bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral health’s role in diabetes risk: a cross-sectional study with sociodemographic and lifestyle insights
Authors: Ghanem Amr Sayed , Nagy Attila Csaba
Published: March 2024

Introduction

Diabetes, a key chronic non-communicable disease, poses a substantial public health burden. The role of oral health as a determinant in the epidemiology of diabetes mellitus, particularly in the Central Eastern European region, remains underexplored. This research aims to examine the impact of specific oral health parameters, including gum bleeding, active dental caries, tooth mobility, and tooth loss, on diabetes prevalence. Additionally, it seeks to clarify the moderating effects of socio-demographic and lifestyle variables on this relationship.

Materials and methods

Data were extracted from the 2014 and 2019 datasets of the Hungarian European Health Interview Survey, comprising a combined nationally representative sample of 11,429 participants. Descriptive statistics were presented as weighted proportions and unweighted counts, and weighted Pearson’s chi-squared tests were employed for assessing associations and goodness-of-fit. Significant predictors were integrated into weighted multiple logistic regression models for analysis. Sensitivity analysis was then conducted to confirm the robustness of the findings.

Results

The study identified ‘Bad’ self-perceived oral health as a diabetes risk (OR=1.35; 95% CI: [1.04-1.75]), with filled teeth being protective (0.65 [0.51-0.84]). Subgroup analysis revealed higher diabetes odds among individuals with primary education (1.41 [1.02-1.96]) and rural residents with tooth loss from decay (3.54 [1.36-9.19]). The bootstrap analysis with 1,000 iterations reaffirmed the model’s stability and predictive accuracy for diabetes.

Discussion

Enhanced oral health is associated with lower risk factors for diabetes. This research highlights the importance of including oral health measures in comprehensive diabetes management approaches.
ERCC4: a potential regulatory factor in inflammatory bowel disease and inflammation-associated colorectal cancer
Authors: Shi Runjie , Wang Shanping , Jiang Ying , Zhong Guoqiang , Li Mingsong , Sun Yan
Published: March 2024

The pathogenesis of inflammatory bowel disease (IBD) remains unclear and is associated with an increased risk of developing colitis-associated cancer (CAC). Under sustained inflammatory stimulation in the intestines, loss of early DNA damage response genes can lead to tumor formation. Many proteins are involved in the pathways of DNA damage response and play critical roles in protecting genes from various potential damages that DNA may undergo. ERCC4 is a structure-specific endonuclease that participates in the nucleotide excision repair (NER) pathway. The catalytic site of ERCC4 determines the activity of NER and is an indispensable gene in the NER pathway. ERCC4 may be involved in the imbalanced process of DNA damage and repair in IBD-related inflammation and CAC. This article primarily reviews the function of ERCC4 in the DNA repair pathway and discusses its potential role in the processes of IBD-related inflammation and carcinogenesis. Finally, we explore how this knowledge may open novel avenues for the treatment of IBD and IBD-related cancer.
Multi-objective optimization of the organic Rankine cycle cascade refrigeration cycle driven by sugar mills waste heat
Authors: Wang Zongrun , Guan Wei , Zhang Song , Sang Hailang , Que Wenshuai , Liang Lu
Published: March 2024

The research on the recovery of low-grade thermal energy carried away by boiler flue gas is significant for sugar mills. This paper designs a waste heat recovery system based on sugar plant flue gas, integrating absorption refrigeration cycle and the organic Rankine cycle, and the effects of nine working fluids on the system are investigated. The aim is to realize the multi-form conversion of energy. The performance of the system is evaluated in terms of energy, exergy, and economic metrics. Multi-objective optimization is performed with the method of the NSGA-II genetic algorithm. The results show that Butane is the most suitable working fluid for ORC. The exergy efficiency of the system is 32.125% before optimisation, with an increased space cooling capacity of 15820.56 MW per year for the sugar mill. The exergy destruction analysis of the system reveals that the generator accounts for the highest proportion of exergy destruction (50.8%). The entire system shows the LCOE is as low as 0.0406$/kWh under the optimized condition. The optimized system can obtain an estimated annual electricity sales revenue of $136,300, and the sugar mill can save $308,600 in cooling costs. In addition, the payback period can be shortened to 5.79 years.
Frequency prediction of a post-disturbance power system using a hybrid ARIMA and DBN model
Authors: Wang Huimin , Li Zhaojun Steven , Pan Jun , Chen Wenhua
Published: March 2024

The online prediction of power system dynamic frequency helps to guide the choice of control measures quickly and accurately after a disturbance, and this then ensures the reliable and stable operations of a power system. However, the prediction performance of the traditional single model is not accurate enough, and the prediction method cannot reflect the dynamic mechanism of the power system. To address these challenges, based on the analysis of the mechanism of the dynamic operation of a power system, a dynamic frequency online prediction method using the autoregressive integrated moving average (ARIMA) model and the deep belief network (DBN) is proposed in this paper. First, according to the mechanism of the dynamic operation of a power system, the dynamic frequency can be regarded as having two stages after the disturbance occurs. In the first stage, the frequency changes monotonously in the short term, which is predicted by the ARIMA model. Furthermore, the second stage is an oscillation phase with changing amplitude, which is predicted by the DBN. The calibration process is used to combine the two predicted results. Second, the three metrics including the frequency nadir (fnadir), the quasi-steady state frequency (fss), and the frequency curve obtained through the prediction are analyzed to measure the accuracy of the prediction results. Finally, to verify the accuracy of the proposed model, the IEEE 10-generator 39-bus benchmark system is used for verification.
High-resolution genomic profiling and locus-specific FISH in subcutaneous and visceral adipose tissue of obese patients
Authors: Brandt Vivian-Pascal , Holland Heidrun , Blüher Matthias , Klöting Nora
Published: March 2024

Obesity is known as a heterogeneous and multifactorial disease. The distribution of body fat is crucial for the development of metabolic complications. Comprehensive genetic analyses on different fat tissues are rare but necessary to provide more detailed information. Therefore, we performed genetic analyses of three patients with obesity using high resolution genome wide SNP array (blood, visceral fat tissue) and fluorescence in situ hybridization (FISH) analyses (visceral and subcutaneous fat tissue). Altogether, we identified 31 small Copy Number Variations (losses: 1p31.1, 1p22.2, 1q21.3, 2q34, 2q37.1, 3q28, 6p25.3, 7q31.33, 7q33, 8p23.3, 10q22.3, 11p15.4, 11p15.1, 11p14.2, 11p12, 13q12.3, 15q11.2-q13.1, 15q13.3, 20q13.2, 22q11.21; gains: 2q22.1-q22.2, 3p14.3, 4p16.3, 4q32.2, 6q27, 7p14.3, 7q34, 11p12, 12p11.21, 16p11.2-p11.1, 17q21.31) and 289 small copy-neutral Loss of Heterozygosity (cn-LOH). For the chromosomal region 15q11.2-q13.1, we detected a microdeletion (Prader-Willi-Syndrome) in one patient. Interestingly, we identified chromosomal SNP differences between EDTA-blood and visceral fat tissue (deletion and gain). Small losses of 7q31.33, 7q33, 11p14.2, 11p12, 13q12.3 as well as small gain of 7q34 were detected only in fat tissue and not in blood. Furthermore, FISH analyses on 7q31.33, 7q33 and 11p12 revealed differences between subcutaneous and visceral fat tissue. Generally, the deletions were detected more frequent in visceral fat tissue. Predominantly detected cn-LOH vs. CNV suggests a meaning of these cn-LOH for the pathogenesis of obesity. We conclude that the SNP array and FISH analyses used is applicable to generate more information for basic research on difficult cell subpopulations (e.g., visceral adipose tissue) and could opens up new diagnostic aspects in the field of obesity. Altogether, the significance of these mostly not yet described genetic aberrations in different fat tissues needs to confirmed in a larger series.
Autoimmune nodopathy with anti-contactin 1 antibody characterized by cerebellar dysarthria: a case report and literature review
Authors: Chen Jiajie , Liu Lingchun , Zhu Hongyan , Han Jinming , Li Rong , Gong Xiarong , Fu Hao , Long Jingjing , Li Haixia , Meng Qiang
Published: March 2024

Background

Autoimmune nodopathy (AN) has emerged as a novel diagnostic category that is pathologically different from classic chronic inflammatory demyelinating polyneuropathy. Clinical manifestations of AN include sensory or motor neuropathies, sensory ataxia, tremor, and cranial nerve involvement. AN with a serum-positive contactin-1 (CNTN1) antibody usually results in peripheral nerve demyelination. In this study, we reported a rare case of AN with CNTN1 antibodies characterized by the presence of CNTN1 antibodies in both serum and cerebrospinal fluid, which is associated with cerebellar dysarthria.

Methods

A 25-year-old man was admitted to our hospital due to progressive dysarthria with limb tremors. The patient was initially diagnosed with peripheral neuropathy at a local hospital. Three years after onset, he was admitted to our hospital due to dysarthria, apparent limb tremor, and limb weakness. At that time, he was diagnosed with spinocerebellar ataxia. Eight years post-onset, during his second admission, his condition had notably deteriorated. His dysarthria had evolved to typical distinctive cerebellar characteristics, such as tremor, loud voice, stress, and interrupted articulation. Additionally, he experienced further progression in limb weakness and developed muscle atrophy in the distal limbs. Magnetic resonance imaging (MRI), nerve conduction studies (NCS), and autoimmune antibody tests were performed.

Results

The results of the NCS suggested severe demyelination and even axonal damage to the peripheral nerves. MRI scans revealed diffuse thickening of bilateral cervical nerve roots, lumbosacral nerve roots, cauda equina nerve, and multiple intercostal nerve root sheath cysts. Furthermore, anti-CNTN1 antibody titers were 1:10 in the cerebrospinal fluid (CSF) and 1:100 in the serum. After one round of rituximab treatment, the patient showed significant improvement in limb weakness and dysarthria, and the CSF antibodies turned negative.

Conclusion

Apart from peripheral neuropathies, cerebellar dysarthria (central nervous system involvement) should not be ignored in AN patients with CNTN1 antibodies.
A novel type-2 innate lymphoid cell-based immunotherapy for cancer
Authors: Saranchova Iryna , Xia Clara Wenjing , Besoiu Stephanie , Finkel Pablo L. , Ellis Samantha L. S. , Kari Suresh , Munro Lonna , Pfeifer Cheryl G. , Fazli Ladan , Gleave Martin E. , Jefferies Wilfred A.
Published: March 2024

Cell-based cancer immunotherapy has achieved significant advancements, providing a source of hope for cancer patients. Notwithstanding the considerable progress in cell-based immunotherapy, the persistently low response rates and the exorbitant costs associated with their implementation still present a formidable challenge in clinical settings. In the landscape of cell-based cancer immunotherapies, an uncharted territory involves Type 2 innate lymphoid cells (ILC2s) and interleukin-33 (IL-33) which promotes ILC2 functionality, recognized for their inherent ability to enhance immune responses. Recent discoveries regarding their role in actuating cytolytic T lymphocyte responses, including curbing tumor growth rates and hindering metastasis, have added a new dimension to our understanding of the IL-33/ILC2 axis. These recent insights may hold significant promise for ILC2 cell-based immunotherapy. Nevertheless, the prospect of adoptively transferring ILC2s to confer immune protection against tumors has yet to be investigated. The present study addresses this hypothesis, revealing that ILC2s isolated from the lungs of tumor-bearing mice, and tumor infiltrating ILC2s when adoptively transferred after tumor establishment at a ratio of one ILC2 per sixty tumor cells, leads to an influx of tumor infiltrating CD4+ and CD8+ T lymphocytes as well as tumor infiltrating eosinophils resulting in a remarkable reduction in tumor growth. Moreover, we find that post-adoptive transfer of ILC2s, the number of tumor infiltrating ILC2s is inversely proportional to tumor size. Finally, we find corollaries of the IL-33/ILC2 axis enhancing the infiltration of eosinophils in human prostate carcinomas patients' expressing high levels of IL-33 versus those expressing low levels of IL-33. Our results underscore the heightened efficacy of adoptively transferred ILC2s compared to alternative approaches, revealing an approximately one hundred fifty-fold superiority on a cell-per-cell basis over CAR T-cells in the specific targeting and elimination of tumors within the same experimental model. Overall, this study demonstrates the functional significance of ILC2s in cancer immunosurveillance and provides the proof of concept of the potential utility of ILC2 cell-based cancer immunotherapies.
Efbalropendekin Alfa enhances human natural killer cell cytotoxicity against tumor cell lines in vitro
Authors: Shehata Hesham M. , Dogra Pranay , Gierke Sarah , Holder Patrick , Sanjabi Shomyseh
Published: March 2024

IL-15 has shown preclinical activity by enhancing the functional maturation of natural killer (NK) cells. Clinical evaluation of the potential anticancer activity of most cytokines, including IL-15, has been limited by low tolerability and rapid in vivo clearance. Efbalropendekin Alfa (XmAb24306) is a soluble IL15/IL15-receptor alpha heterodimer complex fused to a half-life extended Fc domain (IL15/IL15Rα-Fc), engineered with mutations to reduce IL-15 affinity for CD122. Reduced affinity drives lower potency, leading to prolonged pharmacodynamic response in cynomolgus monkeys. We show that in vitro, human NK cells treated with XmAb24306 demonstrate enhanced cytotoxicity against various tumor cell lines. XmAb24306-treated NK cells also exhibit enhanced killing of 3D colorectal cancer spheroids. Daratumumab (dara), a monoclonal antibody (mAb) that targets CD38 results in antibody-dependent cellular cytotoxicity (ADCC) of both multiple myeloma (MM) cells and NK cells. Addition of XmAb24306 increases dara-mediated NK cell ADCC against various MM cell lines in vitro. Because NK cells express CD38, XmAb24306 increases dara-mediated NK cell fratricide, but overall does not negatively impact the ADCC activity against a MM cell line likely due to increased NK cell activity of the surviving cells. These data show that XmAb24306 increases direct and ADCC-mediated human NK cell cytotoxicity in vitro.
Effect of pancreas disease vaccines on infection levels and virus transmission in Atlantic salmon (Salmo salar) challenged with salmonid alphavirus, genotype 2
Authors: Thorarinsson Ragnar , Ramstad Anne , Wolf Jeffrey C. , Sindre Hilde , Skjerve Eystein , Rimstad Espen , Evensen Øystein , Rodriguez Jose F.
Published: March 2024

Salmonid alphavirus (SAV) causes pancreas disease (PD), which negatively impacts farmed Atlantic salmon. In this study, fish were vaccinated with a DNA-PD vaccine (DNA-PD) and an oil-adjuvanted, inactivated whole virus PD vaccine (Oil-PD). Controls were two non-PD vaccinated groups. Fish were kept in one tank and challenged by cohabitation with SAV genotype 2 in seawater. Protection against infection and mortality was assessed for 84 days (Efficacy study). Nineteen days post challenge (dpc), subgroups of fish from all treatment groups were transferred to separate tanks and cohabited with naïve fish (Transmission study 1) or fish vaccinated with a homologous vaccine (Transmission study 2), to evaluate virus transmission for 26 days (47 dpc). Viremia, heart RT-qPCR and histopathological scoring of key organs affected by PD were used to measure infection levels. RT-droplet digital PCR quantified shedding of SAV into water for transmission studies. The Efficacy study showed that PD associated growth-loss was significantly lower and clearance of SAV2 RNA significantly higher in the PD-DNA group compared to the other groups. The PD-DNA group had milder lesions in the heart and muscle. Cumulative mortality post challenge was low and not different between groups, but the DNA-PD group had delayed time-to-death. In Transmission study 1, the lowest water levels of SAV RNA were measured in the tanks containing the DNA-PD group at 21 and 34 dpc. Despite this, and irrespective of the treatment group, SAV2 was effectively transmitted to the naïve fish during 26-day cohabitation. At 47 dpc, the SAV RNA concentrations in the water were lower in all tanks compared to 34 dpc. In Transmission study 2, none of the DNA-PD immunized cohabitants residing with DNA-PD-vaccinated, pre-challenged fish got infected. In contrast, Oil-PD immunized cohabitants residing with Oil-PD-vaccinated, pre-challenged fish, showed infection levels similar to the naïve cohabitants in Transmission study 1. The results demonstrate that the DNA-PD vaccine may curb the spread of SAV infection as the DNA-PD vaccinated, SAV2 exposed fish, did not spread the infection to cohabiting DNA-PD vaccinated fish. This signifies that herd immunity may be achieved by the DNA-PD vaccine, a valuable tool to control the PD epizootic in farmed Atlantic salmon.
An antigen-specific immunotherapeutic, AKS-107, deletes insulin-specific B cells and prevents murine autoimmune diabetes
Authors: Alleva David G. , Delpero Andrea R. , Sathiyaseelan Thillainaygam , Murikipudi Sylaja , Lancaster Thomas M. , Atkinson Mark A. , Wasserfall Clive H. , Yu Liping , Ragupathy Ramya , Bonami Rachel H. , Zion Todd C.
Published: March 2024

Introduction

The antigen-presenting cell function of insulin-reactive B cells promotes type 1 diabetes (T1D) in non-obese diabetic (NOD) mice by stimulating pathogenic T cells leading to destruction of insulin-producing β-cells of pancreatic islets.

Methods/Results

To target insulin-reactive B cells, AKS-107, a human IgG1 Fc molecule fused with human insulin A and B chains, was engineered to retain conformational insulin epitopes that bound mouse and human B cell receptors but prevented binding to the insulin metabolic receptor. AKS-107 Fc-mediated deletion of insulin-reactive B cells was demonstrated via ex vivo and in vivo experiments with insulin-reactive B cell receptor transgenic mouse strains, VH125Tg/NOD and Tg125(H+L)/NOD. As an additional immune tolerance feature, the Y16A mutation of the insulin B(9-23) dominant T cell epitope was engineered into AKS-107 to suppress activation of insulin-specific T cells. In mice and non-human primates, AKS-107 was well-tolerated, non-immunogenic, did not cause hypoglycemia even at high doses, and showed an expectedly protracted pharmacokinetic profile. AKS-107 reproducibly prevented spontaneous diabetes from developing in NOD and VH125Tg/NOD mice that persisted for months after cessation of treatment, demonstrating durable immune tolerance.

Discussion

These preclinical outcomes position AKS-107 for clinical development in T1D prevention settings.
Interactions between krill and its predators in the western Ross Sea
Authors: De Felice Andrea , Biagiotti Ilaria , Costantini Ilaria , Canduci Giovanni , Leonori Iole
Published: March 2024

Krill is a fundamental resource in the pelagic food web of the Ross Sea, constituting an important link between primary production and top predators. A series of Italian research voyages to the Ross Sea from 1994 to 2016 have contributed to our understanding of the dynamics of krill populations inhabiting the Ross Sea. Only the surveys in 1994 and 2004 reported information on krill’s predators through visual census data, and 2004 data were not object of publication until now. Analyzing Euphausia superba and Euphausia crystallorophias abundance spatial distribution in the study area in relation to the distribution of its key natural predators have shown a significant relationship between the spatial distribution of minke whales’ abundance and the density of E. superba biomass, indicating a classical predator-prey interaction. Moreover, krill biomass density data in the water column were analyzed together with the main environmental data from CTD samplings. The analysis of krill density data in relation to environmental factors throughout the water column revealed a significant relation between E. superba abundance and salinity, a result that may be linked to the presence of ice melting effects improving environment productivity conditions.
Overview of the population genetics and connectivity of sea turtles in the East Asia Region and their conservation implications
Authors: Ng Connie Ka Yan , Ishihara Takashi , Hamabata Tomoko , Nishizawa Hideaki , Liu Min , Song Jia-hao , Li Tsung Hsien , Fong Chia-Ling , Moon Dae Yeon , Kim Il Hun
Published: March 2024

Understanding the current status and recent development of the population genetics and connectivity of sea turtles is crucial for effective conservation management of the species. Five sea turtle species, green turtle (Chelonia mydas), loggerhead turtle (Caretta caretta), hawksbill turtle (Eretmochelys imbricata), olive ridley turtle (Lepidochelys olivacea) and leatherback turtle (Dermochelys coriacea), are recorded in the East Asia Region situated in the western side of the North Pacific Ocean. We compiled information from 35 published genetic studies on the five sea turtle species, with a focus on green turtle and loggerhead turtle, which are the most studied species (in 30 studies) in view of their commonness and occurrence of nesting populations. We provided an overview of the key methods and findings of these previous studies, addressing two main objectives on genetic structure of the rookeries and their differences compared to other populations, and connectivity of the rookeries and foraging aggregations. By identifying information gaps and conservation needs, we discussed future developments for sea turtle genetic studies and conservation implications in the region.
Behavior of functionally graded carbon nanotube reinforced composite sandwich beams with pultruded GFRP core under bending effect
Authors: Madenci Emrah , Özkılıç Yasin Onuralp , Bahrami Alireza , Hakeem Ibrahim Y. , Aksoylu Ceyhun , Asyraf Muhammad Rizal Muhammad , Beskopylny Alexey N. , Stel’makh Sergey A. , Shcherban’ Evgenii M. , Fayed Sabry
Published: March 2024

A novel generation of composite sandwich beams with laminated carbon fiber-reinforced polymer skins and pultruded glass fiber-reinforced polymer core materials was examined for their flexural behavior. The strength and failure mechanisms of the composite sandwich beams in flatwise and edgewise configurations were investigated using three-point static bending tests. These sophisticated composite structures must be designed and used in a variety of sectors, and our research provides vital insights into their performance and failure patterns. In comparison to the reference specimens (FGM-1), the carbon nanotube-reinforced specimens’ bending capacity was affected and ranged from −2.5% to 7.75%. The amount of the carbon nanotube addition had a substantial impact on the beams’ application level and load-carrying capacity. Particularly, the application of 0.5 wt% additive in the outermost fiber region of the beams, such as in FGM-4, led to an increase in the bending capacity. However, the stiffness values at the maximum load were decreased by 0.3%–18.6% compared to FGM-1, with the minimum level of the decrease in FGM-4. The experimental results were compared with the theoretical calculations based on the high-order shear deformation theory, which yielded an approximation between 11.99% and 12.98% by applying the Navier’s solution.
Integrated CFD-FEM approach for external gear pump vibroacoustic field prediction
Authors: Ferrari Cristian , Morselli Serena , Miccoli Giuseppe , Hamiche Karim
Published: March 2024

In this work, a three-dimensional fluid-structural and vibro-acoustics coupled model of a gear pump is presented. Gear pumps represent the majority of the positive displacement machines used for flow generation in fluid power systems. Typically, the dynamics of gear pumps are dependent on the characteristics of the fluid dynamics inside the pump, which translates into vibrations to the housing. These vibrations then propagate to the surrounding medium and emit sound. The purpose of this study is to propose a three-dimensional fully integrated computational model to simulate the complete gear pump behaviour from the fluid dynamics to the structural vibrations, up to the vibroacoustic response. In this hybrid configuration, a transient CFD (Computational Fluid Dynamics) model is first developed to simulate the 3D flow field with a deforming and re-meshing approach to take into account the variation of the volume between the gears. Second, the internal pressure field calculated at each time step is then used as a loading into a structural FEM (Finite Element Method) model of the gear pump to compute the actual stresses and deformations of the housing. Third, the results of the structural response are used as excitation in a vibroacoustic sub-model to simulate the radiated noise using a high-order FEM technique. The comparison between the numerical and experimental flow curves validates the CFD model. The sound power calculations from the vibroacoustic model show good comparison with the sound intensity measurements around the pump casing, confirming the validity of the proposed coupled model. The described CFD-FEM approach proves to be a powerful gear pump design tool: it provides a reliable estimate of gear pump working parameters such as fluid power and vibroacoustic characteristics, starting from the CAD (Computer-Aided Design) geometry of the components. Furthermore, being one of the first multi-domain simulation models of a gear pump, this work can be useful to researchers as a starting point to correlate the noise emitted with the internal flow in full 3D conditions.
Insights into the diversity and survival strategies of soil bacterial isolates from the Atacama Desert
Authors: Reverdy Alicyn , Hathaway Daniel , Jha Jessica , Michaels Gabriel , Sullivan Jeffrey , McAdoo Daniela Diaz , Riquelme Carlos , Chai Yunrong , Godoy-Carter Veronica
Published: March 2024

The Atacama Desert, the driest, with the highest radiation, and one of the most ancient deserts in the world, is a hostile environment for life. We have a collection of 74 unique bacterial isolates after cultivation and confirmation by 16S rRNA gene sequencing. Pigmentation, biofilm formation, antimicrobial production against Escherichia coli MG1655 and Staphylococcus aureus HG003, and antibiotic resistance were assessed on these isolates. We found that approximately a third of the colonies produced pigments, 80% of isolates formed biofilms, many isolates produce growth inhibiting activities against E. coli and/or S. aureus, and many were resistant to antibiotics. The functional characterization of these isolates gives us insight into the adaptive bacterial strategies in harsh environments and enables us to learn about their possible use in agriculture, healthcare, or biotechnology.
Characteristics of intestinal microbiota in preterm infants and the effects of probiotic supplementation on the microbiota
Authors: Yang Sen , He Jing , Shi Jing , Xie Liang , Liu Yang , Xiong Ying , Liu Hanmin
Published: March 2024

Objective

In this study, we investigated the characteristics of the intestinal microbiota of preterm infants, and then analyzed the effects of probiotics supplementation on intestinal microbiota in preterm infants.

Methods

This study enrolled 64 infants born between 26 and 32 weeks gestational age (GA) and 22 full-term infants. 34 premature infants received oral probiotic supplementation for 28 days. Stool samples were obtained on the first day (D1) and the 28th day (D28) after birth for each infant. Total bacterial DNA was extracted and sequenced using the Illumina MiSeq Sequencing System, specifically targeting the V3-V4 hyper-variable regions of the 16S rDNA gene. The sequencing results were then used to compare and analyze the composition and diversity index of the intestinal microbiota.

Results

There was no significant difference in meconium bacterial colonization rate between premature and full-term infants after birth (p > 0.05). At D1, the relative abundance of Bifidobacterium, Bacteroides, and Lactobacillus in the stool of preterm infants was lower than that of full-term infants, and the relative abundance of Acinetobacter was higher than that of full-term infants. The Shannon index and Chao1 index of intestinal microbiota in preterm infants are lower than those in full-term infants (p < 0.05). Supplementation of probiotics can increase the relative abundance of Enterococcus and Enterobacter, and reduce the relative abundance of Escherichia and Clostridium in premature infants. The Chao1 index of intestinal microbiota decreased in preterm infants after probiotic supplementation (p < 0.05).

Conclusion

The characteristics of intestinal microbiota in preterm infants differ from those in full-term infants. Probiotic supplementation can reduce the relative abundance of potential pathogenic bacteria and increase the abundance of beneficial microbiota in premature infants.
A GC–MS-based untargeted metabolomics approach for comprehensive metabolic profiling of mycophenolate mofetil-induced toxicity in mice
Authors: Zhao Tongfeng , Zhao Yaxin , Chen Haotian , Sun Wenxue , Guan Yun
Published: March 2024

Background: Mycophenolate mofetil (MMF), the morpholinoethyl ester of mycophenolic acid, is widely used for maintenance immunosuppression in transplantation. The gastrointestinal toxicity of MMF has been widely uncovered. However, the comprehensive metabolic analysis of MMF-induced toxicity is lacking. This study is aimed to ascertain the metabolic changes after MMF administration in mice.

Methods: A total of 700 mg MMF was dissolved in 7 mL dimethyl sulfoxide (DMSO), and then 0.5 mL of mixture was diluted with 4.5 mL of saline (100 mg/kg). Mice in the treatment group (n = 9) were given MMF (0.1 mL/10 g) each day via intraperitoneal injection lasting for 2 weeks, while those in the control group (n = 9) received the same amount of blank solvent (DMSO: saline = 1:9). Gas chromatography-mass spectrometry was utilized to identify the metabolic profiling in serum samples and multiple organ tissues of mice. The potential metabolites were identified using orthogonal partial least squares discrimination analysis. Meanwhile, we used the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (http://www.kegg.jp) to depict the metabolic pathways. The percentages of lymphocytes in spleens were assessed by multiparameter flow cytometry analysis.

Results: Compared to the control group, we observed that MMF treatment induced differential expression of metabolites in the intestine, hippocampus, lung, liver, kidney, heart, serum, and cortex tissues. Subsequently, we demonstrated that multiple amino acids metabolism and fatty acids biosynthesis were disrupted following MMF treatment. Additionally, MMF challenge dramatically increased CD4+ T cell percentages but had no significant influences on other types of lymphocytes.

Conclusion: MMF can affect the metabolism in various organs and serum in mice. These data may provide preliminary judgement for MMF-induced toxicity and understand the metabolic mechanism of MMF more comprehensively.
Transfer of membrane(s) matter(s)—non-genetic inheritance of (metabolic) phenotypes?
Authors: Müller Günter A. , Müller Timo D.
Published: March 2024

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) are anchored at the outer phospholipid layer of eukaryotic plasma membranes exclusively by a glycolipid. GPI-APs are not only released into extracellular compartments by lipolytic cleavage. In addition, certain GPI-APs with the glycosylphosphatidylinositol anchor including their fatty acids remaining coupled to the carboxy-terminus of their protein components are also detectable in body fluids, in response to certain stimuli, such as oxidative stress, radicals or high-fat diet. As a consequence, the fatty acid moieties of GPI-APs must be shielded from access of the aqueous environment by incorporation into membranes of extracellular vesicles or into micelle-like complexes together with (lyso)phospholipids and cholesterol. The GPI-APs released from somatic cells and tissues are transferred via those complexes or EVs to somatic as well as pluripotent stem cells with metabolic consequences, such as upregulation of glycogen and lipid synthesis. From these and additional findings, the following hypotheses are developed: i) Transfer of GPI-APs via EVs or micelle-like complexes leads to the induction of new phenotypes in the daughter cells or zygotes, which are presumably not restricted to metabolism. ii) The membrane topographies transferred by the concerted action of GPI-APs and interacting components are replicated by self-organization and self-templation and remain accessible to structural changes by environmental factors. iii) Transfer from mother cells and gametes to their daughter cells and zygotes, respectively, is not restricted to DNA and genes, but also encompasses non-genetic matter, such as GPI-APs and specific membrane constituents. iv) The intergenerational transfer of membrane matter between mammalian organisms is understood as an epigenetic mechanism for phenotypic plasticity, which does not rely on modifications of DNA and histones, but is regarded as molecular mechanism for the inheritance of acquired traits, such as complex metabolic diseases. v) The missing interest in research of non-genetic matter of inheritance, which may be interpreted in the sense of Darwin’s “Gemmules” or Galton’s “Stirps”, should be addressed in future investigations of the philosophy of science and sociology of media.
Illumination of understudied ciliary kinases
Authors: Flax Raymond G. , Rosston Peter , Rocha Cecilia , Anderson Brian , Capener Jacob L. , Durcan Thomas M. , Drewry David H. , Prinos Panagiotis , Axtman Alison D.
Published: March 2024

Cilia are cellular signaling hubs. Given that human kinases are central regulators of signaling, it is not surprising that kinases are key players in cilia biology. In fact, many kinases modulate ciliogenesis, which is the generation of cilia, and distinct ciliary pathways. Several of these kinases are understudied with few publications dedicated to the interrogation of their function. Recent efforts to develop chemical probes for members of the cyclin-dependent kinase like (CDKL), never in mitosis gene A (NIMA) related kinase (NEK), and tau tubulin kinase (TTBK) families either have delivered or are working toward delivery of high-quality chemical tools to characterize the roles that specific kinases play in ciliary processes. A better understanding of ciliary kinases may shed light on whether modulation of these targets will slow or halt disease onset or progression. For example, both understudied human kinases and some that are more well-studied play important ciliary roles in neurons and have been implicated in neurodevelopmental, neurodegenerative, and other neurological diseases. Similarly, subsets of human ciliary kinases are associated with cancer and oncological pathways. Finally, a group of genetic disorders characterized by defects in cilia called ciliopathies have associated gene mutations that impact kinase activity and function. This review highlights both progress related to the understanding of ciliary kinases as well as in chemical inhibitor development for a subset of these kinases. We emphasize known roles of ciliary kinases in diseases of the brain and malignancies and focus on a subset of poorly characterized kinases that regulate ciliary biology.
The underlying mechanisms of arenaviral entry through matriglycan
Authors: Katz Michael , Diskin Ron
Published: March 2024

Matriglycan, a recently characterized linear polysaccharide, is composed of alternating xylose and glucuronic acid subunits bound to the ubiquitously expressed protein α-dystroglycan (α-DG). Pathogenic arenaviruses, like the Lassa virus (LASV), hijack this long linear polysaccharide to gain cellular entry. Until recently, it was unclear through what mechanisms LASV engages its matriglycan receptor to initiate infection. Additionally, how matriglycan is synthesized onto α-DG by the Golgi-resident glycosyltransferase LARGE1 remained enigmatic. Recent structural data for LARGE1 and for the LASV spike complex informs us about the synthesis of matriglycan as well as its usage as an entry receptor by arenaviruses. In this review, we discuss structural insights into the system of matriglycan generation and eventual recognition by pathogenic viruses. We also highlight the unique usage of matriglycan as a high-affinity host receptor compared with other polysaccharides that decorate cells.
Fear of disease in patients with epilepsy – a network analysis
Authors: Yin Xiaoxiao , Niu Shan , Yu Qun , Xuan Yejing , Feng Xiuqin
Published: March 2024

Background

Disease-related fear among patients with epilepsy has significantly impacted their quality of life. The Disease-Related Fear Scale (D-RFS), comprising three dimensions, serves as a relatively well-established tool for assessing fear in these patients. However, certain problems potentially exist within the D-RFS’s attribution of items, and its internal structure is still unclear. To establish an appropriate dimensional structure and gain deeper comprehension of its internal structure—particularly its core variables—is vital for developing more effective interventions aimed at alleviating disease-related fear among patients with epilepsy.

Methods

This study employed a cross-sectional survey involving 609 patients with epilepsy. All participants underwent assessment using the Chinese version of the D-RFS. We used exploratory network analysis to discover a new structure and network analysis to investigate the interrelationships among fear symptom domains. In addition to the regularized partial correlation network, we also estimated the node and bridge centrality index to identify the importance of each item within the network. Finally, it was applied to analyze the differences in network analysis outcomes among epilepsy patients with different seizure frequencies.

Results

The research findings indicate that nodes within the network of disease-related fear symptoms are interconnected, and there are no isolated nodes. Nodes within groups 3 and 4 present the strongest centrality. Additionally, a tight interconnection exists among fear symptoms within each group. Moreover, the frequency of epileptic episodes does not significantly impact the network structure.

Conclusion

In this study, a new 5-dimension structure was constructed for D-RFS, and the fear of disease in patients with epilepsy has been conceptualized through a network perspective. The goal is to identify potential targets for relevant interventions and gain insights for future research.
Eptinezumab for the preventive treatment of episodic and chronic migraine: a narrative review
Authors: Irimia Pablo , Santos-Lasaosa Sonia , Pozo-Rosich Patricia , Leira Rogelio , Pascual Julio , Láinez José Miguel
Published: March 2024

Eptinezumab, a monoclonal antibody that targets calcitonin gene-related peptide (CGRP), was recently approved in Europe for the prophylactic treatment of migraine in adults who have at least four migraine days a month. Eptinezumab is administered by intravenous infusion every 12 weeks. During recent months, a considerable amount of evidence from eptinezumab trials has been published. The aim of this review is to describe the existing evidence on the tolerability, safety and efficacy of eptinezumab in patients with migraine. Data from randomized (PROMISE-1, PROMISE-2, RELIEF and DELIVER) and open-label (PREVAIL) phase 3 clinical trials have demonstrated the favorable effect of eptinezumab in migraine symptoms from first day of treatment. These studies showed that eptinezumab results in an overall reduction in mean monthly migraine days (MMDs), increases in the ≥50% and ≥ 75% migraine responder rates (MRRs) and improvements in patient-reported outcome measures in both patients with episodic migraine (EM) and with chronic migraine (CM), including patients who failed previous preventive treatments. The RELIEF trial also showed that eptinezumab, within 2 h of administration, reduced headache pain, migraine-associated symptoms and acute medication use when administered during a migraine attack. Eptinezumab benefits manifested as early as day 1 after dosing and with the subsequent doses lasted up to at least 2 years. Treatment-emergent adverse events reported by ≥2% of patients included upper respiratory tract infection and fatigue. Current evidence demonstrates that eptinezumab has a potent, fast-acting, sustained migraine preventive effect in patients with EM and CM. Eptinezumab has also shown to be well tolerated, supporting its use in the treatment of patients with migraine and inclusion in the current migraine therapeutic options.
Correlation of telomere length in brain tissue with peripheral tissues in living human subjects
Authors: Carver Annemarie J. , Hing Benjamin , Elser Benjamin A. , Lussier Stephanie J. , Yamanashi Takehiko , Howard Matthew A. , Kawasaki Hiroto , Shinozaki Gen , Stevens Hanna E.
Published: March 2024

Telomeres are important to chromosomal stability, and changes in their length correlate with disease, potentially relevant to brain disorders. Assessing telomere length in human brain is invasive, but whether peripheral tissue telomere length correlates with that in brain is not known. Saliva, buccal, blood, and brain samples were collected at time points before, during, and after subjects undergoing neurosurgery (n = 35) for intractable epilepsy. DNA was isolated from samples and average telomere length assessed by qPCR. Correlations of telomere length between tissue samples were calculated across subjects. When data were stratified by sex, saliva telomere length correlated with brain telomere length in males only. Buccal telomere length correlated with brain telomere length when males and females were combined. These findings indicate that in living subjects, telomere length in peripheral tissues variably correlates with that in brain and may be dependent on sex. Peripheral tissue telomere length may provide insight into brain telomere length, relevant to assessment of brain disorder pathophysiology.
Post-translational modifications of beta-amyloid alter its transport in the blood-brain barrier in vitro model
Authors: Varshavskaya Kseniya B. , Petrushanko Irina Yu , Mitkevich Vladimir A. , Barykin Evgeny P. , Makarov Alexander A.
Published: March 2024

One of the hallmarks of Alzheimer's disease (AD) is the accumulation of beta-amyloid peptide (Aβ) leading to formation of soluble neurotoxic Aβ oligomers and insoluble amyloid plaques in various parts of the brain. Aβ undergoes post-translational modifications that alter its pathogenic properties. Aβ is produced not only in brain, but also in the peripheral tissues. Such Aβ, including its post-translationally modified forms, can enter the brain from circulation by binding to RAGE and contribute to the pathology of AD. However, the transport of modified forms of Aβ across the blood–brain barrier (BBB) has not been investigated. Here, we used a transwell BBB model as a controlled environment for permeability studies. We found that Aβ42 containing isomerized Asp7 residue (iso-Aβ42) and Aβ42 containing phosphorylated Ser8 residue (pS8-Aβ42) crossed the BBB better than unmodified Aβ42, which correlated with different contribution of endocytosis mechanisms to the transport of these isoforms. Using microscale thermophoresis, we observed that RAGE binds to iso-Aβ42 an order of magnitude weaker than to Aβ42. Thus, post-translational modifications of Aβ increase the rate of its transport across the BBB and modify the mechanisms of the transport, which may be important for AD pathology and treatment.
Extracellular vesicles derived from SARS-CoV-2 M-protein-induced triple negative breast cancer cells promoted the ability of tissue stem cells supporting cancer progression
Authors: Nguyen Hoai-Nga Thi , Vuong Cat-Khanh , Fukushige Mizuho , Usuda Momoko , Takagi Liora Kaho , Yamashita Toshiharu , Obata-Yasuoka Mana , Hamada Hiromi , Osaka Motoo , Tsukada Toru , Hiramatsu Yuji , Ohneda Osamu
Published: March 2024

Introduction

SARS-CoV-2 infection increases the risk of worse outcomes in cancer patients, including those with breast cancer. Our previous study reported that the SARS-CoV-2 membrane protein (M-protein) promotes the malignant transformation of triple-negative breast cancer cells (triple-negative BCC).

Methods

In the present study, the effects of M-protein on the ability of extracellular vesicles (EV) derived from triple-negative BCC to regulate the functions of tissue stem cells facilitating the tumor microenvironment were examined.

Results

Our results showed that EV derived from M-protein-induced triple-negative BCC (MpEV) significantly induced the paracrine effects of adipose tissue-derived mesenchymal stem cells (ATMSC) on non-aggressive BCC, promoting the migration, stemness phenotypes, and in vivo metastasis of BCC, which is related to PGE2/IL1 signaling pathways, in comparison to EV derived from normal triple-negative BCC (nEV). In addition to ATMSC, the effects of MpEV on endothelial progenitor cells (EPC), another type of tissue stem cells, were examined. Our data suggested that EPC uptaking MpEV acquired a tumor endothelial cell-like phenotype, with increasing angiogenesis and the ability to support the aggressiveness and metastasis of non-aggressive BCC.

Discussion

Taken together, our findings suggest the role of SARS-CoV-2 M-protein in altering the cellular communication between cancer cells and other non-cancer cells inside the tumor microenvironment via EV. Specifically, M-proteins induced the ability of EV derived from triple-negative BCC to promote the functions of non-cancer cells, such as tissue stem cells, in tumorigenesis.
The histologic features, molecular features, detection and management of serrated polyps: a review
Authors: Wang Jin-Dong , Xu Guo-Shuai , Hu Xin-Long , Li Wen-Qiang , Yao Nan , Han Fu-Zhou , Zhang Yin , Qu Jun
Published: March 2024

The serrated pathway to colorectal cancers (CRCs) is a significant pathway encompassing five distinct types of lesions, namely hyperplastic polyps (HPs), sessile serrated lesions (SSLs), sessile serrated lesions with dysplasia (SSL-Ds), traditional serrated adenomas (TSAs), and serrated adenoma unclassified. In contrast to the conventional adenoma–carcinoma pathway, the serrated pathway primarily involves two mechanisms: BRAF/KRAS mutations and CpG island methylator phenotype (CIMP). HPs are the most prevalent non-malignant lesions, while SSLs play a crucial role as precursors to CRCs, On the other hand, traditional serrated adenomas (TSAs) are the least frequently encountered subtype, also serving as precursors to CRCs. It is crucial to differentiate these lesions based on their unique morphological characteristics observed in histology and colonoscopy, as the identification and management of these serrated lesions significantly impact colorectal cancer screening programs. The management of these lesions necessitates the crucial steps of removing premalignant lesions and implementing regular surveillance. This article provides a comprehensive summary of the epidemiology, histologic features, molecular features, and detection methods for various serrated polyps, along with recommendations for their management and surveillance.