bluuebunny/crossref_metadata_2025 huggingface dataset:
ATTITUDES TOWARDS DISEASE IN PATIENTS WITH CHRONIC PHASE OF ISCHEMIC STROKE BY THE RESULTS OF THE PERSONAL QUESTIONNAIRE OF THE BEKHTEREV INSTITUTE
Authors: Babirad A.M.
Published: July 2021

Every year, strokes are diagnosed in about 16 million people, of whom 5.7 million die and about the same number become disabled (Feigin V.L., Forouzanfar M.H., Krishnamurthi R., et al., 2014; Virani S.S., Alonso A., Benjamin E.J., et al., 2020; Kim J., Thayabaranathan T., Donnan G.A., et al. 2020). The objective of our research was to study the attitudes towards disease in patients with chronic phase of ischemic stroke. Material and methods. 100 consecutive patients with chronic phase of ischemic stroke and 17 patients with chronic cerebral ischemia were questioned in neurology in-patient department. The types of attitude towards disease were identified with the help of the Personal Questionnaire of the Bekhterev Institute. Results. We found that pathological types of attitude towards disease begin to form before the development of a stroke as a result of chronic cerebral ischemia. Among patients with chronic phase of ischemic stroke, pathological types of attitude towards disease prevailed significantly, and the harmonious type was rare (84.0% vs 16.0%, p < 0.001). The most frequently observed were neurasthenic (36.0%), harmonious (16.0%), anxious (16.0%), ergopathic (10.0%) and sensitive (8.0%) types of attitude towards disease. Our study has shown that any ischemic stroke, even in the case of complete recovery of the lost functions, can be associated with pathological types of attitude towards disease.
Keywords: ischemic stroke, the Personal Questionnaire of the Bekhterev Institute, attitudes towards disease.
Spatial variation in vital rates and population growth of thick-billed murres in the Atlantic Arctic
Authors: Frederiksen M , Descamps S , Elliott KH , Gaston AJ , Huffeldt NP , Kolbeinsson Y , Linnebjerg JF , Lorentzen E , Merkel FR , Strøm H , Thórarinsson TL
Published: July 2021

Understanding spatiotemporal variation in vital rates and population growth rates is a central aim of population ecology, and is critical to conservation of migratory species where different populations may spend the non-breeding season in sometimes widely separated areas. However, estimating those parameters and identifying the underlying drivers of variation for species migrating to remote areas is challenging. The thick-billed murre Uria lomvia is a colonial seabird with a pan-Arctic distribution. Previous studies have documented large-scale spatial variation in population growth in the species’ Atlantic range, with eastern populations declining and western populations being stable, and suggested that this variation was linked to conditions in the wintering areas. We analyse variation in breeding success and adult survival from colonies throughout the Atlantic range, construct region-specific stochastic population models, and compare model predictions to observed colony growth rates. Breeding success was uniformly high in Greenland and Iceland, lower and more variable in Spitsbergen, Bjørnøya and Hudson Bay, and low at Jan Mayen. Adult survival was average or high in all colonies during the 2010s. Observed colony growth rates were lower than modelled growth rates for most populations. This suggests that pre-breeding survival or breeding propensity must have been lower than assumed in many of these populations. Low pre-breeding survival could be linked to poor feeding conditions in fall and winter, possibly influenced by large-scale oceanographic variation. Our results support the idea that seabird populations not subject to breeder mortality due to anthropogenic causes are regulated mainly through variation in pre-breeding survival.
Spatio-temporal patterns in harbour porpoise density: citizen science and conservation in UK seas
Authors: Nielsen KA , Robbins JR , Embling CB
Published: July 2021

Fisheries-induced mortality poses a threat to the conservation of small cetaceans, particularly those found in productive coastal waters. Harbour porpoisesPhocoena phocoenaare ubiquitous in UK seas, but despite their prevalence, knowledge gaps remain on fine-scale space use. A deeper understanding of how distributions vary in space and time is required for appropriate management. Citizen science programs which collect standardized data aboard platforms of opportunity can help uncover patterns and identify higher density areas in the time between surveys of absolute abundance. Here, we analyze citizen science data collected from ferries to investigate spatio-temporal patterns in porpoise densities along routes in UK waters. Region-specific detection functions and generalized additive models were used to estimate abundance and elucidate relationships between distributions and environmental variables. The highest densities during the study period (2006-2017) were found southwest of Cornwall, followed by the North Sea and the English Channel. Average density in the North Sea increased substantially during this time, suggesting new high-use areas along these routes. Density surface models showed strong relationships with coastal waters, sea surface temperature, chlorophyll, and water column dynamics. Contrasting preferences for stratified waters in the North Sea and well-mixed areas in the channel suggest distinct foraging behaviours. Higher density areas were identified in the southwestern and northeastern UK, indicating priority areas for conservation efforts, especially in Cornish waters where porpoises are highly vulnerable to bycatch. Findings highlight how citizen science, together with robust density estimation, can contribute to the conservation management of a common, although threatened, species.
Fine-scale spatial and diel dynamics of zooplanktivorous fish on temperate rocky and artificial reefs
Authors: Holland MM , Becker A , Smith JA , Everett JD , Suthers IM
Published: July 2021

Plankton is an important component of the food web in coastal reef ecosystems. Ocean currents subsidise local production by supplying plankton to resident and reef-associated planktivorous fishes. Measuring the fine-scale distribution of these schooling fishes provides insight into their habitat use and how they balance risk and reward while foraging for plankton. Maintaining their proximity to benthic structure can provide refuge from predation but may also limit foraging opportunities. We used a portable multibeam echosounder to survey schooling fish at 5 natural and 3 artificial reefs, during day and night and under different current conditions. We isolated midwater acoustic targets and used generalised linear models to explain the distribution of schools as a function of current exposure, distance from structure and seafloor complexity. We also isolated individual schools and used generalised least squares to model how school characteristics differed between night and day, using spatial metrics of school area, perimeter length and height above the seafloor. Modelling revealed that the occurrence of schools was almost twice as likely upstream versus downstream of artificial reefs, although distance to reef structure was the main influence. School occurrence was also more likely on artificial versus natural reefs. Schools at artificial reefs exhibited greater volume and areal coverage at night, and during the day they rose higher in the water column while aggregating more closely around the reef. These findings suggest that artificial and natural reefs featuring enhanced vertical relief and direct exposure to the prevailing current are preferred habitats for planktivorous fish.
Bilayer Membrane Composed of Mineralized Collagen and Chitosan Cast Film Coated With Berberine-Loaded PCL/PVP Electrospun Nanofiber Promotes Bone Regeneration
Authors: Zhang Yuhan , Wang Ting , Li Juan , Cui Xiaoming , Jiang Mingxia , Zhang Mogen , Wang Xiaoli , Zhang Weifen , Liu Zhijun
Published: July 2021

Bone defects are difficult to repair and reconstruct as bone regeneration remains technically challenging, with exogenous factors required to accelerate this process. Biodegradable synthetic scaffolds are promising materials for stimulating bone tissue repair. In this study, we investigated whether a bilayer membrane that includes mineralized collagen (MC) and chitosan (CS) delivering berberine (BER)—a typical Chinese herbal monomer—could promote bone healing in a rat model. An MC/CS cast film was coated with polycaprolactone (PCL)/polyvinylpyrrolidone (PVP) electrospun nanofibers loaded with BER, yielding the BER@PCL/PVP-MC/CS bilayer membrane. The 3-dimensional structure had nanofibers of uniform diameter and showed good hydrophilicity; the bilayer membrane showed favorable mechanical properties. BER@PCL/PVP-MC/CS enhanced the proliferation and attachment of MC3T3-E1 cells in vitro and induced bone regeneration when implanted into a rat femoral bone defect. These findings provide evidence that BER@PCL/PVP-MC/CS has clinical potential for effective bone repair.
Effects of Mechanical Compression on Chondrogenesis of Human Synovium-Derived Mesenchymal Stem Cells in Agarose Hydrogel
Authors: Ge Yuxiang , Li Yixuan , Wang Zixu , Li Lan , Teng Huajian , Jiang Qing
Published: July 2021

Mechanical compression is a double-edged sword for cartilage remodeling, and the effect of mechanical compression on chondrogenic differentiation still remains elusive to date. Herein, we investigate the effect of mechanical dynamic compression on the chondrogenic differentiation of human synovium-derived mesenchymal stem cells (SMSCs). To this aim, SMSCs encapsulated in agarose hydrogels were cultured in chondrogenic-induced medium with or without dynamic compression. Dynamic compression was applied at either early time-point (day 1) or late time-point (day 21) during chondrogenic induction period. We found that dynamic compression initiated at early time-point downregulated the expression level of chondrocyte-specific markers as well as hypertrophy-specific markers compared with unloaded control. On the contrary, dynamic compression applied at late time-point not only enhanced the levels of cartilage matrix gene expression, but also suppressed the hypertrophic development of SMSCs compared with unloaded controls. Taken together, our findings suggest that dynamic mechanical compression loading not only promotes chondrogenic differentiation of SMSCs, but also plays a vital role in the maintenance of cartilage phenotype, and our findings also provide an experimental guide for stem cell-based cartilage repair and regeneration.
RPL19 Is a Prognostic Biomarker and Promotes Tumor Progression in Hepatocellular Carcinoma
Authors: Rao Benchen , Li Jianhao , Ren Tong , Yang Jing , Zhang Guizhen , Liu Liwen , Wang Haiyu , Huang Maoxin , Ren Zhigang , Yu Zujiang
Published: July 2021

Background

Hepatocellular carcinoma (HCC) is one of the most common malignancies, and the therapeutic outcome remains undesirable due to its recurrence and metastasis. Gene dysregulation plays a pivotal role in the occurrence and progression of cancer, and the molecular mechanisms are largely unknown.

Methods

The differentially expressed genes of HCC screened from the GSE39791 dataset were used to conduct weighted gene co-expression network analysis. The selected hub genes were validated in The Cancer Genome Atlas (TCGA) database and 11 HCC datasets from the Gene Expression Omnibus (GEO) database. Then, a tissue microarray comprising 90 HCC specimens and 90 adjacent normal specimens was used to validate the hub genes. Moreover, the Hallmark, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases were used to identify enriched pathways. Then, we conducted the immune infiltration analysis.

Results

A total of 17 co-expression modules were obtained by weighted gene co-expression network analysis. The green, blue, and purple modules were the most relevant to HCC samples. Four hub genes, RPL19, RPL35A, RPL27A, and RPS12, were identified. Interestingly, we found that all four genes were highly expressed in HCC and that their high expression was related to a poor prognosis by analyzing the TCGA and GEO databases. Furthermore, we investigated RPL19 in HCC tissue microarrays and demonstrated that RPL19 was overexpressed in tumor tissues compared with non-tumor tissues (p = 0.016). Moreover, overexpression of RPL19 predicted a poor prognosis in hepatocellular carcinoma (p < 0.0007). Then, enrichment analysis revealed that cell cycle pathways were significantly enriched, and bile acid metabolism-related pathways were significantly down-regulated when RPL19 was highly expressed. Furthermore, immune infiltration analysis showed that immune response was suppressed.

Conclusion

Our study demonstrates that RPL19 may play an important role in promoting tumor progression and is correlated with a poor prognosis in HCC. RPL19 may serve as a promising biomarker and therapeutic target for the precise diagnosis and treatment of HCC in the future.
QSOX2 Is an E2F1 Target Gene and a Novel Serum Biomarker for Monitoring Tumor Growth and Predicting Survival in Advanced NSCLC
Authors: Li Yaqi , Liu Mei , Zhang Zhuoxian , Deng Libin , Zhai ZhenYu , Liu Hua , Wang Yiting , Zhang Cheng , Xiong Jianping , Shi Chao
Published: July 2021

Background

Quiescin Q6 sulfhydryl oxidase 2 (QSOX2), an enzyme that can be directly secreted into the extracellular space, is known to be associated with oxidative protein folding. However, whether QSOX2 is abnormally expressed in non-small cell lung cancer (NSCLC) and its role in tumor growth remains unclear.

Methods

Real-time quantitative PCR (qPCR), immunohistochemistry (IHC), bioinformatics analyses were applied to analyze the expression pattern and prognostic significance of QSOX2 in NSCLC. Xenografts model, enzyme-linked immunosorbent assays (ELISA), western blot analysis (WB), and IHC were preformed to examine in vivo tumor suppression and intracellular and extracellular expression of QSOX2. Flow cytometry, WB and qPCR analyses were used to elucidate the role of QSOX2 in cell cycle regulation. Chromatin immunoprecipitation assay (ChIP) assay and Dual-Luciferase reporter assay were employed to investigate transcriptional regulation of QSOX2 by E2F Transcription Factor 1 (E2F1).

Results

Quiescin sulfhydryl oxidase 2 was significantly overexpressed in NSCLC and associated with poor survival in advanced-stage patients. The intracellular and extracellular expression of QSOX2 by tumor cells markedly decreased after anti-cancer therapy in vitro, in vivo and in the clinic. Moreover, QSOX2 silencing in NSCLC cell lines resulted in inhibition of cancer cell proliferation, induction of apoptosis, and decreased expression of cell division-related genes (CENPF and NUSAP1) and Wnt pathway activators (PRRX2 and Nuc-β-catenin). Mechanistically, QSOX2 was expressed periodically during cell cycle and directly regulated by E2F1.

Conclusions

Our findings demonstrate that QSOX2 is directly regulated by E2F1 in the cell cycle, which is essential for the proliferation of NSCLC cells. Furthermore, QSOX2 is a prognostic indicator for NSCLC and may be developed into a biomarker for monitoring tumor burden and therapeutic progress.
Mitochondrial Structure and Polarity in Dendrites and the Axon Initial Segment Are Regulated by Homeostatic Plasticity and Dysregulated in Fragile X Syndrome
Authors: Bülow Pernille , Wenner Peter A. , Faundez Victor , Bassell Gary J.
Published: July 2021

Mitochondrial dysfunction has long been overlooked in neurodevelopmental disorders, but recent studies have provided new links to genetic forms of autism, including Rett syndrome and fragile X syndrome (FXS). Mitochondria show plasticity in morphology and function in response to neuronal activity, and previous research has reported impairments in mitochondrial morphology and function in disease. We and others have previously reported abnormalities in distinct types of homeostatic plasticity in FXS. It remains unknown if or how activity deprivation triggering homeostatic plasticity affects mitochondria in axons and/or dendrites and whether impairments occur in neurodevelopmental disorders. Here, we test the hypothesis that mitochondria are structurally and functionally modified in a compartment-specific manner during homeostatic plasticity using a model of activity deprivation in cortical neurons from wild-type mice and that this plasticity-induced regulation is altered in Fmr1-knockout (KO) neurons. We uncovered dendrite-specific regulation of the mitochondrial surface area, whereas axon initial segment (AIS) mitochondria show changes in polarity; both responses are lost in the Fmr1 KO. Taken together, our results demonstrate impairments in mitochondrial plasticity in FXS, which has not previously been reported. These results suggest that mitochondrial dysregulation in FXS could contribute to abnormal neuronal plasticity, with broader implications to other neurodevelopmental disorders and therapeutic strategies.
Prediction of Gut Microbial Community Structure and Function in Polycystic Ovary Syndrome With High Low-Density Lipoprotein Cholesterol
Authors: Zhu Xuping , Li Yanyu , Jiang Yanmin , Zhang Jisheng , Duan Ru , Liu Lin , Liu Chao , Xu Xiang , Yu Lu , Wang Qian , Xiong Fan , Ni Chengming , Xu Lan , He Qing
Published: July 2021

Gut microbiota has been proved to be involved in the occurrence and development of many diseases, such as type 2 diabetes, obesity, coronary heart disease, etcetera. It provides a new idea for the pathogenesis of polycystic ovary syndrome (PCOS). Our study showed that the gut microbial community of PCOS with high low-density lipoprotein cholesterol (LDLC) has a noticeable imbalance. Gut microbiota of PCOS patients was significantly changed compared with CON, and these changes were closely related to LDLC. Gut microbiota may affect the metabolic level of PCOS patients through multiple metabolic pathways, and lipid metabolism disorder may further aggravate the imbalance of gut microbiota. Actinomycetaceae, Enterobacteriaceae and Streptococcaceae had high accuracy in the diagnosis of PCOS and the differentiation of subgroups, suggesting that they may play an important role in the diagnosis and treatment of PCOS in the future. Also, the model we built showed good specificity and sensitivity for distinguishing PCOS from CON (including L_CON and L_PCOS, H_CON and H_PCOS). In conclusion, this is the first report on the gut microbiota of PCOS with high LDLC, suggesting that in the drug development or treatment of PCOS patients, the difference of gut microbiota in PCOS patients with different LDLC levels should be fully considered.
Integrative Analysis of HTNV Glycoprotein Derived MHC II Epitopes by In Silico Prediction and Experimental Validation
Authors: Sun Hao , Lu Zhenhua , Xuan Guoyun , Liu Ning , Wang Tianhu , Liu Yang , Lan Mingfu , Xu Jiahao , Feng Yuancai , Xu Shuang , Lu Yuchen , Sun Baozeng , Zhang Jinpeng , Zhang Xiyang , Sun Yuanjie , Yang Shuya , Zhang Yun , Zhang Yusi , Cheng Linfeng , Jiang Dongbo , Yang Kun
Published: July 2021

Hantaan virus (HTNV), the causative pathogen of hemorrhagic fever with renal syndrome (HFRS), is a negative RNA virus belonging to the Orthohantaviridae family. HTNV envelope glycoprotein (GP), encoded by the genomic medium segment, is immunogenic and is therefore a promising vaccine candidate. Major histocompatibility complex class I (MHC-I) epitopes derived from HTNV has been extensively studied, but little is known of MHC-II epitopes. In silico predictions based on four databases indicated that the full-length HTNV GP has 1121 15-mer epitopes, of which 289 had a high score for binding to the human and murine MHC-II superfamily. It found that epitope ILTVLKFIANIFHTS could potentially bind most MHC-II molecules covering human and murine haplotypes. Dominant epitopes were validated by enzyme-linked immunospot assay of splenocytes from immunized mice; 6 of 10 epitopes supported the predictions including TATYSIVGPANAKVP, TKTLVIGQCIYTITS, FSLLPGVAHSIAVEL, CETYKELKAHGVSCP, CGLYLDRLKPVGSAY, and NLGENPCKIGLQTSS. Conservation analysis of dominant epitopes revealed host–virus interactions without geographic stratification, thus meeting the requirements of candidate vaccines for large-population prophylaxis. These findings provide insight into hantavirus antigenicity and suggest that vaccines targeting MHC-II could provide immune protection in large population to complement symptomatic therapies for the treatment of HFRS.
Biological Effect of Streptococcus pyogenes-Released Extracellular Vesicles on Human Monocytic Cells, Induction of Cytotoxicity, and Inflammatory Response
Authors: Murase Kazunori , Aikawa Chihiro , Nozawa Takashi , Nakatake Ayako , Sakamoto Kuniyo , Kikuchi Taisei , Nakagawa Ichiro
Published: July 2021

Most bacteria naturally release spherical lipid-bilayered extracellular vesicles (EVs) containing proteins, nucleic acids, and virulence-related molecules, thus contributing to diverse biological functions including transport of virulence factors. The group A streptococcus, Streptococcus pyogenes (GAS), a major human pathogen, also releases EVs; however, it remains unclear how GAS EVs interact physiologically and pathologically with host cells, and what the differences are between invasive and non-invasive strains. The proteome profile in this study revealed that GAS EVs enclosed many virulence-related proteins such as streptolysin O and NAD-glycohydrolase, facilitating their pathogenicity, and invasive GAS EVs were more abundant than non-invasive counterparts. In terms of biological effects, invasive GAS EVs showed slo-dependent cytotoxic activity and the induction of cytokine expression, contributing to GAS pathogenicity directly. Although non-invasive GAS EVs did not show cytotoxic activity, they may be utilized as a means to prevent antibacterial mechanisms such as autophagy, leading to enhancement of their own survival in the intracellular environment after the infection. These results suggest that invasive and non-invasive GAS EVs play different roles in GAS infection strategy and pathogenicity. Our findings also indicate that EVs could be a key factor for GAS pathogenicity in GAS-host interactions.
Understanding Human–Canid Conflict and Coexistence: Socioeconomic Correlates Underlying Local Attitude and Support Toward the Endangered Dhole (Cuon alpinus) in Bhutan
Authors: Thinley Phuntsho , Rajaratnam Rajanathan , Norbu Lam , Dorji Lungten , Tenzin Jigme , Namgyal Chhimi , Yangzom Choney , Wangchuk Tashi , Wangdi Sonam , Dendup Tshering , Tashi Sonam , Wangmo Cheten
Published: July 2021

Understanding human–canid conflict and coexistence must focus on documenting human–canid interactions and identifying the underlying drivers of reciprocal human attitude which enables appropriate strategies to minimize conflict and forge coexistence. The dhole (Cuon alpinus), Asia's most widely distributed wild canid, is highly threatened by human persecution and anthropogenic activities. Despite its “endangered” status, its ecological role as an apex predator, negative interactions with humans, and dhole-specific attitude studies are limited, thus hindering the development of a comprehensive dhole-conservation strategy. Here, we investigate the influence of socioeconomic factors of age, gender, income, residency inside/outside a protected area (PA), and other variables (cultural beliefs, livestock loss, and quantity of livestock loss) on the attitudes of local people and support for dhole conservation in the Himalayan Kingdom of Bhutan. We conducted a semi-structured questionnaire survey of 1,444 households located within the PA and non-PA from four representative regions in the country. Using R programming, we ran Pearson's chi-square test of independence to test the overall difference in the attitude and support for dhole conservation, followed by recursive partitioning through a conditional inference regression tree to identify its significant covariates with the highest explanatory power. Majority (79.1%) of respondents (χ2 = 488.6; df = 1; p < 0.001) disliked the dhole over those who liked it. More than half (57.7%) (χ2 = 412.7; df = 2; p < 0.001) opposed dhole conservation over those who either supported or remained neutral. Experience of livestock loss to dholes was the primary ( p < 0.001) factor influencing the negative attitude and opposition to dhole conservation, despite an acknowledgment of the ecological role of the dhole in controlling agricultural crop predators. Our study, which is the first-ever survey in Bhutan, solely focused on investigating human attitudes and perceptions toward the dhole, indicating that livestock loss to dholes transcends all positive attitudes to the species and drives a predominant dislike and opposition to its conservation. To improve the attitude and support toward the dhole and to foster dhole–human coexistence, livestock predation by dholes needs alleviation by improving the existing animal husbandry, in conjunction with promoting conservation awareness on this species.
Biventricular Morphology and Function Reference Values Derived From a Large Sample of Healthy Chinese Adults by Magnetic Resonance Imaging
Authors: Zhang Zhen , Ma Qiaozhi , Gao Yiyuan , Cao Lizhen , Zhu Chengcheng , Zhao Zhiwei , Zhao Jun , Zeng Linan , Lou Mingwu , Pohost Gerald M. , Li Kuncheng
Published: July 2021

Background: Quantification of cardiac structure and function is essential for diagnostic interpretation and clinical decision making. We sought to establish cardiovascular magnetic resonance (CMR) reference values of left and right ventricular (LV and RV) morphology and function based on a large sample of healthy Chinese adults.

Methods: Five hundred fifty validated healthy Chinese adults (aged 21–70 years; 323 men) free of hypertension, diabetes, and obesity were included in this study. All the subjects were stratified by gender (men and women) and age decades. On cine CMR, measurements of biventricular end-diastolic, end-systolic, and stroke volumes (EDV, ESV, and SV), ejection fraction (EF), and end-diastolic LV wall thickness (LVWT) and mass (LVM) were obtained.

Results: Men had greater LVEDV (111.6 ± 19.8 vs. 94.6 ± 15.6 ml), LVESV (36.5 ± 9.8 vs. 28.2 ± 7.9 ml), LVM (121.1 ± 19.9 vs. 86.1 ± 14.5 g), global end-diastolic LVWT (8.1 ± 1.1 vs. 6.7 ± 1.0 mm), RVEDV (128.0 ± 23.6 vs. 101.7 ± 17.0 ml), and RVESV (53.5 ± 13.7 vs. 36.8 ± 8.9 ml), while women had greater LVEF (67.5 ± 5.4 vs. 70.4 ± 5.7%) and RVEF (58.5 ± 5.2 vs. 64.0 ± 5.3%) (all p < 0.001). For both men and women, age was negatively correlated with LVEDV (r = −0.31 and r = −0.32), LVESV (r = −0.37 and r = −0.47), RVEDV (r = −0.31 and r = −0.29), and RVESV (r = −0.33 and r = −0.44), while it was positively correlated with LVEF (r = 0.28 and r = 0.43) and RVEF (r = 0.28 and r = 0.41) (all p < 0.001). Aging was associated with increasing global end-diastolic LVWT and LVM/LVEDV in both sexes (all p < 0.001). Older age was associated with increasing LVM only in women (r = 0.36, p < 0.001), not in men (r = 0.05, p = 0.359).

Conclusions: We systematically provide age-, sex-, and body size-specific CMR reference values for biventricular morphology and function based on a large sample of healthy Chinese adults. Biventricular structure and function are significantly associated with age and sex.
Surface Mass-Balance Gradients From Elevation and Ice Flux Data in the Columbia Basin, Canada
Authors: Pelto Ben M. , Menounos Brian
Published: July 2021

The mass-balance—elevation relation for a given glacier is required for many numerical models of ice flow. Direct measurements of this relation using remotely-sensed methods are complicated by ice dynamics, so observations are currently limited to glaciers where surface mass-balance measurements are routinely made. We test the viability of using the continuity equation to estimate annual surface mass balance between flux-gates in the absence of in situ measurements, on five glaciers in the Columbia Mountains of British Columbia, Canada. Repeat airborne laser scanning surveys of glacier surface elevation, ice penetrating radar surveys and publicly available maps of ice thickness are used to estimate changes in surface elevation and ice flux. We evaluate this approach by comparing modeled to observed mass balance. Modeled mass-balance gradients well-approximate those obtained from direct measurement of surface mass balance, with a mean difference of +6.6 ± 4%. Regressing modeled mass balance, equilibrium line altitudes are on average 15 m higher than satellite-observations of the transient snow line. Estimates of mass balance over flux bins compare less favorably than the gradients. Average mean error (+0.03 ± 0.07 m w.e.) between observed and modeled mass balance over flux bins is relatively small, yet mean absolute error (0.55 ± 0.18 m w.e.) and average modeled mass-balance uncertainty (0.57 m w.e.) are large. Mass conservation, assessed with glaciological data, is respected (when estimates are within 1σ uncertainties) for 84% of flux bins representing 86% of total glacier area. Uncertainty on ice velocity, especially for areas where surface velocity is low (<10 m a−1) contributes the greatest error in estimating ice flux. We find that using modeled ice thicknesses yields comparable modeled mass-balance gradients relative to using observations of ice thickness, but we caution against over-interpreting individual flux-bin mass balances due to large mass-balance residuals. Given the performance of modeled ice thickness and the increasing availability of ice velocity and surface topography data, we suggest that similar efforts to produce mass-balance gradients using modern high-resolution datasets are feasible on larger scales.
Carbon and Nitrogen Cycle Dynamic in Continental Late-Carboniferous to Early Permian Basins of Eastern Pangea (Northeastern Massif Central, France)
Authors: Mercuzot Mathilde , Thomazo Christophe , Schnyder Johann , Pellenard Pierre , Baudin François , Pierson-Wickmann Anne-Catherine , Sans-Jofre Pierre , Bourquin Sylvie , Beccaletto Laurent , Santoni Anne-Lise , Gand Georges , Buisson Matthieu , Glé Laure , Munier Thomas , Saloume Antonios , Boussaid Mohamed , Boucher Tracy
Published: July 2021

Late Carboniferous to early Permian organic-rich sedimentary successions of late-orogenic continental basins from the northeastern Massif Central (France) coincide with both the Variscan mountain dismantling and the acme of the long-lasting Late Paleozoic Ice Age. Here, we investigate the carbon and nitrogen cycles in the newly dated sedimentary successions of the Decize–La Machine and Autun basins during these geodynamic and climate upheavals. The sedimentary organic matter has been analyzed through Rock-Eval pyrolysis, palynofacies and elemental and isotope geochemistry along cored-wells and outcropping sections, previously accurately defined in terms of paleo-depositional environments. Rock-Eval and palynofacies data have evidenced two origins of organic matter: a phytoplanktonic/bacterial lacustrine origin (Type I organic matter, organic δ13C values around −23.5‰), and a terrestrial origin (vascular land plants, Type III organic matter, organic δ13C values around −20‰), mixed in the deltaic-lacustrine sediments during background sedimentation (mean organic δ13C values around −22‰). Episodes of high organic matter storage, reflected by black shales and coal-bearing deposits (total organic carbon up to 20 and 70%, respectively) are also recognized in the successions, and are characterized by large negative organic carbon isotope excursions down to −29‰. We suggest that these negative isotope excursions reflect secondary processes, such as organic matter remineralization and/or secondary productivity varying under strict local controls, or possibly larger scale climate controls. At times, these negative δ13C excursions are paired with positive δ15N excursions up to +10‰, reflecting water column denitrification and anammox during lake-water stratification episodes. Together, these isotopic signals (i.e., low sedimentary organic δ13C associated with high bulk δ15N values) indicate periods of high primary productivity of surface waters, where nitrogen and carbon cycles are spatially decoupled. These local processes on the sedimentary isotope archives may partially blur our ability to directly reconstruct paleoclimate variations in such continental settings using only C and N isotopes. At last, we explore an organic δ13C-based mixing model to propose ways to disentangle autochthonous versus allochthonous origin of organic matter in lacustrine continental settings.
Thermal Regime and Variations in the Island Permafrost Near the Northern Permafrost Boundary in Xidatan, Qinghai–Tibet Plateau
Authors: Yin Guoan , Luo Jing , Niu Fujun , Lin Zhanju , Liu Minghao
Published: July 2021

Although the thermal regime and degradation of permafrost on the Qinghai-Tibet Plateau (QTP) have been widely documented, little information exists regarding the island permafrost in the area. Ground temperatures were therefore measured for 8 years (2013–2020) at a permafrost island and at two contrasting sites in the Xidatan region to elucidate the permafrost in this area. Results indicate that the ground temperatures in the island permafrost were markedly higher than those at the same depth in the nearby marginal permafrost and the interior continuous permafrost. In addition, a distinct increasing trend was observed in the ground temperature of the island permafrost over the past 8 years, and warming was signficanty faster in the deep soil than in the topsoil, indicating a bottom–up degradation pattern in the island permafrost. Moreover, due to the persistent increase in the thickness of the active-layer and the decrease in the depth of permafrost table, the permafrost island abruptly disappeared in 2018, which may be attributed to the anomalously high air temperatures that occurred in 2016 and 2017. The results of this study may provide references for understanding of the thermal regime and degradation process of island permafrost on the QTP.
Genome-Wide Association Study Reveals PC4 as the Candidate Gene for Thermal Tolerance in Bay Scallop (Argopecten irradians irradians)
Authors: Zhu Xinghai , Liu Pingping , Hou Xiujiang , Zhang Junhao , Lv Jia , Lu Wei , Zeng Qifan , Huang Xiaoting , Xing Qiang , Bao Zhenmin
Published: July 2021

The increasing sea temperature caused by global warming has resulted in severe mortalities in maricultural scallops. Therefore, improving thermal tolerance has become an active research area in the scallop farming industry. Bay scallop (Argopecten irradians irradians) was introduced into China in 1982 and has developed into a vast aquaculture industry in northern China. To date, genetic studies on thermal tolerance in bay scallops are limited, and no systematic screening of thermal tolerance-related loci or genes has been conducted in this species. In the present study, we conducted a genome-wide association study (GWAS) for thermal tolerance using the Arrhenius break temperature (ABT) indicators of 435 bay scallops and 38,011 single nucleotide polymorphism (SNP) markers. The GWAS identified 1,906 significant thermal tolerance-associated SNPs located in 16 chromosomes of bay scallop. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that 638 genes were enriched in 42 GO terms, while 549 annotated genes were enriched in aggregation pathways. Additionally, the SNP (15-5091-20379557-1) with the lowest P value was located in the transcriptional coactivator p15 (PC4) gene, which is involved in regulating DNA damage repair and stabilizing genome functions. Further analysis in another population identified two new thermal tolerance-associated SNPs in the first coding sequence of PC4 in bay scallops (AiPC4). Moreover, AiPC4 expression levels were significantly correlated (r = 0.675–0.962; P < 0.05) with the ABT values of the examined bay scallops. Our data suggest that AiPC4 might be a positive regulator of thermal tolerance and a potential candidate gene for molecular breeding in bay scallop aiming at thermal tolerance improvement.
Exploring the Impact of Cerebrovascular Disease and Major Depression on Non-diseased Human Tissue Transcriptomes
Authors: Poon Chi-Lam , Chen Cho-Yi
Published: July 2021

Background

The development of complex diseases is contributed by the combination of multiple factors and complicated interactions between them. Inflammation has recently been associated with many complex diseases and may cause long-term damage to the human body. In this study, we examined whether two types of complex disease, cerebrovascular disease (CVD) or major depression (MD), systematically altered the transcriptomes of non-diseased human tissues and whether inflammation is linked to identifiable molecular signatures, using post-mortem samples from the Genotype-Tissue Expression (GTEx) project.

Results

Following a series of differential expression analyses, dozens to hundreds of differentially expressed genes (DEGs) were identified in multiple tissues between subjects with and without a history of CVD or MD. DEGs from these disease-associated tissues—the visceral adipose, tibial artery, caudate, and spinal cord for CVD; and the hypothalamus, putamen, and spinal cord for MD—were further analyzed for functional enrichment. Many pathways associated with immunological events were enriched in the upregulated DEGs of the CVD-associated tissues, as were the neurological and metabolic pathways in DEGs of the MD-associated tissues. Eight gene-tissue pairs were found to overlap with those prioritized by our transcriptome-wide association studies, indicating a potential genetic effect on gene expression for circulating cytokine phenotypes.

Conclusion

Cerebrovascular disease and major depression cause detectable changes in the gene expression of non-diseased tissues, suggesting that a possible long-term impact of diseases, lifestyles and environmental factors may together contribute to the appearance of “transcriptomic scars” on the human body. Furthermore, inflammation is probably one of the systemic and long-lasting effects of cerebrovascular events.
Comparative Transcriptome Analysis of Milk Somatic Cells During Lactation Between Two Intensively Reared Dairy Sheep Breeds
Authors: Michailidou Sofia , Gelasakis Athanasios , Banos Georgios , Arsenos George , Argiriou Anagnostis
Published: July 2021

In dairy sheep industry, milk production dictates the value of a ewe. Milk production is directly related to the morphology and physiology of the mammary gland; both being designated targets of breeding strategies. Although within a flock breeding parameters are mutual, large differences in milk production among individual ewes are usually observed. In this work, we tested two of the most productive dairy sheep breeds reared intensively in Greece, one local the Chios breed and one foreign the Lacaune breed. We used transcriptome sequencing to reveal molecular mechanisms that render the mammary gland highly productive or not. While highly expressed genes (caseins and major whey protein genes) were common among breeds, differences were observed in differentially expressed genes. ENSOARG00000008077, as a member of ribosomal protein 14 family, together with LPCAT2, CCR3, GPSM2, ZNF131, and ASIP were among the genes significantly differentiating mammary gland’s productivity in high yielding ewes. Gene ontology terms were mainly linked to the inherent transcriptional activity of the mammary gland (GO:0005524, GO:0030552, GO:0016740, GO:0004842), lipid transfer activity (GO:0005319) and innate immunity (GO:0002376, GO:0075528, GO:0002520). In addition, clusters of genes affecting zinc and iron trafficking into mitochondria were highlighted for high yielding ewes (GO:0071294, GO:0010043). Our analyses provide insights into the molecular pathways involved in lactation between ewes of different performances. Results revealed management issues that should be addressed by breeders in order to move toward increased milk yields through selection of the desired phenotypes. Our results will also contribute toward the selection of the most resilient and productive ewes, thus, will strengthen the existing breeding systems against a spectrum of environmental threats.
Rapid Identification of QTL for Mesocotyl Length in Rice Through Combining QTL-seq and Genome-Wide Association Analysis
Authors: Wang Yamei , Liu Jindong , Meng Yun , Liu Hongyan , Liu Chang , Ye Guoyou
Published: July 2021

Mesocotyl is a crucial organ for pushing buds out of soil, which plays a vital role in seedling emergence and establishment in direct-seeded rice. Thus, the identification of quantitative trait loci (QTL) associated with mesocotyl length (ML) could accelerate genetic improvement of rice for direct seeding cultivation. In this study, QTL sequencing (QTL-seq) applied to 12 F2 populations identified 14 QTL for ML, which were distributed on chromosomes 1, 3, 4, 5, 6, 7, and 9 based on the Δ(SNP-index) or G-value statistics. Besides, a genome-wide association study (GWAS) using two diverse panels identified five unique QTL on chromosomes 1, 8, 9, and 12 (2), respectively, explaining 5.3–14.6% of the phenotypic variations. Among these QTL, seven were in the regions harboring known genes or QTLs, whereas the other 10 were potentially novel. Six of the QTL were stable across two or more populations. Eight high-confidence candidate genes related to ML were identified for the stable loci based on annotation and expression analyses. Association analysis revealed that two PCR gel-based markers for the loci co-located by QTL-seq and GWAS, Indel-Chr1:18932318 and Indel-Chr7:15404166 for loci qML1.3 and qML7.2 respectively, were significantly associated with ML in a collection of 140 accessions and could be used as breeder-friendly markers in further breeding.
The Contribution of Serum Complement Component 3 Levels to 90-Day Mortality in Living Donor Liver Transplantation
Authors: Fukui Saeko , Hidaka Masaaki , Fukui Shoichi , Morimoto Shimpei , Hara Takanobu , Soyama Akihiko , Adachi Tomohiko , Matsushima Hajime , Tanaka Takayuki , Fuchigami Mai , Hasegawa Hiroo , Yanagihara Katsunori , Eguchi Susumu
Published: July 2021

The contributions of the complement system have been elucidated in the process of solid organ transplantation, including kidney transplantation. However, the role of complement in liver transplantation is unknown. We sought to elucidate the time-dependent changes of peritransplantational serum complement levels and the relationships with posttransplant outcomes and other immunological biomarkers. We enrolled 82 patients who underwent living-related donor liver transplantation (LDLT). Nine patients (11%) died within 90 days after LDLT (non-survivors). The following immunomarkers were collected preoperatively and at 1, 2, and 4 week(s) after LDLT: serum C3, C4, immunoglobulin G (IgG), and peripheral blood leukocyte populations characterized by CD3, CD4, CD8, CD16, CD19, CD20, CD22, and CD56. Consequently, C3 and C4 increased time-dependently after LDLT. Preoperatively, C3 was negatively correlated with the MELD score, Child–Pugh score, CD16-positive leukocyte percentage, and the CD56-positive leukocyte percentage. Non-survivors had lower levels of C3 at 2 weeks in comparison to survivors (median [interquartile range]: 56 [49-70] mg/dLvs.88 [71-116] mg/dL, p=0.0059). When the cutoff value of C3 at 2 weeks to distinguish non-survivors was set to 71 mg/dL, the sensitivity, specificity, and area under the ROC curve were 87.5%, 75.0%, and 0.80, respectively. A principal component analysis showed an inverse relationship between the C3 and C4 levels and the percentage of CD8-, CD16-, and CD56-positive leukocytes at 1 and 2 week(s). All non-survivors were included in the cluster that showed higher percentages of CD8-, CD16-, and CD56-positive leukocytes at 2 weeks. In conclusion, we demonstrated the relationship between complement, outcomes, and other immunomarkers in LDLT and suggested the usefulness of C3 at 2 weeks after LDLT in distinguishing the mortality.
Case Report: Local Cytokine Release Syndrome in an Acute Lymphoblastic Leukemia Patient After Treatment With Chimeric Antigen Receptor T-Cell Therapy: A Possible Model, Literature Review and Perspective
Authors: Luan Chengxin , Zhou Junjie , Wang Haixia , Ma Xiaoyu , Long Zhangbiao , Cheng Xin , Chen Xiaowen , Huang Zhenqi , Zhang Dagan , Xia Ruixiang , Ge Jian
Published: July 2021

Chimeric antigen receptor T (CAR-T) cell therapy has achieved remarkable clinical efficacy in treatment of many malignancies especially for B-cell hematologic malignancies. However, the application of CAR-T cells is hampered by potentially adverse events, of which cytokine release syndrome (CRS) is one of the severest and the most studied. Local cytokine-release syndrome (L-CRS) at particular parts of the body has been reported once in a while in B-cell lymphoma or other compartmental tumors. The underlying mechanism of L-CRS is not well understood and the existing reports attempting to illustrate it only involve compartmental tumors, some of which even indicated L-CRS only happens in compartmental tumors. Acute lymphoblastic leukemia (ALL) is systemic and our center treated a B-cell ALL patient who exhibited life threatening dyspnea, L-CRS was under suspicion and the patient was successfully rescued with treatment algorithm of CRS. The case is the firstly reported L-CRS related to systemic malignancies and we tentatively propose a model to illustrate the occurrence and development of L-CRS of systemic malignancies inspired by the case and literature, with emphasis on the new recognition of L-CRS.
New Insights From Single-Cell Sequencing Data: Synovial Fibroblasts and Synovial Macrophages in Rheumatoid Arthritis
Authors: Cheng Liyun , Wang Yanyan , Wu Ruihe , Ding Tingting , Xue Hongwei , Gao Chong , Li Xiaofeng , Wang Caihong
Published: July 2021

Single-cell RNA sequencing (scRNA-seq) technology can analyze the transcriptome expression level of cells with high-throughput from the single cell level, fully show the heterogeneity of cells, and provide a new way for the study of multicellular biological heterogeneity. Synovitis is the pathological basis of rheumatoid arthritis (RA). Synovial fibroblasts (SFs) and synovial macrophages are the core target cells of RA, which results in the destruction of articular cartilage, as well as bone. Recent scRNA-seq technology has made breakthroughs in the differentiation and development of two types of synovial cells, identification of subsets, functional analysis, and new therapeutic targets, which will bring remarkable changes in RA treatment.
Regulation of Early Lymphocyte Development via mRNA Decay Catalyzed by the CCR4-NOT Complex
Authors: Akiyama Taishin , Yamamoto Tadashi
Published: July 2021

Development of lymphocytes is precisely regulated by various mechanisms. In addition to transcriptional rates, post-transcriptional regulation of mRNA abundance contributes to differentiation of lymphocytes. mRNA decay is a post-transcriptional mechanism controlling mRNA abundance. The carbon catabolite repression 4 (CCR4)-negative on TATA-less (NOT) complex controls mRNA longevity by catalyzing mRNA deadenylation, which is the rate-limiting step in the mRNA decay pathway. mRNA decay, regulated by the CCR4-NOT complex, is required for differentiation of pro-B to pre-B cells and V(D)J recombination in pro-B cells. In this process, it is likely that the RNA-binding proteins, ZFP36 ring finger protein like 1 and 2, recruit the CCR4-NOT complex to specific target mRNAs, thereby inducing cell quiescence of pro-B cells. A recent study showed that the CCR4-NOT complex participates in positive selection of thymocytes. Mechanistically, the CCR4-NOT deadenylase complex inhibits abnormal apoptosis by reducing the expression level of mRNAs encoding pro-apoptotic proteins, which are otherwise up-regulated during positive selection. We discuss mechanisms regulating CCR4-NOT complex-dependent mRNA decay in lymphocyte development and selection.