ma Mingyue , Li Yongyue , Chen Bingpeng , Wang Jincheng
Published: July 2022

Purpose: The management of bone defects is a crucial content of total knee revision. This study compared the biomechanical performance of porous Ti6Al4V block and tumor prosthesis UHMWPE block in treating distal femoral bone defects.

Methods: The finite element models of AORI type 3 distal femoral bone defect treated with porous Ti6Al4V block and UHMWPE block were established. Sensitivity analysis was performed to obtain the appropriate mesh size. The biomechanical performance of treatment methods in bone defects were evaluated according to the peak stress, the Von Mises stress distribution, and the average stresses of regions of interest under the condition of standing on one foot and flexion of the knee. Statistical analysis was conducted by independent samples t-test in SPSS (p < 0.05).

Results: In the standing on one-foot state, the peak stress of the porous Ti6Al4V block was 12.42 MPa and that of the UHMWPE block was 19.97 MPa, which is close to its yield stress (21 MPa). Meanwhile, the stress distribution of the UHMWPE block was uneven. In the flexion state, the peak stress of the porous Ti6Al4V block was 16.28 MPa, while that of the UHMWPE block was 14.82 MPa. Compared with the porous Ti6Al4V block group, the average stress of the region of interest in UHMWPE block group was higher in the standing on one foot state and lower in the flexion state (p < 0.05).

Conclusion: More uniform stress distribution was identified in the porous Ti6Al4V block application which could reserve more bone. On the contrary, uneven stress distribution and a larger high-stress concentration area were found in the UHMWPE block. Hence, the porous Ti6Al4V block is recommended for the treatment of AORI type 3 distal femoral bone defect.
Augmenting Blockchain With Competition Law for a Sustainable Economic Evolution
Authors: Yawar Syed Mohammad , Shaw Rahul
Published: July 2022

Since its introduction, blockchain technology has been revered, ridiculed, dismissed, embraced, and presently has become too large to ignore, witnessing exponential growth. The obvious indicator of this growth is that research revolving around blockchain technology has already raised competition in the form of directed acyclic graphs and hashgraph, all of which fall under the umbrella of distributed ledger technology (DLT). Segueing on the back of visibly positive effects of competition, we arrive at the essence of our paper. We show that the current competition regimes around the world are inefficient at promoting and maintaining competition around the world, dominated by the behemoth technology enterprises that have successfully monopolized and monetized data, which is indubitably, one of the most important assets in today’s digital age. Data gathered from users fuels the algorithms, machine learning, and artificial intelligence programs employed by these tech giants, which further entrenches their monopolistic hold over cyberspace. Blockchain and DLTs, just like any other technology, pose new threats to the competition law regimes, while also allowing the authorities to utilize the technology themselves to explore new horizons involving smart contracts, Decentralized Autonomous Organizations (DAOs), Web 3.0, and enforce competition more effectively. In our paper, we briefly illustrate the challenges presented before the competition authorities by the assimilation of blockchain in the existing establishments, and how the competition authorities can themselves collude with blockchain stakeholders to take a holistic approach and establish a symbiotic relationship, which ensures that both, survive, prosper, and enhance consumer welfare.
Single-Cell Transcriptome Analysis Reveals Mesenchymal Stem Cells in Cavernous Hemangioma
Authors: Ji Fulong , Liu Yong , Shi Jinsong , Liu Chunxiang , Fu Siqi , Wang Heng , Ren Bingbing , Mi Dong , Gao Shan , Sun Daqing
Published: July 2022

A cavernous hemangioma, well-known as vascular malformation, is present at birth, grows proportionately with the child, and does not undergo regression. Although a cavernous hemangioma has well-defined histopathological characteristics, its origin remains controversial. In the present study, we characterized the cellular heterogeneity of a cavernous hemangioma using single-cell RNA sequencing (scRNA-seq). The main contribution of the present study is that we discovered a large number of embryonic mesenchymal stem cells (MSCs) in a cavernous hemangioma and proposed that cavernous hemangiomas may originate from embryonic MSCs. Further analysis of the embryonic MSCs revealed that: 1) proinflammatory cytokines and related genes TNF, TNFSF13B, TNFRSF12A, TNFAIP6, and C1QTNF6 are significantly involved in the MSC-induced immune responses in cavernous hemangiomas; 2) UCHL1 is up-regulated in the embryonic MSC apoptosis induced by proinflammatory cytokines; 3) the UCHL1-induced apoptosis of MSCs may play an important role in the MSC-induced immune responses in cavernous hemangiomas; and 4) UCHL1 can be used as a marker gene to detect embryonic MSCs at different apoptosis stages. In addition to MSCs, ECs, macrophages, T lymphocytes and NKCs were intensively investigated, revealing the genes and pathways featured in cavernous hemangiomas. The present study revealed the origin of cavernous hemangiomas and reported the marker genes, cell types and molecular mechanisms, which are associated with the origin, formation, progression, diagnosis and therapy of cavernous hemangiomas. The better understanding of the MSC-induced immune responses in benign tumours helps to guide future investigation and treatment of embryonic MSC-caused tumours. Our findings initiated future research for the rediscovery of MSCs, cancers/tumours and the UCHL1-induced apoptosis.
The Development of Microscopic Imaging Technology and its Application in Micro- and Nanotechnology
Authors: Wang Yong , Zhang Xiushuo , Xu Jing , Sun Xiangyu , Zhao Xiaolong , Li Hongsheng , Liu Yanping , Tian Jingjing , Hao Xiaorui , Kong Xiaofei , Wang Zhiwei , Yang Jie , Su Yuqing
Published: July 2022

As a typical microscopic imaging technology, the emergence of the microscope has accelerated the pace of human exploration of the micro world. With the development of science and technology, microscopes have developed from the optical microscopes at the time of their invention to electron microscopes and even atomic force microscopes. The resolution has steadily improved, allowing humans to expand the field of research from the initial animal and plant tissues to microorganisms such as bacteria, and even down to the nanolevel. The microscope is now widely used in life science, material science, geological research, and other fields. It can be said that the development of microscopes also promotes the development of micro- and nanotechnology. It is foreseeable that microscopes will play a significant part in the exploration of the microworld for a long time to come. The development of microscope technology is the focus of this study, which summarized the properties of numerous microscopes and discussed their applications in micro and nanotechnology. At the same time, the application of microscopic imaging technology in micro- and nanofields was investigated based on the properties of various microscopes.
Isolation and Characterization of vB_kpnM_17-11, a Novel Phage Efficient Against Carbapenem-Resistant Klebsiella pneumoniae
Authors: Bai Jiawei , Zhang Feiyang , Liang Shuang , Chen Qiao , Wang Wei , Wang Ying , Martín-Rodríguez Alberto J. , Sjöling Åsa , Hu Renjing , Zhou Yingshun
Published: July 2022

Phages and phage-encoded proteins exhibit promising prospects in the treatment of Carbapenem-Resistant Klebsiella pneumoniae (CRKP) infections. In this study, a novel Klebsiella pneumoniae phage vB_kpnM_17-11 was isolated and identified by using a CRKP host. vB_kpnM_17-11 has an icosahedral head and a retractable tail. The latent and exponential phases were 30 and 60 minutes, respectively; the burst size was 31.7 PFU/cell and the optimal MOI was 0.001. vB_kpnM_17-11 remained stable in a wide range of pH (4-8) and temperature (4-40°C). The genome of vB_kpnM_17-11 is 165,894 bp, double-stranded DNA (dsDNA), containing 275 Open Reading Frames (ORFs). It belongs to the family of Myoviridae, order Caudovirales, and has a close evolutionary relationship with Klebsiella phage PKO111. Sequence analysis showed that the 4530 bp orf022 of vB_kpnM_17-11 encodes a putative depolymerase. In vitro testing demonstrated that vB_kpnM_17-11 can decrease the number of K. pneumoniae by 105-fold. In a mouse model of infection, phage administration improved survival and reduced the number of K. pneumoniae in the abdominal cavity by 104-fold. In conclusion, vB_kpnM_17-11 showed excellent in vitro and in vivo performance against K. pneumoniae infection and constitutes a promising candidate for the development of phage therapy against CRKP.
Risk of Ischemic Bowel Disease in Patients With Atrial Fibrillation Receiving Warfarin or Non-vitamin K Antagonist Oral Anticoagulants
Authors: Liao Jo-Nan , Chan Yi-Hsin , Kuo Ling , Tsai Chuan-Tsai , Lim Su-Shen , Chao Tze-Fan
Published: July 2022

Background

Although atrial fibrillation (AF) is a risk factor for ischemic bowel disease, data regarding the incidence of ischemic bowel disease in patients with anticoagulated AF were limited.

Methods

The present study used the Taiwan NHIRD and included newly diagnosed patients with AF aged ≥ 20 years without ischemic bowel disease from 2012 to 2018. A total of 69,549 patients taking warfarin or non-vitamin K antagonist oral anticoagulants (NOACs) constituted the final study group. We aimed to study the incidence of ischemic bowel disease in patients with AF receiving warfarin or NOACs. Secondary endpoints were also analyzed, including ischemic stroke, systemic embolism, myocardial infarction, mortality, intracranial hemorrhage (ICH), major bleeding, and composite adverse events (ischemic bowel disease or ICH or major bleeding).

Results

There were 43,787 patients taking NOACs and 25,762 patients taking warfarin. The overall incidence rate of ischemic bowel disease was 0.036% per year and increased with the CHA2DS2-VASc scores [0.013% for patients with a CHA2DS2-VASc score of 0 (men) or 1 (women), 0.022% for those with a CHA2DS2-VASc score of 1 (men) or 2 (women), and 0.039% for those with a CHA2DS2-VASc score ≥ 2 (men) or ≥ 3 (women)]. The risk of ischemic bowel disease was similar between NOAC and warfarin groups (0.036%/year vs. 0.037%/year; adjusted hazard ratio 0.802, p = 0.430), whereas the NOAC group had a significantly lower risk of secondary endpoints compared to the warfarin group.

Conclusion

We reported the incidence of ischemic bowel disease in patients with anticoagulated AF from a nationwide cohort database and observed a positive correlation between the increase of CHA2DS2-VASc scores and the incidence rate. Moreover, NOAC was as effective as warfarin for the risk of ischemic bowel disease.
Comparison of Influence of Blood Pressure and Carotid-Femoral Pulse Wave Velocity on Target Organ Damage in Hypertension
Authors: Chao Huijuan , He Yan , Wang Qian , Bai Yaya , Avolio Alberto , Deng Xueqin , Zuo Junli
Published: July 2022

Objectives

Assessment of target organ damage (TOD) is an important part of the diagnosis and evaluation of hypertension. Carotid-femoral pulse wave velocity (cf-PWV) is considered to be the gold-standard for noninvasive arterial stiffness assessment. This study aims to analyze the risk of TOD in people with different phenotypes of peripheral blood pressure and cf-PWV.

Methods

The study cohort was recruited from December 2017 to September 2021 at Ruijin Hospital in Shanghai. It was divided into 4 groups according to peripheral blood pressure (pBP) and cf-PWV. TOD was assessed as carotid intima-media thickness (CIMT), chronic kidney disease (CKD), urinary albumin-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR) and left ventricular mass index (LVMI).

Results

A total of 1,257 subjects (mean age 53.13 ± 12.65 years, 64.2% males) was recruited. Age, body mass index (BMI) and fasting blood glucose (FBG), as well as peripheral systolic blood pressure (pSBP), peripheral diastolic blood pressure (pDBP), peripheral pulse pressure (pPP) were significantly different in the four groups (P < 0.01). eGFR, ACR, LVMI and CIMT were significantly different among different groups (P < 0.01). The risk of ACR abnormality was significantly higher in the group with elevated pBP (P = 0.005, OR 2.264, 95%CI 1.277–4.016; and in the group with elevated pBP and cf-PWV (P = 0.003, OR 1.482, 95%CI 1.144–1.920), while left ventricular hypertrophy (LVH) was significantly higher in the group with elevated cf-PWV (P = 0.002, OR 1.868, 95%CI 1.249–2.793).

Conclusion

Different profiles based on the status of PBP and cf-PWV associated with different TOD. Individuals with higher pBP have an increased risk of ACR abnormality, while individuals with only cf-PWV elevated have a higher risk of LVH.
Optimization and Characterization of a Liposomal Azithromycin Formulation for Alternative Macrophage Activation
Authors: Masud Abdullah A. , Alsharif Fahd M. , Creameans Jarrod W. , Perdeh Jasmine , Feola David J. , Venditto Vincent J.
Published: July 2022

Liposomal azithromycin (L-AZM) promotes macrophage polarization toward an M2-like phenotype in the context of myocardial infarction that results in improved cardiovascular outcomes in mice. To improve upon this formulation, we sought to identify optimized formulation, stability, and biological activity parameters necessary to enhance the immunomodulatory activity and efficacy of L-AZM. While our parent formulation contains a mixture of long-chain saturated phosphatidylcholine and phosphatidylglycerol lipids, we evaluated a series of formulations with different amounts of unsaturated lipids and cholesterol with the goal of improving the loading capacity and stability of the formulations. We also introduce fusogenic lipids to improve the cytosolic delivery to enhance the immune modulatory properties of the drug. To achieve these goals, we initially prepared a library of 24 formulations using thin film hydration and assessed the resultant liposomes for size and polydispersity. Five lead formulations were identified based on low polydispersity (<0.3) and stability over time. The lead formulations were then evaluated for stability in serum using dialysis and macrophage polarization activity in vitro as measured by decreased IL-12 expression. Collectively, our data indicate that the formulation components drive the balance between encapsulation efficiency and stability and that all the lead liposomal formulations improve in vitro alternative macrophage activation as compared to free AZM.
The Calculation of Inelastic Zone Width of Coal Pillar in Highwall Mining With Backfill
Authors: Jiang Juyu , Lu Ye , Cao Lanzhu , Wang Dong , Wang Laigui , Han Xinping , Yang Huiwen , Jia Zhengzhao
Published: July 2022

Highwall mining with backfill technology will be one of the main techniques of raising the recovery rate of coal resources under the end-slope all over the world in the future, in which the coal pillar setting is the key to ensure the successful application of this technology, and the calculation of inelastic zone width of a coal pillar has important guiding significance for the coal pillar setting in highwall mining with backfill. However, at present, in order to accurately calculate the inelastic zone width of a coal pillar under the condition of highwall mining with backfill, a calculation model of the inelastic zone width of highwall mining with backfill independent of empirical parameters is established by using a limit equilibrium method, orthogonal experiment method, and non-linear fitting method. In order to verify the correctness and reliability of the model, this study takes the geological conditions of the Antaibao open-pit mine in Pingshuo, Shanxi Province, China, as the engineering background to verify the calculation accuracy of the model. The results show that the calculation model established in this study can accurately calculate the inelastic zone width of the coal pillar under highwall mining with backfill and can meet the engineering needs.
Association of Sarcopenia and A Body Shape Index With Overall and Cause-Specific Mortality
Authors: Qiao Yu-Shun , Tang Xingyao , Chai Yin-He , Gong Hong-Jian , Zhang Xin , Stehouwer Coen D. A. , Zhou Jian-Bo
Published: July 2022

Aim

This observational study aimed to examine the association between the A Body Shape Index (ABSI) and/or sarcopenia and total, cardiovascular, and cancer mortality.

Methods

The associations of sarcopenia and ABSI with all-cause, cardiovascular, and cancer mortality were assessed in 4,488 participants from the 1999–2004 National Health and Nutrition Examination Survey (NHANES) who were followed up until December 31, 2015. Models were analyzed separately for men and women and adjusted for age, race, and other confounding factors. ABSI was assessed as a continuous measurement by quartile for men and women. Population attributable fractions (PAFs) were calculated to assess mortality caused by sarcopenia and/or ABSI in the study population.

Results

When ABSI was assessed as a continuous variable, the ABSI quartile showed a linear trend for total (p = 0.0001), cardiovascular (p = 0.04), and cancer (p = 0.02) mortality in men and for total (p = 0.06) and cardiovascular (p = 0.06) mortality in women. The hazard ratios (HRs) of the fourth ABSI quartile were 1.51 [95% confidence interval (CI): 1.20–1.89] in men and 1.23 (95% CI: 0.93–1.64) in women, compared with those in the first quartile. When ABSI was assessed by quartile, the appendicular skeletal mass index (ASMI) was lower in the groups with high ABSI. When high ABSI was combined with sarcopenia, the HRs of all-cause mortality were 2.05 (95% CI: 1.60–2.62) in men and 1.51 (95% CI: 1.19–1.92) in women. In the subpopulation (sarcopenia group or higher ABSI), the PAFs of mortality due to sarcopenia were 26.16% (95% CI: 12.68–37.56) in men and 21.89% (95% CI: 5.64–35.35) in women, and the PAF of mortality due to higher ABSI was 23.70% (95% CI: 12.11–33.77) in men.

Conclusion

The ABSI value was significantly associated with all-cause and cardiovascular mortality, and the co-existence of higher ABSI values and sarcopenia can contribute to a more significant death risk in comparison with high ABSI values or sarcopenia. Moreover, the ABSI values in combination with the ASMI can be used to preliminarily evaluate the content and distribution of fat and muscle and to predict the risk of death in obese and sarcopenic populations.
Research on Restrictive Factors and Planning of Charging Piles for Electric Vehicles in the Park Based on the Interpretative Structural Model
Authors: Zhang Chao , Zhao Yihang , Zhao Huiru , Wang Qiang
Published: July 2022

At present, the world is vigorously promoting the innovative development concept of “green development, park first,” prompting the park to vigorously promote the construction of electric vehicle charging stations and charging pile projects. However, the development of the construction is not satisfactory due to a series of restrictive factors. Under this background, this article studies the constraints of EV charging stations in the park and further studies the impact on park planning. First, this article outlines the constraints of charging piles in the park based on the field research. Then, interpretive structural modeling (ISM) is adopted in this article for in-depth analysis of the restrictive factors. Finally, the impact on the industrial park’s planning is analyzed as a case study. The improved countermeasures provide a basis for the scientific planning and design of electric vehicle charging stations in industrial parks.
Coupling Coordination Analysis of Natural Resource Utilization Benefits in Beijing From 1978 to 2018
Authors: Yin Ziyan , Zhao Chunjiang , Liu Yu , Pan Yuchun , Zhou Wei
Published: July 2022

With the acceleration of economic and social development, the demand for natural resources has increased. To realize the sustainable utilization of natural resources (SUNRs), it is necessary to seek ways to improve natural resource utilization benefits (NRUBs) and promote the coordinated development of economic, social, and ecological benefits. This study explores the coupling coordination relationships of NRUBs in Beijing from 1978 to 2018 and analyzes the influencing factors. We first establish a comprehensive evaluation index system covering economic, social, and ecological benefits to quantify NRUBs. Then, a coupling coordination degree (CCD) model is applied to reveal the evolution characteristics of the coupling coordination relationships among the NRUB system. Finally, the main factors affecting the coordinated development of NRUBs are identified through gray relational analysis (GRA). Three main results are found: 1) from 1978 to 2018, the economic, social, ecological, and comprehensive benefits all have been significantly improved, although with some fluctuations. 2) The coupling coordination relationships of NRUBs show upward trends during the study period, and their coordination types transform from imbalance to coordination. 3) Urbanization, industrial structure, technology innovation, economic development, and environmental awareness all have significant impacts on the coupling coordination relationships of NRUBs. Measures such as transformation of the economic development mode, improvement of public facilities, construction of spiritual culture, ecological protection, and technological innovation need to be recognized to achieve coordinated development. This study can provide a reference for other comprehensive evaluations of natural resources and the formulation of natural resource utilization policies.
Case Report: Severe Gonadal Dysgenesis Causing 46,XY Disorder of Sex Development Due to a Novel NR5A1 Variant
Authors: Alhamoudi Kheloud M. , Alghamdi Balgees , Aljomaiah Abeer , Alswailem Meshael , Al-Hindi Hindi , Alzahrani Ali S.
Published: July 2022

Mutations in the nuclear receptor subfamily 5 group A member 1 (NR5A1) are the underlying cause of 10–20% of 46,XY disorders of sex development (DSDs). We describe a young girl with 46,XY DSD due to a unique novel mutation of the NR5A1 gene. An 11-year-old subject, raised as a female, was noticed to have clitromegly. She looked otherwise normal. However, her evaluation revealed a 46,XY karyotype, moderate clitromegly but otherwise normal female external genitalia, undescended atrophied testes, rudimentary uterus, no ovaries, and lack of breast development. Serum testosterone and estradiol were low, and gonadotropins were elevated. Adrenocortical function was normal. DNA was isolated from the peripheral leucocytes and used for whole exome sequencing. The results were confirmed by Sanger sequencing. We identified a novel mutation in NR5A1 changing the second nucleotide of the translation initiation codon (ATG>ACG) and resulting in a change of the first amino acid, methionine to threonine (p.Met1The). This led to severe gonadal dysgenesis with deficiency of testosterone and anti-Müllerian hormone (AMH) secretion. Lack of the former led to the development of female external genitalia, and lack of the latter allowed the Müllerian duct to develop into the uterus and the upper vagina. The patient has a female gender identity. Bilateral orchidectomy was performed and showed severely atrophic testes. Estrogen/progesterone therapy was initiated with excellent breast development and normal cyclical menses. In summary, we describe a severely affected case of 46,XY DSD due to a novel NR5A1 mutation involving the initiation codon that fully explains the clinical phenotype in this subject.
Ginsenoside Rh2 Inhibits NLRP3 Inflammasome Activation and Improves Exosomes to Alleviate Hypoxia-Induced Myocardial Injury
Authors: Qi Zhongwen , Yan Zhipeng , Wang Yueyao , Ji Nan , Yang Xiaoya , Zhang Ao , Li Meng , Xu Fengqin , Zhang Junping
Published: July 2022

The inflammatory microenvironment after acute myocardial infarction (MI) is a key limiting factor in the clinical application of stem cell transplantation and paracrine exosome therapy. Qishen Yiqi Pills contain a saponin ingredient called Ginsenoside Rh2 (Rh2) which exhibits a certain therapeutic effect on MI. However, the mechanism by which Rh2 alleviates the inflammatory microenvironment and improves the therapeutic efficiency of exosomes remains enigmatic. Here, we found that Rh2 attenuated the adverse effect of oxygen-glucose deprivation (OGD)-induced cellular injury, an in vitro pathological model of MI. Confocal microscopy revealed that DiI-labeled BMSCs-derived exosomes exhibited an increased homing ability of cardiomyocytes, which, in turn, inhibited the nuclear translocation of NF-κB p65 and NLRP3 inflammasome activation, thereby alleviating the inflammatory microenvironment and further facilitating the homing of exosomes to cardiomyocytes by forming a feed-forward enhancement loop. Additionally, we found that Rh2 could regulate the HMGB1/NF-κB signaling pathway to improve the OGD environment of cardiomyocytes, increasing the efficiency of the feed-forward loop. In conclusion, we found that Rh2 can improve the inflammatory microenvironment by enhancing the protection of exosomes against myocardial injury, providing new insights into the indirect modification of exosomes by Rh2 in MI treatment.
Mechanics-Based Failure Model of Tube Hydro-Bulging Test
Authors: Di Bozhou , Liu Heli , Dhawan Saksham , Wang Kehuan , Liu Xiaochuan , Politis Denis J.
Published: July 2022

Tube hydroforming has been widely applied by the automotive sector to produce hollow parts. As a popular tube hydroforming test method, tube hydro-bulging needs an analytical failure model to analyze the formability of tubular materials. In the present work, a failure prediction model has been developed to predict the bulging height limit (BHL) of the hydro-bulging test. The model utilized Hill’s orthogonal anisotropic model to characterize the tube material, a geometry model to characterize the non-loading path and the M-K model to predict failure. Defects in multiple directions were taken into consideration. The developed model was applied on two tubes of different materials as case studies to verify its validity. It is shown that the developed model is capable of predicting the forming limit or determining the imperfection factor of tubular materials.
Return-to-Work Predictions for Chinese Patients With Occupational Upper Extremity Injury: A Prospective Cohort Study
Authors: Bai Zhongfei , Zhang Jiaqi , Tang Chaozheng , Wang Lejun , Xia Weili , Qi Qi , Lu Jiani , Fang Yuan , Fong Kenneth N. K. , Niu Wenxin
Published: July 2022

Objective

We created predictive models using machine learning algorithms for return-to-work (RTW) in patients with traumatic upper extremity injuries.

Methods

Data were obtained immediately before patient discharge and patients were followed up for 1 year. K-nearest neighbor, logistic regression, support vector machine, and decision tree algorithms were used to create our predictive models for RTW.

Results

In total, 163 patients with traumatic upper extremity injury were enrolled, and 107/163 (65.6%) had successfully returned to work at 1-year of follow-up. The decision tree model had a lower F1-score than any of the other models (t values: 7.93–8.67, p < 0.001), while the others had comparable F1-scores. Furthermore, the logistic regression and support vector machine models were significantly superior to the k-nearest neighbors and decision tree models in the area under the receiver operating characteristic curve (t values: 6.64–13.71, p < 0.001). Compared with the support vector machine, logistical regression selected only two essential factors, namely, the patient's expectation of RTW and carrying strength at the waist, suggesting its superior efficiency in the prediction of RTW.

Conclusion

Our study demonstrated that high predictability for RTW can be achieved through use of machine learning models, which is helpful development of individualized vocational rehabilitation strategies and relevant policymaking.
Reduced Insulin Signaling Targeted to Serotonergic Neurons but Not Other Neuronal Subtypes Extends Lifespan in Drosophila melanogaster
Authors: Dravecz Nikolett , Shaw Tommy , Davies Isabella , Brown Casey , Ormerod Lewis , Vu Gin , Walker Tyler , Taank Taran , Shirras Alan D. , Broughton Susan J.
Published: July 2022

Reduced Insulin/IGF-like signaling (IIS) plays an evolutionarily conserved role in improving longevity and some measures of health-span in model organisms. Recent studies, however, have found a disconnection between lifespan extension and behavioral health-span. We have previously shown that reduction of IIS in Drosophila neurons extends female lifespan but does not improve negative geotaxis senescence and has a detrimental effect on exploratory walking senescence in both sexes. We hypothesize that individual neuronal subtypes respond differently to IIS changes, thus the behavioral outcomes of pan-neuronal IIS reduction are the balance of positive, negative and neutral functional effects. In order to further understand how reduced IIS in neurons independently modulates lifespan and locomotor behavioral senescence we expressed a dominant negative Insulin receptor transgene selectively in individual neuronal subtypes and measured the effects on lifespan and two measures of locomotor senescence, negative geotaxis and exploratory walking. IIS reduction in cholinergic, GABAergic, dopaminergic, glutamatergic, and octopaminergic neurons was found to have either no affect or a detrimental effect on lifespan and locomotor senescence. However, reduction of IIS selectively in serotonergic neurons resulted in extension of lifespan in females with no effect on locomotor senescence. These data indicate that individual neuronal subtypes respond differently to IIS changes in the modulation of lifespan and locomotor senescence, and identify a specific role for the insulin receptor in serotonergic neurons in the modulation of lifespan.
Case Report: A Case of Adult Methylmalonic Acidemia With Bilateral Cerebellar Lesions Caused by a New Mutation in MMACHC Gene
Authors: Wang Shengnan , Wang Xu , Xi Jianxin , Yang Wenzhuo , Zhu Mingqin
Published: July 2022

Methylmalonic acidemia is a severe heterogeneous disorder of methylmalonate and cobalamin (Cbl; vitamin B12) metabolism with poor prognosis. Around 90% of reported patients with methylmalonic acidemia (MMA) are severe infantile early onset, while cases with late-onset MMA have been rarely reported. Few reported late-onset MMA patients presented with atypical clinical symptoms, therefore, often misdiagnosed if without family history. Herein, we report a 29-year-old female who was admitted to our hospital due to symptoms manifested as encephalitis. The brain MRI showed symmetrical bilateral cerebellar lesions with Gd enhancement. Laboratory tests showed significantly elevated levels of homocysteine and methylmalonic acid. A genetic analysis identified a novel homozygous mutation (c.484G>A; p.Gly162 Arg) in the MMACHC gene. The patient was diagnosed with MMA, and her symptoms improved dramatically with intramuscular adenosine cobalamin treatment. In conclusion, for patients with symmetrical lesions in the brain, the possibility of metabolic diseases should be considered, detailed medical and family history should be collected, and metabolic screening tests as well as gene tests are necessary for correct diagnosis. The mutation diversity in MMACHC gene is an important factor leading to the heterogeneity of clinical manifestations of patients with MMA.
Congenital Anomalous Origin of Coronary Artery Disease in Children With Syncope: A Case Series
Authors: Gao Yumeng , Zhang Qingyou , Sun Yan , Du Junbao
Published: July 2022

Objective

This study is aimed to analyze the characteristics of congenital anomalous origin of coronary artery in pediatric patients with syncope.

Methods

A total of eight patients were retrospectively analyzed from August 2018 to August 2020 who were admitted to the Peking University First Hospital with the complaint of syncope and were diagnosed with congenital coronary artery disease.

Results

In total, eight patients were included in the study with a median age of 12.5 ± 2.7 (8–16) years. In total, four of them were males, and four were females. Six of the eight patients were diagnosed with right anomalous coronary artery from the opposite sinus (R-ACAOS), while two patients were diagnosed with left anomalous coronary artery from the opposite sinus (L-ACAOS). The most frequent inducement was exercise, and the commonest prodromes were dizziness and blurred vision. Serum cardiac markers and exercise electrocardiography test (EET) were normal in seven of the patients. The majority of cases had abnormal electrocardiograms (ECGs), but only two of them manifested elevated/depressed ST-T segments. In total, seven patients had positive head-up tilt test (HUT). Echocardiography and coronary artery computed tomography angiography (CTA) were performed to aid the diagnosis. Coronary unroofing procedures were conducted in four patients, and none of them reported syncope after the surgery. The other four patients received routine medical treatment for vasovagal-like syncope. In total, two patients out of them became asymptomatic, and in the other two patients, episodes of syncope were reduced, but they still required medical treatment.

Conclusion

Congenital coronary artery anomalies in children with syncope need prompt attention. Though ECG and echocardiography are the common methods for investigating cardiac syncope, they have limited ability to find coronary artery anomalies. When coronary artery anomalies are suspected, coronary CTA should be considered.
Comprehensive Assessment of Indian Variations in the Druggable Kinome Landscape Highlights Distinct Insights at the Sequence, Structure and Pharmacogenomic Stratum
Authors: Panda Gayatri , Mishra Neha , Sharma Disha , Kutum Rintu , Bhoyar Rahul C. , Jain Abhinav , Imran Mohamed , Senthilvel Vigneshwar , Divakar Mohit Kumar , Mishra Anushree , Garg Parth , Banerjee Priyanka , Sivasubbu Sridhar , Scaria Vinod , Ray Arjun
Published: July 2022

India confines more than 17% of the world’s population and has a diverse genetic makeup with several clinically relevant rare mutations belonging to many sub-group which are undervalued in global sequencing datasets like the 1000 Genome data (1KG) containing limited samples for Indian ethnicity. Such databases are critical for the pharmaceutical and drug development industry where diversity plays a crucial role in identifying genetic disposition towards adverse drug reactions. A qualitative and comparative sequence and structural study utilizing variant information present in the recently published, largest curated Indian genome database (IndiGen) and the 1000 Genome data was performed for variants belonging to the kinase coding genes, the second most targeted group of drug targets. The sequence-level analysis identified similarities and differences among different populations based on the nsSNVs and amino acid exchange frequencies whereas a comparative structural analysis of IndiGen variants was performed with pathogenic variants reported in UniProtKB Humsavar data. The influence of these variations on structural features of the protein, such as structural stability, solvent accessibility, hydrophobicity, and the hydrogen-bond network was investigated. In-silico screening of the known drugs to these Indian variation-containing proteins reveals critical differences imparted in the strength of binding due to the variations present in the Indian population. In conclusion, this study constitutes a comprehensive investigation into the understanding of common variations present in the second largest population in the world and investigating its implications in the sequence, structural and pharmacogenomic landscape. The preliminary investigation reported in this paper, supporting the screening and detection of ADRs specific to the Indian population could aid in the development of techniques for pre-clinical and post-market screening of drug-related adverse events in the Indian population.
Effects of Image Dataset Configuration on the Accuracy of Rice Disease Recognition Based on Convolution Neural Network
Authors: Zhou Huiru , Deng Jie , Cai Dingzhou , Lv Xuan , Wu Bo Ming
Published: July 2022

In recent years, the convolution neural network has been the most widely used deep learning algorithm in the field of plant disease diagnosis and has performed well in classification. However, in practice, there are still some specific issues that have not been paid adequate attention to. For instance, the same pathogen may cause similar or different symptoms when infecting plant leaves, while the same pathogen may cause similar or disparate symptoms on different parts of the plant. Therefore, questions come up naturally: should the images showing different symptoms of the same disease be in one class or two separate classes in the image database? Also, how will the different classification methods affect the results of image recognition? In this study, taking rice leaf blast and neck blast caused by Magnaporthe oryzae, and rice sheath blight caused by Rhizoctonia solani as examples, three experiments were designed to explore how database configuration affects recognition accuracy in recognizing different symptoms of the same disease on the same plant part, similar symptoms of the same disease on different parts, and different symptoms on different parts. The results suggested that when the symptoms of the same disease were the same or similar, no matter whether they were on the same plant part or not, training combined classes of these images can get better performance than training them separately. When the difference between symptoms was obvious, the classification was relatively easy, and both separate training and combined training could achieve relatively high recognition accuracy. The results also, to a certain extent, indicated that the greater the number of images in the training data set, the higher the average classification accuracy.
Ectopic Overexpression of CsECR From Navel Orange Increases Cuticular Wax Accumulation in Tomato and Enhances Its Tolerance to Drought Stress
Authors: Liu Dechun , Guo Wenfang , Guo Xinyue , Yang Li , Hu Wei , Kuang Liuqing , Huang Yingjie , Xie Jingheng , Liu Yong
Published: July 2022

Drought stress often occurred in citrus to limit its growth, distribution, and fruit quality. Cuticular waxes play an important role in regulating plant tolerance to drought stress. Plant enoyl-CoA reductase (ECR) is involved in the biosynthesis of cuticular waxes and catalyzes the last step of very long-chain fatty acids (VLCFAs) elongation. In this study, a putative ECR gene, named CsECR, was cloned from “Newhall” navel orange. CsECR protein has high identities with other plant ECR proteins and contained a conserved NADP/NAD-binding motif and three conserved functional sites. The highest expression of CsECR was observed in leaves, followed by stems, flavedos, ovaries, juice sacs, stigmas, stamens, albedos, and petals. Besides, the expression of CsECR was significantly induced by PEG6000 and ABA treatments. Ectopic overexpression of CsECR increased the contents of total waxes and aliphatic wax fractions (n-fatty acids, unsaturated fatty acids, n-alkanes, alkenes, iso-, and anteiso-alkanes) in the leaves and fruits of the transgenic tomato. Furthermore, ectopic overexpression of CsECR reduced the cuticle permeability in the leaves and fruits of the transgenic tomato and increased its tolerance to drought stress. Taken together, our results revealed that CsECR plays an important role in plant response to drought stresses by regulating cuticular wax biosynthesis.
Memorable Tourism Experiences in Red Tourism: The Case of Jiangxi, China
Authors: Zhou Xuefei , Wong Jose Weng Chou , Wang Shan (Anna)
Published: July 2022

Red tourism, as a form of special interest tourism (SIT), becomes widespread among Chinese tourists. This study aims to explore memorable tourism experiences (MTEs) in red tourism destinations and examines how country competence affects intention to visit similar destinations through the influences on MTEs, destination image, red tourism place attachment, and overall satisfaction. The partial least squares structural equation modeling (PLS-SEM) analysis is utilized to analyze the data from 556 tourists. Empirical results reveal that country competence positively influences MTEs and destination image. Furthermore, both MTEs and destination image influence overall satisfaction and red tourism place attachment, but do not influence intention to visit other similar destinations; the relationships between overall satisfaction, intention to visit other similar destinations, and place attachment are all confirmed as well. This study represents one of the few studies that classify red tourism as a form of historical-based SIT, with the purpose of promoting country competence. The outcomes provide a better understanding of both scholars and practitioners of historical-based SIT planning and businesses on how to promote destination image and country competence.
The Relationship Between Public Risk Familiarity and Mental Health During the COVID-19 Epidemic: A Moderated Mediation Model
Authors: Qiu Rui , Zhu Xia
Published: July 2022

In order to explore, from the perspective of the social ecological model, the relationship and its mechanism linking public risk familiarity and mental health during the new coronary pneumonia epidemic, the new coronary pneumonia epidemic risk perception scale, psychological resilience scale, Chinese mental health scale, and SARS familiarity scale were used 741 members of the public were surveyed as research objects. The results show that: (1) When gender, age, and educational background are controlled, risk familiarity has a significant positive predictive effect on public mental health; (2) Risk familiarity predicts mental health through the mediating effect of mental toughness; (3) The mediating effect of mental toughness is moderated by the public’s familiarity with SARS. Specifically, for members of the public with low SARS familiarity, the indirect effect of risk familiarity on mental health through mental toughness is smaller than that for those with high SARS familiarity. The results of this study integrate psychological resilience into the theory of risk cognition, which has implications for the improvement of public mental health.