bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mast cells selectively produce inflammatory mediators and impact the early response to Chlamydia reproductive tract infection
Authors: Mayavannan Animamalar , Shantz Emily , Haidl Ian D. , Wang Jun , Marshall Jean S. 
Published: April 2023

IntroductionChlamydia trachomatis (C. trachomatis) is a Gram-negative obligate intracellular bacterium that causes reproductive tract complications in women, including ectopic pregnancies and tubal factor infertility. We hypothesized that mast cells, which are common at mucosal barriers, may contribute to responses to Chlamydia infection and aimed to define human mast cell responses to C. trachomatis.MethodsHuman cord blood-derived mast cells (CBMCs) were exposed to C. trachomatis to assess bacterial uptake, mast cell degranulation, gene expression, and production of inflammatory mediators. The role of formyl peptide receptors and Toll-like receptor 2 (TLR2) were investigated using pharmacological inhibitors and soluble TLR2. Mast cell-deficient mice and littermate controls were used to examine the in vivo role of mast cells in influencing the immune response to Chlamydia infection in the female reproductive tract.ResultsC. trachomatis bacteria were taken up by human mast cells but did not replicate efficiently inside CBMCs. C. trachomatis-activated mast cells did not degranulate but maintained viability and exhibited cellular activation with homotypic aggregation and upregulation of ICAM-1. However, they significantly enhanced the gene expression of IL1B, CCL3, NFKB1, CXCL8, and IL6. Inflammatory mediators were produced, including TNF, IL-1β, IL-1RA, IL-6, GM-CSF, IL-23, CCL3, CCL5, and CXCL8. Endocytic blockade resulted in reduced gene expression of IL6, IL1B, and CCL3, suggesting C. trachomatis induced mast cell activation in both extracellular and intracellular locations. The IL-6 response to C. trachomatis was reduced when CBMCs were treated with C. trachomatis coated with soluble TLR2. Mast cells derived from TLR2-deficient mice also demonstrated a reduced IL-6 response to C. muridarum. Five days following C. muridarum infection, mast cell-deficient mice showed attenuated CXCL2 production and significantly reduced numbers of neutrophils, eosinophils, and B cells in the reproductive tract when compared with mast cell-containing littermates.DiscussionTaken together, these data demonstrate that mast cells are reactive to Chlamydia spp. through multiple mechanisms that include TLR2-dependent pathways. Mast cells also play an important role in shaping in vivo immune responses in Chlamydia reproductive tract infection through both effector cell recruitment and modification of the chemokine microenvironment.
Lamellar macular defects: are degenerative lamellar macular holes truly degenerative?
Authors: Pertile Grazia , Iacovello Daniela , Maraone Giorgia , Bottega Elisa , Guerriero Massimo , Maggio Emilia 
Published: April 2023

PurposeTo investigate morpho-functional changes after surgical treatment for ERM foveoschisis or lamellar macular hole (LMH), and to evaluate whether the two entities are associated with different healing processes and long-term outcomes.DesignRetrospective interventional case series.MethodsA total of 56 eyes, treated for lamellar macular defects and followed up for 24 months, were enrolled. The eyes were divided into two groups: 34 with ERM foveoschisis and 22 with LMH. Changes in the following features were evaluated and compared between the two groups: best-corrected visual acuity (BCVA), external limiting membrane (ELM) and ellipsoid zone (EZ) defects, central foveal thickness (CFT), and autofluorescence (FAF) diameter and area.ResultsAfter surgery, progressive BCVA improvement was observed with no significant difference between the two groups (p-value: 0.06). An increased number of eyes with intact outer-retinal layers was found both in the ERM foveoschisis and LMH groups. FAF diameter and area decreased significantly throughout the FU with no significant difference between the two groups (p-value: 0.2).ConclusionIn the present study, significant functional and microstructural improvements were observed after surgery for both ERM foveoschisis and LMH, demonstrating considerable repair potential in both types of lamellar defects. These findings question the true “degenerative” nature of LMH.
A westernized diet changed the colonic bacterial composition and metabolite concentration in a dextran sulfate sodium pig model for ulcerative colitis
Authors: Panah Farhad M. , Nielsen Katrine D. , Simpson Gavin L. , Schönherz Anna , Schramm Andreas , Lauridsen Charlotte , Nielsen Tina S. , Højberg Ole , Fredborg Marlene , Purup Stig , Canibe Nuria 
Published: April 2023

IntroductionUlcerative colitis (UC) is characterized by chronic inflammation in the colonic epithelium and has a blurred etiology. A western diet and microbial dysbiosis in the colon were reported to play a role in UC development. In this study, we investigated the effect of a westernized diet, i.e., increasing fat and protein content by including ground beef, on the colonic bacterial composition in a dextran sulfate sodium (DexSS) challenged pig study.MethodsThe experiment was carried out in three complete blocks following a 2×2 factorial design including 24 six-week old pigs, fed either a standard diet (CT) or the standard diet substituted with 15% ground beef to simulate a typical westernized diet (WD). Colitis was induced in half of the pigs on each dietary treatment by oral administration of DexSS (DSS and WD+DSS, respectively). Samples from proximal and distal colon and feces were collected.Results and discussionBacterial alpha diversity was unaffected by experimental block, and sample type. In proximal colon, WD group had similar alpha diversity to CT group and the WD+DSS group showed the lowest alpha diversity compared to the other treatment groups. There was a significant interaction between western diet and DexSS for beta diversity, based on Bray-Curtis dissimilarly. The westernized diet and DexSS resulted in three and seven differentially abundant phyla, 21 and 65 species, respectively, mainly associated with the Firmicutes and Bacteroidota phyla followed by Spirochaetota, Desulfobacterota, and Proteobacteria. The concentration of short-chain fatty acids (SCFA) was lowest in the distal colon. Treatment had a slight effect on the estimates for microbial metabolites that might have valuable biological relevance for future studies. The concentration of putrescine in the colon and feces and that of total biogenic amines was highest in the WD+DSS group. We conclude that a westernized diet could be a potential risk factor and an exacerbating agent for UC by reducing the abundance of SCFA-producing bacteria, increasing the abundance of pathogens such asHelicobacter trogontum, and by increasing the concentration of microbial proteolytic-derived metabolites in the colon.
Complex probiotics alleviate ampicillin-induced antibiotic-associated diarrhea in mice
Authors: Li Wenwen , Zhang Siyu , Wang Yanyan , Bian Hongsheng , Yu Shuang , Huang Lili , Ma Weiwei 
Published: April 2023

AimAntibiotic-associated diarrhea (AAD) is a common side effect during antibiotic treatment, which can cause dysbacteriosis of the gut microbiota. Previous studies have shown beneficial effects in AAD treatment with Bifidobacterium lactis XLTG11, Lactobacillus casei Zhang, Lactobacillus plantarum CCFM8661, and Lactobacillus rhamnosus Probio-M9. However, no studies have been conducted on the immunomodulatory effects and protective intestinal barrier function of four complex probiotics. The aim of our study is to investigate the alleviation effects of complex probiotics on ampicillin-induced AAD.MethodsThirty-six BALB/c mice were randomly divided into six groups: normal control group (NC), model control group (MC), low-, medium-, and high-dose probiotics groups (LD, MD, and HD), and positive drug (Bifico, 1 × 107 cfu) control group (PDC; Bifico, also known as Bifidobacterium Triple Live Capsule, is composed of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis). An AAD model was established by intragastric administration of ampicillin, by gavage of different doses of complex probiotics and Bifico. The weight gain, fecal water content, loose stool grade, intestinal permeability, total protein and albumin levels, intestinal barrier, cytokine levels, and gut microbiota were determined.ResultsThe results showed that complex probiotics significantly decreased the fecal water content, loose stool grade, intestinal permeability, and ileum tissue damage. Their application increased the weight gain, SIgA, TP, and ALB levels. Additionally, complex probiotics significantly decreased the levels of pro-inflammatory cytokines and increased those of anti-inflammatory cytokines. Meanwhile, the mRNA expression levels of ZO-1, occludin, claudin-1, and MUC2 were significantly upregulated in the probiotic-treated group. Furthermore, the complex probiotics increased the gut microbiota diversity and modulated the changes in the gut microbiota composition caused by ampicillin. At the phylum level, the abundance of Proteobacteria in the HD group was lower than that in the MC group, whereas that of Bacteroidetes was higher. At the genus level, the abundances of Klebsiella and Parabacteroides in the HD group were lower, whereas those of Bacteroides, Muribaculaceae, and Lactobacillus were higher than those in the MC group. Moreover, Spearman’s correlation analysis also found that several specific gut microbiota were significantly correlated with AAD-related indicators.ConclusionWe found that complex probiotics improved the diarrhea-related indexes, regulated gut microbiota composition and diversity, increased the expression levels of intestinal protective barrier-related genes, preserved the intestinal barrier function, and relieved inflammation and intestinal injury, thereby effectively improving AAD-associated symptoms.
A spitting image: molecular diagnostics applied to saliva enhance detection of Streptococcus pneumoniae and pneumococcal serotype carriage
Authors: Miellet Willem R. , van Veldhuizen Janieke , Litt David , Mariman Rob , Wijmenga-Monsuur Alienke J. , Nieuwenhuijsen Tessa , Christopher Jennifer , Thombre Rebecca , Eletu Seyi , Bosch Thijs , Rots Nynke Y. , van Houten Marianne Alice , Miller Elizabeth , Fry Norman K. , Sanders Elisabeth A. M. , Trzciński Krzysztof 
Published: April 2023

BackgroundDespite strong historical records on the accuracy of saliva testing, oral fluids are considered poorly suited for pneumococcal carriage detection. We evaluated an approach for carriage surveillance and vaccine studies that increases the sensitivity and specificity of pneumococcus and pneumococcal serotype detection in saliva samples.MethodsQuantitative PCR (qPCR)-based methods were applied to detect pneumococcus and pneumococcal serotypes in 971 saliva samples collected from 653 toddlers and 318 adults. Results were compared with culture-based and qPCR-based detection in nasopharyngeal samples collected from children and in nasopharyngeal and oropharyngeal samples collected from adults. Optimal Cq cut-offs for positivity in qPCRs were determined via receiver operating characteristic curve analysis and accuracy of different approaches was assessed using a composite reference for pneumococcal and for serotype carriage based on isolation of live pneumococcus from the person or positivity of saliva samples determined with qPCR. To evaluate the inter-laboratory reproducibility of the method, 229 culture-enriched samples were tested independently in the second center.ResultsIn total, 51.5% of saliva samples from children and 31.8% of saliva samples from adults were positive for pneumococcus. Detection of pneumococcus by qPCR in culture-enriched saliva exhibited enhanced sensitivity and higher agreement with a composite reference compared to diagnostic culture of nasopharyngeal samples in children (Cohen’s κ: 0.69–0.79 vs. 0.61–0.73) and in adults (κ: 0.84–0.95 vs. 0.04–0.33) and culture of oropharyngeal samples in adults (κ: 0.84–0.95 vs. −0.12–0.19). Similarly, detection of serotypes with qPCR in culture-enriched saliva exhibited enhanced sensitivity and higher agreement with a composite reference compared to nasopharyngeal culture in children (κ: 0.73–0.82 vs. 0.61–0.73) and adults (κ: 0.90–0.96 vs. 0.00–0.30) and oropharyngeal culture in adults (κ: 0.90–0.96 vs. −0.13 to 0.30). However, results of qPCRs targeting serotype 4, 5, and 17F and serogroups 9, 12, and 35 were excluded due to assays’ lack of specificity. We observed excellent quantitative agreement for qPCR-based detection of pneumococcus between laboratories. After exclusion of serotype/serogroup-specific assays with insufficient specificity, moderate agreement (κ 0.68, 95% CI 0.58–0.77) was observed.ConclusionMolecular testing of culture-enriched saliva samples improves the sensitivity of overall surveillance of pneumococcal carriage in children and adults, but limitations of qPCR-based approaches for pneumococcal serotypes carriage detection should be considered.
Abnormal prenatal brain development in Chiari II malformation
Authors: Masse Olivia , Kraft Emily , Ahmad Esha , Rollins Caitlin K. , Velasco-Annis Clemente , Yang Edward , Warfield Simon Keith , Shamshirsaz Alireza A. , Gholipour Ali , Feldman Henry A. , Estroff Judy , Grant Patricia Ellen , Vasung Lana 
Published: April 2023

IntroductionThe Chiari II is a relatively common birth defect that is associated with open spinal abnormalities and is characterized by caudal migration of the posterior fossa contents through the foramen magnum. The pathophysiology of Chiari II is not entirely known, and the neurobiological substrate beyond posterior fossa findings remains unexplored. We aimed to identify brain regions altered in Chiari II fetuses between 17 and 26 GW.MethodsWe used in vivo structural T2-weighted MRIs of 31 fetuses (6 controls and 25 cases with Chiari II).ResultsThe results of our study indicated altered development of diencephalon and proliferative zones (ventricular and subventricular zones) in fetuses with a Chiari II malformation compared to controls. Specifically, fetuses with Chiari II showed significantly smaller volumes of the diencephalon and significantly larger volumes of lateral ventricles and proliferative zones.DiscussionWe conclude that regional brain development should be taken into consideration when evaluating prenatal brain development in fetuses with Chiari II.
Sensory organization of postural control after long term space flight
Authors: Shishkin Nikita , Kitov Vladimir , Sayenko Dimitry , Tomilovskaya Elena 
Published: April 2023

BackgroundAlterations in motor control systems is an inevitable consequence of space flights of any duration. After the flight, the crew-members have significant difficulties with maintaining upright balance and locomotion, which last several days following landing. At the same time, the specific mechanisms of these effects remain unclear.ObjectivesThe aim of the study was to assess effects of long-term space flight on postural control and to define the changes of sensory organization caused by microgravity.Methods33 cosmonauts of Russian Space Agency, the members of International Space Station (ISS) flights of duration between 166 and 196 days took part in this study. Computerized Dynamic Posturography (CDP) tests, which include assessment of visual, proprioceptive and vestibular function in postural stability, was performed twice before the flight and on the 3rd, 7th, and 10th days after landing. The video analysis of ankle and hip joints fluctuations was performed to investigate the basis of postural changes.ResultsExposure to long-term space flight was followed by considerable changes of postural stability (−27% of Equilibrium Score value in the most complicated test, SOT5m). Changes in postural strategies to maintain balance were observed in the tests which provide the challenge for vestibular system. In particular, increased hip joint involvement (+100% in median value and +135% in 3rd quartile of hip angle fluctuation RMS in SOT5m) into postural control process was revealed.ConclusionDecrease of postural stability after long-term space flight was associated with alterations in vestibular system and biomechanically was revealed by increased hip strategy which is less accurate, but simpler in terms of the central control.
Intracranial electrophysiological recordings on a swine model of mesial temporal lobe epilepsy
Authors: Zhu Fengjun , Wang Hanwen , Li Lin , Bragin Anatol , Cao Dezhi , Cheng Yuan 
Published: April 2023

ObjectiveTo test the feasibility and reliability of intracranial electrophysiological recordings in an acute status epilepticus model on laboratory swine.MethodIntrahippocampal injection of kainic acid (KA) was performed on 17 male Bama pigs (Sus scrofa domestica) weighing between 25 and 35 kg. Two stereoelectroencephalography (SEEG) electrodes with a total of 16 channels were implanted bilaterally along the sensorimotor cortex to the hippocampus. Brain electrical activity was recorded 2 h daily for 9–28 days. Three KA dosages were tested to evaluate the quantities capable of evoking status epilepticus. Local field potentials (LFPs) were recorded and compared before and after the KA injection. We quantified the epileptic patterns, including the interictal spikes, seizures, and high-frequency oscillations (HFOs), up to 4 weeks after the KA injection. Test–retest reliability using intraclass correlation coefficients (ICCs) were performed on interictal HFO rates to evaluate the recording stability of this model.ResultsThe KA dosage test suggested that a 10 μl (1.0 μg/μl) intrahippocampal injection could successfully evoke status epilepticus lasting from 4 to 12 h. At this dosage, eight pigs (50% of total) had prolonged epileptic events (tonic-chronic seizures + interictal spikes n = 5, interictal spikes alone n = 3) in the later 4 weeks of the video-SEEG recording period. Four pigs (25% of total) had no epileptic activities, and another four (25%) had lost the cap or did not complete the experiments. Animals that showed epileptiform events were grouped as E + (n = 8) and the four animals showing no signs of epileptic events were grouped as E– (n = 4). A total of 46 electrophysiological seizures were captured in the 4-week post-KA period from 4 E + animals, with the earliest onset on day 9. The seizure durations ranged from 12 to 45 s. A significant increase of hippocampal HFOs rate (num/min) was observed in the E+ group during the post-KA period (weeks 1, 2,4, p &lt; 0.05) compared to the baseline. But the E-showed no change or a decrease (in week 2, p = 0.43) compared to their baseline rate. The between-group comparison showed much higher HFO rates in E + vs. E – (F = 35, p &lt; 0.01). The high ICC value [ICC (1, k) = 0.81, p &lt; 0.05] quantified from the HFO rate suggested that this model had a stable measurement of HFOs during the four-week post-KA periods.SignificanceThis study measured intracranial electrophysiological activity in a swine model of KA-induced mesial temporal lobe epilepsy (mTLE). Using the clinical SEEG electrode, we distinguished abnormal EEG patterns in the swine brain. The high test–retest reliability of HFO rates in the post-KA period suggests the utility of this model for studying mechanisms of epileptogenesis. The use of swine may provide satisfactory translational value for clinical epilepsy research.
Short-term effects of intravenous batroxobin in treatment of sudden sensorineural hearing loss: a propensity score-matched study
Authors: Jiang Mengzhu , Huang Huping , Mei Lingyun , He Chufeng , Cai Xinzhang , Jiang Lu , Wu Hong , Wang Xin , Wu Xuewen 
Published: April 2023

BackgroundSudden sensorineural hearing loss (SSNHL) can cause great panic in patients. Whether it is advantageous to add intravenous batroxobin in the treatment of SSNHL remains to be determined. This study aimed to compare the short-term efficacy of therapy combined with intravenous batroxobin and that without intravenous batroxobin in SSNHL patients.MethodsThis retrospective study harvested the data of SSNHL patients hospitalized in our department from January 2008 to April 2021. The hearing levels on the admitted day (before treatment) and the discharge day were considered pre-treatment hearing and post-treatment hearing, respectively. The hearing gain was the difference value of pre-treatment hearing and post-treatment hearing. We used Siegel's criteria and the Chinese Medical Association of Otolaryngology (CMAO) criteria to evaluate hearing recovery. The complete recovery rate, overall effective rate, and hearing gain at each frequency were considered outcomes. Propensity score matching (PSM) was conducted to balance the baseline characteristics between the batroxobin group and the non-batroxobin group. Sensitivity analysis was carried out in flat-type and total-deafness SSNHL patients.ResultsDuring the study period, 657 patients with SSNHL were admitted to our department. Among them, a total of 274 patients met the enrolled criteria of our study. After PSM, 162 patients (81 in each group) were included in the analysis. Once the hospitalized treatment was completed, the patients would be discharged the next day. Logistic regression analysis of the propensity score-matched cohort indicated that both the complete recovery rates [Siegel's criteria, OR: 0.734, 95% CI: 0.368–1.466, p = 0.381; CMAO criteria, OR: 0.879, 95% CI: 0.435–1.777, p = 0.720] and the overall effective rates [Siegel's criteria and CMAO criteria, OR: 0.741, 95% CI: 0.399–1.378, p = 0.344] were not significantly different between the two treatment groups. Sensitivity analysis has shown similar results. For flat-type and total-deafness SSNHL patients, no significant difference was found in post-treatment hearing gain at each frequency between the two groups after PSM.ConclusionThere was no significant difference in short-term hearing outcomes between treatment with batroxobin and treatment without batroxobin in SSNHL patients by Siegel's and CMAO criteria after PSM. Future studies for better therapy regimens of SSNHL are still needed.