bluuebunny/crossref_metadata_2025 huggingface dataset:
Big Insights From a Small Country: The Added Value of Integrated Assessment in the Marine Environmental Status Evaluation of Malta
Authors: Borja Angel , Menchaca Iratxe , Garmendia Joxe Mikel , Franco Javier , Larreta Joana , Sagarminaga Yolanda , Schembri Yasmin , González Rocío , Antón Rocío , Micallef Tamara , Camilleri Sarah , Solaun Oihana , Uriarte Ainhize , Uyarra María C.
Published: April 2021

In the last few years, the concept of ecosystem-based approach has led to the need for developing integrative assessments that consider the different ecosystem components all together. In Europe, the Marine Strategy Framework Directive (MSFD) aims at achieving the Good Environmental Status for all regional seas. This requires Member States (MS) to implement monitoring networks and assess the status in 6-years management cycles, based on 11 qualitative descriptors, ranging from biodiversity to noise. For that assessment MS must apply criteria and methodological standards, following certain specifications. However, the number of MS which have undertaken quantitative assessments, or aggregated the different criteria and/or descriptors in holistic assessments, remains low. This is probably due to the few available tools that enable the aggregation of information at different scales (spatial and temporal) and the integration of a diverse range of indicators. In order to identify the main constraints tied to the integration of data from different indicators, criteria and descriptors, this study involved a comparative analysis of a national assessment of official marine data reported by Malta with the integrative Nested Environmental status Assessment Tool (NEAT). In total, we have used 282 indicators, 24 criteria, seven descriptors, and 12 ecosystem components. The results showed a good agreement in the assessment at the indicator level (as applied in the national assessment) and threw light on the advantages of integrating the information at criteria, descriptor or ecosystem component levels, when using NEAT. Such integration allows for a global assessment of status of Malta’s marine waters whilst allowing for the identification of management measures at different spatial levels and for different ecosystem components. Lessons learnt from this case study are applicable to remaining assessments for other European MS.
Intelligent Hydrogel Actuators With Controllable Deformations and Movements
Authors: Zhao Qian , Yu Zhenglei , Liang Yunhong , Ren Lei , Ren Luquan
Published: April 2021

Near infrared laser- (NIR-) driven intelligent hydrogel actuator systems including printable N-isopropylacrylamide- (NIPAm-) nanosized synthetic hectorite clay-nanofibrillated cellulose (NFC) hydrogels and NIPAm-4-hydroxybutyl acrylate- (4HBA-) NFC hydrogels with a high response rate were prepared via three-dimensional (3D) printing and hydrothermal synthesis, respectively. The addition of NFC was beneficial to the improvement in rheology. The 3D printed intelligent hydrogel actuators with a structure pattern of Model I and Model II exhibited the saddle and inverted saddle deformations, respectively, to prove the validity of 3D printing. In order to improve the response rate and enrich movement patterns, the hydrothermal synthesized intelligent hydrogel actuators were prepared on the base of the 3D printed intelligent hydrogel compositions. The addition of NFC maintained the controllable NIR response. Based on a wedge-shaped design, the hydrothermal synthesized intelligent hydrogel pushed the resin ball with weight of 130 mg forward 8 mm in 39 s. By changing the torque values of a hydrogel in a different direction, the actuator realized controllable continuous rollover movement. Attributed to the longilineal shape, the intelligent hydrogel actuator reached an effective displacement of 20 mm in 10 s via a forward movement. The characteristics and structure design of a hydrogel material significantly realized multiple controllable functional four-dimensional (4D) printed deformations and movements. The combination of advantages of the 3D printed and hydrothermal synthesized intelligent hydrogels provided a new direction of development and abundant material candidates for the practical applications of 4D printing in soft robot, information sensing, and health engineering.
Increased TPSAB1 Copy Number in a Family With Elevated Basal Serum Levels of Tryptase
Authors: Hernández-Hernández Laura , Sanz Catalina , Marcos-Vadillo Elena , García-Sánchez Asunción , Moreno Esther , Lorente Félix , González-de-Olano David , Dávila Ignacio , Isidoro-García María
Published: April 2021

Background: Some recent familial studies have described a pattern of autosomal dominant inheritance for increased basal serum tryptase (BST), but no correlation with mRNA expression and gene dose have been reported.

Objective: We analyzed TPSAB1 mRNA expression and gene dose in a four-member family with high BST and in two control subjects.

Methods: Blood samples were collected from the family and control subjects. Complete morphologic, immunophenotypical, and molecular bone marrow mast cell (MC) studies were performed. mRNA gene expression and gene dose were performed in a LightCycler 480 instrument. Genotype and CNV were performed by quantitative real-time digital PCR (qdPCR).

Results: CNV analysis revealed a hereditary copy number gain genotype (3β2α) present in all the family members studied. The elevated total BST in the family members correlated with a significant increase in tryptase gene expression and dose.

Conclusions and Clinical Relevance: We present a family with hereditary α-tryptasemia and elevated BST which correlated with a high expression of tryptase genes and an increased gene dose. The family members presented with atypical MC-mediator release symptoms or were even asymptomatic. Clinicians should be aware that elevated BST does not always mean an MC disorder.
Development of a Simple and Practical Screening Tool for Detection of Sarcopenia in Older People: The Bushehr Elderly Health Program
Authors: Shafiee Gita , Ostovar Afshin , Maleki Birjandi Saba , Nabipour Iraj , Larijani Bagher , Heshmat Ramin
Published: April 2021

Background: Sarcopenia is defined by the loss of muscle mass and function with a considerable prevalence which increases morbidity and mortality. We aimed to develop and validate a simple tool for screening of sarcopenia in Iranian older population.

Methods: In this study, we included 2,211 adults aged 60 years or older that participated in the stage II of Bushehr Elderly Health (BEH) program, a population-based prospective cohort study. We defined sarcopenia as reduced skeletal muscle strength plus low muscle mass. The study sample was divided into two parts; development set which were allocated to the development of the model (n = 1,499) and validation set (n = 712) were allocated to validation of the model.

Results: There were 22.9% of men and 23.2% women classified as having sarcopenia based on EWGSOP-2.After selection of variables, the final models named SarSA-Mod (Sarcopenia Scoring Assessment Models) were developed with area to under curves (AUC) of 0.82 (0.79–0.86) and 0.87 (0.84–0.90) in men and women, respectively. The final model included “age,” “weight,” and “calf circumference” in both sexes. The sensitivity and specificity and positive and negative predictive values for sarcopenia were 84.3, 76.0, 49.8, and 94.5% for women, 85.4, 64.8, 40.2, and 94.2% for men, respectively. The model performance was tested in the validation set with accuracy 91 and 84% among women and men, respectively.

Conclusions: Sarcopenia could be detected using SarSA-Mod, as a simple screening test with high accuracy among both sexes. Also, this screening test is valid, feasible, reliable and cost-effective compared to other tools.
Uremia-Associated Immunological Aging and Severity of COVID-19 Infection
Authors: Betjes Michiel G. H.
Published: April 2021

One year after the start of the COVID-19 pandemic it has become clear that some groups of individuals are at particular high risk of a complicated course of infection resulting in high morbidity and mortality. Two specific risk factors are most prominent, old age and the presence of co-morbidity. Recent studies have shown that patients with compromised renal function, especially those treated with renal replacement therapy or having received a kidney transplant are at a much higher risk for severe COVID infection and increased mortality. This may be in part due to the increased prevalence of co-morbid conditions in these patients but specific alterations in their immune system, reflecting premature immunological aging, may be equally important. In this review the different aspects, in particular thymus function and memory T cell expansion, of uremia-associated immunological aging are reviewed with respect to COVID 19 infection. In essence, the decreased generation of naïve T cells may be instrumental in suboptimal anti-viral immune responses while the relatively uncontrolled expansion of effector T cells may facilitate the feared phase of the COVID-19 infection with excessive and live-threatening inflammation of the lung parenchyma.
Polymorphisms in Genes Encoding Glutathione Transferase Pi and Glutathione Transferase Omega Influence Prostate Cancer Risk and Prognosis
Authors: Santric Veljko , Dragicevic Dejan , Matic Marija , Djokic Milica , Pljesa-Ercegovac Marija , Radic Tanja , Suvakov Sonja , Nikitovic Marina , Stankovic Vesna , Milojevic Bogomir , Radovanovic Milan , Dzamic Zoran , Simic Tatjana , Savic-Radojevic Ana
Published: April 2021

Considering the pleiotropic roles of glutathione transferase (GST) omega class members in redox homeostasis, we hypothesized that polymorphisms in GSTO1 and GSTO2 might contribute to prostate cancer (PC) development and progression. Therefore, we performed a comprehensive analysis of GSTO1 and GSTO2 SNPs’ role in susceptibility to PC, as well as whether they might serve as prognostic biomarkers independently or in conjunction with other common GST polymorphisms (GSTM1, GSTT1, and GSTP1). Genotyping was performed in 237 PC cases and 236 age-matched controls by multiplex PCR for deletion of GST polymorphisms and quantitative PCR for SNPs. The results of this study, for the first time, demonstrated that homozygous carriers of both GSTO1*A/A and GSTO2*G/G variant genotypes are at increased risk of PC. This was further confirmed by haplotype analysis, which showed that H2 comprising both GSTO1*A and GSTO2*G variant alleles represented a high-risk combination. However, the prognostic relevance of polymorphisms in GST omega genes was not found in our cohort of PC patients. Analysis of the role of other investigated GST polymorphisms (GSTM1, GSTT1, and GSTP1) in terms of PC prognosis has shown shorter survival in carriers of GSTP1*T/T (rs1138272) genotype than in those carrying at least one referent allele. In addition, the presence of GSTP1*T/T genotype independently predicted a four-fold higher risk of overall mortality among PC patients. This study demonstrated a significant prognostic role of GST polymorphism in PC.
Comprehensive Metabolomics Identified the Prominent Role of Glycerophospholipid Metabolism in Coronary Artery Disease Progression
Authors: Chen Hui , Wang Zixian , Qin Min , Zhang Bin , Lin Lu , Ma Qilin , Liu Chen , Chen Xiaoping , Li Hanping , Lai Weihua , Zhong Shilong
Published: April 2021

Background: Coronary stenosis severity determines ischemic symptoms and adverse outcomes. The metabolomic analysis of human fluids can provide an insight into the pathogenesis of complex disease. Thus, this study aims to investigate the metabolomic and lipidomic biomarkers of coronary artery disease (CAD) severity and to develop diagnostic models for distinguishing individuals at an increased risk of atherosclerotic burden and plaque instability.

Methods: Widely targeted metabolomic and lipidomic analyses of plasma in 1,435 CAD patients from three independent centers were performed. These patients were classified as stable coronary artery disease (SCAD), unstable angina (UA), and myocardial infarction (MI). Associations between CAD stages and metabolic conditions were assessed by multivariable-adjusted logistic regression. Furthermore, the least absolute shrinkage and selection operator logistic-based classifiers were used to identify biomarkers and to develop prediagnostic models for discriminating the diverse CAD stages.

Results: On the basis of weighted correlation network analysis, 10 co-clustering metabolite modules significantly (p < 0.05) changed at different CAD stages and showed apparent correlation with CAD severity indicators. Moreover, cross-comparisons within CAD patients characterized that a total of 72 and 88 metabolites/lipid species significantly associated with UA (vs. SCAD) and MI (vs. UA), respectively. The disturbed pathways included glycerophospholipid metabolism, and cysteine and methionine metabolism. Furthermore, models incorporating metabolic and lipidomic profiles with traditional risk factors were constructed. The combined model that incorporated 11 metabolites/lipid species and four traditional risk factors represented better discrimination of UA and MI (C-statistic = 0.823, 95% CI, 0.783–0.863) compared with the model involving risk factors alone (C-statistic = 0.758, 95% CI, 0.712–0.810). The combined model was successfully used in discriminating UA and MI patients (p < 0.001) in a three-center validation cohort.

Conclusion: Differences in metabolic profiles of diverse CAD subtypes provided a new approach for the risk stratification of unstable plaque and the pathogenesis decipherment of CAD progression.
Generative Models for Active Vision
Authors: Parr Thomas , Sajid Noor , Da Costa Lancelot , Mirza M. Berk , Friston Karl J.
Published: April 2021

The active visual system comprises the visual cortices, cerebral attention networks, and oculomotor system. While fascinating in its own right, it is also an important model for sensorimotor networks in general. A prominent approach to studying this system is active inference—which assumes the brain makes use of an internal (generative) model to predict proprioceptive and visual input. This approach treats action as ensuring sensations conform to predictions (i.e., by moving the eyes) and posits that visual percepts are the consequence of updating predictions to conform to sensations. Under active inference, the challenge is to identify the form of the generative model that makes these predictions—and thus directs behavior. In this paper, we provide an overview of the generative models that the brain must employ to engage in active vision. This means specifying the processes that explain retinal cell activity and proprioceptive information from oculomotor muscle fibers. In addition to the mechanics of the eyes and retina, these processes include our choices about where to move our eyes. These decisions rest upon beliefs about salient locations, or the potential for information gain and belief-updating. A key theme of this paper is the relationship between “looking” and “seeing” under the brain's implicit generative model of the visual world.
Afterdischarges in Myasthenia Gravis
Authors: Yang Li , Guo Shougang , Chen Xiuying
Published: April 2021

Introduction: This study aimed to analyze the clinical features of myasthenia gravis (MG) in combination with the afterdischarges and compare the characteristics of afterdischarges in MG with different serum antibodies.

Methods: Ninety-two patients with MG were analyzed retrospectively. The afterdischarges were investigated using motor nerve conduction examination, F-wave examination, and repetitive nerve stimulation (RNS).

Results: Afterdischarges were observed after the M wave in 14 of 92 patients. Three of these 14 patients tested positive for the muscle-specific tyrosine kinase antibody (MuSK-Ab), and 11 patients tested positive for the acetylcholine receptor antibody (AchR-Ab). The characteristics of the afterdischarges on RNS differed distinctly between the two antibody groups. The afterdischarges occurred on the first stimulation, but decreased on the second and subsequent stimulations in patients with MuSK-MG, while the afterdischarges continued to occur on each stimulation in patients with AchR-MG.

Discussion: The characteristics of the afterdischarges on RNS enabled easy identification of their synaptic or neurogenic nature.
A P300 Brain-Computer Interface Paradigm Based on Electric and Vibration Simple Command Tactile Stimulation
Authors: Chu Chenxi , Luo Jingjing , Tian Xiwei , Han Xiangke , Guo Shijie
Published: April 2021

This paper proposed a novel tactile-stimuli P300 paradigm for Brain-Computer Interface (BCI), which potentially targeted at people with less learning ability or difficulty in maintaining attention. The new paradigm using only two types of stimuli was designed, and different targets were distinguished by frequency and spatial information. The classification algorithm was developed by introducing filters for frequency bands selection and conducting optimization with common spatial pattern (CSP) on the tactile evoked EEG signals. It features a combination of spatial and frequency information, with the spatial information distinguishing the sites of stimuli and frequency information identifying target stimuli and disturbances. We investigated both electrical stimuli and vibration stimuli, in which only one target site was stimulated in each block. The results demonstrated an average accuracy of 94.88% for electrical stimuli and 95.21% for vibration stimuli, respectively.
Brain Oscillation Entrainment by Perceptible and Non-perceptible Rhythmic Light Stimulation
Authors: Lingelbach Katharina , Dreyer Alexander M. , Schöllhorn Isabel , Bui Michael , Weng Michael , Diederichs Frederik , Rieger Jochem W. , Petermann-Stock Ina , Vukelić Mathias
Published: April 2021

Objective and Background:Decades of research in the field of steady-state visual evoked potentials (SSVEPs) have revealed great potential of rhythmic light stimulation for brain–computer interfaces. Additionally, rhythmic light stimulation provides a non-invasive method for entrainment of oscillatory activity in the brain. Especially effective protocols enabling non-perceptible rhythmic stimulation and, thereby, reducing eye fatigue and user discomfort are favorable. Here, we investigate effects of (1) perceptible and (2) non-perceptible rhythmic light stimulation as well as attention-based effects of the stimulation by asking participants to focus (a) on the stimulation source directly in an overt attention condition or (b) on a cross-hair below the stimulation source in a covert attention condition.

Method:SSVEPs at 10 Hz were evoked with a light-emitting diode (LED) driven by frequency-modulated signals and amplitudes of the current intensity either below or above a previously estimated individual threshold. Furthermore, we explored the effect of attention by asking participants to fixate on the LED directly in the overt attention condition and indirectly attend it in the covert attention condition. By measuring electroencephalography, we analyzed differences between conditions regarding the detection of reliable SSVEPs via the signal-to-noise ratio (SNR) and functional connectivity in occipito-frontal(-central) regions.

Results:We could observe SSVEPs at 10 Hz for the perceptible and non-perceptible rhythmic light stimulation not only in the overt but also in the covert attention condition. The SNR and SSVEP amplitudes did not differ between the conditions and SNR values were in all except one participant above significance thresholds suggested by previous literature indicating reliable SSVEP responses. No difference between the conditions could be observed in the functional connectivity in occipito-frontal(-central) regions.

Conclusion:The finding of robust SSVEPs even for non-intrusive rhythmic stimulation protocols below an individual perceptibility threshold and without direct fixation on the stimulation source reveals strong potential as a safe stimulation method for oscillatory entrainment in naturalistic applications.
Red Clover Isoflavones Influence Estradiol Concentration, Exercise Performance, and Gut Microbiota in Female Mice
Authors: Chen Yi-Ming , Wang I-Lin , Zhu Xin-Yi , Chiu Wan-Chun , Chiu Yen-Shuo
Published: April 2021

In red clover (Trifolium pratense L.; RC) the main compound is isoflavones, which are selective estrogen receptor modulators for maintaining female health. Isoflavones exert antifatigue effects during exercise in high-temperature environments. This study aimed to investigate the effect of RC supplementation on gut microbiota composition to determine whether it improves intestinal barrier function and exercise performance. Female ICR mice were divided into four groups (n = 8 per group) and orally administered RC once daily for 6 weeks at 0 (vehicle), 308 (RC-1X), 615 (RC-2X), and 1,538 (RC-5X) mg/kg. RC supplementation decreased the fat mass and increased exhaustive swimming time, grip strength, and muscle glycogen in female mice. In the RC supplementation group, serum levels of lactate, ammonia, and creatine kinase decreased after swimming. The estradiol and progesterone levels were higher in the RC group than in the vehicle group. Regarding gut microbiota composition, the RC-2X group may increase intestinal health related to the microorganisms Pseudobutyrivibrio and Parabacteroide. Thus, the use of RC supplements as nutraceuticals could have positive effects on athletes' gut and overall health.
Effects of Coronavirus Disease 2019 (COVID-19) on Peripheral Blood Lymphocytes and Their Subsets in Children: Imbalanced CD4+/CD8+ T Cell Ratio and Disease Severity
Authors: Mahmoudi Shima , Yaghmaei Bahareh , Sharifzadeh Ekbatani Meisam , Pourakbari Babak , Navaeian Amene , Parvaneh Nima , Haghi Ashtiani Mohammad Taghi , Mamishi Setareh
Published: April 2021

Introduction: While pathogenesis in COVID-19 is not fully known and the effects between SARS-CoV-2 and the immune system are complicated, it is known that lymphopenia, hyper-inflammatory responses, and cytokines play an important role in the pathology of COVID-19. While some hematological abnormalities have been described among the laboratory features of COVID-19, there have not been studies reported on lymphocyte subset analyses in children. The aim of this study was to describe lymphocyte subsets in pediatric patients with mild/moderate or severe COVID-19.

Methods: The subjects in the study were children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia confirmed with the real-time RT-PCR. The subjects were admitted to the Children's Medical Center, affiliated with the Tehran University of Medical Sciences, between March 7th and June 10th of 2020. The complete blood counts and lymphocyte subpopulations were analyzed for each patient.

Results: The study included 55 hospitalized patients with confirmed SARS-CoV-2 infection (34 patients (62%) with an observed mild/moderate case of the disease and 21 patients (38%) with severedisease). Lymphocyte counts were found to be lower in patients with a severe case (mean ± SD 1.6 ± 0.9 in the severe group vs. 2.3 ± 2.2 in the mild group). Compared to the group with mild/moderate pneumonia, children with severe pneumonia had an increased count of CD8+ T cell and a lower percentage of CD4+ T cell. However, the differences between the groups were negligible. Interestingly, the severe group had a lower CD4+/CD8+ T cell ratio compared to the mild group (1.1 ± 0.47 vs. 1.4 ± 0.8, p-value: 0.063). CD4+/CD8+ T cell ratio <2, 1.5, and 1 was found in 48 (87%), 40 (73%), and 19 cases (35%). All of the seven cases in which the subject passed (13%) had CD4+/CD8+ T cell ratio of <2, 86% had CD4+/CD8+ T cell ratio of <1.5, and 29% had CD4+/CD8+ T cell ratio of <1.

Conclusion: The CD4+/CD8+ T cell ratio was lower in patients with severe COVID-19 compared to those with mild/moderate form of disease. However, although a decline in CD4+/CD8+ ratio may serve as a useful metric in analyzing of the derangement in immune responses in patients with severe COVID-19, further study with larger sample sizes is highly recommended.
Using MEST-C Scores and the International Study of Kidney Disease in Children Classification to Predict Outcomes of Henoch–Schönlein Purpura Nephritis in Children
Authors: Wang Meiqiu , Wang Ren , He Xu , Zhang Pei , Kuang Qianhuining , Yao Jun , Fang Xiang , Shi Zhuo , Wu Heyan , Peng Yingchao , Xia Zhengkun , Gao Chunlin
Published: April 2021

Introduction: Henoch–Schönlein purpura nephritis (HSPN) and IgA nephropathy (IgAN) bear similarities in some aspects. The histological classification of HSPN was built on the International Study of Kidney Disease in Children (ISKDC) criteria, while IgAN was established on the 2016 Oxford classification (MEST-C scores). The purpose of this paper was to discuss the predictive value of the ISKDC classification and MEST-C scores in children with HSPN.

Methods: We performed a retrospective study of 877 children with HSPN in a single center between 2001 and 2019. The primary outcome was defined as chronic kidney disease—estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2.

Results: During the follow-up period of 23.3 (10.9–47.9) months, 51 (5.8%) patients reached the primary outcome. As revealed in a Kaplan–Meier plot, segmental glomerulosclerosis (S) (P < 0.001) and tubular atrophy/interstitial fibrosis (T) (P < 0.001) significantly predict poor renal outcome. Other Oxford lesions and the ISKDC classification, however, did not show a significant difference in a worse outcome. In a multivariate Cox model adjusted for pathological and clinical factors, eGFR [hazard ratio (HR) = 2.831, 95% confidence interval (95% CI) = 1.359–5.896], S lesion (HR = 3.936, 95% CI = 2.078–7.457), and T lesion (HR = 4.002, 95% CI = 1.733–9.242) were independent risk factors for the renal outcome.

Conclusion: This series constitutes the largest series reported so far in the literature of such patients. According to our findings, S and T of the Oxford classification, which are ignored by the ISKDC classification, could be applied to predict the renal prognosis of children with HSPN.
Metabolomic Profiling of Aqueous Humor and Plasma in Primary Open Angle Glaucoma Patients Points Towards Novel Diagnostic and Therapeutic Strategy
Authors: Tang Yizhen , Pan Yiqiong , Chen Yuhong , Kong Xiangmei , Chen Junyi , Zhang Hengli , Tang Guangxian , Wu Jihong , Sun Xinghuai
Published: April 2021

Glaucoma is the second leading cause of blindness globally characterized by progressive loss of retinal ganglion cells (RGCs) and irreversible visual deficiency. As the most common type of glaucoma, primary open angle glaucoma (POAG) is currently an unmet medical need with limited therapy by lowering intraocular pressure (IOP). However, some patients continue to progress even though their IOP are controlled. Although early diagnosis and prompt treatment are crucial in preventing irreversible visual impairment, there are currently no biomarkers for screening POAG. Metabolomics has the advantages of illustrating the final downstream products of the genome and establishing the closest link to the phenotype. So far, there is no study investigating the metabolomic profiles in both aqueous humor and plasma of POAG patients. Therefore, to explore diagnostic biomarkers, unveil underlying pathophysiology and potential therapeutic strategies, a widely targeted metabolomic approach was applied using ultrahigh-resolution mass spectrometry with C18 liquid chromatography to characterize the metabolomic profiles in both aqueous humor and plasma of 28 POAG patients and 25 controls in our study. Partial least squares-discriminant analysis (PLS-DA) was performed to determine differentially expressed metabolites (DEMs) between POAG and age-matched controls. The area under the receiver operating characteristic curve (AUC) was calculated to assess the prediction accuracy of the DEMs. The correlation of DEMs with the clinical parameters was determined by Pearson correlation, and the metabolic pathways were analyzed using MetaboAnalyst 4.0. PLS-DA significantly separated POAG from controls with 22 DEMs in the aqueous humor and 11 DEMs in the plasma. Additionally, univariate ROC analysis and correlation analysis with clinical parameters revealed cyclic AMP (AUC = 0.87), 2-methylbenzoic acid (AUC = 0.75), 3′-sialyllactose (AUC = 0.73) in the aqueous humor and N-lac-phe (AUC = 0.76) in the plasma as potential biomarkers for POAG. Moreover, the metabolic profiles pointed towards the alteration in the purine metabolism pathway. In conclusion, the study identified potential and novel biomarkers for POAG by crosslinking the metabolomic profiles in aqueous humor and plasma and correlating with the clinical parameters. These findings have important clinical implications given that no biomarkers are currently available for glaucoma in the clinic, and the study provided new insights in exploring diagnostic biomarkers and potential therapeutic strategies of POAG by targeting metabolic pathways.
Catfish Epidermal Preparation Accelerates Healing of Damaged Nerve in a Sciatic Nerve Crush Injury Rat Model
Authors: Renno Waleed M. , Afzal Mohammad , Paul Bincy , Nair Divya , Kumar Jijin , Al-Hassan Jassim M.
Published: April 2021

Preliminary investigations showed that preparations from Arabian Gulf catfish (Arius bilineatus, Val) epidermal gel secretion (PCEGS) exhibit potent anti-inflammatory and healing properties as shown in our previous clinical trials for the healing of non-healing diabetic foot ulcers, chronic back pain, and some other neurological disorders. Here, we report for the first time a unique preparation containing only proteins and lipids (soluble protein fraction B, SPF-FB), derived from the PCEGS accelerated the healing and recovery of sensory-motor functions of experimental sciatic nerve crush injury in rats with its unique neuroprotective and neuroregenerative properties on the spinal neurons and peripheral nerve fibers. Male rats were randomly assigned to five groups: (I) NAÏVE, (II) SHAM, (III) CRUSH treated with saline, (IV) CRUSH + SPF-FB treated with 3 mg/kg intraperitoneally (IP) and (V) CRUSH + SPF-FB treated with 6 mg/kg subcutaneously (SC) groups. The crush groups III, IV and V underwent sciatic nerve crush injury, followed by treatment daily for 14 days with saline, SPF-FB IP and SPF-FB SC. All animals were tested for the neurobehavioral parameters throughout the 6 weeks of the study. Sciatic nerve and spinal cord tissues were processed for light and electron histological examinations, stereological analysis, immunohistochemical and biochemical examinations at Week 4 and Week 6 post-injury. Administration of SPF-FB IP or SC significantly enhanced the neurobehavioral sensory and motor performance and histomorphological neuroregeneration of the sciatic nerve-injured rats. The stereological evaluation of the axon area, average axon perimeters, and myelin thickness revealed significant histomorphological evidence of neuroregeneration in the FB-treated sciatic nerve crush injured groups compared to controls at 4 and 6 weeks. SPF-FB treatment significantly prevented the increased in NeuN-immunoreactive neurons, increased GFAP immunoreactive astrocytes, and decreased GAP-43. We conclude that SPF-FB treatment lessens neurobehavioral deficits, enhances axonal regeneration following nerve injury. We conclude that SPF-FB treatment lessens neurobehavioral deficits and enhances axonal regeneration following nerve injury, as well as protects spinal neurons and enhances subcellular recovery by increasing astrocytic activity and decreasing GAP-43 expression.
Type I Interferons in Systemic Autoimmune Diseases: Distinguishing Between Afferent and Efferent Functions for Precision Medicine and Individualized Treatment
Authors: Chasset François , Dayer Jean-Michel , Chizzolini Carlo
Published: April 2021

A sustained increase in type I interferon (IFN-I) may accompany clinical manifestations and disease activity in systemic autoimmune diseases (SADs). Despite the very frequent presence of IFN-I in SADs, clinical manifestations are extremely varied between and within SADs. The present short review will address the following key questions associated with high IFN-I in SADs in the perspective of precision medicine. 1) What are the mechanisms leading to high IFN-I? 2) What are the predisposing conditions favoring high IFN-I production? 3) What is the role of IFN-I in the development of distinct clinical manifestations within SADs? 4) Would therapeutic strategies targeting IFN-I be helpful in controlling or even preventing SADs? In answering these questions, we will underlie areas of incertitude and the intertwined role of autoantibodies, immune complexes, and neutrophils.
Event-Chain Monte-Carlo Simulations of Dense Soft Matter Systems
Authors: Kampmann Tobias Alexander , Müller David , Weise Lukas Paul , Vorsmann Clemens Franz , Kierfeld Jan
Published: April 2021

We discuss the rejection-free event-chain Monte-Carlo algorithm and several applications to dense soft matter systems. Event-chain Monte-Carlo is an alternative to standard local Markov-chain Monte-Carlo schemes, which are based on detailed balance, for example the well-known Metropolis-Hastings algorithm. Event-chain Monte-Carlo is a Markov chain Monte-Carlo scheme that uses so-called lifting moves to achieve global balance without rejections (maximal global balance). It has been originally developed for hard sphere systems but is applicable to many soft matter systems and particularly suited for dense soft matter systems with hard core interactions, where it gives significant performance gains compared to a local Monte-Carlo simulation. The algorithm can be generalized to deal with soft interactions and with three-particle interactions, as they naturally arise, for example, in bead-spring models of polymers with bending rigidity. We present results for polymer melts, where the event-chain algorithm can be used for an efficient initialization. We then move on to large systems of semiflexible polymers that form bundles by attractive interactions and can serve as model systems for actin filaments in the cytoskeleton. The event chain algorithm shows that these systems form networks of bundles which coarsen similar to a foam. Finally, we present results on liquid crystal systems, where the event-chain algorithm can equilibrate large systems containing additional colloidal disks very efficiently, which reveals the parallel chaining of disks.
Mechanical Stretch Induces Smooth Muscle Cell Dysfunction by Regulating ACE2 via P38/ATF3 and Post-transcriptional Regulation by miR-421
Authors: Liu Xiaolin , Liu Xinxin , Li Mengmeng , Zhang Yu , Chen Weijia , Zhang Meng , Zhang Cheng , Zhang Mei
Published: April 2021

Graphical Abstract

Mechanical stretch may decrease the level of the protective factor ACE2 via the p38 MAPK/ATF3 pathway by prompting ATF3 translocation into the nucleus, which could directly bind to the ACE2 promoter via post-transcriptional regulation by miR-421.
Characterizing the Role of Orco Gene in Detecting Aggregation Pheromone and Food Resources in Protaetia brevitarsis Leiws (Coleoptera: Scarabaeidae)
Authors: Zhang Xiaofang , Liu Panjing , Qin Qiuju , Li Min , Meng Runjie , Zhang Tao
Published: April 2021

An accurate olfactory system for recognizing semiochemicals and environmental chemical signals plays crucial roles in survival and reproduction of insects. Among all olfaction-related proteins, olfactory receptors (ORs) contribute to the conversion of chemical stimuli to electric signals and thereby are vital in odorant recognition. Olfactory receptor co-receptor (Orco), one of the most conserved ORs, is extremely essential in recognizing odorants through forming a ligand-gated ion channel complex with conventional ligand-binding odorant receptors. We have previously identified aggregation pheromone in Protaetia brevitarsis (Coleoptera: Scarabaeidae), a native agricultural and horticultural pest in East-Asia. However, to our best knowledge, its olfaction recognition mechanisms are still veiled. To illustrate how P. brevitarsis recognize aggregation pheromone and host plants, in the present study we cloned and sequenced the full-length Orco gene from P. brevitarsis antennae (named PbreOrco) and found that PbreOrco is highly conserved and similar to Orcos from other Coleoptera insects. Our real-time quantitative PCR (qRT-PCR) results showed that PbreOrco is mainly expressed in antenna. We also demonstrated that silencing PbreOrco using RNA interference through injecting dsOrco fragment significantly inhibited PbreOrco expression in comparison with injecting control dsGFP and subsequently revealed using electroantennogram and behavioral bioassays that decreasing PbreOrco transcript abundance significantly impaired the responses of P. brevitarsis to intraspecific aggregation pheromone and prolonged the time of P. brevitarsis spending on food seeking. Overall, our results demonstrated that PbreOrco is crucial in mediating odorant perception in P. brevitarsis.
Seed Dormancy and Soil Seed Bank of the Two Alpine Primula Species in the Hengduan Mountains of Southwest China
Authors: Peng De-Li , Yang Li-E , Yang Juan , Li Zhi-Min
Published: April 2021

The timing of germination has long been recognized as a key seedling survival strategy for plants in highly variable alpine environments. Seed dormancy and germination mechanisms are important factors that determining the timing of germination. To gain an understanding of how these mechanisms help to synchronize the germination event to the beginning of the growing season in two of the most popular Primula species (P. secundiflora and P. sikkimensis) in the Hengduan Mountains, Southwest China, we explored their seed dormancy and germination characteristics in the laboratory and their soil seed bank type in the field. Germination was first tested using fresh seeds at two alternating temperatures (15/5 and 25/15°C) and five constant temperatures (5, 10, 15, 20, and 25°C) in light and dark, and again after dry after-ripening at room temperature for 6 months. Germination tests were also conducted at a range of temperatures (5–30, 25/15, and 15/5°C) in light and dark for seeds dry cold stored at 4°C for 4 years, after which they were incubated under the above-mentioned incubation conditions after different periods (4 and 8 weeks) of cold stratification. Base temperatures (Tb) and thermal times for 50% germination (θ50) were calculated. Seeds were buried at the collection site to test persistence in the soil for 5 years. Dry storage improved germination significantly, as compared with fresh seeds, suggesting after-ripening released physiological dormancy (PD); however, it was not sufficient to break dormancy. Cold stratification released PD completely after dry storage, increasing final germination, and widening the temperature range from medium to both high and low; moreover, the Tb and θ50 for germination decreased. Fresh seeds had a light requirement for germination, facilitating formation of a persistent soil seed bank. Although the requirement reduced during treatments for dormancy release or at lower alternating temperatures (15/5°C), a high proportion of viable seeds did not germinate even after 5 years of burial, showing that the seeds of these two species could cycle back to dormancy if the conditions were unfavorable during spring. In this study, fresh seeds of the two Primula species exhibited type 3 non-deep physiological dormancy and required light for germination. After dormancy release, they had a low thermal requirement for germination control, as well as rapid seed germination in spring and at/near the soil surface from the soil seed bank. Such dormancy and germination mechanisms reflect a germination strategy of these two Primula species, adapted to the same alpine environments.
Induced Local and Systemic Defense Responses in Tomato Underlying Interactions Between the Root-Knot Nematode Meloidogyne incognita and the Potato Aphid Macrosiphum euphorbiae
Authors: Mbaluto Crispus M. , Ahmad Esraa M. , Mädicke Anne , Grosser Katharina , van Dam Nicole M. , Martínez-Medina Ainhoa
Published: April 2021

Plants mediate interactions between different herbivores that attack simultaneously or sequentially aboveground (AG) and belowground (BG) organs. The local and systemic activation of hormonal signaling pathways and the concomitant accumulation of defense metabolites underlie such AG-BG interactions. The main plant-mediated mechanisms regulating these reciprocal interactions via local and systemic induced responses remain poorly understood. We investigated the impact of root infection by the root-knot nematode (RKN) Meloidogyne incognita at different stages of its infection cycle, on tomato leaf defense responses triggered by the potato aphid Macrosiphum euphorbiae. In addition, we analyzed the reverse impact of aphid leaf feeding on the root responses triggered by the RKN. We focused specifically on the signaling pathways regulated by the phytohormones jasmonic acid (JA), salicylic acid (SA), abscisic acid (ABA), and indole-3-acetic acid (IAA) as well as steroidal glycoalkaloids as induced defense compounds. We found that aphid feeding did not induce AG hormonal signaling, but it repressed steroidal glycoalkaloids related responses in leaves, specifically when feeding on plants in the vegetative stage. Root infection by the RKN impeded the aphid-triggered repression of the steroidal glycoalkaloids-related response AG. In roots, the RKN triggered the SA pathway during the entire infection cycle and the ABA pathway specifically during its reproduction stage. RKN infection also elicited the steroidal glycoalkaloids related gene expression, specifically when it was in the galling stage. Aphid feeding did not systemically alter the RKN-induced defense responses in roots. Our results point to an asymmetrical interaction between M. incognita and Ma. euphorbiae when co-occurring in tomato plants. Moreover, the RKN seems to determine the root defense response regardless of a later occurring attack by the potato aphid AG.
A Rationally Designed Bovine IgA Fc Scaffold Enhances in planta Accumulation of a VHH-Fc Fusion Without Compromising Binding to Enterohemorrhagic E. coli
Authors: Chin-Fatt Adam , Saberianfar Reza , Menassa Rima
Published: April 2021

We previously isolated a single domain antibody (VHH) that binds Enterohemorrhagic Escherichia coli (EHEC) with the end-goal being the enteromucosal passive immunization of cattle herds. To improve the yield of a chimeric fusion of the VHH with an IgA Fc, we employed two rational design strategies, supercharging and introducing de novo disulfide bonds, on the bovine IgA Fc component of the chimera. After mutagenizing the Fc, we screened for accumulation levels after transient transformation in Nicotiana benthamiana leaves. We identified and characterized five supercharging and one disulfide mutant, termed ‘(5 + 1)Fc’, that improve accumulation in comparison to the native Fc. Combining all these mutations is associated with a 32-fold increase of accumulation for the Fc alone, from 23.9 mg/kg fresh weight (FW) to 599.5 mg/kg FW, as well as a twenty-fold increase when fused to a VHH that binds EHEC, from 12.5 mg/kg FW tissue to 236.2 mg/kg FW. Co-expression of native or mutated VHH-Fc with bovine joining chain (JC) and bovine secretory component (SC) followed by co-immunoprecipitation suggests that the stabilizing mutations do not interfere with the capacity of VHH-Fc to assemble with JC and FC into a secretory IgA. Both the native and the mutated VHH-Fc similarly neutralized the ability of four of the seven most prevalent EHEC strains (O157:H7, O26:H11, O111:Hnm, O145:Hnm, O45:H2, O121:H19 and O103:H2), to adhere to HEp-2 cells as visualized by immunofluorescence microscopy and quantified by fluorometry. These results collectively suggest that supercharging and disulfide bond tethering on a Fc chain can effectively improve accumulation of a VHH-Fc fusion without impacting VHH functionality.
A Holistic Approach to Study Photosynthetic Acclimation Responses of Plants to Fluctuating Light
Authors: Gjindali Armida , Herrmann Helena A. , Schwartz Jean-Marc , Johnson Giles N. , Calzadilla Pablo I.
Published: April 2021

Plants in natural environments receive light through sunflecks, the duration and distribution of these being highly variable across the day. Consequently, plants need to adjust their photosynthetic processes to avoid photoinhibition and maximize yield. Changes in the composition of the photosynthetic apparatus in response to sustained changes in the environment are referred to as photosynthetic acclimation, a process that involves changes in protein content and composition. Considering this definition, acclimation differs from regulation, which involves processes that alter the activity of individual proteins over short-time periods, without changing the abundance of those proteins. The interconnection and overlapping of the short- and long-term photosynthetic responses, which can occur simultaneously or/and sequentially over time, make the study of long-term acclimation to fluctuating light in plants challenging. In this review we identify short-term responses of plants to fluctuating light that could act as sensors and signals for acclimation responses, with the aim of understanding how plants integrate environmental fluctuations over time and tailor their responses accordingly. Mathematical modeling has the potential to integrate physiological processes over different timescales and to help disentangle short-term regulatory responses from long-term acclimation responses. We review existing mathematical modeling techniques for studying photosynthetic responses to fluctuating light and propose new methods for addressing the topic from a holistic point of view.
Performance-Based Accountability and Teacher Emotions: Role of Zhongyong Thinking
Authors: Zhang Ying , Tsang Kwok Kuen
Published: April 2021

Teachers’ emotions may be affected by structural reforms of education that emphasizes performance-based accountability (PBA) and by individual psychological processes like thinking style, but there is a lack of research concerning the relationship between the three factors. In this study, thus, we attempted to test the influence of PBA on teacher emotions and to examine whether the relationship was moderated by a zhongyong thinking (ZYT) style in a Chinese context. A sample of 402 primary and secondary schoolteachers from Hubei, Liaoning, and Beijing in China participated in this study. Structural equation modeling was applied to develop moderation models. The results demonstrated that PBA is a singificant factor with respect to teachers’ joy, sadness/frustration, anger, and fear, as related to their job of teaching, but not love of their profession. Moreover, the ZYT style may moderate the relationship between PBA and joy.