bluuebunny/crossref_metadata_2025 huggingface dataset:
The association between pregnancy outcomes and frozen-thawed embryo transfer cycles based on D3 cell count in high-quality blastocysts
Authors: Li Xiang , Zeng Youman , Zhu Lingling , Yang Zengyu , Luo Yudi , Jia Jun-Long
Published: October 2024

Objective

To investigate the number of cells in D3-stage embryos of high-quality blastocysts as a contributing factor, to evaluate the clinical pregnancy outcomes in frozen-thawed embryo transfer cycles, and to determine the impact of D3-stage cell count on pregnancy outcomes.

Methods

Patients under 38 years old who underwent frozen-thawed single high-quality blastocyst transfer at our center were selected. Based on the cell count of D3 cleavage-stage embryos forming blastocysts, patients were divided into three groups: ≤6 cells, 7-9 cells, and ≥10 cells. A multivariate regression analysis was used to establish the prediction model, analyzing the impact of different D3 cleavage-stage cell counts on clinical pregnancy outcomes to guide clinical laboratories in selecting blastocysts with the best pregnancy outcomes for transfer.

Results

This study identified a significant association between D3 cell count, blastocyst development stage, and embryo age. Embryos with a higher D3 cell count (≥10) were more likely to reach advanced blastocyst stages and form blastocysts by D5, whereas embryos with fewer D3 cells (≤6) were more likely to form blastocysts on D6. While D3 cell count significantly influenced blastocyst stage and timing of embryo development, no significant differences were observed between groups regarding clinical pregnancy, implantation, or live birth rates. Notably, embryos with fewer D3 cells exhibited a significantly lower miscarriage rate than other groups. Multivariate regression analysis showed a significant correlation between blastocyst stage, embryo age, and D3 cell count, particularly in D5 embryos and more advanced blastocysts. The increased miscarriage rate may be related to lower D3 cell count, and inadequate endometrial preparation was associated with poorer pregnancy outcomes. The type of infertility was also linked to D3 cell count, with secondary infertility patients showing more significant influencing factors.

Conclusion

D3 cell count and related factors play a critical role in pregnancy outcomes during frozen-thawed high-quality blastocyst transfer cycles. Optimizing embryo age, selecting blastocysts at different stages, and refining endometrial preparation protocols are likely to enhance clinical pregnancy and live birth rates.
Mixed comparison of different exercise interventions on physical functioning in adult patients with morbid obesity following bariatric surgery: a systematic review and network meta-analysis
Authors: Hu Chen , Sun Dong , Fang Yufei , Cen Xuanzhen , Xu Yining , Baker Julien S. , Gu Yaodong
Published: October 2024

Introduction

People who are overweight following bariatric surgery (BS) often need physical exercise to help with body function. However, it is not known which exercise interventions are more effective in improving physical function.

Methods

PubMed, Web of Science, Embase, and Cochrane Library databases were systematically searched for randomized controlled trials evaluating the effects of different exercise interventions on physical function in patients with excessive obesity following bariatric surgery. Outcome measures included effect sizes for physical function (PF), expressed as the number of stand-sit passes or the maximum distance walked within a time limit, body mass index (BMI), and blood pressure (BP). A systematic review was conducted to screen and synthesize the included studies, followed by a network meta-analysis for quantitative data analysis.

Results

A total of 15 studies involving 1011 patients were included. For PF, telehealth core exercise had the highest probability (0.46) of being the most effective intervention. For BMI, nutritional behavior and guided exercise, intervention had the highest probability (0.27) of being the most effective. Regarding BP, exercise prescription had the highest probability (0.47) for improving systolic blood pressure, while aerobic and strength and flexibility training had the highest probability (0.6) for improving diastolic blood pressure.

Discussion

Telehealth core exercise may be the most effective intervention for enhancing PF in overweight patients after bariatric surgery. Changes in BMI and BP with different postoperative exercise interventions may depend more on the surgery itself than the exercise modality. More specifically designed RCTs are needed for reliable conclusions.

Systematic review registration

https://www.crd.york.ac.uk/prospero, identifier CRD42024507209.
Analysis on the relationship among green finance, government environmental governance and green economic efficiency: evidence from China
Authors: Wu Yangyulong
Published: October 2024

Investigating the relationship between green finance (GF), government environmental governance (GEG), and green economic efficiency (GEE) is essential for developing sustainable development policies. This study uses panel data from 30 provincial administrative regions in China, covering the period from 2011 to 2021, to assess the effects of GF and GEG on GEE through the Spatial Durbin Model. The findings reveal several key points. First, most provinces are in low-low spatial clusters in terms of GEE, though there is a gradual improvement over time. Second, GF significantly enhances GEE, while GEG has a notable inhibitory effect. Third, GF exhibits a positive spatial spillover effect on the GEE of neighboring regions, whereas GEG shows a negative spatial spillover effect. Fourth, these spillover effects are mainly observed in the eastern regions, with little significance in the central and western areas. Moreover, one of the GEG indicators, environmental regulation, demonstrates a positive spatial spillover effect in the eastern region, contrary to the overall negative national trend. In general, this paper examines the interplay among the three variables within a unified analytical framework, filling the gaps in existing research. Furthermore, the paper delineates GEG into environmental regulation and environmental investment, which is a dimension frequently neglected in current research.
Integrated temporal transcriptional and epigenetic single-cell analysis reveals the intrarenal immune characteristics in an early-stage model of IgA nephropathy during its acute injury
Authors: Xu Chen , Zhang Yiwei , Zhou Jian , Zhang Jiangnan , Dong Hui , Chen Xiangmei , Tian Yi , Wu Yuzhang
Published: October 2024

Rationale

Kidney inflammation plays a crucial role in the pathogenesis of IgA nephropathy (IgAN), yet the specific phenotypes of immune cells involved in disease progression remain incompletely understood. Utilizing joint profiling through longitudinal single-cell RNA-sequencing (scRNAseq) and single-cell assay for transposase-accessible chromatin sequencing (scATACseq) can provide a comprehensive framework for elucidating the development of cell subset diversity and how chromatin accessibility regulates transcription.

Objective

We aimed to characterize the dynamic immune cellular landscape at a high resolution in an early IgAN mouse model with acute kidney injury (AKI).

Methods and results

A murine model was utilized to mimic 3 immunological states –”immune stability (IS), immune activation (IA) and immune remission (IR)” in early human IgAN-associated glomerulopathy during AKI, achieved through lipopolysaccharide (LPS) injection. Urinary albumin to creatinine ratio (UACR) was measured to further validate the exacerbation and resolution of kidney inflammation during this course. Paired scRNAseq and scATACseq analysis was performed on CD45+ immune cells isolated from kidney tissues obtained from CTRL (healthy vehicle), IS, IA and IR (4 or 5 mice each). The analyses revealed 7 major cell types and 24 clusters based on 72304 single-cell transcriptomes, allowing for the identification and characterization of various immune cell types within each cluster. Our data offer an impartial depiction of the immunological characteristics, as the proportions of immune cell types fluctuated throughout different stages of the disease. Specifically, these analyses also revealed novel subpopulations, such as a macrophage subset (Nlrp1b Mac) with distinct epigenetic features and a unique transcription factor motif profile, potentially exerting immunoregulatory effects, as well as an early subset of Tex distinguished by their effector and cytolytic potential (CX3CR1-transTeff). Furthermore, in order to investigate the potential interaction between immune cells and renal resident cells, we conducted single-cell RNA sequencing on kidney cells obtained from a separate cohort of IS and IA mice without isolating immune cells. These findings underscored the diverse roles played by macrophages and CD8+ T cells in maintaining homeostasis of endothelial cells (ECs) under stress.

Conclusions

This study presents a comprehensive analysis of the dynamic changes in immune cell profiles in a model of IgAN, identifying key cell types and their roles and interactions. These findings significantly contribute to the understanding of the pathogenesis of IgAN and may provide potential targets for therapeutic intervention.
Polymorphic positions 349 and 725 of the autoimmunity-protective allotype 10 of ER aminopeptidase 1 are key in determining its unique enzymatic properties
Authors: Georgaki Galateia , Mpakali Anastasia , Trakada Myrto , Papakyriakou Athanasios , Stratikos Efstratios
Published: October 2024

Introduction

ER aminopeptidase 1 (ERAP1) is a polymorphic intracellular aminopeptidase with key roles in antigen presentation and adaptive immune responses. ERAP1 allotype 10 is highly protective toward developing some forms of autoimmunity and displays unusual functional properties, including very low activity versus some substrates.

Methods

To understand the molecular mechanisms that underlie the biology of allotype 10, we studied its enzymatic and biophysical properties focusing on its unique polymorphisms V349M and Q725R.

Results

Compared to ancestral allotype 1, allotype 10 is much less effective in trimming small substrates but presents allosteric kinetics that ameliorate activity differences at high substrate concentrations. Furthermore, it is inhibited by a transition-state analogue via a non-competitive mechanism and is much less responsive to an allosteric small-molecule modulator. It also presents opposite enthalpy, entropy, and heat capacity of activation compared to allotype 1, and its catalytic rate is highly dependent on viscosity. Polymorphisms V349M and Q725R significantly contribute to the lower enzymatic activity of allotype 10 for small substrates, especially at high substrate concentrations, influence the cooperation between the regulatory and active sites, and regulate viscosity dependence, likely by limiting product release.

Conclusions

Overall, our results suggest that allotype 10 is not just an inactive variant of ERAP1 but rather carries distinct enzymatic properties that largely stem from changes at positions 349 and 725. These changes affect kinetic and thermodynamic parameters that likely control rate-limiting steps in the catalytic cycle, resulting in an enzyme optimized for sparing small substrates and contributing to the homeostasis of antigenic epitopes in the ER.
Serum and mucosal antibody-mediated protection and identification of asymptomatic respiratory syncytial virus infection in community-dwelling older adults in Europe
Authors: Öner Deniz , Vernhes Charlotte , Balla-Jhagjhoorsingh Sunita , Moureau Annick , Crabbe Marjolein , Salaun Bruno , Bastian Arangassery Rosemary , Thys Kim , De Smedt Jonathan , Ooft Salo N. , Korsten Koos , Adriaenssens Niels , Coenen Samuel , Butler Christopher C. , Verheij Theo J. M. , Drysdale Simon B. , Wildenbeest Joanne G. , Pollard Andrew J. , Openshaw Peter J. M. , Bont Louis , Aerssens Jeroen
Published: October 2024

Introduction

Respiratory syncytial virus (RSV) causes acute respiratory tract infection (ARTI) and reinfects adults throughout life, posing a risk for hospitalization in older adults (>60 years) with frailty and comorbidities.

Methods

To investigate serum and mucosal antibodies for protection against RSV infections, baseline serum samples were compared for RSV-pre- and -post-fusion (F) binding, and RSV-A2 neutralizing IgG antibodies between symptomatic RSV-ARTI (N = 30), non-RSV (RSV negative) ARTI (N = 386), and no ARTI (N = 338). Mucosal RSV-pre-F IgA and IgG levels, as well as serum RSV-G IgG antibodies, were analyzed to determine their association with protection from symptomatic RSV-ARTI in a subset study.

Results

Using a receiver operating characteristic (ROC) analysis, we established thresholds of 1.4- to 1.6-fold change (FC) for RSV-pre-F and -post-F, and RSV-A2 neutralizing IgG antibodies, respectively, enabling the identification of asymptomatic RSV cases with high sensitivity and specificity (>80% and >90%, respectively). As a result, serum RSV-pre-F, RSV-G IgG, and mucosal pre-F binding IgA antibodies showed correlations with protection against symptomatic RSV infection. RSV-pre-F IgG antibodies were correlated with protection from RSV infections irrespective of the symptoms.

Discussion

This study provides insights into antibody-mediated protection for symptomatic RSV infection in a community-dwelling older-adult population and establishes a threshold to identify asymptomatic RSV infection using a data-driven approach.
Proteomic profiling of neutrophils and plasma in community-acquired pneumonia reveals crucial proteins in diverse biological pathways linked to clinical outcome
Authors: Michels Erik H. A. , Chouchane Osoul , de Brabander Justin , de Vos Alex F. , Faber Daniël R. , Douma Renée A. , Smit Eva R. , Wiersinga W. Joost , Biggelaar Maartje van den , Poll Tom van der , Hoogendijk Arie J.
Published: October 2024

Introduction

Neutrophils play a dichotomous role in community-acquired pneumonia (CAP), providing protection and potentially causing damage. Existing research on neutrophil function in CAP relies on animal studies, leaving a gap in patient-centered investigations.

Methods

We used mass spectrometry to characterize the neutrophil proteome of moderately ill CAP patients at general ward admission and related the proteome to controls and clinical outcomes.

Results

We prospectively included 57 CAP patients and 26 controls and quantified 3482 proteins in neutrophil lysates and 386 proteins in concurrently collected plasma. The extensively studied granule-related proteins in animal models did not drive the neutrophil proteome changes associated with human CAP. Proteome alterations were primarily characterized by an increased abundance of proteins related to (aerobic) metabolic activity and (m)RNA translation/processing, concurrent with a diminished presence of cytoskeletal organization-related proteins (all pathways p<0.001). Higher and lower abundances of specific proteins, primarily constituents of these pathways, were associated with prolonged time to clinical stability in CAP. Moreover, we identified a pronounced presence of platelet-related proteins in neutrophil lysates of particularly viral CAP patients, suggesting the existence of neutrophil-platelet complexes in non-critically ill CAP patients. Of the proteins measured in neutrophils, 4.3% were detected in plasma.

Discussion

Our study presents new perspectives on the neutrophil proteome associated with CAP, laying the groundwork for forthcoming patient-centred investigations. Our results could pave the way for targeted strategies to fine-tune neutrophil responses, potentially improving CAP outcomes.
NF-κB signaling pathway in tumor microenvironment
Authors: Cao Yaning , Yi Yanan , Han Chongxu , Shi Bingwei
Published: October 2024

The genesis and progression of tumors are multifaceted processes influenced by genetic mutations within the tumor cells and the dynamic interplay with their surrounding milieu, which incessantly impacts the course of cancer. The tumor microenvironment (TME) is a complex and dynamic entity that encompasses not only the tumor cells but also an array of non-cancerous cells, signaling molecules, and the extracellular matrix. This intricate network is crucial in tumor progression, metastasis, and response to treatments. The TME is populated by diverse cell types, including immune cells, fibroblasts, endothelial cells, alongside cytokines and growth factors, all of which play roles in either suppressing or fostering tumor growth. Grasping the nuances of the interactions within the TME is vital for the advancement of targeted cancer therapies. Consequently, a thorough understanding of the alterations of TME and the identification of upstream regulatory targets have emerged as a research priority. NF-κB transcription factors, central to inflammation and innate immunity, are increasingly recognized for their significant role in cancer onset and progression. This review emphasizes the crucial influence of the NF-κB signaling pathway within the TME, underscoring its roles in the development and advancement of cancer. By examining the interactions between NF-κB and various components of the TME, targeting the NF-κB pathway appears as a promising cancer treatment approach.
Exploring the mechanism of action of Modified Simiao Powder in the treatment of osteoarthritis: an in-silico study
Authors: Xu Zhouhengte , Su Pingping , Zhou Xiahui , Zheng Zhihui , Zhu Yibo , Wang Qinglai
Published: October 2024

Introduction

Osteoarthritis (OA) is the most common form of arthritis and the leading musculoskeletal disorders in adults. Modified Simiao Powder (MSMP) has been widely used in the treatment of OA with remarkable clinical ecaciousness.

Objective

This study aimed to elucidate underlying mechanisms of MSMP in OA by employing network pharmacology, molecular docking, and molecular dynamics simulations, due to the unclear mode of action.

Methods

Bioinformatic analysis was used to evaluate the major chemical constituents of MSMP, determine prospective target genes, and screen genes associated with OA. Network pharmacology methods were then applied to identify the crucial target genes of MSMP in OA treatment. Further analyses included gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. These key targets within the pertinent pathways was further confirmed by molecular docking, binding energy evaluation, and molecular dynamics simulations.

Results

Network pharmacology analysis identified an MSMP component–target–pathway network comprising 11 central active compounds, 25 gene targets, and 12 biological pathways.

Discussion

These findings imply that the therapeutic effects of MSMP was potentially mediated by targeting several pivotal genes, such as androgen receptor (AR), NFKB1, AKT1, MAPK1, and CASP3, and regulating some pathways, including lipid metabolism and atherosclerosis, the AGE–RAGE signaling pathway in diabetic complications, the PI3K–Akt signaling pathway, fluid shear stress, atherosclerosis, and Kaposi's sarcoma-associated herpesvirus infection. Molecular docking assessments demonstrated that these compounds of MSMP, such as berberine, kaempferol, quercetin, and luteolin, exhibit high binding anities to AR and AKT1. Molecular dynamics simulations validated the interactions between these compounds and targets.

Conclusion

The therapeutic effect of MSMP likely attributed to the modulation of multiple pathways, including lipid metabolism, atherosclerosis, the AGE-RAGE signaling pathway, and the PI3K-Akt signaling pathway, by the active components such as berberine, kaempferol, luteolin, and quercetin. Especially, their actions on target genes like AR and AKT1 contribute to the therapeutic benefits of MSMP observed in the treatment of OA.
Effects of peer-led education on knowledge, attitudes, practices of stoma care, and quality of life in bladder cancer patients after permanent ostomy
Authors: Ding Juan-Ying , Pan Ting-Ting , Lu Xu-Jing , You Xiao-Ming , Qi Jia-Xian
Published: October 2024

Objective

To investigate the effects of peer-led intervention on knowledge, attitudes, and practices (KAP) of stoma care, as well as quality of life in bladder cancer patients post-permanent ostomy.

Methods

A series of 340 eligible bladder cancer patients who underwent permanent ostomy from January 2019 to December 2022 were enrolled in this study. These participants were randomly assigned to the intervention group (peer-led intervention) and the control group (routine health intervention) using random number table, with 170 cases in each group. A 30-item questionnaire was used to evaluate knowledge, healthy attitudes, and healthy practices (KAP) of disease; the WHO Quality of Life-100 (WHOQOL-100) was utilized to assess the quality of life among patients; and the incidence of complications in two groups were also recorded during six-month intervention. For the comparison of continuous variables within and between groups, paired sample and independent t-test were applied. The categorical variables analyzed using x2 test or rank-sum test.

Results

After six-month intervention, 144 participants in the intervention group and 151 participants in the control group were finally retained in this study. The scores of the 20 items in KAP (including basic knowledge of disease, basic knowledge of ostomy, observation of stoma, etc.) in the intervention group were significantly higher than those in the control group (all p < 0.05); the scores of 12 items in WHOQOL-100 (including the positive feelings, thinking, learning, memory and concentration, etc.) in the intervention group were markedly higher than those in the control group, while negative feelings and dependence on medical support in the intervention group were significantly lower than those in the control group (all p < 0.05); the total rate of complications in the intervention group was significantly lower than that in the control group (18.31% vs. 31.13%, p < 0.05).

Conclusion

The peer-led intervention has a positive effect on improving patients’ KAP of stoma care and quality of life and reducing the rate of complications, which enables it to be a favorable intervention approach for patients with permanent ostomy.
Case report of disseminated borrelial lymphocytoma with isolation of Borrelia burgdorferi sensu stricto in chronic lymphatic leukemia stage Binet A—an 11 year follow up
Authors: Hofmann Heidelore , Margos Gabriele , Todorova Antonia , Ringshausen Ingo , Kuleshov Konstantin , Fingerle Volker
Published: October 2024

We report a rare manifestation of cutaneous borreliosis in a patient with pre-existing malignant lymphoproliferative disease, in particular chronic lymphocytic B cell leukemia (B-CLL). The patient’s cutaneous lesions were initially diagnosed histologically as leukemia cutis. Distribution pattern of the skin lesions were in typical localizations for borrelial lymphocytoma. Borrelia burgdorferi sensu stricto was isolated and cultured from two sites (ear, mammilla). Antibiotic therapy improved the cutaneous lesions and the general condition of the patient. However, a second round of antibiotic therapy was required to resolve the lesions. At eleven years of follow-up the patient’s skin was clear and she still had a stable condition of B-CLL without chemotherapy. In conclusion, the patient suffered from Lyme borreliosis (Borrelia lymphocytoma) and the cutaneous symptoms were aggravated by the underlying condition of chronic B-CLL condition.
Skin senescence—from basic research to clinical practice
Authors: Dorf Natalia , Maciejczyk Mateusz
Published: October 2024

The most recognizable implications of tissue aging manifest themselves on the skin. Skin laxity, roughness, pigmentation disorders, age spots, wrinkles, telangiectasia or hair graying are symptoms of physiological aging. Development of the senescent phenotype depends on the interaction between aging cells and remodeling of the skin’s extracellular matrix (ECM) that contains collagen and elastic fiber. Aging changes occur due to the combination of both endogenous (gene mutation, cellular metabolism or hormonal agents) and exogenous factors (ultraviolet light, environmental pollutants, and unsuitable diet). However, overproduction of mitochondrial reactive oxygen species (ROS) is a key factor driving cellular senescence. Aging theories have disclosed a range of diverse molecular mechanisms that are associated with cellular senescence of the body. Theories best supported by evidence include protein glycation, oxidative stress, telomere shortening, cell cycle arrest, and a limited number of cell divisions. Accumulation of the ECM damage is suggested to be a key factor in skin aging. Every cell indicates a functional and morphological change that may be used as a biomarker of senescence. Senescence-associated β-galactosidase (SA-β-gal), cell cycle inhibitors (p16INK4a, p21CIP1, p27, p53), DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS), senescence-associated heterochromatin foci (SAHF), shortening of telomeres or downregulation of lamina B1 constitute just an example of aging biomarkers known so far. Aging may also be assessed non-invasively through measuring the skin fluorescence of advanced glycation end-products (AGEs). This review summarizes the recent knowledge on the pathogenesis and clinical conditions of skin aging as well as biomarkers of skin senescence.
Succeed to culture a novel lineage symbiotic bacterium of Mollicutes which widely found in arthropods intestine uncovers the potential double-edged sword ecological function
Authors: Zhang Lingyu , Chen Qi , Zeng Shenzheng , Deng Zhixuan , Liu Zhongcheng , Li Xuanting , Hou Qilu , Zhou Renjun , Bao Shicheng , Hou Dongwei , Weng Shaoping , He Jianguo , Huang Zhijian
Published: October 2024

Symbiotic gut bacteria play crucial role in host health. Symbionts are widely distributed in arthropod intestines, but their ecological functions are poorly understood due to the inability to cultivate them. Members of Candidatus Bacilliplasma (CB) are widely distributed in crustacean intestine and maybe commensals with hosts, but the paucity of pure cultures has limited further insights into their physiologies and functions. Here, four strains of representative CB bacteria in shrimp intestine were successfully isolated and identified as members of a novel Order in the Phylum Mycoplasmatota. Through genome assembly, the circular genome maps of the four strains were obtained, and the number of coding genes ranged from 1,886 to 1,980. Genomic analysis suggested that the bacteria were missing genes for many critical pathways including the TCA cycle and biosynthesis pathways for amino acids and coenzyme factors. The analysis of 16S amplification data showed that Shewanella, Pseudomonas and CB were the dominant at the genera level in the intestine of Penaeus vannamei. Ecological functional experiments revealed that the strains were symbionts and colonized shrimp intestines. Our valued findings can greatly enhance our understanding and provides new insights into the potentially significant role of uncultured symbiotic bacteria in modulating host health.
Distribution diversity and expression regulation of class 1 integron promoters in clinical isolates of Morganella morganii
Authors: Yang Ye , Zhang Hui , Zhao Rongqing , Qiu Xuedan , Ye Jinglu , Lu Wenjun , Li Qingcao , Wu Guangliang
Published: October 2024

Background

Morganella morganii is an emerging nosocomial opportunistic pathogen with increasing multidrug resistance. Antibiotic resistance, driven primarily by the horizontal transfer of resistance genes, has become a global health crisis. Integrons, mobile genetic elements, are now understood to facilitate the transfer of these genes, contributing to the rapid proliferation of resistant strains. Understanding the regulatory role of integrons in drug resistance gene expression is crucial for developing novel strategies to combat this pressing public health issue.

Objective

To investigate the distribution of promoter types in the variable regions of class 1 integrons isolated from clinical isolates of M. morganii and their regulatory role in the expression of downstream drug resistance gene cassettes.

Methods

Ninety seven clinical isolates of M. morganii were screened for the presence of class 1 integrons (intI1) using polymerase chain reaction (PCR). Gene cassettes within the variable regions of positive isolates were characterized, and the gene cassette promoter Pc variants and downstream auxiliary promoter P2 were identified. Enterobacterial repetitive intergenic consensus (ERIC)-PCR was employed for homology analysis. Recombinant plasmids containing different variable region promoters and gene cassettes were constructed to evaluate drug resistance genes and integrase (intI1) expression levels using reverse transcription-quantitative PCR (RT-qPCR) and antimicrobial susceptibility testing.

Results

Of the clinical isolates, 28.9% (n = 28/97) were positive for class 1 integrons. 24.7% (n = 24/97) of these isolates carried gene cassettes encoding resistance to aminoglycosides and trimethoprim. Three Pc promoter types (PcH1, PcS, and PcW) were identified, while all P2 promoters were inactive with a 14-base pair spacing between the −35 and −10 regions. ERIC-PCR analysis classified the integron-positive strains into 6 genotypes, with high consistency in promoter types and gene cassettes within each genotype. RT-qPCR and antimicrobial susceptibility testing demonstrated that strong promoters significantly enhanced the expression of downstream drug resistance gene cassettes compared to weak promoters. Additionally, RT-qPCR revealed a negative correlation between intI1 expression and Pc promoter strength.

Conclusion

Class 1 integrons are prevalent in M. morganii. The promoter types within these integrons are diverse, and promoter strength is closely linked to downstream gene cassette expression. Integron-positive strains exhibit high homology, suggesting horizontal gene transfer and dissemination in clinical settings.
Functional correlates of executive dysfunction in primary progressive aphasia: a systematic review
Authors: Thomsen Kristin , Keulen Stefanie , Arslan Seçkin
Published: October 2024

Introduction

Recent research has recognized executive dysfunction as another component affected in Primary Progressive Aphasia (PPA). This systematic review aimed to examine what information distinctive neurophysiological markers can provide in the evaluation of executive function (EF) deficits in PPA, and to what effect executive function deficits can be assessed through the characteristics of functional markers.

Methods

We conducted a systematic literature search following the PRISMA guidelines across studies that employed neuropsychological assessments and neurophysiological imaging techniques (EEG, MEG; PET, SPECT, fMRI, fNIRS) to investigate executive dysfunction correlates in PPA.

Results

Findings from nine articles including a total number of 111 individuals with PPA met our inclusion criteria and were synthesized. Although research on the neural correlates of EF deficits is scarce, MEG studies revealed widespread oscillatory slowing, with increased delta and decreased alpha power, where alterations in alpha, theta, and beta activities were significant predictors of executive function deficits. PET findings demonstrated significant correlations between executive dysfunction and hypometabolism in frontal brain regions. fMRI results indicated elevated homotopic connectivity in PPA patients, with a broader and more anterior distribution of abnormal hippocampal connections of which were associated with reduced executive performance.

Conclusion

Our study provides indirect support for the assumption regarding the significance of the frontal regions and inferior frontal junction in executive control and demonstrates that neurophysiological tools can be a useful aid to further investigate clinical-neurophysiological correlations in PPA.
Neurophysiological markers of early cognitive decline in older adults: a mini-review of electroencephalography studies for precursors of dementia
Authors: Tanaka Mutsuhide , Yamada Emi , Mori Futoshi
Published: October 2024

The early detection of cognitive decline in older adults is crucial for preventing dementia. This mini-review focuses on electroencephalography (EEG) markers of early dementia-related precursors, including subjective cognitive decline, subjective memory complaints, and cognitive frailty. We present recent findings from EEG analyses identifying high dementia risk in older adults, with an emphasis on conditions that precede mild cognitive impairment. We also cover event-related potentials, quantitative EEG markers, microstate analysis, and functional connectivity approaches. Moreover, we discuss the potential of these neurophysiological markers for the early detection of cognitive decline as well as their correlations with related biomarkers. The integration of EEG data with advanced artificial intelligence technologies also shows promise for predicting the trajectory of cognitive decline in neurodegenerative disorders. Although challenges remain in its standardization and clinical application, EEG-based approaches offer non-invasive, cost-effective methods for identifying individuals at risk of dementia, which may enable earlier interventions and personalized treatment strategies.
The role of astrocytes from synaptic to non-synaptic plasticity
Authors: Sanz-Gálvez Rafael , Falardeau Dominic , Kolta Arlette , Inglebert Yanis
Published: October 2024

Information storage and transfer in the brain require a high computational power. Neuronal network display various local or global mechanisms to allow information storage and transfer in the brain. From synaptic to intrinsic plasticity, the rules of input–output function modulation have been well characterized in neurons. In the past years, astrocytes have been suggested to increase the computational power of the brain and we are only just starting to uncover their role in information processing. Astrocytes maintain a close bidirectional communication with neurons to modify neuronal network excitability, transmission, axonal conduction, and plasticity through various mechanisms including the release of gliotransmitters or local ion homeostasis. Astrocytes have been significantly studied in the context of long-term or short-term synaptic plasticity, but this is not the only mechanism involved in memory formation. Plasticity of intrinsic neuronal excitability also participates in memory storage through regulation of voltage-gated ion channels or axonal morphological changes. Yet, the contribution of astrocytes to these other forms of non-synaptic plasticity remains to be investigated. In this review, we summarized the recent advances on the role of astrocytes in different forms of plasticity and discuss new directions and ideas to be explored regarding astrocytes-neuronal communication and regulation of plasticity.
Association between serum calcium and in-hospital mortality in intensive care unit patients with cerebral infarction: a cohort study
Authors: Meng Kaiwu , Lei Xiaoyang , He Dian
Published: October 2024

Background

The relationship between serum calcium levels and the prognosis of cerebral infarction remains controversial.

Purpose

This study aims to investigate the correlation between serum calcium levels and in-hospital mortality in critically ill patients with ischemic stroke admitted to the intensive care unit (ICU).

Methods

A retrospective cohort study was conducted using data from the MIMIC-IV database. Demographic and clinical data of all participants were collected including gender, age, hypertension, diabetes, myocardial infarction, heart failure, chronic obstructive pulmonary disease, hemoglobin, potassium, sodium, anion gap, platelets, white blood cells, glucose, creatinine, Glasgow coma score (GCS), IV-tPA administration (rt-PA), and mechanical thrombectomy (MT). The outcome measure was in-hospital death. Multivariable-adjusted logistic regression analysis, curve fitting, interaction analysis, and threshold effect analysis were employed to evaluate the relationship between serum calcium levels and in-hospital mortality among ICU patients with cerebral infarction.

Results

A total of 2,680 critically ill patients with cerebral infarction were enrolled, with a mean serum calcium level of 8.6 ± 0.8 mg/dL. The overall in-hospital mortality rate was 19.5%, where Group 1 (serum calcium < 8.0 mg/dL) had a mortality rate of 27.7%, Group 2 (serum calcium 8–9 mg/dL) had a rate of 19.8%, and Group 3 (serum calcium ≥ 9 mg/dL) had a rate of 13.9%. There was a non-linear, S-shaped relationship between serum calcium levels and in-hospital mortality. Serum calcium levels within the range of 7.70–9.50 mg/dL were found to be independently associated with increased in-hospital mortality in ICU patients with cerebral infarction. No significant interactions were detected in subgroup analyses, and the results of sensitivity analyses remained stable.

Conclusion

Serum calcium levels are independently associated with in-hospital mortality in critically ill patients with cerebral infarction in the ICU setting. Within the range of 7.70–9.50 mg/dL, lower serum calcium levels increase the risk of in-hospital death among these patients, emphasizing the importance of close monitoring by ICU physicians.
Assessment of intraventricular hemorrhage risk in preterm infants using mathematically simulated cerebral blood flow
Authors: Sidorenko Irina , Brodkorb Silke , Felderhoff-Müser Ursula , Rieger-Fackeldey Esther , Krüger Marcus , Feddahi Nadia , Kovtanyuk Andrey , Lück Eva , Lampe Renée
Published: October 2024

Intraventricular hemorrhage (IVH)4 is one of the most threatening neurological complications associated with preterm birth which can lead to long-term sequela such as cerebral palsy. Early recognition of IVH risk may prevent its occurrence and/or reduce its severity. Using multivariate logistic regression analysis, risk factors significantly associated with IVH were identified and integrated into risk scales. A special aspect of this study was the inclusion of mathematically calculated cerebral blood flow (CBF) as an independent predictive variable in the risk score. Statistical analysis was based on clinical data from 254 preterm infants with gestational age between 23 and 30 weeks of pregnancy. Several risk scores were developed for different clinical situations. Their efficacy was tested using ROC analysis, and validation of the best scores was performed on an independent cohort of 63 preterm infants with equivalent gestational age. The inclusion of routinely measured clinical parameters significantly improved IVH prediction compared to models that included only obstetric parameters and medical diagnoses. In addition, risk assessment with numerically calculated CBF demonstrated higher predictive power than risk assessments based on standard clinical parameters alone. The best performance in the validation cohort (with AUC = 0.85 and TPR = 0.94 for severe IVH, AUC = 0.79 and TPR = 0.75 for all IVH grades and FPR = 0.48 for cases without IVH) was demonstrated by the risk score based on the MAP, pH, CRP, CBF and leukocytes count.
Surgical site infections after sarcoma resections in the peripelvic region: do we need perioperative antibiotic prophylaxis?
Authors: Klein Alexander , Chudamani Chataut , Wieser Andreas , Goller Sophia S. , Berclaz Luc M. , Di Gioia Dorit , Holzapfel Boris M. , Dürr Hans Roland
Published: October 2024

Introduction

Surgical site infections (SSI) are one of the most common complications after extensive sarcoma resections and represent a daily challenge. SSI occur in up to 50% of cases particularly in the peripelvic area. One possible approach to reduce infection rate is perioperative antibiotic prophylaxis. The aim of this study therefore was to investigate the influence of perioperative antibiotic prophylaxis on the infection rate and the possible influence of location-specific antibiotic prophylaxis with ampicillin/sulbactam.

Methods

This monocentric retrospective study included 366 patients who underwent sarcoma resections in the groin, proximal thigh, or gluteal region. All patients were operated on by 2 surgeons after neoadjuvant pretreatment if necessary. 3 groups of patients were defined. Group 1: In 60.4% of all cases, antibiotic prophylaxis was administered with cephalosporins (also clindamycin in case of penicillin allergy). Group2: In 9.8% of cases, ampicillin/sulbactam was used. Group 3: 29.8% of patients did not receive any antibiotic prophylaxis.

Results

In 31.1% of treated cases, antibiotic therapy was prolonged due to extended tumor resections. Postoperative infections occurred in 23.2% (85 cases), in 77 cases within the first 90 days (on average after 20 days). The median operating time, blood loss was higher, and tumor size were significantly larger in cases with infections, compared to patients without infection. In group 1 and 2 with perioperative single-shot prophylaxis, infection occurred in 24.1% of cases, compared to 13.5% of cases without prophylaxis (group 3) (p= 0.032). In the patients with prolonged antibiotic therapy, infection occurred in 31.6% of cases, compared to 16.3% of cases without prolongation (p< 0.001). In the group 2, infection occurred in 19.4% of cases compared to 24.9% of cases in the group 1 (p= 0.479). In the multivariate analysis, surgery time longer 80 min, blood substitution, neoadjuvant radio- and chemotherapy proved to be a risk factor for SSI.

Discussion

Region adapted perioperative antibiotic prophylaxis may reduce the risk of infection after extended sarcoma resection in the peripelvic area. However, the particular bacterial spectrum of this anatomic region should be taken into account when deciding which antibiotics to use.
Immune-related toxic epidermal necrolysis affecting trachea mucosal epithelium: a case report and literature review
Authors: Zhang Mingbo , Fu Yang , Song Yuxiao , Gao Xia , Wang Jun , Zhang Bicheng
Published: October 2024

Background

Monoclonal antibodies against programmed cell death protein-1 (PD-1)/programmed death-ligand-1 (PD-L1) have emerged as critical tools in cancer treatment. However, concerns regarding their potential cutaneous and mucosal toxicity, along with severe complications, have drawn clinical attention. Further research is warranted to investigate the adverse reactions and treatment strategies associated with PD-1 monoclonal antibodies.

Methods

We present a detailed case report of a laryngeal cancer patient who developed toxic epidermal necrolysis (TEN) after treatment with PD-1 monoclonal antibody. We analyzed the etiology, diagnosis, and treatment approaches by integrating clinical manifestations, pathological examinations, and literature research.

Results

After PD-1 monoclonal antibody therapy, the patient exhibited systemic rash, bullae, and epidermal detachment, which subsequently involved the tracheal and bronchial mucosa, resulting in dyspnea. The patient recovered after treatments with steroids, macrolides, immunoglobulins, and etanercept, along with repeated removal of scabs via bronchoscopy. Literature reviewing suggests a potential association between PD-1 monoclonal antibodies and the pathogenesis of Steven Johnson’s Syndrome (SJS) and Toxic epidermal necrolysis (TEN), possibly due to immune dysregulation. Treatment consists of immediate discontinuation of suspicious drugs, essential supportive therapy, and systemic corticosteroid administration, with the addition of immunosuppressants and/or immunoglobulins needed.

Conclusion

The mucocutaneous toxicity induced by PD-1 monoclonal antibodies is not limited to the surface of the skin but also in deep mucosal layers, potentially leading to life-threatening complications. Therefore, when using PD-1 monoclonal antibodies, clinicians should closely monitor adverse events and apply appropriate treatments as soon as possible to prevent severe complications.
The role of NOP58 in prostate cancer progression through SUMOylation regulation and drug response
Authors: Guo Wei , Zong Shi , Liu Tao , Chao Yi , Wang Kaichen
Published: October 2024

Background

Prostate cancer is one of the leading causes of cancer-related deaths in men. Its molecular pathogenesis is closely linked to various genetic and epigenetic alterations, including posttranslational modifications like SUMOylation. Identifying biomarkers that predict outcomes and specific therapeutic targets depends on a comprehensive understanding of these processes. With growing interest in SUMOylation as a mechanism affecting prostate cancer-related genes, this study aimed to investigate the central role of SUMOylation in prostate cancer prognostics, focusing on the significance of NOP58.

Methods

We conducted a comprehensive bioinformatics analysis, integrating differential expression analysis, survival analysis, gene set enrichment analysis (GSEA), and single-cell transcriptomic analyses using data from The Cancer Genome Atlas (TCGA). Key genes were identified through intersections of Venn diagrams, Boralta algorithm signatures, and machine learning models. These signaling mechanisms were validated through experimental studies, including immunohistochemical staining and gene ontology analyses.

Results

The dual-gene molecular subtype analysis with SUMO1, SUMO2, and XPO1 genes revealed significant differences in survival outcomes across molecular subtypes, further emphasizing the potential impact of NOP58 on SUMOylation, a key post-translational modification, in prostate cancer. NOP58 overexpression was strongly associated with shorter overall survival (OS), progression-free interval (PFI), and disease-specific death in prostate cancer patients. Immunohistochemical analysis confirmed that NOP58 was significantly overexpressed in prostate cancer tissues compared to normal tissues. ROC curve analysis demonstrated that NOP58 could distinguish prostate cancer from control samples with high diagnostic accuracy. Gene Ontology analysis, along with GSVA and GSEA, suggested that NOP58 may be involved in cell cycle regulation and DNA repair pathways. Moreover, NOP58 knockdown led to increased BCL2 expression and decreased Ki67 levels, promoting apoptosis and inhibiting cell proliferation. Colony formation assays further showed that NOP58 knockdown inhibited, while its overexpression promoted, colony formation, highlighting the critical role of NOP58 in prostate cancer cell growth and survival. Additionally, NOP58 was linked to drug responses, including Methotrexate, Rapamycin, Sorafenib, and Vorinostat.

Conclusion

NOP58 is a key regulator of prostate cancer progression through its mediation of the SUMOylation pathway. Its expression level serves as a reliable prognostic biomarker and an actionable therapeutic target, advancing precision medicine for prostate cancer. Targeting NOP58 may enhance therapeutic efficacy and improve outcomes in oncology.