bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perfil epidemiológico de hospitalizações por asma no Estado de Roraima: análise de dados do Departamento de Informática do Sistema Único de Saúde (DATASUS)
Authors: Ferreira Wellington Fernando da Silva , Bridi Aline Lopes da Silva , Siczkoriz Natalli Tedesco , Reis Denny Rafael Perusso dos , Oliveira Elia Machado de , Dutra Denecir de Almeida 
Published: July 2023

Objetivo: Descrever parte do perfil epidemiológico comparando dados de internações e óbitos por asma no Estado de Roraima-RR entre os anos de 2018 a 2022 com dados do Departamento de Informática do Sistema Único de Saúde (DATASUS). Metodologia: Trata-se de um estudo descritivo epidemiológico retrospectivo, baseado em dados secundários, proveniente do Sistema de Informação Hospitalar (SIH), no DATASUS. Resultados: Foram catalogadas 667 internações hospitalares por ‘’Asma’’ CID: (J45 e J46), considerando hospitais públicos e privados, e todas as categorias de atendimento. A cor/raça, predominantemente apontada foi a ‘’parda’’ e a variável ‘’sem informação’’. Os gêneros evidenciados nas internações nestes períodos, sobressaíram ao sexo masculino. Quanto à faixa etária, entre 1 a 4 anos, apresentaram maior quantitativo de internações, seguida da faixa etária de 5 a 9 anos. Apresentou-se ainda, as variáveis referentes à média de permanência de hospitalizações, os valores de serviços hospitalares, valores médios de internações. No período levantado, foram registrados 05 óbitos, com variáveis distintas das descritas nas internações, como predominância dos óbitos ao gênero feminino e faixa etária diversas. Conclusão: Os asmáticos devem ser diagnosticados e acompanhados pelas equipes de Atenção Primária à Saúde (APS). A asma não tem cura, mas o tratamento visa alcançar e manter o controle da doença, com medicação possível, e melhorar a qualidade de vida. Percebe-se, a atual lacuna dos serviços de saúde quanto à prevenção de uma patologia controlável, bem como a necessidade de fomentar a compreensão do perfil epidemiológico da patologia pós emergência global pandêmica.
Palladio: Citta ideale
Authors: Farkas Julianna 
Published: July 2023

Tanulmányom fókuszában alapvetően nem az építészeti megoldások állnak, bár a témából adódóan természetesen ezekre is kitértem, sokkal inkább arra voltam kíváncsi, hogy milyen eszmények, értékrendszerek, kulturális hatások álltak ezen építészeti eszközök alkalmazásának hátterében. Írásomban a következő kérdésekre kerestem a választ: Mit jelent az ideális város a reneszánszban, mit jelent Palladio műveiben? Milyen szemlélet áll mindennek a hátterében és miben tükröződik ez vissza? Honnan merítette Palladio az építészeti eszményeit, miért érdeklődtek a művei iránt oly intenzíven a későbbi történelmi korszakokban is? A téma megértéséhez megvizsgáltam az érett reneszánsz korszakának szellemi, kulturális, városépítészeti sajátosságait, áttekintettem azokat a hatásrendszereket, amelyek Palladio gondolkodására és művészi kifejezésmódjára meghatározók voltak. Elsősorban az ókori építész és teoretikus, Vitruvius elméleti munkáját tanulmányoztam, hiszen alapmű volt általában véve a reneszánsz építészek, így Palladio számára is. Ezek után a reneszánsz alkotó, Leon Battista Alberti munkásságát és összefoglaló építészeti művét mutattam be, hiszen Palladióra nagy valószínűséggel ő volt a legnagyobb hatással. A reneszánsz ideális város egy megvalósult példája volt Bernardo Rossellino városépítő műve, aki II. Pius pápától kapta a megbízatást egy tökéletes város felépítésére, amely a pápa nevét kapta, s így lett Pienza. Palladiónak először a teoretikus munkásságáról írtam, majd az általa elképzelt ideális várost, Vicenzát mutattam be, az általa épített, legfontosabb épületek elemzésével. Végül Palladio hatására hívtam fel a figyelmet, vagyis a palladianizmus jelenségére Európában és Észak-Amerikában. Célom, a szakirodalmi elemzés és saját tapasztalataim alapján az egyes korszakokon átívelő eszmék művészi kifejezésének vizsgálata volt, egy konkrét művész, Palladio tevékenységén keresztül.
Role of mitochondria-bound HK2 in rheumatoid arthritis fibroblast-like synoviocytes
Authors: Torres Alyssa , Kang Sarah , Mahony Christopher B. , Cedeño Martha , Oliveira Patricia G. , Fernandez-Bustamante Marta , Kemble Samuel , Laragione Teresina , Gulko Percio S. , Croft Adam P. , Sanchez-Lopez Elsa , Miyamoto Shigeki , Guma Monica 
Published: July 2023

BackgroundGlucose metabolism, specifically, hexokinase 2 (HK2), has a critical role in rheumatoid arthritis (RA) fibroblast-like synoviocyte (FLS) phenotype. HK2 localizes not only in the cytosol but also in the mitochondria, where it protects mitochondria against stress. We hypothesize that mitochondria-bound HK2 is a key regulator of RA FLS phenotype.MethodsHK2 localization was evaluated by confocal microscopy after FLS stimulation. RA FLSs were infected with Green fluorescent protein (GFP), full-length (FL)–HK2, or HK2 lacking its mitochondrial binding motif (HK2ΔN) expressing adenovirus (Ad). RA FLS was also incubated with methyl jasmonate (MJ; 2.5 mM), tofacitinib (1 µM), or methotrexate (1 µM). RA FLS was tested for migration and invasion and gene expression. Gene associations with HK2 expression were identified by examining single-cell RNA sequencing (scRNA-seq) data from murine models of arthritis. Mice were injected with K/BxN serum and given MJ. Ad-FLHK2 or Ad-HK2ΔN was injected into the knee of wild-type mice.ResultsCobalt chloride (CoCl2) and platelet-derived growth factor (PDGF) stimulation induced HK2 mitochondrial translocation. Overexpression of the HK2 mutant and MJ incubation reversed the invasive and migrative phenotype induced by FL-HK2 after PDGF stimulation, and MJ also decreased the expression of C-X-C Motif Chemokine Ligand 1 (CXCL1) and Collagen Type I Alpha 1 Chain (COL1A1). Of interest, tofacitinib but not methotrexate had an effect on HK2 dissociation from the mitochondria. In murine models, MJ treatment significantly decreased arthritis severity, whereas HK2FL was able to induce synovial hypertrophy as opposed to HK2ΔN.ConclusionOur results suggest that mitochondrial HK2 regulates the aggressive phenotype of RA FLS. New therapeutic approaches to dissociate HK2 from mitochondria offer a safer approach than global glycolysis inhibition.
Plasma PD-L1 as a biomarker in the clinical management of glioblastoma multiforme—a retrospective cohort study
Authors: Masood Aetsam Bin , Batool Sajida , Bhatti Sajid Nazir , Ali Asad , Valko Marian , Jomova Klaudia , Kuca Kamil 
Published: July 2023

Background and objectivesGlioblastoma multiforme (GBM) is the most aggressive, malignant, and therapy-resistant tumor of the brain. Blockade therapy targeting the programmed cell death protein 1 (PD-1)/programmed death ligand (PD-L1) axis is currently under investigation for the clinical management of the GBM. This study has quantified the plasma levels of PD-L1 as a biomarker for the clinical management of GBM.MethodsA cohort (n = 128) of Pakistani adult glioblastoma patients together with age- and sex-matched healthy controls was used for quantification of pre-surgery levels of plasma PD-L1. PD-L1 protein and mRNA were measured by PD-L1 platinum enzyme-linked immunosorbent assay and quantitative real-time PCR, respectively. Receiver operating characteristic (ROC) curve analysis was used to compute area under the curve (AUC) for specificity and sensitivity analyses. The Kaplan–Meier survival analysis was employed to compute overall survival.ResultsPD-L1 protein and mRNA were significantly higher in GBM compared to the healthy controls (p &lt; 0.0001). Mean PD-L1 concentration for the GBM was found to be 48.98 ± 2.290 pg/ml compared to 27.63 ± 1.281 pg/ml for controls. Gene expression analysis showed statistically significant upregulation (p &lt; 0.0001) of PD-L1 in blood of GBM compared to healthy controls. Plasma PD-L1 showed an AUC of 0.840 (p &lt; 0.0001; 95% CI = 0.7716 to 0.9090) where a cutoff value higher than 46 pg/ml demonstrated 100% specificity and 57.81% sensitivity. Higher pre-surgery levels of PD-L1 were found to be associated with overall poor survival [p &lt; 0.0001; HR (log-rank) = 0.08; 95% CI = 0.04 to 0.15]. Age, gender, and ethnic background were not found to be associated with plasma PD-L1 levels.ConclusionThe study concludes that blood-based measurements of PD-L1 in GBM can be a promising prognostic marker and therapeutic target besides a rapid and relatively non-invasive screening tool for routine clinical management. Future work extending the analysis to larger cohorts through multi-center collaborations involving pre-treatment and post-treatment groups is required to fully explore the usefulness of circulating PD-L1 for effective clinical applications.
A d-peptide-based oral nanotherapeutic modulates the PD-1/PD-L1 interaction for tumor immunotherapy
Authors: Liu Dan , Wang Jingmei , You Weiming , Ma Fang , Sun Qi , She Junjun , He Wangxiao , Yang Guang 
Published: July 2023

BackgroundPD-1/PD-L1 immune checkpoint inhibitors are currently the most commonly utilized agents in clinical practice, which elicit an immunostimulatory response to combat malignancies. However, all these inhibitors are currently administered via injection using antibody-based therapies, while there is a growing need for oral alternatives.MethodsThis study has developed and synthesized exosome-wrapped gold–peptide nanocomplexes with low immunogenicity, which can target PD-L1 and activate antitumor immunity in vivo through oral absorption. The SuperPDL1exo was characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR), X-ray photoelectron spectroscopy (XPS), and gel silver staining. The transmembrane ability of SuperPDL1exo was evaluated by flow cytometry and immunofluorescence. Cell viability was determined using the Cell Counting Kit-8 (CCK-8) assay. ELISA experiments were conducted to detect serum and tissue inflammatory factors, as well as serum biochemical indicators. Tissue sections were stained with H&amp;E for the evaluation of the safety of SuperPDL1exo. An MC38 colon cancer model was established in immunocompetent C56BL/6 mice to evaluate the effects of SuperPDL1exo on tumor growth in vivo. Immunohistochemistry (IHC) staining was performed to detect cytotoxicity factors such as perforin and granzymes.ResultsFirst, SuperPDL1 was successfully synthesized, and milk exosome membranes were encapsulated through ultrasound, repeated freeze–thaw cycles, and extrusion, resulting in the synthesis of SuperPDL1exo. Multiple characterization results confirmed the successful synthesis of SuperPDL1exo nanoparticles. Furthermore, our data demonstrated that SuperPDL1exo exhibited excellent colloidal stability and superior cell transmembrane ability. In vitro and in vivo experiments revealed that SuperPDL1exo did not cause damage to multiple systemic organs, demonstrating its good biocompatibility. Finally, in the MC38 colon cancer mouse model, it was discovered that SuperPDL1exo could inhibit the progression of colon cancer, and this tumor-suppressive effect was mediated through the activation of tumor-specific cytotoxic T lymphocyte (CTL)-related immune responses.ConclusionThis study has successfully designed and synthesized an oral nanotherapeutic, SuperPDL1exo, which demonstrates small particle size, excellent colloidal stability, transmembrane ability in tumor cells, and biocompatibility. In vivo experiments have shown that it effectively activates T-cell immunity and exerts antitumor effects.
Combination of Chinese herbal medicine and conventional western medicine for coronavirus disease 2019: a systematic review and meta-analysis
Authors: Tong Lei , Ma Zhenyu , Zhou Yixiao , Yang Shuping , Yang Yalin , Luo Jingran , Huang Junbo , Wang Fucai 
Published: July 2023

ObjectiveThis study aimed to assess the efficacy and safety of Chinese herbal medicine (CHM) plus conventional western medicine (CWM) in comparison with CWM against COVID-19.MethodsWe searched eight electronic databases and three trial registers spanning from January 1, 2020 to May 18, 2023. We included randomized controlled trials (RCTs) comparing the effectiveness and safety of CHM plus CWM and CWM against COVID-19 in our study. The Cochrane Risk of Bias tool 2.0 (RoB2) was applied to evaluate the methodological quality of the included RCTs. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was employed to assess the certainty of evidence. Statistical analysis was implemented in R version 4.1.2.ResultsOur study included 50 RCTs involving 11,624 patients. In comparison with sole CWM, CHM plus CWM against COVID-19 significantly enhanced clinical effective rate (RR = 1.18, 95% CI [1.13, 1.22]), improved chest image (RR = 1.19, 95% CI [1.11, 1.28]), inhibited clinical deterioration (RR = 0.45, 95% CI [0.33, 0.60]), lowered mortality (RR = 0.53, 95% CI [0.40, 0.70]), and reduced the total score of TCM syndrome (SMD = −1.24, 95% CI [−1.82, −0.66]). SARS-CoV-2 nucleic acid conversion time (MD = −2.66, 95% CI [−3.88, −1.44]), duration of hospitalization (MD = −2.36, 95% CI [−3.89, −0.82]), and clinical symptom (fever, cough, fatigue, and shortness of breath) recovery times were shorter in CHM plus CWM groups than in CWM groups. Further, CHM plus CWM treatment was more conducive for some laboratory indicators returning to normal levels. No statistical difference was found in the incidence of total adverse reactions between the two groups (RR = 0.97, 95% CI [0.88, 1.07]). We assessed the risk of bias for 246 outcomes, and categorized 55 into “low risk”, 151 into “some concerns”, and 40 into “high risk”. Overall, the certainty of the evidence ranged from moderate to very low.ConclusionsPotentially, CHM listed in this study, as an adjunctive therapy, combining with CWM is an effective and safe therapy mode for COVID-19. However, more high-quality RCTs are needed to draw more accurate conclusions.Clinical trial registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=293963.
Focal epilepsy without overt epileptogenic lesions: no evidence of microstructural brain tissue damage in multi-parametric quantitative MRI
Authors: Hamid Celona , Maiworm Michelle , Wagner Marlies , Knake Susanne , Nöth Ulrike , Deichmann Ralf , Gracien René-Maxime , Seiler Alexander 
Published: July 2023

Background and purposeIn patients with epilepsies of structural origin, brain atrophy and pathological alterations of the tissue microstructure extending beyond the putative epileptogenic lesion have been reported. However, in patients without any evidence of epileptogenic lesions on diagnostic magnetic resonance imaging (MRI), impairment of the brain microstructure has been scarcely elucidated. Using multiparametric quantitative (q) magnetic resonance imaging MRI, we aimed to investigate diffuse impairment of the microstructural tissue integrity in MRI-negative focal epilepsy patients.Methods27 MRI-negative patients with focal epilepsy (mean age 33.1 ± 14.2 years) and 27 matched healthy control subjects underwent multiparametric qMRI including T1, T2, and PD mapping at 3 T. After tissue segmentation based on synthetic anatomies, mean qMRI parameter values were extracted from the cerebral cortex, the white matter (WM) and the deep gray matter (GM) and compared between patients and control subjects. Apart from calculating mean values for the qMRI parameters across the respective compartments, voxel-wise analyses were performed for each tissue class.ResultsThere were no significant differences for mean values of quantitative T1, T2, and PD obtained from the cortex, the WM and the deep GM between the groups. Furthermore, the voxel-wise analyses did not reveal any clusters indicating significant differences between patients and control subjects for the qMRI parameters in the respective compartments.ConclusionsBased on the employed methodology, no indication for an impairment of the cerebral microstructural tissue integrity in MRI-negative patients with focal epilepsy was found in this study. Further research will be necessary to identify relevant factors and mechanisms contributing to microstructural brain tissue damage in various subgroups of patients with epilepsy.
Using MemTrax memory test to screen for post-stroke cognitive impairment after ischemic stroke: a cross-sectional study
Authors: Zhao Xiaoxiao , Dai Shujuan , Zhang Rong , Chen Xinjie , Zhao Mingjie , Bergeron Michael F. , Zhou Xianbo , Zhang Junyan , Zhong Lianmei , Ashford J. Wesson , Liu Xiaolei 
Published: July 2023

BackgroundWhereas the Montreal Cognitive Assessment (MoCA) and Addenbrooke’s cognitive examination-revised (ACE-R) are commonly used tests for the detection of post-stroke cognitive impairment (PSCI), these instruments take 10–30 min to administer and do not assess processing speed, which is a critical impairment in PSCI. MemTrax (MTx) is a continuous recognition test, which evaluates complex information processing, accuracy, speed, and attention, in 2 min.AimTo evaluate whether MTx is an effective and practical tool for PSCI assessment.MethodsThis study enrolled acute ischemic stroke (AIS) patients who have assessed the cognitive status including MTx, clinical dementia rating (CDR), MoCA, Neuropsychiatric Inventory (NPI), Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA), the National Institute of Health Stroke Scale (NIHSS), modified Rankin scale (mRS), and Barthel Index of activity of daily living (BI) combined with the physical examinations of the neurologic system at the 90-day (D90) after the AIS. The primary endpoint of this study was establishing MTx cut-offs for distinguishing PSCI from AIS.ResultsOf the 104 participants, 60 were classified to the PSCI group. The optimized cut-off value of MTx-%C (percent correct) was 78%, with a sensitivity and specificity for detecting PSCI from Non-PSCI of 90.0 and 84.1%, respectively, and an AUC of 0.919. Regarding the MTx-Cp (Composite score = MTx-%C/MTx-RT), using 46.3 as a cut-off value, the sensitivity and specificity for detecting PSCI from Non-PSCI were 80.0 and 93.2%, with an AUC of 0.925. Multivariate linear regression showed that PSCI reduced the MTx-%C (Coef. −14.18, 95% CI −18.41∼−9.95, p &lt; 0.001) and prolonged the MTx-RT (response time) (Coef. 0.29, 95% CI 0.16∼0.43, p &lt; 0.001) and reduced the MTx-CP (Coef. −19.11, 95% CI −24.29∼−13.93, p &lt; 0.001).ConclusionMemTrax (MTx) is valid and effective for screening for PSCI among target patients and is a potentially valuable and practical tool in the clinical follow-up, monitoring, and case management of PSCI.
Factors that predict weight loss success differ by diet intervention type
Authors: Losavio Jordan , Keenan Michael J. , Gollub Elizabeth A. , Silver Heidi J. 
Published: July 2023

BackgroundMany types of diet intervention can achieve negative energy balance and successful weight loss in persons with obesity. However, within any dietary strategy, there is large inter-individual variation in the weight loss response. The aim of this study is to determine factors that predict weight loss success for diet interventions that vary by macronutrient and caloric composition.MethodsParticipants with BMI 30.0 to 49.9 kg/m2 self-selected one of three diet intervention trials for weight loss: low carbohydrate (LOW CHO), low fat (LOW FAT), or low calorie (LOW KCAL). Multivariable regression models were developed to determine the significance of predictor demographic, body composition, metabolic, clinical, and dietary variables for each diet type.ResultsWeight loss over 12–16 weeks averaging −5.1 ± 4.0 kg from baseline weight, p &lt; 0.001, was not significantly different among diet types. Several different factors were identified that account for the inter-individual variance in weight loss success. Regardless of diet type, the most robust predictor of weight loss success was completion of the intervention, accounting for 20–30% of the variance. Factors predicting diet intervention completion were age, physical activity level, blood leptin level, blood pressure, and the amount of weight loss occurring. Differences by diet type in cardiometabolic risk factor reduction were identified with LOW CHO decreasing glycemia/insulinemia factors, LOW FAT decreasing lipidemia factors, and LOW KCAL decreasing inflammatory factors.ConclusionThese data provide evidence to inform more precise and personalized approaches to diet intervention for weight loss and cardiometabolic health.
T-type calcium channel modulation by hydrogen sulfide in neuropathic pain conditions
Authors: Rangel-Galván Maricruz , Rangel-Galván Violeta , Rangel-Huerta Alejandro 
Published: July 2023

Neuropathic pain can appear as a direct or indirect nerve damage lesion or disease that affects the somatosensory nervous system. If the neurons are damaged or indirectly stimulated, immune cells contribute significantly to inflammatory and neuropathic pain. After nerve injury, peripheral macrophages/spinal microglia accumulate around damaged neurons, producing endogenous hydrogen sulfide (H2S) through the cystathionine-γ-lyase (CSE) enzyme. H2S has a pronociceptive modulation on the Cav3.2 subtype, the predominant Cav3 isoform involved in pain processes. The present review provides relevant information about H2S modulation on the Cav3.2 T-type channels in neuropathic pain conditions. We have discussed that the dual effect of H2S on T-type channels is concentration-dependent, that is, an inhibitory effect is seen at low concentrations of 10 µM and an augmentation effect on T-current at 100 µM. The modulation mechanism of the Cav3.2 channel by H2S involves the direct participation of the redox/Zn2+ affinity site located in the His191 in the extracellular loop of domain I of the channel, involving a group of extracellular cysteines, comprising C114, C123, C128, and C1333, that can modify the local redox environment. The indirect interaction pathways involve the regulation of the Cav3.2 channel through cytokines, kinases, and post-translational regulators of channel expression. The findings conclude that the CSE/H2S/Cav3.2 pathway could be a promising therapeutic target for neuropathic pain disorders.
The effect of auricular vagus nerve stimulation on electroencephalography and electromyography measurements in healthy persons
Authors: Konakoğlu Gülşah , Özden Ali Veysel , Solmaz Hakan , Bildik Celaleddin 
Published: July 2023

Objectives: Auricular vagus nerve stimulation (VNS) is a non-invasive treatment modality. Opinions that it can be used in the treatment of various clinical problems have gained importance in recent years. In this study, it was aimed to lay the groundwork for the use of the auricular VNS in different ears.Methods: Healthy individuals (n = 90) were divided into three groups: unilateral left (n = 30), unilateral right (n = 30), and bilateral (n = 30) auricular VNS. Electroencephalography (EEG) and electromyography (EMG) measurements were performed before and after auricular VNS (10 Hz, 300 µs, 20 min) for a single session.Results: An increase in wrist extensor muscles activation was detected on the contralateral side of the auricular VNS application side. It has been observed that there is a general decrease in the power of high-frequency waves and an increase in the power of lower-medium frequency waves in various parts of the brain.Conclusion: Our findings suggest that the projection of the auricular VNS in the central nervous system may also affect the corticospinal tracts.