bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulator Contamination Perception Based on Feature Fusion of Infrared Image and Meteorological Parameters
Authors: Wang Hongxia , Wang Bo , Li Min , Luo Peng , Ma Hengrui , Ma Fuqi
Published: September 2021

Polluted insulators seriously threaten the safe and stable operation of power grids, which attaches great significance to insulator contamination perception. Among the present methods, the non-contact approaches based on infrared images have gradually been widely used, as they are much more safe and are of low cost. However, the thermal effect of insulators is largely affected by meteorological conditions, which makes the infrared image-based methods less accurate. To solve the above problem, we take infrared image and meteorological parameters including humidity and temperature as input, and propose a feature fusion model to perceive insulator contamination in different weather conditions. Firstly, different feature extraction networks are used to perform feature extraction on the two types of data; secondly, the two features are concatenated to fuse together; thirdly, further feature extraction is performed and contamination is classified according to the pollution severity. Case studies show that the proposed method can better explore the relationship between humidity, temperature and pollution level of the insulators, thus can better separate the contamination grades and outperform the conventional infrared image based methods.
Maternal Serotonin: Shaping Developmental Patterns and Behavioral Strategy on Progeny in Molluscs
Authors: Voronezhskaya Elena E.
Published: September 2021

Serotonin is a well-known neurotransmitter and neurohormone regulating mood, sleep, feeding, and learning in high organisms. Serotonin also affects the embryonic events related to neurogenesis and maturation of hormonal systems, the underlying organism adaptation to a changing environment. Such serotonin-based mother-to-embryo signaling is realized via direct interactions in case of internal fertilization and embryonic development inside the mother body. However, the possibility of such signaling is less obvious in organisms with the ancestral type of embryogenesis and embryo development within the egg, outside the mother body. Our data, based on the investigation of freshwater gastropod molluscs (LymnaeaandHelisoma), demonstrated a correlation between seasonal variations of serotonin content within the female reproductive system, and developmental patterns and the behavioral characteristics of progeny. The direct action of serotonin via posttranslational protein modification—serotonylation—during early development, as well as classical receptor-mediated effects, underlies such serotonin-modulated developmental changes. In the present paper, I will shortly overview our results on freshwater molluscs and parallel the experimental data with the living strategy of these species occupying almost all Holarctic regions.
Competitive Advantage of Geosmithia morbida in Low-Moisture Wood May Explain Historical Outbreaks of Thousand Cankers Disease and Predict the Future Fate of Juglans nigra Within Its Native Range
Authors: Williams Geoffrey M. , Ginzel Matthew D.
Published: September 2021

Bark beetles vector symbiotic fungi and the success of these mutualisms may be limited by competition from other microbes. The outcome of fungal competition is strongly influenced by the physical and chemical conditions of the wood they inhabit. These conditions are in turn subject to climatic variation. In particular, wood moisture content (MC) influences fungal competition and, therefore, could help determine environmental suitability for thousand cankers disease (TCD) caused by Geosmithia morbida and its vector Pityophthorus juglandis. We conducted competition experiments in Juglans nigra wood that was naturally or artificially colonized by G. morbida and other fungi over a range of wood MC expected across prevailing United States climatic conditions. G. morbida outcompeted antagonistic fungi Clonostachys and Trichoderma spp. at <5% equilibrium moisture content. Aspergillus spp. outcompeted G. morbida at low moisture in wood from Indiana. We fit a logistic regression model to results of the competition experiments to predict survival of G. morbida across the United States. Expected survival of G. morbida was highest in historical TCD epicenters and accounted for the low incidence and severity of TCD in the eastern United States. Our results also predict that under future climate scenarios, the area impacted by TCD will expand into the native range of J. nigra. Given its role in emergent forest health threats, climate change should be a key consideration in the assessment of risks to hardwood resources.
Species and Phenotypic Distribution Models Reveal Population Differentiation in Ethiopian Indigenous Chickens
Authors: Kebede Fasil Getachew , Komen Hans , Dessie Tadelle , Alemu Setegn Worku , Hanotte Olivier , Bastiaansen John W. M.
Published: September 2021

Smallholder poultry production dominated by indigenous chickens is an important source of livelihoods for most rural households in Ethiopia. The long history of domestication and the presence of diverse agroecologies in Ethiopia create unique opportunities to study the effect of environmental selective pressures. Species distribution models (SDMs) and Phenotypic distribution models (PDMs) can be applied to investigate the relationship between environmental variation and phenotypic differentiation in wild animals and domestic populations. In the present study we used SDMs and PDMs to detect environmental variables related with habitat suitability and phenotypic differentiation among nondescript Ethiopian indigenous chicken populations. 34 environmental variables (climatic, soil, and vegetation) and 19 quantitative traits were analyzed for 513 adult chickens from 26 populations. To have high variation in the dataset for phenotypic and ecological parameters, animals were sampled from four spatial gradients (each represented by six to seven populations), located in different climatic zones and geographies. Three different ecotypes are proposed based on correlation test between habitat suitability maps and phenotypic clustering of sample populations. These specific ecotypes show phenotypic differentiation, likely in response to environmental selective pressures. Nine environmental variables with the highest contribution to habitat suitability are identified. The relationship between quantitative traits and a few of the environmental variables associated with habitat suitability is non-linear. Our results highlight the benefits of integrating species and phenotypic distribution modeling approaches in characterization of livestock populations, delineation of suitable habitats for specific breeds, and understanding of the relationship between ecological variables and quantitative traits, and underlying evolutionary processes.
Genome-Wide Analysis of the HSP20 Gene Family and Expression Patterns of HSP20 Genes in Response to Abiotic Stresses in Cynodon transvaalensis
Authors: Cui Fengchao , Taier Geli , Wang Xiangfeng , Wang Kehua
Published: September 2021

African bermudagrass (Cynodon transvaalensis Burtt–Davy) is an important warm-season turfgrass and forage grass species. Heat shock protein 20 (HSP20) is a diverse, ancient, and important protein family. To date, HSP20 genes have not been characterized genome-widely in African bermudagrass. Here, we confirmed 41 HSP20 genes in African bermudagrass genome. On the basis of the phylogenetic tree and cellular locations, the HSP20 proteins were classified into 12 subfamilies. Motif composition was consistent with the phylogeny. Moreover, we identified 15 pairs of paralogs containing nine pairs of tandem duplicates and six pairs of WGD/segmental duplicates of HSP20 genes. Unsurprisingly, the syntenic genes revealed that African bermudagrass had a closer evolutionary relationship with monocots (maize and rice) than dicots (Arabidopsis and soybean). The expression patterns of HSP20 genes were identified with the transcriptome data under abiotic stresses. According to the expression profiles, HSP20 genes could be clustered into three groups (Groups I, II, and III). Group I was the largest, and these genes were up-regulated in response to heat stress as expected. In Group II, one monocot-specific HSP20, CtHSP20-14 maintained higher expression levels under optimum temperature and low temperature, but not high temperature. Moreover, a pair of WGD/segmental duplicates CtHSP20-9 and CtHSP20-10 were among the most conserved HSP20s across different plant species, and they seemed to be positively selected in response to extreme temperatures during evolution. A total of 938 cis-elements were captured in the putative promoters of HSP20 genes. Almost half of the cis-elements were stress responsive, indicating that the expression pattern of HSP20 genes under abiotic stresses might be largely regulated by the cis-elements. Additionally, three-dimensional structure simulations and protein–protein interaction networks were incorporated to resolve the function mechanism of HSP20 proteins. In summary, the findings fulfilled the HSP20 family analysis and could provide useful information for further functional investigations of the specific HSP20s (e.g., CtHSP20-9, CtHSP20-10, and CtHSP20-14) in African bermudagrass.
AdImpute: An Imputation Method for Single-Cell RNA-Seq Data Based on Semi-Supervised Autoencoders
Authors: Xu Li , Xu Yin , Xue Tong , Zhang Xinyu , Li Jin
Published: September 2021

Motivation:The emergence of single-cell RNA sequencing (scRNA-seq) technology has paved the way for measuring RNA levels at single-cell resolution to study precise biological functions. However, the presence of a large number of missing values in its data will affect downstream analysis. This paper presents AdImpute: an imputation method based on semi-supervised autoencoders. The method uses another imputation method (DrImpute is used as an example) to fill the results as imputation weights of the autoencoder, and applies the cost function with imputation weights to learn the latent information in the data to achieve more accurate imputation.

Results:As shown in clustering experiments with the simulated data sets and the real data sets, AdImpute is more accurate than other four publicly available scRNA-seq imputation methods, and minimally modifies the biologically silent genes. Overall, AdImpute is an accurate and robust imputation method.
Unexpected Favorable Outcome to PD-1 Antibody Plus Lenvatinib in a Patient With Recurrent Intestinal Follicular Dendritic Cell Sarcoma: A Case Report and Literature Review
Authors: Lei Yanna , Zhao Sha , Jiang Ming
Published: September 2021

Background

Follicular dendritic cell sarcoma (FDCS) is an uncommon malignant cancer, and there is no standard treatment to date. Resection followed by adjuvant chemotherapy or radiation is considered the most commonly used strategy for treatment. However, the treatment for patients who have progressed after systemic treatment is more controversial.

Case summary

In this case report, we describe a 57-year-old man with primary small intestine FDCS where surgery and second-line systemic chemotherapy failed. After disease progression (PD), the patient received sintilimab plus lenvatinib as third-line treatment and achieved a progression-free survival (PFS) with 7 months.

Conclusion

This is the first report of a FDCS patient treated with immune checkpoint inhibitors (ICIs) and antiangiogenic agents, sintilimab and lenvatinib, as third-line therapy. Our case provides a potential therapeutic option for patients with FDCS who progressed after multiline therapy.
Shared Genetic Liability Between Major Depressive Disorder and Atopic Diseases
Authors: Cao Hongbao , Li Sheng , Baranova Ancha , Zhang Fuquan
Published: September 2021

Objectives

Deciphering the genetic relationships between major depressive disorder (MDD) and atopic diseases (asthma, hay fever, and eczema) may facilitate understanding of their biological mechanisms as well as the development of novel treatment regimens. Here we tested the genetic correlation between MDD and atopic diseases by linkage disequilibrium score regression.

Methods

A polygenic overlap analysis was performed to estimate shared genetic variations between the two diseases. Causal relationships between MDD and atopic diseases were investigated using two-sample bidirectional Mendelian randomization analysis. Genomic loci shared between MDD and atopic diseases were identified using cross-trait meta-analysis. Putative functional genes were evaluated by fine-mapping of transcriptome-wide associations.

Results

The polygenic analysis revealed approximately 15.8 thousand variants causally influencing MDD and 0.9 thousand variants influencing atopic diseases. Among these variants, approximately 0.8 thousand were shared between the two diseases. Mendelian randomization analysis indicates that genetic liability to MDD has a causal effect on atopic diseases (b = 0.22, p = 1.76 × 10-6), while genetic liability to atopic diseases confers a weak causal effect on MDD (b = 0.05, p = 7.57 × 10-3). Cross-trait meta-analyses of MDD and atopic diseases identified 18 shared genomic loci. Both fine-mapping of transcriptome-wide associations and analysis of existing literature suggest the estrogen receptor β-encoding gene ESR2 as one of the potential risk factors for both MDD and atopic diseases.

Conclusion

Our findings reveal shared genetic liability and causal links between MDD and atopic diseases, which shed light on the phenotypic relationship between MDD and atopic diseases.
Induction of IL-22-Producing CD4+ T Cells by Segmented Filamentous Bacteria Independent of Classical Th17 Cells
Authors: Roy Urmi , de Oliveira Rômulo S. , Galvez Eric J. C. , Gronow Achim , Basic Marijana , Perez Laura Garcia , Gagliani Nicola , Bleich Andre , Huber Samuel , Strowig Till
Published: September 2021

The intestinal microbiota modulates IL-22 production in the intestine, including the induction of IL-22-producing CD4+ T helper cells. Which specific bacteria are responsible for the induction of these cells is less well understood. Here, we demonstrate through the use of novel gnotobiotic knock-in reporter mice that segmented filamentous bacteria (SFB), which are known for their ability to induce Th17 cells, also induce distinct IL-17A negative CD4+ T cell populations in the intestine. A subset of these cells instead produces IL-22 upon restimulation ex vivo and also during enteric infections. Furthermore, they produce a distinct set of cytokines compared to Th17 cells including the differential expression of IL-17F and IFN-γ. Importantly, genetic models demonstrate that these cells, presumably Th22 cells, develop independently of intestinal Th17 cells. Together, our data identifies that besides Th17, SFB also induces CD4+ T cell populations, which serve as immediate source of IL-22 during intestinal inflammation.
Advancing the Sea Ice Hypothesis: Trophic Interactions Among Breeding Pygoscelis Penguins With Divergent Population Trends Throughout the Western Antarctic Peninsula
Authors: Gorman Kristen B. , Ruck Kate E. , Williams Tony D. , Fraser William R.
Published: September 2021

We evaluated annual and regional variation in the dietary niche ofPygoscelispenguins including the sea ice-obligate Adélie penguin (Pygoscelis adeliae), and sea ice-intolerant chinstrap (Pygoscelis antarcticus) and gentoo (Pygoscelis papua) penguins, three species that nest throughout the western Antarctic Peninsula (AP) to test thesea ice trophic interaction hypothesis, which posits that penguin breeding populations with divergent trends, i.e., declining or increasing, are reliant on differing food webs. Our study relies on values of naturally occurring carbon (13C/12C, δ13C) and nitrogen (15N/14N, δ15N) stable isotopes as integrated proxies of penguin food webs measured over three years at three different breeding colonies. At Anvers Island in the north, where reductions in sea ice and changes in breeding population trends among sympatric sea ice-obligate (Adélie) and sea ice-intolerant (chinstrap and gentoo) penguins have been most notable, our analyses show that all three species ofPygoscelispenguins became more similar isotopically over the reproductive period. By late chick-rearing at Anvers Island, crèched chicks at 5-weeks-old for all species occupied similar trophic positions. Isotopic mixing models indicated that the proportions of prey provisioned by adult penguins to 5-week-old chicks at Anvers Island were generally similar across species within years, consisting primarily of Antarctic krill (Euphausia superba). Crèched Adélie chicks had higher δ13C and δ15N values at Avian and Charcot Islands, southern breeding colonies where sea ice is more prominent and populations of Adélie penguins have increased or remain stable. Trophic position increased with latitude, while the proportions of prey provisioned by Adélie penguin adults to chicks at southern breeding colonies included species typical of high Antarctic marine food webs, especially crystal krill (Euphausia crystallorophias). A Bayesian metric for dietary niche width, standard ellipse area (SEA-B), indicated thatPygoscelispenguins with greater population changes in the north had more variability in dietary niche width than stable populations further south. Our results lend insight on marine food web drivers ofPygoscelispenguin reproduction at the regional scale and question the long-standing paradigm that Antarctic krill are the only food web component critical to penguin reproductive survival in this region of the Southern Ocean.
Differing Visual Behavior Between Inexperienced and Experienced Critical Care Nurses While Using a Closed-Loop Ventilation System—A Prospective Observational Study
Authors: Buehler Philipp K. , Herling Anique , Bienefeld Nadine , Klinzing Stephanie , Wegner Stephan , Wendel Garcia Pedro David , Karbach Michael , Lohmeyer Quentin , Schaubmayr Elisabeth , Schuepbach Reto A. , Hofmaenner Daniel A.
Published: September 2021

Introduction: Closed-loop ventilation modes are increasingly being used in intensive care units to ensure more automaticity. Little is known about the visual behavior of health professionals using these ventilation modes. The aim of this study was to analyze gaze patterns of intensive care nurses while ventilating a patient in the closed-loop mode with Intellivent adaptive support ventilation® (I-ASV) and to compare inexperienced with experienced nurses.

Materials and Methods: Intensive care nurses underwent eye-tracking during daily care of a patient ventilated in the closed-loop ventilation mode. Five specific areas of interest were predefined (ventilator settings, ventilation curves, numeric values, oxygenation Intellivent, ventilation Intellivent). The main independent variable and primary outcome was dwell time. Secondary outcomes were revisits, average fixation time, first fixation and fixation count on areas of interest in a targeted tracking-time of 60 min. Gaze patterns were compared between I-ASV inexperienced (n = 12) and experienced (n = 16) nurses.

Results: In total, 28 participants were included. Overall, dwell time was longer for ventilator settings and numeric values compared to the other areas of interest. Similar results could be obtained for the secondary outcomes. Visual fixation of oxygenation Intellivent and ventilation Intellivent was low. However, dwell time, average fixation time and first fixation on oxygenation Intellivent were longer in experienced compared to inexperienced intensive care nurses.

Discussion: Gaze patterns of intensive care nurses were mainly focused on numeric values and settings. Areas of interest related to traditional mechanical ventilation retain high significance for intensive care nurses, despite use of closed-loop mode. More visual attention to oxygenation Intellivent and ventilation Intellivent in experienced nurses implies more routine and familiarity with closed-loop modes in this group. The findings imply the need for constant training and education with new tools in critical care, especially for inexperienced professionals.
Effects of Esketamine on Acute and Chronic Pain After Thoracoscopy Pulmonary Surgery Under General Anesthesia: A Multicenter-Prospective, Randomized, Double-Blind, and Controlled Trial
Authors: Lei Yishan , Liu Huayue , Xia Fan , Gan Shulin , Wang Yulan , Huo Wenwen , Wang Qinyun , Ji Fuhai
Published: September 2021

Background: Post-operative pain management for patients undergoing thoracoscopy surgery is challenging for clinicians which increase both health and economic burden. The non-selective NMDA receptor antagonist esketamine possesses an analgesic effect twice that of ketamine. The application of esketamine might be beneficial in alleviating acute and chronic pain after thoracic surgery. The current study describes the protocol aiming to evaluate the analgesic effect of esketamine after pulmonary surgery via visual analog scale (VAS) score for acute and chronic pain.

Methods: A multi-center, prospective, randomized, controlled, double-blind study is designed to explore the analgesic effect of esketamine in randomized patients undergoing video-assisted thoracoscopic surgery (VATS) with general anesthesia. Patients will be randomly assigned to Esketamine Group (Group K) and Control Group (Group C) in a ratio of 1:1. Group K patients will receive esketamine with a bolus of 0.1 mg/kg after anesthesia induction, 0.1 mg/kg/h throughout the operation and 0.015 mg/kg/h in PCIA after surgery while Group C patients will receive the same volume of normal saline. The primary outcome is to measure the pain intensity through the VAS score at 3 months after the operation. The secondary outcome includes VAS score at 1, 4, 8, 24, and 48 h and on the 7th day and 1 month after the operation, complications, ketamine-related neurological side effects, recovery time of bowel function, and total amount of supplemental analgesics.

Discussion: The results of the current study might illustrate the analgesic effect of esketamine for patients undergoing thoracoscopy pulmonary surgery and provide evidence and insight for perioperative pain management.

Study Registration: The trial was registered with Chinese Clinical Trial Registry (CHICTR) on Nov 18th, 2020 (ChiCTR2000040012).
Copper Isotopes and Copper to Zinc Ratio as Possible Biomarkers for Thyroid Cancer
Authors: Kazi Tani Latifa Sarra , Gourlan Alexandra T. , Dennouni-Medjati Nouria , Telouk Philippe , Dali-Sahi Majda , Harek Yahia , Sun Qian , Hackler Julian , Belhadj Moussa , Schomburg Lutz , Charlet Laurent
Published: September 2021

Thyroid cancer is the most common endocrine cancer. There is no systematic screening for such cancer, and the current challenge is to find potential biomarkers to facilitate an early diagnosis. Copper (Cu) and zinc (Zn) are essential micronutrients involved in the proper functioning of the thyroid gland, and changes in their concentrations have been observed in the development of cancer. Previous studies have highlighted the potential 65Cu/63Cu ratio (δ65Cu) to be a cancer biomarker. This study tests its sensitivity on plasma samples (n = 46) of Algerian patients with papillary thyroid carcinoma and a set of corresponding biopsies (n = 11). The δ65Cu ratio in blood and tumor samples was determined using multi collector inductively coupled plasma-mass spectrometry (MC-ICP-MS), and their corresponding Cu and Zn plasma total concentrations using total reflection X-ray fluorescence (TXRF). Plasma concentrations of Cu were significantly higher (1346.1 ± 328.3 vs. 1060.5 ± 216.1 μg/L, p < 0.0001), and Zn significantly lower (942.1 ± 205.2 vs. 1027.9 ± 151.4 μg/L, p < 0.05) in thyroid cancer patients as compared to healthy controls (n = 50). Accordingly, the Cu/Zn ratio was significantly different between patients and controls (1.5 ± 0.4 vs. 1.0 ± 0.3, p < 0.0001). Furthermore, the δ65Cu plasma levels of patients were significantly lower than healthy controls (p < 0.0001), whereas thyroid tumor tissues presented high δ65Cu values. These results support the hypothesis that Cu isotopes and plasma trace elements may serve as suitable biomarkers of thyroid cancer diagnosis.
Multi-Trait Genomic Risk Stratification for Type 2 Diabetes
Authors: Rohde Palle Duun , Nyegaard Mette , Kjolby Mads , Sørensen Peter
Published: September 2021

Type 2 diabetes mellitus (T2DM) is continuously rising with more disease cases every year. T2DM is a chronic disease with many severe comorbidities and therefore remains a burden for the patient and the society. Disease prevention, early diagnosis, and stratified treatment are important elements in slowing down the increase in diabetes prevalence. T2DM has a substantial genetic component with an estimated heritability of 40–70%, and more than 500 genetic loci have been associated with T2DM. Because of the intrinsic genetic basis of T2DM, one tool for risk assessment is genome-wide genetic risk scores (GRS). Current GRS only account for a small proportion of the T2DM risk; thus, better methods are warranted for more accurate risk assessment. T2DM is correlated with several other diseases and complex traits, and incorporating this information by adjusting effect size of the included markers could improve risk prediction. The aim of this study was to develop multi-trait (MT)-GRS leveraging correlated information. We used phenotype and genotype information from the UK Biobank, and summary statistics from two independent T2DM studies. Marker effects for T2DM and seven correlated traits, namely, height, body mass index, pulse rate, diastolic and systolic blood pressure, smoking status, and information on current medication use, were estimated (i.e., by logistic and linear regression) within the UK Biobank. These summary statistics, together with the two independent training summary statistics, were incorporated into the MT-GRS prediction in different combinations. The prediction accuracy of the MT-GRS was improved by 12.5% compared to the single-trait GRS. Testing the MT-GRS strategy in two independent T2DM studies resulted in an elevated accuracy by 50–94%. Finally, combining the seven information traits with the two independent T2DM studies further increased the prediction accuracy by 34%. Across comparisons, body mass index and current medication use were the two traits that displayed the largest weights in construction of the MT-GRS. These results explicitly demonstrate the added benefit of leveraging correlated information when constructing genetic scores. In conclusion, constructing GRS not only based on the disease itself but incorporating genomic information from other correlated traits as well is strongly advisable for obtaining improved individual risk stratification.
Testosterone and Estradiol as Novel Prognostic Indicators for HBV-Related Acute-on-Chronic Liver Failure
Authors: Sun Shuning , Xu Baoyan , Tan Wenting , Xiang Xiaomei , Zhou Yi , Dan Yunjie , Guo Yanzhi , Tan Zhaoxia , Deng Guohong
Published: September 2021

Background: HBV-related acute-on-chronic liver failure (HBV-ACLF) has a high short-term mortality and urgently needs an early warning system with simplicity and high accuracy. Previous studies show that sex hormones play potential roles in the progression of HBV-related liver diseases.

Aims: To explore the effect of testosterone and estradiol on the occurrence and prognosis of HBV-ACLF.

Methods: A prospective cohort of 300 chronic hepatitis B (CHB) patients was enrolled among which 108 were diagnosed with HBV-ACLF at admission and 20 developed to HBV-ACLF during hospitalization. We compared the level of serum testosterone and estradiol of patients with varied ACLF background, disease severity and cirrhosis conditions and analyzed the predictive ability of short-term prognosis. A novel prognostic model involving testosterone was developed and further validated in the HBV-ACLF group.

Results: The baseline estradiol level of HBV-ACLF group was significantly higher while testosterone was lower than that of non-ACLF group. The estradiol level increased while the testosterone level decreased as the number of organ failures increased. Testosterone had high accuracy in predicting the short-term mortality in HBV-ACLF (AUROC = 0.726) and estradiol did better in predicting the occurrence of ACLF during hospitalization (AUROC = 0.695). The novel prognostic model involving testosterone (TATIM model) was proved to have considerable prediction efficiency in HBV-ACLF cohort with or without cirrhosis.

Conclusion: Testosterone could be utilized as short-term prognostic indicator for HBV-related ACLF and estradiol can help to predict its occurrence. TATIM model is a novel prognostic model for HBV-related ACLF with simplicity and good performance irrespectively of liver cirrhosis.

Clinical Trial Registration Number: This study was based on a sub-cohort from the prospective multicenter cohort (NCT02457637).
Hypothetical Interventions for Falls Among Older Adults: An Application of the Parametric G-Formula
Authors: Ren Jiaojiao , Li Guangyou , Zhang Liju , Zhang Na , Ren Juan
Published: September 2021

Introduction: Falls, which have a higher incidence and mortality due to accidental injuries, are a major global health challenge. The effects of lifestyle factor, health indicator, psychological condition, and functional status interventions on the risk of falls are unknown and the conventional regression model would not adjust for the confounders. This study aimed to evaluate the 4-year risk of falls on the basis of these hypothetical interventions among Chinese older adults.

Methods: Data were obtained from 9,692 aged 65 years and over older adults in the China Health and Retirement Longitudinal Study wave, from 2011 to 2015. We used the parametric g-formula to evaluate the risk of falls on the basis of independent hypothetical interventions of sleep duration, social activities, smoking status, drinking status, body mass index (BMI), systolic blood pressure (SBP), vision, depression, activities of daily living (ADL), and their different joint intervention combinations.

Results: During the follow-up of 4 years, we documented 1,569 falls. The observed risk of falls was 23.58%. The risk ratios (95% confidence intervals [CIs]) of falls under the intensive hypothetical interventions on increasing sleep duration, participating in more social activities, quit smoking and drinking, reducing BMI and SBP, better vision, alleviating depressive symptoms, and improving ADL capability were 0.93 (0.87–0.96), 0.88 (0.79–0.92), 0.98 (0.95–1.03), 0.97 (0.95–1.02), 0.92 (0.86–1.03), 0.93 (0.87–1.04), 0.86 (0.74–0.91), 0.91 (0.85–0.96), and 0.79 (0.74–0.85), respectively. The feasible and intensive joint hypothetical intervention reduced the 4-year fall risk by 22% (95% CI: 0.52–0.91) and 33% (95% CI: 0.56–0.72), respectively.

Conclusions: Hypothetical interventions for increasing sleep duration, participating in more social activities, better vision, alleviating depressive symptoms, and improving ADL capability help protect older adults from falls. Our findings suggest that a combination of lifestyle factors, health indicators, psychological conditions, and functional status may prove to be an effective strategy for preventing falls among older adults.
RNA-seq Insights Into the Impact of Alteromonas macleodii on Isochrysis galbana
Authors: Cao Jia-Yi , Wang Ying-Ying , Wu Min-Nan , Kong Zhou-Yan , Lin Jing-Hao , Ling Ting , Xu Si-Min , Ma Shuo-Nan , Zhang Lin , Zhou Cheng-Xu , Yan Xiao-Jun , Xu Ji-Lin
Published: September 2021

Phycospheric bacteria may be the key biological factors affecting the growth of algae. However, the studies about interaction between Isochrysis galbana and its phycospheric bacteria are limited. Here, we show that a marine heterotrophic bacterium, Alteromonas macleodii, enhanced the growth of I. galbana, and inhibited non-photochemical quenching (NPQ) and superoxide dismutase (SOD) activities of this microalgae. Further, we explored this phenomenon via examining how the entire transcriptomes of I. galbana changed when it was co-cultured with A. macleodii. Notable increase was observed in transcripts related to photosynthesis, carbon fixation, oxidative phosphorylation, ribosomal proteins, biosynthetic enzymes, and transport processes of I. galbana in the presence of A. macleodii, suggesting the introduction of the bacterium might have introduced increased production and transport of carbon compounds and other types of biomolecules. Besides, the transcriptome changed largely corresponded to reduced stress conditions for I. galbana, as inferred from the depletion of transcripts encoding DNA repair enzymes, superoxide dismutase (SOD) and other stress-response proteins. Taken together, the presence of A. macleodii mainly enhanced photosynthesis and biosynthesis of I. galbana and protected it from stress, especially oxidative stress. Transfer of fixed organic carbon, but perhaps other types of biomolecules, between the autotroph and the heterotroph might happen in I. galbana-A. macleodii co-culture. The present work provides novel insights into the transcriptional consequences of I. galbana of mutualism with its heterotrophic bacterial partner, and mutually beneficial associations existing in I. galbana-A. macleodii might be explored to improve productivity and sustainability of aquaculture algal rearing systems.
A Global Analysis of Photoreceptor-Mediated Transcriptional Changes Reveals the Intricate Relationship Between Central Metabolism and DNA Repair in the Filamentous Fungus Trichoderma atroviride
Authors: Pola-Sánchez Enrique , Villalobos-Escobedo José Manuel , Carreras-Villaseñor Nohemí , Martínez-Hernández Pedro , Beltrán-Hernández Emma Beatriz , Esquivel-Naranjo Edgardo Ulises , Herrera-Estrella Alfredo
Published: September 2021

Light provides critical information for the behavior and development of basically all organisms. Filamentous fungi sense blue light, mainly, through a unique transcription factor complex that activates its targets in a light-dependent manner. In Trichoderma atroviride, the BLR-1 and BLR-2 proteins constitute this complex, which triggers the light-dependent formation of asexual reproduction structures (conidia). We generated an ENVOY photoreceptor mutant and performed RNA-seq analyses in the mutants of this gene and in those of the BLR-1, CRY-1 and CRY-DASH photoreceptors in response to a pulse of low intensity blue light. Like in other filamentous fungi BLR-1 appears to play a central role in the regulation of blue-light responses. Phenotypic characterization of the Δenv-1 mutant showed that ENVOY functions as a growth and conidiation checkpoint, preventing exacerbated light responses. Similarly, we observed that CRY-1 and CRY-DASH contribute to the typical light-induced conidiation response. In the Δenv-1 mutant, we observed, at the transcriptomic level, a general induction of DNA metabolic processes and strong repression of central metabolism. An analysis of the expression level of DNA repair genes showed that they increase their expression in the absence of env-1. Consistently, photoreactivation experiments showed that Δenv-1 had increased DNA repair capacity. Our results indicate that light perception in T. atroviride is far more complex than originally thought.
Strategies for Zinc Uptake in Pseudomonas aeruginosa at the Host–Pathogen Interface
Authors: Wang Shuaitao , Cheng Juanli , Niu Yanting , Li Panxin , Zhang Xiangqian , Lin Jinshui
Published: September 2021

As a structural, catalytic, and signaling component, zinc is necessary for the growth and development of plants, animals, and microorganisms. Zinc is also essential for the growth of pathogenic microorganisms and is involved in their metabolism as well as the regulation of various virulence factors. Additionally, zinc is necessary for infection and colonization of pathogenic microorganisms in the host. Upon infection in healthy organisms, the host sequesters zinc both intracellularly and extracellularly to enhance the immune response and prevent the proliferation and infection of the pathogen. Intracellularly, the host manipulates zinc levels through Zrt/Irt-like protein (ZIP)/ZnT family proteins and various zinc storage proteins. Extracellularly, members of the S100 protein family, such as calgranulin C, sequester zinc to inhibit microbial growth. In the face of these nutritional limitations, bacteria rely on an efficient zinc transport system to maintain zinc supplementation for proliferation and disruption of the host defense system to establish infection. Here, we summarize the strategies for zinc uptake in conditional pathogenic Pseudomonas aeruginosa, including known zinc uptake systems (ZnuABC, HmtA, and ZrmABCD) and the zinc uptake regulator (Zur). In addition, other potential zinc uptake pathways were analyzed. This review systematically summarizes the process of zinc uptake by P. aeruginosa to provide guidance for the development of new drug targets.
Insights Into Unveiling a Potential Role of Tertiary Lymphoid Structures in Metastasis
Authors: Mustapha Rami , Ng Kenrick , Monypenny James , Ng Tony
Published: September 2021

Tertiary lymphoid structures (TLSs) develop in non-lymphatic tissue in chronic inflammation and cancer. TLS can mature to lymph node (LN) like structures with germinal centers and associated vasculature. TLS neogenesis in cancer is highly varied and tissue dependent. The role of TLS in adaptive antitumor immunity is of great interest. However, data also show that TLS can play a role in cancer metastasis. The importance of lymphatics in cancer distant metastasis is clear yet the precise detail of how various immunosurveillance mechanisms interplay within TLS and/or draining LN is still under investigation. As part of the tumor lymphatics, TLS vasculature can provide alternative routes for the establishment of the pre-metastatic niche and cancer dissemination. The nature of the cytokine and chemokine signature at the heart of TLS induction can be key in determining the success of antitumor immunity or in promoting cancer invasiveness. Understanding the biochemical and biomechanical factors underlying TLS formation and the resulting impact on the primary tumor will be key in deciphering cancer metastasis and in the development of the next generation of cancer immunotherapeutics.
Position Specific Alternative Splicing and Gene Expression Profiles Along the Tonotopic Axis of Chick Cochlea
Authors: Koo Heiyeun , Hwang Jae Yeon , Jung Sungbo , Park Hyeyoung , Bok Jinwoong , Park Juw Won
Published: September 2021

Alternative splicing (AS) refers to the production of multiple mRNA isoforms from a single gene due to alternative selection of exons or splice sites during pre-mRNA splicing. It is a primary mechanism of gene regulation in higher eukaryotes and significantly expands the functional complexity of eukaryotic organisms, contributing to animal development and disease. Recent studies have shown that AS also influences functional diversity by affecting the transcriptomic and proteomic profiles in a position-dependent manner in a single organ. The peripheral hearing organ, the cochlea, is organized to detect sounds at different frequencies depending on its location along the longitudinal axis. This unique functional configuration, the tonotopy, is known to be facilitated by differential gene expression along the cochlear duct. We profiled transcriptome-wide gene expression and AS changes that occur within the different positions of chick cochlea. These analyses revealed distinct gene expression profiles and AS, including a splicing program that is unique to tonotopy. Changes in the expression of splicing factors PTBP3, ESRP1, and ESRP2 were demonstrated to contribute to position-specific AS. RNA-binding motif enrichment analysis near alternatively spliced exons provided further insight into the combinatorial regulation of AS at different positions by different RNA-binding proteins. These data, along with gene ontology (GO) analysis, represent a comprehensive analysis of the dynamic regulation of AS at different positions in chick cochlea.
Vascular Dementia and Underlying Sex Differences
Authors: Akhter Firoz , Persaud Alicia , Zaokari Younis , Zhao Zhen , Zhu Donghui
Published: September 2021

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer’s disease (AD); where Alzheimer’s accounts for 60–70% of cases of dementia and VaD accounts for 20% of all dementia cases. VaD is defined as a reduced or lack of blood flow to the brain that causes dementia. VaD is also known occasionally as vascular contributions to cognitive impairment and dementia (VCID) or multi-infarct dementia (MID). VCID is the condition arising from stroke and other vascular brain injuries that cause significant changes to memory, thinking, and behavior, and VaD is the most severe stage while MID is produced by the synergistic effects caused by multiple mini strokes in the brain irrespective of specific location or volume. There are also subtle differences in the presentation of VaD in males and females, but they are often overlooked. Since 1672 when the first case of VaD was reported until now, sex and gender differences have had little to no research done when it comes to the umbrella term of dementia in general. This review summarizes the fundamentals of VaD followed by a focus on the differences between sex and gender when an individual is diagnosed. In addition, we provide critical evidence concerning sex and gender differences with a few of the main risk factors of VaD including pre-existing health conditions and family history, gene variants, aging, hormone fluctuations, and environmental risk factors. Additionally, the pharmaceutical treatments and possible mitigation of risk factors is explored.
Associations Between Polyvascular Disease and Stroke Recurrence in Patients With Lacunar Stroke
Authors: Ma Lin , Wang Anxin , Zhang Yijun , Wang Yilong , Wang Yongjun , Meng Xia
Published: September 2021

Background and purpose: This study aimed to examine the association of polyvascular disease and clinical outcomes in patients with lacunar stroke.

Methods: Data of patients with recent lacunar stroke were collected from The Third China National Stroke Registry. Polyvascular disease is defined as the existence of atherosclerosis across two or more vascular beds. For the present study, polyvascular disease patients were grouped as follows: coronary heart disease (CHD) and lacunar stroke, peripheral arterial disease (PAD) and lacunar stroke, and CHD/PAD and lacunar stroke. The major clinical outcome was recurrence, and the secondary clinical outcome was major adverse cardiovascular events (MACEs). A Cox proportional multivariable hazards regression model was applied to estimate the association between polyvascular disease and outcomes.

Results: Among 3,165 patients with recent lacunar stroke, CHD was present in 375 (11.8%) and peripheral arterial disease in 168 (5.3%). The hazard ratio (HR) for stroke recurrence was 0.98 (95% confidence interval [CI], 0.65–1.46; p = 0.91) for patients with CHD and lacunar stroke, 1.07 (95% CI, 0.61–1.87; p = 0.82) for patients with PAD and lacunar stroke, and 0.95 (95% CI, 0.66–1.35; p = 0.75) for patients with CHD/PAD and lacunar stroke compared with patients with isolated lacunar stroke. The HR for MACEs was 1.01 (95% CI, 0.69–1.49; p = 0.94) for patients with CHD and lacunar stroke, 1.11 (95% CI, 0.65–1.90; p = 0.71) for patients with PAD and lacunar stroke, and 0.99 (95% CI, 0.70–1.40; p = 0.95) for patients with CHD/PAD and lacunar stroke.

Conclusion: Polyvascular disease is not associated with recurrence of stroke and MACEs in patients with recent lacunar stroke at 1 year.
Age-at-Injury Determines the Extent of Long-Term Neuropathology and Microgliosis After a Diffuse Brain Injury in Male Rats
Authors: Doust Yasmine V. , Rowe Rachel K. , Adelson P. David , Lifshitz Jonathan , Ziebell Jenna M.
Published: September 2021

Traumatic brain injury (TBI) can occur at any age, from youth to the elderly, and its contribution to age-related neuropathology remains unknown. Few studies have investigated the relationship between age-at-injury and pathophysiology at a discrete biological age. In this study, we report the immunohistochemical analysis of naïve rat brains compared to those subjected to diffuse TBI by midline fluid percussion injury (mFPI) at post-natal day (PND) 17, PND35, 2-, 4-, or 6-months of age. All brains were collected when rats were 10-months of age (n = 6–7/group). Generalized linear mixed models were fitted to analyze binomial proportion and count data with R Studio. Amyloid precursor protein (APP) and neurofilament (SMI34, SMI32) neuronal pathology were counted in the corpus callosum (CC) and primary sensory barrel field (S1BF). Phosphorylated TAR DNA-binding protein 43 (pTDP-43) neuropathology was counted in the S1BF and hippocampus. There was a significantly greater extent of APP and SMI34 axonal pathology and pTDP-43 neuropathology following a TBI compared with naïves regardless of brain region or age-at-injury. However, age-at-injury did determine the extent of dendritic neurofilament (SMI32) pathology in the CC and S1BF where all brain-injured rats exhibited a greater extent of pathology compared with naïve. No significant differences were detected in the extent of astrocyte activation between brain-injured and naïve rats. Microglia counts were conducted in the S1BF, hippocampus, ventral posteromedial (VPM) nucleus, zona incerta, and posterior hypothalamic nucleus. There was a significantly greater proportion of deramified microglia, regardless of whether the TBI was recent or remote, but this only occurred in the S1BF and hippocampus. The proportion of microglia with colocalized CD68 and TREM2 in the S1BF was greater in all brain-injured rats compared with naïve, regardless of whether the TBI was recent or remote. Only rats with recent TBI exhibited a greater proportion of CD68-positive microglia compared with naive in the hippocampus and posterior hypothalamic nucleus. Whilst, only rats with a remote brain-injury displayed a greater proportion of microglia colocalized with TREM2 in the hippocampus. Thus, chronic alterations in neuronal and microglial characteristics are evident in the injured brain despite the recency of a diffuse brain injury.
A Novel Spectrum Contrast Mapping Method for Functional Magnetic Resonance Imaging Data Analysis
Authors: Yu Qin , Cai Zenglin , Li Cunhua , Xiong Yulong , Yang Yang , He Shuang , Tang Haitong , Zhang Bo , Du Shouyun , Yan Hongjie , Chang Chunqi , Wang Nizhuan
Published: September 2021

Many studies reported that spontaneous fluctuation of the blood oxygen level-dependent signal exists in multiple frequency components and changes over time. By assuming a reliable energy contrast between low- and high-frequency bands for each voxel, we developed a novel spectrum contrast mapping (SCM) method to decode brain activity at the voxel-wise level and further validated it in designed experiments. SCM consists of the following steps: first, the time course of each given voxel is subjected to fast Fourier transformation; the corresponding spectrum is divided into low- and high-frequency bands by given reference frequency points; then, the spectral energy ratio of the low- to high-frequency bands is calculated for each given voxel. Finally, the activity decoding map is formed by the aforementioned energy contrast values of each voxel. Our experimental results demonstrate that the SCM (1) was able to characterize the energy contrast of task-related brain regions; (2) could decode brain activity at rest, as validated by the eyes-closed and eyes-open resting-state experiments; (3) was verified with test-retest validation, indicating excellent reliability with most coefficients > 0.9 across the test sessions; and (4) could locate the aberrant energy contrast regions which might reveal the brain pathology of brain diseases, such as Parkinson’s disease. In summary, we demonstrated that the reliable energy contrast feature was a useful biomarker in characterizing brain states, and the corresponding SCM showed excellent brain activity-decoding performance at the individual and group levels, implying its potentially broad application in neuroscience, neuroimaging, and brain diseases.