bluuebunny/crossref_metadata_2025_split huggingface dataset:
Objects detection theory for evaluating the city environmental quality
Authors: Liu Tong , Han Xiaowei , Xie Yinghong , Tu Binbin , Gao Yuan , Wang Wenfeng 
Published: December 2023

IntroductionThe primary focus of this paper is to assess urban ecological environments by employing object detection on spatial-temporal data images within a city, in conjunction with other relevant information through data mining.MethodsFirstly, an improved YOLOv7 algorithm is applied to conduct object detection, particularly counting vehicles and pedestrians within the urban spatial-temporal data. Subsequently, the k-means superpixel segmentation algorithm is utilized to calculate vegetation coverage within the urban spatial-temporal data, allowing for the quantification of vegetation area. This approach involves the segmentation of vegetation areas based on color characteristics, providing the vegetation area’s measurements. Lastly, an ecological assessment of the current urban environment is conducted based on the gathered data on human and vehicle density, along with vegetation coverage.ResultsThe enhanced YOLOv7 algorithm employed in this study yields a one-percent improvement in mean AP (average precision) compared to the original YOLOv7 algorithm. Furthermore, the AP values for key categories of interest, namely, individuals and vehicles, have also improved in this ecological assessment.DiscussionSpecifically, the AP values for the ‘person’ and ‘pedestrian’ categories have increased by 13.9% and 9.3%, respectively, while ‘car’ and ‘van’ categories have seen AP improvements of 6.7% and 4.9%. The enhanced YOLOv7 algorithm contributes to more accurate data collection regarding individuals and vehicles in subsequent research. In the conclusion of this paper, we further validate the reliability of the urban environmental assessment results by employing the Recall-Precision curve.
Exploring the joint potential of inflammation, immunity, and receptor-based biomarkers for evaluating ME/CFS progression
Authors: Berkis Uldis , Svirskis Simons , Krumina Angelika , Gravelsina Sabine , Vilmane Anda , Araja Diana , Nora-Krukle Zaiga , Murovska Modra 
Published: December 2023

BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a debilitating chronic condition with no identified diagnostic biomarkers to date. Its prevalence is as high as 0.89% according to metastudies, with a quarter of patients bed- or home-bound, which presents a serious public health challenge. Investigations into the inflammation–immunity axis is encouraged by links to outbreaks and disease waves. Recently, the research of our group revealed that antibodies to beta2-adrenergic (anti-β2AdR) and muscarinic acetylcholine (anti-M4) receptors demonstrate sensitivity to the progression of ME/CFS. The purpose of this study is to investigate the joint potential of inflammatome—characterized by interferon (IFN)-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-21, Il-23, IL-6, IL-17A, Activin-B, immunome (IgG1, IgG2, IgG3, IgG4, IgM, and IgA), and receptor-based biomarkers (anti-M3, anti-M4, and anti-β2AdR)—for evaluating ME/CFS progression, and to identify an optimal selection for future validation in prospective clinical studies.MethodsA dataset was used originating from 188 individuals, namely, 54 healthy controls, 30 patients with a “mild” condition, 73 patients with a “moderate” condition, and 31 patients with a “severe” condition, clinically assessed by Fukuda/CDC 1994 and international consensus criteria. Inflammatome, immunome, and receptor-based biomarkers were determined in blood plasma via ELISA and multiplex methods. Statistical analysis was done via correlation analysis, principal component analysis, linear discriminant analysis, and random forest classification; inter-group differences were tested via nonparametric Kruskal–Wallis H test followed by the two-stage linear step-up procedure of Benjamini, Krieger, and Yekutieli, and via Mann–Whitney U test.ResultsThe association between inflammatome and immunome markers is broader and stronger (coupling) in the severe group. Principal component factoring separates components associated with inflammatome, immunome, and receptor biomarkers. Random forest modeling demonstrates an excellent accuracy of over 90% for splitting healthy/with condition groups, and 45% for splitting healthy/severity groups. Classifiers with the highest potential are anti-β2AdR, anti-M4, IgG4, IL-2, and IL-6.DiscussionThe association between inflammatome and immunome markers is a candidate for controlled clinical study of ME/CFS progression markers that could be used for treatment individualization. Thus, the coupling effects between inflammation and immunity are potentially beneficial for the identification of prognostic factors in the context of ME/CFS progression mechanism studies.
Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC
Authors: Gémes Nikolett , Balog József Á. , Neuperger Patrícia , Schlegl Erzsébet , Barta Imre , Fillinger János , Antus Balázs , Zvara Ágnes , Hegedűs Zoltán , Czimmerer Zsolt , Manczinger Máté , Balogh Gergő Mihály , Tóvári József , Puskás László G. , Szebeni Gábor J. 
Published: December 2023

IntroductionTobacco smoking generates airway inflammation in chronic obstructive pulmonary disease (COPD), and its involvement in the development of lung cancer is still among the leading causes of early death. Therefore, we aimed to have a better understanding of the disbalance in immunoregulation in chronic inflammatory conditions in smoker subjects with stable COPD (stCOPD), exacerbating COPD (exCOPD), or non-small cell lung cancer (NSCLC).MethodsSmoker controls without chronic illness were recruited as controls. Through extensive mapping of single cells, surface receptor quantification was achieved by single-cell mass cytometry (CyTOF) with 29 antibodies. The CyTOF characterized 14 main immune subsets such as CD4+, CD8+, CD4+/CD8+, CD4−/CD8−, and γ/δ T cells and other subsets such as CD4+ or CD8+ NKT cells, NK cells, B cells, plasmablasts, monocytes, CD11cdim, mDCs, and pDCs. The CD4+ central memory (CM) T cells (CD4+/CD45RA−/CD45RO+/CD197+) and CD4+ effector memory (EM) T cells (CD4+/CD45RA−/CD45RO+/CD197−) were FACS-sorted for RNA-Seq analysis. Plasma samples were assayed by Luminex MAGPIX® for the quantitative measurement of 17 soluble immuno-oncology mediators (BTLA, CD28, CD80, CD27, CD40, CD86, CTLA-4, GITR, GITRL, HVEM, ICOS, LAG-3, PD-1, PD-L1, PD-L2, TIM-3, TLR-2) in the four studied groups.ResultsOur focus was on T-cell-dependent differences in COPD and NSCLC, where peripheral CD4+ central memory and CD4+ effector memory cells showed a significant reduction in exCOPD and CD4+ CM showed elevation in NSCLC. The transcriptome analysis delineated a perfect correlation of differentially expressed genes between exacerbating COPD and NSCLC-derived peripheral CD4+ CM or CD4+ EM cells. The measurement of 17 immuno-oncology soluble mediators revealed a disease-associated phenotype in the peripheral blood of stCOPD, exCOPD, and NSCLC patients.DiscussionThe applied single-cell mass cytometry, the whole transcriptome profiling of peripheral CD4+ memory cells, and the quantification of 17 plasma mediators provided complex data that may contribute to the understanding of the disbalance in immune homeostasis generated or sustained by tobacco smoking in COPD and NSCLC.
FOXP3+ regulatory T cells are associated with the severity and prognosis of sarcoidosis
Authors: Patterson Karen C. , Miller Wallace T. , Hancock Wayne W. , Akimova Tatiana 
Published: December 2023

RationaleSarcoidosis is an inflammatory granulomatous disease of unknown etiology with predominant lung involvement. Organ involvement and disease severity, as well as the nature of immune alterations, vary among patients leading to a range of clinical phenotypes and outcomes. Our objective was to evaluate the association of disease course and immune responses in pulmonary sarcoidosis.MethodsIn this prospective cohort study of 30 subjects, most of whom were followed for one year, we evaluated 14 inflammatory markers in plasma, 13 Treg/T cell flow cytometry markers and 8 parameters of FOXP3+ Treg biology, including suppressive function, epigenetic features and stability.ResultsWe identified a set of 13 immunological parameters that differ in sarcoidosis subjects in comparison with healthy donors. Five of those were inversely correlated with suppressive function of Tregs in sarcoidosis, and six (TNFα, TNFR I and II, sCD25, Ki-67 and number of Tregs) were particularly upregulated or increased in subjects with thoracic lymphadenopathy. Treg suppressive function was significantly lower in patients with thoracic lymphadenopathy, and in patients with higher burdens of pulmonary and systemic symptoms. A combination of five inflammatory markers, Ki-67 expression, Treg function, and lung diffusion capacity evaluated at study entry predicted need for therapy at one year follow-up in 90% of cases.ConclusionTregs may suppress ongoing inflammation at local and systemic levels, and TNFα, TNFR I and II, sCD25 and Ki-67 emerge as attractive biomarkers for in vivo sarcoid inflammatory activity.
Pediatric humoral immune responses and infection risk after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and two-dose vaccination during SARS-CoV-2 omicron BA.5 and BN.1 variants predominance in South Korea
Authors: Choi Hyun-Woo , Achangwa Chiara , Park Joonhong , Lee Sun Min , Lee Nan Young , Jeon Chae-Hyeon , Choi Jeong-Hwa , Do Hyun Kyung , Nam Jeong-Hyun , Lee June-Woo , Kim Byoungguk , Ryu Sukhyun , Kee Seung-Jung 
Published: December 2023

BackgroundHumoral immune responses and infection risk after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) vaccination during the Omicron BA.5 and BN.1 variants predominant period remains unexplored in pediatric population.MethodsWe examined anti-spike (anti-S) immunoglobulin G (IgG) responses in a total of 986 children aged 4−18 years who visited outpatient clinics between June 2022 and January 2023, with a history of SARS-CoV-2 infection alone, completed two doses of COVID-19 vaccination alone, vaccine-breakthrough infection (i.e., infection after the single dose of vaccination), and no antigenic exposure. Furthermore, to determine SARS-CoV-2 infection risk, the incidence of newly developed SARS-CoV-2 infection was investigated up to March 2023.ResultsThe anti-S IgG levels in the ‘vaccine-breakthrough infection’ group exceeded those in the ‘infection alone’ and ‘vaccination alone’ groups (both P &lt;0.01). Furthermore, the ‘vaccination alone’ group experienced more rapid anti-S IgG waning than the ‘infection alone’ and ‘vaccine-breakthrough infection’ groups (both P &lt;0.01). We could not identify newly developed SARS-CoV-2 infection in the ‘vaccine-breakthrough infection’ group.ConclusionOur findings suggest that hybrid immunity, acquired from SARS-CoV-2 infection and COVID-19 vaccination, was a potentially higher and longer-lasting humoral immune response and protected against SARS-CoV-2 infection in pediatric population during Omicron BA.5 and BN.1 variants predominant.
Positive association between different triglyceride glucose index-related indicators and psoriasis: evidence from NHANES
Authors: Huang Dawei , Ma Rui , Zhong Xiaoyuan , Jiang Yuxiong , Lu Jiajing , Li Ying , Shi Yuling 
Published: December 2023

BackgroundPsoriasis is a chronic inflammatory skin disease with effects that extend beyond the skin. Insulin resistance (IR) has been associated with psoriasis, but it remains unclear how indicators related to the triglyceride glucose (TyG) index, which were associate with IR, are associated with the condition.ObjectiveThe purpose of this study was to investigate the association between psoriasis and three TyG-related indicators: triglyceride glucose-body mass index (TyG-BMI), triglyceride glucose-waist to height ratio (TyG-WHtR), and triglyceride glucose-waist circumference (TyG-WC).MethodsData from adults aged 20 to 80 years in the National Health and Nutrition Examination Survey (NHANES) from 2003 to 2006 and 2009 to 2014 were utilized. Institutional Review Board approval and documented written consent was obtained from participants by NHANES (Protocol #2005–06). The patients were divided into three groups based on TyG-BMI, TyG-WC, and TyG-WHtR: Q1 (1st quintile), Q2 (2nd-3rd quintiles), and Q3 (4th-5th quintiles). Differences between the groups were further explored. Multivariate logistic regressions were used to investigate the correlation between these three indicators and psoriasis, with results expressed as odds ratios (OR) and 95% confidence intervals (CI). Subgroup analysis and supplementary analysis was further conducted to explore potential influencing factors.ResultsThe study included 9,291 participants, of which 260 had psoriasis. Compared Q2 and Q3 of TyG-BMI, TyG-WC, and TyG-WHtR to Q1, there were significantly associate with psoriasis. Among the three indicators, TyG-WC consistently had the highest OR values in Models 1 and 2 (Model 1: Q3 OR (95% CI) = 2.155 (1.442-3.220); Model 2: Q3 OR (95% CI) = 2.029 (1.341-3.069)). While in Model 3, the TyG-BMI shows more significant relationship with psoriasis (Model 3 of TyG-BMI: Q3 OR (95% CI) = 1.948 (1.300-3.000)). Similar results were observed in the majority of subgroups and in supplementary analysis.ConclusionThis study identified a stable and strong positive association between TyG-related indicators (TyG-BMI, TyG-WC, and TyG-WHtR) and psoriasis. This association persisted even after adjusting for multiple factors. It is suggested that high IR is significantly associated with psoriasis.
SON-1210 - a novel bifunctional IL-12 / IL-15 fusion protein that improves cytokine half-life, targets tumors, and enhances therapeutic efficacy
Authors: Cini John K. , Dexter Susan , Rezac Darrel J. , McAndrew Stephen J. , Hedou Gael , Brody Rich , Eraslan Rukiye-Nazan , Kenney Richard T. , Mohan Pankaj 
Published: December 2023

BackgroundThe potential synergy between interleukin-12 (IL-12) and IL-15 holds promise for more effective solid tumor immunotherapy. Nevertheless, previous clinical trials involving therapeutic cytokines have encountered obstacles such as short pharmacokinetics, limited tumor microenvironment (TME) targeting, and substantial systemic toxicity.MethodsTo address these challenges, we fused single-chain human IL-12 and native human IL-15 in cis onto a fully human albumin binding (FHAB) domain single-chain antibody fragment (scFv). This novel fusion protein, IL12-FHAB-IL15 (SON-1210), is anticipated to amplify the therapeutic impact of interleukins and combination immunotherapies in human TME. The molecule was studied in vitro and in animal models to assess its pharmacokinetics, potency, functional characteristics, safety, immune response, and efficacy.ResultsSON-1210 demonstrated robust binding affinity to albumin and exhibited the anticipated in vitro activity and tumor model efficacy that might be expected based on decades of research on native IL-12 and IL-15. Notably, in the B16F10 melanoma model (a non-immunogenic, relatively “cold” tumor), the murine counterpart of the construct, which had mouse (m) and human (h) cytokine sequences for the respective payloads (mIL12-FHAB-hIL15), outperformed equimolar doses of the co-administered native cytokines in a dose-dependent manner. A single dose caused a marked reduction in tumor growth that was concomitant with increased IFNγ levels; increased Th1, CTL, and activated NK cells; a shift in macrophages from the M2 to M1 phenotype; and a reduction in Treg cells. In addition, a repeat-dose non-human primate (NHP) toxicology study displayed excellent tolerability up to 62.5 µg/kg of SON-1210 administered three times, which was accompanied by the anticipated increases in IFNγ levels. Toxicokinetic analyses showed sustained serum levels of SON-1210, using a sandwich ELISA with anti-IL-15 for capture and biotinylated anti-IL-12 for detection, along with sustained IFNγ levels, indicating prolonged kinetics and biological activity.ConclusionCollectively, these findings support the suitability of SON-1210 for patient trials in terms of activity, efficacy, and safety, offering a promising opportunity for solid tumor immunotherapy. Linking cytokine payloads to a fully human albumin binding domain provides an indirect opportunity to target the TME using potent cytokines in cis that can redirect the immune response and control tumor growth.
Effectiveness of transcranial alternating current stimulation for controlling chronic pain: a systematic review
Authors: Chang Min Cheol , Briand Marie-Michèle , Boudier-Revéret Mathieu , Yang Seoyon 
Published: December 2023

BackgroundChronic pain is common, disruptive, and often treatment-resistant. Hence, researchers and clinicians seek alternative therapies for chronic pain. Transcranial alternating current stimulation (tACS) is an emerging neuromodulation technique that non-invasively modulates neural oscillations in the human brain. tACS induces pain relief by allowing the neural network to restore adequate synchronization. We reviewed studies on the effectiveness of tACS in controlling chronic pain.MethodsThe PubMed, SCOPUS, Embase, and Cochrane Library databases were systematically searched for relevant studies published until December 6, 2023. The key search phrase for identifying potentially relevant articles was [(Transcranial Alternating Current Stimulation OR tACS) AND pain]. The following inclusion criteria were applied for article selection: (1) studies involving patients with chronic pain; (2) tACS was applied for controlling pain; and (3) follow-up evaluations were performed to assess the degree of pain reduction after the application of tACS.ResultsWe identified 2,330 potentially relevant articles. After reading the titles and abstracts and assessing eligibility based on the full-text articles, we included four articles in our review. Among the included studies, tACS was used for fibromyalgia in one study, low back pain (LBP) in two studies, and migraine in one study. In the study on fibromyalgia, it did not show a better pain-reducing effect of tACS compared with sham stimulation. Two studies on LBP showed conflicting results. In migraine, tACS showed a positive pain-reducing effect 24–48 h after its application.ConclusionThere is insufficient research to draw a conclusive judgment on the effectiveness of tACS in controlling chronic pain. More studies across various chronic pain-related diseases are required for a definitive conclusion.
Development and feasibility of a virtual reality-based exergaming program to enhance cardiopulmonary fitness in children with developmental coordination disorder
Authors: Ju Ya-Ju , Du Yi-Chun , Huang Hsien-Chun , Hu Kao Po-Sen , Cherng Rong-Ju 
Published: December 2023

IntroductionDevelopmental coordination disorder (DCD) is a neurodevelopmental disorder characterized by motor skill deficits. Such deficits often limit children's participation in physical activities, further affecting their overall health, including through reduced cardiopulmonary fitness. Because virtual reality (VR) devices offer interactive games and activities that require various movements and coordination, they can serve as motivating and enjoyable means for children to perform physical exercise. In this study, we developed a VR-based exergaming system and tested its ability to enhance the cardiopulmonary fitness of children with DCD.Materials and methodsA total of 13 children with DCD and 10 young adults were recruited in phase I to examine the test–retest reliability and concurrent validity of our system (including a custom-made heart rate monitor) with a commercial heart rate device. In phase II, we included an additional 13 children with DCD to test the feasibility of the system. We tested the outcomes using the enjoyment rating scale, intrinsic motivation inventory (IMI), and 20-m shuttle run test (20mSRT).ResultsIn phase I, test–retest reliability was good to excellent in the static task and moderate to good in the dynamic task. Concurrent validity was excellent in both tasks. In phase II, more than half of the children (18 out of 26) assigned the maximum rating for their enjoyment of the game; they also had high average scores on the IMI. Furthermore, after the 8-week training using the VR program, the average running distance of the 26 children in the 20mSRT had increased significantly from 129.23 m to 176.92 m (p &lt; 0.001).ConclusionOur VR-based exergaming program can serve as an alternative intervention for enhancing cardiopulmonary fitness in children with DCD.
Decoding signaling mechanisms: unraveling the targets of guanylate cyclase agonists in cardiovascular and digestive diseases
Authors: Yin Qinan , Zheng Xingyue , Song Yujie , Wu Liuyun , Li Lian , Tong Rongsheng , Han Lizhu , Bian Yuan 
Published: December 2023

Graphical AbstractPossible therapeutic indications for sGC agonists and GC-C agonists.
Club cell CREB regulates the goblet cell transcriptional network and pro-mucin effects of IL-1B
Authors: Sponchiado Mariana , Bonilla Angelina L. , Mata Luz , Jasso-Johnson Kalene , Liao Yan-Shin J. , Fagan Amy , Moncada Victor , Reznikov Leah R. 
Published: December 2023

Introduction: Club cells are precursors for mucus-producing goblet cells. Interleukin 1β (IL-1B) is an inflammatory mediator with pro-mucin activities that increases the number of mucus-producing goblet cells. IL-1B-mediated mucin production in alveolar adenocarcinoma cells requires activation of the cAMP response element-binding protein (CREB). Whether the pro-mucin activities of IL-1B require club cell CREB is unknown.Methods: We challenged male mice with conditional loss of club cell Creb1 and wild type littermates with intra-airway IL-1B or vehicle. Secondarily, we studied human “club cell-like” H322 cells.Results: IL-1B increased whole lung mRNA of secreted (Mucin 5ac, Mucin 5b) and tethered (Mucin 1, Mucin 4) mucins independent of genotype. However, loss of club cell Creb1 increased whole lung mRNA of member RAS oncogene family (Rab3D), decreased mRNA of the muscarinic receptor 3 (M3R) and prevented IL-1B mediated increases in purinergic receptor P2Y, (P2ry2) mRNA. IL-1B increased the density of goblet cells containing neutral mucins in wildtype mice but not in mice with loss of club cell Creb1. These findings suggested that club cell Creb1 regulated mucin secretion. Loss of club cell Creb1 also prevented IL-1B-mediated impairments in airway mechanics. Four days of pharmacologic CREB inhibition in H322 cells increased mRNA abundance of forkhead box A2 (FOXA2), a repressor of goblet cell expansion, and decreased mRNA expression of SAM pointed domain containing ETS transcription factor (SPDEF), a driver of goblet cell expansion. Chromatin immunoprecipitation demonstrated that CREB directly bound to the promoter region of FOXA2, but not to the promoter region of SPDEF. Treatment of H322 cells with IL-1B increased cAMP levels, providing a direct link between IL-1B and CREB signaling.Conclusion: Our findings suggest that club cell Creb1 regulates the pro-mucin properties of IL-1B through pathways likely involving FOXA2.