bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Investigation of the Effects of Aquatic Vegetation on Wind-Induced Wave and Current Characteristics in Shallow Lakes
Authors: Wu Chenhui , Wu Shiqiang , Wu Xiufeng , Dai Jiangyu , Gao Ang , Yang Fan
Published: January 2022

Aquatic vegetation is one of the important parts of the shallow lake ecosystem, which has an important impact on the characteristics of wind-driven wave and current. In this article, we embed the vegetation module into the flow model TELEMAC-3D and the wave model TOMAWAC, respectively, and construct the coupling model of flow–wave–vegetation in the open source model Open TELEMAC-MASCARET. Through the verification of two sets of experimental data, it has been proven that the model can well reproduce the influence of vegetation on current and wave. Then, the model is applied to the wind-driven wave and current simulation of a typical shallow lake, Taihu Lake. The results show that the model can accurately reproduce the characteristics of wind-driven wave and current. Aquatic vegetation significantly changes the velocity, wave height, and local three-dimensional circulation flow in the vegetation patches. At the same time, the existence of aquatic vegetation reduces the material exchange rate between the vegetation area and the outside world, which has a significant impact on the material transport characteristics of the lake. Sensitivity analysis shows that the influence of aquatic vegetation should not be ignored in the simulation of wind-induced wave current and material transport in shallow lakes.
Estuarine Fish Feeding Changes as Indicator to Mangrove Restoration Success in Seasonal Karstic Wetlands
Authors: Hernández-Mendoza Lesli C. , Escalera-Vázquez Luis , Arceo-Carranza Daniel
Published: January 2022

The loss of mangrove areas due to anthropogenic activities has triggered efforts to recover or restore these ecosystems, their functions, and associated diversity. Such functions include nursery areas and energy flow through trophic relationships for a large variety of inhabitant species (e.g., fish). The food webs and trophic dynamics of estuarine fish provide important information on the food resources in mangrove ecosystems and their response to restoration processes. Nonetheless, few studies focus on using fish feeding characteristics as an approximation to assess the conservation or recovery status of these aquatic ecosystems. Thus, the aim of the present study was to compare the trophic dynamics of an ichthyic community in a mangrove ecosystem related to karstic wetlands in the Mexican–Caribbean using freshwater, estuarine, and marine fish species as bioindicators of the restoration process in mangroves. Stomach contents were analyzed for eight species of fish inhabiting specific mangrove zones (1—conserved zone, and 2—restored zone; a zone exposed to ecological restoration processes due to impacts of anthropic activities) related to karstic wetlands in the Mexican–Caribbean. Four feeding characteristics were considered: trophic guild, trophic level, feeding strategy, and prey abundance. Results showed differences and changes in the use of food sources at the trophic level mainly for Floridichthys polyommus, changing from a secondary consumer in the conserved zones to a primary consumer in the restored zones. This suggests that the feeding characteristics of the inhabiting fish are related to the mangrove’s conservation/restoration status and the trophic dynamics in the community. The results of this study are relevant as a tool for mangrove restoration plans regarding the analysis of fish and their food prey, in order to perform an easy and rapid assessment to determine the conservation/restoration status of these aquatic ecosystems from a functional perspective.
A Syndrome of Variable Allergy, Short Stature, and Fatty Liver
Authors: Qiao Jing , Chen Yue , Lu Ying , Wang Tiejun , Li Xiaoli , Qin Wei , Li Aifen , Chen Guangquan
Published: January 2022

SLC22A18 (solute carrier family 22 member 18) is an imprinted gene, but its role in growth and development is not clear. In the present study, we recorded the clinical information of six male patients of six unrelated families. Real-time quantitative PCR, Sanger sequencing, and DNA methylation sequencing were performed in these patients. The results suggested that the patients with the clinical characteristics of allergic allergy, short stature, and fatty liver had a lower expression of SLC22A18. One novel variant (chr11: 2899732 delA) with clinical significance was found in the core promoter region of the patients. Overall, this study found a syndrome associated with SLC22A18.
Analysis of Pathogenic Pseudoexons Reveals Novel Mechanisms Driving Cryptic Splicing
Authors: Keegan Niall P. , Wilton Steve D. , Fletcher Sue
Published: January 2022

Understanding pre-mRNA splicing is crucial to accurately diagnosing and treating genetic diseases. However, mutations that alter splicing can exert highly diverse effects. Of all the known types of splicing mutations, perhaps the rarest and most difficult to predict are those that activate pseudoexons, sometimes also called cryptic exons. Unlike other splicing mutations that either destroy or redirect existing splice events, pseudoexon mutations appear to create entirely new exons within introns. Since exon definition in vertebrates requires coordinated arrangements of numerous RNA motifs, one might expect that pseudoexons would only arise when rearrangements of intronic DNA create novel exons by chance. Surprisingly, although such mutations do occur, a far more common cause of pseudoexons is deep-intronic single nucleotide variants, raising the question of why these latent exon-like tracts near the mutation sites have not already been purged from the genome by the evolutionary advantage of more efficient splicing. Possible answers may lie in deep intronic splicing processes such as recursive splicing or poison exon splicing. Because these processes utilize intronic motifs that benignly engage with the spliceosome, the regions involved may be more susceptible to exonization than other intronic regions would be. We speculated that a comprehensive study of reported pseudoexons might detect alignments with known deep intronic splice sites and could also permit the characterisation of novel pseudoexon categories. In this report, we present and analyse a catalogue of over 400 published pseudoexon splice events. In addition to confirming prior observations of the most common pseudoexon mutation types, the size of this catalogue also enabled us to suggest new categories for some of the rarer types of pseudoexon mutation. By comparing our catalogue against published datasets of non-canonical splice events, we also found that 15.7% of pseudoexons exhibit some splicing activity at one or both of their splice sites in non-mutant cells. Importantly, this included seven examples of experimentally confirmed recursive splice sites, confirming for the first time a long-suspected link between these two splicing phenomena. These findings have the potential to improve the fidelity of genetic diagnostics and reveal new targets for splice-modulating therapies.
Predicting Ischemic Stroke Outcome Using Deep Learning Approaches
Authors: Fang Gang , Huang Zhennan , Wang Zhongrui
Published: January 2022

Predicting functional outcomes after an Ischemic Stroke (IS) is highly valuable for patients and desirable for physicians. This facilitates physicians to set reasonable goals for patients and cooperate with patients and relatives effectively, and furthermore to reach common after-stroke care decisions for recovery and make exercise plans to facilitate rehabilitation. The objective of this research is to apply three current Deep Learning (DL) approaches for 6-month IS outcome predictions, using the openly accessible International Stroke Trial (IST) dataset. Furthermore, another objective of this research is to compare these DL approaches with machine learning (ML) for performing in clinical prediction. After comparing various ML methods (Deep Forest, Random Forest, Support Vector Machine, etc.) with current DL frameworks (CNN, LSTM, Resnet), the results show that DL doesn’t outperform ML significantly. DL methods and reporting used for analyzing structured medical data should be developed and improved.
Plastome Phylogenomics of Aucuba (Garryaceae)
Authors: Huang Yuan , Fan Linyuan , Huang Jian , Zhou Guohua , Chen Xiong , Chen Jiahui
Published: January 2022

Aucuba (Garryaceae), which includes approximately ten evergreen woody species, is a genus endemic to East Asia. Their striking morphological features give Aucuba species remarkable ornamental value. Owing to high levels of morphological divergence and plasticity, species definitions of Aucuba remain perplexing and problematic. Here, we sequenced and characterized the complete plastid genomes (plastomes) of three Aucuba species: Aucuba chlorascens, Aucuba eriobotryifolia, and Aucuba japonica. Incorporating Aucuba plastomes available in GenBank, a total of seven Aucuba plastomes, representing six out of ten species of Aucuba, were used for comparative plastome analysis, phylogenetic analysis and divergence time estimation in this study. Comparative analyses revealed that plastomes of Aucuba are highly conserved in size, structure, gene content, and organization, and exhibit high levels of sequence similarity. Phylogenetic reconstruction based on 68 plastid protein-coding genes strongly supported the monophyly of Garryales, Garryaceae and Aucuba. Aucuba eriobotryifolia was sister to the other Aucuba species examined, consistent with its unique fused anther locule. The divergence time of Aucuba was estimated to be approximately late Miocene. Extant Aucuba species derived from recent divergence events associated with the establishment of monsoonal climates in East Asia and climatic fluctuations.
Is There a Crucial Link Between Vitamin D Status and Inflammatory Response in Patients With COVID-19?
Authors: Saponaro Federica , Franzini Maria , Okoye Chukwuma , Antognoli Rachele , Campi Beatrice , Scalese Marco , Neri Tommaso , Carrozzi Laura , Monzani Fabio , Zucchi Riccardo , Celi Alessandro , Paolicchi Aldo , Saba Alessandro
Published: January 2022

Background

Hypovitaminosis D has been suggested to play a possible role in coronavirus disease 2019 (COVID-19) infection.

Methods

The aim of this study is to analyze the relationship between vitamin D status and a biochemical panel of inflammatory markers in a cohort of patients with COVID-19. A secondary endpoint was to evaluate the correlation between 25OHD levels and the severity of the disease. Ninety-three consecutive patients with COVID-19-related pneumonia were evaluated from March to May 2020 in two hospital units in Pisa, in whom biochemical inflammatory markers, 25OHD levels, P/F ratio at nadir during hospitalization, and complete clinical data were available.

Results

Sixty-five percent of patients presented hypovitaminosis D (25OHD ≤ 20 ng/ml) and showed significantly higher IL-6 [20.8 (10.9–45.6) vs. 12.9 (8.7–21.1) pg/ml, p = 0.02], CRP [10.7 (4.2–19.2) vs. 5.9 (1.6–8.1) mg/dl, p = 0.003], TNF-α [8.9 (6.0–14.8) vs. 4.4 (1.5–10.6) pg/ml, p = 0.01], D-dimer [0.53 (0.25–0.72) vs. 0.22 (0.17–0.35) mg/l, p = 0.002], and IL-10 [3.7 (1.8–6.9) vs. 2.3 (0.5–5.8) pg/ml, p = 0.03]. A significant inverse correlation was found between 25OHD and all these markers, even adjusted for age and sex. Hypovitaminosis D was prevalent in patients with severe ARDS, compared with the other groups (75% vs. 68% vs. 55%, p < 0.001), and 25OHD levels were lower in non-survivor patients.

Conclusions

The relationship between 25OHD levels and inflammatory markers suggests that vitamin D status needs to be taken into account in the management of these patients. If vitamin D is a marker of poor prognosis or a possible risk factor with beneficial effects from supplementation, this still needs to be elucidated.
The PDE4 Inhibitor Tanimilast Blunts Proinflammatory Dendritic Cell Activation by SARS-CoV-2 ssRNAs
Authors: Nguyen Hoang Oanh , Schioppa Tiziana , Tiberio Laura , Facchinetti Fabrizio , Villetti Gino , Civelli Maurizio , Del Prete Annalisa , Sozio Francesca , Gaudenzi Carolina , Passari Mauro , Barbazza Ilaria , Sozzani Silvano , Salvi Valentina , Bosisio Daniela
Published: January 2022

Phosphodiesterase 4 (PDE4) inhibitors are immunomodulatory drugs approved to treat diseases associated with chronic inflammatory conditions, such as COPD, psoriasis and atopic dermatitis. Tanimilast (international non-proprietary name of CHF6001) is a novel, potent and selective inhaled PDE4 inhibitor in advanced clinical development for the treatment of COPD. To begin testing its potential in limiting hyperinflammation and immune dysregulation associated to SARS-CoV-2 infection, we took advantage of anin vitromodel of dendritic cell (DC) activation by SARS-CoV-2 genomic ssRNA (SCV2-RNA). In this context, Tanimilast decreased the release of pro-inflammatory cytokines (TNF-α and IL-6), chemokines (CCL3, CXCL9, and CXCL10) and of Th1-polarizing cytokines (IL-12, type I IFNs). In contrast to β-methasone, a reference steroid anti-inflammatory drug, Tanimilast did not impair the acquisition of the maturation markers CD83, CD86 and MHC-II, nor that of the lymph node homing receptor CCR7. Consistent with this, Tanimilast did not reduce the capability of SCV2-RNA-stimulated DCs to activate CD4+T cells but skewed their polarization towards a Th2 phenotype. Both Tanimilast and β-methasone blocked the increase of MHC-I molecules in SCV2-RNA-activated DCs and restrained the proliferation and activation of cytotoxic CD8+T cells. Our results indicate that Tanimilast can modulate the SCV2-RNA-induced pro-inflammatory and Th1-polarizing potential of DCs, crucial regulators of both the inflammatory and immune response. Given also the remarkable safety demonstrated by Tanimilast, up to now, in clinical studies, we propose this inhaled PDE4 inhibitor as a promising immunomodulatory drug in the scenario of COVID-19.
Sarcodia suiae Water Extract Promotes the Expression of Proinflammatory and Th1-Type Cytokines and Delay the Onset of Mortality in Cobia (Rachycentron canadum) During Photobacterium damselae subsp. damselae Infection
Authors: Lee Po-Tsang , Nan Fan-Hua , Chiu Po-Yu , Tseng Chung-Chih , Lee Meng-Chou
Published: January 2022

Cobia (Rachycentron canadum) is a marine fish of high economic value that grows at a fast rate. However, intensive fish farming has led to disease outbreaks in cobia cultures, which is highly costly to the industry. The impact of infectious diseases on cobia production has led to the inappropriate and increased use of chemicals and antibiotics, which negatively affects the environment and human health and promotes the spread of drug-resistant pathogens. Hence, prophylactic measurements, such as the use of immunomodulators, are required to improve the health of cultured animals against pathogens. In this study, we examined the effects ofSarcodia suiaewater extract (SSWE) in cobiain vitroandin vivo. We found that treatment with SSWE could significantly increase the expression of cytokines (e.g.,IL-1β,IL-6,IL-10,IL-12, andTNF-α) and chemokines (e.g.,IL-8) in primary cultured head kidney leukocytes. Intraperitoneal injection of SSWE (20 μg/g body weight) promoted higher expression ofIL-6,IL-8,IL-10,IL-12, chemokines (e.g.,CC1), and antibodies (e.g.,IgT) in head kidney and spleen tissues of the fish compared with other dose levels. Additionally, we describe for the second time (only after India) of the isolation ofPhotobacterium damselaesubsp.damselae(Phdd) from a deadly epizootic in cage-farmed cobia. An intraperitoneal inoculation of SSWE beforePhddchallenge showed that SSWE treatment could delay the onset of mortality of cobia. Finally, fish that received SSWE intraperitoneally before infection withPhddexhibited elevated expression of Th1-type cytokines, namely,IL-8,IL-12,TNF-α, andIFN-γ. At the same time, the expression of Th2-related factors (such asIL-10in the head kidney, andIgMandIgTin the spleen) were lower for the fish that received SSWE instead of PBS before thePhddchallenge. The results indicate that SSWE treatment facilitates the induction of Th1-type cytokines in cobia to fight againstPhddinfection and has the potential to be used as an immunostimulant and vaccine adjuvant for fish.
Regulating Histone Deacetylase Signaling Pathways of Myeloid-Derived Suppressor Cells Enhanced T Cell-Based Immunotherapy
Authors: Adeshakin Adeleye O. , Adeshakin Funmilayo O. , Yan Dehong , Wan Xiaochun
Published: January 2022

Immunotherapy has emerged as a promising approach to combat immunosuppressive tumor microenvironment (TME) for improved cancer treatment. FDA approval for the clinical use of programmed death receptor 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors revolutionized T cell-based immunotherapy. Although only a few cancer patients respond to this treatment due to several factors including the accumulation of immunosuppressive cells in the TME. Several immunosuppressive cells within the TME such as regulatory T cells, myeloid cells, and cancer-associated fibroblast inhibit the activation and function of T cells to promote tumor progression. The roles of epigenetic modifiers such as histone deacetylase (HDAC) in cancer have long been investigated but little is known about their impact on immune cells. Recent studies showed inhibiting HDAC expression on myeloid-derived suppressor cells (MDSCs) promoted their differentiation to less suppressive cells and reduced their immunosuppressive effect in the TME. HDAC inhibitors upregulated PD-1 or PD-L1 expression level on tumor or immune cells sensitizing tumor-bearing mice to anti-PD-1/PD-L1 antibodies. Herein we discuss how inhibiting HDAC expression on MDSCs could circumvent drawbacks to immune checkpoint inhibitors and improve cancer immunotherapy. Furthermore, we highlighted current challenges and future perspectives of HDAC inhibitors in regulating MDSCs function for effective cancer immunotherapy.
A New Trend in Cancer Treatment: The Combination of Epigenetics and Immunotherapy
Authors: Liu Zaoqu , Ren Yuqing , Weng Siyuan , Xu Hui , Li Lifeng , Han Xinwei
Published: January 2022

In recent years, immunotherapy has become a hot spot in the treatment of tumors. As an emerging treatment, it solves many problems in traditional cancer treatment and has now become the main method for cancer treatment. Although immunotherapy is promising, most patients do not respond to treatment or develop resistance. Therefore, in order to achieve a better therapeutic effect, combination therapy has emerged. The combination of immune checkpoint inhibition and epigenetic therapy is one such strategy. In this review, we summarize the current understanding of the key mechanisms of how epigenetic mechanisms affect cancer immune responses and reveal the key role of epigenetic processes in regulating immune cell function and mediating anti-tumor immunity. In addition, we highlight the outlook of combined epigenetic and immune regimens, particularly the combination of immune checkpoint blockade with epigenetic agents, to address the limitations of immunotherapy alone.
B-Cell Dysregulation in Idiopathic Nephrotic Syndrome: What We Know and What We Need to Discover
Authors: Colucci Manuela , Oniszczuk Julie , Vivarelli Marina , Audard Vincent
Published: January 2022

The therapeutic efficacy of B-cell depletion by anti-CD20 treatment in pediatric and, more recently, in adult idiopathic nephrotic syndrome patients suggests a key role of B cells in the pathogenesis of the disease. However, their exact role is still unclear. B cells are able to secrete a large variety of antibodies that can protect against infections. However, B-cell dysregulation is well-established in a variety of autoimmune diseases. In parallel with their ability to produce antibodies, pathogenic B cells display altered effector functions by expressing activating surface molecules, which can strongly modify the immune homeostasis, or by producing specific cytokines, which can directly affect either podocyte structure and functions or modulate T-cell homeostasis. Herein, we report the most relevant clinical and experimental evidences of a pathogenic role of B cells in idiopathic nephrotic syndrome. We further highlight similarities and differences between children and adults affected by non-genetic forms of the disease and discuss what needs to be investigated in order to define the exact mechanisms underlying the pathogenic role of B cells and to identify more tailored therapeutic approaches.
Epigenetic Modifications in Tumor-Associated Macrophages: A New Perspective for an Old Foe
Authors: Niu Yuqin , Chen Jianxiang , Qiao Yiting
Published: January 2022

Tumorigenesis is frequently accompanied by chronic inflammation, and the tumor microenvironment (TME) can be considered an ecosystem that consists of tumor cells, endotheliocytes, fibroblasts, immune cells and acellular components such as extracellular matrix. For tumor cells, their survival advantages are dependent on both genetic and epigenetic alterations, while other cells mainly present epigenetic modifications. Macrophages are the most plastic type of immune cells and undergo diverse epigenetic alterations in the TME. Some of these epigenetic modifications mitigate against cancer progression, and others accelerate this process. Due to the complex roles of macrophages in the TME, it is urgent to understand their epigenetic modifications associated with the TME. Here, we mainly summarize recent findings on TME-associated epigenetic alterations of tumor-associated macrophages (TAMs), including DNA methylation, posttranslational modifications of histone proteins, chromatin remodeling, and noncoding RNA-mediated epigenetic regulation. At the end of this review, we also discuss the translational potential of these epigenetic modifications for developing novel cancer therapies targeting TAMs.
The Influence of the River Discharge on Residence Time, Exposure Time and Integrated Water Fractions for the Tagus Estuary (Portugal)
Authors: de Pablo Hilda , Sobrinho João , Garaboa-Paz Daniel , Fonteles Caio , Neves Ramiro , Gaspar Miguel B.
Published: January 2022

Understanding how long water is retained in an estuary and how quickly it is completely flushed is essential to estimate an estuary’s health in areas with significant pollutant loadings. The present study analyses the effect of five different Tagus River discharge scenarios ranging from low to extreme on residence time (RT), exposure time (ET) and integrated water fractions inside pre-established Tagus estuary areas, to identify its most vulnerable areas to pollution. The 3D version of the MOHID hydrodynamic model coupled to a lagrangian tool was used. The increase of the river discharge generated high current velocities which, in turn, led to an increased rate of tracers leaving the estuary. As a consequence, RT and ET decreased from 59 to 3.5 days under a low and extreme river discharge scenario, respectively. Under a low river discharge, significant differences were observed between RT and ET in the areas located in the main body of the estuary and in the bays. As river discharge increased, RT and ET decreased in all areas of the estuary and those differences faded, with the greatest differences observed in the areas situated along the south margin. In general, results showed that with high river discharges the tracers released in the upper estuary are spread throughout the estuary, but mainly in downstream areas. However, when the river discharge reached exceptionally high values, local eddies were formed, leading to the retention of the tracers in the estuary’s south margin and inner bays. The results in this study allowed to identify the most vulnerable areas within the estuary as a function of the river discharge.
Beach Wrack Dynamics Using a Camera Trap as the Real-Time Monitoring Tool
Authors: Pan Yaoru , Ayoub Naeem , Schneider-Kamp Peter , Flindt Mogens , Holmer Marianne
Published: January 2022

As part of Blue Carbon ecosystems (BCEs), detached macrophytes can be transported to the coast due to current and wave actions, and then deposited on the shore as beach wrack. To date, the role of beach wrack in the material cycle in BCEs is still unclear. In order to track the fate of beach wrack, this study conducted a monitoring survey on a semi-sheltered beach in Odense Fjord (Denmark) using camera trap data. Deep learning with a VGG network architecture was used to classify the image dataset acquired by the camera trap. The VGG network demonstrated the capability to identify beach wrack from different beach scenes, and the method can provide results on large datasets within a short time (187 images analyzed within 5 min) compared to manual identification of images. By combining the VGG detection with color-based segmentation, beach wrack coverage was determined. To evaluate the impact of ambient conditions on wrack deposition on the shore and relocation back to the sea, wind (including speed and direction), water temperature, and tidal amplitude were analyzed as environmental variables. Partial least squares regression (PLSR) analysis revealed that micro-tidal action with an average amplitude of 0.41 m accelerated the movement of floating macrophytes between the shore and the sea. Despite being exposed to the prevailing southwesterly winds (average speed of 11 m/s), the beach was sheltered due to the location in the inner part of Odense Fjord, limiting the transport of drifting macrophytes from sea to the shore. By using the camera trap to conduct continuous monitoring, this study presents a labor-saving and practical approach to track the dynamics of detached macrophytes deposited on the shore. Furthermore, the application of deep learning in image identification provides a study case for using a large image dataset to assist in ecological studies of dynamic environments.
Crowned Dens Syndrome: A Case Report and Literature Review
Authors: Huang Pan , Xu Min , He Xiao-Ying
Published: January 2022

Crowned Dens Syndrome (CDS) is the leading cause of acute neck pain and a major cause of reduced neck mobility. The diagnosis of CDS is challenging as clinicians currently have limited awareness of the symptoms of the disease. In this article, we report a case of odontoid syndrome as a reference for the diagnosis and treatment of CDS.
Clinical and Echographic Features of Morning Glory Disc Anomaly in Children: A Retrospective Study of 249 Chinese Patients
Authors: Zou Yihua , She Kaiqin , Hu Yiqian , Ren Jianing , Fei Ping , Xu Yu , Peng Jie , Zhao Peiquan
Published: January 2022

Purpose

To report the clinical and echographic features, the prevalence of retinal detachment (RD), and associated visual acuity in a cohort of pediatric patients with morning glory disc anomaly (MGDA).

Methods

This was a retrospective review of 249 pediatric patients with MGDA (271 eyes) seen at the Dept. of Ophthalmology, Xinhua Hospital. Their medical records were reviewed for demographic data and ocular and systemic findings. The maximal depth and width of the cavity were measured using standardized echographic images. The ratios of cavitary depth to axial length, cavitary depth to maximal cavitary width, and the product of cavitary depth and width were calculated and used to indicate the relative size of the excavation. The clinical and echographic findings were correlated with visual acuity and the occurrence of RD of the patient.

Results

The relative size of the excavation and the presence of RD were positively associated with increased risk of poor vision (p < 0.05). The presence of persistent fetal vasculature was not associated with the risk of RD and poor vision. The ratio of cavitary depth to axial length more than or equal to 0.25 conferred an increased risk of RD (OR, 2.101; 95% CI, 1.469–3.003).

Conclusions

Clinical and echographic features of MGDA may be used in predicting the risk of RD. Measuring the relative size of excavation via echography may guide the follow-ups and assist in the early diagnosis of RD.
Sex Differences in Kidney Transplantation: Austria and the United States, 1978–2018
Authors: Hödlmoser Sebastian , Gehrig Teresa , Antlanger Marlies , Kurnikowski Amelie , Lewandowski Michał , Krenn Simon , Zee Jarcy , Pecoits-Filho Roberto , Kramar Reinhard , Carrero Juan Jesus , Jager Kitty J. , Tong Allison , Port Friedrich K. , Posch Martin , Winkelmayer Wolfgang C. , Schernhammer Eva , Hecking Manfred , Ristl Robin
Published: January 2022

Background

Systematic analyses about sex differences in wait-listing and kidney transplantation after dialysis initiation are scarce. We aimed at identifying sex-specific disparities along the path of kidney disease treatment, comparing two countries with distinctive health care systems, the US and Austria, over time.

Methods

We analyzed subjects who initiated dialysis from 1979–2018, in observational cohort studies from the US and Austria. We used Cox regression to model male-to-female cause-specific hazard ratios (csHRs, 95% confidence intervals) for transitions along the consecutive states dialysis initiation, wait-listing, kidney transplantation and death, adjusted for age and stratified by country and decade of dialysis initiation.

Results

Among 3,053,206 US and 36,608 Austrian patients starting dialysis, men had higher chances to enter the wait-list, which however decreased over time [male-to-female csHRs for wait-listing, 1978–1987: US 1.94 (1.71, 2.20), AUT 1.61 (1.20, 2.17); 2008–2018: US 1.35 (1.32, 1.38), AUT 1.11 (0.94, 1.32)]. Once wait-listed, the advantage of the men became smaller, but persisted in the US [male-to-female csHR for transplantation after wait-listing, 2008–2018: 1.08 (1.05, 1.11)]. The greatest disparity between men and women occurred in older age groups in both countries [male-to-female csHR for wait-listing after dialysis, adjusted to 75% age quantile, 2008–2018: US 1.83 (1.74, 1.92), AUT 1.48 (1.02, 2.13)]. Male-to-female csHRs for death were close to one, but higher after transplantation than after dialysis.

Conclusions

We found evidence for sex disparities in both countries. Historically, men in the US and Austria had 90%, respectively, 60% higher chances of being wait-listed for kidney transplantation, although these gaps decreased over time. Efforts should be continued to render kidney transplantation equally accessible for both sexes, especially for older women.
Therapeutic Approaches for Treating Pulmonary Arterial Hypertension by Correcting Imbalanced TGF-β Superfamily Signaling
Authors: Andre Patrick , Joshi Sachindra R. , Briscoe Steven D. , Alexander Mark J. , Li Gang , Kumar Ravindra
Published: January 2022

Pulmonary arterial hypertension (PAH) is a rare disease characterized by high blood pressure in the pulmonary circulation driven by pathological remodeling of distal pulmonary arteries, leading typically to death by right ventricular failure. Available treatments improve physical activity and slow disease progression, but they act primarily as vasodilators and have limited effects on the biological cause of the disease—the uncontrolled proliferation of vascular endothelial and smooth muscle cells. Imbalanced signaling by the transforming growth factor-β (TGF-β) superfamily contributes extensively to dysregulated vascular cell proliferation in PAH, with overactive pro-proliferative SMAD2/3 signaling occurring alongside deficient anti-proliferative SMAD1/5/8 signaling. We review the TGF-β superfamily mechanisms underlying PAH pathogenesis, superfamily interactions with inflammation and mechanobiological forces, and therapeutic strategies under development that aim to restore SMAD signaling balance in the diseased pulmonary arterial vessels. These strategies could potentially reverse pulmonary arterial remodeling in PAH by targeting causative mechanisms and therefore hold significant promise for the PAH patient population.
Deciphering Cadmium (Cd) Tolerance in Newly Isolated Bacterial Strain, Ochrobactrum intermedium BB12, and Its Role in Alleviation of Cd Stress in Spinach Plant (Spinacia oleracea L.)
Authors: Renu S. , Sarim Khan Mohd. , Singh Dhananjaya Pratap , Sahu Upasana , Bhoyar Manish S. , Sahu Asha , Kaur Baljeet , Gupta Amrita , Mandal Asit , Thakur Jyoti Kumar , Manna Madhab C. , Saxena Anil Kumar
Published: January 2022

A cadmium (Cd)–tolerant bacterium Ochrobactrum intermedium BB12 was isolated from sewage waste collected from the municipal sewage dumping site of Bhopal, India. The bacterium showed multiple heavy metal tolerance ability and had the highest minimum inhibitory concentration of 150 mg L–1 of Cd. Growth kinetics, biosorption, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy studies on BB12 in the presence of Cd suggested biosorption as primary mode of interaction. SEM and TEM studies revealed surface deposition of Cd. FTIR spectra indicated nitrogen atom in exopolysaccharides secreted by BB12 to be the main site for Cd attachment. The potential of BB12 to alleviate the impact of Cd toxicity in spinach plants (Spinacia oleracea L.) var. F1-MULAYAM grown in the soil containing Cd at 25, 50, and 75 mg kg–1 was evaluated. Without bacterial inoculation, plants showed delayed germination, decrease in the chlorophyll content, and stunted growth at 50 and 75 mg kg–1 Cd content. Bacterial inoculation, however, resulted in the early germination, increased chlorophyll, and increase in shoot (28.33%) and root fresh weight (72.60%) at 50 mg kg–1 of Cd concentration after 75 days of sowing. Due to bacterial inoculation, elevated proline accumulation and lowered down superoxide dismutase (SOD) enzyme activity was observed in the Cd-stressed plants. The isolate BB12 was capable of alleviating Cd from the soil by biosorption as evident from significant reduction in the uptake/translocation and bioaccumulation of Cd in bacteria itself and in the plant parts of treated spinach. Potential PGP prospects and heavy metal bioremediation capability of BB12 can make the environmental application of the organism a promising approach to reduce Cd toxicity in the crops grown in metal-contaminated soils.
Identification and Action Patterns of Two Chondroitin Sulfate Sulfatases From a Marine Bacterium Photobacterium sp. QA16
Authors: Wei Lin , Zhang Qingdong , Lu Danrong , Du Min , Xu Xiangyu , Wang Wenshuang , Zhang Yu-Zhong , Yuan Xunyi , Li Fuchuan
Published: January 2022

Chondroitin sulfate (CS)/dermatan sulfate (DS) is a kind of sulfated polyanionic, linear polysaccharide belonging to glycosaminoglycan. CS/DS sulfatases, which specifically hydrolyze sulfate groups from CS/DS oligo-/polysaccharides, are potential tools for structural and functional studies of CD/DS. However, only a few sulfatases have been reported and characterized in detail to date. In this study, two CS/DS sulfatases, PB_3262 and PB_3285, were identified from the marine bacterium Photobacterium sp. QA16 and their action patterns were studied in detail. PB_3262 was characterized as a novel 4-O-endosulfatase that can effectively and specifically hydrolyze the 4-O-sulfate group of disaccharide GlcUAβ1–3GalNAc(4-O-sulfate) but not GlcUAβ1–3GalNAc(4,6-O-sulfate) and IdoUAα1–3GalNAc(4-O-sulfate) in CS/DS oligo-/polysaccharides, which is very different from the identified 4-O-endosulfatases in the substrate profile. In contrast, PB_3285 specifically hydrolyzes the 6-O-sulfate groups of GalNAc(6-O-sulfate) residues located at the reducing ends of the CS chains and is the first recombinantly expressed 6-O-exosulfatase to effectively act on CS oligosaccharides.
In vivo Assessment of Cold Atmospheric Pressure Plasma Technology on the Bioactivity of Spirulina
Authors: Pina-Pérez María Consuelo , Úbeda-Manzanaro María , Beyrer Michael , Martínez Antonio , Rodrigo Dolores
Published: January 2022

The present study challenges the in vivo assessment of cold atmospheric pressure plasma (CAPP) technology on the bioactive activity (antioxidant/antiaging and antimicrobial potential) of Spirulina powder, using Caenorhabditis elegans as an animal model. Surface microdischarge cold atmospheric pressure plasma (SMD-CAPP) treatment was 3.3 W discharge power for 7 min. C. elegans lifespan and egg laying were used as indicators of antioxidant/antiaging potential of Spirulina (1 mg/mL), when grown with Spirulina CP-treated [E_SCP] and untreated [E_S], compared with a control [E_0] (non-supplemented with Spirulina). According to our results, under both Spirulina supplemented media [E_SCP and E_S] and for the first 17 days, nematodes experienced an increase in lifespan but without significant differences (p > 0.05) between control and Spirulina CP-treated. Regarding the in vivo assay of the antimicrobial potential of Spirulina against Salmonella enterica serovar Typhimurium (infected worms), no significant differences (p > 0.05) were found between the three exposure scenarios (control [S_0]; Spirulina supplemented media [S_S]; CP-treated Spirulina supplemented media [S_SCP]). According to present results, CAPP-treatment do not influence negatively the lifespan of C. elegans but a reduction in the Spirulina antiaging potential was found. No in vivo modifications in antimicrobial activity seem to be linked to CAPP-processed Spirulina.
Repurposing Eltrombopag as an Antimicrobial Agent Against Methicillin-Resistant Staphylococcus aureus
Authors: She Pengfei , Li Shijia , Zhou Linying , Liu Yaqian , Xu Lanlan , Hussain Zubair , Li Yimin , Li Zehao , Liu Shasha , Wu Yong
Published: January 2022

Because of the excessive use of antibiotics, methicillin-resistant Staphylococcus aureus (MRSA) has become prevalent worldwide. Moreover, the formation of S. aureus biofilms often cause persistence and relapse of infections. Thus, the discovery of antibiotics with excellent antimicrobial and anti-biofilm activities is urgently needed. In the present study, eltrombopag (EP), a classic thrombopoietin receptor agonist, exhibited potential antimicrobial activity against S. aureus and its biofilms. Through our mechanistic studies, EP was found to interfere with proton motive force in S. aureus. The in vivo anti-infective efficacy of EP was further confirmed in the wound infection model, thigh infection model and peritonitis model by MRSA infection. In addition, the cytotoxicity of EP against mammalian cells and the in vivo toxicity of EP in animal models were not observed at the tested concentrations. Collectively, these results indicate that EP could be considered a potential novel antimicrobial agent against recalcitrant infections caused by MRSA.
Relative and Quantitative Rhizosphere Microbiome Profiling Results in Distinct Abundance Patterns
Authors: Azarbad Hamed , Tremblay Julien , Bainard Luke D. , Yergeau Etienne
Published: January 2022

Next-generation sequencing is one of the most popular and cost-effective ways of characterizing microbiome in multiple samples. However, most of the currently available amplicon sequencing approaches are limited, as they result in relative abundance profiles of microbial taxa, which does not represent actual abundance in the environment. Here, we combined amplicon sequencing (16S rRNA gene for bacteria and ITS region for fungi) with real-time quantitative PCR (qPCR) to characterize the rhizosphere microbiome of wheat. We show that changes in the relative abundance of major microbial phyla do not necessarily follow the same pattern as the estimated quantitative abundance. Most of the bacterial phyla linked with the rhizosphere of plants grown in soil with no history of water stress showed enrichment patterns in their estimated absolute abundance, which was in contradiction with the trends observed in the relative abundance data. However, in the case of the fungal groups (except for Basidiomycota), such an enrichment pattern was not observed and the abundance of fungi remained relatively unchanged under different soil water stress history when estimated absolute abundance was considered. Comparing relative and estimated absolute abundances of dominant bacterial and fungal phyla, as well as their correlation with the functional processes in the rhizosphere, our results suggest that the estimated absolute abundance approach gives a different and more realistic perspective than the relative abundance approach. Such a quantification approach provides complementary information that helps to better understand the rhizosphere microbiomes and their associated ecological functional processes.
The Epidemiology of Meningococcal Disease and Carriage, Genotypic Characteristics and Antibiotic Resistance of Neisseria meningitidis Isolates in Zhejiang Province, China, 2011–2021
Authors: Zhang Yunyi , Deng Xuan , Jiang Yan , Zhang Junyan , Zhan Li , Mei Lingling , Lu Hangjing , Yao Pingping , He Hanqing
Published: January 2022

Neisseria meningitidis (Nm) remains a worldwide leading cause of epidemic meningitis. During 2011–July 2021, 55 meningococcal disease (MD) cases were reported with a case fatality rate of 5.45% in Zhejiang Province, China. The median age was 7 years. The annual incidence was 0.0017–0.0183 per 100,000 population. The highest age-specific incidence was observed in the group younger than 1 year. Serogroup was identified in 30 laboratory-confirmed MD cases, and MenB was most predominant. MenB was mainly observed in two age groups: younger than 5 and older than 35 years. MenB incidence was significantly increasing from 0.0018 per 100,000 in 2013 to 0.0070 per 100,000 in 2019. During 2015–2020, 17 positive samples were detected from 2,827 throat swabs from healthy population, of which 70.59% was MenB. Twenty multilocus sequence typing sequence types (STs) containing eight newly assigned STs (ST15881–ST15888) were determined in all Nm isolates. Either in MD cases or in healthy population, MenB CC ST-4821 was the predominant ST. It was worth noting that two MenY CC ST-23 cases occurred in 2019 and 2021, respectively. MenY CC ST-23 MD cases increased gradually in China. Phylogeny results based on genome sequencing indicated that Chinese MenW CC ST-11 isolates were genetically linked and grouped together with Japanese isolates, separated from MenW CC ST-11 isolates from Saudi Arabia Hajj outbreak, Europe, South Africa, South America, North America, and Oceania. MenW CC ST-11 isolates from East Asia might have evolved locally. Antibiotic susceptibility tests revealed a relatively high resistance rate (22.86%) of Nm isolates to penicillin. This study provided valuable data for Chinese public health authorities to grasp the temporal epidemiological characteristics of MD and healthy carriage.
Towards Elucidating Structure–Spectra Relationships in Rhamnogalacturonan II: Computational Protocols for Accurate 13C and 1H Shifts for Apiose and Its Borate Esters
Authors: Bharadwaj Vivek S. , Westawker Luke P. , Crowley Michael F.
Published: January 2022

Apiose is a naturally occurring, uncommon branched-chain pentose found in plant cell walls as part of the complex polysaccharide Rhamnogalacturonan II (RG-II). The structural elucidation of the three-dimensional structure of RG-II by nuclear magnetic resonance (NMR) spectroscopy is significantly complicated by the ability of apiose to cross-linkviaborate ester linkages to form RG-II dimers. Here, we developed a computational approach to gain insight into the structure–spectra relationships of apio–borate complexes in an effort to complement experimental assignments of NMR signals in RG-II. Our protocol involved structure optimizations using density functional theory (DFT) followed by isotropic magnetic shielding constant calculations using the gauge-invariant atomic orbital (GIAO) approach to predict chemical shifts. We evaluated the accuracy of 23 different functional–basis set (FBS) combinations with and without implicit solvation for predicting the experimental1H and13C shifts of a methyl apioside and its three borate derivatives. The computed NMR predictions were evaluated on the basis of the overall shift accuracy, relative shift ordering, and the ability to distinguish between dimers and monomers. We demonstrate that the consideration of implicit solvation during geometry optimizations in addition to the magnetic shielding constant calculations greatly increases the accuracy of NMR chemical shift predictions and can correctly reproduce the ordering of the13C shifts and yield predictions that are, on average, within 1.50 ppm for13C and 0.12 ppm for1H shifts for apio–borate compounds.
Immune Response on Optimal Timing and Fractionation Dose for Hypofractionated Radiotherapy in Non–Small-Cell Lung Cancer
Authors: Zhao Xianlan , Li Jixi , Zheng Linpeng , Yang Qiao , Chen Xu , Chen Xiewan , Yu Yongxin , Li Feng , Cui Jianxiong , Sun Jianguo
Published: January 2022

Background: The intervention timing of immune checkpoint inhibitors (ICIs) and radiotherapy fractionations are critical factors in clinical efficacy. This study aims to explore dynamic changes of the tumor immune microenvironment (TIME) after hypofractionated radiotherapy (HFRT) at different timepoints and fractionation doses in non–small-cell lung cancer (NSCLC).

Methods: In the implanted mouse model, the experimental groups received HFRT 3.7 Gy × 4 F, 4.6 Gy × 3 F, 6.2 Gy × 2 F, and 10 Gy × 1 F, respectively, with the same biological equivalent dose (BED) of 20Gy. Tumor volume and survival time were compared with those of the control group. Flow cytometry was performed to detect immune cells and their PD-1/PD-L1 expressions using tail-tip blood at different timepoints and tumor tissues at 48 h after radiotherapy. In NSCLC patients, immune cells, PD-1/PD-L1, and cytokines were detected in peripheral blood for 4 consecutive days after different fractionation radiotherapy with the same BED of 40Gy.

Results: Tumor volumes were significantly reduced in all experimental groups compared with the control group, and the survival time in 6.2 Gy × 2 F (p < 0.05) was significantly prolonged. In tail-tip blood of mice, CD8+ T counts increased from 48 h to 3 weeks in 4.6 Gy × 3 F and 6.2 Gy × 2 F, and CD8+ PD-1 shortly increased from 48 h to 2 weeks in 6.2 Gy × 2 F and 10 Gy × 1 F (p < 0.05). Dentritic cells (DCs) were recruited from 2 to 3 weeks (p < 0.01). As for NSCLC patients, CD8+ T counts and PD-1 expression increased from 24 h in 6.2 Gy × 4 F, and CD8+ T counts increased at 96 h in 10 Gy × 2 F (p < 0.05) in peripheral blood. DC cells were tentatively recruited at 48 h and enhanced PD-L1 expression from 24 h in both 6.2 Gy × 4 F and 10 Gy × 2 F (p < 0.05). Besides, serum IL-10 increased from 24 h in 6.2 Gy × 4 F (p < 0.05). Conversely, serum IL-4 decreased at 24 and 96 h in 10 Gy × 2 F (p < 0.05).

Conclusion: HFRT induces the increase in CD8+ T cells and positive immune cytokine response in specific periods and fractionation doses. It was the optimal time window from 48 h to 2 weeks for the immune response, especially in 6.2 Gy fractionation. The best immune response was 96 h later in 10 Gy fractionation, delivering twice instead of a single dose. During this time window, the intervention of immunotherapy may achieve a better effect.