bluuebunny/crossref_metadata_2025_split huggingface dataset:
Progressive cognitive impairment after recovery from neuroinvasive and non-neuroinvasive Listeria monocytogenes infection
Authors: Cassidy Benjamin R. , Logan Sreemathi , Farley Julie A. , Owen Daniel B. , Sonntag William E. , Drevets Douglas A. 
Published: April 2023

BackgroundNeuro-cognitive impairment is a deleterious complication of bacterial infections that is difficult to treat or prevent. Listeria monocytogenes (Lm) is a neuroinvasive bacterial pathogen and commonly used model organism for studying immune responses to infection. Antibiotic-treated mice that survive systemic Lm infection have increased numbers of CD8+ and CD4+ T-lymphocytes in the brain that include tissue resident memory (TRM) T cells, but post-infectious cognitive decline has not been demonstrated. We hypothesized that Lm infection would trigger cognitive decline in accord with increased numbers of recruited leukocytes.MethodsMale C57BL/6J mice (age 8 wks) were injected with neuroinvasive Lm 10403s, non-neuroinvasive Δhly mutants, or sterile saline. All mice received antibiotics 2-16d post-injection (p.i.) and underwent cognitive testing 1 month (mo) or 4 mo p.i. using the Noldus PhenoTyper with Cognition Wall, a food reward-based discrimination procedure using automated home cage based observation and monitoring. After cognitive testing, brain leukocytes were quantified by flow cytometry.ResultsChanges suggesting cognitive decline were observed 1 mo p.i. in both groups of infected mice compared with uninfected controls, but were more widespread and significantly worse 4 mo p.i. and most notably after Lm 10403s. Impairments were observed in learning, extinction of prior learning and distance moved. Infection with Lm 10403s, but not Δhly Lm, significantly increased numbers of CD8+ and CD4+ T-lymphocytes, including populations expressing CD69 and TRM cells, 1 mo p.i. Numbers of CD8+, CD69+CD8+ T-lymphocytes and CD8+ TRM remained elevated at 4 mo p.i. but numbers of CD4+ cells returned to homeostatic levels. Higher numbers of brain CD8+ T-lymphocytes showed the strongest correlations with reduced cognitive performance.ConclusionsSystemic infection by neuroinvasive as well as non-neuroinvasive Lm triggers a progressive decline in cognitive impairment. Notably, the deficits are more profound after neuroinvasive infection that triggers long-term retention of CD8+ T-lymphocytes in the brain, than after non-neuroinvasive infection, which does not lead to retained cells in the brain. These results support the conclusion that systemic infections, particularly those that lead to brain leukocytosis trigger a progressive decline in cognitive function and implicate CD8+ T-lymphocytes, including CD8+TRM in the etiology of this impairment.
Presence of tophi and carotid plaque were risk factors of MACE in subclinical artherosclerosis patients with gout: a longitudinal cohort study
Authors: Wang Yu , Deng Xuerong , Zhang Xiaohui , Geng Yan , Ji Lanlan , Song Zhibo , Zhang Zhuoli 
Published: April 2023

BackgroundPatients with gout carry an excess risk for cardiovascular disease (CVD), but the contribution of subclinical atherosclerosis to the CVD risk has never been reported. In this study, we aimed to explore the predictive factors for incident major adverse cardiovascular events (MACE) in gout patients without a previous history of CVD or cerebral vascular disease.MethodsA single-center, long-term follow-up cohort analysis was performed to assess subclinical atherosclerosis at baseline since 2008. Patients with a previous history of CVD or cerebrovascular disease were excluded. The outcome of the study was the first MACE. The presence of subclinical atherosclerosis was assessed by carotid plaque (CP), and carotid intima-media thickness (CMIT) was determined by ultrasound. An ultrasound scan of bilateral feet and ankles was performed at baseline. The association between tophi, carotid atherosclerosis, and the risk of developing incident MACE was evaluated using Cox proportional hazards models with adjustment for the CVD risk scores.ResultsA total of 240 consecutive patients with primary gout were recruited. Their mean age was 44.0 years, with male predominance (238, 99.2%). During a median follow-up of 10.3 years, incident MACE was ascertained in 28 (11.7%) patients. In a Cox hazards model, controlling for the CV risk scores, the presence of at least two tophi (HR, 2.12–5.25, p &lt; 0.05) and carotid plaque (HR, 3.72–4.01, p &lt; 0.05) were identified as independent predictors of incident MACE in gout patients.ConclusionsThe presence of at least two tophi and carotid plaque on an ultrasound could independently predict MACE in addition to conventional cardiovascular risk factors in gout patients.
Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion
Authors: Shao Ming-Ming , Pei Xue-Bin , Chen Qing-Yu , Wang Feng , Wang Zhen , Zhai Kan 
Published: April 2023

IntroductionTumor-associated macrophages are one of the key components of the tumor microenvironment. The immunomodulatory activity and function of macrophages in malignant pleural effusion (MPE), a special tumor metastasis microenvironment, have not been clearly defined.MethodsMPE-based single-cell RNA sequencing data was used to characterize macrophages. Subsequently, the regulatory effect of macrophages and their secreted exosomes on T cells was verified by experiments. Next, miRNA microarray was used to analyze differentially expressed miRNAs in MPE and benign pleural effusion, and data from The Cancer Genome Atlas (TCGA) was used to evaluate the correlation between miRNAs and patient survival.ResultsSingle-cell RNA sequencing data showed macrophages were mainly M2 polarized in MPE and had higher exosome secretion function compared with those in blood. We found that exosomes released from macrophages could promote the differentiation of naïve T cells into Treg cells in MPE. We detected differential expression miRNAs in macrophage-derived exosomes between MPE and benign pleural effusion by miRNA microarray and found that miR-4443 was significantly overexpressed in MPE exosomes. Gene functional enrichment analysis showed that the target genes of miR-4443 were involved in the regulation of protein kinase B signaling and lipid biosynthetic process.ConclusionsTaken together, these results reveal that exosomes mediate the intercellular communication between macrophages and T cells, yielding an immunosuppressive environment for MPE. miR-4443 expressed by macrophages, but not total miR-4443, might serve as a prognostic marker in patients with metastatic lung cancer.
Complete variable domain sequences of monoclonal antibody light chains identified from untargeted RNA sequencing data
Authors: Nau Allison , Shen Yun , Sanchorawala Vaishali , Prokaeva Tatiana , Morgan Gareth J. 
Published: April 2023

IntroductionMonoclonal antibody light chain proteins secreted by clonal plasma cells cause tissue damage due to amyloid deposition and other mechanisms. The unique protein sequence associated with each case contributes to the diversity of clinical features observed in patients. Extensive work has characterized many light chains associated with multiple myeloma, light chain amyloidosis and other disorders, which we have collected in the publicly accessible database, AL-Base. However, light chain sequence diversity makes it difficult to determine the contribution of specific amino acid changes to pathology. Sequences of light chains associated with multiple myeloma provide a useful comparison to study mechanisms of light chain aggregation, but relatively few monoclonal sequences have been determined. Therefore, we sought to identify complete light chain sequences from existing high throughput sequencing data.MethodsWe developed a computational approach using the MiXCR suite of tools to extract complete rearranged IGVL-IGJL sequences from untargeted RNA sequencing data. This method was applied to whole-transcriptome RNA sequencing data from 766 newly diagnosed patients in the Multiple Myeloma Research Foundation CoMMpass study.ResultsMonoclonal IGVL-IGJL sequences were defined as those where &gt;50% of assigned IGK or IGL reads from each sample mapped to a unique sequence. Clonal light chain sequences were identified in 705/766 samples from the CoMMpass study. Of these, 685 sequences covered the complete IGVL-IGJL region. The identity of the assigned sequences is consistent with their associated clinical data and with partial sequences previously determined from the same cohort of samples. Sequences have been deposited in AL-Base.DiscussionOur method allows routine identification of clonal antibody sequences from RNA sequencing data collected for gene expression studies. The sequences identified represent, to our knowledge, the largest collection of multiple myeloma-associated light chains reported to date. This work substantially increases the number of monoclonal light chains known to be associated with non-amyloid plasma cell disorders and will facilitate studies of light chain pathology.
Nomogram to predict postpartum hemorrhage in cesarean delivery for twin pregnancies: a retrospective cohort study in China
Authors: Zhang Yanhua , Chen Lu , Zhou Weixiao , Lin Jun , Wen Hong 
Published: April 2023

BackgroundPostpartum hemorrhage (PPH) is the most common cause of maternal morbidity and mortality worldwide. A reliable risk assessment tool for PPH could optimize available interventions to reduce adverse maternal outcomes.ObjectiveThe objective of this study was to explore a nomogram predicting the risk of postpartum hemorrhage after cesarean delivery for twin pregnancies.MethodsThis single-center retrospective cohort study conducted twin pregnancies who underwent cesarean delivery between January 2014 and July 2021. Propensity score matching at baseline was used to match PPH (blood loss ≥1000 mL) and non-PPH group (blood loss &lt;1000 mL). A nomogram was developed to predict the risk of PPH in cesarean delivery for twin pregnancies. The receiver operating characteristic curve (ROC), calibration plot, and decision curve analysis (DCA) were, respectively, used to evaluate the discrimination, calibration, and clinical utility of the prediction models.ResultsAfter propensity score matching, 186 twin pregnancies in the PPH group were matched with 186 controls in the non-PPH group. Seven independent prognostic variables, including antepartum albumin, assisted reproductive technology, hypertensive disorders of pregnancy, placenta previa, placenta accrete spectrum, intrapartum cesarean delivered, and estimated weights of twins, were used to build the nomogram. Based on the performance of the model, it appears that a good calibration (Hosmer–Lemeshow χ2 = 4.84, P &gt; 0.05), an excellent predictive ability (area under the curve: 0.778, 95% CI: 0.732–0.825), and a good positive net benefit in the predictive model have been achieved.ConclusionThe nomogram was first generated to predict PPH in cesarean delivery for twin pregnancies, which could help clinicians to provide a reference for the preoperative surgical plan, choose optimal treatments, optimize healthcare resources, and thereby reduce the associated adverse maternal outcomes.
Streptomyces catenulae as a Novel Marine Actinobacterium Mediated Silver Nanoparticles: Characterization, Biological Activities, and Proposed Mechanism of Antibacterial Action
Authors: Khalil Maha A. , El-Shanshoury Abd El-Raheem R. , Alghamdi Maha A. , Sun Jianzhong , Ali Sameh S. 
Published: April 2023

Graphical AbstractBiological applications of silver nanoparticles derived from Streptomyces catenulae.
Virotyping and genetic antimicrobial susceptibility testing of porcine ETEC/STEC strains and associated plasmid types
Authors: Vereecke Nick , Van Hoorde Sander , Sperling Daniel , Theuns Sebastiaan , Devriendt Bert , Cox Eric 
Published: April 2023

IntroductionEnterotoxigenicEscherichia coli(ETEC) infections are the most common cause of secretory diarrhea in suckling and post-weaning piglets. For the latter, Shiga toxin-producingEscherichia coli(STEC) also cause edema disease. This pathogen leads to significant economic losses. ETEC/STEC strains can be distinguished from generalE. coliby the presence of different host colonization factors (e.g., F4 and F18 fimbriae) and various toxins (e.g., LT, Stx2e, STa, STb, EAST-1). Increased resistance against a wide variety of antimicrobial drugs, such as paromomycin, trimethoprim, and tetracyclines, has been observed. Nowadays, diagnosing an ETEC/STEC infection requires culture-dependent antimicrobial susceptibility testing (AST) and multiplex PCRs, which are costly and time-consuming.MethodsHere, nanopore sequencing was used on 94 field isolates to assess the predictive power, using the meta R package to determine sensitivity and specificity and associated credibility intervals of genotypes associated with virulence and AMR.ResultsGenetic markers associated with resistance for amoxicillin (plasmid-encoded TEM genes), cephalosporins (ampCpromoter mutations), colistin (mcrgenes), aminoglycosides (aac(3)andaph(3)genes), florfenicol (floR), tetracyclines (tetgenes), and trimethoprim-sulfa (dfrAgenes) could explain most acquired resistance phenotypes. Most of the genes were plasmid-encoded, of which some collocated on a multi-resistance plasmid (12 genes against 4 antimicrobial classes). For fluoroquinolones, AMR was addressed by point mutations within the ParC and GyrA proteins and theqnrS1gene. In addition, long-read data allowed to study the genetic landscape of virulence- and AMR-carrying plasmids, highlighting a complex interplay of multi-replicon plasmids with varying host ranges.ConclusionOur results showed promising sensitivity and specificity for the detection of all common virulence factors and most resistance genotypes. The use of the identified genetic hallmarks will contribute to the simultaneous identification, pathotyping, and genetic AST within a single diagnostic test. This will revolutionize future quicker and more cost-efficient (meta)genomics-driven diagnostics in veterinary medicine and contribute to epidemiological studies, monitoring, tailored vaccination, and management.
Traditional mineral medicine realgar and Realgar-Indigo naturalis formula potentially exerted therapeutic effects by altering the gut microbiota
Authors: Luo Lu , Li Chaofeng , Huang Nanxi , Wang Qiaochu , Zhang Zihao , Song Chen , Yang Hui , Yuan Maowen , Xu Ziwen , Sun Jialei , Zhang Zhijie 
Published: April 2023

IntroductionRealgar has a long history ofuse in traditional medicines. However, the mechanism through which Realgar or Realgar-Indigo naturalis formula (RIF) exert therapeutic effects is only partially understood.MethodsIn this study, 60 feces and 60 ileum samples from rats administered with realgar or RIF were collected to examine the gut microbiota.ResultsThe results showed that realgar and RIF influenced different microbiota in both feces and ileum. Compared with realgar, RIF at low dosage (0.1701 g/3 ml) significantly increased the microbiota diversity. LEfSe and random forest analyses showed that the bacterium Bacteroidales was significantly altered after RIF administration, and it was predicted that these microorganisms contribute to the inorganic arsenic metabolic process.DiscussionOur results suggest that realgar and RIF may exert their therapeutic effects through influencing microbiota. The low dose of RIF had greater effects on increasing the diversity of microbiota, and Bacteroidales in feces might participate in the inorganic arsenic metabolic process to exert therapeutic effects for realgar.
Identifying genetic variants for amyloid β in subcortical vascular cognitive impairment
Authors: Kim Hang-Rai , Jung Sang-Hyuk , Kim Beomsu , Kim Jaeho , Jang Hyemin , Kim Jun Pyo , Kim So Yeon , Na Duk L. , Kim Hee Jin , Nho Kwangsik , Won Hong-Hee , Seo Sang Won 
Published: April 2023

BackgroundThe genetic basis of amyloid β (Aβ) deposition in subcortical vascular cognitive impairment (SVCI) is still unknown. Here, we investigated genetic variants involved in Aβ deposition in patients with SVCI.MethodsWe recruited a total of 110 patients with SVCI and 424 patients with Alzheimer’s disease-related cognitive impairment (ADCI), who underwent Aβ positron emission tomography and genetic testing. Using candidate AD-associated single nucleotide polymorphisms (SNPs) that were previously identified, we investigated Aβ-associated SNPs that were shared or distinct between patients with SVCI and those with ADCI. Replication analyses were performed using the Alzheimer’s Disease Neuroimaging Initiative (ADNI) and Religious Orders Study and Rush Memory and Aging Project cohorts (ROS/MAP).ResultsWe identified a novel SNP, rs4732728, which showed distinct associations with Aβ positivity in patients with SVCI (Pinteraction = 1.49 × 10–5); rs4732728 was associated with increased Aβ positivity in SVCI but decreased Aβ positivity in ADCI. This pattern was also observed in ADNI and ROS/MAP cohorts. Prediction performance for Aβ positivity in patients with SVCI increased (area under the receiver operating characteristic curve = 0.780; 95% confidence interval = 0.757–0.803) when rs4732728 was included. Cis-expression quantitative trait loci analysis demonstrated that rs4732728 was associated with EPHX2 expression in the brain (normalized effect size = −0.182, P = 0.005).ConclusionThe novel genetic variants associated with EPHX2 showed a distinct effect on Aβ deposition between SVCI and ADCI. This finding may provide a potential pre-screening marker for Aβ positivity and a candidate therapeutic target for SVCI.
Diaphragmatic ultrasound can help evaluate pulmonary dysfunction in patients with stroke
Authors: Chen Yifei , Zhou Shuyan , Liao Lixia , He Jinyan , Tang Danzhe , Wu Wen , Wang Kangling 
Published: April 2023

ObjectivePulmonary dysfunction after stroke is increasingly gaining attention from clinical and rehabilitation specialists. However, owing to cognitive and motor dysfunction in patients with stroke, determining the pulmonary function of these patients remains challenging. The present study aimed to devise a simple method for an early evaluation of pulmonary dysfunction in patients with stroke.MethodsOverall, 41 patients with stroke in the recovery period (stroke group) and 22 matched healthy controls (control group) were included in the study. We first collected data regarding baseline characteristics for all participants. Furthermore, the participants with stroke were examined using additional scales, such as the National Institutes of Health Stroke Scale (NIHSS), Fugl–Meyer assessment scale (FMA), and modified Barthel Index (MBI). Subsequently, we examined the participants with simple pulmonary function detection and diaphragm ultrasound (B-mode). Ultrasound indices calculated were as follows: the thickness of the diaphragm under the position of functional residual capacity (TdiFRC), the thickness of the diaphragm under the position of forced vital capacity (TdiFVC), thickness fraction, and diaphragmatic mobility. Finally, we compared and analyzed all data to identify group differences, the correlation between pulmonary function and diaphragmatic ultrasound indices, and the correlation between pulmonary function and assessment scale scores in patients with stroke, respectively.ResultsCompared with the control group, patients in the stroke group exhibited lower values for indices of pulmonary and diaphragmatic function (p &lt; 0.001), except for TdiFRC (p &gt; 0.05). The majority of the patients with stroke had restrictive ventilatory dysfunction, as indicated by a significantly higher incidence ratio (36 in 41 patients) than that in the control group (0 in 22 patients) (p &lt; 0.001). Moreover, significant correlations were found between pulmonary function and diaphragmatic ultrasound indices (p &lt; 0.05), with the strongest correlation between TdiFVC and pulmonary indices. In the stroke group, pulmonary function indices were negatively correlated with the NIHSS scores (p &lt; 0.001) and positively correlated with the FMA scores (p &lt; 0.001). No (p &gt; 0.05) or weak (p &lt; 0.05) correlation was found between pulmonary function indices and the MBI scores.ConclusionWe found that patients with stroke had pulmonary dysfunction even in the recovery period. Diaphragmatic ultrasound can be used as a simple and effective tool for detecting pulmonary dysfunction in patients with stroke, with TdiFVC being the most effective index.
Plasma levels of VIP are not elevated during PACAP- and VIP-induced cluster headache attacks: an exploratory study
Authors: Deligianni Christina , Pellesi Lanfranco , Chaudhry Basit Ali , Haulund Vollesen Anne Luise , Snoer Agneta Henriette , Hannibal Jens , Jensen Rigmor Højland , Ashina Messoud 
Published: April 2023

BackgroundPituitary adenylate cyclase-activating peptide (PACAP) and vasoactive intestinal peptide (VIP) provoked cluster headache attacks in individuals with episodic cluster headache during their active phase and individuals with chronic cluster headache. In this study, we investigated whether infusions of PACAP and VIP caused alterations in plasma levels of VIP and their potential contribution to induced cluster headache attacks.MethodsParticipants received either PACAP or VIP infusion for 20 min on 2 separate days with an interval of at least 7 days in between. Blood collection was performed at T0, T20, T30, and T90. Plasma levels of VIP were measured using a validated radioimmunoassay method.ResultsBlood samples were collected from participants with episodic cluster headache in the active phase (eCHA, n = 14), remission (eCHR, n = 15), and from participants with chronic cluster headache (cCH, n = 15). Baseline levels of VIP did not differ among the three groups (p = 0.1161). During PACAP infusion, mixed-effects analysis revealed a significant increase in plasma levels of VIP in eCHA (p = 0.0300) and eCHR (p = 0.0058) but not in cCH (p = 0.2930). We found no difference in the increase of plasma VIP levels between patients who developed PACAP38- or VIP-induced attacks.ConclusionCluster headache attacks induced by PACAP38 or VIP infusion are not associated with changes in plasma levels of VIP. Further studies are needed to investigate the role of VIP and the parasympathetic system in cluster headache.Clinical trial registrationThe parent study is registered at ClinicalTrials.gov (NCT03814226).