bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Autopsy of a Reverse Osmosis Membrane Module
Authors: Gonzalez-Gil Graciela , Behzad Ali Reza , Farinha Andreia S. F. , Zhao Chengyan , Bucs Szilard S. , Nada Tariq , Das Ratul , Altmann Thomas , Buijs Paulus J. , Vrouwenvelder Johannes S.
Published: May 2021

The desalination of seawater using reverse osmosis membranes is an attractive solution to global freshwater scarcity. However, membrane performance is reduced by (bio)fouling. Membrane autopsies are essential for identifying the type of fouling material, and applying corrective measures to minimize membrane fouling. Information from full-scale membrane autopsies guiding improved plant operations is scant in the formal literature. In this case-study, a reverse osmosis membrane from a full-scale seawater desalination plant with a feed channel pressure drop increase of about 218% over the pressure vessel was autopsied. The simultaneous determination of microbial cells, ATP, and total organic carbon (TOC) abundances per membrane area allowed estimating the contributions of biofouling and organic fouling. The abundance of microbial cells determined by flow cytometry (up to 7 × 108 cells/cm2), and ATP (up to 21,000 pg/cm2) as well as TOC (up to 98 μg/cm2) were homogeneously distributed on the membrane. Inorganic fouling was also measured, and followed a similar coverage distribution to that of biofouling. Iron (∼150 μg/cm2, estimated by ICP-MS) was the main inorganic foulant. ATR-FTIR spectra supported that membrane fouling was both organic/biological and inorganic. High-resolution SEM-EDS imaging of cross-sectioned membranes allowed assessing the thickness of the fouling layer (up to 20 μm) and its elemental composition. Imaging results further supported the results of homogeneous fouling coverage. Moreover, imaging revealed both zones with and without compression of the polysulfone membrane layer, suggesting that the stress due to operating pressure was heterogeneous. The procedure for this membrane autopsy provided a reasonable overview of the diverse contributors of fouling and might be a starting point to building a consensus autopsy protocol. Next, it would be valuable to build a RO membrane autopsy database, which can be used as a guidance and diagnostic tool to improve the management and operation of RO desalination plants.
Bandgap Engineering of an Aryl-Fused Tetrathianaphthalene for Visible-Blind Organic Field-Effect Transistors
Authors: Zhang Lijuan , Tian Xinzi , Sun Yantao , Yao Jiarong , Yang Shuyuan , Liu Zheyuan , Ge Zhen , Zhang Hongtao , Sun Yan , Shao Xiangfeng , Li Rongjin , Hu Wenping
Published: May 2021

Stability problem of organic semiconductors (OSCs) because of photoabsorption has become a major barrier to large scale applications in organic field-effect transistors (OFETs). It is imperative to design OSCs which are insensitive to visible and near-infrared (VNIR) light to obtain both environmental and operational stability. Herein, taking a 2,3,8,9-tetramethoxy [1,4]benzodithiino[2,3-b][1,4]benzodithiine (TTN2) as an example, we show that controlling molecular configuration is an effective strategy to tune the bandgaps of OSCs for visible-blind OFETs. TTN2 adopts an armchair-like configuration, which is different from the prevailing planar structure of common OSCs. Because of the large bandgap, TTN2 exhibits no photoabsorption in the VNIR region and OFETs based on TTN2 show high environmental stability. The devices worked well after being stored in ambient air, (i.e. in the presence of oxygen and water) and light for over two years. Moreover, the OFETs show no observable response to light irradiation from 405–1,020 nm, which is also favorable for high operational stability.
Developmental Sequences in Second Language Phonology: Effects of Instruction on the Acquisition of Foreign sC Onsets
Authors: Cardoso Walcir , Collins Laura , Cardoso Walciléa
Published: May 2021

This study investigates the effects of three types of instruction on the acquisition of foreign /s/-initial onset clusters (/sl/, /sn/, and /st/-sC clusters), a process characterized by a developmental sequence in which /sl/ is acquired before /sn/ and /st/. 118 native speakers of Brazilian Portuguese participated in a 4-week language course to learn a set of vocabulary and associated pronunciation of Taki, a self-constructed miniature linguistic system. The participants were divided into three groups, each corresponding to one of the hypotheses that characterize three types of explicit second language instruction: Teachability, Projection of Markedness (Projection), and a combination of the two (Mixed). A mixed analysis of variance (ANOVA) analysis of the participants’ production of sC clusters revealed that, in one of the tasks employed (read aloud), the group that focused exclusively on the more marked/st/ (Projection Group) had the best overall performance in the acquisition of the three clusters: this group was able to generalize their knowledge to the sC clusters they were not taught. In general, the results support Zobl’s Projection Model of Markedness for explaining the phonological development of syllable structure, wherein the instructional effect of a focus on the most marked /st/ projects to knowledge of the less marked structures.
High-Sensitivity Cardiac Troponin Predicts Major Cardiovascular Events in Diabetic Patients With Critical Limb Ischemia and Foot Lesions
Authors: Cimaglia Paolo , Dalla Paola Luca , Carone Anna , Scavone Giuseppe , Manfrini Marco , Brogneri Simona , Tenti Elena , Pavasini Rita , Bernucci Davide , Passarini Giulia , Vitali Francesco , Gaudenzi Eleonora , Ferrari Roberto , Campo Gianluca
Published: May 2021

Background: Diabetic patients with critical limb ischemia (CLI) and foot lesions show a poor prognosis. Optimal risk stratification to guide tailored intervention is still uncertain. The aim of the present study was to assess the prognostic role of high-sensitivity cardiac troponin T (hs-TnT) in such a high-risk population.

Methods and Results: Clinical, laboratory, and interventional data, as well as the SPINACH score, were collected. Hs-TnT was measured at hospital admission. All patients were followed up for at least 1 year. The primary endpoint was the cumulative occurrence of major cardiovascular events (MACEs, all-cause death, myocardial infarction, or stroke). The secondary endpoint was all-cause mortality. Overall, 618 patients were included and followed for a median of 981 (557–1,325) days. Diagnosis of coronary artery disease (CAD) was established in 270 (43.7%) patients. Median hs-TnT at admission was 31 (20–59) ng/L, with 525 (85%) patients over the upper reference limit. Hs-TnT values were significantly higher in patients with established CAD (39 vs. 29 ng/L, p < 0.01). Hs-TnT was an independent predictor of MACE (HR 2.440, 95% CI 1.706–3.489, p < 0.001). The best cut-offs were 40 ng/L (AUC 0.711) for patients with established CAD and 25 ng/L (AUC 0.725) for those without. Hs-TnT emerged also as an independent predictor of all-cause mortality. The addition of hs-TnT improved prognostic value of the SPINACH score.

Conclusions: Hs-TnT is a powerful biomarker for prognostic stratification of diabetic CLI patients with foot lesions. This is confirmed independently to CAD diagnosis and permits the identification of higher risk patients requiring tailored intervention.
Transcriptome and N6-Methyladenosine RNA Methylome Analyses in Aortic Dissection and Normal Human Aorta
Authors: Zhou Xianwu , Chen Zerui , Zhou Jianrong , Liu Yaorong , Fan Ruixin , Sun Tucheng
Published: May 2021

Objective: To investigate the N6-methyladenosine (m6A) modification and the expressions of the m6A regulatory genes in the acute aortic dissection (AD).

Methods: MeRIP-seq and RNA-seq experiments of aortic media tissue samples obtained from AD (n = 4) and Controls (n = 4) were conducted. m6A methylation quantification was used to measure the total mRNA m6A level. The five m6A regulators mRNA expressions were analyzed by quantitative polymerase chain reaction (qPCR). Western blot analyses and immunofluorescence staining were used to detect the difference of METTL14 protein expression in the aortas of AD and Normal.

Results: Among AD patients, we detected significantly elevated levels of m6A in total RNA. Compared with the normal group, the up methylated coding genes of AD were primarily enriched in the processes associated with extracellular fibril organization, while the genes with down methylation were enriched in the processes associated with cell death regulation. Furthermore, many differentially methylated m6A sites (DMMSs) coding proteins were mainly annotated during the extracellular matrix and inflammatory responses.

Conclusions: These findings indicate that differential m6A methylation and m6A regulatory genes, including MTEEL14 and FTO, may act on functional genes through RNA modification, thereby regulating the pathogenesis of aortic dissection.
Leisure-Time Physical Activity and Cardiovascular Disease Risk Among Hypertensive Patients: A Longitudinal Cohort Study
Authors: Li Jiqing , Zhang Zhentang , Si Shucheng , Xue Fuzhong
Published: May 2021

Objective: Few studies estimated the effect of leisure-time physical activity (LTPA) on cardiovascular disease (CVD) risk among hypertensive patients in a longitudinal cohort. This study aims to evaluate the association between LTPA and CVD in a longitudinal management cohort of hypertensive patients.

Methods: A total of 58,167 hypertensive patients without baseline CVD from a longitudinal cohort were included in this study. LTPA and other covariates were measured at the follow-up four times annually. The primary outcome was CVD events. The association between LTPA and CVD was assessed by the marginal structure model (MSM) and Cox model with adjustment for age, gender, body mass index (BMI), smoking, drinking, diabetes, hyperlipidemia, and antihypertensive medication. The restricted cubic spline and segmented regression were used to assess the dose–response relationship between LTPA and CVD.

Results: We recorded 16,332 CVD events; crude incidence of CVD were 89.68, 80.39, 62.64, and 44.04 per 1,000 person-years for baseline 0, 1–150, 151–300, and >300 min/week LTPA, respectively. Compared with inactive LTPA, the adjusted hazard ratios (HRs) estimated by Cox model and MSM-Cox model for CVD associated with 1–150,151–300, and 300 min/week LTPA were 0.85 (95% CI, 0.83–0.88), 0.67 (95% CI, 0.64–0.71), 0.47 (95% CI, 0.44–0.51), and 0.83 (95% CI, 0.76–0.91), 0.58 (95% CI, 0.52–0.63), and 0.39 (95% CI, 0.35–0.44), respectively. Per 60 min/week increase in LTPA was associated with a 13% reduction in CVD risk. LTPA breakpoint was 417 min/week for CVD. Before and after the break-point, the slopes of the piecewise-linear relationship between LTPA and CVD risk were −0.0017 and −0.0003, respectively.

Conclusion: LTPA was more strongly associated with the CVD risk than that estimated by conventional analyses based on baseline LTPA; 417 min/week is a breakpoint, after which the incremental health benefits on CVD prevention obtained from the increase in LTPA are much less than before.
Pilose Antler Peptide-3.2KD Ameliorates Adriamycin-Induced Myocardial Injury Through TGF-β/SMAD Signaling Pathway
Authors: Xu Yan , Qu Xiaobo , Zhou Jia , Lv Guangfu , Han Dong , Liu Jinlong , Liu Yuexin , Chen Ying , Qu Peng , Huang Xiaowei
Published: May 2021

Adriamycin (ADR)-based combination chemotherapy is the standard treatment for some patients with tumors in clinical, however, long-term application can cause dose-dependent cardiotoxicity. Pilose Antler, as a traditional Chinese medicine, first appeared in the Han Dynasty and has been used to treat heart disease for nearly a thousand years. Previous data revealed pilose antler polypeptide (PAP, 3.2KD) was one of its main active components with multiple biological activities for cardiomyopathy. PAP-3.2KD exerts protective effects againt myocardial fibrosis. The present study demonstrated the protective mechanism of PAP-3.2KD against Adriamycin (ADR)-induced myocardial injury through using animal model with ADR-induced myocardial injury. PAP-3.2KD markedly improved the weight increase and decreased the HW/BW index, heart rate, and ST height in ADR-induced groups. Additionally, PAP-3.2KD reversed histopathological changes (such as disordered muscle bundles, myocardial fibrosis and diffuse myocardial cellular edema) and scores of the heart tissue, ameliorated the myocardial fibrosis and collagen volume fraction through pathological examination, significantly increased the protein level of Bcl-2, and decreased the expression levels of Bax and caspase-3 in myocardial tissue by ELISA, compared to those in ADR-induced group. Furthermore, ADR stimulation induced the increased protein levels of TGF-β1 and SMAD2/3/4, the increased phosphorylation levels of SMAD2/3 and the reduced protein levels of SMAD7. The expression levels of protein above in ADR-induced group were remarkably reversed in PAP-3.2KD-treated groups. PAP-3.2KD ameliorated ADR-induced myocardial injury by regulating the TGF-β/SMAD signaling pathway. Thus, these results provide a strong rationale for the protective effects of PAP against ADR-induced myocardial injury, when ADR is used to treat cancer.
Global Circumferential Strain by Cardiac Magnetic Resonance Tissue Tracking Associated With Ventricular Arrhythmias in Hypertrophic Cardiomyopathy Patients
Authors: Pu Cailing , Fei Jingle , Lv Sangying , Wu Yan , He Chengbin , Guo Danling , Mabombo Pierre Umba , Chooah Outesh , Hu Hongjie
Published: May 2021

Background: Hypertrophic cardiomyopathy (HCM) is prone to myocardial heterogeneity and fibrosis, which are the substrates of ventricular arrhythmias (VAs). Cardiac magnetic resonance tissue tracking (CMR-TT) can quantitatively reflect global and regional left ventricular strain from different directions. It is uncertain whether the change of myocardial strain detected by CMR-TT is associated with VAs. The aim of the study is to explore the differential diagnostic value of VAs in HCM by CMR-TT.

Materials and Methods: We retrospectively included 93 HCM patients (38 with VAs and 55 without VAs) and 30 healthy cases. Left ventricular function, myocardial strain parameters and percentage of late gadolinium enhancement (%LGE) were evaluated.

Results: Global circumferential strain (GCS) and %LGE correlated moderately (r = 0.51, P < 0.001). HCM patients with VAs had lower left ventricular ejection fraction (LVEF), global radial strain (GRS), GCS, and global longitudinal strain (GLS), but increased %LGE compared with those without VAs (P < 0.01 for all). %LGE and GCS were indicators of VAs in HCM patients by multivariate logistic regression analysis. HCM patients with %LGE >5.35% (AUC 0.81, 95% CI 0.70–0.91, P < 0.001) or GCS >-14.73% (AUC 0.79, 95% CI 0.70–0.89, P < 0.001) on CMR more frequently had VAs. %LGE + GCS were able to better identify HCM patients with VAs (AUC 0.87, 95% CI 0.79–0.95, P < 0.001).

Conclusion: GCS and %LGE were independent risk indicators of VAs in HCM. GCS is expected to be a good potential predictor in identifying HCM patients with VAs, which may provide important values to improve risk stratification in HCM in clinical practice.
Case Report: Giant Biatrial Myxoma Mimicking Malignant Cardiac Tumor in a Patient With a Hepatic Angiomatous Mass
Authors: Fan Chengming , Zhang Hao , Zhuang Huanwei , Jiang Zenan , Tan Haoyu , Iroegbu Chukwuemeka Daniel , Song Long , Liu Liming
Published: May 2021

Cardiac myxomas, primarily originating from the left atrium, are the most prevalent types of benign cardiac tumors; however, biatrial myxomas are extremely rare. Herein, we present a rare case of a 55-year old male with exertional dyspnea and intermittent chest discomfort due to a giant biatrial mass with concomitant atrial fibrillation and hepatic hemangioma. The giant tumor with its peduncle at the interatrial septum involved both atria; however, bulging through the tricuspid valve to the right ventricle during systole. Hence, excision of the giant cardiac tumor (which grossly composed of three parts: stiff, fleshy, and soft) and Cox-Maze IV procedure was performed with the resected specimen measuring 100 × 80 × 40 mm. The patient who was in a stable condition was discharged home on the 12th post-operative day. Thus, given the excellent post-operative results achieved, surgical treatment in large multi-cavitary benign cardiac tumors is feasible and should be considered a potentially curative therapy.
Fluorescence-Based Quantitative and Spatial Analysis of Tumour Spheroids: A Proposed Tool to Predict Patient-Specific Therapy Response
Authors: Spoerri Loredana , Gunasingh Gency , Haass Nikolas K.
Published: May 2021

Tumour spheroids are widely used to pre-clinically assess anti-cancer treatments. They are an excellent compromise between the lack of microenvironment encountered in adherent cell culture conditions and the great complexity of in vivo animal models. Spheroids recapitulate intra-tumour microenvironment-driven heterogeneity, a pivotal aspect for therapy outcome that is, however, often overlooked. Likely due to their ease, most assays measure overall spheroid size and/or cell death as a readout. However, as different tumour cell subpopulations may show a different biology and therapy response, it is paramount to obtain information from these distinct regions within the spheroid. We describe here a methodology to quantitatively and spatially assess fluorescence-based microscopy spheroid images by semi-automated software-based analysis. This provides a fast assay that accounts for spatial biological differences that are driven by the tumour microenvironment. We outline the methodology using detection of hypoxia, cell death and PBMC infiltration as examples, and we propose this procedure as an exploratory approach to assist therapy response prediction for personalised medicine.
Radiocarbon and Luminescence Dating of Lacustrine Sediments in Zhari Namco, Southern Tibetan Plateau
Authors: Cong Lu , Wang Yixuan , Zhang Xiying , Chen Tianyuan , Gao Donglin , An Fuyuan
Published: May 2021

There are more than 1,000 lakes within the Tibetan Plateau (TP), all of which are sensitive to changes in regional climate and local hydrology. Lacustrine sediments within these lakes preserve a good record of these changes. However, determining their precise ages is difficult due to the complex nature of lake reservoir effects (LRE), which limit our understanding of paleoenvironmental changes. Focusing on an exposed 600 cm thick lacustrine sediment profile located in western Zhari Namco, we used a combination of both radiocarbon and optically stimulated luminescence (OSL) dating methods in order to evaluate the carbon reservoirs of bulk organic matter (BOM) and aquatic plant remnants (APR), and to explore the age differences between14C and OSL and their respective reliability. We demonstrated that (i) OSL ages were changed in stratigraphic order, and the OSL age just below the beach gravel layer was consistent with previously reported paleoshoreline ages; (ii)14C ages were divergent between BOM and grass leaves; (iii)14C ages of BOM were older than14C ages of APR; and (iv) all14C ages were older than OSL ages. This could be attributed to changing LRE in the past, causing the14C ages to appear unstable during the deposition period. Although the14C ages of terrestrial plant remnants (TPR) were not affected by LRE, an analyzed twig nonetheless returned a14C age older than its respective layer’s OSL age, suggesting it may have been preserved on land prior to transportation into the lake. Our study suggests that OSL ages are more reliable than14C ages with respect to Zhari Namco lacustrine sediments. We recommend caution when interpreting paleoenvironmental changes based on lacustrine sediment14C ages alone.
High Crystal Number Densities From Mechanical Damage
Authors: Lindoo Amanda , Cashman Katharine V.
Published: May 2021

Laboratory experiments investigating syn-eruptive crystallization are fundamental for interpreting crystal and vesicle textures in pyroclasts. Previous experiments have advanced our understanding by varying decompression and cooling pathways, volatile components, and melt composition. However, they have largely failed to produce the high crystal number densities seen in many cryptodome and dome samples. This is feasibly due to the relatively simple decompression pathways employed in experimental studies. In this study, we approach the problem by exploring non-linear decompression pathways. We present two series of experiments: (1) decompression from low initial starting pressure and (2) a compression-and-release step after the initial decompression. The purpose of each series was to simulate (1) decompression of magma that stalls during ascent and (2) pressure cycling that occurs in non-erupted magma during episodic explosive activity. The experiments were carried out on a synthetic rhyodacite (SiO2 = 69 wt%) held initially at 50 MPa and 885°C then decompressed at rates of 0.026 and 0.05 MPa s−1 to 10 MPa A subset of experiments was then subjected to a compression step to 110 MPa followed by near-instantaneous release back to 10 MPa. A substantial volume fraction of dendritic microlites (ϕxtl = 0.27–0.32, Na = 4.79 × 103 mm–2) formed during the initial hold at 50 MPa; additional crystallization during subsequent decompression to ≥ 10 MPa was minimal, as evidenced by only small increases in crystallinity (ϕxtl = 0.28–0.33) and comparable crystal number densities (4.11–7.81 × 103 mm–2). Samples that underwent recompression followed by a second decompression showed no increase in crystal volume fraction but did show extensive disruption of the initial dendritic, box-work microlite structures that produced high number densities (Na = 43.5–87.2 × 103 mm–2) of small individual crystals. The disruption was driven by a combination of rapid vesiculation, expansion and resulting shear along the capsule walls. From these results, we suggest that high crystal number densities may be a signature of rapid deformation occurring after magma stalling in the subsurface, perhaps related to pressure cycling and accompanying rapid changes in vesicularity during repeated small and shallow-sourced explosions. We compare our experiments to pyroclasts from shallow intrusions that preceded the 18 May 1980 eruption of Mount St Helens. These pyroclasts were erupted both prior to 18 May, during episodic precursory explosive activity, and by the 18 May initial lateral blast. The pattern of precursory activity indicates multiple episodes of pressurization (prior to explosive events) and rapid decompression (during explosive events) that we use to illustrate the significance of our experimental results.
Drivers of Recurring Seasonal Cycle of Glacier Calving Styles and Patterns
Authors: Kneib-Walter Andrea , Lüthi Martin P. , Moreau Luc , Vieli Andreas
Published: May 2021

Calving is a crucial process for the mass loss of outlet glaciers draining the Greenland ice sheet. Moreover, due to a lack of observations, calving contributes to large uncertainties in current glacier flow models and projections. Here we investigate the frequency, volume and style of calving events by using high-resolution terrestrial radar interferometer (TRI) data from six field campaigns, continuous daily and hourly time-lapse images over 6 years and 10-s time-lapse images recorded during two field campaigns. The results demonstrate that the calving front of Eqip Sermia, a fast flowing, highly crevassed outlet glacier in West Greenland, follows a clear seasonal cycle showing a distinct pattern in areas with subglacial discharge plumes, shallow bed topography and during the presence and retreat of proglacial ice mélange. Calving event volume, frequency and style vary strongly over time depending on the state in the seasonal cycle. Strong spatial differences between three distinctive front sectors with differing bed topography, water depth and calving front slope were observed. A distinct increase in calving activity occurs in the early melt season simultaneously when ice mélange disappears and meltwater plumes become visible at the fjord surface adjacent to the ice front. While reduced retreat of the front is observed in shallow areas, accelerated retreat occurred at locations with subglacial meltwater plumes. With the emergence of these plumes at the beginning of the melt season, larger full thickness calving events occur likely due to undercutting of the calving front. Later in the melt season the calving activity at subglacial meltwater plumes is similar to the neighboring areas, suggesting the presence of plumes to become less important for calving. The results highlight the significance of subglacial discharge and bed topography on the front geometry, the temporal variability of the calving process and the variability of calving styles.
Effects of U-Mo Irradiation Creep Performance on the Thermo-Mechanical Coupling Behavior in U-Mo/Al Monolithic Fuel Assemblies
Authors: Mao Xiaoxiao , Jian Xiaobin , Zhang Jingyu , Yan Feng , Ding Shurong , Huo Yongzhong , Wang Haoyu , Zhang Lin , Li Yuanming
Published: May 2021

To obtain the optimized fuel performance, the effects of U-Mo irradiation creep rate coefficient on the thermo-mechanical behavior of a fuel assembly are investigated. In this study, three cases of creep rate coefficient are considered. The distribution and evolution results of temperature, displacement, stress/strain and fuel foil micro-structure are analyzed. The simulation results indicate that with the increase of creep rate coefficient 1) the temperature field in the fuel assembly changes slightly; 2) the maximum out-of-plane displacements in the side plates decrease slightly; the maximum out-of-plane displacements in the fuel plates adjacent to the outside Al plates rise distinctly, induced by the enhanced bending deformation contributions; 3) the peak values of the first principal stresses and skeleton normal stresses in the fuel foils are reduced, while the through-thickness creep strains are enlarged; 4) with an increase of fuel creep rate coefficient from 500 × 10−22 mm3/(fission MPa) to 2,000 × 10−22 mm3/(fission·MPa), the maximum Von Mises stress in the fuel cladding decreases by ∼24% on the 308th day. This work is helpful for advanced fabrication and optimization design of U-Mo/Al fuel assemblies.
Green Experiential Marketing, Experiential Value, Relationship Quality, and Customer Loyalty in Environmental Leisure Farm
Authors: Lee Tzai-Chiao , Peng Michael Yao-Ping
Published: May 2021

Environmental/green marketing has emerged as one of the dominant paradigms of marketing in recent years. However, aspects, such as internationalization, the development of artificial intelligence, and stress from growing global competitive forces, have brought about changes in the way leisure farms approach experiential marketing with a significant environmental focus. In this context, the concept of relationship quality offers an opportunity for environmental leisure farms to understand how green experiential marketing impacts consumers’ perceived value and the ongoing interaction relationship. This study adopts a comprehensive perspective that includes green experiential marketing and relationship marketing that leisure farms use in order to enhance customer loyalty, and analyzes the effect of a series of elements inherent to customer psychic or personal needs. Seven hundred fifty-four valid copies of questionnaire were adopted in total. To verify the proposed model empirically, a survey of customers of environmental leisure farms in Taiwan was conducted. Structural equation modeling is conducted to examine the research hypotheses. The findings show that, overall, green experiential marketing has positive direct effects on experiential value and experiential value has positive direct effects on trust, commitment, and satisfaction. At the same time, trust and satisfaction have positive effects on attitudinal and behavioral loyalty. In addition, attitudinal loyalty has a positive influence on behavioral loyalty.
Changes of Periphyton Abundance and Biomass Driven by Factors Specific to Flooding Inflow in a River Inlet Area in Erhai Lake, China
Authors: Ren Wenjing , Yao Yiqian , Zhang Zhonghai , Cao Yu , Yuan Changbo , Wang Hao , Chou Qing Chuan , Ni Leyi , Zhang Xiaolin , Cao Te
Published: May 2021

Periphyton is an ecological essential in freshwater lakes and rivers. Its abundance and biomass are very dynamic in various habitats and subject to various factors, for example, nutrient and light. Following flooding events, the transitional area adjacent to a river inlet and the shallow lake generates diverse habitats for periphyton with gradients in current velocity, suspended matters, nutrients, and light, which would strongly shape the growth and community of periphyton. In this study, three sampling sites were established around a river inlet in Erhai Lake, China, and a field survey was conducted in the sites from April to August (flooding seasons) in 2019 to investigate the abundance and biomass of periphyton and explore influential factors. The results showed that three study areas have different gradients of current velocity depending on the distance to the river inlet, thereby regulating the concentrations of nutrients and suspended matters, which strongly affected the periphyton community; to be specific, the biomass of periphyton was inhibited by the concentration of suspended matters and high concentrations of silicate mainly reduced the diversity of periphyton. Our results imply that the study on the driving factors of periphyton could help to understand its community assembly mechanism and biomass and species composition of periphyton can provide some reference for trophic state of the lake.
A Computational Framework for Pattern Detection on Unaligned Sequences: An Application on SARS-CoV-2 Data
Authors: Pechlivanis Nikolaos , Togkousidis Anastasios , Tsagiopoulou Maria , Sgardelis Stefanos , Kappas Ilias , Psomopoulos Fotis
Published: May 2021

The exponential growth of genome sequences available has spurred research on pattern detection with the aim of extracting evolutionary signal. Traditional approaches, such as multiple sequence alignment, rely on positional homology in order to reconstruct the phylogenetic history of taxa. Yet, mining information from the plethora of biological data and delineating species on a genetic basis, still proves to be an extremely difficult problem to consider. Multiple algorithms and techniques have been developed in order to approach the problem multidimensionally. Here, we propose a computational framework for identifying potentially meaningful features based on k-mers retrieved from unaligned sequence data. Specifically, we have developed a process which makes use of unsupervised learning techniques in order to identify characteristic k-mers of the input dataset across a range of different k-values and within a reasonable time frame. We use these k-mers as features for clustering the input sequences and identifying differences between the distributions of k-mers across the dataset. The developed algorithm is part of an innovative and much promising approach both to the problem of grouping sequence data based on their inherent characteristic features, as well as for the study of changes in the distributions of k-mers, as the k-value is fluctuating within a range of values. Our framework is fully developed in Python language as an open source software licensed under the MIT License, and is freely available at https://github.com/BiodataAnalysisGroup/kmerAnalyzer.
Methylome Patterns of Cattle Adaptation to Heat Stress
Authors: Del Corvo Marcello , Lazzari Barbara , Capra Emanuele , Zavarez Ludmilla , Milanesi Marco , Utsunomiya Yuri Tani , Utsunomiya Adam Taiti Harth , Stella Alessandra , de Paula Nogueira Guilherme , Garcia Josè Fernando , Ajmone-Marsan Paolo
Published: May 2021

Heat stress has a detrimental impact on cattle health, welfare and productivity by affecting gene expression, metabolism and immune response, but little is known on the epigenetic mechanisms mediating the effect of temperature at the cellular and organism level. In this study, we investigated genome-wide DNA methylation in blood samples collected from 5 bulls of the heat stress resilient Nellore breed and 5 bulls of the Angus that are more heat stress susceptible, exposed to the sun and high temperature-high humidity during the summer season of the Brazilian South-East region. The methylomes were analyzed during and after the exposure by Reduced Representation Bisulfite Sequencing, which provided genome-wide single-base resolution methylation profiles. Significant methylation changes between stressful and recovery periods were observed in 819 genes. Among these, 351 were only seen in Angus, 366 were specific to Nellore, and 102 showed significant changes in methylation patterns in both breeds. KEGG and Gene Ontology (GO) enrichment analyses showed that responses were breed-specific. Interestingly, in Nellore significant genes and pathways were mainly involved in stress responses and cellular defense and were under methylated during heat stress, whereas in Angus the response was less focused. These preliminary results suggest that heat challenge induces changes in methylation patterns in specific loci, which should be further scrutinized to assess their role in heat tolerance.
Transcriptional Start Site Coverage Analysis in Plasma Cell-Free DNA Reveals Disease Severity and Tissue Specificity of COVID-19 Patients
Authors: Chen Xinping , Wu Tao , Li Lingguo , Lin Yu , Ma Zhichao , Xu Jinjin , Li Hui , Cheng Fanjun , Chen Ruoyan , Sun Kun , Luo Yuxue , Zhang Chen , Chen Fang , Wang Jiao , Kuo Tingyu , Li Xiaojuan , Geng Chunyu , Lin Feng , Huang Chaojie , Hu Junjie , Yin Jianhua , Liu Ming , Tao Ye , Zhang Jiye , Ou Rijing , Zheng Fang , Jin Yan , Yang Huanming , Wang Jian , Xu Xun , Fu Shengmiao , Jiang Hongyan , Jin Xin , Zhang Haiqiang
Published: May 2021

Symptoms of coronavirus disease 2019 (COVID-19) range from asymptomatic to severe pneumonia and death. A deep understanding of the variation of biological characteristics in severe COVID-19 patients is crucial for the detection of individuals at high risk of critical condition for the clinical management of the disease. Herein, by profiling the gene expression spectrum deduced from DNA coverage in regions surrounding transcriptional start site in plasma cell-free DNA (cfDNA) of COVID-19 patients, we deciphered the altered biological processes in the severe cases and demonstrated the feasibility of cfDNA in measuring the COVID-19 progression. The up- and downregulated genes in the plasma of severe patient were found to be closely related to the biological processes and functions affected by COVID-19 progression. More importantly, with the analysis of transcriptome data of blood cells and lung cells from control group and cases with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection, we revealed that the upregulated genes were predominantly involved in the viral and antiviral activity in blood cells, reflecting the intense viral replication and the active reaction of immune system in the severe patients. Pathway analysis of downregulated genes in plasma DNA and lung cells also demonstrated the diminished adenosine triphosphate synthesis function in lung cells, which was evidenced to correlate with the severe COVID-19 symptoms, such as a cytokine storm and acute respiratory distress. Overall, this study revealed tissue involvement, provided insights into the mechanism of COVID-19 progression, and highlighted the utility of cfDNA as a noninvasive biomarker for disease severity inspections.
SMARThealth Pregnancy: Feasibility and Acceptability of a Complex Intervention for High-Risk Pregnant Women in Rural India: Protocol for a Pilot Cluster Randomised Controlled Trial
Authors: Nagraj Shobhana , Kennedy Stephen H. , Jha Vivekananda , Norton Robyn , Hinton Lisa , Billot Laurent , Rajan Eldho , Arora Varun , Praveen Devarsetty , Hirst Jane E.
Published: May 2021

Introduction: India is in the process of a major epidemiological transition towards non-communicable diseases. Cardiovascular disease (CVD) is the leading cause of death in women in India. Predisposing independent risk factors include pregnancy-related conditions, e.g., hypertensive disorders of pregnancy (HDP) and gestational diabetes (GDM) - also associated with significant perinatal mortality and morbidity. Early identification, referral and management of pregnant women at increased risk of future CVD may offer opportunities for prevention. In rural India, Community Health Workers (CHWs) provide most antenatal and postnatal care. Innovative solutions are required to address integrated care for rural women during transitions between antenatal, postnatal and general health services. The George Institute's SMARThealth Programme has shown that CHWs in rural India screening non-pregnant adults for cardiovascular risk, using a decision support system, is feasible. Building on this, we developed a targeted training programme for CHWs and a complex system-level intervention that uses mobile clinical decision support for CHWs and primary care doctors to screen high-risk pregnant women. In addition to addressing HDP and GDM, the intervention also screens for anaemia in pregnancy.

Methods/Design: A pilot study will be undertaken in two diverse rural districts of India: Jhajjar (Haryana) and Guntur (Andhra Pradesh). Two Primary Health Centre clusters will be randomised to intervention or control groups at each study site. The primary objective of this pilot study is to explore the feasibility and acceptability of the SMARThealth Pregnancy intervention. Secondary objectives are to estimate: (a) prevalence rates of moderate to severe anaemia, HDPs and GDM at the study sites; (b) referral and follow-up rates, and (c) mean haemoglobin and blood pressure values at the routine 6 week postnatal visit. A process evaluation will be conducted to explore the acceptability of the SMARThealth Pregnancy intervention for pregnant women and healthcare workers using qualitative methods.

Discussion: It is anticipated that the findings of this pilot study will help determine the feasibility and acceptability of the SMARThealth Pregnancy intervention, and highlight how the intervention might be further developed for evaluation in a larger, cluster randomised controlled trial.

Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT03968952.
Immune Response to Enterococcus gallinarum in Lupus Patients Is Associated With a Subset of Lupus-Associated Autoantibodies
Authors: Bagavant Harini , Araszkiewicz Antonina M. , Ingram Jessica K. , Cizio Katarzyna , Merrill Joan T. , Arriens Cristina , Guthridge Joel M. , James Judith A. , Deshmukh Umesh S.
Published: May 2021

Interactions between gut microbes and the immune system influence autoimmune disorders like systemic lupus erythematosus (SLE). Recently,Enterococcus gallinarum, a gram-positive commensal gut bacterium, was implicated as a candidate pathobiont in SLE. The present study was undertaken to evaluate the influence ofE. gallinarumexposure on clinical parameters of SLE. Since circulating IgG antibodies to whole bacteria have been established as a surrogate marker for bacterial exposure, anti-E. gallinarumIgG antibodies were measured in banked serum samples from SLE patients and healthy controls in the Oklahoma Cohort for Rheumatic Diseases. The associations between anti-E. gallinarumantibody titers and clinical indicators of lupus were studied. Antibodies to human RNA were studied in a subset of patients. Our results show that sera from both patients and healthy controls had IgG and IgA antibodies reactive withE. gallinarum. The antibody titers between the two groups were not different. However, SLE patients with Ribosomal P autoantibodies had higher anti-E. gallinarumIgG titers compared to healthy controls. In addition to anti-Ribosomal P, higher anti-E. gallinarumtiters were also significantly associated with the presence of anti-dsDNA and anti-Sm autoantibodies. In the subset of patients with anti-Ribosomal P and anti-dsDNA, the anti-E. gallinarumtiters correlated significantly with antibodies to human RNA. Our data show that both healthy individuals and SLE patients were sero-reactive toE. gallinarum.In SLE patients, the immune response toE. gallinarumwas associated with antibody response to a specific subset of lupus autoantigens. These findings provide additional evidence thatE. gallinarummay be a pathobiont for SLE in susceptible individuals.
LPS Mediates Bovine Endometrial Epithelial Cell Pyroptosis Directly Through Both NLRP3 Classical and Non-Classical Inflammasome Pathways
Authors: Ma Xiaoyu , Li Yajuan , Shen Wenxiang , Oladejo Ayodele Olaolu , Yang Jie , Jiang Wei , Imam Bereket Habte , Wu Xiaohu , Ding Xuezhi , Yang Ying , Wang Shengyi , Yan Zuoting
Published: May 2021

As a highly inflammatory form of programmed cell death, pyroptosis is triggered by pro-inflammatory signals and associated with inflammation. It is characterized by cell swelling and large bubbles emerging from the plasma membrane, which release cytokines during inflammation. Compared with other types of cell death, pyroptosis has a distinct morphology and mechanism and involves special inflammasome cascade pathways. However, the inflammasome mechanism through which endometrial epithelial cell pyroptosis occurs in LPS-mediated inflammation remains unclear. We confirmed that there was an increased mRNA and protein expression of the IL-6, TNF-α, IL-1β, IL-18 cytokines, the inflammasome molecules NLRP3, CASPASE-1, CASPASE-4, and GSDMD in LPS-induced primary bovine endometrial epithelial cells (BEECs) in an in vitro established inflammatory model using ELISA, real-time PCR (RT-PCR), vector construction and transfection, and Western blotting. Scanning electron microscopy and lactate dehydrogenase (LDH) activity assays revealed induced cell membrane rupture, which is the main characteristic of pyroptosis. In conclusion, the cytolytic substrate GSDMD’s cleavage by caspase-1 or caspase-4 through the NLRP3 classical and non-classical inflammasome pathways, GSDMD N-terminus bind to the plasma membrane to form pores and release IL -18, IL-1β cause cell death during LPS induced BEECs inflammation.
Mesenchymal Stem Cell Protects Injured Renal Tubular Epithelial Cells by Regulating mTOR-Mediated Th17/Treg Axis
Authors: Luo Yongsheng , Guo Jingjing , Zhang Pingbao , Cheuk Yin Celeste , Jiang Yamei , Wang Jiyan , Xu Shihao , Rong Ruiming
Published: May 2021

The increase in T helper 17 cell (Th17)-mediated pro-inflammatory response and decrease in regulatory T cell (Treg)-mediated anti-inflammatory effect aggravate renal tubular epithelial cell (RTEC) injury. However, increasing evidence indicated that mesenchymal stem cell (MSC) possessed the ability to control the imbalance between Th17 and Treg. Given that Th17 and Treg are derived from a common CD4+ T cell precursor, we summarize the current knowledge of MSC-mediated inhibition of the mammalian target of rapamycin (mTOR), which is a master regulator of CD4+ T cell polarization. During CD4+ T cell differentiation, mTOR signaling mediates Th17 and Treg differentiation via hypoxia-inducible factor-1α (HIF-1α)-dependent metabolic regulation and signaling pathway, as well as mTOR-mediated phosphorylation of signal transducer and activator of transcription (STAT) 3 and 5. Through interfering with mTOR signaling, MSC restrains CD4+ T cell differentiation into Th17, but in turn promotes Treg generation. Thus, this review indicates that MSC-mediated Th17-to-Treg polarization is expected to act as new immunotherapy for kidney injury.
Absolute Baltic Sea Level Trends in the Satellite Altimetry Era: A Revisit
Authors: Passaro Marcello , Müller Felix L. , Oelsmann Julius , Rautiainen Laura , Dettmering Denise , Hart-Davis Michael G. , Abulaitijiang Adili , Andersen Ole B. , Høyer Jacob L. , Madsen Kristine S. , Ringgaard Ida Margrethe , Särkkä Jani , Scarrott Rory , Schwatke Christian , Seitz Florian , Tuomi Laura , Restano Marco , Benveniste Jérôme
Published: May 2021

The absolute sea level trend from May 1995 to May 2019 in the Baltic Sea is analyzed by means of a regional monthly gridded dataset based on a dedicated processing of satellite altimetry data. In addition, we evaluate the role of the North Atlantic Oscillation and the wind patterns in shaping differences in sea level trend and variability at a sub-basin scale. To compile the altimetry dataset, we use information collected in coastal areas and from leads within sea-ice. The dataset is validated by comparison with tide gauges and the available global gridded altimetry products. The agreement between trends computed from satellite altimetry and tide gauges improves by 9%. The rise in sea level is statistically significant in the entire region of study and higher in winter than in summer. A gradient of over 3 mm/yr in sea level rise is observed, with the north and east of the basin rising more than the south-west. Part of this gradient (about 1 mm/yr) is directly explained by a regression analysis of the wind contribution on the sea level time series. A sub-basin analysis comparing the northernmost part (Bay of Bothnia) with the south-west reveals that the differences in winter sea level anomalies are related to different phases of the North-Atlantic Oscillation (0.71 correlation coefficient). Sea level anomalies are higher in the Bay of Bothnia when winter wind forcing pushes waters through Ekman transport from the south-west toward east and north. The study also demonstrates the maturity of enhanced satellite altimetry products to support local sea level studies in areas characterized by complex coastlines or sea-ice coverage. The processing chain used in this study can be exported to other regions, in particular to test the applicability in regions affected by larger ocean tides.
An Experimental Framework for Selectively Breeding Corals for Assisted Evolution
Authors: Humanes Adriana , Beauchamp Elizabeth A. , Bythell John C. , Carl Mitch K. , Craggs Jamie R. , Edwards Alasdair J. , Golbuu Yimnang , Lachs Liam , Martinez Helios M. , Palmowski Pawel , Paysinger Faith , Randle Janna L. , van der Steeg Eveline , Sweet Michael , Treumann Achim , Guest James R.
Published: May 2021

Coral cover on tropical reefs has declined during the last three decades due to the combined effects of climate change, destructive fishing, pollution, and land use change. Drastic reductions in greenhouse gas emissions combined with effective coastal management and conservation strategies are essential to slow this decline. Innovative approaches, such as selective breeding for adaptive traits combined with large-scale sexual propagation, are being developed with the aim of pre-adapting reefs to increased ocean warming. However, there are still major gaps in our understanding of the technical and methodological constraints to producing corals for such restoration interventions. Here we propose a framework for selectively breeding corals and rearing them from eggs to 2.5-year old colonies using the coral Acropora digitifera as a model species. We present methods for choosing colonies for selective crossing, enhancing early survivorship in ex situ and in situ nurseries, and outplanting and monitoring colonies on natal reefs. We used a short-term (7-day) temperature stress assay to select parental colonies based on heat tolerance of excised branches. From six parental colonies, we produced 12 distinct crosses, and compared survivorship and growth of colonies transferred to in situ nurseries or outplanted to the reef at different ages. We demonstrate that selectively breeding and rearing coral colonies is technically feasible at small scales and could be upscaled as part of restorative assisted evolution initiatives. Nonetheless, there are still challenges to overcome before selective breeding can be implemented as a viable conservation tool, especially at the post-settlement and outplanting phases. Although interdisciplinary approaches will be needed to overcome many of the challenges identified in this study, selective breeding has the potential to be a viable tool within a reef managers toolbox to support the persistence of selected reefs in the face of climate change.