bluuebunny/crossref_metadata_2025 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

Objective

The 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.

Methods

A 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.

Results

In 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 < 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.

Conclusion

According 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

Aims

To evaluate the effects of different durations of continuous aerobic exercise on prediabetic patients.

Materials and methods

The 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.

Results

A 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).

Conclusion

In 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 registration

PROSPERO 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

Introduction

In 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.

Methods

We 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.

Results

The 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<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<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.

Conclusions

Although 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.
Extraction and monitoring of vegetation coverage based on uncrewed aerial vehicle visible image in a post gold mining area
Authors: Chen Rui , Han Lei , Zhao Yonghua , Zhao Zilin , Liu Zhao , Li Risheng , Xia Longfei , Zhai Yunmeng
Published: July 2023

Vegetation coverage reflects the degree of environmental degradation. Timely and effective monitoring of vegetation conditions is the basis for promoting vegetation protection and improving the ecological environment of mining areas. Exploring vegetation coverage extraction methods and selecting the optimal vegetation index in mining areas can provide scientific reference for estimating vegetation coverage based on vegetation index in mining areas. Uncrewed aerial vehicles (UAVs) are widely used because of their fast real-time performance, high spatial resolution, and easy accessibility. In this study, the performances of nine visible vegetation indices and two threshold segmentation methods for extracting vegetation coverage in a post-gold mining area in the Qinling Mountains were comprehensively compared using visible spectrum UAV images. Of the nine indices, the excess green index (EXG) and visible-band difference vegetation index (VDVI) were the most effective in discriminating between vegetation and non-vegetation by visual interpretation. In addition, the accuracy of the bimodal histogram threshold method in extracting vegetation coverage was higher than that of Otsu’s threshold method. The bimodal histogram threshold method combined with EXG yielded optimal extraction results. Based on optimal methods, the total percentages of fractional vegetation coverage in 2019, 2020, and 2021 were 31.47%, 34.08%, and 42.77%, respectively, indicating that the vegetation in the mining area improved. These results provide valuable guidance for extracting vegetation information and evaluating vegetation restoration in mining areas.
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 < 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.
Maize stover transfers from maize fields to banana-based agroforestry homegardens and the corresponding nutrient flows in central-northern Tanzania
Authors: Meya Akida I. , Swennen Rony , Ndakidemi Patrick A. , Mtei Kelvin M. , Merckx Roel
Published: July 2023

Maize (Zea mays) stover produced in the drier lowland areas on the volcanic foot slopes of Mount Kilimanjaro serves as an important additional fodder for smallholder zero-grazed dairy cattle farming in the humid highland areas of the region. The obtained cattle manure is used to replenish nutrients and manage soil fertility in banana-based agroforestry homegardens of the highlands, which contributes significantly to sustaining crop production, thus food security and the livelihoods of the community. The study aims to provide a preliminary evaluation of the amounts of stover removed from smallholder maize-based fields in the lowlands and the subsequent nutrient flows to the banana-based agroforestry homegardens of the highlands. In 54 smallholder maize fields selected at random from 11 villages in the Hai and Siha districts of the Kilimanjaro region, we conducted an agronomic survey to record the types and amounts of fertilizer used, plant spacing at harvest, and maize stover biomass yield. Most of the surveyed maize-based fields received inadequate nutrient inputs, which were limited to mineral nitrogen alone if any. Of the surveyed fields, 16.7% received recommended amounts of 74 kg N ha–1 by the Ministry of Agriculture, 46.3% sub-optimal amounts and 37.0% did not receive fertilizer at all. Plant density was only 50% of the recommended population density. While this was only a preliminary study on nutrient flows between maize and banana-based agroecosystems, our findings demonstrated that potassium exports via harvested banana bunches exceeded the inputs in the homegardens. We conclude that (i) soil fertility management techniques, preferably integrated soil fertility management, suitable for small-scale maize production in the lowlands should be formulated while optimizing plant density to increase production, (ii) maize-based agroforestry farming system adapted to drier conditions to deal with windstorm and soil erosion problems in the lowlands is urgently needed, and (iii) wider and more detailed research on nutrient flows between maize and banana-based agroecosystems should be conducted to document their respective soil nutrient balances and the sustainability of such practice.
CRISPR library screening to develop HEK293-derived cell lines with improved lentiviral vector titers
Authors: Iaffaldano Brian J. , Marino Michael P. , Reiser Jakob
Published: July 2023

Lentiviral (LV) vectors have emerged as powerful tools for treating genetic and acquired human diseases. As clinical studies and commercial demands have progressed, there has been a growing need for large amounts of purified LV vectors. To help meet this demand, we developed CRISPR library screening methods to identify genetic perturbations in human embryonic kidney 293 (HEK293) cells and their derivatives that may increase LV vector titers. Briefly, LV vector-based Human CRISPR Activation and Knockout libraries (Calabrese and Brunello) were used to modify HEK293 and HEK293T cells. These cell populations were then expanded, and integrated LV vector genomes were rescued by transfection. LV vectors were harvested, and the process of sequential transduction and rescue-transfection was iterated. Through this workflow, guide RNAs (gRNAs) that target genes that may suppress or enhance LV vector production were enriched and identified with Next-Generation Sequencing (NGS). Though more work is needed to test genes identified in this screen, we expect that perturbations of genes we identified here, such as TTLL12, which is an inhibitor of antiviral innate immunity may be introduced and multiplexed to yield cell lines with improved LV vector productivity.
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

Rationale

Sarcoidosis 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.

Objectives

We 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.

Methods

We 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 results

An 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.

Conclusion

A 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.
Bispecific antibody targeting TGF-β and PD-L1 for synergistic cancer immunotherapy
Authors: Li Tianye , Wang Xinrun , Niu Mengke , Wang Mingli , Zhou Jianwei , Wu Kongming , Yi Ming
Published: July 2023

The PD-1/PD-L1 signaling pathway plays a crucial role in cancer immune evasion, and the use of anti-PD-1/PD-L1 antibodies represents a significant milestone in cancer immunotherapy. However, the low response rate observed in unselected patients and the development of therapeutic resistance remain major obstacles to their clinical application. Accumulating studies showed that overexpressed TGF-β is another immunosuppressive factor apart from traditional immune checkpoints. Actually, the effects of PD-1 and TGF-β pathways are independent and interactive, which work together contributing to the immune evasion of cancer cell. It has been verified that blocking TGF-β and PD-L1 simultaneously could enhance the efficacy of PD-L1 monoclonal antibody and overcome its treatment resistance. Based on the bispecific antibody or fusion protein technology, multiple bispecific and bifunctional antibodies have been developed. In the preclinical and clinical studies, these updated antibodies exhibited potent anti-tumor activity, superior to anti-PD-1/PD-L1 monotherapies. In the review, we summarized the advances of bispecific antibodies targeting TGF-β and PD-L1 in cancer immunotherapy. We believe these next-generation immune checkpoint inhibitors would substantially alter the cancer treatment paradigm, especially in anti-PD-1/PD-L1-resistant patients.
Intravesical BCG in bladder cancer induces innate immune responses against SARS-CoV-2
Authors: Pichler Renate , Diem Gabriel , Hackl Hubert , Koutník Jiří , Mertens Laura S. , D`Andrea David , Pradere Benjamin , Soria Francesco , Mari Andrea , Laukhtina Ekaterina , Krajewski Wojciech , Teoh Jeremy Yuen-Chun , Del Guidice Francesco , Moschini Marco , Thurnher Martin , Posch Wilfried
Published: July 2023

BCG is the most efficient adjuvant therapy for high-risk, non-muscle-invasive bladder cancer (NMIBC). Both innate and adaptive immune responses have been implicated in BCG-mediated effects. BCG vaccination can boost innate immune responses via trained immunity (TI), resulting in an increased resistance to respiratory viral infections. Here we evaluated for the first time whether intravesical application of BCG triggers increased immunity against SARS-CoV-2 in patients with high-risk NMIBC. Serum and peripheral blood mononuclear cells (PBMCs) from heparinized whole blood samples of 11 unvaccinated SARS-CoV-2-naïve high-risk NMIBC patients were collected at baseline and during BCG treatment in a pre-COVID-19 era. To examine B-cell or T cell-dependent adaptive immunity against SARS-CoV-2, sera were tested for the presence of SARS-CoV-2 neutralizing antibodies. Using a SARS-CoV-2 peptide pool, virus-specific T cells were quantified via IFNγ ELISpot assays. To analyze innate immune responses, mRNA and protein expression levels of pro- and anti-inflammatory cytokines were measured after a 24-hour stimulation of PBMCs with either BCG or SARS-CoV-2 wildtype. ATAC- sequencing was performed to identify a potential epigenetic reprogramming in immune cells. We neither identified SARS-CoV-2 neutralizing antibodies nor SARS-CoV-2- reactive T cells, indicating that intravesical BCG did not induce adaptive immunity against SARS-CoV-2. However, a significant increase in mRNA as well as protein expression of IL-1β, IL-6 and TNFα, which are key cytokines of trained immunity, could be observed after at least four intravesical BCG instillations. Genomic regions in the proximity of TI genes (TLR2, IGF1R, AKT1, MTOR, MAPK14, HSP90AA1) were more accessible during BCG compared to baseline. Although intravesical BCG did not induce adaptive immune responses, repetitive intravesical instillations of BCG induced circulating innate immune cells that produce TI cytokines also in response to SARS-CoV-2.
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

Introduction

Myelin-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.

Methods

The 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.

Results

The results revealed that patients with OCB-positivity had a significantly higher frequency of relapse, and their IgG index was significantly higher.

Discussion

OCBs 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

Background

The 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.

Methods

By 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).

Results

In 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.

Conclusion

Our 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.
Low-level jets drive the summer intra-seasonal variability of the Canary upwelling system
Authors: Alves José M. R. , Miranda Pedro M.A. , Caldeira Rui M.A.
Published: July 2023

The role of low-level jets in the intra-seasonal variability of the Canary upwelling system during summer is assessed with a fully coupled, high resolution (3km) ocean-atmosphere numerical simulation. Here, low-level jets include the main continental coastal jet, the tip jets of Madeira and the tip-jets of the steep Canary Islands. The coastline shape, orography of northwest Africa and the proximity of Canary islands lead to complex interactions between the jets, that result in strong surface wind intra-seasonal variability on the multiweek time scale. That variability is forced by oscillations in the shape and position of the Azores subtropical anticyclone, through a strong oscillation in the atmospheric boundary layer height. At the coast, coastal-trapped oscillations with a propagation speed, planetary boundary height, offshore extension, and surface pressure compatible with a Kelvin wave occasionally propagate northward, against the synoptic scale surface pressure. While similar processes have already been observed in California, the mechanisms here described appear to result from interactions of continental coastal processes with a set of steep islands close to the coast. The sensitivity of these dynamics to climate change is a challenging question.
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.
A review on synthesis and antibacterial potential of bio-selenium nanoparticles in the food industry
Authors: Ao Bo , Du Qingquan , Liu Decheng , Shi Xiaoshan , Tu Junming , Xia Xian
Published: July 2023

Effective control of foodborne pathogen contamination is a significant challenge to the food industry, but the development of new antibacterial nanotechnologies offers new opportunities. Notably, selenium nanoparticles have been extensively studied and successfully applied in various food fields. Selenium nanoparticles act as food antibacterial agents with a number of benefits, including selenium as an essential trace element in food, prevention of drug resistance induction in foodborne pathogens, and improvement of shelf life and food storage conditions. Compared to physical and chemical methods, biogenic selenium nanoparticles (Bio-SeNPs) are safer and more multifunctional due to the bioactive molecules in Bio-SeNPs. This review includes a summarization of (1) biosynthesized of Bio-SeNPs from different sources (plant extracts, fungi and bacteria) and their antibacterial activity against various foodborne bacteria; (2) the antibacterial mechanisms of Bio-SeNPs, including penetration of cell wall, damage to cell membrane and contents leakage, inhibition of biofilm formation, and induction of oxidative stress; (3) the potential antibacterial applications of Bio-SeNPs as food packaging materials, food additives and fertilizers/feeds for crops and animals in the food industry; and (4) the cytotoxicity and animal toxicity of Bio-SeNPs. The related knowledge contributes to enhancing our understanding of Bio-SeNP applications and makes a valuable contribution to ensuring food safety.
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

Background

Freezing 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.

Methods

The 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.

Results

Compared 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.

Conclusion

The 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.
Avenues within the gut-liver-brain axis linking chronic liver disease and symptoms
Authors: Nguyen Henry H. , Swain Mark G.
Published: July 2023

Symptoms of fatigue, social withdrawal and mood disturbances are commonly encountered in patients with chronic liver disease and have a detrimental effect on patient quality of life. Treatment options for these symptoms are limited and a current area of unmet medical need. In this review, we will evaluate the potential mechanistic avenues within the gut-liver-brain axis that may be altered in the setting of chronic liver disease that drive the development of these symptoms. Both clinical and pre-clinical studies will be highlighted as we discuss how perturbations in host immune response, microbiome, neural responses, and metabolites composition can affect the central nervous system.
In light of breathing: environmental light is an important modulator of breathing with clinical implications
Authors: Jones Aaron A. , Arble Deanna M.
Published: July 2023

In vertebrate animals, the automatic, rhythmic pattern of breathing is a highly regulated process that can be modulated by various behavioral and physiological factors such as metabolism, sleep–wake state, activity level, and endocrine signaling. Environmental light influences many of these modulating factors both indirectly by organizing daily and seasonal rhythms of behavior and directly through acute changes in neural signaling. While several observations from rodent and human studies suggest that environmental light affects breathing, few have systematically evaluated the underlying mechanisms and clinical relevance of environmental light on the regulation of respiratory behavior. Here, we provide new evidence and discuss the potential neurobiological mechanisms by which light modulates breathing. We conclude that environmental light should be considered, from bench to bedside, as a clinically relevant modulator of respiratory health and disease.
Upcycling post-harvest biomass residues from native European Lupinus species: from straws and pod shells production to nutritive value and alkaloids content for ruminant animals
Authors: Maia Margarida R. G. , Monteiro André , Valente Inês M. , Sousa Carla , Miranda Carla , Castro Carlos , Cortez Paulo P. , Cabrita Ana R. J. , Trindade Henrique , Fonseca António J. M.
Published: July 2023

The production of Lupinus seeds for food and feed is increasing worldwide, which results in large amounts of post-harvest biomass residues, considered of low value and left in the field to be burned or incorporated in the soil. To valorize these agricultural wastes, this work aimed to assess their potential as an alternative feed for ruminants. Thus, the production yield, nutritive value, and alkaloid content of straws and pod shells from three native European Lupinus species, L. albus ‘Estoril’ (white), L. angustifolius ‘Tango’ (narrow-leafed), and L. luteus ‘Cardiga’ (yellow), cultivated in two locations, were evaluated. The dry matter (DM) yield of straws and pod shells were the highest for L. albus ‘Estoril’ (4.10 t ha−1) and the lowest for L. angustifolius ‘Tango’ (1.78 t ha−1), suggesting a poor adaptation of narrow-leafed lupin to the particularly dry and warm agronomic year. Despite species-specific differences, lupin biomass residues presented higher crude protein (53.0–68.9 g kg−1 DM) and lignin (103–111 g kg−1 DM) content than cereal straws usually used in ruminant feeding, thus resulting in higher metabolizable energy (6.43–6.58 MJ kg−1 DM) content. In vitro digestibility was similar among lupin species (47.7–50.6%) and higher in pod shells (53.7%) than in straws (44.6%). Lupinus albus ‘Estoril’ and L. luteus ‘Cardiga’ presented considerable amounts of alkaloids in straws (23.9 and 119 mg kg−1 DM) and pod shells (20.5 and 298 mg kg−1 DM), while no alkaloids were detected in L. angustifolius ‘Tango’ biomass residues. Considering the combined production of straw and pod shells per lupin species, it is anticipated that lupin biomass residues produced per ha can fulfill 85% of the energy and nearly 50% of protein requirements of a flock of 4 to 9 dry and mid-pregnancy sheep with 50 kg body weight for one year. No negative effects on small (ovine) and large (bovine) ruminant species due to alkaloids are expected, even if biomass residues are consumed at up to 85% DM intake. The large production yield along with its nutritive value unveils the potential of lupin biomass residues valorization as alternative fodder for ruminants, promoting sustainability under a circular economy approach.
Epigenetics in myeloproliferative neoplasms
Authors: Greenfield Graeme , McMullin Mary Frances
Published: July 2023

The myeloproliferative neoplasms (MPNs) are a group of acquired clonal disorders where mutations drive proliferative disease resulting in increased blood counts and in some cases end-stage myelofibrosis. Epigenetic changes are the reversible modifications to DNA- and RNA-associated proteins that impact gene activity without changing the DNA sequence. This review summarizes mechanisms of epigenetic changes and the nucleosome. The drivers and epigenetic regulators in MPNs are outlined. In MPNs, distinct patterns of epigenetic dysregulation have been seen in chronic and in advanced phases. Methylation age and histone modification are altered in MPNs and by further treatment. The alterations found in methylation age in MPNs and with treatment are discussed, and the changes in histone modification with Janus kinase (JAK) inhibition are evaluated. Currently available therapeutic areas where the epigenome can be altered are outlined. Thus, we review the current knowledge and understanding of epigenetics in MPN and consider further management options. Understanding the epigenome and its alteration in MPNs and epigenetic changes associated with the progression of disease will lead to advances in therapeutic options.
The association between maternal diabetes and neonatal seizures: a nested case–Control study
Authors: Liang Yanjin , Liu Juman , Lin Xianbin
Published: July 2023

Aim

We aimed to evaluate the association of pregestational diabetes mellitus (PGDM) and gestational diabetes mellitus (GDM) with neonatal seizures during neonatal hospitalization.

Methods

In this nested case–control study, all data were collected from the data files of the National Vital Statistics System (NVSS) 2016–2021. Considering the effect of confounders, we used the propensity-score matching (PSM; case:control = 1:4) method to select the study population. The outcome was considered the occurrence of neonatal seizures. Univariate and multivariate logistic regression analyses were adopted to assess the association of PGDM and GDM with neonatal seizures. We also conducted stratified analyses according to gestational age, birthweight, 5 min Apgar score, and maternal age to explore the potential disparities.

Results

After using the PSM method, a total of 6,674 cases of neonatal seizures and 26,696 controls were included. After adjusting for covariates, PGDM was associated with an increased risk of neonatal seizures [odds ratio (OR) = 1.51, 95% confidence interval (CI): 1.15–1.98], whereas the association between GDM and neonatal seizures is not statistically significant. In addition, the correlation between PGDM and increased risk of neonatal seizures was observed in neonates with a gestational age of 37–42 weeks and ≥42 weeks, with a 5 min Apgar score of ≥7, and with a maternal age of ≤40 years.

Conclusion

PGDM was found to be closely associated with an increased risk of neonatal seizures. The findings of our study indicated that neonatologists should consider monitoring the incidence of neonatal seizures in neonates born to mothers with PGDM.
Altered offspring neurodevelopment in an L-NAME-induced preeclampsia rat model
Authors: Nakamura Noriyuki , Ushida Takafumi , Onoda Atsuto , Ueda Kazuto , Miura Ryosuke , Suzuki Toshihiko , Katsuki Satoru , Mizutani Hidesuke , Yoshida Kosuke , Tano Sho , Iitani Yukako , Imai Kenji , Hayakawa Masahiro , Kajiyama Hiroaki , Sato Yoshiaki , Kotani Tomomi
Published: July 2023

Introduction

To investigate the mechanism underlying the increased risk of subsequent neurodevelopmental disorders in children born to mothers with preeclampsia, we evaluated the neurodevelopment of offspring of a preeclampsia rat model induced by the administration of N-nitro-L-arginine methyl ester (L-NAME) and identified unique protein signatures in the offspring cerebrospinal fluid.

Methods

Pregnant rats received an intraperitoneal injection of L-NAME (250 mg/kg/day) during gestational days 15–20 to establish a preeclampsia model. Behavioral experiments (negative geotaxis, open-field, rotarod treadmill, and active avoidance tests), immunohistochemistry [anti-neuronal nuclei (NeuN) staining in the hippocampal dentate gyrus and cerebral cortex on postnatal day 70], and proteome analysis of the cerebrospinal fluid on postnatal day 5 were performed on male offspring.

Results

Offspring of the preeclampsia dam exhibited increased growth restriction at birth (52.5%), but showed postnatal catch-up growth on postnatal day 14. Several behavioral abnormalities including motor development and vestibular function (negative geotaxis test: p < 0.01) in the neonatal period; motor coordination and learning skills (rotarod treadmill test: p = 0.01); and memory skills (active avoidance test: p < 0.01) in the juvenile period were observed. NeuN-positive cells in preeclampsia rats were significantly reduced in both the hippocampal dentate gyrus and cerebral cortex (p < 0.01, p < 0.01, respectively). Among the 1270 proteins in the cerebrospinal fluid identified using liquid chromatography-tandem mass spectrometry, 32 were differentially expressed. Principal component analysis showed that most cerebrospinal fluid samples achieved clear separation between preeclampsia and control rats. Pathway analysis revealed that differentially expressed proteins were associated with endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins, which are involved in various nervous system disorders including autism spectrum disorders, schizophrenia, and Alzheimer's disease.

Conclusion

The offspring of the L-NAME-induced preeclampsia model rats exhibited key features of neurodevelopmental abnormalities on behavioral and pathological examinations similar to humans. We found altered cerebrospinal fluid protein profiling in this preeclampsia rat, and the unique protein signatures related to endoplasmic reticulum translocation, Rab proteins, and ribosomal proteins may be associated with subsequent adverse neurodevelopment in the offspring.