bluuebunny/crossref_metadata_2025 huggingface dataset:
Fidelity of a Bacterial DNA Polymerase in Microgravity, a Model for Human Health in Space
Authors: Rosenstein Aaron H , Walker Virginia K
Published: December 2021

Long-term space missions will expose crew members, their cells as well as their microbiomes to prolonged periods of microgravity and ionizing radiation, environmental stressors for which almost no earth-based organisms have evolved to survive. Despite the importance of maintaining genomic integrity, the impact of these stresses on DNA polymerase-mediated replication and repair has not been fully explored. DNA polymerase fidelity and replication rates were assayed under conditions of microgravity generated by parabolic flight and compared to earth-like gravity. Upon commencement of a parabolic arc, primed synthetic single-stranded DNA was used as a template for one of two enzymes (Klenow fragment exonuclease+/−; with and without proofreading exonuclease activity, respectively) and were quenched immediately following the 20 s microgravitational period. DNA polymerase error rates were determined with an algorithm developed to identify experimental mutations. In microgravity Klenow exonuclease+ showed a median 1.1-fold per-base decrease in polymerization fidelity for base substitutions when compared to earth-like gravity (p = 0.02), but in the absence of proofreading activity, a 2.4-fold decrease was observed (p = 1.98 × 10−11). Similarly, 1.1-fold and 1.5-fold increases in deletion frequencies in the presence or absence of exonuclease activity (p = 1.51 × 10−7 and p = 8.74 × 10−13), respectively, were observed in microgravity compared to controls. The development of this flexible semi-autonomous payload system coupled with genetic and bioinformatic approaches serves as a proof-of-concept for future space health research.
Glycine Ameliorates Endoplasmic Reticulum Stress Induced by Thapsigargin in Porcine Oocytes
Authors: Yu Sicong , Gao Lepeng , Zhang Chang , Wang Yumeng , Lan Hainan , Chu Qianran , Li Suo , Zheng Xin
Published: December 2021

The endoplasmic reticulum (ER) is a multifunctional organelle in the cytoplasm that plays important roles in female mammalian reproduction. The endoplasmic reticulum and mitochondria interact to maintain the normal function of cells by maintaining intracellular calcium homeostasis. As proven by previous research, glycine (Gly) can regulate the intracellular free calcium concentration ([Ca2+]i) and enhance mitochondrial function to improve oocyte maturation in vitro. The effect of Gly on ER function during oocyte in vitro maturation (IVM) is not clear. In this study, we induced an ER stress model with thapsigargin (TG) to explore whether Gly can reverse the ER stress induced by TG treatment and whether it is associated with calcium regulation. The results showed that the addition of Gly could improve the decrease in the average cumulus diameter, the first polar body excretion rate caused by TG-induced ER stress, the cleavage rate and the blastocyst rate. Gly supplementation could reduce the ER stress induced by TG by significantly improving the ER levels and significantly downregulating the expression of genes related to ER stress (Xbp1, ATF4, and ATF6). Moreover, Gly also significantly alleviated the increase in reactive oxygen species (ROS) levels and the decrease in mitochondrial membrane potential (ΔΨ m) to improve mitochondrial function in porcine oocytes exposed to TG. Furthermore, Gly reduced the [Ca2+]i and mitochondrial Ca2+ ([Ca2+]m) levels and restored the ER Ca2+ ([Ca2+]ER) levels in TG-exposed porcine oocytes. Moreover, we found that the increase in [Ca2+]i may be caused by changes in the distribution and expression of inositol 1,4,5-triphosphate receptor (IP3R1) and voltage-dependent anion channel 1 (VDAC1), while Gly can restore the distribution and expression of IP3R1 and VDAC1 to normal levels. Apoptosis-related indexes (Caspase 3 activity and Annexin-V) and gene expression Bax, Cyto C, and Caspase 3) were significantly increased in the TG group, but they could be restored by adding Gly. Our results suggest that Gly can ameliorate ER stress and apoptosis in TG-exposed porcine oocytes and can further enhance the developmental potential of porcine oocytes in vitro.
Molecular and Mechanical Cues for Somite Periodicity
Authors: Linde-Medina Marta , Smit Theodoor H.
Published: December 2021

Somitogenesis refers to the segmentation of the paraxial mesoderm, a tissue located on the back of the embryo, into regularly spaced and sized pieces, i.e., the somites. This periodicity is important to assure, for example, the formation of a functional vertebral column. Prevailing models of somitogenesis are based on the existence of a gene regulatory network capable of generating a striped pattern of gene expression, which is subsequently translated into periodic tissue boundaries. An alternative view is that the pre-pattern that guides somitogenesis is not chemical, but of a mechanical origin. A striped pattern of mechanical strain can be formed in physically connected tissues expanding at different rates, as it occurs in the embryo. Here we argue that both molecular and mechanical cues could drive somite periodicity and suggest how they could be integrated.
Construction and Validation of a Novel Pyroptosis-Related Gene Signature to Predict the Prognosis of Uveal Melanoma
Authors: Cao Yuan , Xie Jiaheng , Chen Liang , Hu Yiming , Zhai Leili , Yuan Jin , Suo Long , Shen Yaming , Ye Rong , Li Jiajun , Gong Zixuan , Dong Yunfan , Bao Wei , Li Huan , Wang Ming
Published: December 2021

Uveal melanoma is the most common primary intraocular tumor with a poor prognosis. Currently, treatment for UVM is limited, and the development of drug resistance and tumor recurrence are common. Therefore, it is important to identify new prognostic biomarkers of UVM and explore their role in the tumor microenvironment. Pyroptosis is a way of cell programmed death, and related research is in full throttle. However, the role of pyroptosis in UVM is unclear. In this study, we constructed the prognosis model of pyroptosis-related genes of UVM. This model can accurately guide the prognosis of UVM, and different groups differ in immune infiltration. We further verified our results in cell experiments. To some extent, our study can provide new ideas for the diagnosis and treatment of UVM.
Multiple DSB Resection Activities Redundantly Promote Alternative End Joining-Mediated Class Switch Recombination
Authors: Sun Xikui , Bai Jingning , Xu Jiejie , Xi Xiaoli , Gu Mingyu , Zhu Chengming , Xue Hongman , Chen Chun , Dong Junchao
Published: December 2021

Alternative end joining (A-EJ) catalyzes substantial level of antibody class switch recombination (CSR) in B cells deficient for classical non-homologous end joining, featuring increased switch (S) region DSB resection and junctional microhomology (MH). While resection has been suggested to initiate A-EJ in model DSB repair systems using engineered endonucleases, the contribution of resection factors to A-EJ-mediated CSR remains unclear. In this study, we systematically dissected the requirement for individual DSB resection factors in A-EJ-mediated class switching with a cell-based assay system and high-throughput sequencing. We show that while CtIP and Mre11 both are mildly required for CSR in WT cells, they play more critical roles in mediating A-EJ CSR, which depend on the exonuclease activity of Mre11. While DNA2 and the helicase/HRDC domain of BLM are required for A-EJ by mediating long S region DSB resection, in contrast, Exo1’s resection-related function does not play any obvious roles for class switching in either c-NHEJ or A-EJ cells, or mediated in an AID-independent manner by joining of Cas9 breaks. Furthermore, ATM and its kinase activity functions at least in part independent of CtIP/Mre11 to mediate A-EJ switching in Lig4-deficient cells. In stark contrast to Lig4 deficiency, 53BP1-deficient cells do not depend on ATM/Mre11/CtIP for residual joining. We discuss the roles for each resection factor in A-EJ-mediated CSR and suggest that the extent of requirements for resection is context dependent.
Chromatin Interaction Responds to Breast Muscle Development and Intramuscular Fat Deposition Between Chinese Indigenous Chicken and Fast-Growing Broiler
Authors: Tian Weihua , Wang Zhang , Wang Dandan , Zhi Yihao , Dong Jiajia , Jiang Ruirui , Han Ruili , Li Zhuanjian , Kang Xiangtao , Li Hong , Liu Xiaojun
Published: December 2021

Skeletal muscle development and intramuscular fat (IMF) content, which positively contribute to meat production and quality, are regulated by precisely orchestrated processes. However, changes in three-dimensional chromatin structure and interaction, a newly emerged mediator of gene expression, during the skeletal muscle development and IMF deposition have remained unclear. In the present study, we analyzed the differences in muscle development and IMF content between one-day-old commercial Arbor Acres broiler (AA) and Chinese indigenous Lushi blue-shelled-egg chicken (LS) and performed Hi-C analysis on their breast muscles. Our results indicated that significantly higher IMF content, however remarkably lower muscle fiber diameter was detected in breast muscle of LS chicken compared to that of AA broiler. The chromatin intra-interaction was prior to inter-interaction in both AA and LS chicken, and chromatin inter-interaction was heavily focused on the small and gene-rich chromosomes. For genomic compartmentalization, no significant difference in the number of B type compartments was found, but AA had more A type compartments versus LS. The A/B compartment switching of AA versus LS showed more A to B switching than B to A switching. There were no significant differences in the average sizes and distributions of topologically associating domains (TAD). Additionally, approximately 50% of TAD boundaries were overlapping. The reforming and disappearing events of TAD boundaries were identified between AA and LS chicken breast muscles. Among these, the HMGCR gene was located in the TAD-boundary regions in AA broilers, but in TAD-interior regions in LS chickens, and the IGF2BP3 gene was located in the AA-unique TAD boundaries. Both HMGCR and IGF2BP3 genes exhibited increased mRNA expression in one-day-old AA broiler breast muscles. It was demonstrated that the IGF2BP3 and HMGCR genes regulated by TAD boundary sliding were potential biomarkers for chicken breast muscle development and IMF deposition. Our data not only provide a valuable understanding of higher-order chromatin dynamics during muscle development and lipid accumulation but also reveal new insights into the regulatory mechanisms of muscle development and IMF deposition in chicken.
RETRACTED: A Green Synthesis Strategy of Binuclear Catalyst for the C-C Cross-Coupling Reactions in the Aqueous Medium: Hiyama and Suzuki–Miyaura Reactions as Case Studies
Authors: Ghamari Kargar Pouya , Bagherzade Ghodsieh
Published: December 2021

Cellulose, as a green and available phytochemical, was immobilized on the surface of magnetite nanoparticles then doped with imidazole and Co. complex (Fe3O4@CNF ∼ ImSBL ∼ Co.) and used as a water-dispersible, recyclable and efficient nano catalyst for the synthesis of C−C cross-coupling reactions including fluoride-free Hiyama and Suzuki reactions in an aqueous medium as an efficient and vital solvent, due to their high application and importance in various fields of science. Different spectroscopic and microscopic techniques were used for the catalyst characterization such XRD, FESEM, TEM, FT-IR, EDX, DLS, VSM, UV-Vis, and ICP analyses. The presence of imidazole as ionic section tags with hydrophilic character on the Co-complex supported on magnetic nanoparticles provides dispersion of the catalyst particles in water, which leads to both higher catalytic performance and also facile catalyst recovery and reuse six times by successive extraction and final magnetic separation. High catalytic activity was found for the catalyst and high to excellent efficiency was obtained for all Suzuki (80–98% yield; E factor: 1.1–1.9) and Hiyama (87–98% yield; E factor: 0.26–1.1) derivatives in short reaction times under mild reaction conditions in the absence of any hazardous or expensive materials. There is not any noticeable by-product found whether for Suzuki or Hiyama derivatives, which reflects the high selectivity and also the lower the E factor the more favorable is the process in view of green chemistry. The bi-aryls were achieved from the reaction of various aryl iodides/bromides and even chlorides as the highly challenging substrates, which are more available and cheaper, with triethoxyphenylsilane or phenylboronic acid. To prove the performance of the catalyst components (synergistic of SBL ∼ Co. and IL), its different homologs were incorporated individually and studied for a model reaction. Exclusively, this is an introductory statement on the use of Cobalt binuclear symmetric ionic liquid catalysts in Hiyama reactions.
Azole Compounds as Inhibitors of Candida albicans: QSAR Modelling
Authors: Gheidari Davood , Mehrdad Morteza , Ghahremani Mahboubeh
Published: December 2021

Candida albicans is a pathogenic opportunistic yeast found in the human gut flora. It may also live outside of the human body, causing diseases ranging from minor to deadly. Candida albicans begins as a budding yeast that can become hyphae in response to a variety of environmental or biological triggers. The hyphae form is responsible for the development of multidrug resistant biofilms, despite the fact that both forms have been associated to virulence Here, we have proposed a linear and SPA-linear quantitative structure activity relationship (QSAR) modeling and prediction of Candida albicans inhibitors. A data set that consisted of 60 derivatives of benzoxazoles, benzimidazoles, oxazolo (4, 5-b) pyridines have been used. In this study, that after applying the leverage analysis method to detect outliers’ molecules, the total number of these compounds reached 55. SPA-MLR model shows superiority over the multiple linear regressions (MLR) by accounting 90% of the Q2 of anti-fungus derivatives ‘activity. This paper focuses on investigating the role of SPA-MLR in developing model. The accuracy of SPA-MLR model was illustrated using leave-one-out (LOO). The mean effect of descriptors and sensitivity analysis show that RDF090u is the most important parameter affecting the as behavior of the inhibitors of Candida albicans.
Successful Deer Management in Scotland Requires Less Conflict Not More
Authors: Kirkland Hannah , Hare Darragh , Daniels Mike , Krofel Miha , Rao Shaila , Chapman Tatiana , Blossey Bernd
Published: December 2021

What would successful deer management look like in Scotland? To some, flourishing populations of native wild deer represent success. But to others, negative impacts such as damage to woodlands and peatlands, agricultural and forestry losses, deer-vehicle collisions, and facilitating Lyme disease spread represent failure. Conflicting interests and incentives among people involved in deer management mean a common definition of success, and therefore clear management targets, remain elusive. While some environmental groups urgently call for an increase in the number of deer culled (shot) each year, other stakeholders aim to maximize deer numbers. Overcoming this governance failure will require clearly articulated, scientifically valid, and socially acceptable socio-ecological objectives to be co-produced by a broad range of stakeholders. Systematic monitoring of deer impacts will also be needed to evaluate the ability of specific management interventions to achieve defined objectives. Reintroducing Eurasian lynx (Lynx lynx) has been suggested as a means to reduce deer numbers and their negative ecological and socioeconomic impacts. However, evidence of lynx impacts on deer numbers, deer impacts, and social conflicts over deer suggest lynx reintroduction alone would not effectively reduce negative impacts of deer in Scotland, though it could be part of a broader solution. In the short-term, achieving sustainable numbers of deer in Scotland will require a substantial increase in the number of deer culled and effective changes to the way deer management is incentivized, regulated, implemented, and monitored.
Does Warfarin or Rivaroxaban at Low Anticoagulation Intensity Provide a Survival Benefit to Asian Patients With Atrial Fibrillation?
Authors: Lin Dong , Chen Yequn , Yong Jian , Wu Shiwan , Zhou Yan , Li Weiping , Tan Xuerui , Liu Ruisheng
Published: December 2021

Background: Low-dose rivaroxaban and low-intensity warfarin are widely used in Asia for patients with atrial fibrillation (AF). However, in Asians, it is unclear whether low-dose rivaroxaban and low-intensity warfarin can improve the prognosis of AF. In this study, we investigate the survival benefits of low-dose rivaroxaban and low-intensity warfarin in Asian patients with AF in clinical practice.

Methods: This cohort study used medical records in a single tertiary hospital in China, between 2019 and 2020, to identify patients with AF who used rivaroxaban or warfarin, or had no anticoagulant therapy. Follow-ups were performed through telephone contact or medical record review. Cox proportional hazards models were used to compare the risk of mortality of patients in the anticoagulant-untreated group vs. warfarin-treated groups and rivaroxaban-treated groups.

Results: A total of 1727 AF patients, discharged between 2019 and 2020, were enrolled in this cohort, of which 873 patients did not use any anticoagulant, 457 patients received warfarin and 397 patients used rivaroxaban. Multivariable analysis showed that, of all the warfarin groups, patients with an international normalized ratio (INR) below 2, good INR control, or poor INR control had a significantly lower risk of mortality compared with that of patients without anticoagulants (HR 0.309, p = 0.0001; HR 0.387, p = 0.0238; HR 0.363, p < 0.0001). Multivariable Cox proportional hazard analyses also demonstrated that, compared with the no anticoagulant group, all rivaroxaban dosage groups (≤10 mg, HR 0.456, p = 0.0129; 15 mg, HR 0.246, p = 0.0003; 20 mg, HR 0.264, p = 0.0237) were significantly associated with a lower risk of mortality.

Conclusion: Despite effects being smaller than observed with recommended optimal anticoagulation, the use of warfarin with an INR below 2, poor INR control and the use of low-dose rivaroxaban may still provide survival benefits, suggesting viable alternatives that enable physicians to better resolve decisional conflicts concerning the risks and benefits of anticoagulant therapies, as well as for patients in need of but unable to receive standard anticoagulant therapy due to bleeding risk or other factors, such as financial burden, concerns of adverse outcomes, as well as low treatment compliance and persistence.
Machine Learning to Predict Long-Term Cardiac-Relative Prognosis in Patients With Extra-Cardiac Vascular Disease
Authors: Lin Guisen , Liu Qile , Chen Yuchen , Zong Xiaodan , Xi Yue , Li Tingyu , Yang Yuelong , Zeng An , Chen Minglei , Liu Chen , Liang Yanting , Xu Xiaowei , Huang Meiping
Published: December 2021

Aim: Patients with ischemic stroke (IS), transient ischemic attack (TIA), and/or peripheral artery disease (PAD) represent a population with an increased risk of coronary artery disease. Prognostic risk assessment to identify those with the highest risk that may benefit from more intensified treatment remains challenging. To explore the feasibility and capability of machine learning (ML) to predict long-term adverse cardiac-related prognosis in patients with IS, TIA, and/or PAD.

Methods: We analyzed 636 consecutive patients with a history of IS, TIA, and/or PAD. All patients underwent a coronary CT angiography (CCTA) scan. Thirty-five clinical data and 34 CCTA metrics underwent automated feature selection for ML model boosting. The clinical outcome included all-cause mortality (ACM) and major adverse cardiac events (MACE) (ACM, unstable angina requiring hospitalization, non-fatal myocardial infarction (MI), and revascularization 90 days after the index CCTA).

Results: During the follow-up of 3.9 ± 1.6 years, 21 patients had unstable angina requiring hospitalization, eight had a MI, 23 had revascularization and 13 deaths. ML demonstrated a significant higher area-under-curve compared with the modified Duke index (MDI), segment stenosis score (SSS), segment involvement score (SIS), and Framingham risk score (FRS) for the prediction of ACM (ML:0.92 vs. MDI:0.66, SSS:0.68, SIS:0.67, FRS:0.51, all P < 0.001) and MACE (ML:0.84 vs. MDI:0.82, SSS:0.76, SIS:0.73, FRS:0.53, all P < 0.05).

Conclusion: Among the patients with IS, TIA, and/or PAD, ML demonstrated a better capability of predicting ACM and MCAE than clinical scores and CCTA metrics.
Arrhythmogenic Hearts in PKD2 Mutant Mice Are Characterized by Cardiac Fibrosis, Systolic, and Diastolic Dysfunctions
Authors: Amirrad Farideh , Pala Rajasekharreddy , Shamloo Kiumars , Muntean Brian S. , Nauli Surya M.
Published: December 2021

Autosomal dominant polycystic kidney disease (PKD) is a hereditary disorder affecting multiple organs, including the heart. PKD has been associated with many cardiac abnormalities including the arrhythmogenic remodeling in clinical evaluations. In our current study, we hypothesized that Pkd2 gene mutation results in structural and functional defects in the myocardium. The structural and functional changes of Pkd2 mutant hearts were analyzed in the myocardial-specific Pkd2 knockout (KO) mouse. We further assessed a potential role of TGF-b1 signaling in the pathology of Pkd2-KO hearts. Hearts from age-matched 6-month-old MyH6•Pkd2wt/wt (control or wild-type) and MyH6•Pkd2flox/flox (mutant or Pkd2-KO) mice were used to study differential heart structure and function. Cardiac histology was used to study structure, and the “isolated working heart” system was adapted to mount and perfuse mouse heart to measure different cardiac parameters. We found that macrophage1 (M1) and macrophage 2 (M2) infiltration, transforming growth factor (TGF-b1) and TGF-b1 receptor expressions were significantly higher in Pkd2-KO, compared to wild-type hearts. The increase in the extracellular matrix in Pkd2-KO myocardium led to cardiac hypertrophy, interstitial and conduction system fibrosis, causing cardiac dysfunction with a predisposition to arrhythmia. Left ventricular (LV) expansion or compliance and LV filling were impaired in fibrotic Pkd2-KO hearts, resulted in diastolic dysfunction. LV systolic contractility and elastance decreased in fibrotic Pkd2-KO hearts, resulted in systolic dysfunction. Compared to wild-type hearts, Pkd2-KO hearts were less responsive to the pharmacological stress-test and changes in preload. In conclusion, Pkd2-KO mice had systolic and diastolic dysfunction with arrhythmogenic hearts.
A Systematic Review on Model Watermarking for Neural Networks
Authors: Boenisch Franziska
Published: December 2021

Machine learning (ML) models are applied in an increasing variety of domains. The availability of large amounts of data and computational resources encourages the development of ever more complex and valuable models. These models are considered the intellectual property of the legitimate parties who have trained them, which makes their protection against stealing, illegitimate redistribution, and unauthorized application an urgent need. Digital watermarking presents a strong mechanism for marking model ownership and, thereby, offers protection against those threats. This work presents a taxonomy identifying and analyzing different classes of watermarking schemes for ML models. It introduces a unified threat model to allow structured reasoning on and comparison of the effectiveness of watermarking methods in different scenarios. Furthermore, it systematizes desired security requirements and attacks against ML model watermarking. Based on that framework, representative literature from the field is surveyed to illustrate the taxonomy. Finally, shortcomings and general limitations of existing approaches are discussed, and an outlook on future research directions is given.
Young People's Use of Digital Tools to Support Their Mental Health During Covid-19 Restrictions
Authors: Pretorius Claudette , Coyle David
Published: December 2021

Young adulthood represents a sensitive period for young people's mental health. The lockdown restrictions associated with the COVID-19 pandemic have reduced young people's access to traditional sources of mental health support. This exploratory study aimed to investigate the online resources young people were using to support their mental health during the first lockdown period in Ireland. It made use of an anonymous online survey targeted at young people aged 18–25. Participants were recruited using ads on social media including Facebook, Twitter, Instagram, and SnapChat. A total of 393 respondents completed the survey. Many of the respondents indicated that they were using social media (51.4%, 202/393) and mental health apps (32.6%, 128/393) as sources of support. Fewer were making use of formal online resources such as charities (26%, 102/393) or professional counseling services (13.2%, 52/393). Different social media platforms were used for different purposes; Facebook was used for support groups whilst Instagram was used to engage with influencers who focused on mental health issues. Google search, recommendations from peers and prior knowledge of services played a role in how resources were located. Findings from this survey indicate that digital technologies and online resources have an important role to play in supporting young people's mental health. The COVID-19 pandemic has highlighted these digital tool's potential as well as how they can be improved to better meet young people's needs.
Study on the Long-Term Performance and Efficiency of Single-Well Circulation Coupled Groundwater Heat Pump System Based on Field Test
Authors: Zhu Ke , Zeng Yifan , Wu Qiang , Xu Shengheng , Tu Kun , Liu Xiaoxiu
Published: December 2021

Although buildings are often heated and cooled by single-well circulation coupled groundwater heat pump systems, few studies have evaluated the long-term performance of these systems. Therefore, the present study investigated the performance of these systems by analyzing the efficiency and energy consumption using 4 years of operating data. The results indicate that the coefficient of performance (COP) of the system gradually decreases because of thermal breakthrough or an accumulation of cold. In addition, the sealing clapboards could effectively slow down thermal breakthrough. In addition, compared with the heating period, the COP of the heat pump unit (HPU) and system increases, and its energy consumption decreases in the cooling period. It was also found that partial heat loss occurs when water from the single-well circulation outlet penetrates the main pipeline. Moreover, the heat-exchange efficiency of a single HPU exceeds that of multiple HPUs, and the COP of a HPU decreases during operation with increasing indoor temperature. Accordingly, we improved the performance of system by increasing the underground heat storage. Herein, we focus on optimizing the system design during long-term operation, which includes taking steps such as lengthening the sealing clapboards, using insulated pipes, discharging the remaining water and adding intelligent control devices.
Case Report: Insulinoma Presenting as Excessive Daytime Somnolence
Authors: Yu Zhennan , Wang Yongliang , Sun Yaqi , Wang Yumei , Tian Yayun , Ma Qinying , Fu Ying
Published: December 2021

Currently, undiagnosed insulinomas remain a difficult clinical dilemma because its symptoms in most cases can easily be misdiagnosed as other diseases. In this article, we present the case of a 14-year-old girl who presented to our hospital with recurrent episodes of excessive daytime sleepiness and abnormal behavior during sleep that had been going on for 3 months. Insulinoma is a rare neuroendocrine tumor that causes excessive release of insulin, resulting in episodes of hypoglycemia. It usually manifests as autonomic sympathetic symptoms. These symptoms resolved rapidly with the administration of glucose. After successful removal of the tumor, daytime sleepiness and abnormal nighttime behavior of the patient did not reappear.
The Polymorphism at PLCB4 Promoter (rs6086746) Changes the Binding Affinity of RUNX2 and Affects Osteoporosis Susceptibility: An Analysis of Bioinformatics-Based Case-Control Study and Functional Validation
Authors: Tsai Dung-Jang , Fang Wen-Hui , Wu Li-Wei , Tai Ming-Cheng , Kao Chung-Cheng , Huang Shih-Ming , Chen Wei-Teing , Hsiao Po-Jen , Chiu Chih-Chien , Su Wen , Wu Chia-Chun , Su Sui-Lung
Published: December 2021

Purpose

Genome-wide association studies have identified numerous genetic variants that are associated with osteoporosis risk; however, most of them are present in the non-coding regions of the genome and the functional mechanisms are unknown. In this study, we aimed to investigate the potential variation in runt domain transcription factor 2 (RUNX2), which is an osteoblast-specific transcription factor that normally stimulates bone formation and osteoblast differentiation, regarding variants within RUNX2 binding sites and risk of osteoporosis in postmenopausal osteoporosis (PMOP).

Methods

We performed bioinformatics-based prediction by combining whole genome sequencing and chromatin immunoprecipitation sequencing to screen functional SNPs in the RUNX2 binding site using data from the database of Taiwan Biobank; Case-control studies with 651 postmenopausal women comprising 107 osteoporosis patients, 290 osteopenia patients, and 254 controls at Tri-Service General Hospital between 2015 and 2019 were included. The subjects were examined for bone mass density and classified into normal and those with osteopenia or osteoporosis by T-scoring with dual-energy X-ray absorptiometry. Furthermore, mRNA expression and luciferase reporter assay were used to provide additional evidence regarding the associations identified in the association analyses. Chi-square tests and logistic regression were mainly used for statistical assessment.

Results

Through candidate gene approaches, 3 SNPs in the RUNX2 binding site were selected. A novel SNP rs6086746 in the PLCB4 promoter was identified to be associated with osteoporosis in Chinese populations. Patients with AA allele had higher risk of osteoporosis than those with GG+AG (adjusted OR = 6.89; 95% confidence intervals: 2.23–21.31, p = 0.001). Moreover, the AA genotype exhibited lower bone mass density (p < 0.05). Regarding mRNA expression, there were large differences in the correlation between PLCB4 and different RUNX2 alleles (Cohen’s q = 0.91). Functionally, the rs6086746 A allele reduces the RUNX2 binding affinity, thus enhancing the suppression of PLCB4 expression (p < 0.05).

Conclusions

Our results provide further evidence to support the important role of the SNP rs6086746 in the etiology of osteopenia/osteoporosis, thereby enhancing the current understanding of the susceptibility to osteoporosis. We further studied the mechanism underlying osteoporosis regulation by PLCB4.
Comprehensive Analyses of Type 1 Diabetes Ketosis- or Ketoacidosis-Related Genes in Activated CD56+CD16+ NK Cells
Authors: Shi Ruifeng , Dai Fang , He Yong , Sun Li , Xu Min , Deng Datong , Zhang Qiu
Published: December 2021

Objectives

Alterations in natural killer (NK) cells activity cause damage to pancreatic islets in type 1 diabetes mellitus (T1DM). The aim of this study is to identify T1DM ketosis- or ketoacidosis-related genes in activated CD56+CD16+ NK cells.

Methods

Microarray datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using the GEO2R tool. Enrichment analyses were performed using Metascape online database and GSEA software. Cell-specific gene co-expression network was built using NetworkAnalyst tools. Cytoscape software was used to identify hub genes and construct co-expressed networks. Target miRNAs were predicted based on the DIANA-micro T, miRDB, and miRWalk online databases.

Results

A total of 70 DEGs were identified between T1DM patients recovered from ketosis or ketoacidosis and healthy control blood samples in GSE44314. Among the DEGs, 10 hub genes were screened out. The mature NK cell-specific gene co-expression network for DEGs in T1DM was built using NetworkAnalyst tools. DEGs between activated CD56+CD16+ NK cells and CD56brightCD16- NK cells were identified from GSE1511. After intersection, 13 overlapping genes between GSE44314 and GSE1511 microarray datasets were screened out, in which 7 hub genes were identified. Additionally, 59 target miRNAs were predicted according to the 7 hub genes. After validating with the exosome miRNA expression profile dataset of GSE97123, seven differentially expressed miRNAs (DEmiRNAs) in plasma-derived exosome were selected. Finally, a mRNA–miRNA network was constructed, which was involved in the T1DM ketosis or ketoacidosis process.

Conclusion

This work identified seven hub genes in activated CD56+CD16+ NK cells and seven miRNAs in plasma-derived exosome as potential predictors of T1DM ketoacidosis, which provided a novel insight for the pathogenesis at the transcriptome level.
Transition of Lipid Accumulation Product Status and the Risk of Type 2 Diabetes Mellitus in Middle-Aged and Older Chinese: A National Cohort Study
Authors: Yu Jinyue , Yi Qian , Hou Leying , Chen Ge , Shen Yaojia , Song Yuan , Zhu Yimin , Song Peige
Published: December 2021

Background

Lipid accumulation product (LAP), a product of waist circumference (WC) and fasting triglycerides (TG), is a measure of lipid accumulation and an effective predictor of metabolic syndrome. This study aimed to evaluate the associations of LAP and its longitudinal transitions with type 2 diabetes mellitus (T2DM) among middle-aged and older Chinese.

Methods

Data were extracted from the China Health and Retirement Longitudinal Study (2011, 2013, 2015, and 2018). LAP was defined as (WC-65) ×TG for men, and (WC-58) ×TG for women. Participants were classified into high- and low-LAP groups at baseline, and subsequently into four transition patterns during 2011-2015: maintained-high, maintained-low, high-to-low, and low-to-high LAP. The longitudinal transition patterns of LAP on the development of T2DM were assessed by multivariable Cox frailty models.

Results

Overall, 7397 participants were included for analysis, among whom 849 (11.5%) developed T2DM between 2011 and 2018. Women with high-LAP levels at baseline presented a higher risk of T2DM (hazard ratios [HR]=1.37, 95% confidence interval [CI]: 1.07-1.77), while no significant association was found in men. Compared with women with maintained-low LAP pattern, those with transition patterns of low-to-high LAP and maintained-high LAP were at higher risk of T2DM (HR =1.99 and 1.98, both P<0.05); however, for men, the significantly positive association was only observed in maintained-high LAP transition pattern (HR=1.53, 95% CI: 1.04-2.23).

Conclusions

Elevated LAP levels and the transition patterns of maintained-high LAP and low-to-high LAP are significant risk factors for T2DM in women. Preventions are needed to combat T2DM at an early dyslipidemic stage.
Intersections in Neuropsychiatric and Metabolic Disorders: Possible Role of TRPA1 Channels
Authors: Sodhi Rupinder Kaur , Singh Raghunath , Bansal Yashika , Bishnoi Mahendra , Parhar Ishwar , Kuhad Anurag , Soga Tomoko
Published: December 2021

Neuropsychiatric disorders (NPDs) are a huge burden to the patient, their family, and society. NPDs have been greatly associated with cardio-metabolic comorbidities such as obesity, type-2 diabetes mellitus, dysglycaemia, insulin resistance, dyslipidemia, atherosclerosis, and other cardiovascular disorders. Antipsychotics, which are frontline drugs in the treatment of schizophrenia and off-label use in other NPDs, also add to this burden by causing severe metabolic perturbations. Despite decades of research, the mechanism deciphering the link between neuropsychiatric and metabolic disorders is still unclear. In recent years, transient receptor potential Ankyrin 1 (TRPA1) channel has emerged as a potential therapeutic target for modulators. TRPA1 agonists/antagonists have shown efficacy in both neuropsychiatric disorders and appetite regulation and thus provide a crucial link between both. TRPA1 channels are activated by compounds such as cinnamaldehyde, allyl isothiocyanate, allicin and methyl syringate, which are present naturally in food items such as cinnamon, wasabi, mustard, garlic, etc. As these are present in many daily food items, it could also improve patient compliance and reduce the patients’ monetary burden. In this review, we have tried to present evidence of the possible involvement of TRPA1 channels in neuropsychiatric and metabolic disorders and a possible hint towards using TRPA1 modulators to target appetite, lipid metabolism, glucose and insulin homeostasis and inflammation associated with NPDs.
Intelligent Fault Diagnosis Method of Wind Turbines Planetary Gearboxes Based on a Multi-Scale Dense Fusion Network
Authors: Huang Xinghua , Li Yuanyuan , Chai Yi
Published: December 2021

Due to the powerful capability of feature extraction, convolutional neural network (CNN) is increasingly applied to the fault diagnosis of key components of rotating machineries. Due to the shortcomings of traditional CNN-based fault diagnosis methods, the continuous convolution and pooling operations result in the constant decrease of feature resolution, which may cause the loss of some subtle fault information in the samples. This paper proposes a CNN-based model with improved structure multi-scale dense fusion network (MSDFN) to realize the fault diagnosis of wind turbines planetary gearboxes under complicated working conditions. First, the continuous wavelet transform is applied to preprocess the vibration signals, and the two-dimensional wavelet time-frequency diagrams are used as the network input. Then, the multi-scale feature fusion (MSFF) module and a feature of maximum (FoM) module are used in the extraction and classification stages of fault features, respectively. Next, the multi-scale features of each network layer are fused to enhance the fault features. Finally, the high fault diagnosis accuracy is achieved by extracting the separable fusion result of fault features. The proposed method achieves more than 99% fault diagnosis average accuracy on a planetary gearbox dataset. The comparative experimental results verify the effectiveness of the proposed method and its superiority to some mainstream approaches. The ablation study further confirms that MSFF module and FoM module play the positive role in fault diagnosis.
Characterizing the Influence of Organic Polymers on the Specific Reactivity of Particulate Remedial Amendments
Authors: Muller Katherine A. , Zhong Lirong , Bagwell Christopher E.
Published: December 2021

Commercially available particulate amendments demonstrate high reactivity for effective treatment of water soluble organic and inorganic contaminants in laboratory studies; however, transport of these particles is constrained in the subsurface. In many field applications, particulate amendments are mixed with organic polymers to enhance mobility for direct push applications or stabilize suspensions for high mass loadings. As such, the interactions between particulate amendments, organic polymers and contaminant species need to be systematically investigated to properly understand mechanistic processes that facilitate predictive performance metrics for specific applications in situ. In this study, batch experiments were conducted to quantify the effects of organic polymers (xanthan gum, guar gum, and sodium alginate), polymer concentration (800 and 4,000 mg/L), and aging (up to 28 days) on chromate treatment rate and capacity by two classes of amendments: reductants [granular zero-valent iron (gZVI), micron-ZVI (mZVI), sulfur modified iron (SMI)], and an adsorbent (bismuth sub-nitrate). When particulate amendments were suspended in polymer solutions, reductants retained between 84–100% of the amendment treatment capacity. Conversely, the adsorbent maintained 63–97% relative treatment capacity of the no-polymer control. Polymer solutions had a more pronounced impact on the rate of chromate removal; first order rates of chemical reduction decreased by as much as 70% and adsorption by up to 81% relative to the no-polymer controls. Polymer–amendment aging experiments also showed decreased Cr(VI) treatment capacity; reductants decreased by as much as 24% and adsorption decreased by as much as 44% after 28 days of incubation. While polymer suspensions are needed to aid the injection of particulate amendments into the subsurface, the results from this study indicate potential losses of treatment capacity and a decrease in the rate of remedial performance due to the physical and chemical interactions between polymer suspensions and reactive particulate amendments. Simple batch systems provide baseline characterization of tripartite interactions for the removal of Cr(VI). Additional work is needed to quantify the full impact of polymers on remedial outcomes under site relevant conditions at field scale.
Estimating Nitrogen Flows and Nitrogen Footprint for Agro-Food System of Rwanda Over the Last Five Decades: Challenges and Measures
Authors: Harerimana Barthelemy , Zhou Minghua , Shaaban Muhammad , Zhu Bo
Published: December 2021

This study presents the first detailed estimate of Rwanda’s nitrogen (N) flows and N footprint for food (NFfood) from 1961 to 2018. Low N fertilizer inputs, substandard production techniques, and inefficient agricultural management practices are focal causes of low crop yields, environmental pollution, and food insecurity. We therefore assessed the N budget, N use efficiency (NUE), virtual N factors (VNFs), soil N mining factors (SNMFs), and N footprint for the agro-food systems of Rwanda with consideration of scenarios of fertilized and unfertilized farms. The total N input to croplands increased from 14.6 kg N ha−1 yr−1 (1960s) to 34.1 kg N ha−1 yr−1 (2010–2018), while the total crop N uptake increased from 18 kg N ha−1yr−1 (1960s) to 28.2 kg N ha−1yr−1 (2010–2018), reflecting a decline of NUE from 124% (1960s) to 85% (2010–2018). Gaseous N losses of NH3, N2O, and NO increased from 0.45 (NH3), 0.03 (N2O), and 0.00 (NO) Gg N yr−1 (1960s) to 6.98 (NH3), 0.58 (N2O), and 0.10 (NO) Gg N yr−1 (2010–2018). Due to the low N inputs, SNMFs were in the range of 0.00 and 2.99 and the rice production, cash-crop production, and livestock production systems have greater SNMFs in Rwanda. The weighted NFfood per capita that presents the actual situation of fertilized and unfertilized croplands increased from 4.0 kg N cap−1 yr−1 (1960s) to 6.3 kg N cap−1 yr−1 (2010–2018). The NFfood per capita would increase from 3.5 kg N cap−1 yr−1 to 4.8 kg N cap−1 yr−1 under a scenario of all croplands without N fertilizer application and increase from 6.0 to 8.7 kg N cap−1 yr−1 under the situation of all croplands receiving N fertilizer. The per capita agro-food production accounted for approximately 58% of the national NFfood. The present study indicates that Rwanda is currently suffering from low N inputs, high soil N depletion, food insecurity, and environmental N losses. Therefore, suggesting that the implementation of N management policies of increasing agricultural N inputs and rehabilitating the degraded soils with organic amendments of human and animal waste needs to be carefully considered in Rwanda.
Landscape-Scale Effects of Fire, Cats, and Feral Livestock on Threatened Savanna Mammals: Unburnt Habitat Matters More Than Pyrodiversity
Authors: Radford Ian J. , Corey Ben , Carnes Karin , Shedley Erica , McCaw Lachie , Woolley Leigh-Ann
Published: December 2021

Northern Australia has undergone significant declines among threatened small and medium-sized mammals in recent decades. Conceptual models postulate that predation by feral cats is the primary driver, with changed disturbance regimes from fire and feral livestock in recent decades reducing habitat cover and exacerbating declines. However, there is little guidance on what scale habitat and disturbance attributes are most important for threatened mammals, and what elements and scale of fire mosaics actually support mammals. In this study, we test a series of hypotheses regarding the influence of site-scale (50 × 50 m) habitat and disturbance attributes, as well as local-scale (1 km radius), meta-local scale (3 km), landscape-scale (5 km) and meta-landscape scale (10 km) fire mosaic attributes on mammal abundance and richness. We found that habitat cover (rock, perennial grass, and shrub cover) at the site-scale had a positive effect, and disturbance factors (feral cats, fire, feral livestock) had a negative influence on mammal abundance and richness. Models supported site-scale habitat and disturbance factors as more important for mammals than broader-scale (local up to meta-landscape scale) fire mosaic attributes. Finally, we found that increasing the extent of ≥ 4 year unburnt habitat, and having an intermediate percentage (ca. 25%) of recently burnt (1-year burnt) habitat within the mosaic, were the most important functional elements of the fire mosaic at broad scales for mammals. Contrary to expectations, diversity of post-fire ages (‘pyrodiversity’) was negatively associated with mammal abundance and richness. These results highlight the need for management to promote retention of longer unburnt vegetation in sufficient patches across savanna landscapes (particularly of shrub and fruiting trees), maintain low-intensity patchy fire regimes, reduce the extent of intense late dry season wildfires, and to reduce the impact of feral livestock. This study provides further evidence for the role of feral cats in northern Australian mammal declines, and highlights the need for increased research into the efficacy of cat control methodologies in reducing biodiversity impacts in these extensive landscapes.
Natural and Anthropogenic Variation of Stand Structure and Aboveground Biomass in Niger Delta Mangrove Forests
Authors: Nwobi Chukwuebuka J. , Williams Mathew
Published: December 2021

Mangrove forests are important coastal wetlands because of the ecosystem services they provide especially their carbon potential. Mangrove forests productivity in the Niger Delta are poorly quantified and at risk of loss from oil pollution, deforestation, and invasive species. Here, we report the most extensive stem girth survey yet of mangrove plots for stand and canopy structure in the Niger Delta, across tidal and disturbance gradients. We established twenty-five geo-referenced 0.25-ha plots across two estuarine basins. We estimated aboveground biomass (AGB) from established allometric equations based on stem surveys. Leaf area index (LAI) was recorded using hemispherical photos. We estimated a mean AGB of 83.7 Mg ha–1 with an order of magnitude range, from 11 to 241 Mg ha–1. We found significantly higher plot biomass in close proximity to a protected site and tidal channels, and the lowest in the sites where urbanization and wood exploitation was actively taking place. The mean LAI was 1.45 and ranged fivefold from 0.46 to 2.41 and there was a significant positive correlation between AGB and LAI (R2 = 0.31). We divided the plots into two disturbance regimes and three nipa palm (Nypa fruticans) invasion levels. Lower stem diameter (5–15 cm) accounted for 70% of the total biomass in disturbed plots, while undisturbed regimes had a more even (∼25%) contribution of different diameter at breast height (DBH) size classes to AGB. Nipa palm invasion also showed a significant link to larger variations in LAI and the proportion of basal area removed from plots. We conclude that mangrove forest degradation and exploitation is removing larger stems (>15 cm DBH), preferentially from these mangroves forests and creates an avenue for nipa palm colonization. This research identifies opportunities to manage the utilization of mangrove resources and reduce any negative impact. Our data can be used with remote sensing to estimate biomass in the Niger Delta and the inclusion of soil, leaf properties and demographic rates can analyze mangrove-nipa competition in the region.