bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Verification of Feature Immune-Related Genes in Patients With Hypertrophic Cardiomyopathy Based on Bioinformatics Analyses
Authors: Zheng Xifeng , Liu Guangyan , Huang Ruina
Published: October 2021

Objective: To identify feature immune-related genes (IRGs) in patients with hypertrophic cardiomyopathy (HCM) and verify their ability to diagnose HCM.

Methods: The GSE160997 dataset on cardiac tissue from 18 HCM patients and 5 controls was downloaded from the Gene Expression Omnibus database. A false discovery rate <0.05 and |log2 fold change| >1 were the filters applied to identify the differentially expressed genes (DEGs). The differentially expressed IRGs were the intersection results between the DEGs and an IRG dataset from the IMMPORT database. The protein-protein interaction network of differentially expressed IRGs was constructed, and the top 20 hub genes with the most adjacent nodes in the network were selected. The least absolute shrinkage and selection operator regression algorithm and a random forest algorithm were used to identify the feature IRGs as biomarkers that were then verified against GSE36961.

Results: A total of 1079 DEGs were identified in GSE160997. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that immune-related mechanisms play an important role in the pathogenesis of HCM. A total of 121 differentially expressed IRGs were identified, and 5 feature IRGs were selected, 4 of which were confirmed as potential biomarkers of HCM by external verification with excellent discrimination ability. A diagnosis model of HCM based on the four feature IRGs was developed and visualized as a nomogram with a C-index of 0.925 (95% confidence interval 0.869–0.981).

Conclusion: Our study identified four feature IRGs as biomarkers for the diagnosis of HCM, offering an innovative perspective of the underlying immune-related pathological molecular mechanisms.
Delay-Dependent Stability Analysis of Load Frequency Control for Power System With EV Aggregator
Authors: Yuan Zhe-Li , Xu Da , Jin Li , Wang Hong-Zhang
Published: October 2021

In this paper, the stability of load frequency control (LFC) for delayed power systems with an electric vehicle (EV) aggregator is studied based on Lyapunov theory and linear matrix inequalities (LMIs). Through mechanism analysis, the LFC of power systems with an EV aggregator based on a proportional–integral–differential (PID) controller is modeled. By constructing a delay interval information correlation functional and estimating its derivative using Wirtinger inequality and extended reciprocally convex matrix inequality, a new stability analysis criterion is proposed. Finally, in order to verify its advantage, the proposed method is used to discuss the influence of EV aggregator gains and PID controller gains on the delay margins for LFC of power systems with EV aggregator participation in frequency regulation.
Socio-Economic Analysis of Climate Services in Disaster Risk Reduction: A Perspective on Pacific SIDS
Authors: Newth David , Gooley Geoff , Gunasekera Don
Published: October 2021

This paper explores methods and the key factors influencing socio-economic analysis of the role of climate services in disaster risk reduction, with a regional emphasis on Small Island Developing States in the western tropical Pacific. We analyse the role of traditional benefit-cost analysis especially in the context of evaluating the importance of science-based climate change services (i.e., relevant to current and future climate change over multi-decadal timescales) in disaster risk reduction at a national economy level. Our analysis is premised on a range of relevant social and economic metrics at a national economy scale, including surrogate indicators for specific disaster risk reduction sensitive sectors in context of both mitigation (transitional risk) and adaptation (physical risk) to climate change. Relative importance of different methodologies of socio-economic analysis (i.e., partial/sectoral vs economy-wide modelling), gaps in relevant data and information, and the role of the public and private sectors in mobilising resources and capability for facilitating such analysis are explored. Our paper also discusses the issues relating to investing in, producing and undertaking on-ground applications associated with disaster risk reduction using climate change services for both public good and private (-for-profit) benefit outcomes, and provides suggestions for further research to improve socio-economic analysis of Climate Information Services impacts.
Phenotypic Variation Through Ontogeny: Thyroid Axis Disruption During Larval Development in the Frog Pleurodema borellii
Authors: Fabrezi Marissa , Cruz Julio César
Published: October 2021

Studies of the effects of thyroid hormones on larval development in the frog Xenopus spp. have provided baseline information to identify developmental constraints and elucidate genetic and hormonal mechanisms driving development, growth, and life history transitions. However, this knowledge requires data based on other anurans to complete a comprehensive approach to the understanding of larval developmental diversity and phenotypic variation through ontogeny. Mesocosm experiments provide realistic data about environmental conditions and timing; this information is useful to describe anuran larval development and/or analyze endocrine disruption. In this study, mesocosm experiments of the larval development of the frog Pleurodema borellii were conducted to explore the consequences of thyroid axis disruption; the sensitivity of tadpoles to the methimazole (2.66 mg/l) and thyroxine (T4) (1.66 μg/l) was compared. These concentrations were selected based on previous studies in Pleurodema borellii. We test the effects of methimazole and thyroxine on development in early exposure (from beginning of larval development) and late exposure, 18 days after hatching, with doses administered every 48 h. Tadpoles were evaluated 31 days after hatching. Methimazole caused moderate hypertrophy of the thyroid gland, alteration in the growth rates, differentiation without inhibition of development, and an increase of developmental variability. Thyroxine produced slight atrophy of the thyroid gland, accelerated growth rates and differentiation, and minor developmental variability. In tadpoles at stages previous to metamorphose, skull development (differentiation of olfactory capsules, appearance of dermal bones, and cartilage remodeling) seemed to be unaltered by the disruptors. Moreover, similar abnormal morphogenesis converged in specimens under methimazole and thyroxine exposures. Abnormalities occurred in pelvic and pectoral girdles, and vent tube, and could have been originated at the time of differentiation of musculoskeletal tissues of girdles. Our results indicate that premetamorphic stages (Gosner Stages 25–35) are sensitive to minimal thyroid axis disruption, which produces changes in developmental rates; these stages would also be critical for appendicular musculoskeletal morphogenesis to achieve the optimal condition to start metamorphosis.
Axitinib Reverses Resistance to Anti-Programmed Cell Death-1 Therapy in a Patient With Renal Cell Carcinoma
Authors: Yang Yonghao , Huang Hao , Li Tiepeng , Gao Quanli , Song Yongping , Wang Zibing
Published: October 2021

Owing to broad and notable clinical anti-tumor activity, anti-programmed cell death-1 (PD-1)/anti-programmed cell death-ligand 1 (PD-L1) antibodies have been indicated for almost all types of cancer, and form a part of the current standard of care. However, a large proportion of patients do not respond to anti-PD-1/PD-L1 therapy (primary resistance), and responders often develop progressive disease (acquired resistance). The mechanisms of resistance are complex and largely unknown; therefore, overcoming resistance remains clinically challenging, and data on reversing anti-PD-1 resistance are scarce. Herein, we report the case of a 58-year-old woman with renal cell carcinoma associated with Xp11.2 translocation/transcription factor E3 gene fusion, who had already showed resistance to both anti-PD-1 monotherapy and standard-dose axitinib. However, she finally achieved a partial response with a continuous combination therapy comprising low-dose axitinib and anti-PD-1. We speculate that axitinib played a key role in reversing the primary resistance to anti-PD-1 therapy. Interestingly, we observed that the number of peripheral regulatory T cells increased after the standard-dose axitinib therapy, with accompanied tumor enlargement; however, after the dose was reduced, the number of regulatory T cells decreased gradually, and the tumor regressed. We also reviewed relevant literature, which supported the fact that low-dose axitinib might be more beneficial than standard-dose axitinib in assisting immunotherapy. Given that this is a single-case report, the immunomodulatory effect of axitinib requires further investigation.
Disruption of Glucocorticoid Action on CD11c+ Dendritic Cells Favors the Generation of CD4+ Regulatory T Cells and Improves Fetal Development in Mice
Authors: Diao Lianghui , Hierweger Alexandra Maximiliane , Wieczorek Agnes , Arck Petra Clara , Thiele Kristin
Published: October 2021

A wealth of innate and adaptive immune cells and hormones are involved in mounting tolerance towards the fetus, a key aspect of successful reproduction. We could recently show that the specific cross talk between the pregnancy hormone progesterone and dendritic cells (DCs) is significantly engaged in the generation of CD4+ FoxP3+ regulatory T (Treg) cells while a disruption led to placental alterations and intra-uterine growth restriction. Apart from progesterone, also glucocorticoids affect immune cell functions. However, their functional relevance in the context of pregnancy still needs clarification. We developed a mouse line with a selective knockout of the glucocorticoid receptor (GR) on DCs, utilizing the cre/flox system. Reproductive outcome and maternal immune and endocrine adaptation of Balb/c-mated C57Bl/6 GRflox/floxCD11ccre/wt (mutant) females was assessed on gestation days (gd) 13.5 and 18.5. Balb/c-mated C57Bl/6 GRwt/wtCD11ccre/wt (wt) females served as controls. The number of implantation and fetal loss rate did not differ between groups. However, we identified a significant increase in fetal weight in fetuses from mutant dams. While the frequencies of CD11c+ cells remained largely similar, a decreased expression of co-stimulatory molecules was observed on DCs of mutant females on gd 13.5, along with higher frequencies of CD4+ and CD8+ Treg cells. Histomorphological and gene expression analysis revealed an increased placental volume and an improved functional placental capacity in mice lacking the GR on CD11c+ DCs. In summary, we here demonstrate that the disrupted communication between GCs and DCs favors a tolerant immune microenvironment and improves placental function and fetal development.
Identification of Two Subsets of Murine DC1 Dendritic Cells That Differ by Surface Phenotype, Gene Expression, and Function
Authors: Hongo David , Zheng Pingping , Dutt Suparna , Pawar Rahul D. , Meyer Everett , Engleman Edgar G. , Strober Samuel
Published: October 2021

Classical dendritic cells (cDCs) in mice have been divided into 2 major subsets based on the expression of nuclear transcription factors: a CD8+Irf8+Batf3 dependent (DC1) subset, and a CD8-Irf4+ (DC2) subset. We found that the CD8+DC1 subset can be further divided into CD8+DC1a and CD8+DC1b subsets by differences in surface receptors, gene expression, and function. Whereas all 3 DC subsets can act alone to induce potent Th1 cytokine responses to class I and II MHC restricted peptides derived from ovalbumin (OVA) by OT-I and OT-II transgenic T cells, only the DC1b subset could effectively present glycolipid antigens to natural killer T (NKT) cells. Vaccination with OVA protein pulsed DC1b and DC2 cells were more effective in reducing the growth of the B16-OVA melanoma as compared to pulsed DC1a cells in wild type mice. In conclusion, the Batf3-/- dependent DC1 cells can be further divided into two subsets with different immune functional profiles in vitro and in vivo.
Implications of Community-Based Management of Marine Reserves in the Philippines for Reef Fish Communities and Biodiversity
Authors: Marriott Sara E. , Cox Courtney , Amolo Rizaller C. , Apistar Dean , Mancao Roquelito H. , de Mutsert Kim
Published: October 2021

Overfishing and destructive fishing practices are major threats to marine biodiversity in the Philippines, where over 1.9 million small-scale fishers are supported by these biodiverse marine communities. Nearly 50% of all marine fish capture in the Philippines is from artisanal fisheries, with much of it not reported or under-reported. Marine reserves, where fishing is prohibited have been created in many local government units to help restore and preserve this biodiversity. The success of these marine reserves is still under serious debate with effective management still representing a significant challenge. The lack of a governance system to centrally managed marine reserves has resulted in non-governmental organizations developing community-based management schemes. Using independent fisheries data from Rare’s Fish Forever program, we applied PERMANOVA, SIMPER and biodiversity index analyses to evaluate the community structure of reef fish in 20 sites within the Philippines. We analyzed the differences in fish assemblage inside and outside of these marine reserves, before and after community-based management had been implemented. We provide evidence that: (i) fish community structure changes within marine reserves after community-based management strategies are implemented; and (ii) community-based management of marine fisheries resources protects and promotes biodiversity inside, and in some cases, outside marine reserves. Variability across sites suggests that other social or ecological factors may be influencing the ability of marine reserves to fully protect biodiversity and marine resources. Small-scale fishers in the Philippines participate in mixed-catch harvests and depend on biodiversity and reef community structure for their livelihoods. Thus, this work has implications on how community-based management strategies for marine reserves and adjacent waters may be beneficial for the sustainability of small-scale fishers.
Ecological Trap or Favorable Habitat? First Evidence That Immature Sea Turtles May Survive at Their Range-Limits in the North-East Atlantic
Authors: Chambault Philippine , Gaspar Philippe , Dell’Amico Florence
Published: October 2021

Unusual environmental events can push marine animals outside their physiological tolerances through changes in trophic and/or thermal conditions. Such events typically increase the risk of stranding. Rescue Centers offer a unique opportunity to report animals in distress and satellite track rehabilitated individuals to identify potential new habitats and support an effective conservation of these endangered species. By combining sightings (1988–2020) and tracking data (2008–2020) collected along the French Atlantic and English Channel coasts, our study assessed if the Bay of Biscay is an ecological trap or a favorable habitat for immature sea turtles. The largest tracked individuals migrated westward to pelagic waters, likely toward their natal beaches, while smaller individuals remained within the Bay of Biscay (BoB) and crossed colder (mean: 17.8 ± 3.0°C) but more productive waters. The turtles’ directions differed from the ones of ocean currents, excluding a passive advection to these unexpected habitats. Although the BoB might be thermally unsuitable in winter, the higher micronekton biomass predicted in this region could offer a productive foraging habitat for immature turtles. However, the majority of the sightings referred to individuals stranded alive (75%), suggesting this area could also act as an ecological trap for the smallest individuals that are mostly reported in winter suffering cold-stunning. Assumed to be outside the species range, our results reveal a potential foraging ground in the North-East Atlantic for these young turtles, confirming the crucial role of the rehabilitation centers and the need to continue prioritizing conservation of these endangered species, particularly vulnerable at this stage and at such temperate latitudes.
Proteomic Response to Environmental Stresses in the Stolon of a Highly Invasive Fouling Ascidian
Authors: Li Xi , Li Shiguo , Cheng Jiawei , Fu Ruiying , Zhan Aibin
Published: October 2021

Ascidians, particularly those highly invasive ones, are typical fouling organisms to cause significantly negative ecological and economic influence in coastal ecosystems. Stolon, which is the unique structure of some solitary ascidians to complete the essential process of adhesion, possesses extremely high tolerance to environmental stresses during biofouling and invasions. However, the mechanisms underlying environmental tolerance remain largely unknown. Here, we used the quantitative proteomics technology, isobaric tags for relative and absolute quantitation (iTRAQ), to investigate the molecular response to environmental challenges (temperature and salinity) in the stolon of a highly invasive fouling ascidian, Ciona robusta. When compared with the control, a total of 75, 86, 123, and 83 differential abundance proteins were identified under low salinity, high salinity, low temperature, and high temperature stress, respectively. Bioinformatic analyses uncovered the key pathways under both temperature and salinity stresses, including “cytoskeleton,” “signal transduction,” and “posttranslational modification,” which were involved in stolon structure stability, protein synthesis, and stress response activation. Under the low salinity stress, the “extracellular matrix” pathway was identified to play a crucial role by regulating cell signal transduction and protein synthesis. To deal with the high salinity stress, stolon could store more energy by activating “carbohydrate/lipid transport” and “catabolism” pathways. The energy generated by “lipid metabolism” pathway might be beneficial to resist the low temperature stress. The upregulation of “cell cycle” pathway could inhibit cell growth, thus helping stolon conserve more energy against the high temperature stress. Our results here provide valuable references of candidate pathways and associated genes for studying mechanisms of harsh environmental adaptation and developing antifouling strategies in marine and coastal ecosystems.
Increased Cu(II) Adsorption Onto UV-Aged Polyethylene, Polypropylene, and Polyethylene Terephthalate Microplastic Particles in Seawater
Authors: Han Xiaoxin , Vogt Rolf D. , Zhou Jiaying , Zheng Boyang , Yu Xue , Feng Jianfeng , Lu Xueqiang
Published: October 2021

Environmental effects of microplastic are rather due to their adsorption capacity of contaminants than themselves. Aging is a key factor influencing adsorption properties of environmental microplastics. In order to clarify this influence, polyethylene (PE), polypropylene (PP), and polyethylene terephthalate (PET) microplastics with particle sizes of <0.9 mm, 0.9–2 mm, and 2–5 mm were artificially aged in seawater for 12 months. This enabled an assessment of the change in Cu(II) adsorption capacity to the microplastics particles under aging. According to the FTIR spectra, fresh microplastics were oxidized during the UV induced aging process. The adsorption capacities of microplastic were positively correlated with their aging time. After 12-months aging, the amount of Cu(II) adsorbed to the aged microplastics was 1.45–2.92 times higher than on the fresh microplastic particles. For PP and PET, the aging effect increased with decreasing size of the microplastic particles. In the case of PE, particles with the medium particle size (0.9–2 mm) had the strongest aging effect.
Long-Term Effects of Financial Incentives for General Practitioners on Quality Indicators in the Treatment of Patients With Diabetes Mellitus in Primary Care—A Follow-Up Analysis of a Cluster Randomized Parallel Controlled Trial
Authors: Meier Rahel , Chmiel Corinne , Valeri Fabio , Muheim Leander , Senn Oliver , Rosemann Thomas
Published: October 2021

Background: The effect of financial incentives on the quality of primary care is of high interest, and so is its sustainability after financial incentives are withdrawn.

Objective: To assess both long-term effects and sustainability of financial incentives for general practitioners (GPs) in the treatment of patients with diabetes mellitus based on quality indicators (QIs) calculated from routine data from electronic medical records.

Design/Participants: Randomized controlled trial using routine data from electronic medical records of patients with diabetes mellitus of Swiss GPs.

Intervention: During the study period of 24 months, all GPs received bimonthly feedback reports with information on their actual treatment as reflected in QIs. In the intervention group, the reports were combined with financial incentives for quality improvement. The incentive was stopped after 12 months.

Measurements: Proportion of patients meeting the process QI of annual HbA1c measurements and the clinical QI of blood pressure levels below 140/85 mmHg.

Results: A total of 71 GPs from 43 different practices were included along with 3,854 of their patients with diabetes mellitus. Throughout the study, the proportion of patients with annual HbA1c measurements was stable in the intervention group (78.8–78.9%) and decreased slightly in the control group (81.5–80.2%) [odds ratio (OR): 1.21; 95% CI: 1.04–1.42, p < 0.05]. The proportion of patients achieving blood pressure levels below 140/85 mmHg decreased in the control group (51.2–47.2%) and increased in the intervention group (49.7–51.9%) (OR: 1.18; 95% CI: 1.04–1.35, p < 0.05) where it peaked at 54.9% after 18 months and decreased steadily over the last 6 months.

Conclusion: After the withdrawal of financial incentives for the GPs after 12 months, some QIs still improved, indicating that 1 year might be too short to observe the full effect of such interventions. The decrease in QI achievement rates after 18 months suggests that the positive effects of time-limited financial incentives eventually wane.
Recent Advances in the Diagnosis, Staging, Treatment, and Prognosis of Advanced Gastric Cancer: A Literature Review
Authors: Chen Zhi-da , Zhang Peng-fei , Xi Hong-qing , Wei Bo , Chen Lin , Tang Yun
Published: October 2021

Gastric cancer is one of the most common cause of cancer related deaths worldwide which results in malignant tumors in the digestive tract. The only radical treatment option available is surgical resection. Recently, the implementation of neoadjuvant chemotherapy resulted in 5-year survival rates of 95% for early gastric cancer. The main reason of treatment failure is that early diagnosis is minimal, with many patients presenting advanced stages. Hence, the greatest benefit of radical resection is missed. Consequently, the main therapeutic approach for advanced gastric cancer is combined surgery with neoadjuvant chemotherapy, targeted therapy, or immunotherapy. In this review, we will discuss the various treatment options for advanced gastric cancer. Clinical practice and clinical research is the most practical way of reaching new advents in terms of patients' characteristics, optimum drug choice, and better prognosis. With the recent advances in gastric cancer diagnosis, staging, treatment, and prognosis, we are evident that the improvement of survival in this patient population is just a matter of time.
Lessons From APOL1 Animal Models
Authors: Yoshida Teruhiko , Latt Khun Zaw , Heymann Jurgen , Kopp Jeffrey B.
Published: October 2021

African-Americans have a three-fold higher rate of chronic kidney disease compared to European-Americans. Much of this excess risk is attributed to genetic variants in APOL1, encoding apolipoprotein L1, that are present only in individuals with sub-Saharan ancestry. Although 10 years have passed since the discovery of APOL1 renal risk variants, the mechanisms by which APOL1 risk allele gene products damage glomerular cells remain incompletely understood. Many mechanisms have been reported in cell culture models, but few have been demonstrated to be active in transgenic models. In this narrative review, we will review existing APOL1 transgenic models, from flies to fish to mice; discuss findings and limitations from studies; and consider future research directions.
Quantitative Examination of Five Stochastic Cell-Cycle and Cell-Size Control Models for Escherichia coli and Bacillus subtilis
Authors: Le Treut Guillaume , Si Fangwei , Li Dongyang , Jun Suckjoon
Published: October 2021

We examine five quantitative models of the cell-cycle and cell-size control in Escherichia coli and Bacillus subtilis that have been proposed over the last decade to explain single-cell experimental data generated with high-throughput methods. After presenting the statistical properties of these models, we test their predictions against experimental data. Based on simple calculations of the defining correlations in each model, we first dismiss the stochastic Helmstetter-Cooper model and the Initiation Adder model, and show that both the Replication Double Adder (RDA) and the Independent Double Adder (IDA) model are more consistent with the data than the other models. We then apply a recently proposed statistical analysis method and obtain that the IDA model is the most likely model of the cell cycle. By showing that the RDA model is fundamentally inconsistent with size convergence by the adder principle, we conclude that the IDA model is most consistent with the data and the biology of bacterial cell-cycle and cell-size control. Mechanistically, the Independent Adder Model is equivalent to two biological principles: (i) balanced biosynthesis of the cell-cycle proteins, and (ii) their accumulation to a respective threshold number to trigger initiation and division.
Fractional Wavelet-Based Generative Scattering Networks
Authors: Wu Jiasong , Qiu Xiang , Zhang Jing , Wu Fuzhi , Kong Youyong , Yang Guanyu , Senhadji Lotfi , Shu Huazhong
Published: October 2021

Generative adversarial networks and variational autoencoders (VAEs) provide impressive image generation from Gaussian white noise, but both are difficult to train, since they need a generator (or encoder) and a discriminator (or decoder) to be trained simultaneously, which can easily lead to unstable training. To solve or alleviate these synchronous training problems of generative adversarial networks (GANs) and VAEs, researchers recently proposed generative scattering networks (GSNs), which use wavelet scattering networks (ScatNets) as the encoder to obtain features (or ScatNet embeddings) and convolutional neural networks (CNNs) as the decoder to generate an image. The advantage of GSNs is that the parameters of ScatNets do not need to be learned, while the disadvantage of GSNs is that their ability to obtain representations of ScatNets is slightly weaker than that of CNNs. In addition, the dimensionality reduction method of principal component analysis (PCA) can easily lead to overfitting in the training of GSNs and, therefore, affect the quality of generated images in the testing process. To further improve the quality of generated images while keeping the advantages of GSNs, this study proposes generative fractional scattering networks (GFRSNs), which use more expressive fractional wavelet scattering networks (FrScatNets), instead of ScatNets as the encoder to obtain features (or FrScatNet embeddings) and use similar CNNs of GSNs as the decoder to generate an image. Additionally, this study develops a new dimensionality reduction method named feature-map fusion (FMF) instead of performing PCA to better retain the information of FrScatNets,; it also discusses the effect of image fusion on the quality of the generated image. The experimental results obtained on the CIFAR-10 and CelebA datasets show that the proposed GFRSNs can lead to better generated images than the original GSNs on testing datasets. The experimental results of the proposed GFRSNs with deep convolutional GAN (DCGAN), progressive GAN (PGAN), and CycleGAN are also given.
The Effect of the Severity of Obstructive Sleep Apnea on Leukocyte Telomere Length, 25 Hydroxy Vitamin D, and Parathyroid Hormonal Concentrations in Asian Indians
Authors: Bhatt Surya Prakash , Guleria Randeep , Vikram Naval K.
Published: October 2021

Background: Obstructive sleep apnea (OSA) is a common disorder in which breathing repeatedly stops during sleep. Leukocyte telomere length (LTL) and OSA are linked with an increased risk of oxidative stress and inflammation. The possible link between LTL and OSA in Asian Indians has not been evaluated. Thus, the present study aims to compare the link between LTL and OSA in Asian Indians.

Methods: In this study, 300 subjects (120 obese with OSA, 110 obese without OSA, and 70 non-obese without OSA) were included after overnight polysomnography and a fasting blood sample. Clinical, anthropometry, metabolic markers, insulin, 25-hydroxyvitamin D [25(OH) D], and parathyroid hormones (PTH) levels were investigated. LTL was investigated by a QPCR. Univariate and stepwise multivariate linear regression analyses adjusting for age, gender, BMI, and % body fat were conducted while treating LTL as a dependent variable in relation to AHI and other covariates.

Results: Obese subjects with OSA had significantly decreased 25(OH)D and increased PTH levels. The mean telomere length (T/S) ratio was significantly shorter in patients with OSA. The adjusted correlation analysis showed that shortening of telomere length correlated with increasing age, apnea-hypopnea index (AHI), oxygen desaturation index, and RDI. Univariate analysis showed that LTL revealed a trend toward a negative correlation with a mean age (β + SE, −0.015 + 0.0006; p = 0.01) and positive correlation with AHI [β +slandered error (SE), 0.042 + 0.017; p = 0.008]. In the multiple regression analysis, LTL was positively associated with AHI (β + SE, 0.281 + 0.04; p = 0.001) after adjusting for age, sex, BMI, and % body fat. Even when adjusted for confounding factors, 25(OH)D, and PTH levels, LTL still was related to AHI (β + SE, 0.446 + 0.02; p = 0.05).

Conclusion: Our study indicates the presence of an association between LTL and OSA and a significant impact of OSA severity and telomeres shortening in Asian Indians.
Bilateral Representation of Sensorimotor Responses in Benign Adult Familial Myoclonus Epilepsy: An MEG Study
Authors: Matsubara Teppei , Ahlfors Seppo P. , Mima Tatsuya , Hagiwara Koichi , Shigeto Hiroshi , Tobimatsu Shozo , Goto Yoshinobu , Stufflebeam Steven
Published: October 2021

Patients with cortical reflex myoclonus manifest typical neurophysiologic characteristics due to primary sensorimotor cortex (S1/M1) hyperexcitability, namely, contralateral giant somatosensory-evoked potentials/fields and a C-reflex (CR) in the stimulated arm. Some patients show a CR in both arms in response to unilateral stimulation, with about 10-ms delay in the non-stimulated compared with the stimulated arm. This bilateral C-reflex (BCR) may reflect strong involvement of bilateral S1/M1. However, the significance and exact pathophysiology of BCR within 50 ms are yet to be established because it is difficult to identify a true ipsilateral response in the presence of the giant component in the contralateral hemisphere. We hypothesized that in patients with BCR, bilateral S1/M1 activity will be detected using MEG source localization and interhemispheric connectivity will be stronger than in healthy controls (HCs) between S1/M1 cortices. We recruited five patients with cortical reflex myoclonus with BCR and 15 HCs. All patients had benign adult familial myoclonus epilepsy. The median nerve was electrically stimulated unilaterally. Ipsilateral activity was investigated in functional regions of interest that were determined by the N20m response to contralateral stimulation. Functional connectivity was investigated using weighted phase-lag index (wPLI) in the time-frequency window of 30–50 ms and 30–100 Hz. Among seven of the 10 arms of the patients who showed BCR, the average onset-to-onset delay between the stimulated and the non-stimulated arm was 8.4 ms. Ipsilateral S1/M1 activity was prominent in patients. The average time difference between bilateral cortical activities was 9.4 ms. The average wPLI was significantly higher in the patients compared with HCs in specific cortico-cortical connections. These connections included precentral-precentral, postcentral-precentral, inferior parietal (IP)-precentral, and IP-postcentral cortices interhemispherically (contralateral region-ipsilateral region), and precentral-IP and postcentral-IP intrahemispherically (contralateral region-contralateral region). The ipsilateral response in patients with BCR may be a pathologically enhanced motor response homologous to the giant component, which was too weak to be reliably detected in HCs. Bilateral representation of sensorimotor responses is associated with disinhibition of the transcallosal inhibitory pathway within homologous motor cortices, which is mediated by the IP. IP may play a role in suppressing the inappropriate movements seen in cortical myoclonus.
Pre- and Postnatal Damage to the Retro-Geniculate Visual Pathways Cause Retinal Degeneration Predictive for Visual Function
Authors: Lennartsson Finn , Öhnell HannaMaria , Jacobson Lena , Nilsson Maria
Published: October 2021

To increase the understanding of the relationship between structure and function in individuals with damage to the brain from different stages of maturation of the visual system, we examined 16 teenagers and young adults. We used diffusion-weighted magnetic resonance imaging (MRI) and fiber tractography of the optic radiation (OR) and optical coherence tomography (OCT) of the peripapillary retinal nerve fiber layer (pRNFL) and the ganglion cell layer + inner plexiform layer (GC+IPL) in the macula. Visual field (VF) function was assessed with the Humphrey Field Analyzer (HFA). Injuries to the immature OR were associated with thinning of the pRNFL and GC+IPL, and corresponding VF defects irrespectively of timing of the lesion. However, in cases with bilateral white-matter damage of immaturity (WMDI) we noticed a well preserved central VF despite a very thin GC+IPL. We speculate that this is due to plasticity in the immature visual system. Similar results were not noticed among cases with unilateral damage, acquired pre- or postnatally, in which the central VF was affected in most cases. OCT has proved to be a valuable targeted tool in children with damage to the retro-geniculate visual pathways, and that focal thinning of the GC+IPL predicts VF defects. This brief research report includes a review of four previously published papers. In addition, we present one new case and apply a recently developed classification system for CVI. The classification was applied on cases with bilateral WMDI to investigate its relation to retinal structure.
Prediction of Deep Brain Stimulation Outcome in Parkinson’s Disease With Connectome Based on Hemispheric Asymmetry
Authors: Wang Jingqi , Shang Ruihong , He Le , Zhou Rongsong , Chen Zhensen , Ma Yu , Li Xuesong
Published: October 2021

Parkinson’s disease (PD) is a neurodegenerative disease that is associated with motor and non-motor symptoms and caused by lack of dopamine in the substantia nigra of the brain. Subthalamic nucleus deep brain stimulation (STN-DBS) is a widely accepted therapy of PD that mainly inserts electrodes into both sides of the brain. The effect of STN-DBS was mainly for motor function, so this study focused on the recovery of motor function for PD after DBS. Hemispherical asymmetry in the brain network is considered to be a potential indicator for diagnosing PD patients. This study investigated the value of hemispheric brain connection asymmetry in predicting the DBS surgery outcome in PD patients. Four types of brain connections, including left intra-hemispheric (LH) connection, right intra-hemispheric (RH) connection, inter-hemispheric homotopic (Ho) connection, and inter-hemispheric heterotopic (He) connection, were constructed based on the resting state functional magnetic resonance imaging (rs-fMRI) performed before the DBS surgery. We used random forest for selecting features and the Ridge model for predicting surgical outcome (i.e., improvement rate of motor function). The functional connectivity analysis showed that the brain has a right laterality: the RH networks has the best correlation (r = 0.37, p = 5.68E-03) between the predicted value and the true value among the above four connections. Moreover, the region-of-interest (ROI) analysis indicated that the medioventral occipital cortex (MVOcC)–superior temporal gyrus (STG) and thalamus (Tha)–precentral gyrus (PrG) contributed most to the outcome prediction model for DBS without medication. This result provides more support for PD patients to evaluate DBS before surgery.
Co-grafts of Human Embryonic Stem Cell Derived Retina Organoids and Retinal Pigment Epithelium for Retinal Reconstruction in Immunodeficient Retinal Degenerate Royal College of Surgeons Rats
Authors: Thomas Biju B. , Lin Bin , Martinez-Camarillo Juan Carlos , Zhu Danhong , McLelland Bryce T. , Nistor Gabriel , Keirstead Hans S. , Humayun Mark S. , Seiler Magdalene J.
Published: October 2021

End-stage age-related macular degeneration (AMD) and retinitis pigmentosa (RP) are two major retinal degenerative (RD) conditions that result in irreversible vision loss. Permanent eye damage can also occur in battlefields or due to accidents. This suggests there is an unmet need for developing effective strategies for treating permanent retinal damages. In previous studies, co-grafted sheets of fetal retina with its retinal pigment epithelium (RPE) have demonstrated vision improvement in rat retinal disease models and in patients, but this has not yet been attempted with stem-cell derived tissue. Here we demonstrate a cellular therapy for irreversible retinal eye injuries using a “total retina patch” consisting of retinal photoreceptor progenitor sheets and healthy RPE cells on an artificial Bruch’s membrane (BM). For this, retina organoids (ROs) (cultured in suspension) and polarized RPE sheets (cultured on an ultrathin parylene substrate) were made into a co-graft using bio-adhesives [gelatin, growth factor-reduced matrigel, and medium viscosity (MVG) alginate]. In vivo transplantation experiments were conducted in immunodeficient Royal College of Surgeons (RCS) rats at advanced stages of retinal degeneration. Structural reconstruction of the severely damaged retina was observed based on histological assessments and optical coherence tomography (OCT) imaging. Visual functional assessments were conducted by optokinetic behavioral testing and superior colliculus electrophysiology. Long-term survival of the co-graft in the rat subretinal space and improvement in visual function were observed. Immunohistochemistry showed that co-grafts grew, generated new photoreceptors and developed neuronal processes that were integrated into the host retina. This novel approach can be considered as a new therapy for complete replacement of a degenerated retina.
Comparison of the Nutritional Properties and Transcriptome Profiling Between the Two Different Harvesting Periods of Auricularia polytricha
Authors: Wang Wenliang , Wang Yansheng , Gong Zhiqing , Yang Shifa , Jia Fengjuan
Published: October 2021

Auricularia polytricha (A. polytricha), regarded as an edible and medical mushroom, has attracted toward the research interests because of the high nutrition and bioactivity. The nutritional and medical properties of A. polytricha have been well-studied; however, research about the difference of the nutritional properties and transcriptome profiling between the two different harvesting periods of A. polytricha was limited. In this study, the nutritional properties and transcriptome profiling were compared between the two different harvesting periods of A. polytricha: AP_S1 (the stage for the first harvesting period) and AP_S2 (the stage for the third harvesting period). This study showed that AP_S1 had the more growth advantages than AP_S2 including biomass, auricle area and thickness, protein and calcium contents, and most species of the amino acid contents, which contributed to the higher sensory evaluation and acceptability of AP_S1. Transcriptome profiling showed that a total of 30,298 unigenes were successfully annotated in the two different harvesting periods of A. polytricha. At a threshold of two-fold change, 1,415 and 3,213 unigenes were up- and downregulated, respectively. All the differentially expressed genes (DEGs) analysis showed that the some synthesis and metabolic processes were strengthened in AP_S1, especially the synthesis and metabolism of the amino acids and protein. The enhanced energy metabolism pathways could provide more energy for AP_S1 to synthesize the nutritional substance. Moreover, the expressions of 10 selected DEGs involved in the amino acid and protein synthesis pathways and energy metabolism pathways were higher in AP_S1 compared to AP_S2, consistent with Illumina analysis. To the best of our knowledge, this is the first study that compares the nutritional properties and transcriptome profiling between the two different harvesting periods of A. polytricha and the results can present insights into the growth and genetic characteristics of A. polytricha.
Development and Validation of a Radiomics Model Based on 18F-FDG PET of Primary Gastric Cancer for Predicting Peritoneal Metastasis
Authors: Xue Beihui , Jiang Jia , Chen Lei , Wu Sunjie , Zheng Xuan , Zheng Xiangwu , Tang Kun
Published: October 2021

Objectives

The aim of this study was to develop a preoperative positron emission tomography (PET)-based radiomics model for predicting peritoneal metastasis (PM) of gastric cancer (GC).

Methods

In this study, a total of 355 patients (109PM+, 246PM-) who underwent preoperative fluorine-18-fludeoxyglucose (18F-FDG) PET images were retrospectively analyzed. According to a 7:3 ratio, patients were randomly divided into a training set and a validation set. Radiomics features and metabolic parameters data were extracted from PET images. The radiomics features were selected by logistic regression after using maximum relevance and minimum redundancy (mRMR) and the least shrinkage and selection operator (LASSO) method. The radiomics models were based on the rest of these features. The performance of the models was determined by their discrimination, calibration, and clinical usefulness in the training and validation sets.

Results

After dimensionality reduction, 12 radiomics feature parameters were obtained to construct radiomics signatures. According to the results of the multivariate logistic regression analysis, only carbohydrate antigen 125 (CA125), maximum standardized uptake value (SUVmax), and the radiomics signature showed statistically significant differences between patients (P<0.05). A radiomics model was developed based on the logistic analyses with an AUC of 0.86 in the training cohort and 0.87 in the validation cohort. The clinical prediction model based on CA125 and SUVmax was 0.76 in the training set and 0.69 in the validation set. The comprehensive model, which contained a rad-score and the clinical factor (CA125) as well as the metabolic parameter (SUVmax), showed promising performance with an AUC of 0.90 in the training cohort and 0.88 in the validation cohort, respectively. The calibration curve showed the actual rate of the nomogram-predicted probability of peritoneal metastasis. Decision curve analysis (DCA) also demonstrated the good clinical utility of the radiomics nomogram.

Conclusions

The comprehensive model based on the rad-score and other factors (SUVmax, CA125) can provide a novel tool for predicting peritoneal metastasis of gastric cancer patients preoperatively.
Primary Squamous Cell Carcinomas Arising in Intracranial Epidermoid Cysts: A Series of Nine Cases and Systematic Review
Authors: Zuo Pengcheng , Sun Tao , Wang Yi , Geng Yibo , Zhang Peng , Wu Zhen , Zhang Junting , Zhang Liwei
Published: October 2021

Objective

Primary squamous cell carcinomas (PSCCs) arising in intracranial epidermoid cysts (IECs) are very rare, and their management and prognostic factors remain unclear. This study aimed to enunciate the clinical features and suggest a treatment protocol based on cases from the literature and the cases from our institution.

Methods

The clinicoradiological data were obtained from nine patients with PSCCs arising in IECs, who underwent surgical treatment at Beijing Tiantan Hospital between July 2012 and June 2018. We also searched the PubMed database using the keywords “epidermoid cyst(s)” or “epidermoid tumor(s)” combined with “malignant” or “malignancy” or “intracranial” or “brain” or “squamous cell carcinoma” between 1960 and 2020. Risk factors for overall survival (OS) were evaluated in the pooled cohort.

Results

The mean age of our cohort was 51.2 ± 8.3 years (range: 39–61 years), which included eight males and one female. Gross total resection (GTR) was achieved in three patients, while non-GTR was achieved in six patients. Radiotherapy was administered to five patients. After a median follow-up of 16.7 ± 21.6 months (range: 3–72 months), eight patients died with a mean OS time of 9.75 ± 6.6 months (range: 3–23 months). In the literature between 1965 and 2020, 45 cases of PSCCs arising in IECs were identified in 23 males and 22 females with a mean age of 55.2 ± 12.4 years. GTR, non-GTR, and biopsy were achieved in six (13.3%), 36 (80%), and three (6.7%) cases, respectively. After a mean follow-up of 12.7 ± 13.4 months (range: 0.33–60 months), 54.1% (20/37) patients died, and recurrence occurred in 53.6% (15/28) patients. A multivariate analysis demonstrated that postoperative radiotherapy (p = 0.002) was the only factor that favored OS. The Kaplan–Meier analysis showed that, compared with no radiotherapy (median survival time: 4 months), radiotherapy (median survival time: 24 months) had significantly prolonged OS (p = 0.0011), and GTR could not improve OS (p = 0.5826), compared with non-GTR. The 1-year OS of patients with or without radiotherapy was 72.5% or 18.2%, respectively.

Conclusion

Malignant transformation of IEC into PSCC was prevalent in elderly patients, with slight male predominance. GTR of previous benign IECs is recommended. For remnant benign IECs, close follow-up should be performed. Postoperative radiotherapy for PSCCs could bring survival benefit. GTR of these malignant intracranial tumors is difficult when they involve important brain structures. Future studies with larger cohorts are necessary to verify our findings.