bluuebunny/crossref_metadata_2025 huggingface dataset:
Passive Way of Measuring QOL/Well-Being Levels Using Smartphone Log
Authors: Yao Wenhao , Kaminishi Kohei , Yamamoto Naoki , Hamatani Takashi , Yamada Yuki , Kawada Takahiro , Hiyama Satoshi , Okimura Tsukasa , Terasawa Yuri , Maeda Takaki , Mimura Masaru , Ota Jun
Published: March 2022

Research on mental health states involves paying increasing attention to changes in daily life. Researchers have attempted to understand such daily changes by relying on self-reporting through frequent assessment using devices (smartphones); however, they are mostly focused on a single aspect of mental health. Assessing the mental health of a person from various perspectives may help in the primary prevention of mental illness and the comprehensive measurement of mental health. In this study, we used users' smartphone logs to build a model to estimate whether the scores on three types of questionnaires related to quality of life and well-being would increase compared to the previous week (fluctuation model) and whether they would be higher compared to the average for that user (interval model). Sixteen participants completed three questionnaires once per week, and their smartphone logs were recorded over the same period. Based on the results, estimation models were built, and the F-score ranged from 0.739 to 0.818. We also analyzed the features that the estimation model emphasized. Information related to “physical activity,” such as acceleration and tilt of the smartphone, and “environment,” such as atmospheric pressure and illumination, were given more weight in the estimation than information related to “cyber activity,” such as usage of smartphone applications. In particular, in the Positive and Negative Affect Schedule (PANAS), 9 out of 10 top features in the fluctuation model and 7 out of 10 top features in the interval model were related to activities in the physical world, suggesting that short-term mood may be particularly heavily influenced by subjective activities in the human physical world.
Miocene Provenance Changes in Taiwan Caused by Southward Input of Sediments From East China Sea Basin
Authors: Fu Xiaowei , Hu Lichen , Zhu Weilin , Huang Xiangtong , Feng Kailong , Zhou Zengyuan
Published: March 2022

The Cenozoic sediments in marginal basins of East Asia ultimately reflected coupling between the tectonics, landscape evolution, and drainage reorganization. Recently, the provenance of Miocene sediments in the East China Sea Basin (ECSB) and Taiwan has been in hot debate, and several models were proposed to interpret the provenance changes. Most of them are related to river reorganization in East Asia and highly relied on detrital zircon U-Pb dating. In this study, a large number of detrital zircon U-Pb ages of Miocene sediments from the ECSB, Taiwan region, and the potential source areas have been compiled for quantitative provenance analysis. The results suggested that all the early–middle Miocene sediments in Taiwan and the ECSB were closely linked to North China and the Korean Peninsula. Over 80% sediments in Taiwan were delivered from the ECSB whose sediments were predominantly contributed by North China and the Korean Peninsula (70%). However, for the late Miocene to Quaternary sediments in the ECSB, the contribution of the Yangtze River system was 72%, which indicates distinct reorganization of river networks and initial formation of the Yangtze River in the late Miocene. The quantitative provenance analysis together with southward environmental changes from dominantly fluvial sediments in the northern and middle ECSB to shallow marine sediments in Taiwan region suggested that the early–middle Miocene sediments of Taiwan were mainly sourced from the North China and the Korean Peninsula by passing the ECSB. Thus, these sediments in Taiwan region would experience the river–delta–shallow marine route from the ECSB to Taiwan region.
Simulation of Fracturing and Well Pattern Optimization of Fractured Tight Sandstone Reservoirs
Authors: Liao Jianbo , Zhang Zhongyi , Tang Haizhong , Yang Jun , Zhang Xiaolei , Wang Bing
Published: March 2022

The fracturing and well pattern optimization of fractured reservoirs is a hot spot in petroleum engineering. In this study, taking the tight oil reservoirs of the Yanchang Formation in the Ordos Basin as an example, an optimized plan of hydraulic fracturing and well pattern deployment of the fractured tight reservoir were systematically studied using a fluid-solid coupling model. The results show that the Chang 6 Member of Yanchang Formation mainly develop feldspar sandstone. A large number of vertical fractures are developed in Chang 6 Member, and they have significant shearing properties. The target sandstone reservoir is in the mid-diagenetic A stage. Natural fractures have a significant effect on the extension of hydraulic fractures. When the fracturing direction is parallel to the main strike of natural fractures, the extension distance of the hydraulic fractures is long and the fracturing scale is large; however, when the fracturing direction is orthogonal or oblique to the main strike of natural fractures, the extension distance of the hydraulic fractures is limited. Statistics show that the average length of hydraulic fractures when fracturing parallel to natural fractures is 1.3 times of that when fracturing perpendicular to natural fractures. In addition, after optimization of fracturing parameters, we found that the displacement should be controlled at 2–3 cubic meters/min, and the sand ratio should be controlled at 25%. The smaller the horizontal minimum principal stress difference between the fracturing layer and the shielding layer, the lower the elastic modulus, and the easier it is to control the fracture height. Microseismic monitoring results show that the half-fracture length and fracture height are mainly distributed in 80–140 m and 15–25 m, respectively. The optimized fracture half-length was 120 m and the half-fracture height was 20 m. Finally, the well pattern of the target layer is optimized considering natural fractures. Through this study, we found that the reverse five-spot well pattern is suitable for the efficient development of tight oil reservoirs of the Chang 6 Member in this area.
Comparing College Students’ Motivation Trajectories Before and During COVID-19: A Self-Determination Theory Approach
Authors: Corpus Jennifer Henderlong , Robinson Kristy A. , Liu Zhaoying
Published: March 2022

College students’ retrospective reports commonly indicate motivational declines associated with the COVID-19 pandemic. Using Self-Determination Theory, the present study provided a more nuanced examination of the pandemic’s motivational effect by measuring actual change in six distinct types of motivation. We compared motivation trajectories from the first to the fourth year of college for two cohorts of students, with the fourth-year measurement taken prior to the pandemic in one cohort (n = 206) but during the pandemic in the other (n = 270). Compared to the pre-pandemic cohort, the COVID cohort showed sharper declines in identified and intrinsic motivation but no differences in controlled motivation or amotivation. Motivational declines associated with the COVID-19 pandemic appeared to be both real and specific to autonomous motives.
MicroRNAs in Serum Exosomes as Circulating Biomarkers for Postmenopausal Osteoporosis
Authors: Shi Hongli , Jiang Xin , Xu Cuidi , Cheng Qun
Published: March 2022

Postmenopausal osteoporosis (PMOP) is the most common skeletal disease in postmenopausal women and has become a global public health issue. Emerging evidence demonstrated the important relationship between microRNAs and PMOP. However, miRNAs have not yet been reported in PMOP. Hence, the present study aimed to investigate the differences in miRNA expression profiles in PMOP with fragility fractures to identify the key circulating miRNAs in serum exosomes and to validate these molecules as potential biomarkers. Postmenopausal women with osteoporotic fracture and normal bone mass were enrolled. Serum exosomes were isolated by traditional differential ultracentrifugation from participants. Isolated exosomes were identified by electron microscopy, western blotting and nanoparticle-tracking analysis and then examined for exosomal small RNA sequencing. The expression of miRNAs was compared by sRNA deep sequencing and bioinformatics analysis. Three miRNAs (mir-324-3p, mir-766-3p and mir-1247-5p) were found to be associated with BMD of L1-L4, FN (femur neck) and TH (total hip), while mir-330-5p and mir-3124-5p were associated with BMD of FN and TH. Furthermore, mir-330-5p was found to promote the ALP activity of hBMSCs, while mir-3124-5p showed the opposite result. The results showed that serum exosomal miRNAs were differentially expressed in postmenopausal osteoporosis patients with fragility fractures. Our study provides the first evidence that exosomal miRNA profiling revealed aberrant circulating miRNA in postmenopausal osteoporosis. Mir-324-3p, mir-766-3p, mir-1247-5p, mir-330-5p and mir-3124-5p, which were associated with bone mineral density (BMD), may serve as candidate diagnostic biomarkers as well as potentially contribute to pathophysiology of PMOP.
Differences Between Cancer-Specific Survival of Patients With Anaplastic and Primary Squamous Cell Thyroid Carcinoma and Factors Influencing Prognosis: A SEER Database Analysis
Authors: Jin Shuai , Liu Xiangmei , Peng Dandan , Li Dahuan , Ye Yuan-Nong
Published: March 2022

Purpose

Anaplastic thyroid carcinoma (ATC) and primary squamous cell carcinoma of the thyroid (PSCCTh) have similar histological findings and are currently treated using the same approaches; however, the characteristics and prognosis of these cancers are poorly researched. The objective of this study was to determine the differences in characteristics between ATC and PSCCTh and establish prognostic models.

Patients and Methods

All variables of patients with ATC and PSCCTh, diagnosed from 2004–2015, were retrieved from the Surveillance, Epidemiology, and End Results Program (SEER) database. Percentage differences for categorical data were compared using the Chi-square test. Kaplan-Meier curves, log-rank test, and Cox-regression for survival analysis, and C-index value was used to evaluate the performance of the prognostic models.

Results

After application of the inclusion and exclusion criteria, a total of 1164 ATC and 124 PSCCTh patients, diagnosed from 2004 to 2015, were included in the study. There were no differences in sex, ethnicity, age, marital status, or percentage of proximal metastases between the two cancers; however, radiotherapy, chemotherapy, incidence of surgical treatment, and presence of multiple primary tumors were higher in patients with ATC than those with PSCCTh. Further cancer-specific survival (CSS) of patients with PSCCTh was better than that of patients with ATC. Prognostic factors were not identical for the two cancers. Multivariate Cox model analysis indicated that age, sex, radiotherapy, chemotherapy, surgery, multiple primary tumors, marital status, and distant metastasis status are independent prognostic factors for CSS in patients with ATC, while for patients with PSCCTh, the corresponding factors are age, radiotherapy, multiple primary tumors, and surgery. The C-index values of the two models were both > 0.8, indicating that the models exhibited good discriminative ability.

Conclusion

Prognostic factors influencing CSS were not identical in patients with ATC and PSCCTh. These findings indicate that different clinical treatment and management plans are required for patients with these two types of thyroid cancer.
Metabolic Surgery on Patients With Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis
Authors: Yue Wenwen , Huang Xin , Zhang Wenjing , Li Shumin , Liu Xu , Zhao Yian , Shu Jiaxin , Liu Teng , Li Weihua , Liu Shaozhuang
Published: March 2022

Polycystic ovary syndrome (PCOS) is a complicated reproductive endocrine disease that is closely related to obesity. Metabolic surgery ameliorates a series of clinical manifestations and related comorbidities of PCOS. However, the overall efficacy of metabolic surgery on PCOS remains uncertain. This systematic review and meta-analysis aimed to evaluate the therapeutic effects of metabolic surgery on obese patients with PCOS. A systematic literature search for relevant studies was conducted on PubMed, Embase, Web of Science, and the Cochrane Library from inception to June 2021. Data extraction and quality evaluation were performed by three researchers, and RevMan 5.4 software was used to conduct the meta-analysis. A total of 14 studies involving 501 obese patients with PCOS were included. Incidence of PCOS in obese women ranged from 5.5% to 63.5% among the included studies. The results showed the incidence of abnormal menstruation decreased from 81% to 15% (OR=0.03, 95% confidence interval (CI): 0.01–0.08), while the incidence of hirsutism dropped from 71% to 38% (OR=0.21, 95% CI: 0.06–0.74). Serum total testosterone and free testosterone levels decreased by 25.92 ng/dL (MD = -25.92, 95% CI: -28.90– -22.93) and 2.28 ng/dL (SMD = -2.28, 95% CI: -3.67– -0.89), respectively. Sex hormone-binding globulin (SHBG) levels increased by 26.46 nmol/L (MD = 26.46, 95% CI: 12.97–39.95). Serum anti-Mullerian hormone (AMH) levels decreased by 1.29 ng/mL (MD = -1.29, 95% CI: -1.92– -0.66). Small sample size studies revealed that pregnancy rates ranged from 95.2% to 100% postoperatively. Metabolic surgery contributed to marked improvement of abnormal menstruation, hirsutism, and levels of free testosterone, total testosterone, SHBG, and AMH in patients with PCOS. Our findings indicate that patients with PCOS are expected to benefit from metabolic surgery, and could help potentially improve their reproductive outcomes. Metabolic surgery could thus be a new viable option for the clinical treatment of PCOS.

Systematic Review Registration

PROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021251524.
Effect of Economic Indicators, Renewable Energy Consumption and Human Development on Climate Change: An Empirical Analysis Based on Panel Data of Selected Countries
Authors: Hao Yuanyuan
Published: March 2022

Global warming is mainly influenced by factors such as energy consumption, human development, and economic activities, but there is no consensus among researchers and there is relatively little research literature on less developed countries. Therefore, this study attempts to explore the impact of renewable energy consumption, human development and economic growth on climate change from a macroeconomic perspective for 105 countries worldwide over the period 1990–2019 by constructing a panel vector autoregressive (PVAR) model and using generalized method of moments (GMM) and panel impulse response analysis. The analysis includes four panels of high-income, upper-middle-income, lower-middle-income, and low-income countries. The results of the study find that economic growth, FDI, trade openness, industrialization, renewable energy consumption and HDI have different impacts on climate change (CO2 emissions) in different regions during the sample period. Specifically, in the four panels, economic growth, industrialization, FDI, and trade openness all play a varied role in aggravating environmental pollution (CO2 emissions). In high-income and upper-middle-income countries, industrialization has a positive effect on CO2 emissions, while FDI has a negative impact, which supports the pollution halo hypothesis. However, both have a positive impact on CO2 emissions in lower-middle-income and low-income countries. The results also found that except for upper-middle-income countries, trade openness and renewable energy consumption help reduce CO2 emissions, while renewable energy consumption has little effect on suppressing CO2 emissions in low-income countries. In addition, HDI has promoted CO2 emissions in upper-middle-income and lower-middle-income countries, but has curbed CO2 emissions in high-income countries. Therefore, under the premise of not affecting economic growth and HDI, those empirical results will not only help decision-makers formulate appropriate renewable energy policies, but also are of great significance to the realization of a healthy and sustainable global environment.
Gone With the Water: The Loss of Genetic Variability in Black and Gold Howler Monkeys (Alouatta caraya) Due to Dam Construction
Authors: Oklander Luciana Inés , Caputo Mariela , Fernández Gabriela P. , Jerusalinsky Leandro , de Oliveira Silviene F. , Bonatto Sandro L. , Corach Daniel
Published: March 2022

Black and gold howler monkeys (Alouatta caraya) inhabit several eco-regions in South America with the highest population densities in riverine forests. Dam construction for electricity production represents a severe human alteration of ecosystems with consequences for primate conservation. To evaluate the possible loss of genetic diversity in A. caraya, we analysed and compared the genetic structure of the species across 22 study sites in Argentina (14), Paraguay (1), and Brazil (7). Four of these study sites (referred to as flooded) were sampled before dam-linked flooding which most likely caused a drastic decline or functional extinction of these populations. The genetic variability of 256 individuals was evaluated using 10 autosomal microsatellites (STRs) and 112 individuals by sequencing a fragment of 507 bp of mtDNA. DNA was extracted from tissue, blood, and faecal samples. Significantly higher values of genetic variability were observed for the flooded populations both in mtDNA and STRs. Population genetic structure showed a K = 1, 2, or 5 depending on the method, separating Argentinian and Paraguayan sites from Brazilian sites and, in the case of K = 5, two clusters were mostly represented by flooded populations. Isolation-by-distance analyses showed that geographic distances influence gene flow. Analytical methods, such as Pairwise Fst’s and Nei’s and regression model of Harpending and Ward, were concordant in detecting significant genetic structuring between flooded and remaining sites examined. Although some sites have very low sample sizes, these samples are of great importance since these sampling sites are currently flooded. Our results show that the study sites where dams were built had the greatest genetic diversity. As A. caraya is currently severely threatened by yellow fever outbreaks, the remaining populations may be more vulnerable to disease outbreaks due to impoverished genetic variability. Accordingly, it is essential to implement management actions to conserve the remaining populations. Our results underline the importance for Environmental Impact Assessments (EIA) to include data on the genetic structure of species in the affected sites prior to their alteration or destruction. These genetic data are also remarkably important for determining where to relocate specific individuals to help avoid biodiversity loss.
Flow Intermittence Drives the Benthic Algal Composition, Biodiversity and Diatom-Based Quality of Small Hilly Streams in the Pannonian Ecoregion, Hungary
Authors: B-Béres Viktória , Kókai Zsuzsanna , Várbíró Gábor , Mustazhapova Gulperizat , Csabai Zoltán , Pernecker Bálint , Borics Gábor , Bácsi István , Boda Pál
Published: March 2022

Climate change is putting increasing pressure on flowing waters. Drastic water level fluctuations in rivers or drying up of small and medium-sized streams all contribute to the biodiversity crisis threatening freshwater ecosystems. Benthic diatoms are important elements of biofilm in small streams. However, knowledge on the relationship between benthic diatoms and flow intermittence is incomplete, especially in regions recently impacted by recurrent drying. Thus, we investigated benthic diatom flora of small intermittent, hilly streams in the warm temperate region of Europe (the Pannonian Ecoregion). Our hypotheses were addressed to compositional changes, biodiversity loss and diatom-based ecological assessment. The results revealed clear flow intermittence-induced differences in taxa and trait composition of diatoms. Altogether six species for the dry phase and three species in the aquatic phase were identified as indicative ones by using indicator value analyses. In contrast to water regime induced changes in assemblages, there was a seasonal overlap in taxa and trait composition. During the study period, the drying up of streams did not result in significant biodiversity loss either at taxa or trait levels. Functional dispersion, however, reduced significantly by summer. Overall, neither the hydrological regime nor seasonal changes had a significant effect on diatom-based quality indices, except for the Rott trophic index (TID index). The TID index values were significantly lower in dry phases than in aquatic ones. These results suggested that the drying up of streams has a very complex influence on benthic diatoms. It seems that taxonomical and functional redundancy can reduce the negative impact of short-time flow intermittence on assemblages. As a practical benefit, the results are the first to support the use of diatom-based quality indices in the assessment of flow intermittence in the temperate region.
Identification of Novel FBN2 Variants in a Cohort of Congenital Contractural Arachnodactyly
Authors: Sun Liying , Huang Yingzhao , Zhao Sen , Zhong Wenyao , Shi Jile , Guo Yang , Zhao Junhui , Xiong Ge , Yin Yuehan , Chen Zefu , Zhang Nan , Zhao Zongxuan , Li Qingyang , Chen Dan , Niu Yuchen , Li Xiaoxin , Qiu Guixing , Wu Zhihong , Zhang Terry Jianguo , Tian Wen , Wu Nan
Published: March 2022

Congenital contractural arachnodactyly (CCA) is a rare autosomal dominant disorder of connective tissue characterized by crumpled ears, arachnodactyly, camptodactyly, large joint contracture, and kyphoscoliosis. The nature course of CCA has not been well-described. We aim to decipher the genetic and phenotypic spectrum of CCA. The cohort was enrolled in Beijing Jishuitan Hospital and Peking Union Medical College Hospital, Beijing, China, based on Deciphering disorders Involving Scoliosis and COmorbidities (DISCO) study (http://www.discostudy.org/). Exome sequencing was performed on patients’ blood DNA. A recent published CCA scoring system was validated in our cohort. Seven novel variants and three previously reported FBN2 variants were identified through exome sequencing. Two variants outside of the neonatal region of FBN2 gene were found. The phenotypes were comparable between patients in our cohort and previous literature, with arachnodactyly, camptodactyly and large joints contractures found in almost all patients. All patients eligible for analysis were successfully classified into likely CCA based on the CCA scoring system. Furthermore, we found a double disease-causing heterozygous variant of FBN2 and ANKRD11 in a patient with blended phenotypes consisting of CCA and KBG syndrome. The identification of seven novel variants broadens the mutational and phenotypic spectrum of CCA and may provide implications for genetic counseling and clinical management.
Variants Within Genes EDIL3 and ADGRB3 are Associated With Divergent Fecal Egg Counts in Katahdin Sheep at Weaning
Authors: Becker Gabrielle M. , Burke Joan M. , Lewis Ronald M. , Miller James E. , Morgan James L. M. , Rosen Benjamin D. , Van Tassell Curtis P. , Notter David R. , Murdoch Brenda M.
Published: March 2022

Gastrointestinal nematodes (GIN) pose a severe threat to sheep production worldwide. Anthelmintic drug resistance coupled with growing concern regarding potential environmental effects of drug use have demonstrated the necessity of implementing other methods of GIN control. The aim of this study was to test for genetic variants associated with resistance or susceptibility to GIN in Katahdin sheep to improve the current understanding of the genetic mechanisms responsible for host response to GIN. Linear regression and case-control genome-wide association studies were conducted with high-density genotype data and cube-root transformed weaning fecal egg counts (tFEC) of 583 Katahdin sheep. The case-control GWAS identified two significant SNPs (P-values 1.49e-08 to 1.01e-08) within introns of the gene adhesion G protein-coupled receptor B3 (ADGRB3) associated with lower fecal egg counts. With linear regression, four significant SNPs (P-values 7.82e-08 to 3.34e-08) were identified within the first intron of the gene EGF-like repeats and discoidin domains 3 (EDIL3). These identified SNPs were in very high linkage disequilibrium (r2 of 0.996–1), and animals with alternate homozygous genotypes had significantly higher median weaning tFEC phenotypes compared to all other genotypes. Significant SNPs were queried through public databases to identify putative transcription factor binding site (TFBS) and potential lncRNA differences between reference and alternate alleles. Changes in TFBS were predicted at two SNPs, and one significant SNP was found to be within a predicted lncRNA sequence with greater than 90% similarity to a known lncRNA in the bovine genome. The gene EDIL3 has been described in other species for its roles in the inhibition and resolution of inflammation. Potential changes of EDIL3 expression mediated through lncRNA expression and/or transcription factor binding may impact the overall immune response and reduce the ability of Katahdin sheep to control GIN infection. This study lays the foundation for further research of EDIL3 and ADGRB3 towards understanding genetic mechanisms of susceptibility to GIN, and suggests these SNPs may contribute to genetic strategies for improving parasite resistance traits in sheep.
Novel Biallelic Variant in the BRAT1 Gene Caused Nonprogressive Cerebellar Ataxia Syndrome
Authors: Qi Yiming , Ji Xueqi , Ding Hongke , Liu Ling , Zhang Yan , Yin Aihua
Published: March 2022

Recessive mutations in BRAT1 cause lethal neonatal rigidity and multifocal seizure syndrome (RMFSL), a phenotype characterized by neonatal microcephaly, hypertonia, and refractory epilepsy with premature death. Recently, attenuated disease variants have been described, suggesting that a wider clinical spectrum of BRAT1-associated neurodegeneration exists than was previously thought. Here, we reported a 10-year-old girl with severe intellectual disability, rigidity, ataxia or dyspraxia, and cerebellar atrophy on brain MRI; two BRAT1 variants in the trans configuration [c.1014A > C (p.Pro338 = ); c.706delC (p.Leu236Cysfs*5)] were detected using whole-exome sequencing. RNA-seq confirmed significantly decreased BRAT1 transcript levels in the presence of the variant; further, it revealed an intron retention between exon 7 and exon 8 caused by the synonymous base substitute. Subsequent prenatal diagnosis for these two variants guided the parents to reproduce. We expand the phenotypic spectrum of BRAT1-associated disorders by first reporting the pathogenic synonymous variant of the BRAT1 gene, resulting in clinical severity that is mild compared to the severe phenotype seen in RMFSL. Making an accurate diagnosis and prognostic evaluation of BRAT1-associated neurodegeneration is important for reproductive consultation and disease management.
Serum Antibody Binding and Cytotoxicity to Pig Cells in Chinese Subjects: Relevance to Clinical Renal Xenotransplantation
Authors: Li Tao , Feng Hao , Du Jiaxiang , Xia Qiangbing , Cooper David K. C. , Jiang Hongtao , He Songzhe , Pan Dengke , Chen Gang , Wang Yi
Published: March 2022

Kidney xenotransplantation is expected to contribute to resolving the shortage of kidneys from deceased human donors. Although progress in experimental life-supporting pig renal xenotransplantation has been encouraging, there are still issues to be considered before a clinical trial can be initiated. We attempted to clarify some of these by an in vitro study. Blood was drawn from healthy volunteers (Volunteers, n=20), patients with end-stage renal disease (ESRD, n=20) pre-operation (Pre), and on Day 1 (POD 1) and Day 14 (POD 14) after renal allotransplantation, brain-dead organ donors (DBD, n=20), and renal allotransplant recipients who were currently experiencing T cell-mediated rejection (Allo-TCMR, n=20). Serum IgM/IgG binding to, and complement-dependent cytotoxicity (CDC) of, PBMCs and RBCs from (a) wild-type (WT), (b) α1,3-galactosyltransferase gene-knockout (GTKO), (c) GTKO/beta-1,4-N-acety1 galactosaminyltransferase 2-knockout (GTKO/β4GalNT2KO), (d) GTKO/cytidine monophosphate-N-acetylneuraminic acid hydroxylase-knockout (GTKO/CMAHKO), and (e) GTKO/β4GalNT2KO/CMAHKO/hCD55 (TKO/hCD55) pigs were measured by flow cytometry. We obtained the following results: (i) Serum IgM/IgG binding and CDC in Volunteers were significantly greater to WT, GTKO, and GTKO/β4GalNT2KO PBMCs or RBCs than to GTKO/CMAHKO and TKO/hCD55 cells; (ii) ESRD, DBD, and Allo-TCMR serum antibody binding and CDC to WT pig PBMCs were significantly greater than to GTKO, GTKO/β4GalNT2KO, GTKO/CMAHKO, and TKO/hCD55 cells; (iii) antibody binding to GTKO/CMAHKO pig cells was significantly lower in hemodialysis than peritoneal dialysis patients. (iv) Two of twenty allotransplantation recipients’ serum IgG binding to GTKO pig PBMCs increased on POD14 compared with Pre, but IgG binding to GTKO pig RBCs did not; (v) In all sera, the lowest antibody binding and CDC were to GTKO/CMAHKO and TKO/CD55 pig cells. We conclude (i) CMAHKO in the pig may be critical to the success of clinical pig kidney xenotransplantation, and may be the most important after GTKO, at least in Chinese patients; (ii) subjects with ESRD, or who are immunosuppressed after kidney allotransplantation, and DBD, have lower levels of antibody binding and CDC to genetically-engineered pig cells than do volunteers; (iii) TKO pigs with selected human ‘protective’ transgenes, e.g., CD55, are likely to prove to be the optimal sources of kidneys for clinical xenotransplantation.
Three-Dimensional Visualization With Tissue Clearing Uncovers Dynamic Alterations of Renal Resident Mononuclear Phagocytes After Acute Kidney Injury
Authors: Kim Kipyo , Kim Yun-Gyeong , Jung Su Woong , Kim Yang Gyun , Lee Sang-Ho , Kwon Seung-Hae , Moon Ju-Young
Published: March 2022

Traditional histologic methods are limited in detecting dynamic changes in immune cells during acute kidney injury (AKI). Recently, optical tissue clearing combined with multiphoton microscopy (MPM) or light sheet fluorescence microscopy (LSFM) has become an emerging method for deep tissue evaluation and three-dimensional visualization. These new approaches have helped expand our understanding of tissue injury and repair processes, including tracing the changes in immune cells. We designed this study to investigate the morphological and functional alterations of renal mononuclear phagocytes (MNPs) in lipopolysaccharide (LPS)-induced AKI using renal clearing in CD11c-YFP mice. We also evaluated the effect of the NLRP3 inhibitor MCC950 to determine whether NLRP3 inhibition attenuates the activation of CD11c+ cells in an LPS-induced AKI model. Transverse sectioned whole mouse kidney imaging by LSFM showed that CD11c+ cells were mainly distributed in the cortex, especially the tubulointerstitial area. The number of CD11c+ cells was significantly more densely interspersed, particularly in periglomerular and perivascular lesions, in the saline-treated LPS-exposed kidney than in the control kidney. Deep imaging of the kidney cortex by MPM demonstrated an increased number of CD11c+ cells in the saline-treated LPS group compared with the control group. This quantitative alteration of CD11c+ cells in AKI was accompanied by morphological changes at high resolution, showing an increased number and level of dendrites. These morphological and behavioral changes in the saline-treated LPS group were accompanied by increased MHC class II and CD86 on CD11c-YFP+ cells. MCC950 attenuated the activation of CD11c+ cells after AKI and improved renal function. In conclusion, wide and deep three-dimensional visualization using MPM or LSFM combined with kidney clearing uncovers dynamic changes of renal MNPs, which are directly linked to renal function in AKI.
Direct Effects of Glyphosate on In Vitro T Helper Cell Differentiation and Cytokine Production
Authors: Maddalon Ambra , Iulini Martina , Galbiati Valentina , Colosio Claudio , Mandić-Rajčević Stefan , Corsini Emanuela
Published: March 2022

Glyphosate (G) is the active ingredient of the most used herbicides worldwide. Its use is currently very debated, as several studies indicating its hazard and toxicity are emerging. Among them, there is evidence of adverse effects on the immune system. The aim of this work was to investigate if G could directly affect immune cells. Peripheral blood mononuclear cells (PBMC) obtained from healthy donors were used as experimental model. PBMC were expose to G and stimulated with PMA/ionomycin, T helper (Th) cell differentiation and cytokine production were assessed by flow cytometry and enzyme-linked immunosorbent assay, respectively. A reduction of Th1/Th2 ratio, mainly due to a decrease in Th1 cells, was observed following G exposure. Results show an enhancement of IL-4 and IL-17A production, and a reduction of IFN-γ. Based on literature evidence that suggest G being an endocrine disruptor, we investigated the role of nuclear estrogen receptors (ER). ERα/ERβ inhibition by ICI 182,780 abolished the effects of G on IFN-γ and IL-4 release, suggesting a role of ER in the observed effects. To further characterize the mechanism of action of G, miRNAs, both in exosome and intracellular, were investigated. A statistically significant increase in miR-500a-5p was observed following G treatment. The blockage of miR-500a-5p, using a specific antagomir, prevented G-induced reduction of IFN-γ production. Finally a relationship between miR-500a-5p up-regulation and ER was observed. Overall, these results suggest that G can directly act on T cells, altering T cell differentiation and cytokines production.
The Environmental Drivers of Benthic Fauna Diversity and Community Composition
Authors: Saeedi Hanieh , Warren Dan , Brandt Angelika
Published: March 2022

Establishing management programs to preserve the benthic communities along the NW Pacific and the Arctic Ocean (AO) requires a deep understanding of the composition of communities and their responses to environmental stressors. In this study, we thus examine patterns of benthic community composition and patterns of species richness along the NW Pacific and Arctic Seas and investigate the most important environmental drivers of those patterns. Overall we found a trend of decreasing species richness toward higher latitudes and deeper waters, peaking in coastal waters of the eastern Philippines. The most dominant taxa along the entire study area were Arthropoda, Mollusca, Cnidaria, Echinodermata, and Annelida. We found that depth, not temperature, was the main driver of community composition along the NW Pacific and neighboring Arctic Seas. Depth has been previously suggested as a factor driving species distribution in benthic fauna. Following depth, the most influential environmental drivers of community composition along the NW Pacific and the Arctic Ocean were silicate, light, and currents. For example, silicate in Hexactinellida, Holothuroidea, and Ophiuroidea; and light in Cephalopoda and Gymnolaemata had the highest correlations with community composition. In this study, based on a combination of new samples and open-access data, we show that different benthic communities might respond differently to future climatic changes based on their taxon-specific biological, physiological, and ecological characteristics. International conservation efforts and habitat preservation should take an adaptive approach and apply measures that take the differences among benthic communities in responding to future climate change into account. This facilitates implementing appropriate conservation management strategies and sustainable utilization of the NW Pacific and Arctic marine ecosystems.
Diversity and Zonation of Benthic Amphipod Crustaceans Affected by the Mississippi Submarine Canyon in the Northern Gulf of Mexico
Authors: Soliman Yousria S. , Rowe Gilbert T. , Wicksten Mary , Wei Chih-Lin
Published: March 2022

Amphipod crustacean diversity and zonation are described from the large Mississippi Canyon that extends from the continental shelf across the entire continental margin. Benthic amphipods were sampled on four cruises from 2000 to 2004 from six locations in the Mississippi Canyon from depths of 480 through 2,750 m, and compared with five locations in a second transect on the open continental slope approximately 100 km west of the canyon to assess the canyon effect on the structure and composition of amphipod assemblages. Five replicates were collected from each location using 0.2 m–2 GOMEX box corer. Amphipods amounted to 40% of the total faunal abundance within the canyon compared to only 4% in the non-canyon samples. Of the seventy-two species (19 families) collected, 61 were encountered in the canyon compared to 38 on the non-canyon transect. The trough-like head of the canyon (480 m) supported high densities (4,446–26,933 ind./m2) of the filter feeding, tube dwelling ampeliscid amphipod (Ampelisca mississippiana), the highest densities sampled compared to any other single species, at any other location, either within or outside the canyon, reflecting extreme flux of organic detritus from the continental shelf. The dominance by this single species suppressed the within – habitat (alpha) diversity and evenness, compared to relatively high diversity within the 1,000–1,500 m depths interval both in and outside the canyon. The species richness and alpha diversity exhibited mid-depth maxima at ca. 1,100 m both in and out of the canyon. High species richness (61) over the entire length of the canyon is presumed to be a function of greater topographic complexity and intermittent mass wasting of sediment down the canyon axis. The absence of nestedness is attributed to the amphipod reproductive pattern that lacks dispersive larval stages and brooding comparatively small numbers of eggs in this taxon. Despite depressed diversity at the head of the canyon, the fact that the number of amphipod species in the Mississippi Canyon was 1.5 times their numbers on the adjacent slope suggests that this physiographic feature enriches geographic-scale species diversity.
Increased Heat Resilience of Intraspecific Outbred Compared to Inbred Lineages in the Kelp Laminaria digitata: Physiology and Transcriptomics
Authors: Liesner Daniel , Pearson Gareth A. , Bartsch Inka , Rana Shivani , Harms Lars , Heinrich Sandra , Bischof Kai , Glöckner Gernot , Valentin Klaus
Published: March 2022

Marine forests and kelps as their foundation species are threatened by ocean warming especially at the warm distributional edges. Previously identified genetic divergence and ecotypic differentiation within kelp species may allow to produce more resilient lineages by intraspecific outbreeding among populations. In a mechanistic investigation of heat stress, heterosis (hybrid vigour), and underlying gene expression patterns, we assessed the thermal performance of inbred (selfings) and outbred (reciprocal crosses) sporophytes of the N-Atlantic kelp Laminaria digitata among clonal isolates from two divergent populations; one from the temperate North Sea (Helgoland) and one from the Arctic (Spitsbergen). First, we investigated the upper thermal tolerance of microscopic sporophytes in a 14-day experiment applying sublethal to lethal 20–23°C. The upper survival temperature of microscopic sporophytes was lower for the inbred Arctic selfing (21°C) than for the temperate selfing and the reciprocal crosses (22°C). Only in the temperate selfing, 4.5% of sporophytes survived 23°C. We then subjected 4–7 cm long sporophytes to a control temperature (10°C), moderate (19°C) and sublethal to lethal heat stress (20.5°C) for 18 days to assess gene expression in addition to physiological parameters. Growth and optimum quantum yield decreased similarly in the reciprocal crosses and the temperate selfing at 19 and 20.5°C, while inbred Arctic sporophytes died within seven days at both 19 and 20.5°C. In response to 20.5°C, 252 genes were constitutively regulated across all surviving lineages, which we use to describe metabolic regulation patterns in response to heat stress in kelp. At sublethal 20.5°C, ca. 150 genes were differentially expressed by either crossed lineage in comparison to the temperate selfing, indicating that they maintained a growth response similar to the temperate selfing with differential metabolic regulation during sublethal heat stress. Subtle differences in physiology and the differential expression of nine genes between the reciprocal crosses at 20.5°C indicate that female and male gametophytes may contribute differently to offspring traits. We consider potential inbreeding depression in the Spitsbergen selfing and quantify the better performance of both crosses using heterosis-related parameters. We discuss the potential and risks of outbreeding to produce more resilient crops for mariculture and marine forest restoration.
Metal-Organic Framework-Based Nanotherapeutics With Tumor Hypoxia-Relieving Ability for Synergistic Sonodynamic/Chemo-therapy
Authors: Zhong Lichang , Yang Tian , Li Pei , Shi Lin , Lai JinYu , Gu Liping
Published: March 2022

Hypoxia, a hallmark of cancer, compromises the efficacy of chemotherapy and other oxygen-dependent modalities (e.g., sonodynamic therapy). For monotherapy, this effect becomes more pronounced because of drug resistance and an adaptive tumor microenvironment. To overcome this, here, we reported metal–organic framework (MOF)-based nanotherapeutics (DOX/Ce6@ZIF-8@PDA) to simultaneously deliver Ce6 and doxorubicin for synergistic sonodynamic/chemotherapy. Notably, O2 storage ability of MOFs relieves tumor hypoxia to sensitize the tumor to sonodynamic therapy and chemotherapy. Moreover, polydopamine (PDA) promotes endocytosis and enhances intracellular drug concentration. The pH-responsive property of MOFs enables controlled drug release. The in vitro and in vivo results validate the impressive tumor inhibition, implying the potential of this combination therapy for cancer treatment.
Prediction of the Fundus Tessellation Severity With Machine Learning Methods
Authors: Shao Lei , Zhang Xiaomei , Hu Teng , Chen Yang , Zhang Chuan , Dong Li , Ling Saiguang , Dong Zhou , Zhou Wen Da , Zhang Rui Heng , Qin Lei , Wei Wen Bin
Published: March 2022

Purpose

To predict the fundus tessellation (FT) severity with machine learning methods.

Methods

A population-based cross-sectional study with 3,468 individuals (mean age of 64.6 ± 9.8 years) based on Beijing Eye Study 2011. Participants underwent detailed ophthalmic examinations including fundus images. Five machine learning methods including ordinal logistic regression, ordinal probit regression, ordinal log-gamma regression, ordinal forest and neural network were used.

Main Outcome Measure

FT precision, recall, F1-score, weighted-average F1-score and AUC value.

Results

Observed from the in-sample fitting performance, the optimal model was ordinal forest, which had correct classification rate (precision) of 81.28%, while 34.75, 93.73, 70.03, and 24.82% in each classified group by FT severity. The AUC value was 0.7249. And the F1-score was 65.05%, weighted-average F1-score was 79.64% on the whole dataset. For out-of-sample prediction performance, the optimal model was ordinal logistic regression, which had precision of 77.12% on the validation dataset, while 19.57, 92.68, 64.74, and 6.76% in each classified group by FT severity. The AUC value was 0.7187. The classification accuracy of light FT group was the highest, while that of severe FT group was the lowest. And the F1-score was 54.46%, weighted-average F1-score was 74.19% on the whole dataset.

Conclusions

The ordinal forest and ordinal logistic regression model had the strong prediction in-sample and out-sample performance, respectively. The threshold ranges of the ordinal forest model for no FT and light, moderate, severe FT were [0, 0.3078], [0.3078, 0.3347], [0.3347, 0.4048], [0.4048, 1], respectively. Likewise, the threshold ranges of ordinal logistic regression model were ≤ 3.7389, [3.7389, 10.5053], [10.5053, 13.9323], > 13.9323. These results can be applied to guide clinical fundus disease screening and FT severity assessment.
Bone and Mineral Disorder in Renal Transplant Patients: Overview of Pathology, Clinical, and Therapeutic Aspects
Authors: Molinari Paolo , Alfieri Carlo Maria , Mattinzoli Deborah , Campise Mariarosaria , Cervesato Angela , Malvica Silvia , Favi Evaldo , Messa Piergiorgio , Castellano Giuseppe
Published: March 2022

Renal transplantation (RTx) allows us to obtain the resolution of the uremic status but is not frequently able to solve all the metabolic complications present during end-stage renal disease. Mineral and bone disorders (MBDs) are frequent since the early stages of chronic kidney disease (CKD) and strongly influence the morbidity and mortality of patients with CKD. Some mineral metabolism (MM) alterations can persist in patients with RTx (RTx-p), as well as in the presence of complete renal function recovery. In those patients, anomalies of calcium, phosphorus, parathormone, fibroblast growth factor 23, and vitamin D such as bone and vessels are frequent and related to both pre-RTx and post-RTx specific factors. Many treatments are present for the management of post-RTx MBD. Despite that, the guidelines that can give clear directives in MBD treatment of RTx-p are still missed. For the future, to obtain an ever-greater individualisation of therapy, an increase of the evidence, the specificity of international guidelines, and more uniform management of these anomalies worldwide should be expected. In this review, the major factors related to post-renal transplant MBD (post-RTx-MBD), the main mineral metabolism biochemical anomalies, and the principal treatment for post-RTx MBD will be reported.
Efficacy and Safety of Cryobiopsy vs. Forceps Biopsy for Interstitial Lung Diseases, Lung Tumors, and Peripheral Pulmonary Lesions: An Updated Systematic Review and Meta-Analysis
Authors: Giri Mohan , Huang Guichuan , Puri Anju , Zhuang Rongjuan , Li Yishi , Guo Shuliang
Published: March 2022

Background

Cryobiopsy has emerged as a novel alternative to conventional forceps biopsy for the diagnosis of interstitial lung diseases (ILDs), lung tumors, and peripheral pulmonary lesions (PPLs). This study aims to compare cryobiopsy and forceps biopsy for the diagnosis of these lung pathologies with respect to efficacy and safety by performing a meta-analysis of updated evidence.

Methods

A number of databases, such as PubMed, Embase, Web of Science, the Cochrane Library, OVID, CNKI, and Wanfang database, were searched for eligible studies. Randomized and non-randomized comparative studies investigating the efficacy and safety of cryobiopsy vs. forceps biopsy for lung pathologies were included. Pooled results were calculated as an odds ratio (OR) or standardized mean difference (SMD) with 95% CI.

Results

A total of 39 studies, such as 9 RCTs with 3,586 biopsies (1,759 cryobiopsies and 1,827 flexible forceps biopsies) were analyzed. Cryobiopsy was associated with a significant increase in the diagnostic rates of ILDs (OR, 4.29; 95% CI, 1.85–9.93; p < 0.01), lung tumors (OR, 3.58; 95% CI, 2.60–4.93; p < 0.01), and PPLs (OR, 1.70; 95% CI, 1.23–2.34; p < 0.01). Cryobiopsy yielded significantly larger specimens compared with flexible forceps biopsy (SMD, 3.06; 95% CI, 2.37–3.74; p < 0.01). The cryobiopsy group had a significantly higher (moderate to severe) bleeding risk than the forceps group (OR, 2.17; 95% CI, 1.48–3.19; p < 0.01). No significant difference was observed in the incidence of pneumothorax between the groups (OR, 0.90; 95% CI, 0.44–1.85; p = 0.78).

Conclusion

Our results demonstrate that cryobiopsy is a safe and efficacious alternative to conventional forceps biopsy.