bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting regulatory T cells by E7777 enhances CD8 T-cell–mediated anti-tumor activity and extends survival benefit of anti-PD-1 in solid tumor models
Authors: Mahdi Haider S. , Woodall-Jappe Mary , Singh Preeti , Czuczman Myron S. 
Published: October 2023

IntroductionRegulatory T cell (Treg)-targeting cancer immunotherapy aims to transiently deplete Treg cells in the tumor microenvironment, without affecting effector T cells (Teff), thus both enhancing anti-tumor activity and avoiding autoimmunity. This study evaluated whether adding E7777 (a new formulation of denileukin diftitox [DD]) improved the efficacy of anti-PD-1 antibody therapy. DD is a recombinant protein containing the hydrophobic and catalytic portions of diphtheria toxin fused to full-length human IL-2. E7777 has the same amino acid sequence and brief circulatory half-life as DD, but with greater purity and potency.MethodsSubcutaneous syngeneic murine solid tumor models (colon cancer CT-26 and liver cancer H22) were used to evaluate safety, efficacy, and overall survival with E7777 and anti-PD-1 antibodies, each administered as monotherapy or in concurrent or sequential combination. In Experiment 1, treatments were compared to assess anti-tumor activity at various time points, with tumors excised and dissociated and tumor leukocytes characterized. In Experiment 2, tumor growth, response, and overall survival were characterized for 100 days following a 3-week treatment.ResultsE7777 administered in combination with anti-PD-1 led to significantly increased anti-tumor activity and durable, extended overall survival compared to either treatment alone. In both tumor models, the Treg cell infiltration induced by anti-PD-1 treatment was counterbalanced by co-treatment with E7777, suggesting potential synergistic activity. Combination therapy showed the most favorable results. Treatment with E7777 was safe and well-tolerated.DiscussionCombined E7777 and anti-PD-1 therapy was well tolerated and more effective than monotherapy with either drug.
Experimental procedures for flow cytometry of wild-type mouse brain: a systematic review
Authors: Sharp Robert C. , Guenther Dylan T. , Farrer Matthew J. 
Published: October 2023

ObjectiveThe aim of this study was to systematically review the neuroimmunology literature to determine the average immune cell counts reported by flow cytometry in wild-type (WT) homogenized mouse brains.BackgroundMouse models of gene dysfunction are widely used to study age-associated neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease. The importance of the neuroimmune system in these multifactorial disorders has become increasingly evident, and methods to quantify resident and infiltrating immune cells in the brain, including flow cytometry, are necessary. However, there appears to be no consensus on the best approach to perform flow cytometry or quantify/report immune cell counts. The development of more standardized methods would accelerate neuroimmune discovery and validation by meta-analysis.MethodsThere has not yet been a systematic review of ‘neuroimmunology’ by ‘flow cytometry’ via examination of the PROSPERO registry. A protocol for a systematic review was subsequently based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) using the Studies, Data, Methods, and Outcomes (SDMO) criteria. Literature searches were conducted in the Google Scholar and PubMed databases. From that search, 900 candidate studies were identified, and 437 studies were assessed for eligibility based on formal exclusion criteria.ResultsOut of the 437 studies reviewed, 58 were eligible for inclusion and comparative analysis. Each study assessed immune cell subsets within homogenized mouse brains and used flow cytometry. Nonetheless, there was considerable variability in the methods, data analysis, reporting, and results. Descriptive statistics have been presented on the study designs and results, including medians with interquartile ranges (IQRs) and overall means with standard deviations (SD) for specific immune cell counts and their relative proportions, within and between studies. A total of 58 studies reported the most abundant immune cells within the brains were TMEM119+ microglia, bulk CD4+ T cells, and bulk CD8+ T cells.ConclusionExperiments to conduct and report flow cytometry data, derived from WT homogenized mouse brains, would benefit from a more standardized approach. While within-study comparisons are valid, the variability in methods of counting of immune cell populations is too broad for meta-analysis. The inclusion of a minimal protocol with more detailed methods, controls, and standards could enable this nascent field to compare results across studies.
Development and validation of a diagnostic model for the identification of chronic ocular graft-versus-host disease (oGVHD)
Authors: Shen Zhan , Hu Bohao , Tao Liyuan , Ma Jiao , Peng Rongmei , Zhao Yinghan , Hong Jing 
Published: October 2023

PurposeTo verify the International Chronic Ocular Graft-Versus-Host Disease (ICCGVHD) Group diagnostic criteria and establish an easy-to-use and reliable diagnosis model for quick identification of chronic oGVHD.MethodsThis study included 180 patients (355 eyes) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) and visited the Peking University Third Hospital Cornea and Ocular Surface Disease Specialist Clinic from July 2020 to February 2021. The proportion of chronic oGVHD was 76.06% (279/355).ResultsFive complaints, including eye dryness, photophobia, foreign body sensation, eye redness, and burning sensation; six ophthalmic examinations, including Ocular Surface Disease Index (OSDI) score, corneal fluorescein staining (CFS), tear break-up time (TBUT), Schirmer’s test score without anesthesia, conjunctival score, tear meniscus height, and non-ocular GVHD-involved organs were significantly different between patients with chronic oGVHD and control group (p &lt; 0.05). Binary logistic regression (backward LR algorithm) selection demonstrated that three variables retained diagnostic significance for chronic oGVHD: CFS (OR = 2.71 (1.92–3.81), p &lt; 0.001), Schirmer’s test score without anesthesia (OR = 0.83 (0.76–0.91), p &lt; 0.001), and conjunctival score (OR = 1.96 (1.13–3.42), p = 0.031). A nomogram for the identification of chronic oGVHD was developed, and its performance was examined using an internal validation cohort (118 eyes). The areas under the curve (AUCs) for the three-variable-based nomogram were 0.976 (95% CI (0.959–0.992), p &lt; 0.01) and 0.945 (95% CI (0.904–0.986), p &lt; 0.01) in the development and internal validation cohorts, respectively.ConclusionThis concise three-variable-based nomogram based on ICCGVHD criteria could serve as an easy-to-use and reliable tool for rapid screening of chronic oGVHD.
Role of carotid duplex in the assessment of carotid artery restenosis after endarterectomy or stenting
Authors: Szegedi István , Potvorszki Fanni , Mészáros Zsófia Réka , Daniel Cecilia , Csiba László , Oláh László 
Published: October 2023

IntroductionRedo carotid endarterectomy (CEA) and carotid stenting (CAS) are often performed when there is evidence of post-procedural restenosis. The incidence of restenosis after carotid reconstruction is not negligible, ranging from 5 to 33%. The diagnosis of significant internal carotid artery (ICA) restenosis is usually based on duplex ultrasound (US) criteria, mostly on peak-systolic flow velocity (PSV). However, there have been no generally accepted duplex US criteria for carotid restenosis after CAS or CEA.MethodsIn this systematic review, the PubMed/ Medline and Scopus databases were screened to find trials that reported duplex US criteria for significant restenosis after CEA and/or CAS. Only those reports were analyzed in which the restenoses were also assessed by CT/MR or digital subtraction angiography as comparators for duplex US.ResultsFourteen studies met the predetermined search criteria and were included in this review. In most studies, PSV thresholds for significant in-stent ICA restenosis after CAS were higher than those for significant stenosis in non-procedurally treated (native) ICA. Many fewer studies investigated the US criteria for ICA restenosis after CEA. Despite the heterogeneous data, there is a consensus to use higher flow velocity thresholds for assessment of stenosis in stented ICA than in native ICA; however, there have been insufficient data about the flow velocity criteria for significant restenosis after CEA. Although the flow velocity thresholds for restenosis after CAS and CEA seem to be different, the large studies used the same duplex criteria to define restenosis after the two procedures. Moreover, different studies used different flow velocity thresholds to define ICA restenosis, leading to variable restenosis rates.DiscussionWe conclude that (1) further examinations are warranted to determine appropriate duplex US criteria for restenosis after CAS and CEA, (2) single duplex US parameter cannot be used to reliably determine the degree of ICA restenosis, (3) inappropriate US criteria used in large studies may have led to false restenosis rates, and (4) studies are required to determine if there is a benefit from redo carotid artery procedure, such as redo-CEA or redo-CAS, starting with prospective risk stratification studies using current best practice non-invasive care alone.
A Chinese patient with POLR3A-related leukodystrophy: a case report and literature review
Authors: Sun Lei , Lin Weihong , Meng Hongmei , Zhang Wuqiong , Hou Shuai 
Published: October 2023

BackgroundLeukodystrophies are hereditary white matter diseases characterized by genetic polymorphisms and considerable phenotypic variability. They can be classified into myelin and non-myelin malformations. These diseases are rare, affecting 1 out of 250,000–500,000 individuals and can manifest at any age. A subtype of leukodystrophy, associated with missense mutations in the RNA polymerase subunit III (POLR3A) gene, is inherited in an autosomal recessive manner.Case reportWe report and analyse a case of a 34-year-old female who presented with ataxia. Magnetic Resonance Imaging (MRI) of the brain revealed demyelinating lesions in the white matter. Genetic testing identified the c.4044C &gt; G and c.1186-2A &gt; G variants in the POLR3A gene. The patient was diagnosed with hypomyelinating leukodystrophy type 7 and received neurotrophic and symptomatic supportive therapy. However, after 1 month of follow-up, there was no improvement in her symptoms.ConclusionPOLR3A-induced leukodystrophy is relatively rare and not well understood, making it challenging to diagnose and easy to overlook. The prognosis for this disease is generally poor, significantly impacting the quality of life of affected individuals. Currently, no cure is available for this condition, and treatment is limited to managing symptoms. Further research into new treatment methods for POLR3A-induced leukodystrophy is imperative to improve the quality of life and potentially extend the life expectancy of patients.
Ultrasound radiomics models based on multimodal imaging feature fusion of papillary thyroid carcinoma for predicting central lymph node metastasis
Authors: Dai Quan , Tao Yi , Liu Dongmei , Zhao Chen , Sui Dong , Xu Jinshun , Shi Tiefeng , Leng Xiaoping , Lu Man 
Published: October 2023

ObjectiveThis retrospective study aimed to establish ultrasound radiomics models to predict central lymph node metastasis (CLNM) based on preoperative multimodal ultrasound imaging features fusion of primary papillary thyroid carcinoma (PTC).MethodsIn total, 498 cases of unifocal PTC were randomly divided into two sets which comprised 348 cases (training set) and 150 cases (validition set). In addition, the testing set contained 120 cases of PTC at different times. Post-operative histopathology was the gold standard for CLNM. The following steps were used to build models: the regions of interest were segmented in PTC ultrasound images, multimodal ultrasound image features were then extracted by the deep learning residual neural network with 50-layer network, followed by feature selection and fusion; subsequently, classification was performed using three classical classifiers—adaptive boosting (AB), linear discriminant analysis (LDA), and support vector machine (SVM). The performances of the unimodal models (Unimodal-AB, Unimodal-LDA, and Unimodal-SVM) and the multimodal models (Multimodal-AB, Multimodal-LDA, and Multimodal-SVM) were evaluated and compared.ResultsThe Multimodal-SVM model achieved the best predictive performance than the other models (P &lt; 0.05). For the Multimodal-SVM model validation and testing sets, the areas under the receiver operating characteristic curves (AUCs) were 0.910 (95% CI, 0.894-0.926) and 0.851 (95% CI, 0.833-0.869), respectively. The AUCs of the Multimodal-SVM model were 0.920 (95% CI, 0.881-0.959) in the cN0 subgroup-1 cases and 0.828 (95% CI, 0.769-0.887) in the cN0 subgroup-2 cases.ConclusionThe ultrasound radiomics model only based on the PTC multimodal ultrasound image have high clinical value in predicting CLNM and can provide a reference for treatment decisions.
Validation of the Chinese version of PedsQL™ brain tumor module
Authors: Wang Juan , Li Jin , Jiang Xiaofan , Sun Pei , Li Xia , Wang Guanyi 
Published: October 2023

BackgroundThe study introduced the Pediatric Quality of Life Inventory™ (PedsQL™) brain tumor module for the first time in China. Further, the Chinese version of the PedsQL™ brain tumor module was developed and its feasibility, reliability, and validity were investigated.MethodsA total 129 cases completed the assessment. Feasibility was evaluated according to the percentage of missing items and the time required to complete the questionnaire. Internal consistency, retest reliability, and split-half reliability were tested to confirm reliability. We evaluated validity by testing content validity, construct validity, and criterion-related validity. The consistency between the child-self and parent-proxy reports was analyzed by calculating the correlation coefficient (r value) between them.ResultsThe Cronbach's alpha values for all subscales were above 0.7 and many subscales scored more than 0.9. The intra-class correlation coefficients of retest reliability were higher than 0.9. The split-half reliability scores for all subscales were higher than 0.6. The factor-item correlations ranged between 0.575–0.922 in the child report and 0.492–0.949 in the parent report. Exploratory factor analyses produced five factors corresponding to each subscale in the child report and six factors in the parent report.ConclusionThe feasibility, reliability, and validity of the Chinese PedsQL™ brain tumor module were ascertained through this study. This module can be used to effectively monitor children with brain tumors and conduct descriptive or exploratory studies to determine the risk factors affecting their quality of life. This would help develop a new basis for formulating measures to improve patient prognosis and quality of life.
Mental health and post-traumatic stress disorder in firefighters: an integrated analysis from an action research study
Authors: Oliveira Joana , Aires Dias Joana , Duarte Isabel Catarina , Caldeira Salomé , Marques António Reis , Rodrigues Vítor , Redondo João , Castelo-Branco Miguel 
Published: October 2023

IntroductionThe presence of post-traumatic stress disorder (PTSD) symptomatology in firefighters is an ever-pressing issue that requires close attention for adequate interventions. The present study investigated PTSD and global psychopathology prevalence in a sample of highly risk-exposed Portuguese firefighters, collected after the widespread deadly wildfires in 2017 that ravaged the country. Following an action research approach, the aim of this study was to depict this sample and examine the impact of cumulative adverse experiences on their mental health, which is a phenomenon worth attention.MethodFrom an initial sample of 283 firefighters who manifested interest in participating, a total of 139 firefighters from the Coimbra District, of whom 130 unequivocally experienced a potentially traumatic/adverse event as a firefighter, completed BSI (to obtain indicators on psychopathology), QEPAT (an inventory of adverse events possibly experienced as a firefighter), and PCL-5 (a measure of PTSD symptomatology) through an online survey during the year 2018 by the Regional Medical Organization, as proposed and supervised by the local Centre for Prevention and Treatment of Psychological Trauma (CPTTP).ResultsWe found a global prevalence of 8.6% of possible PTSD and 14.4% of possible psychopathology (n = 139). When considering only firefighters who unequivocally reported a potentially traumatic/adverse event as a firefighter (n = 130), 9.2% present possible PTSD, and 13.8% present possible global psychopathology. This sample experienced a mean of 28 adverse events during firefighting work. Linear regressions (n = 118) demonstrated that the perceived severity of the most traumatic event reported and the experience of more adverse events were both related to an increase in PTSD symptomatology. Global psychopathology was associated with PCL-5 scores, with an emphasis on paranoid ideation, hostility, depression, anxiety, and phobic anxiety.DiscussionThe severe wildfires of 2017 did not impact PTSD scores in this sample (collected the year after), suggesting that cumulative adverse events are more important than particular episodes. However, the number of reported events was related to PTSD scores. These results can be used to develop interventions that target all firefighters by addressing risk and protective factors. This action research study motivated specialized aid for firefighters involved in this study.
Late preterm and very preterm infants differ in the acquisition time and quantity of reaches with grasping at reaching onset: an exploratory study
Authors: França Andressa Lagoa Nascimento , Teruia Priscila Maier , de Oliveira Arguelho Amanda , Tudella Eloisa , Soares-Marangoni Daniele Almeida 
Published: October 2023

IntroductionThe onset of manual reaching allows the expansion of the infant’s interaction with the environment. When born preterm, infants become vulnerable to problems in the development of reaching. However, it is still unknown whether there are differences in reaching according to the degree of prematurity.ObjectiveThis study aimed to explore the differences in reaching acquisition and behavior between late preterm and very preterm infants, as well as whether age and clinical variables influence the results.MethodThis is an exploratory, comparative, observational study. In total, 24 infants were included soon after reaching onset; 12 infants were born late preterm (35.55 ± 0.67 gestational weeks) and 12 very preterm (30.60 ± 0.05 gestational weeks). Infants were placed in a baby seat, and a toy was placed at a reachable distance for 2 min. Reaching behavior was the primary variable; birth weight and length of hospital stay were secondary variables.ResultsThe age of reaching onset was higher in the very preterm group. The proportion of reaches with grasping was higher in the late preterm group. These differences were affected by the lower birth weight and longer length of hospital stay in the very preterm group. The proportions of proximal and distal adjustments did not differ between groups.ConclusionVery preterm infants presented disadvantages in the acquisition time and the number of reaches with grasping, but not in the proportions of proximal and distal adjustments of reaching, relative to late preterm infants. Group differences were influenced by clinical variables.
Health surveillance for SARS-CoV-2: infection spread and vaccination coverage in the schools of Modena province, Italy
Authors: Paduano Stefania , Facchini Maria Chiara , Borsari Lucia , D’Alterio Alessandra , Iacuzio Laura , Greco Antonella , Fioretti Elisabetta , Creola Giacomo , Kahfian Zaynalabedin , Zona Stefano , Bargellini Annalisa , Filippini Tommaso 
Published: October 2023

IntroductionIn Italy, over 4.8 million individuals aged 0–19 years have been infected with SARS-CoV-2. This study aims to evaluate the spread of SARS-CoV-2 within schools in Modena province and the influence of anti-SARS-CoV-2 vaccination coverage.MethodsWe performed a survey in the period 1 September-15 December 2021, involving student population aged 0–19 years and related teachers screened for SARS-CoV-2 infection using nasopharyngeal swab after the detection of an index case within their class. During the study period, vaccination against SARS-CoV-2 was actively offered to all subjects aged ≥12 years.ResultsA total of 13,934 subjects were tested, 12,534 students and 1,400 teachers (594 classes). We identified a total of 594 and 779 index and secondary cases, respectively. We found that 9.8% of students and 10.6% of teachers were positive for SARS-CoV-2. Overall at the test time, 32.5% were vaccinated with at least one dose of anti-SARS-CoV-2 vaccine. Among secondary cases, 7.8% were vaccinated compared to 34.9% among negative tested subjects. A higher secondary attack rate was for non-vaccinated subjects rather than vaccinated ones (8.1% vs. 1.4%). Higher secondary attack rates were reported for subjects attending infant and primary school (5.9 and 9.6%, respectively). Lower secondary attack rates were for those who attended middle school (4.9%) and especially high school (1.7%).ConclusionOur results highlight the differential spread of the infection within various educational settings and that the vaccination, available in the study period for the population aged ≥12, have mitigated SARS-CoV-2 spread in high and middle schools.