bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rhinovirus-induced anti-viral interferon secretion is not deficient and not delayed in sinonasal epithelial cells of patients with chronic rhinosinusitis with nasal polyp
Authors: Lee Sang Hag , Han Mun Soo , Lee Tae Hoon , Lee Da Bin , Park Jae Hyung , Lee Seung Hyeok , Kim Tae Hoon 
Published: October 2022

Dysregulated innate and adaptive immune response to rhinoviral infection plays an important role in the exacerbation or progressive course of chronic rhinosinusitis (CRS). However, few studies have evaluated whether rhinovirus-induced production of anti-viral interferon is deficient or delayed in inflammatory epithelial cells of patients with CRS with nasal polyps. The aim of the present study is to investigate the replication rates of rhinovirus 16 (RV 16), RV16-induced antiviral interferon secretion, and the expression levels of pattern recognition receptors after RV 16 infection or TLR3 stimulation with poly (I: C) in normal and inflammatory epithelial cells. Inflammatory epithelial cells were obtained from CRS patients with nasal polyps and normal epithelial cells were derived from ethmoid sinus mucosa during endoscopic reduction of blowout fracture or uncinate process mucosa of patients with septal deviation. Cultured cells were infected with RV 16 or treated with poly (I: C) for 24, 48, and 72 h. Cells and media were harvested at each time point and used to evaluate RV16 replication rates, the secretion of IFN-β, -λ1, -λ2, viperin, Mx, and OAS, and the expression levels of TRL3, RIG-I, MDA5, phospho-NFκB, and phospho-IRF3. RV replication rates reached peak levels 48 h after inoculation in both normal and inflammatory epithelial cells and showed no difference between both groups of epithelial cells at any time point. The release of IFN-β, -λ1, and -λ2 in normal and inflammatory epithelial cells was also strongly induced 48 h after RV16 inoculation but reached peak levels 24 h after poly (I: C) treatment. The expression levels of viperin, Mx, OAS, TLR3, RIG-I, MDA5, phospho-NFκB, and phospho-IRF3 showed similar patterns in both groups of epithelial cells. These results suggest that the production of RV16-induced antiviral interferons is not deficient or delayed in inflammatory epithelial cells from CRS patients with nasal polyps.
Effects of hypoxia on antigen presentation and T cell-based immune recognition of HPV16-transformed cells
Authors: Mohan Nitya , Wellach Kathrin , Özerdem Ceren , Veits Nisha , Förster Jonas D. , Foehr Sophia , Bonsack Maria , Riemer Angelika B. 
Published: October 2022

Attempts to develop a therapeutic vaccine against human papillomavirus (HPV)-induced malignancies have mostly not been clinically successful to date. One reason may be the hypoxic microenvironment present in most tumors, including cervical cancer. Hypoxia dysregulates the levels of human leukocyte antigen (HLA) class I molecules in different tumor entities, impacts the function of cytotoxic T cells, and leads to decreased protein levels of the oncoproteins E6 and E7 in HPV-transformed cells. Therefore, we investigated the effect of hypoxia on the presentation of HPV16 E6- and E7-derived epitopes in cervical cancer cells and its effect on epitope-specific T cell cytotoxicity. Hypoxia induced downregulation of E7 protein levels in all analyzed cell lines, as assessed by Western blotting. However, contrary to previous reports, no perturbation of antigen processing and presentation machinery (APM) components and HLA-A2 surface expression upon hypoxia treatment was detected by mass spectrometry and flow cytometry, respectively. Cytotoxicity assays performed in hypoxic conditions showed differential effects on the specific killing of HPV16-positive cervical cancer cells by epitope-specific CD8+ T cell lines in a donor- and peptide-specific manner. Effects of hypoxia on the expression of PD-L1 were ruled out by flow cytometry analysis. Altogether, our results under hypoxia show a decreased expression of E6 and E7, but an intact APM, and epitope- and donor-dependent effects on T cell cytotoxicity towards HPV16-positive target cells. This suggests that successful immunotherapies can be developed for hypoxic HPV-induced cervical cancer, with careful choice of target epitopes, and ideally in combination with hypoxia-alleviating measures.
Research trends on clinical fecal microbiota transplantation: A biliometric analysis from 2001 to 2021
Authors: Li Yu , Ouyang Yaobin , He Cong 
Published: October 2022

BackgroundNumerous studies on fecal microbiota transplantation (FMT) have been conducted in the past two decades. We aimed to assess the research trends and hotspots in the field of FMT through a quantitative method.Materials and MethodsThe clinical studies of FMT published from 2001 to 2021 were extracted from the Web of Science database. We analyzed the countries, institutions, authors, and keywords of these articles and visually illustrated using VOSviewer and CiteSpace software. The current application of FMT in clinical practice, including indications, efficacy, adverse events, as well as its methodology, such as donor, delivery route, were also evaluated.ResultsA total of 227 records were finally identified. The number and rate of annual publications increased gradually. The USA ranked highest in the number of publications. Harvard University was the most influential institution, and Digestive Diseases and Sciences was the most productive journal. Kassam Zain published the most papers, and the high-frequency keywords were mainly related to diseases and techniques. Healthy donors were the most widely used donors, and frozen stool had the highest frequency of use. The predominant delivery route was endoscopy followed by oral capsules and enema. FMT was most frequently performed for the treatment of recurrent Clostridium Difficile Infection. The overall efficacy of FMT was 76.88%, and the incidence of minor and severe adverse events were 11.63% and 1.59%, respectively.ConclusionsThis study delineated a comprehensive landscape of the advancement in FMT field. Although in its infancy, FMT is a burgeoning option for the treatment of a variety of diseases associated with gut dysbiosis. To improve the efficacy and reduce adverse events, future studies are warranted to optimize the methodology of FMT.
Biological screening of a unique drug library targeting MRGPRX2
Authors: Yang Fan , Limjunyawong Nathachit , Peng Qi , Schroeder John T. , Saini Sarbjit , MacGlashan Donald , Dong Xinzhong , Gao Li 
Published: October 2022

BackgroundAllergic drug reaction or drug allergy is an immunologically mediated drug hypersensitivity reaction (DHR). G-protein coupled receptors (GPCRs) are common drug targets and communicate extracellular signals that initiate cellular responses. Recent evidence shows that GPCR MRGPRX2 is of major importance in IgE-independent pseudo-allergic DHRs based on the suspected interactions between many FDA-approved peptidergic compounds and MRGPRX2.ObjectiveOur aim was to uncover novel MRGPRX2-selective and -potent agonists as drug candidates responsible for clinical features of pseudo-allergic DHRs.MethodsWe conducted a primary high-throughput screening (HTS), coupled with mutagenesis targeting the MRGPRX2 N62S mutation, on a panel of 3,456 library compounds. We discovered pharmacologically active hit compounds as agonists of the MRGPRX2 protein according to high degrees of potency evaluated by the calcium response and validated by the degranulation assay. Using the molecular tool Forge, we also characterized the structure-activity relationship shared by identified hit compounds.ResultsThe alternative allele of single nucleotide polymorphism rs10833049 (N62S) in MRGPRX2 demonstrated loss-of-function property in response to substance P and antineoplastic agent daunorubicin hydrochloride. We applied a unique assay system targeting the N62S mutation to the HTS and identified 84 MRGPRX2-selective active hit compounds representing diverse classes according to primary drug indications. The top five highly represented groups included fluoroquinolone and non-fluoroquinolone antibiotics; antidepressive/antipsychotic; antihistaminic and antineoplastic agents. We classified hit compounds into 14 clusters representing a variety of chemical and drug classes beyond those reported, such as opioids, neuromuscular blocking agents, and fluoroquinolones. We further demonstrated MRGPRX2-dependent degranulation in the human mast cell line LAD2 cells induced by three novel agonists representing the non-fluoroquinolone antibiotics (bacitracin A), anti-allergic agents (brompheniramine maleate) and tyrosine-kinase inhibitors (imatinib mesylate).ConclusionOur findings could facilitate the development of interventions for personalized prevention and treatment of DHRs, as well as future pharmacogenetic investigations of MRGPRX2 in relevant disease cohorts.
Effects of air-entraining agent and polypropylene fiber on the mechanical properties, autogenous shrinkage, and fracture properties of fully recycled aggregate concrete
Authors: Ding Dong , Zhang Lijuan , Zhao Jun , Li Changbin , Wang Zhi 
Published: October 2022

The effects of air-entraining agent (AEA) and polypropylene fiber (PPF) on the autogenous shrinkage and fracture properties of fully recycled aggregate concrete (FRAC) are studied to obtain FRAC with low density, low autogenous shrinkage, and superior fracture properties. Six groups of FRAC with different AEA (0, 5%, 10%) and PPF (0, 1.2 kg/m3) contents were prepared for test. The results illustrate that AEA can slightly reduce density but that it has an adverse effect on the strength and fracture properties of FRAC. The incorporation of PPFs can reduce the adverse effect of AEA on compressive strength and splitting tensile strength, but it will increase the adverse effect on fracture properties. Furthermore, the addition of PPFs alone will significantly reduce compressive strength and splitting tensile strength, whereas flexural strength and fracture properties are increased. The addition of AEA can improve the adverse effect of PPFs on compressive strength and splitting tensile strength, but flexural strength and fracture properties will decrease rather than increase. The addition of 10% AEA can greatly reduce autogenous shrinkage, and 5% AEA can reduce autogenous shrinkage at an early age. Incorporating PPFs can further reduce autogenous shrinkage. The study mainly examines the effects of AEA and PPF on the autogenous shrinkage of FRAC, and provides some new ideas for producing high-performance FRAC. At the same time, the cooperative effect of AEA and PPF on the properties of FRAC is also studied.
Mechanism of long-term strength retrogression of silica-enriched Portland cement assessed by quantitative X-ray diffraction analysis
Authors: Qin Jiankun , Pang Xueyu , Li Hailong , Zhang Zhen 
Published: October 2022

In order to clarify on the driving force of cement long-term strength retrogression, a comprehensive quantitative X-ray diffraction (XRD) analysis were conducted on silica-enriched (60%–80% by weight of cement) cement samples set and cured under the condition of 200°C and 50 MPa with a maximum duration of 180 days. The phase content evolution with time was determined by three different methods on the average of three specimens: the external standard method; the partial or no known crystal structure (PONKCS) method; and the hybrid method. Although the specific phase content estimated by different methods varied slightly, the overall trend of change of all phases were similar. The phase transformation in set cement at high temperature condition is dependent on the slurry composition. In silica-deficient system, tobermorite and amorphous C-S-H were transformed to xonotlite; while in silica-sufficient system, tobermorite and amorphous C-S-H were transformed to gyrolite. These phase transformations involve gradual structural changes of cement hydration products, which may be the driving force of long-term strength retrogression. However, such structural changes can only be detected by XRD once the transformation is complete.
Case report: Incidence and prognostic value of brain MRI lesions and elevated cerebrospinal fluid protein in children with Guillain-Barré syndrome
Authors: Pizzo Francesco , Di Nora Alessandra , Di Mari Alessia , Costanza Giuseppe , Testa Elisabetta , Strazzieri Marianna , Greco Filippo , Timpanaro Tiziana , Basile Antonio , Belfiore Giuseppe , Giugno Andrea , Rocca Roberta , Ruggieri Martino , Fiumara Agata , Pavone Piero 
Published: October 2022

BackgroundGuillain-Barrè syndrome (GBS) is an acute immune-mediated disorder affecting peripheral nerves and nerve roots with a variable clinical course and outcome. Epidemiologic analyses have revealed that the incidence of the syndrome increases linearly among the age. The clinical diagnosis of GBS is based on the family history, physical and neurological examination, electrodiagnostic exams, and cerebrospinal fluid analysis with the classical presence of albumin-cytologic dissociation. Prognosis is associated with the severity of clinical signs and the type of peripheral nerves involved.MethodsThis study aims to clarify which clinical features can be used for prognostic purposes. We evaluated the correlation between (1) brain MRI lesions and grade of disability; (2) brain MRI lesions and elevated cerebrospinal fluid (CSF) protein; and (3) increased levels of CSF protein and grade of disability. Statistical analysis extracted from these data indicated a good correlation to be a prognostic indicator in children affected by GBS. We found little evidence regarding laboratory tests, imaging, and prognosis. We enrolled 12 continuous patients who met the Brighton criteria for GBS in this retrospective study. Each patient was clinically evaluated at the time of disease onset to assess the GBS disability score and after 2 weeks.ResultsWe estimated Pearson's correlation index to evaluate the possible correlation between MRI and disability and CSF protein levels and disability. The correlation coefficient was 0.92 and 0.85, respectively. In addition, we developed a graph to see the trend of the disability values, proteins in the CSF, and damage assessed with MRI in the 12 patients. It seems that these parameters have a parallel trend and a good correlation in each patient. Finally, we calculated the correlation between MRI and CSF protein values, with an r-value of 0.87. The values suggest a correlation among the MRI score, CSF protein, and prognosis.ConclusionThe MRI and CSF laboratory parameters can be important tools for the clinician not only for diagnosis but also to evaluate the possible worsening of general conditions or the need to prepare measures to support life parameters. Patients who need ventilatory support could be established early from patients who have less severe GBS and can begin rehabilitation earlier. We suggest MRI should be performed routinely in children with GBS to be able to estimate the evolution of the clinical condition.
Case report: Ventricular primary central nervous system lymphoma with partial hypointensity on diffusion-weighted imaging
Authors: Li Xintong , Xiong Hua 
Published: October 2022

IntroductionPrimary central nervous system lymphoma (PCNSL) is infrequent and represents 3. 1% of primary brain tumors. And the lesions that are restricted to the ventricular system, particularly the third ventricle, are even rarer. There are few pieces of literature or case reports to date. We report a case of PCNSL with partial hypointense on diffusion-weighted imaging (DWI) located in the lateral and third ventricles. Then we reviewed almost all case reports of ventricular PCNSLs in the last 20 years, discuss the imaging presentation, other ventricular tumors with similar imaging findings, and primary treatment measures.Case presentationA 78-year-old man presented with memory loss and poor responsiveness for one week without obvious precipitating factors. Magnetic resonance imaging (MRI) showed lesions in the third ventricle and left lateral ventricles, which were slightly hypointense on T1-weighted imaging (T1WI), and isointense to slightly hypointense on T2-weighted imaging (T2WI). On DWI, the left lateral ventricular lesion was hyperintense, while the third ventricular lesion was hypointense. After the surgical procedure, the pathology and immunohistochemistry revealed diffuse large B-cell lymphoma (DLBCL).ConclusionsVentricular PCNSL is quite rare, and may be confused with other tumors in the same position. However, PCNSL differs from other central nervous system tumors in that it is primarily treated with chemotherapy and/or radiation therapy. So, it is important to recognize PCNSL and differentiate it from other tumors, considering its implications for management planning.
On the feasibility of simple brain-computer interface systems for enabling children with severe physical disabilities to explore independent movement
Authors: Floreani Erica D. , Rowley Danette , Kelly Dion , Kinney-Lang Eli , Kirton Adam 
Published: October 2022

IntroductionChildren with severe physical disabilities are denied their fundamental right to move, restricting their development, independence, and participation in life. Brain-computer interfaces (BCIs) could enable children with complex physical needs to access power mobility (PM) devices, which could help them move safely and independently. BCIs have been studied for PM control for adults but remain unexamined in children. In this study, we explored the feasibility of BCI-enabled PM control for children with severe physical disabilities, assessing BCI performance, standard PM skills and tolerability of BCI.Materials and methodsPatient-oriented pilot trial. Eight children with quadriplegic cerebral palsy attended two sessions where they used a simple, commercial-grade BCI system to activate a PM trainer device. Performance was assessed through controlled activation trials (holding the PM device still or activating it upon verbal and visual cueing), and basic PM skills (driving time, number of activations, stopping) were assessed through distance trials. Setup and calibration times, headset tolerability, workload, and patient/caregiver experience were also evaluated.ResultsAll participants completed the study with favorable tolerability and no serious adverse events or technological challenges. Average control accuracy was 78.3 ± 12.1%, participants were more reliably able to activate (95.7 ± 11.3%) the device than hold still (62.1 ± 23.7%). Positive trends were observed between performance and prior BCI experience and age. Participants were able to drive the PM device continuously an average of 1.5 meters for 3.0 s. They were able to stop at a target 53.1 ± 23.3% of the time, with significant variability. Participants tolerated the headset well, experienced mild-to-moderate workload and setup/calibration times were found to be practical. Participants were proud of their performance and both participants and families were eager to participate in future power mobility sessions.DiscussionBCI-enabled PM access appears feasible in disabled children based on evaluations of performance, tolerability, workload, and setup/calibration. Performance was comparable to existing pediatric BCI literature and surpasses established cut-off thresholds (70%) of “effective” BCI use. Participants exhibited PM skills that would categorize them as “emerging operational learners.” Continued exploration of BCI-enabled PM for children with severe physical disabilities is justified.
Problematic smartphone use is associated with differences in static and dynamic brain functional connectivity in young adults
Authors: Liu Dayi , Liu Xiaoxuan , Long Yicheng , Xiang Zhibiao , Wu Zhipeng , Liu Zhening , Bian Dujun , Tang Shixiong 
Published: October 2022

IntroductionThis study aimed to investigate the possible associations between problematic smartphone use and brain functions in terms of both static and dynamic functional connectivity patterns.Materials and methodsResting-state functional magnetic resonance imaging data were scanned from 53 young healthy adults, all of whom completed the Short Version of the Smartphone Addiction Scale (SAS-SV) to assess their problematic smartphone use severity. Both static and dynamic functional brain network measures were evaluated for each participant. The brain network measures were correlated the SAS-SV scores, and compared between participants with and without a problematic smartphone use after adjusting for sex, age, education, and head motion.ResultsTwo participants were excluded because of excessive head motion, and 56.9% (29/51) of the final analyzed participants were found to have a problematic smartphone use (SAS-SV scores ≥ 31 for males and ≥ 33 for females, as proposed in prior research). At the global network level, the SAS-SV score was found to be significantly positively correlated with the global efficiency and local efficiency of static brain networks, and negatively correlated with the temporal variability using the dynamic brain network model. Large-scale subnetwork analyses indicated that a higher SAS-SV score was significantly associated with higher strengths of static functional connectivity within the frontoparietal and cinguloopercular subnetworks, as well as a lower temporal variability of dynamic functional connectivity patterns within the attention subnetwork. However, no significant differences were found when directly comparing between the groups of participants with and without a problematic smartphone use.ConclusionOur results suggested that problematic smartphone use is associated with differences in both the static and dynamic brain network organizations in young adults. These findings may help to identify at-risk population for smartphone addiction and guide targeted interventions for further research. Nevertheless, it might be necessary to confirm our findings in a larger sample, and to investigate if a more applicable SAS-SV cutoff point is required for defining problematic smartphone use in young Chinese adults nowadays.