bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrothermally treated coral scaffold promotes proliferation of mesenchymal stem cells and enhances segmental bone defect healing
Authors: Huang Jianping , Park Jaehan , Jung Narae , Moon Hong Seok , Zong Zhixian , Li Gang , Lin Sien , Cho Sung-Won , Park Youngbum
Published: December 2023

Introduction: Synthetic hydroxyapatite (HAp) scaffolds have shown promising therapeutic outcomes in both animals and patients. In this study, we aim to evaluate the chemical and physical phenotype, biocompatibility, and bone repair effects of hydrothermally treated coral with natural coral and synthetic HAp.

Methods: The phase composition, surface pattern, 3D structures, and porosity of the scaffolds were characterized, and cell viability, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) after seeding onto the scaffold were determined. The scaffolds were implanted into rats to assess their bone repair effects using micro-CT analysis, mechanical testing, and histological staining.

Results: The results showed that the phase composition, porous structure, and porosity of hydrothermally treated coral were comparable to pure HAp scaffold. While only the natural coral happens to be dominantly calcium carbonate. Higher cell proliferation and osteogenic differentiation potential were observed in the hydrothermally treated coral scaffold compared to natural coral and pure HAp. Histological results also showed increased new bone formation in the hydrothermally treated coral group.

Discussion: Overall, our study suggests that hydrothermal modification enhances the cytocompatibility and therapeutic capacity of coral without altering its physical properties, showing superior effectiveness in bone repair to synthetic HAp.
Cost-benefit analysis of solar energy integration in buildings: a case study of affordable housing in Brazil
Authors: De Arruda Roberto Nonato , Figueiredo Karoline , Vasco Diego A. , Haddad Assed , Najjar Mohammad K.
Published: December 2023

Introduction: The construction sector plays a pivotal role in global natural resource consumption, underscoring the urgency of promoting energy efficiency in buildings. With the escalating demand for renewable energy, solar power has gained significant traction. This study focuses on conducting a comprehensive cost-benefit analysis of solar energy integration in residential buildings.

Methods: The approach involves a novel comparison between photovoltaic panels and Solar Heating Systems (SHS) based on both environmental and financial considerations. To evaluate the practical implications, a case study was undertaken on an affordable housing complex in Brazil. Three distinct models were simulated for analysis: Model 1, featuring a grid-connected photovoltaic project with zero energy balance; Model 2, incorporating a grid-connected photovoltaic project with two solar panels generating 340 W each; and Model 3, integrating an SHS.

Results: The findings reveal the technical and economic feasibility of all proposed models. Model 1 stands out with superior performance in terms of estimated energy generation, energy savings, and annual reduction of CO2 emissions. On the other hand, Model 3 excels in the financial analysis, indicating its viability from a cost perspective.

Discussion: This research contributes to informed decision-making processes regarding the utilization of photovoltaic panels and SHS, thereby fostering energy efficiency and sustainability in buildings. The nuanced comparison of environmental and financial aspects provides valuable insights for stakeholders in the construction and renewable energy sectors. The identified strengths and trade-offs of each model enable a more holistic understanding of the implications of solar energy integration in residential buildings.
Application of the electrical resistivity method and the estimation of limestone volume: a case study
Authors: Ndam Njikam Mohamed Moustapha , Yem Mbida , Ribodetti Alessandra , Mohamed Ahmed , Soumah Aboubacar , Junior Moaboulou Prosper , Alarifi Saad S. , Abdelrady Ahmed
Published: December 2023

The present work used the electrical resistivity approach to conduct a three-dimensional modeling and initial volume estimation of the limestone layer in the Mintom region located in southern Cameroon. In order to achieve the objectives of the study, a total of 21 electrical soundings spaced 250 m were first collected in the field using the Schlumberger array. These soundings were conducted along three profiles oriented in an east–west direction, spaced 500 m. Additionally, a geological survey was conducted to identify and emphasize the presence of limestone formations within the designated study region. The interpretation of the sounding data was conducted based on the analysis of the sounding curves. The interpretation outcomes, specifically resistivity and thickness, were compared with the geological field data, resulting in the development of lithostratigraphic logs for each sounding. The geological sections were constructed using the logs of the designated profile. The lithological logs were utilized to establish a lithological interface model and calculate the volume of the limestone layer at 260 ± 13 × 106 m3, utilizing the inverse distance method built into RockWorks software. A resistivity value is assigned to each geological layer in a sounding curve, allowing for the development of a resistivity variation model specific to the limestone layer. The proposed model facilitates the categorization of limestone layers based on their resistivity variations, thus serving as a fundamental reference for prospective exploratory activities within the designated study region. Our integrated approach provides a replicable model for a better understanding of the limestone reserve and effective management of this valuable resource.
SGLT-2 inhibitors and prevention of contrast-induced nephropathy in patients with diabetes undergoing coronary angiography and percutaneous coronary interventions: systematic review and meta-analysis
Authors: Meregildo-Rodriguez Edinson Dante , Asmat-Rubio Martha Genara , Vásquez-Tirado Gustavo Adolfo
Published: December 2023

Introduction

SGLT2 inhibitors (SGLT2Is) have demonstrated cardioprotective and nephroprotective effects in patients with and without diabetes. Recent studies suggest that SGLT2Is may reduce the risk of contrast-induced nephropathy (CIN) in patients with diabetes undergoing coronary arteriography (CAG) or percutaneous coronary interventions (PCI). However, the evidence is still inconclusive. We aimed to systematically review the evidence regarding the potential nephroprotective role of SGLT2Is in preventing CIN in this population.

Methods

We searched for studies in six databases published up to September 30, 2023, following a PECO/PICO strategy. Initially, we meta-analyzed five studies, but due to several reasons, mainly methodological concerns, we excluded one RCT. In our final meta-analysis, we included four observational studies.

Results

This meta-analysis comprised 2,572 patients with diabetes undergoing CAG or PCI, 512 patients treated with SGLT2Is, and 289 events of CIN. This is the first meta-analysis demonstrating that SGLT2Is may reduce the risk of developing CIN by up to 63% (RR 0.37; 95% CI 0.24–0.58) in patients with diabetes undergoing CAG or PCI, compared to not using SGLT2Is. Statistical heterogeneity was not significant (I2 = 0%, p = 0.91). We assessed the certainty of the evidence of this systematic review and meta-analysis, according to the GRADE criteria, as moderate.

Conclusion

SGLT2Is significantly reduce the risk of CIN by up to 63% in patients with diabetes undergoing CAG or PCI. Clinical trials are needed; several are already underway, which could confirm our findings and investigate other unresolved issues, such as the optimal dose, type, and duration of SGLT2 inhibitor therapy to prevent CIN.

Systematic Review

PROSPERO, identifier CRD42023412892.
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

Introduction

The 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.

Methods

Firstly, 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.

Results

The 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.

Discussion

Specifically, 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.
Comparative miRNA expression profile analysis of porcine ovarian follicles: new insights into the initiation mechanism of follicular atresia
Authors: Liu Jingge , Ning Caibo , Zhang Jinbi , Xu Shiyong , Wu Jiege , Tao Chenyu , Ma Fanhua , Chen Qing , Pan Zengxiang
Published: December 2023

Follicular atresia occurs in every stage of ovarian development, which is relevant to female fertility. In the past decade, increasing studies have confirmed that miRNAs, a class of short non-coding RNAs, play an important role in follicular atresia by post-transcription regulation of their target genes. However, the function of miRNAs on follicular atresia initiation is unknown. In the present study, high-throughput small RNA sequencing was performed to analyze differential miRNA expression profiles between healthy (HF) follicles and early atretic (EAF) follicles. A total of 237 conserved miRNA were detected, and the miR-143 is the highest expressed in follicles. Meanwhile, we also found wide sequence variations (isomiRs) in porcine ovarian miRNA, including in 5′un-translation region, core seed sequences and 3′untranslation region. Furthermore, we identified 22 differentially expressed miRNAs in EAF groups compared to HF group, of which 3 miRNAs were upregulated, as well as 19 miRNAs were downregulated, and then the RT-PCR was performed to validate these profiles. The target genes of these differentially expressed miRNAs were predicted by using miRwalk, miRDB, and Targetscan database, respectively. Moreover, the gene ontology and KEGG pathway enrichment established that the regulating functions and signaling pathways of these miRNAs contribute to follicular atresia initiation and cell fate. In conclusion, this study provides new insights into the changes of miRNAs in early atretic follicles to demonstrate their molecular regulation in ovarian follicular atretic initiation.
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

Background

Myalgic 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.

Methods

A 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.

Results

The 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.

Discussion

The 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

Introduction

Tobacco 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).

Methods

Smoker 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.

Results

Our 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.

Discussion

The 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

Rationale

Sarcoidosis 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.

Methods

In 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.

Results

We 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.

Conclusion

Tregs 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

Background

Humoral 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.

Methods

We 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.

Results

The anti-S IgG levels in the ‘vaccine-breakthrough infection’ group exceeded those in the ‘infection alone’ and ‘vaccination alone’ groups (both P <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 <0.01). We could not identify newly developed SARS-CoV-2 infection in the ‘vaccine-breakthrough infection’ group.

Conclusion

Our 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

Background

Psoriasis 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.

Objective

The 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).

Methods

Data 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.

Results

The 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.

Conclusion

This 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.
ILC2-mediated immune crosstalk in chronic (vascular) inflammation
Authors: Kral Maria , van der Vorst Emiel P.C. , Surnov Alexey , Weber Christian , Döring Yvonne
Published: December 2023

Crosstalk between innate and adaptive immunity is pivotal for an efficient immune response and to maintain immune homeostasis under steady state conditions. As part of the innate immune system, type 2 innate lymphoid cells (ILC2s) have emerged as new important regulators of tissue homeostasis and repair by fine-tuning innate-adaptive immune cell crosstalk. ILC2s mediate either pro- or anti-inflammatory immune responses in a context dependent manner. Inflammation has proven to be a key driver of atherosclerosis, resembling the key underlying pathophysiology of cardiovascular disease (CVD). Notably, numerous studies point towards an atheroprotective role of ILC2s e.g., by mediating secretion of type-II cytokines (IL-5, IL-13, IL-9). Boosting these protective responses may be suitable for promising future therapy, although these protective cues are currently incompletely understood. Additionally, little is known about the mechanisms by which chemokine/chemokine receptor signaling shapes ILC2 functions in vascular inflammation and atherosclerosis. Hence, this review will focus on the latest findings regarding the protective and chemokine/chemokine receptor guided interplay between ILC2s and other immune cells like T and B cells, dendritic cells and macrophages in atherosclerosis. Further, we will elaborate on potential therapeutic implications which result or could be distilled from the dialogue of ILC2s with cells of the immune system in cardiovascular diseases.
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

Background

The 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.

Methods

To 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.

Results

SON-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.

Conclusion

Collectively, 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.
On the representation of /h/ by Quebec francophone learners of English
Authors: John Paul , Rigoulot Simon
Published: December 2023

The current study investigates whether some of the variation in h-production observed among Quebec francophone (QF) learners of English could follow from their at times assimilating /h/ to /ʁ/. In earlier research, we attributed variation exclusively to QFs developing an approximate (“fuzzy” or “murky”) representation of /h/ that is not fully reliable as a base for h-perception and production. Nonetheless, two previous studies observed via event-related potentials differences in QF perceptual ability, which may follow from the quality of the vowel used in the stimuli: /ɑ/ vs. /ʌ/ (detection vs. no detection of /h/). Before the vowel /ɑ/, /h/ exhibits phonetic properties that may allow it to be assimilated to and thus underlyingly represented as /ʁ/. If /h/ is at times subject to approximate representation (e.g., before /ʌ/) and at others captured as /ʁ/ (before /ɑ/), we would expect production of /h/ to reflect this representational distinction, with greater accuracy rates in items containing /ɑ/. Two-way ANOVAs and paired Bayesian t-tests on the reading-aloud data of 27 QFs, however, reveal no difference in h-production according to vowel type. We address the consequences of our findings, discussing notably why QFs have such enduring difficulty acquiring /h/ despite the feature [spread glottis] being available in their representational repertoire. We propose the presence of a Laryngeal Input Constraint that renders representations containing only a laryngeal feature highly marked. We also consider the possibility that, rather than having overcome this constraint, some highly advanced learners are “phonological zombies”: these learners become so adept at employing approximate representations in perception and production that they are indistinguishable from speakers with bona fide phonemic representations.
Effect of environmental and anthropogenic factors on the distribution and co-occurrence of cold-water corals
Authors: Palummo Valeria , Milisenda Giacomo , Canese Simonepietro , Salvati Eva , Pica Daniela , Passarelli Augusto , Spanò Nunziacarla , Romeo Teresa , Greco Silvestro
Published: December 2023

Cold-water corals (CWCs) are bioengineering species that can increase habitat heterogeneity and improve the deep sea’s biological diversity and ecosystem functioning. Knowledge of their distribution provides a critical baseline for assessing the effect of natural and anthropogenic impacts on these important deep-sea habitats. The aims of this study are: i) provide new data on the spatial distribution of six CWCs species in the Strait of Sicily, ii) describe the principal environmental and anthropogenic variables that play a role in shaping their distribution, iii) identify hotspots in which individuals belonging to the various species co-occur. Presence-only data of six CWCs species, ten environmental variables (depth, slope, rugosity, aspect, flowdir, temperature, salinity, north bottom current, east bottom current, chlorophyll-a), and one variable relating to bottom trawling effort (Automatic Information System – AIS) were used to predict the suitable habitats. We used Maximum Entropy modelling (MaxEnt) approach and used the AUC (area under the receiver operating characteristic curve) and TSS (true skill statistics) to evaluate the model performance. The results showed excellent AUC, TSS and AUC’s standard deviation mean values for all six species. The validation show high predictive performance. MaxEnt identified slope, depth, and rugosity as the most important predictors, showing the highest percentage contribution for all six species considered. Throughout the study area, highlyinterspecific persistent density hotspot of CWCs co-occurrence were discovered, with a total extension of 4.05 km2 where all species co-occur. Although studies on the effect of environmental and anthropogenic factors that impact the distribution of these species of conservation interest remain scarce, the results of this study offer useful guidance for decision-makers to develop necessary conservation measures.
Extreme waves in the Caribbean Sea: spatial regionalization and long-term analysis
Authors: Morales-Márquez Verónica , Cáceres-Euse Alejandro , Hernández-Carrasco Ismael , Molcard Anne , Orfila Alejandro
Published: December 2023

The extreme wave height distribution in the Caribbean Sea is studied using a new method based on the maximum basin-wide aggregate of significant wave height, Hs, values per month. Besides, by means of the Self-Organizing Maps (SOM) technique, we identify coherent geographical regions with similar extreme wave height variability in the Caribbean Sea. Our findings revealed three primary regions: the eastern side with comparatively lower values, the central region with intermediate values, and the western side with the highest extreme wave heights. The study also examines the wind forcing conditions driving the spatial and temporal variability of the extreme waves, highlighting the influence of the low-pressure belt dynamics as well as the role played by the Caribbean Low-Level Jet (CLLJ) index, and the impact of cold fronts and hurricanes on extreme wave heights. Additionally, we explore the relationship between the extreme wave height distribution and climatic indices, such as the Atlantic Multidecadal Oscillation (AMO), the Atlantic Meridional Mode (AMM), the North Atlantic Oscillation (NAO) and the Oceanic Niño (ONI). The results reveal that the spatial distribution of extreme wave heights in the Caribbean Sea is mostly ruled by the influence of the CLLJ, with correlations close to 80%. In addition, significant correlations were observed between the extreme wave heights and the ENSO in the central Caribbean, as well as positive correlations between the extreme wave heights and NAO in the eastern part of the basin, and significant values of correlation with the negative phases of AMO and AMM in the whole basin. We show that, unlike conventional (or broadly used) methods deployed to identify extreme wave height, such as percentile 99th, Hs99, our methodology allows a further assessment of the wind and climate forcing conditions associated with the extreme wave events. Although, we acknowledge that the method here presented has limitations to capture extreme wave height outliers, it has the advantage of being used concomitant with the wind forcing to develop multivariate wave climate analysis at basin scale, and could be extended to a more local scale when studying coastal processes.
Comparative analysis of fasting effects on the cecum microbiome in three guinea pig breeds: Andina, Inti, and Peru
Authors: Frias Hugo , Murga Valderrama Nilton Luis , Flores Durand Gary J. , Cornejo Victor G. , Romani Ana C. , Bardales William , Segura G. T. , Polveiro Richard C. , Vieira Dielson da S. , Ramos Sanchez Eduardo M. , Lopez Lapa Rainer M. , Maicelo Quintana Jorge Luis
Published: December 2023

Guinea pigs have historically been used as a food source and are also an important model for studying the human intestines. Fasting is the act of temporarily stopping the intake of food. This process can alter the microbiota of various animals. This study is the first to investigate the impact of fasting on the cecum microbiome of three guinea pig breeds. We investigated the impact of fasting on the microbiome population structure in the cecum of three guinea pig breeds. This was done by sequencing and analyzing the V4 hypervariable region of the 16S rRNA gene in bacterial communities found in cecum mucosa samples. To achieve this, we established two treatment groups (fasting and fed), for each of the three guinea pig breeds: Andina, Inti, and Peru. The study involved twenty-eight guinea pigs, which were divided into the following groups: Andina-fed (five), Andina-fasting (five), Inti-fed (four), Inti-fasting (five), Peru-fed (five), and Peru-fasting (four). The results indicated a significant difference in beta diversity between the treatment groups for the Peru breed (P-value = 0.049), but not for the treatment groups of the Andina and Inti breeds. The dominant phyla across all groups were Firmicutes and Bacteroidetes. We observed variations in the abundance of different taxa in the cecum microbiota when comparing the treatment groups for each breed. Additionally, there was a higher number of unique taxa observed in the fasting groups compared to the fed groups. We discovered that the genus Victivallis was the only one present in all fasting groups across all breeds. Despite the findings, the resilience of the gut microbiome was not challenged in all three breeds, which can lead to disruptive changes that may affect the overall maintenance of the cecum microbiome. Based on the observed differences in the treatment groups of the Peru breed, it can be suggested that fasting has a greater impact on this particular breed.
Toward an intensive understanding of sewer sediment prokaryotic community assembly and function
Authors: Xia Jingjing , Yu Kai , Yao Zhiyuan , Sheng Huafeng , Mao Lijuan , Lu Dingnan , Gan HuiHui , Zhang Shulin , Zhu David Z.
Published: December 2023

Prokaryotic communities play important roles in sewer sediment ecosystems, but the community composition, functional potential, and assembly mechanisms of sewer sediment prokaryotic communities are still poorly understood. Here, we studied the sediment prokaryotic communities in different urban functional areas (multifunctional, commercial, and residential areas) through 16S rRNA gene amplicon sequencing. Our results suggested that the compositions of prokaryotic communities varied significantly among functional areas. Desulfomicrobium, Desulfovibrio, and Desulfobacter involved in the sulfur cycle and some hydrolytic fermentation bacteria were enriched in multifunctional area, while Methanospirillum and Methanoregulaceae, which were related to methane metabolism were significantly discriminant taxa in the commercial area. Physicochemical properties were closely related to overall community changes (p < 0.001), especially the nutrient levels of sediments (i.e., total nitrogen and total phosphorus) and sediment pH. Network analysis revealed that the prokaryotic community network of the residential area sediment was more complex than the other functional areas, suggesting higher stability of the prokaryotic community in the residential area. Stochastic processes dominated the construction of the prokaryotic community. These results expand our understanding of the characteristics of prokaryotic communities in sewer sediment, providing a new perspective for studying sewer sediment prokaryotic community structure.
Machine learning reveals neutrophil-to-lymphocyte ratio as a crucial prognostic indicator in severe Japanese encephalitis patients
Authors: Wei Yaxuan , Hao Ying , Li Yuanming , Dan Meiling , Yang Zhiqi , Qiu Huihui , Li Rong , Yin Rong , Fan Pengcheng
Published: December 2023

Japanese encephalitis (JE) is a severe infectious disease affecting the central nervous system (CNS). However, limited risk factors have been identified for predicting poor prognosis (PP) in adults with severe JE. In this study, we analyzed clinical data from thirty-eight severe adult JE patients and compared them to thirty-three patients without organic CNS disease. Machine learning techniques employing branch-and-bound algorithms were used to identify clinical risk factors. Based on clinical outcomes, patients were categorized into two groups: the PP group (mRs ≥ 3) and the good prognosis (GP) group (mRs ≤ 2) at three months post-discharge. We found that the neutrophil-to-lymphocyte ratio (NLR) and the percentage of neutrophilic count (N%) were significantly higher in the PP group compared to the GP group. Conversely, the percentage of lymphocyte count (L%) was significantly lower in the PP group. Additionally, elevated levels of aspartate aminotransferase (AST) and blood glucose were observed in the PP group compared to the GP group. The clinical parameters most strongly correlated with prognosis, as indicated by Pearson correlation coefficient (PCC), were NLR (PCC 0.45) and blood glucose (PCC 0.45). In summary, our findings indicate that increased serum NLR, N%, decreased L%, abnormal glucose metabolism, and liver function impairment are risk factors associated with poor prognosis in severe adult JE patients.
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

Background

Chronic 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.

Methods

The 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.

Results

We 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.

Conclusion

There 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.
Review: therapeutic approaches for circadian modulation of the glioma microenvironment
Authors: Nettnin Ella A. , Nguyen Thien , Arana Sophia , Barros Guinle Maria Isabel , Garcia Cesar A. , Gibson Erin M. , Prolo Laura M.
Published: December 2023

High-grade gliomas are malignant brain tumors that are characteristically hard to treat because of their nature; they grow quickly and invasively through the brain tissue and develop chemoradiation resistance in adults. There is also a distinct lack of targeted treatment options in the pediatric population for this tumor type to date. Several approaches to overcome therapeutic resistance have been explored, including targeted therapy to growth pathways (ie. EGFR and VEGF inhibitors), epigenetic modulators, and immunotherapies such as Chimeric Antigen Receptor T-cell and vaccine therapies. One new promising approach relies on the timing of chemotherapy administration based on intrinsic circadian rhythms. Recent work in glioblastoma has demonstrated temporal variations in chemosensitivity and, thus, improved survival based on treatment time of day. This may be due to intrinsic rhythms of the glioma cells, permeability of the blood brain barrier to chemotherapy agents, the tumor immune microenvironment, or another unknown mechanism. We review the literature to discuss chronotherapeutic approaches to high-grade glioma treatment, circadian regulation of the immune system and tumor microenvironment in gliomas. We further discuss how these two areas may be combined to temporally regulate and/or improve the effectiveness of immunotherapies.
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

Introduction

Developmental 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 methods

A 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).

Results

In 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 < 0.001).

Conclusion

Our 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 Abstract

Possible therapeutic indications for sGC agonists and GC-C agonists.
Decomposing the percolation backbone reveals novel scaling laws of the current distribution
Authors: Sena Wagner R. de , Andrade José S. , Herrmann Hans J. , Moreira André A.
Published: December 2023

The distribution of currents on critical percolation clusters is the fundamental quantity describing the transport properties of weakly connected systems. Nevertheless, its finite-size extrapolation is still one of the outstanding open questions concerning disordered media. By hierarchically decomposing the 3-connected components of the backbone, we disclose that the current distribution is determined from two distributions, namely, the one corresponding to the number of bonds in each level and another one corresponding to the factors by which the current is reduced, when going from one level to the next. The first distribution follows a finite-size scaling, while the second is a power law with an exponent consistent with 3/4 in two dimensions. The standard hierarchical model for the backbone is too simple to reproduce this complex scenario. Our new decomposition method of the backbone also allows to calculate much smaller currents than before, attaining a precision of 10−35 and systems of size L = 81922. Moreover, our method is not restricted to electric currents on critical percolation clusters but could also be applied to other transport problems on sparse graphs including fluid flow and car traffic.