bluuebunny/crossref_metadata_2025 huggingface dataset:
PCGIMA: developing the web server for human position-defined CpG islands methylation analysis
Authors: Xiao Ming , Xiao Yi , Yu Jun , Zhang Le
Published: March 2024

Introduction: CpG island (CGI) methylation is one of the key epigenomic mechanisms for gene expression regulation and chromosomal integrity. However, classical CGI prediction methods are neither easy to locate those short and position-sensitive CGIs (CpG islets), nor investigate genetic and expression pattern for CGIs under different CpG position- and interval- sensitive parameters in a genome-wide perspective. Therefore, it is urgent for us to develop such a bioinformatic algorithm that not only can locate CpG islets, but also provide CGI methylation site annotation and functional analysis to investigate the regulatory mechanisms for CGI methylation.

Methods: This study develops Human position-defined CGI prediction method to locate CpG islets using high performance computing, and then builds up a novel human genome annotation and analysis method to investigate the connections among CGI, gene expression and methylation. Finally, we integrate these functions into PCGIMA to provide relevant online computing and visualization service.

Results: The main results include: (1) Human position-defined CGI prediction method is more efficient to predict position-defined CGIs with multiple consecutive (d) values and locate more potential short CGIs than previous CGI prediction methods. (2) Our annotation and analysis method not only can investigate the connections between position-defined CGI methylation and gene expression specificity from a genome-wide perspective, but also can analysis the potential association of position-defined CGIs with gene functions. (3) PCGIMA (http://www.combio-lezhang.online/pcgima/home.html) provides an easy-to-use analysis and visualization platform for human CGI prediction and methylation.

Discussion: This study not only develops Human position-defined CGI prediction method to locate short and position-sensitive CGIs (CpG islets) using high performance computing to construct MR-CpGCluster algorithm, but also a novel human genome annotation and analysis method to investigate the connections among CGI, gene expression and methylation. Finally, we integrate them into PCGIMA for online computing and visualization.
C1q and HBHA-specific IL-13 levels as surrogate plasma biomarkers for monitoring tuberculosis treatment efficacy: a cross-sectional cohort study in Paraguay
Authors: Russomando Graciela , Sanabria Diana , Díaz Acosta Chyntia Carolina , Rojas Leticia , Franco Laura , Arenas Rossana , Delogu Giovanni , Ndiaye Mame Diarra Bousso , Bayaa Rim , Rakotosamimanana Niaina , Goletti Delia , Hoffmann Jonathan
Published: March 2024

Introduction

New diagnostic tools are needed to rapidly assess the efficacy of pulmonary tuberculosis (PTB) treatment. The aim of this study was to evaluate several immune biomarkers in an observational and cross-sectional cohort study conducted in Paraguay.

Methods

Thirty-two patients with clinically and microbiologically confirmed PTB were evaluated before starting treatment (T0), after 2 months of treatment (T1) and at the end of treatment (T2). At each timepoint plasma levels of IFN-y, 17 pro- and anti-inflammatory cytokines/chemokines and complement factors C1q, C3 and C4 were assessed in unstimulated and Mtb-specific stimulated whole blood samples using QuantiFERON-TB gold plus and recombinant Mycobacterium smegmatis heparin binding hemagglutinin (rmsHBHA) as stimulation antigen. Complete blood counts and liver enzyme assays were also evaluated and correlated with biomarker levels in plasma.

Results

In unstimulated plasma, C1q (P<0.001), C4 (P<0.001), hemoglobin (P<0.001), lymphocyte proportion (P<0.001) and absolute white blood cell count (P=0.01) were significantly higher in PTB patients at baseline than in cured patients. C1q and C4 levels were found to be related to Mycobacterium tuberculosis load in sputum. Finally, a combinatorial analysis identified a plasma host signature comprising the detection of C1q and IL-13 levels in response to rmsHBHA as a tool differentiating PTB patients from cured TB profiles, with an AUC of 0.92 (sensitivity 94% and specificity 79%).

Conclusion

This observational study provides new insights on host immune responses throughout anti-TB treatment and emphasizes the role of host C1q and HBHA-specific IL-13 response as surrogate plasma biomarkers for monitoring TB treatment efficacy.
Mechanisms of inflammation modulation by different immune cells in hypertensive nephropathy
Authors: Hao Xiao-min , Liu Yu , Hailaiti Dilizhawaer , Gong Yu , Zhang Xu-dong , Yue Bing-nan , Liu Ji-peng , Wu Xiao-li , Yang Ke-zhen , Wang Jun , Liu Qing-guo
Published: March 2024

Hypertensive nephropathy (HTN) is the second leading cause of end-stage renal disease (ESRD) and a chronic inflammatory disease. Persistent hypertension leads to lesions of intrarenal arterioles and arterioles, luminal stenosis, secondary ischemic renal parenchymal damage, and glomerulosclerosis, tubular atrophy, and interstitial fibrosis. Studying the pathogenesis of hypertensive nephropathy is a prerequisite for diagnosis and treatment. The main cause of HTN is poor long-term blood pressure control, but kidney damage is often accompanied by the occurrence of immune inflammation. Some studies have found that the activation of innate immunity, inflammation and acquired immunity is closely related to the pathogenesis of HTN, which can cause damage and dysfunction of target organs. There are more articles on the mechanism of diabetic nephropathy, while there are fewer studies related to immunity in hypertensive nephropathy. This article reviews the mechanisms by which several different immune cells and inflammatory cytokines regulate blood pressure and renal damage in HTN. It mainly focuses on immune cells, cytokines, and chemokines and inhibitors. However, further comprehensive and large-scale studies are needed to determine the role of these markers and provide effective protocols for clinical intervention and treatment.
Risk factors for graft-versus-host-disease after donor lymphocyte infusion following T-cell depleted allogeneic stem cell transplantation
Authors: Koster Eva A. S. , von dem Borne Peter A. , van Balen Peter , Marijt Erik W. A. , Tjon Jennifer M. L. , Snijders Tjeerd J. F. , van Lammeren Daniëlle , Veelken Hendrik , Falkenburg J. H. Frederik , Halkes Constantijn J. M. , de Wreede Liesbeth C.
Published: March 2024

Introduction

Unmodified donor lymphocyte infusions (DLI) after allogeneic stem cell transplantation (alloSCT) can boost the beneficial Graft-versus-Leukemia (GvL) effect but may also induce severe Graft-versus-Host-Disease (GvHD). To improve the balance between GvL and GvHD, it is crucial to identify factors that influence the alloreactivity of DLI.

Methods

We investigated the effects of the presence of patient-derived antigen-presenting cells at time of DLI as estimated by the bone marrow (BM) chimerism status, lymphopenia as measured by the absolute lymphocyte count (ALC) at time of DLI, and the presence of a viral infection (de novo or reactivation) close to DLI on the risk of GvHD after DLI. The cohort consisted of patients with acute leukemia or myelodysplastic syndrome who prophylactically or pre-emptively received DLI as standard care after alemtuzumab-based alloSCT. In patients at high risk for relapse, DLI was administered at 3 months after alloSCT (n=88) with a dose of 0.3x106 or 0.15x106 T cells/kg in case of a related or unrelated donor, respectively. All other patients (n=76) received 3x106 or 1.5x106 T cells/kg, respectively, at 6 months after alloSCT.

Results

For both DLIs, patients with reduced-intensity conditioning and an unrelated donor had the highest risk of GvHD. For DLI given at three months, viral infection within 1 week before and 2 weeks after DLI was an additional significant risk factor (hazard ratio (HR) 3.66 compared to no viral infection) for GvHD. At six months after alloSCT, viral infections were rare and not associated with GvHD. In contrast, mixed BM chimerism (HR 3.63 for ≥5% mixed chimerism compared to full donor) was an important risk factor for GvHD after DLI given at six months after alloSCT. ALC of <1000x106/l showed a trend for association with GvHD after this DLI (HR 2.05 compared to ≥1000x106/l, 95% confidence interval 0.94-4.45). Furthermore, the data suggested that the presence of a viral infection close to the DLI at three months or ≥5% mixed chimerism at time of the DLI at six months correlated with the severity of GvHD, thereby increasing their negative impact on the current GvHD-relapse-free survival.

Conclusion

These data demonstrate that the risk factors for GvHD after DLI depend on the setting of the DLI.
HBsAg level defines different clinical phenotypes of HBeAg(−) chronic HBV infection related to HBV polymerase-specific CD8+ cell response quality
Authors: Peña-Asensio Julia , Calvo-Sánchez Henar , Miquel-Plaza Joaquín , Sanz-de-Villalobos Eduardo , González-Praetorius Alejandro , Delgado-Fernandez Alberto , Torralba Miguel , Larrubia Juan-Ramón
Published: March 2024

Background

HBe-antigen(Ag)-negative chronic hepatitis B virus (HBV) infection is characterized by little liver fibrosis progression and vigorous HBV-multispecific CD8+ T-cell response.

Aims

To assess whether HBsAg level could discriminate different HBeAg-negative chronic HBV infection subtypes with dissimilar quality of HBV-specific CD8+ T-cell response.

Methods

We recruited 63 HBeAg-negative chronic HBV infection patients in which indirect markers of liver inflammation/fibrosis, portal pressure, viral load (VL), and HBV-specific CD8+ cell effector function were correlated with HBsAg level.

Results

A positive linear trend between HBsAg level and APRI, liver stiffness (LS), liver transaminases, and HBV VL, and a negative correlation with platelet count were observed. Frequency of cases with HBV-specific CD8+ T-cell proliferation against at least two HBV epitopes was higher in HBsAg < 1,000 IU/ml group. CD8+ T-cell expansion after HBVpolymerase456-63-specific stimulation was impaired in HBsAg > 1,000 IU/ml group, while the response against HBVcore18-27 was preserved and response against envelope183-91 was nearly abolished, regardless of HBsAg level. Cases with preserved HBVpolymerase456-63 CD8+ cell response had lower LS/duration of infection and APRI/duration of infection rates. HBV-polymerase456-63-specific CD8+ T-cell proliferation intensity was negatively correlated with LS/years of infection ratio.

Conclusion

HBsAg > 1,000 IU/ml HBeAg-negative chronic HBV infection group shows indirect data of higher degree of inflammation, liver stiffness, and fibrosis progression speed, which are related to an impaired HBV-polymerase-specific CD8+ T-cell response.
IFN-γ enhances protective efficacy against Nocardia seriolae infection in largemouth bass (Micropterus salmoides)
Authors: Yu Ruying , Zhang Weixiang , Yu Penghui , Zhou Jiancheng , Su Jianguo , Yuan Gailing
Published: March 2024

Introduction

Nocardia seriolae adversely impacts a diverse range of fish species, exhibiting significant pathogenic characteristics that substantially impede the progress of aquaculture. N. seriolae infects in fish has a long incubation period, and clinical symptoms are not obvious in the early stages. There is presently no viable and eco-friendly approach to combat the spread of the disease. According to reports, N. seriolae primarily targets macrophages in tissues after infecting fish and can proliferate massively, leading to the death of fish. Interferon-gamma (IFN-γ) is a crucial molecule that regulates macrophage activation, but little is known about its role in the N. seriolae prevention.

Methods

IFN-γ was first defined as largemouth bass (Micropterus salmoides, MsIFN-γ), which has a highly conserved IFN-γ characteristic sequence through homology analysis. The recombinant proteins (rMsIFN-γ) were obtained in Escherichia coli (E. coli) strain BL21 (DE3). The inflammatory response-inducing ability of rMsIFN-γ was assessed in vitro using monocytes/macrophages. Meanwhile, the protective effect of MsIFN-γ in vivo was evaluated by N. seriolae infection largemouth bass model.

Results

In the inflammatory response of the monocytes/macrophages activated by rMsIFN-γ, various cytokines were significantly increased. Interestingly, interleukin 1β (IL-1β) and tumor necrosis factor alpha (TNF-a) increased by 183- and 12-fold, respectively, after rMsIFN-γ stimulation. rMsIFN-γ improved survival by 42.1% compared with the control. The bacterial load in the liver, spleen and head kidney significantly decreased. rMsIFN-γ was also shown to better induce increased expression of IL-1β, TNF-α, hepcidin-1(Hep-1), major histocompatibility complex I (MHCI), and MHC II in head kidney, spleen and liver. The histopathological examination demonstrated the transformation of granuloma status from an early necrotic foci to fibrosis in the infection period. Unexpectedly, the development of granulomas was successfully slowed in the rMsIFN-γ group.

Discussion

This work paves the way for further research into IFN-γ of largemouth bass and identifies a potential therapeutic target for the prevention of N. seriolae.
Causal association between psoriasis vulgaris and bullous pemphigoid: a two-sample bidirectional Mendelian randomization study
Authors: Zhang Aobei , Yang Zhihui , Huang Tao , Wang Mingyue
Published: March 2024

Background

The association between psoriasis vulgaris and bullous pemphigoid (BP) remains largely unknown.

Objectives

To investigate whether there is a causal effect between psoriasis vulgaris and BP.

Methods

Two-sample bidirectional Mendelian randomization (MR) analyses were conducted using publicly released genome-wide association studies (GWAS) summary statistics. The GWAS summary statistics for BP were downloaded online from FinnGen Biobank Documentation of the R12 release, which includes 219 BP cases and 218,066 controls. The GWAS data for psoriasis vulgaris were extracted from Sakaue et al., which comprises 5072 cases and 478,102 controls. Single-nucleotide polymorphisms (SNPs) associated with exposure were selected as instrumental variables by performing additional quality control steps. The inverse-variance-weighted (IVW) method was used for the primary MR analyses, and the MR-Egger regression, weighted mode method, weighted median method, and simple mode were employed for sensitivity analyses. The MR-Egger intercept test and “leave-one-out” sensitivity analysis were performed to evaluate the horizontal pleiotropy and the potentially influential SNPs, respectively.

Results

Genetically determined log odds of psoriasis vulgaris were associated with an increased risk of BP (IVW: odds ratio (OR) = 1.263, 95% confidence interval (CI): 1.013-1.575, P=0.038). Sensitivity analyses by the weighted mode (OR=1.255, 95%CI: 0.973-1.618, P=0.106), MR Egger (OR=1.315, 95%CI: 0.951-1.817, P=0.126), simple mode (OR=1.414, 95%CI: 0.823-2.429, P=0.234) and weighted median method (OR=1.177, 95%CI: 0.889-1.559, P=0.254) derived directionally consistent relationship between the genetically predicted log odds of psoriasis vulgaris and risks of developing BP. On the contrary, we found that genetically predicted BP had no significant effect on psoriasis vulgaris (IVW: OR=0.996, P= 0.707), indicating the unidirectionality of the relationship. MR-Egger intercept tests showed no evidence of horizontal pleiotropy. No influential SNP driving the results was detected by the leave-one-out sensitivity analysis.

Conclusions

Our results suggested that psoriasis vulgaris causally increases the risk of BP, highlighting the need for potential strategies for the prevention and early diagnosis of comorbid BP in patients with psoriasis vulgaris. Further researches into this association and underlying mechanisms are warranted.
Neglected infectious diseases in the Americas: current situation and perspectives for the control and elimination by 2030
Authors: Saboyá-Díaz Martha Idalí , Maia-Elkhoury Ana Nilce S. , Luciañez Ana , Valadas Samantha Y. O. B. , Carvaho-Scholte Ronaldo Guilherme , Nicholls Rubén Santiago , Vigilato Marco A. N. , Castellanos Luis Gerardo , Espinal Marcos A.
Published: March 2024

Neglected infectious diseases (NID) are a diverse group of conditions including more than 20 parasitic, bacterial, and fungal diseases, and envenoming by poisonous animals. Their risk factors include poverty, income inequality, lack of access to safe drinking water and proper sanitation, and barriers to education and health services, among other social determinants of health. They impose a large burden on marginalized populations globally and in the region of the Americas, including women and ethnic minorities. The region of the Americas has a track record of elimination of communicable diseases and countries have made significant progress in the elimination of NID in recent years. Between 2011 and 2020, one country eliminated trachoma, four eliminated onchocerciasis, one eliminated human rabies transmitted by dogs, and three were declared free of lymphatic filariasis. The COVID-19 pandemic impacted the continuity of actions to eliminate NID and there are challenges in controlling and eliminating NID, particularly in vulnerable and hard-to-reach populations with issues in accessing health services. There are still difficulties in the coordination between health and other sectors to work together on the socioeconomic and environmental determinants of NID. Forwarding the elimination of NID in the Americas involves continuous advocacy and resource mobilization at various levels (international, regional, national, and subnational), ensuring sufficient allocation of human and financial resources, access to essential health supplies, and implementing people-centered services. It also entails engaging and empowering civil society, communities, local governments, and public-private partnerships, while collaborating with stakeholders and donors for effective action.
Large protistan mixotrophs in the North Atlantic Continuous Plankton Recorder time series: associated environmental conditions and trends
Authors: Stamieszkin Karen , Millette Nicole C. , Luo Jessica Y. , Follett Elizabeth , Record Nicholas R. , Johns David G.
Published: March 2024

Aquatic ecologists are integrating mixotrophic plankton – here defined as microorganisms with photosynthetic and phagotrophic capacity – into their understanding of marine food webs and biogeochemical cycles. Understanding mixotroph temporal and spatial distributions, as well as the environmental conditions under which they flourish, is imperative to understanding their impact on trophic transfer and biogeochemical cycling. Mixotrophs are hypothesized to outcompete strict photoautotrophs and heterotrophs when either light or nutrients are limiting, but testing this hypothesis has been hindered by the challenge of identifying and quantifying mixotrophs in the field. Using field observations from a multi-decadal northern North Atlantic dataset, we calculated the proportion of organisms that are considered mixotrophs within individual microplankton samples. We also calculated a “trophic index” that represents the relative proportions of photoautotrophs (phytoplankton), mixotrophs, and heterotrophs (microzooplankton) in each sample. We found that the proportion of mixotrophs was positively correlated with temperature, and negatively with either light or inorganic nutrient concentration. This proportion was highest during summertime thermal stratification and nutrient limitation, and lowest during the North Atlantic spring bloom period. Between 1958 and 2015, changes in the proportion of mixotrophs coincided with changes in the Atlantic Multi-decadal Oscillation (AMO), was highest when the AMO was positive, and showed a significant uninterrupted increase in offshore regions from 1992-2015. This study provides an empirical foundation for future experimental, time series, and modeling studies of aquatic mixotrophs.
Benefits and approaches of incorporating land–sea interactions into coastal spatial planning: evidence from Xiamen, China
Authors: Wang Shuo , Lin Jiaju , Xue Xiongzhi , Lin Yanhong
Published: March 2024

As the land–sea interface, the coastal zone has become an increasingly key life-support system. However, it is also highly threatened by exposure to both ocean- and land-based human activities. The interdependencies of the land and sea systems require the integration of land and sea spatial planning to achieve sustainable development of coastal zones. There are different forms of land–sea spatial management integration globally. Whether a form can positively impact and how different institutional settings affect outcomes need further explanation. Therefore, this study explores the reasons for China’s planning integration through institutional reform by using the Graph Model for Conflicts Resolution and establishes a quantitative contradiction assessment method to examine whether this top-down institutional approach has played a role at the urban level. The results show that the planning of Xiamen city after reform has a lower total contradiction value, grid cell average and cell maximum value. This progress is made possible by unifying the land–sea spatial planning departments. The equilibrium solution of the Graph Model for Conflicts Resolution indicates that due to the different preferences of the land–sea management departments and the central-local governments, it is challenging to implement the Land–sea Coordination policy under separate land–sea management. By integrating land–sea management departments, deep-seated sectoral interests between horizontal departments do not remain. The impacts on integrated management of divergences in preferences of different vertical governments can be reduced. The research results provide a universal method for the contradiction evaluation and a management reference for other regions that want to integrate land–sea coordination into urban spatial planning.
Estimating nearshore infragravity wave conditions at large spatial scales
Authors: Leijnse Tim W. B. , van Ormondt Maarten , van Dongeren Ap , Aerts Jeroen C. J. H. , Muis Sanne
Published: March 2024

Infragravity waves may contribute significantly to coastal flooding, especially during storm conditions. However, in many national and continental to global assessments of coastal flood risk, their contribution is not accounted for, mostly because of the high computational expense of traditional wave-resolving numerical models. In this study, we present an efficient stationary wave energy solver to estimate the evolution of incident and infragravity waves from offshore to the nearshore for large spatial scales. This solver can be subsequently used to provide nearshore wave boundary conditions for overland flood models. The new wave solver builds upon the stationary wave energy balance for incident wave energy and extends it to include the infragravity wave energy balance. To describe the energy transfer from incident to infragravity waves, an infragravity wave source term is introduced. This term acts as a sink term for incident waves and as a complementary source term for infragravity waves. The source term is simplified using a parameterized infragravity wave shoaling parameter. An empirical relation is derived using observed values of the shoaling parameter from a synthetic dataset of XBeach simulations, covering a wide range of wave conditions and beach profiles. The wave shoaling parameter is related to the local bed slope and relative wave height. As validation, we show for a range of cases from synthetic beach profiles to laboratory tests that infragravity wave transformation can be estimated using this wave solver with reasonable to good accuracy. Additionally, the validity in real-world conditions is verified successfully for DELILAH field case observations at Duck, NC, USA. We demonstrate the wave solver for a large-scale application of the full Outer Banks coastline in the US, covering 450 km of coastline, from deep water up to the coast. For this model, consisting of 4.5 million grid cells, the wave solver can estimate the stationary incident and infragravity wave field in a matter of seconds for the entire domain on a regular laptop PC. This computational efficiency cannot be provided by existing process-based wave-resolving models. Using the presented method, infragravity wave-driven flooding can be incorporated into large-scale coastal compound flood models and risk assessments.
Dynamic typhoon visualization based on the integration of vector and scalar fields
Authors: Feng Chongjun , Qin Tao , Ai Bo , Ding Jun , Wu Tianyu , Yuan Ming
Published: March 2024

Typhoons and other marine meteorological disasters often bring significant losses to human beings, and their data are characterized by multiple sources and scales, making traditional visualization methods unable to accurately express the characteristics and movement trends of the disasters. To address the above problems, this study proposes a typhoon dynamic visualization method based on the integration of vector and scalar fields. To address the above problems, this study proposes a typhoon dynamic visualization method based on the integration of vector and scalar fields. The method uses the ray casting method to visualize the volume rendering of typhoon scalar data, proposes a hybrid interpolation method to improve the visualization efficiency, and introduces the Sobel operator to achieve the edge enhancement of the volume rendering effect. Meanwhile, a particle system approach is used for dynamic visualization of typhoon vector data, where the tedious particle motion calculation is divided into two parts: parallel tracking and dynamic rendering to improve the visualization efficiency, and the Lagrangian field representation of the particle system is achieved. The experimental results show that the typhoon visualization method proposed in this study has better comprehensive visual effects, with a rendering frame rate greater than 44, and is able to stably and smoothly express the continuous spatio-temporal dynamic visualization features of typhoon.This study is conducive to the understanding of the evolution law of marine meteorological disasters and the adoption of disaster prevention and mitigation measures, and is of great significance for the expression of marine meteorological data such as typhoons and the analysis of their spatial and temporal changes.
Efficacy and safety of platelet-rich plasma for acute nonarteritic anterior ischemic optic neuropathy: a prospective cohort study
Authors: Jin Xin , Fu Junxia , Lv Ruju , Hao Xiaolu , Wang Song , Sun Mingming , Xu Guangcan , Zhang Qi , Zhang Lei , Li Yan , Xu Quangang , Hou Baoke
Published: March 2024

Background

As the most common acute optic neuropathy in older patients, nonarteritic anterior ischemic optic neuropathy (NAION) presents with varying degrees of visual acuity loss and visual field defect. However, there is no generally accepted treatment for NAION.

Objectives

To evaluate the efficacy and safety of platelet-rich plasma (PRP) for patients with acute NAION within 2 months.

Design

A prospective, nonrandomized controlled trial.

Methods

Twenty-five eyes of 25 patients were enrolled. Of them, 13 received anisodine hydrobromide and butylphthalide-sodium chloride injection continuously for 10 days as basic treatment in the control group, and 12 received two tenon capsule injections of PRP on a 10 days interval as an additional treatment in the PRP group. We compared the best-corrected visual acuity (BCVA) and capillary perfusion density (CPD) of radial peripapillary capillaries and the moth-eaten eara of the peripapillary superficial capillary plexus and deep capillary plexus at 1 day (D1) before the first PRP treatment and 7 days (D7), 14 days (D14), and 30 days (D30) after the first PRP injection. Ocular and systemic adverse effects were assessed.

Results

In the PRP group, a better BCVA occurred at D30 (adjusted p = 0.005, compared with D1, recovered from 0.67 ± 0.59 to 0.43 ± 0.59), and a significant improvement in CPD was observed at D30 (adjusted p < 0.001, p = 0.027, p = 0.027, compared with D1, D7, D14, in sequence, the value was 35.97 ± 4.65, 38.73 ± 4.61, 39.05 ± 5.26, 42.71 ± 4.72, respectively). CPD at D7 in the PRP group was better than that in the control group (p = 0.043). However, neither BCVA nor the moth-eaten area index were significantly different (all p > 0.5) between the two groups. The main adverse effect was local discomfort resolved within 1 week, and no other systemic adverse events occurred.

Conclusion

Tenon capsule injection of PRP was a safe treatment for AION and could improve capillary perfusion of the optic nerve head and might be helpful in increasing short-term vision in patients with acute NAION.
Desirable L-asparaginases for treating cancer and current research trends
Authors: Tsegaye Kindu , Tsehai Berhanu Andualem , Getie Birhan
Published: March 2024

Amino acid depletion therapy is a promising approach for cancer treatment. It exploits the differences in the metabolic processes between healthy and cancerous cells. Certain microbial enzymes induce cancer cell apoptosis by removing essential amino acids. L-asparaginase is an enzyme approved by the FDA for the treatment of acute lymphoblastic leukemia. The enzymes currently employed in clinics come from two different sources: Escherichia coli and Erwinia chrysanthemi. Nevertheless, the search for improved enzymes and other sources continues because of several factors, including immunogenicity, in vivo instability, and protease degradation. Before determining whether L-asparaginase is clinically useful, research should consider the Michaelis constant, turnover number, and maximal velocity. The identification of L-asparaginase from microbial sources has been the subject of various studies. The primary goals of this review are to explore the most current approaches used in the search for therapeutically useful L-asparaginases and to establish whether these investigations identified the crucial characteristics of L-asparaginases before declaring their therapeutic potential.
A multiplex TaqMan real-time PCR assays for the rapid detection of mobile colistin resistance (mcr-1 to mcr-10) genes
Authors: Gong Xinran , Yang Guang , Liu Wei , Wu Di , Duan Chunyuan , Jia Xinjing , Li Zhiqiang , Zou Xiaocang , Yu Renfeng , Zou Dayang , Wang Yong
Published: March 2024

Objective

Recently, 10 plasmid-mediated mobile colistin resistance genes, mcr-1 to mcr-10, and their variants have been identified, posing a new threat to the treatment of clinical infections caused by Gram-negative bacteria. Our objective was to develop a rapid, sensitive, and accurate molecular assay for detecting mcr genes in clinical isolates.

Methods

The primers and corresponding TaqMan-MGB probes were designed based on the sequence characteristics of all reported MCR family genes, multiplex Taqman-MGB probe-based qPCR assays were developed and optimized, and the sensitivity, specificity and reproducibility of the method were evaluated. The assay contained 8 sets of primers and probes in 4 reaction tubes, each containing 2 sets of primers and probes.

Results

The standard curves for both the single and multiplex systems showed good linearity (R2 > 0.99) between the starting template amount and the Ct value, with a lower limit of detection of 102 copies/μL. The specificity test showed positive amplification results only for strains containing the mcr genes, whereas the other strains were negative. The results of intra-and inter-group repeatability experiments demonstrated the stability and reliability of the newly developed method. It was used to detect mcr genes in 467 clinically-obtained Gram-negative isolates, which were multidrug-resistant. Twelve strains containing the mcr genes were detected (seven isolates carrying mcr-1, four isolates carrying mcr-10, and one isolate carrying mcr-9). The products amplified by the full-length PCR primer were identified by sequencing, and the results were consistent with those of the multiplex qPCR method.

Conclusion

The assay developed in this study has the advantages of high specificity, sensitivity, and reproducibility. It can be used to specifically detect drug-resistant clinical isolates carrying the mcr genes (mcr-1 to mcr-10), thus providing a better basis for clinical drug treatment and drug resistance research.
Targeted cultivation of diatoms in mariculture wastewater by nutrient regulation and UV-C irradiation
Authors: Shen Jiacong , Zheng Xiafei , Liu Minhai , Xu Kui , He Lin , Lin Zhihua
Published: March 2024

Mariculture wastewater poses environmental challenges due to pollution and eutrophication. Targeted cultivation of diatoms in wastewater can help alleviate these issues while generating beneficial algae biomass, however reliable operating methods are lacking. We proposed a novel method for treating mariculture wastewater that employed UV-C irradiation and nutrient regulation to achieve targeted diatom cultivation. This study first examined growth of four diatom species (Nitzschia closterium, Chaetoceros muelleri, Cyclotella atomus, and Conticribra weissflogii) in mariculture wastewater. C. muelleri and C. weissflogii demonstrated better adaptability compared to N. closterium and C. atomus. Additionally, the growth and nutrient utilization of C. muelleri were studied under varying concentrations of silicate, phosphate, ammonium, and trace elements in wastewater. Optimal growth was observed at 500 μmol/L silicate, 0.6 mg/L phosphate, and 4 mg/L ammonium. Ammonium proved to be a more effective nitrogen source than urea and nitrate in promoting growth at this low level. Surprisingly, trace element supplementation did not significantly impact growth. Finally, this study utilized UV-C irradiation as a pre-treatment method for wastewater prior to nutrient adjustment, significantly enhancing the growth of C. muelleri. Overall, this study provides guidance on regulating key nutrients and pre-treatment method to optimize diatom biomass production from mariculture wastewater. This approach not only addresses environmental challenges associated with mariculture but also contributes to sustainable aquaculture practices through the recovery of valuable aquatic resources.
An in vitro analysis of an innovative standardized phospholipid carrier-based Melissa officinalis L. extract as a potential neuromodulator for emotional distress and related conditions
Authors: Kara Mehtap , Sahin Sumeyye , Rabbani Fazle , Oztas Ezgi , Hasbal-Celikok Gozde , Kanımdan Ebru , Kocyigit Abdurrahim , Kanwal Ayesha , Wade Ursula , Yakunina Anastasia , Di Pierro Francesco , Khan Amjad
Published: March 2024

Background:Melissa officinalis L. (MO), commonly known as lemon balm, a member of the mint family, is considered a calming herb. In various traditional medicines, it has been utilized to reduce stress and anxiety and promote sleep. A growing body of clinical evidence suggests that MO leaf extract supplementation possesses considerable neuropharmacological properties. However, its possible mechanism of action largely remains unknown.

Objective: In the present in vitro studies, we comparatively investigated the central nervous system (CNS)-calming and antioxidative stress properties of an innovative standardized phospholipid carrier-based (Phytosome™) MO extract (Relissa™) vs. an unformulated dry MO extract.

Methods: The neuropharmacological effect of the extract was studied in the anti-depressant enzymes γ-aminobutyrate transaminase (GABA-T) and monoamine oxidase A (MAO-A) assays and SH-SY5Y cells brain-derived neurotrophic factor (BDNF) expression assay. The neuroprotective effect of the extract against oxidative stress was assessed in SH-SY5Y cell-based (H2O2-exposed) Total Antioxidant Status (TAS) and Total Reactive Oxygen Species (ROS) assays. The cytotoxic effect of the extract was evaluated using MTT and LDH assays. The extract antioxidant effect was also evaluated in cell-free chemical tests, including TEAC-ABTS, DPPH, Ferric Reducing Antioxidant Power (FRAP), Oxygen Radical Antioxidant Capacity (ORAC), and Hydroxyl Radical Antioxidant Capacity (HORAC) assays.

Results: Relissa™ exhibited high GABA-T inhibitory activity, IC50 (mg/mL) = 0.064 vs. unformulated dry MO extract, IC50 (mg/mL) = 0.27. Similar inhibitory effects were also observed for MAO-A. Relissa™ demonstrated an improved neuroprotective antioxidant effect on SH-SY5Y cells against H2O2-induced oxidative stress. Compared to unformulated dry MO extract, Relissa™ exerted high protective effect on H2O2-exposed SH-SY5Y cells, leading to higher cells BDNF expression levels. Moreover, cell-free chemical tests, including TEAC-ABTS, DPPH radical scavenging, FRAP, ORAC, and HORAC assays, validated the improved antioxidant effect of Relissa™ vs. unformulated dry MO extract.

Conclusion: The results of the present study support the neuromodulating and neuroprotective properties of Relissa™, and its supplementation may help in the amelioration of emotional distress and related conditions.
Phylogenetic reduction of the magnocellular red nucleus in primates and inter-subject variability in humans
Authors: Stacho Martin , Häusler A. Niklas , Brandstetter Andrea , Iannilli Francesca , Mohlberg Hartmut , Schiffer Christian , Smaers Jeroen B. , Amunts Katrin
Published: March 2024

Introduction

The red nucleus is part of the motor system controlling limb movements. While this seems to be a function common in many vertebrates, its organization and circuitry have undergone massive changes during evolution. In primates, it is sub-divided into the magnocellular and parvocellular parts that give rise to rubrospinal and rubro-olivary connection, respectively. These two subdivisions are subject to striking variation within the primates and the size of the magnocellular part is markedly reduced in bipedal primates including humans. The parvocellular part is part of the olivo-cerebellar circuitry that is prominent in humans. Despite the well-described differences between species in the literature, systematic comparative studies of the red nucleus remain rare.

Methods

We therefore mapped the red nucleus in cytoarchitectonic sections of 20 primate species belonging to 5 primate groups including prosimians, new world monkeys, old world monkeys, non-human apes and humans. We used Ornstein-Uhlenbeck modelling, ancestral state estimation and phylogenetic analysis of covariance to scrutinize the phylogenetic relations of the red nucleus volume.

Results

We created openly available high-resolution cytoarchitectonic delineations of the human red nucleus in the microscopic BigBrain model and human probabilistic maps that capture inter-subject variations in quantitative terms. Further, we compared the volume of the nucleus across primates and showed that the parvocellular subdivision scaled proportionally to the brain volume across the groups while the magnocellular part deviated significantly from the scaling in humans and non-human apes. These two groups showed the lowest size of the magnocellular red nucleus relative to the whole brain volume and the largest relative difference between the parvocellular and magnocellular subdivision.

Discussion

That is, the red nucleus has transformed from a magnocellular-dominated to a parvocellular-dominated station. It is reasonable to assume that these changes are intertwined with evolutionary developments in other brain regions, in particular the motor system. We speculate that the interspecies variations might partly reflect the differences in hand dexterity but also the tentative involvement of the red nucleus in sensory and cognitive functions.
The SESAMEEG package: a probabilistic tool for source localization and uncertainty quantification in M/EEG
Authors: Luria Gianvittorio , Viani Alessandro , Pascarella Annalisa , Bornfleth Harald , Sommariva Sara , Sorrentino Alberto
Published: March 2024

Source localization from M/EEG data is a fundamental step in many analysis pipelines, including those aiming at clinical applications such as the pre-surgical evaluation in epilepsy. Among the many available source localization algorithms, SESAME (SEquential SemiAnalytic Montecarlo Estimator) is a Bayesian method that distinguishes itself for several good reasons: it is highly accurate in localizing focal sources with comparably little sensitivity to input parameters; it allows the quantification of the uncertainty of the reconstructed source(s); it accepts user-defineda priorihigh- and low-probability search regions in input; it can localize the generators of neural oscillations in the frequency domain. Both a Python and a MATLAB implementation of SESAME are available as open-source packages under the name of SESAMEEG and are well integrated with the main software packages used by the M/EEG community; moreover, the algorithm is part of the commercial software BESA Research (from version 7.0 onwards). While SESAMEEG is arguably simpler to use than other source modeling methods, it has a much richer output that deserves to be described thoroughly. In this article, after a gentle mathematical introduction to the algorithm, we provide a complete description of the available output and show several use cases on experimental M/EEG data.
Complex chemical reaction networks for future information processing
Authors: Csizi Katja-Sophia , Lörtscher Emanuel
Published: March 2024

Tackling the increasing energy demand of our society is one of the key challenges today. With the rise of artificial intelligence, information and communication technologies started to substantially contribute to this alarming trend and therefore necessitate more sustainable approaches for the future. Brain-inspired computing paradigms represent a radically new and potentially more energy-efficient approach for computing that may complement or even replace CMOS in the long term. In this perspective, we elaborate on the concepts and properties of complex chemical reaction networks (CRNs) that may serve as information-processing units based on chemical reactions. The computational capabilities of simpler, oscillatory chemical reactions have already been demonstrated in scenarios ranging from the emulation of Boolean gates to image-processing tasks. CRNs offer higher complexity and larger non-linearity, potentially at lower energy consumption. Key challenges for the successful development of CRN-based computers are associated with their specific physical implementations, operability, and readout modalities. CRNs are sensible to various reaction triggers, and provide multiple and interlinked reaction pathways and a diverse compound space. This bears a high potential to build radically new hardware and software concepts for energy-efficient computing based on neuromorphic architectures—with computing capabilities in real-world applications yet to be demonstrated.
Pediatric CNS tumors and 2021 WHO classification: what do oncologists need from pathologists?
Authors: d’Amati Antonio , Bargiacchi Lavinia , Rossi Sabrina , Carai Andrea , Bertero Luca , Barresi Valeria , Errico Maria Elena , Buccoliero Anna Maria , Asioli Sofia , Marucci Gianluca , Del Baldo Giada , Mastronuzzi Angela , Miele Evelina , D’Antonio Federica , Schiavello Elisabetta , Biassoni Veronica , Massimino Maura , Gessi Marco , Antonelli Manila , Gianno Francesca
Published: March 2024

The fifth edition of the WHO Classification of Tumors of the Central Nervous System (CNS), published in 2021, established new approaches to both CNS tumor nomenclature and grading, emphasizing the importance of integrated diagnoses and layered reports. This edition increased the role of molecular diagnostics in CNS tumor classification while still relying on other established approaches such as histology and immunohistochemistry. Moreover, it introduced new tumor types and subtypes based on novel diagnostic technologies such as DNA methylome profiling. Over the past decade, molecular techniques identified numerous key genetic alterations in CSN tumors, with important implications regarding the understanding of pathogenesis but also for prognosis and the development and application of effective molecularly targeted therapies. This review summarizes the major changes in the 2021 fifth edition classification of pediatric CNS tumors, highlighting for each entity the molecular alterations and other information that are relevant for diagnostic, prognostic, or therapeutic purposes and that patients’ and oncologists’ need from a pathology report.
The altered TBI fecal microbiome is stable and functionally distinct
Authors: Pyles Richard B. , Miller Aaron L. , Urban Randall J. , Sheffield-Moore Melinda , Wright Traver J. , Maxwell Carrie A. , Randolph Kathleen M. , Danesi Christopher P. , McGovern Kristen A. , Vargas Jayson , Armstrong Peyton , Kreber Lisa , Cumpa Giuliana , Randall Kevin , Morrison Melissa , Masel Brent E.
Published: March 2024

Introduction

Patients who suffer a traumatic brain injury (TBI) often experience chronic and sometimes debilitating sequelae. Recent reports have illustrated both acute and long-term dysbiosis of the gastrointestinal microbiome with significant alterations in composition and predicted functional consequences.

Methods

Working with participants from past research, metagenomic stability of the TBI- associated fecal microbiome (FMB) was evaluated by custom qPCR array comparing a fecal sample from 2015 to one collected in 2020. Metatranscriptomics identified differently expressed bacterial genes and biochemical pathways in the TBI FMB. Microbiota that contributed the largest RNA amounts identified a set of core bacteria most responsible for functional consequences of the TBI FMB.

Results

A remarkably stable FMB metagenome with significant similarity (two-tail Spearman nonparametric correlation p < 0.001) was observed between 2015 and 2020 fecal samples from subjects with TBI. Comparing the 2020 TBI FMB metagenome to FMBs from healthy controls confirmed and extended the dysbiotic genera and species. Abundance differences between average TBI and healthy FMBs revealed Bacteroides caccae, B. uniformis, Blautia spp., Collinsella spp., Dialister spp., and Ordoribacter spp. were significantly different. Functionally, the Parabacteroides genus contributed the highest percentage of RNA sequences in control FMBs followed by the Bacteroides genus as the second highest contributor. In the TBI FMB, the Corynebacterium genus contributed the most RNA followed by the Alistipes genus. Corynebacterium and Pseudomonas were distinct in the top 10 contributing genera in the TBI FMB while Parabacteroides and Ruminococcus were unique to the top 10 in controls. Comparing RNA profiles, TBI samples had ∼1.5 fold more expressed genes with almost 700 differently expressed genes (DEGs) mapped to over 100 bacterial species. Bioinformatic analysis associated DEGs with pathways led identifying 311 functions in the average TBI FMB profile and 264 in the controls. By average profile comparison, 30 pathways had significantly different abundance (p < 0.05, t-test) or were detected in >80% of the samples in only one of the cohorts (binary distinction).

Discussion

Functional differences between TBI and healthy control FMBs included amino acid metabolism, energy and carbon source usage, fatty acid metabolism, bacterial cell wall component production and nucleic acid synthesis and processing pathways. Together these data shed light on the functional consequences of the dysbiotic TBI FMB decades after injury.