bluuebunny/crossref_metadata_2025 huggingface dataset:
Advances in phage display based nano immunosensors for cholera toxin
Authors: Li Yang , Yang Kai-di , Kong De-cai , Ye Jun-feng
Published: September 2023

Cholera, a persistent global public health concern, continues to cause outbreaks in approximately 30 countries and territories this year. The imperative to safeguard water sources and food from Vibrio cholerae, the causative pathogen, remains urgent. The bacterium is mainly disseminated via ingestion of contaminated water or food. Despite the plate method’s gold standard status for detection, its time-consuming nature, taking several days to provide results, remains a challenge. The emergence of novel virulence serotypes raises public health concerns, potentially compromising existing detection methods. Hence, exploiting Vibrio cholerae toxin testing holds promise due to its inherent stability. Immunobiosensors, leveraging antibody specificity and sensitivity, present formidable tools for detecting diverse small molecules, encompassing drugs, hormones, toxins, and environmental pollutants. This review explores cholera toxin detection, highlighting phage display-based nano immunosensors’ potential. Engineered bacteriophages exhibit exceptional cholera toxin affinity, through specific antibody fragments or mimotopes, enabling precise quantification. This innovative approach promises to reshape cholera toxin detection, offering an alternative to animal-derived methods. Harnessing engineered bacteriophages aligns with ethical detection and emphasizes sensitivity and accuracy, a pivotal stride in the evolution of detection strategies. This review primarily introduces recent advancements in phage display-based nano immunosensors for cholera toxin, encompassing technical aspects, current challenges, and future prospects.
Rare solid tumors in a patient with Wiskott–Aldrich syndrome after hematopoietic stem cell transplantation: case report and review of literature
Authors: Coppola Emma , Giardino Giuliana , Abate Massimo , Tambaro Francesco Paolo , Bifano Delfina , Toriello Elisabetta , De Rosa Antonio , Cillo Francesca , Pignata Claudio , Cirillo Emilia
Published: September 2023

Background and aims

Wiskott–Aldrich syndrome (WAS) is an X-linked recessive primary immunodeficiency disorder characterized by severe eczema, recurrent infections, and micro-thrombocytopenia. Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic option for patients with classic form. The risk of developing post-transplant tumors appears to be higher in patients with WAS than in other inborn errors of immunity (IEIs), but the actual incidence is not well defined, due to the scarcity of published data.

Methods

Herein, we describe a 10-year-old patient diagnosed with WAS, treated with HSCT in the first year of life, who subsequently developed two rare solid tumors, kaposiform hemangioendothelioma and desmoid tumor. A review of the literature on post-HSCT tumors in WAS patients has been performed.

Results

The patient received diagnosis of classic WAS at the age of 2 months (Zhu score = 3), confirmed by WAS gene sequencing, which detected the nonsense hemizygous c.37C>T (Arg13X) mutation. At 9 months, patient underwent HSCT from a matched unrelated donor with an adequate immune reconstitution, characterized by normal lymphocyte subpopulations and mitogen proliferation tests. Platelet count significantly increased, even though platelet count never reached reference values. A mixed chimerism was also detected, with a residual WASP− population on monocytes (27.3%). The patient developed a kaposiform hemangioendothelioma at the age of 5. A second abdominal tumor was identified, histologically classified as a desmoid tumor when he reached the age of 10 years. Both hematopoietic and solid tumors were identified in long-term WAS survivors after HSCT.

Conclusion

Here, we describe the case of a patient with WAS who developed two rare solid tumors after HSCT. An active surveillance program for the risk of tumors is necessary in the long-term follow-up of post-HSCT WAS patients.
Dynamic atlas of immune cells reveals multiple functional features of macrophages associated with progression of pulmonary fibrosis
Authors: Lv Jiaoyan , Gao Haoxiang , Ma Jie , Liu Jiachen , Tian Yujie , Yang Chunyuan , Li Mansheng , Zhao Yue , Li Zhimin , Zhang Xuegong , Zhu Yunping , Zhang Jianhong , Wu Li
Published: September 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease with a high mortality rate and unclarified aetiology. Immune response is elaborately regulated during the progression of IPF, but immune cells subsets are complicated which has not been detailed described during IPF progression. Therefore, in the current study, we sought to investigate the role of immune regulation by elaborately characterize the heterogeneous of immune cells during the progression of IPF. To this end, we performed single-cell profiling of lung immune cells isolated from four stages of bleomycin-induced pulmonary fibrosis—a classical mouse model that mimics human IPF. The results revealed distinct components of immune cells in different phases of pulmonary fibrosis and close communication between macrophages and other immune cells along with pulmonary fibrosis progression. Enriched signals of SPP1, CCL5 and CXCL2 were found between macrophages and other immune cells. The more detailed definition of the subpopulations of macrophages defined alveolar macrophages (AMs) and monocyte-derived macrophages (mo-Macs)—the two major types of primary lung macrophages—exhibited the highest heterogeneity and dynamic changes in expression of profibrotic genes during disease progression. Our analysis suggested that Gpnmb and Trem2 were both upregulated in macrophages and may play important roles in pulmonary fibrosis progression. Additionally, the metabolic status of AMs and mo-Macs varied with disease progression. In line with the published data on human IPF, macrophages in the mouse model shared some features regarding gene expression and metabolic status with that of macrophages in IPF patients. Our study provides new insights into the pathological features of profibrotic macrophages in the lung that will facilitate the identification of new targets for disease intervention and treatment of IPF.
Case report: IKZF1-related early-onset CID is expected to be missed in TREC-based SCID screening but can be identified by determination of KREC levels
Authors: Äng Christofer , Zetterström Rolf H. , Ramme Kim , Axelsen Emma , Marits Per , Sundin Mikael
Published: September 2023

This report illustrates a case that would have been missed in the most common screening algorithms used worldwide in newborn screening (NBS) for severe combined immunodeficiency (SCID). Our patient presented with a clinical picture that suggested a severe inborn error of immunity (IEI). The 6-month-old baby had normal T-cell receptor excision circle (TREC) levels but no measurable level of kappa-deleting recombination excision circles (KRECs) in the NBS sample. A de novo IKZF1-mutation (c.476A>G, p.Asn159Ser) was found. The clinical picture, immunologic workup, and genetic result were consistent with IKZF1-related combined immunodeficiency (CID). Our patient had symptomatic treatment and underwent allogeneic hematopoietic cell transplantation (HCT). IKZF1-related CID is a rare, serious, and early-onset disease; this case provides further insights into the phenotype, including KREC status.
Autoimmune GFAP astrocytopathy after viral encephalitis: a case report of bimodal overlapping encephalitis
Authors: Cheng Ping , Huang Wenjuan , Yang Meifang , Chen Zhiren , Geng Yifan , Zhang Xia , Chen Weiwei
Published: September 2023

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a treatable autoimmune disorder affecting the central nervous system. Despite extensive research, the exact etiology and pathogenesis of this condition remain unclear. In recent years, autoimmune encephalitis (AE) after viral encephalitis (VE) has gathered significant attention. Here, we present a case report of autoimmune GFAP astrocytopathy after VE in a 43-year-old Asian male with a history of oral and labial herpes. The patient presented with high-grade fever, headache, urinary retention, unresponsiveness, and apathy. Elevated levels of protein and GFAP-IgG were observed in the cerebrospinal fluid (CSF), and enhanced brain magnetic resonance imaging (MRI) revealed linear enhancement oriented radially to the ventricles. Treatment with intravenous immunoglobulin (IVIG) resulted in symptom relief, reduced lesion enhancement, and decreased protein levels. This case report highlights bimodal encephalitis with no discernible interval between VE and autoimmune GFAP astrocytopathy, which poses diagnostic challenges. Notably, autoimmune GFAP astrocytopathy is a novel form of autoimmune encephalitis, and its treatment lacks sufficient clinical experience. Intriguingly, our patient demonstrated sensitivity to IVIG, a treatment that differed from past reports. Therefore, further exploration of treatment strategies for this condition is warranted.
Pre-organized landscape of T cell surface
Authors: Jung Yunmin
Published: September 2023

T cell activation is initiated by the recognition of specific antigenic peptides and subsequently accomplished by complex signaling cascades. These aspects have been extensively studied for decades as pivotal factors in the establishment of adaptive immunity. However, how receptors or signaling molecules are organized in the resting state prior to encountering antigens has received less attention. Recent advancements in super-resolution microscopy techniques have revealed topographically controlled pre-formed organization of key molecules involved in antigen recognition and signal transduction on microvillar projections of T cells before activation and substantial effort has been dedicated to characterizing the topological structure of resting T cells over the past decade. This review will summarize our current understanding of how key surface receptors are pre-organized on the T-cell plasma membrane and discuss the potential role of these receptors, which are preassembled prior to ligand binding in the early activation events of T cells.
25-hydroxycholesterol: an integrator of antiviral ability and signaling
Authors: Zhang Jialu , Zhu Yaohong , Wang Xiaojia , Wang Jiufeng
Published: September 2023

Cholesterol, as an important component in mammalian cells, is efficient for viral entry, replication, and assembly. Oxysterols especially hydroxylated cholesterols are recognized as novel regulators of the innate immune response. The antiviral ability of 25HC (25-Hydroxycholesterol) is uncovered due to its role as a metabolic product of the interferon-stimulated gene CH25H (cholesterol-25-hydroxylase). With the advancement of research, the biological functions of 25HC and its structural functions have been interpreted gradually. Furthermore, the underlying mechanisms of antiviral effect of 25HC are not only limited to interferon regulation. Taken up by the special biosynthetic ways and structure, 25HC contributes to modulate not only the cholesterol metabolism but also autophagy and inflammation by regulating signaling pathways. The outcome of modulation by 25HC seems to be largely dependent on the cell types, viruses and context of cell microenvironments. In this paper, we review the recent proceedings on the regulatory effect of 25HC on interferon-independent signaling pathways related to its antiviral capacity and its putative underlying mechanisms.
Feeding and water temperature modulate the potential activity of gut microbiota in greater amberjack juveniles (Seriola dumerili)
Authors: Navarro-Guillén Carmen , Degré Lorentsen Eirik , Perera Erick , Yúfera Manuel , Vadstein Olav
Published: September 2023

Gut microbial communities are highly dynamic and respond to factors such as diet and host metabolism. However, there is limited knowledge on changes in gut microbiota during the daily cycle. To investigate how interactions between feeding and water temperature affected the diurnal dynamics and activity of the microbiota, we analyzed the qualitative and quantitative composition in feces of the potentially active bacterial community along a day cycle in greater amberjack juveniles (Seriola dumerili). Bacterial density (based on qPCR of 16S rDNA) in feces was relatively stable along the day. In contrast bacterial activity (based on qPCR of 16S rRNA) increased during the period of active feeding, and was reduced to pre-feeding levels four hours after the last meal. The relative potential activity of the bacterial community in fish feces varied with postprandial time. At the phylum level there was a shift from a Spirochaetes-dominated community in the morning to increased potential activity of Proteobacteria after feeding. At lower taxonomic level, i.e. order, the bacterial community was dominated by Mycoplasmoidales, which relative potential activity was maintained throughout the day in all treatments. By contrast, for absolute potential bacterial activity at the order level there was a peak in potential activity of several bacterial orders at 6h after first feeding, with the most noticeable increase observed for Mycoplasmoidales. Results from the present work also indicated a close relation between the effect of water temperature and microbial dynamics. This is the first study assessing the quantitative and qualitative effects of water temperature and daily feeding rhythm on the gut microbiota dynamics in fish. Feeding was the main driver modulating bacterial activity, promoting a peak in bacterial activity 6h after first feeding. However, water temperature also modulated gut microbiota dynamics, with a marked effect on the time scale. In addition, results indicate that analysis of absolute bacterial potential activity provides a better resolution of metabolically active gut microbial community, since a change in the absolute activity of a single taxon can alter the relative activity of all taxa.
DEJKMDR: miRNA-disease association prediction method based on graph convolutional network
Authors: Gao Shiyuan , Kuang Zhufang , Duan Tao , Deng Lei
Published: September 2023

Numerous studies have shown that miRNAs play a crucial role in the investigation of complex human diseases. Identifying the connection between miRNAs and diseases is crucial for advancing the treatment of complex diseases. However, traditional methods are frequently constrained by the small sample size and high cost, so computational simulations are urgently required to rapidly and accurately forecast the potential correlation between miRNA and disease. In this paper, the DEJKMDR, a graph convolutional network (GCN)-based miRNA-disease association prediction model is proposed. The novelty of this model lies in the fact that DEJKMDR integrates biomolecular information on miRNA and illness, including functional miRNA similarity, disease semantic similarity, and miRNA and disease similarity, according to their Gaussian interaction attribute. In order to minimize overfitting, some edges are randomly destroyed during the training phase after DropEdge has been used to regularize the edges. JK-Net, meanwhile, is employed to combine various domain scopes through the adaptive learning of nodes in various placements. The experimental results demonstrate that this strategy has superior accuracy and dependability than previous algorithms in terms of predicting an unknown miRNA-disease relationship. In a 10-fold cross-validation, the average AUC of DEJKMDR is determined to be 0.9772.
Dermatological concerns for women and girls with turner syndrome
Authors: Rodriguez-Buritica David , Mones Meaghan , Prakash Siddharth K. , Rivera Michelle , Aldrich Melissa , Rogge Megan , Richardson Kate
Published: September 2023

Introduction

Turner syndrome (TS) is associated with distinct manifestations in women and girls including short stature, cardiac abnormalities, premature ovarian failure as well as dermatological features, including lymphedema, keloids, onychodystrophy, and acne. Although many dermatological concerns present during the first few decades of life, the overwhelming majority of respondents are not provided with dermatology referrals at diagnosis.

Methods

This cross-sectional study utilized an author designed survey to assess self-reported dermatological manifestations, dermatology referral experience, common therapies for select dermatological conditions, as well as a validated 10-question Dermatology Life Quality Index (DLQI) to assess quality-of-life impact in women and girls with Turner syndrome.

Results

In our cohort, 64% (n = 149) had been referred to a dermatologist at some point in their life time. The majority of individuals self-identified their dermatological concern (79.6%) and were referred after a dermatological concern had already occurred (90.2%). The most common dermatological findings reported were xerosis cutis (78.7%), lymphedema (73%), and more than 20 acquired melanocytic nevi (70%). The overall mean DLQI score was 3.52, indicative of a small effect on the patient’s life. Onychodystrophy, history of skin biopsy, and lymphedema were statistically significant to have a higher impact on quality of life.

Discussion

Our data reveal that skin conditions are highly prevalent in the TS population during the early decades of life and affirm utilizing these conditions in the TS diagnostic process, as well as emphasize the need for specialized dermatology referrals to address the detrimental impacts related to skin concerns on quality of life.
Care pathway analysis and evidence gaps in adult-onset Still’s disease: interviews with experts from the UK, France, Italy, and Germany
Authors: Ursini Francesco , Gregg Emily , Canon-Garcia Viviam , Rabijns Hilde , Toennessen Katrin , Bartlett Kaz , Graziadio Sara
Published: September 2023

Introduction

Adult-onset Still’s disease (AOSD) is a rare systemic inflammatory disease of unknown etiology. Published AOSD data are limited, and clinical guidelines were lacking until recently. Managing AOSD remains largely empirical with uncertainties and high variability about the optimal care pathway. Therefore, we used a qualitative approach to collect clinical judgments from the UK, Italy, France and Germany to inform the development of an agreed care pathway. Our work aimed to decrease the uncertainty associated with clinical practice, inform future research in AOSD, and help identify standardized definitions and outcomes in this population.

Methods

Semi-structured interviews and thematic analysis were conducted. Eleven clinicians were interviewed between May and July 2022: four were based in Italy, three in the UK, two in France, and two in Germany.

Results

In this work, we identified the structure of the typical care pathway for AOSD patients, which can be used to inform future economic models in AOSD. The general structure of the pathway was similar across countries. Non-steroidal anti-inflammatory drugs are prescribed during the diagnostic workup while an additive approach is commonly used in confirmed cases: corticosteroids, conventional synthetic disease-modifying antirheumatic drugs, then biologic disease-modifying antirheumatic drugs (bDMARDs) (dose increased before switching). For severe presentations, more aggressive approaches with higher doses and early use of bDMARDs are used. The main elements of variation among countries and clinicians were the criteria used for diagnosis; order of bDMARDs and preferential treatments for articular and systemic patients; and tests for patient monitoring. There is also a lack of standardized outcome measures making comparisons and evidence synthesis challenging.

Conclusion

We identified important evidence gaps for clinical practice, e.g., reliable tests or scores predictive of disease progression and treatment outcome, and recommendations for research, e.g., reporting of compliance rates and use of the Yamaguchi criteria for clinical study inclusion. Consensus is needed around the use of the Systemic score in clinical practice and the clinical utility of this score. A standardized definition of remission is also required in AOSD, and further research should look to identify and validate the specific laboratory markers to be considered when assessing remission.
A quasi-experimental study of fresh oxygen flow on patients’ oxygen reserve during mask-assisted ventilation under general anesthesia induction
Authors: Shi Yubo , Jin Ying , Song Jianli , Shi Jingfeng , Liu Xiaoying , Zhao Guoqing , Su Zhenbo
Published: September 2023

Background

To compare the effect of different amounts of fresh oxygen flow on oxygen reserve in patients undergoing general anesthesia.

Methods

Seventy-two patients were enrolled in this quasi-experimental study. Patients were randomly divided into experimental groups with a fresh oxygen flow of 1 L/min, 2 L/min, 4 L/min, and 8 L/min (denoted as G1, G2, G3, and G4, respectively) for 2 min of mask-assisted ventilation. Safe apnea time (SAT) was the primary endpoint; SAT was defined as the time from the cessation of ventilation to the time the patient’s pulse oxygen saturation (SpO2) decreased to 90%. Ventilation indicators such as end-tidal oxygen concentration (EtO2), end-tidal carbon dioxide partial pressure (EtCO2), SpO2, and carbon dioxide (CO2) elimination amount, during mask-assisted ventilation, were the secondary endpoints.

Results

The SAT of G1, G2, G3, and G4 were 305.1 ± 97.0 s, 315 ± 112.5 s, 381.3 ± 118.6 s, and 359 ± 104.4 s, respectively (p > 0.05). The EtO2 after 2 min of mask-assisted ventilation in groups G1, G2, G3, and G4 were 69.7 ± 8.8%, 75.2 ± 5.0%, 82.5 ± 3.3%, and 86.8 ± 1.5%, respectively (p < 0.05). Also, there was a moderate positive correlation between the fresh oxygen flow and EtO2 (correlation coefficient r = 0.52, 95% CI 0.31–0.67, p < 0.0001). The CO2 elimination in the G1 and G2 groups was greater than that in the G4 group (p < 0.05). There was no significant difference in other indicators among the groups (all p > 0.05).

Conclusion

The amount of fresh oxygen flow during mask-assisted ventilation was positively correlated with EtO2. Also, even though there was no significant difference, the patients’ oxygen reserves increased with the increase in fresh oxygen flow.
Antivirulence activities of retinoic acids against Staphylococcus aureus
Authors: Park Inji , Lee Jin-Hyung , Ma Jin Yeul , Tan Yulong , Lee Jintae
Published: September 2023

Multidrug-resistant bacteria such as Staphylococcus aureus constitute a global health problem. Gram-positive S. aureus secretes various toxins associated with its pathogenesis, and its biofilm formation plays an important role in antibiotic tolerance and virulence. Hence, we investigated if the metabolites of vitamin A1 might diminish S. aureus biofilm formation and toxin production. Of the three retinoic acids examined, 13-cis-retinoic acid at 10 μg/mL significantly decreased S. aureus biofilm formation without affecting its planktonic cell growth (MIC >400 μg/mL) and also inhibited biofilm formation by Staphylococcus epidermidis (MIC >400 μg/mL), but less affected biofilm formation by a uropathogenic Escherichia coli strain, a Vibrio strain, or a fungal Candida strain. Notably, 13-cis-retinoic acid and all-trans-retinoic acid significantly inhibited the hemolytic activity and staphyloxanthin production by S. aureus. Furthermore, transcriptional analysis disclosed that 13-cis-retinoic acid repressed the expressions of virulence- and biofilm-related genes, such as the two-component arlRS system, α-hemolysin hla, nuclease (nuc1 and nuc2), and psmα (phenol soluble modulins α) in S. aureus. In addition, plant and nematode toxicity assays showed that 13-cis-retinoic acid was only mildly toxic at concentrations many folds higher than its effective antibiofilm concentrations. These findings suggest that metabolites of vitamin A1, particularly 13-cis-retinoic acid, might be useful for suppressing biofilm formation and the virulence characteristics of S. aureus.
Gut microbiota is associated with spatial memory and seed-hoarding behavior of South China field mice (Apodemus draco)
Authors: Feng Enping , Yang Xifu , Zhao Kunming , Li Ying , Zhu Hanyi , Wang Zhenshan , Zhang Zhibin
Published: September 2023

Background

Scatter-hoarding animals store food in multiple locations within their home range and rely on spatial memory for subsequent localization and retrieval. The relationship between memory and scatter-hoarding behavior has been widely demonstrated, but the association of gut microbiota with spatial memory and seed-hoarding behavior of animals remains unclear.

Methods

In this study, by using enclosure behavior tests, memory tests including an object location test (OLT) and a novel object recognition test (NORT), and fecal microbiota transplantation (FMT) experiment, we evaluated the role of gut microbiota in affecting the memory and seed-hoarding behavior of rodents. According to their scatter-hoarding intensity, South China field mice (Apodemus draco) were divided into scatter-hoarding group (SG) and non-scatter-hoarding group (NG).

Results

We found that the SG performed better than the NG in the NORT. FMT from SG donor mice altered the NG recipient mice’s gut microbiota structure. Further tests demonstrated FMT from SG donor mice increased memory of NG recipient mice in laboratory tests and seed larder hoarding intensity of NG recipient mice in enclosures.

Conclusion

Our results suggest gut microbiota could modulate the memory and seed-hoarding behavior of animals.
Probiotic and functional potential of lactic acid bacteria isolated from pulque and evaluation of their safety for food applications
Authors: Ruiz-Ramírez Yesica , Valadez-Blanco Rogelio , Calderón-García Concepción , Chikindas Michael Leonidas , Ponce-Alquicira Edith
Published: September 2023

Pulque is a traditional Mexican non-distilled alcoholic beverage to which several beneficial functions are attributed, mainly associated with gastrointestinal health, which can be explained by the presence of probiotic bacteria in its microbiota. Therefore, the objective of this work was to evaluate the safety, probiotic activity, and functional characteristics of seven strains of lactic acid bacteria (LAB) isolated from pulque using the probiotic strain Lactobacillus acidophilus NCFM as control. The LAB isolates were identified by 16S rRNA sequencing and MALDI Biotyper® MS as belonging to three different Lactobacillaceae genera and species: Lactiplantibacillus plantarum, Levilactobacillus brevis and Lacticaseibacillus paracasei. Most strains showed resistance to gastric juice, intestinal juice and lysozyme (10 mg/L). In addition, all strains exhibited bile salt hydrolase (BSH) activity and antibacterial activity against the pathogenic strain Listeria monocytogenes. Additionally, cell surface characteristics of LAB were evaluated, with most strains showing good hydrophobicity, auto-aggregation, and co-aggregation towards enteropathogenic Escherichia coli and L. monocytogenes. In terms of safety, most of the strains were sensitive to the tested antibiotics and only the Lact. paracasei UTMB4 strain amplified a gene related to antibiotic resistance (mecA). The strains Lact. plantarum RVG2 and Lact. plantarum UTMB1 presented γ-hemolytic activity, and the presence of the virulence-related gene agg was identified only in UTMB1 strain. Regarding functional characterization, the tested bacteria showed good β-galactosidase activity, antioxidant activity and cholesterol reduction Based on principal component analysis (PCA) and heat mapping, and considering the strain Lact. acidophilus NCFM as the probiotic reference, the strains Lacticaseibacillus paracasei UTMB4, Lactiplantibacillus plantarum RVG4 and Levilactobacillus brevis UTMB2 were selected as the most promising probiotic strains. The results of this study highlighted the probiotic, functional and safety traits of LAB strains isolated from pulque thus supporting the health benefits attributed to this ancestral beverage.
Diverse roles of lung macrophages in the immune response to influenza A virus
Authors: Li Haoning , Wang Aoxue , Zhang Yuying , Wei Fanhua
Published: September 2023

Influenza viruses are one of the major causes of human respiratory infections and the newly emerging and re-emerging strains of influenza virus are the cause of seasonal epidemics and occasional pandemics, resulting in a huge threat to global public health systems. As one of the early immune cells can rapidly recognize and respond to influenza viruses in the respiratory, lung macrophages play an important role in controlling the severity of influenza disease by limiting viral replication, modulating the local inflammatory response, and initiating subsequent adaptive immune responses. However, influenza virus reproduction in macrophages is both strain- and macrophage type-dependent, and ineffective replication of some viral strains in mouse macrophages has been observed. This review discusses the function of lung macrophages in influenza virus infection in order to better understand the pathogenesis of the influenza virus.
Assigning function to active site residues of Schistosoma mansoni thioredoxin/glutathione reductase from analysis of transient state reductive half-reactions with variant forms of the enzyme
Authors: Smith Madison M. , Moran Graham R.
Published: September 2023

Thioredoxin/glutathione reductase (TGR) from the platyhelminthic parasitic worms has recently been identified as a drug target for the treatment of schistosomiasis. Schistosomes lack catalase, and so are heavily reliant on the regeneration of reduced thioredoxin (Trx) and glutathione (GSH) to reduce peroxiredoxins that ameliorate oxidative damage from hydrogen peroxide generated by the host immune response. This study focuses on the characterization of the catalytic mechanism of Schistosoma mansoni TGR (SmTGR). Variant forms of SmTGR were studied to assign the function of residues that participate in the electron distribution chain within the enzyme. Using anaerobic transient state spectrophotometric methods, redox changes for the FAD and NADPH were observed and the function of specific residues was defined from observation of charge transfer absorption transitions that are indicative of specific complexations and redox states. The C159S variant prevented distribution of electrons beyond the flavin and as such did not accumulate thiolate-FAD charge transfer absorption. The lack of this absorption facilitated observation of a new charge transfer absorption consistent with proximity of NADPH and FAD. The C159S variant was used to confine electrons from NADPH at the flavin, and it was shown that NADPH and FAD exchange hydride in both directions and come to an equilibrium that yields only fractional FAD reduction, suggesting that both have similar reduction potentials. Mutation of U597 to serine resulted in sustained thiolate-FAD charge transfer absorption and loss of the ability to reduce Trx, indicating that the C596-U597 disulfide functions in the catalytic sequence to receive electrons from the C154 C159 pair and distribute them to Trx. No kinetic evidence for a loss or change in function associated with the distal C28-C31 disulfide was observed when the C31S variant reductive half-reaction was observed. The Y296A variant was shown to slow the rate of but increase extent of reduction of the flavin, and the dissociation of NADP+. The H571 residue was confirmed to be the residue responsible for the deprotonation of the C159 thiol, increasing its reactivity and generating the prominent thiolate-FAD charge transfer absorption that accumulates with oxidation of the flavin.
Addressing depression in older adults with Alzheimer’s through cognitive behavioral therapy: systematic review and meta-analysis
Authors: González-Martín Ana María , Aibar Almazán Agustín , Rivas Campo Yulieth , Rodríguez Sobrino Noelia , Castellote Caballero Yolanda
Published: September 2023

Objectives

This systematic review and meta-analysis was conducted to provide an analysis of the published data about the effects of cognitive behavioral therapies on the depression of older adults with a diagnosis of Alzheimer’s disease.

Methods

This study was performed following the PRISMA 2020 guidelines. The search was performed between March and April 2023, using four electronic databases: PubMed, Web of Science, Cinhal and Scopus. Different keywords combined with Boolean operators were utilized. Only 11 articles were included out of the initial 212.

Results

Cognitive behavioral therapy was found to reduce depression in individuals with Alzheimer’s, including treatments with low frequency but a longer intervention time.

Conclusion

This systematic review and meta-analysis found that the psychosocial therapy cognitive behavioral therapy is effective in improving depression in individuals with a diagnosis of Alzheimer’s. However, results are inconclusive due to the disparity of the findings and the heterogeneity of the applied protocols, so more studies are needed on this topic.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=416396, CRD42023416396.
Health behaviors of people with multiple sclerosis and its associations with MS related outcomes: a German clinical cohort
Authors: Goldin Katharina , Riemann-Lorenz Karin , Daubmann Anne , Pöttgen Jana , Krause Nicole , Schröder Helmut , Heesen Christoph
Published: September 2023

Background

Health behaviors in persons with multiple sclerosis (pwMS) have been associated with MS-related disease outcomes.

Objective

The aim of the study was to gain knowledge about current patient health behaviors in a convenience sample representative for pwMS presenting to a large university-based outpatient clinic and to investigate associations between modifiable risk factors with physical impairment, quality of life (QoL) and cardiovascular comorbidities.

Methods

A questionnaire was administered at the MS Outpatient Clinic of the University Medical Center Hamburg Eppendorf asking for health behaviors regarding dietary habits assessed with the German adaptation of the validated Spanish short Diet Quality Screener (sDQS), level of physical activity assessed with the Godin Leisure Time Questionnaire (GLTEQ) and tobacco smoking. Participants were asked to report cardiovascular comorbidities using items from the Self-Report Comorbidity Questionnaire for Multiple Sclerosis. Additionally, cardiovascular risk factors like blood pressure, height and weight (to calculate BMI) and waist circumference were measured. MS specific clinical data, e.g., disease course, duration, disability and MS-specific QoL were collected from the clinical database. Descriptive analyses were performed and multivariate regression analyses for complete cases were carried out for each of the three outcome variables including all mentioned modifiable risk factors (dietary behavior, smoking, physical activity and BMI) as independent variables.

Results

In this sample of 399 pwMS the mean age was 42 years (SD 12.8) with a mean disease duration since diagnosis of 7.4 years (SD 8.4) and a mean EDSS of 2.8 (SD 1.9). 24% were current smokers, 44% were insufficiently physically active and 54% did not follow a healthy dietary pattern. 49% of this relatively young clinical population was overweight and 27% reported one or more cardiovascular comorbidities. Most modifiable risk factors showed no convincing associations with MS-related disease outcomes in the multiple regression analyses.

Conclusion

This clinical cohort of pwMS shows a high prevalence of critical health behaviors and comorbidities and emphasizes the need for monitoring, education and assistance for behavior change in this population.
Autoimmune encephalitis in COVID-19 patients: a systematic review of case reports and case series
Authors: Xue Hua , Zeng Li , He Hongxian , Xu Dongxun , Ren Kaixin
Published: September 2023

Background

There is mounting evidence suggesting that autoimmune encephalitis (AE) can be observed as a neurological complication in patients with COVID-19. This review aimed to summarize the clinical manifestations, types, and outcomes of COVID-19-associated AE.

Methods

A systematic search was conducted in the PubMed, Embase, and Web of Science databases to identify case reports and case series related to COVID-19-associated AE from 1 January 2020 to 31 March 2023. After a thorough screening and evaluation, irrelevant articles were excluded. Relevant information concerning types, clinical manifestations, and outcomes was extracted and synthesized.

Results

A total of 37 studies, comprising 34 case reports and 3 case series, were included in this review. Among the 42 COVID-19-associated AE patients, 21 (50%) cases were classified as an unknown antibodies (Ab) type of COVID-19-associated AE, 10 (23.80%) cases as anti-N-methyl-D-aspartate (NMDA) encephalitis, 4 (9.5%) cases as limbic encephalitis, and 3 (7.1%) cases as anti-myelin-oligodendrocyte-glycoprotein encephalitis, along with other rare types of AE. Disturbance of consciousness, seizures, and psychiatric symptoms were identified as the main clinical manifestations of COVID-19-associated AE. While the symptoms of AE displayed variation, most patients achieved full recovery although a few experienced residual symptoms of neurological damage.

Conclusion

This systematic review comprehensively describes the characteristics of COVID-19-associated AE. The main type of COVID-19-associated AE identified in this study is an unknown Ab type of COVID-19-associated AE. Despite the potentially life-threatening risks of COVID-19-associated AE, the majority of patients survived, with some patients reporting residual neurological symptoms.
Case report: A case of spinal muscular atrophy in a preterm infant: risks and benefits of treatment
Authors: Nigro Elisa , Grunebaum Eyal , Kamath Binita , Licht Christoph , Malcolmson Caroline , Jeewa Aamir , Campbell Craig , McMillan Hugh , Chakraborty Pranesh , Tarnopolsky Mark , Gonorazky Hernan
Published: September 2023

Spinal muscular atrophy (SMA) is a neuromuscular genetic disorder caused by the loss of lower motor neurons leading to progressive muscle weakness and atrophy. With the rise of novel therapies and early diagnosis on newborn screening (NBS), the natural history of SMA has been evolving. Earlier therapeutic interventions can modify disease outcomes and improve survival. The role of treatment in infants born preterm is an important question given the importance of early intervention. In this study, we discuss the case of an infant born at 32 weeks who was diagnosed with SMA on NBS and was treated with Spinraza® (Nusinersen) and Zolgensma® (Onasemnogene abeparvovec-xioi) within the first 2 months of life. With the scarce evidence that currently exists, clinicians should be aware of the efficacy and safety impact of early therapy particularly in the preterm infant.
Prediction of stress-related gastrointestinal bleeding in patients with aneurysmal subarachnoid hemorrhage using caudate Hounsfield unit value in ASPECT score
Authors: Wang Ke , Yuan Kexin , Li Runting , Lin Fa , Chen Yu , Yang Jun , Han Heze , Li Tu , Jia Yitong , Zhou Yunfan , Zhang Haibin , Li Ruinan , Li Zhipeng , Zhao Yahui , Hao Qiang , Chen Xiaolin , Zhao Yuanli
Published: September 2023

Background

Stress-related gastrointestinal bleeding (SRGB) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH), and it can present challenges in patient care and treatment. The aim of this study was to explore the clinical significance of the caudate Hounsfield unit (HU) value in the Alberta Stroke Program Early CT (ASPECT) score for predicting SRGB in patients with aSAH.

Methods

We retrospectively analyzed the data of 531 aSAH patients admitted to our institution between 2019 and 2022. Potential predictors of SRGB were identified using multivariate Cox regression analysis. We used a restricted cubic spline (RCS) to evaluate whether there is a nonlinear relationship between the right caudate HU value and SRGB. MaxStat analysis (titled as maximally selected rank statistics) was performed to identify the optimal cutoff point for the right caudate HU value. Another Kaplan–Meier method with the log-rank test was used to analyze the right caudate HU value in predicting the occurrence of SRGB.

Results

The incidence rate of SRGB was 17.9%. In the multivariate Cox regression analysis, the right caudate HU value was an independent predictor of SRGB [Hazard ratio (HR) = 0.913; 95% confidence interval (CI): 0.847–0.983, and p = 0.016]. The RCS indicated that the incidence of developing SRGB reduces with increasing right caudate HU values (nonlinear p = 0.78). The optimal cut-off value of the right caudate HU was 25.1.

Conclusion

Among aSAH patients, lower right caudate HU values indicated a higher risk of developing SRGB. Our findings provide further evidence for the relationship between the gastrointestinal system and the brain.
“PNP slows down” – linearly-reduced whole body joint velocities and altered gait patterns in polyneuropathy
Authors: Walz Isabelle D. , Waibel Sarah , Lippi Vittorio , Kammermeier Stefan , Gollhofer Albert , Maurer Christoph
Published: September 2023

Introduction

Gait disturbances are a common consequence of polyneuropathy (PNP) and a major factor in patients’ reduced quality of life. Less is known about the underlying mechanisms of PNP-related altered motor behavior and its distribution across the body. We aimed to capture whole body movements in PNP during a clinically relevant mobility test, i.e., the Timed Up and Go (TUG). We hypothesize that joint velocity profiles across the entire body would enable a deeper understanding of PNP-related movement alterations. This may yield insights into motor control mechanisms responsible for altered gait in PNP.

Methods

20 PNP patients (61 ± 14 years) and a matched healthy control group (CG, 60 ± 15 years) performed TUG at (i) preferred and (ii) fast movement speed, and (iii) while counting backward (dual-task). We recorded TUG duration (s) and extracted gait-related parameters [step time (s), step length (cm), and width (cm)] during the walking sequences of TUG and calculated center of mass (COM) velocity [represents gait speed (cm/s)] and joint velocities (cm/s) (ankles, knees, hips, shoulders, elbows, wrists) with respect to body coordinates during walking; we then derived mean joint velocities and ratios between groups.

Results

Across all TUG conditions, PNP patients moved significantly slower (TUG time, gait speed) with prolonged step time and shorter steps compared to CG. Velocity profiles depend significantly on group designation, TUG condition, and joint. Correlation analysis revealed that joint velocities and gait speed are closely interrelated in individual subjects, with a 0.87 mean velocity ratio between groups.

Discussion

We confirmed a PNP-related slowed gait pattern. Interestingly, joint velocities in the rest of the body measured in body coordinates were in a linear relationship to each other and to COM velocity in space coordinates, despite PNP. Across the whole body, PNP patients reduce, on average, their joint velocities with a factor of 0.87 compared to CG and thus maintain movement patterns in terms of velocity distributions across joints similarly to healthy individuals. This down-scaling of mean absolute joint velocities may be the main source for the altered motor behavior of PNP patients during gait and is due to the poorer quality of their somatosensory information.

Clinical Trial Registration

https://drks.de/search/de, identifier DRKS00016999.
Fear of heights shapes postural responses to vibration-induced balance perturbation at virtual height
Authors: Bzdúšková Diana , Marko Martin , Hirjaková Zuzana , Riečanský Igor , Kimijanová Jana
Published: September 2023

Introduction

Standing upright at height is a challenging situation involving intense threat of balance loss and fall. The ability to maintain balance in such conditions requires properly resolving sensory conflicts and is influenced by fear. To get more insight on the role of fear in balance control at height, we explored the dynamics of postural behavior in the situation of enhanced threat of potential balance loss.

Methods

In 40 young individuals with varying fear of heights, we combined simulated exposure to height in a virtual reality environment with bilateral vibration of tibialis anterior muscles which evokes posture destabilization (the so-called vibration-induced falling).

Results

Under such condition of enhanced postural threat, individuals with intense fear of heights showed stronger stiffening of posture compared with individuals with low fear of heights who react more flexibly and adaptively to posture destabilization. This group difference was evident already at ground level but further increased during virtual height exposure.

Discussion

Our data show that fear of height significantly affects posture adaptation to balance-destabilizing events. Our findings demonstrate that the assessment of postural behavior during threatening situations in the virtual reality environment provides valuable insights into the mechanisms of balance control and may be used to develop novel strategies aimed at prevention of falls.
Investigating the technical feasibility of magnetoencephalography during transcranial direct current stimulation
Authors: Shirota Yuichiro , Fushimi Motofumi , Sekino Masaki , Yumoto Masato
Published: September 2023

Introduction

Magnetoencephalography (MEG) can measure weak magnetic fields produced by electrical brain activity. Transcranial direct current stimulation (tDCS) can affect such brain activities. The concurrent application of both, however, is challenging because tDCS presents artifacts on the MEG signal. If brain activity during tDCS can be elucidated by MEG, mechanisms of plasticity-inducing and other effects of tDCS would be more comprehensively understood. We tested the technical feasibility of MEG during tDCS using a phantom that produces an artificial current dipole simulating focal brain activity. An earlier study investigated estimation of a single oscillating phantom dipole during tDCS, and we systematically tested multiple dipole locations with a different MEG device.

Methods

A phantom provided by the manufacturer was used to produce current dipoles from 32 locations. For the 32 dipoles, MEG was recorded with and without tDCS. Temporally extended signal space separation (tSSS) was applied for artifact rejection. Current dipole sources were estimated as equivalent current dipoles (ECDs). The ECD modeling quality was assessed using localization error, amplitude error, and goodness of fit (GOF). The ECD modeling performance with and without tDCS, and with and without tSSS was assessed.

Results

Mean localization errors of the 32 dipoles were 1.70 ± 0.72 mm (tDCS off, tSSS off, mean ± standard deviation), 6.13 ± 3.32 mm (tDCS on, tSSS off), 1.78 ± 0.83 mm (tDCS off, tSSS on), and 5.73 ± 1.60 mm (tDCS on, tSSS on). Mean GOF findings were, respectively, 92.3, 87.4, 97.5, and 96.7%. Modeling was affected by tDCS and restored by tSSS, but improvement of the localization error was marginal, even with tSSS. Also, the quality was dependent on the dipole location.

Discussion

Concurrent tDCS-MEG recording is feasible, especially when tSSS is applied for artifact rejection and when the assumed location of the source of activity is favorable for modeling. More technical studies must be conducted to confirm its feasibility with different source modeling methods and stimulation protocols. Recovery of single-trial activity under tDCS warrants further research.