bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of large volume subcutaneous injections using computed tomography imaging and simultaneous pressure measurements
Authors: Purcell Mona , Babaee Sahab , Galluppi Michael , Cline John , Hu Guangli , Petrescu Ioan , Hughes Jennifer , Allen Meredith , Messina Eric , Persak Steven , Krishnamachari Yogita , Lay-Fortenbery Ashley , Miller Corin O. 
Published: July 2023

Many commercially available biologics, previously delivered only intravenously, are being re-formulated for subcutaneous delivery to improve patient access and compliance. However, due to inherent solubility limitations, large volume injections (more than 2 mL) are typically required. Different strategies are being explored to improve the tolerability of such injections, including the co-formulation with hyaluronidase and/or implementing different needle designs. While there have been separate reports of measuring injection forces and using imaging to track injection delivery and tissue response, there is no current set of methods to simultaneously characterize the injection delivery (bleb) and measure injection pressures. In this study we describe the development of Computed Tomography imaging methods in minipigs to characterize the morphology of the bleb following injection, along with inline pressure measurements to assess subcutaneous pressure during injection using two different injection volumes, 4.5 mL and 9 mL. We show that these parameters change with injection volume, and that inclusion of hyaluronidase in the injection increases bleb dispersion and reduces skin distention while also lowering the injection pressure. This method will likely be a valuable tool for assessing and comparing different injection delivery methods and formulations.
Multimodal predictive factors of metastasis in lymph nodes posterior to the right recurrent laryngeal nerve in papillary thyroid carcinoma
Authors: Gong Yi , Zuo Zhongkun , Tang Kui , Xu Yan , Zhang Rongsen , Peng Qiang , Niu Chengcheng 
Published: July 2023

ObjectiveThe lymph node posterior to the right recurrent laryngeal nerve (LN-prRLN) is a crucial component of the central lymph nodes (LNs). We aimed to evaluate multimodal predictive factors of LN-prRLN metastasis in patients with papillary thyroid carcinomas (PTCs), including the clinical data, pathologic data, and preoperative sonographic characteristics of PTCs.MethodsA total of 403 diagnosed PTC patients who underwent unilateral, sub-total, or total thyroidectomy with central neck dissection were enrolled in this retrospective study. The clinical data, pathologic data, conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) characteristics of PTCs were collected and evaluated for predicting LN-prRLN metastasis.ResultsIn this study, 96 PTC patients with LN-prRLN metastasis and 307 PTC patients without LN-prRLN metastasis were included. Univariate analysis demonstrated that PTC patients with LN-prRLN metastasis more often had younger age, larger size, multifocal cancers, A/T &lt; 1, well-margins, microcalcification, petal-like calcification, internal vascularity, centripetal perfusion pattern and surrounding ring enhancement. Multivariate logistic regression analysis revealed that the CEUS centripetal perfusion pattern, central LN detected by ultrasound and LN-arRLN metastasis were independent characteristics for predicting LN-prRLN metastasis in PTC patients.ConclusionAccording to our research, it is essential for clinicians to thoroughly dissect central LNs, particularly LN-prRLNs.
Effects of aerobic exercises in prediabetes patients: a systematic review and meta-analysis
Authors: Wang Yifei , Li Honglei , Yang Dongxue , Wang Mengzhao , Han Yanbai , Wang Hongli 
Published: July 2023

AimsTo evaluate the effects of different durations of continuous aerobic exercise on prediabetic patients.Materials and methodsThe research encompassed randomized controlled trials that examined how various durations of aerobic exercise training affected outcomes related to Body Mass Index (BMI), Fasting blood glucose (FBG), 2-hour plasma glucose (2hPG), and glycated hemoglobin (HbA1c) in individuals diagnosed with prediabetes. PubMed, Embase, Web of Science, and the Cochrane Library were searched as of January 7, 2023. The Cochrane Risk of Bias, version 2 (ROB 2) tool was used to assess the risk of bias.ResultsA total of 10 RCTs with 815 prediabetic patients were included. The average age of the participants was 56.1 years, with a standard deviation of 5.1 years. Among the participants, 39.2% were male. The interventions consisted of aerobic dance, treadmill running, walking, and a combination of aerobic exercises. The training sessions occurred three or four times per week. In prediabetic patients, aerobic exercise demonstrated a significant reduction in BMI compared to the control group, with a weighted mean difference (WMD) of -1.44 kg/m2 (95% confidence interval [CI] -1.89, -0.98). There was a decrease in FBG levels, with WMD of -0.51 mmol/L (95% CI -0.70, -0.32). Additionally, aerobic training led to significant improvements in 2hPG levels, with a WMD of -0.76 mmol/L (95% CI -1.14, -0.38). Furthermore, prediabetic patients showed a decrease in HbA1c levels after engaging in aerobic training compared to the control group, with a WMD of -0.34% (95% CI -0.45, -0.23).ConclusionIn summary, engaging in aerobic exercise can have a significant positive impact on glycemic levels in individuals with prediabetes. It can also lead to reductions in BMI, FBG, 2hPG, HbA1c, and other relevant indicators. The extent of these improvements may vary slightly depending on the duration of the aerobic exercise intervention.Systematic review registrationPROSPERO https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023395515.
Trend of pregnancy outcomes in type 1 diabetes compared to control women: a register-based analysis in 1996-2018
Authors: Fazekas-Pongor Vince , Svébis Mark M. , Major David , Pártos Katalin , Dósa Norbert , Mészáros Ágota , Horváth Viktor J. , Domján Beatrix A. , Zsirai László , Tabák Adam G. 
Published: July 2023

IntroductionIn 1989, the St Vincent declaration aimed to approximate pregnancy outcomes of diabetes to that of healthy pregnancies. We aimed to compare frequency and trends of outcomes of pregnancies affected by type 1 diabetes and controls in 1996–2018.MethodsWe used anonymized records of a mandatory nation-wide registry of all deliveries between gestational weeks 24 and 42 in Hungary. We included all singleton births (4,091 type 1 diabetes, 1,879,183 controls) between 1996 and 2018. We compared frequency and trends of pregnancy outcomes between type 1 diabetes and control pregnancies using hierarchical Poisson regression.ResultsThe frequency of stillbirth, perinatal mortality, large for gestational age, caesarean section, admission to neonatal intensive care unit (NICU), and low Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score was 2-4 times higher in type 1 diabetes compared to controls, while the risk of congenital malformations was increased by 51% and SGA was decreased by 42% (all p&lt;0.05). These observations remained significant after adjustment for confounders except for low APGAR scores. We found decreasing rate ratios comparing cases and controls over time for caesarean sections, low APGAR scores (p&lt;0.05), and for NICU admissions (p=0.052) in adjusted models. The difference between cases and controls became non-significant after 2009. No linear trends were observed for the other outcomes.ConclusionsAlthough we found that the rates of SGA, NICU care, and low APGAR score improved in pregnancies complicated by type 1 diabetes, the target of the St Vincent Declaration was only achieved for the occurrence of low APGAR scores.
Can meteorological data and normalized difference vegetation index be used to quantify soil pH in grasslands?
Authors: Dai Erfu , Zhang Guangyu , Fu Gang , Zha Xinjie 
Published: July 2023

Quantifying soil pH at manifold spatio-temporal scales is critical for examining the impacts of global change on soil quality. It is still unclear whether meteorological data and normalized difference vegetation index (NDVI) can be used to quantify soil pH in grasslands. Here, nine methods (i.e., RF: random-forest, GLR: generalized-linear-regression, GBR: generalized-boosted-regression, MLR: multiple-linear-regression, ANN: artificial-neural-network, CIT: conditional-inference-tree, SVM: support-vector-machine, eXGB: eXtreme-gradient-boosting, RRT: recursive-regression-tree) were applied to quantify soil pH. Three independent variables (i.e., AP: annual precipitation, AT: annual temperature, ARad: annual radiation) were used to quantify potential soil pH (pHp), and four independent variables (i.e., AP, AT, ARad and NDVImax: maximum NDVI during growing season) were applied to quantify actual soil pH (pHa). Overall, the developed eXGB models performed the worst (linear regression slope &lt; 0.60; R2 = 0.99; relative deviation ≤ –43.54%; RMSE ≥ 3.14), but developed RF models performed the best (linear regression slope: 0.99–1.01; R2 = 1.00; relative deviation: from –1.26% to 0.65%; RMSE ≤ 0.28). The linear regression slope, R2, absolute value of relative deviation and RMSE between modelled and measured soil pH were 0.96–1.03, 0.99–1.00, ≤ 3.87% and ≤ 0.88 for the other seven methods, respectively. Accordingly, except the developed eXGB approach, the developed other eight methods can have relative greater accuracies in quantifying soil pH. However, the developed RF had the uppermost quantification accuracy for soil pH. Whether or not meteorological data and normalized difference vegetation index can be used to quantify soil pH was dependent on the chosen models. The RF developed by this study can be used to quantify soil pH from measured meteorological data and NDVImax, and may be conducive to scientific studies related to soil quality and degradation (e.g., soil acidification and salinization) at manifold spatial-temporal under future globe change.
Hub genes, diagnostic model, and predicted drugs in systemic sclerosis by integrated bioinformatics analysis
Authors: Yan Yue-Mei , Jin Meng-Zhu , Li Sheng-Hua , Wu Yun , Wang Qiang , Hu Fei-Fei , Shen Chen , Yin Wen-Hao 
Published: July 2023

Background: Systemic sclerosis (scleroderma; SSc), a rare and heterogeneous connective tissue disease, remains unclear in terms of its underlying causative genes and effective therapeutic approaches. The purpose of the present study was to identify hub genes, diagnostic markers and explore potential small-molecule drugs of SSc.Methods: The cohorts of data used in this study were downloaded from the Gene Expression Complex (GEO) database. Integrated bioinformatic tools were utilized for exploration, including Weighted Gene Co-Expression Network Analysis (WGCNA), least absolute shrinkage and selection operator (LASSO) regression, gene set enrichment analysis (GSEA), Connectivity Map (CMap) analysis, molecular docking, and pharmacokinetic/toxicity properties exploration.Results: Seven hub genes (THY1, SULF1, PRSS23, COL5A2, NNMT, SLCO2B1, and TIMP1) were obtained in the merged gene expression profiles of GSE45485 and GSE76885. GSEA results have shown that they are associated with autoimmune diseases, microorganism infections, inflammatory related pathways, immune responses, and fibrosis process. Among them, THY1 and SULF1 were identified as diagnostic markers and validated in skin samples from GSE32413, GSE95065, GSE58095 and GSE125362. Finally, ten small-molecule drugs with potential therapeutic effects were identified, mainly including phosphodiesterase (PDE) inhibitors (BRL-50481, dipyridamole), TGF-β receptor inhibitor (SB-525334), and so on.Conclusion: This study provides new sights into a deeper understanding the molecular mechanisms in the pathogenesis of SSc. More importantly, the results may offer promising clues for further experimental studies and novel treatment strategies.
Imbalanced distribution of regulatory T cells and Th17.1 cells in the peripheral blood and BALF of sarcoidosis patients: relationship to disease activity and the fibrotic radiographic phenotype
Authors: Zhang Hui , Jiang Dingyuan , Zhu Lili , Zhou Guowu , Xie Bingbing , Cui Ye , Costabel Ulrich , Dai Huaping 
Published: July 2023

RationaleSarcoidosis is a granulomatous interstitial lung disease involving a complex interplay among different cluster of differentiation 4 (CD4+) thymus cell (T-cell) subsets. Originally described as a type 1 T-helper (Th1) inflammatory disease, recent evidence suggests that both effector and regulatory T-cell subgroups play a critical role in sarcoidosis, but this remains controversial.ObjectivesWe aimed to investigate the distribution of CD4+ T-cell subpopulations in sarcoidosis patients and its potential associations with clinical disease activity and a radiographic fibrotic phenotype.MethodsWe measured the frequencies of regulatory T cells (Tregs), Th1, Th17, and Th17.1 cells in the peripheral blood and/or bronchoalveolar lavage fluid (BALF) of 62 sarcoidosis patients, 66 idiopathic pulmonary fibrosis (IPF) patients, and 41 healthy volunteers using flow cytometry. We also measured the changes in these T-cell subpopulations in the blood at the follow-up visits of 11 sarcoidosis patients.Measurements and resultsAn increased percentage of Tregs was observed in the peripheral blood of sarcoidosis patients, with a positive association to disease activity and a fibrotic radiographic phenotype. We found a higher frequency of Tregs, a lower proportion of Th17.1 cells, and a lower ratio of Th17.1 cells to total Tregs in the peripheral blood of both active and fibrotic sarcoidosis patients, compared with IPF patients or healthy donors. In contrast, a lower frequency of Tregs and a higher proportion of Th17.1 cells was found in the BALF of sarcoidosis patients than in that of IPF patients. There was an imbalance of Tregs and Th17.1 cells between the peripheral blood and BALF in sarcoidosis patients. Following immunoregulatory therapy, the proportion of circulating Tregs in sarcoidosis patients decreased.ConclusionA higher proportion of Tregs in the peripheral blood of sarcoidosis patients was related to disease activity, fibrotic phenotype, and the need for immunoregulatory therapy. The imbalanced distribution of Tregs and Th17.1 cells in patients’ peripheral blood and BALF suggests that the lung microenvironment has an effect on the immunological pathogenesis of sarcoidosis. Therefore, further studies on the functional analysis of Tregs and Th17.1 cells in sarcoidosis patients are warranted.
Comparing clinical and imaging features of patients with MOG antibody-positivity and with and without oligoclonal bands
Authors: Tomizawa Yuji , Hoshino Yasunobu , Kamo Ryota , Cossu Davide , Yokoyama Kazumasa , Hattori Nobutaka 
Published: July 2023

IntroductionMyelin-oligodendrocyte glycoprotein antibody (MOG)–associated disorder (MOGAD) is a recently identified immune-mediated inflammatory disorder of the central nervous system (CNS). The significance of oligoclonal bands (OCBs) is not fully elucidated. This study investigated the clinical differences between patients with MOGAD who tested positive or negative for OCBs.MethodsThe study was conducted on 23 patients with MOG-IgG-seropositivity who presented with central nervous system (CNS) symptoms. The patients were screened and divided into OCB-positive (n=10) and OCB-negative (n=13) groups, and their demographic, clinical, and magnetic resonance imaging (MRI) features were compared.ResultsThe results revealed that patients with OCB-positivity had a significantly higher frequency of relapse, and their IgG index was significantly higher.DiscussionOCBs were common in MOGAD met the consensus criteria. The study concluded that careful treatment decision-making is necessary in MOG antibody-positive cases with OCB-positivity.
Cytokine profile characterization of naïve patients with psoriasis and psoriatic arthritis: implications for a pathogenic disease continuum
Authors: Ruscitti Piero , Esposito Maria , Di Cola Ilenia , Pellegrini Cristina , De Berardinis Andrea , Mastrangelo Mirco , Gianneramo Camilla , Barile Antonio , Fargnoli Maria Concetta , Cipriani Paola 
Published: July 2023

BackgroundThe idea of psoriatic disease continuum has been progressively prompted based on the advances of the knowledge about the pathogenic steps underpinning the occurrence of psoriasis (PSO) and psoriatic arthritis (PSA). To evaluate biomolecules (inflammatory cytokines, inflammatory chemokines, cell adhesion and cellular mediators) in naïve patients with PSO, PSA with PSO, and PSA sine PSO. To stratify the results considering the presence of psoriatic nail involvement, extensive skin disease and obesity evaluating all involved patients.MethodsBy multiplex technology, 20 serum biomolecules were assessed with the inclusion of pro-inflammatory cytokines (GM-CSF, IFN-γ, IL-1α, IL-1β, IL-6, IL-8, IL-12p70, IL-17A, IL-23, TNF), anti-inflammatory cytokines (IFN-α, IL-4, IL-10, IL-13), inflammatory chemokines (IP-10, MCP-1, MIP-1α, MIP-1β), cell adhesion and cellular mediators (ICAM-1, E-selectin, P-selectin). The assessment of possible statistical differences between the means of the three groups was performed by One-Way ANOVA. In addition, by non-parametric T-tests, we stratified the results according to selected clinical characteristics (psoriatic nail involvement, PASI ≥ 10, BMI ≥ 30).ResultsIn 80 assessed naïve patients, patients with PSO showed significant increases of E-selectin (p=0.021) and IL-8 (0.041) than other groups. In patients with PSA with PSO, significant higher levels of ICAM-1 were observed (p=0.009) than other groups. We did not observe further differences comparing pro-inflammatory and anti-inflammatory cytokines, inflammatory chemokines, and cell adhesion and cellular mediators in patients with PSO, PSA with PSO, and PSA sine PSO. Patients with psoriatic onychopathy showed significant increased levels of ICAM-1 (p=0.010) and IP-10 (0.030) than others. In patients with PASI ≥ 10, significantly enhanced values of IL-8 (p=0.004), TNF (p=0.013), E-selectin (p=0.004), MIP-1α (p=0.003), and MIP-1β (p=0.039). In patients with BMI ≥ 30, significantly higher levels of E-selectin were pointed out (p=0.035) than others.ConclusionOur findings may suggest that a similar cytokine profile may characterize naïve patients with PSO, PSA with PSO, and PSA sine PSO, reinforcing the concept of psoriatic disease continuum. However, some differences may be also shown, underlying possible pathogenic differences and leading to the clinical heterogeneity of these patients.
Acoustic behavior of gray whales tagged with biologging devices on foraging grounds
Authors: Clayton Hannah , Cade David E. , Burnham Rianna , Calambokidis John , Goldbogen Jeremy 
Published: July 2023

Understanding the function of baleen whale acoustic signals requires the investigation of calling behaviors relative to location, timing, and behavioral state. Previous studies of gray whale (Eschrichtius robustus) vocal behavior have principally used passive recorders and been conducted primarily on breeding grounds and along migratory routes, and not areas associated with foraging. We conducted an analysis of accelerometer and acoustic data collected during 12 deployments of animal-borne tags in 2016, 2019, and 2021 on gray whales that return annually to northern Puget Sound, Washington. We identified 141 calls from gray whales in approximately 128 hours of accelerometer and/or acoustic data collected from tag deployments. The most prominent were pulsive ‘rumble-like’ calls, upsweeping tones, and moans. Using the tag’s accelerometer to identify calls produced by tagged animals enabled us to explore the behavioral context behind call production, revealing that vocalizations were made primarily at slow speeds (mean 1.03 ± 0.26 m/s-1), shallow depths (mean 7.63 ± 4.99 m), and temporally proximate to surface behavior (mean 43.3 ± 39.66 sec) most similar to non-foraging associated depth (mean 5.78 ± 1.46 m and speed (mean 1.46 ± 1.11 m/s-1) profiles. Vocalizations originating from the tagged animal occurred closer to the conclusion of a foraging event (mean 87.7 ± 119.32 min) than the beginning, with only 7% of all calls occurring during periods of feeding. This study demonstrates that gray whales remain vocal on foraging grounds and that call-associated accelerometry signals can be a valuable tool in identifying individual callers in animal-borne acoustic data.
Regional homogeneity and functional connectivity of freezing of gait conversion in Parkinson’s disease
Authors: Bao Yiqing , Ya Yang , Liu Jing , Zhang Chenchen , Wang Erlei , Fan Guohua 
Published: July 2023

BackgroundFreezing of gait (FOG) is common in the late stage of Parkinson’s disease (PD), which can lead to disability and impacts the quality of life. Therefore, early recognition is crucial for therapeutic intervention. We aimed to explore the abnormal regional homogeneity (ReHo) and functional connectivity (FC) in FOG converters and evaluate their diagnostic values.MethodsThe data downloaded from the Parkinson’s Disease Progression Markers Project (PPMI) cohort was subdivided into PD-FOG converters (n= 16) and non-converters (n= 17) based on whether FOG appeared during the 3-year follow-up; 16 healthy controls were well-matched. ReHo and FC analyses were used to explore the variations in spontaneous activity and interactions between significant regions among three groups of baseline data. Correlations between clinical variables and the altered ReHo values were assessed in FOG converter group. Last, logistic regression and receiver operating characteristic curve (ROC) were used to predict diagnostic value.ResultsCompared with the non-converters, FOG converters had reduced ReHo in the bilateral medial superior frontal gyrus (SFGmed), which was negatively correlated with the postural instability and gait difficulty (PIGD) score. ReHo within left amygdala/olfactory cortex/putamen (AMYG/OLF/PUT) was decreased, which was correlated with anxiety and autonomic dysfunction. Also, increased ReHo in the left supplementary motor area/paracentral lobule was positively correlated with the rapid eye movement sleep behavior disorder screening questionnaire. FOG converters exhibited diminished FC in the basal ganglia, limbic area, and cognitive control cortex, as compared with non-converters. The prediction model combined ReHo of basal ganglia and limbic area, with PIGD score was the best predictor of FOG conversion.ConclusionThe current results suggested that abnormal ReHo and FC in the basal ganglia, limbic area, and cognitive control cortex may occur in the early stage of FOG. Basal ganglia and limbic area dysfunction combined with higher PIGD score are useful for the early recognition of FOG conversion.