bluuebunny/crossref_metadata_2025 huggingface dataset:
Immunohistochemical expression of beta‐catenin, BMP4 and TGF‐beta in odontomas
Authors: de França Glória Maria , Pires Hévila de Figueiredo , da Silva Weslay Rodrigues , de Morais Éverton Freitas , Freitas Roseana de Almeida , de Souza Lélia Batista , Galvão Hébel Cavalcanti
Published: February 2024

Changes in the expression of nuclear β‐catenin are responsible for tumorigenesis. Beta‐catenin acts synergistically with the TGF‐β/BMPs pathway. This interaction leads to greater dentin deposition and may explain the differences between distinct tooth morphologies and hamartomas. The aim of this study was to investigate the role of β‐catenin, BMP4 and TGF‐β in the development of odontomas. This cross‐sectional, retrospective, immunohistochemical study evaluated 30 compound odontomas, 30 complex odontomas and 17 tooth germs. The results showed that BMP4 and TGF‐β were more immunoexpressed in the ectomesenchyme of complex odontomas (median = 33.7, p < 0.001; median = 76.4, p = 0.002, respectively). Higher immunoexpression of BMP4 and TGF‐β was also observed in the epithelium of tooth germs (median = 2.0, p < 0.001; median = 120.3, p < 0.001, respectively). TGF‐β and BMP4 showed a positive and significant correlation (p < 0.001). Both TGF‐β and BMP4 were positively correlated with nuclear β‐catenin in ectomesenchyme (p = 0.047 and p = 0.023, respectively). Developing teeth exhibited higher concentrations of the proteins studied in odontogenic epithelium, especially during the bud and cap stages. Higher immunoexpression in odontomas occurred mainly in the ectomesenchyme. We therefore suggest that changes in the ectomesenchyme can lead to the development of odontomas.
Prevalence of adenomyosis features in women scheduled for assisted reproductive treatment, using the Morphological Uterus Sonographic Assessment group definitions
Authors: Alson Sara , Jokubkiene Ligita , Henic Emir , Sladkevicius Povilas
Published: February 2024

Introduction

Studies that use standardized ultrasonographic criteria to diagnose adenomyosis in subfertile women are needed. These would improve the understanding of the disease burden and enable further studies on its impact on fertility and assisted reproductive treatment (ART) outcome. The aim of this study was to determine the prevalence of different features of adenomyosis in women scheduled for their first ART, diagnosed at two (2D) and three‐dimensional (3D) transvaginal ultrasonography (TVUS) using the revised Morphological Uterus Sonographic Assessment (MUSA) group definitions.

Material and methods

This was a prospective, observational cross‐sectional study of subfertile women aged 25 to ≤39 years, that were referred to a university hospital for their first ART between December 2018 and May 2021. Of 1224 eligible women, 1160 women fulfilled the inclusion criteria and consented to participate in the study. All women underwent a systematic 2D and 3D TVUS examination. The primary outcome was the presence of direct and indirect features of adenomyosis, as proposed by the MUSA group. Secondary outcomes were to describe the ultrasonographic characteristics of the different features, as well as any difference in the diagnostics at 2D or 3D TVUS and any association with clinical characteristics such as endometriosis.

Results

At least one direct or indirect feature of adenomyosis was observed in 272 (23.4%, 95% confidence interval [CI] 21.0–25.9) women. Direct features that are pathognomonic for the disease were observed in 111 (9.6%, 95% CI, 7.9–11.3) women. Direct features were visible only at 3D TVUS in 56 (4.8%, 95% CI 3.6–6.1) women, that is, 56/111 (50.5%) of women with at least one direct adenomyosis feature. Direct features were more common in women with endometriosis (OR 2.8, 95% CI 1.8–4.3).

Conclusions

We found than one in 10 women scheduled for ART had direct features of adenomyosis at ultrasound examination. The present study suggests that the use of 3D TVUS is an important complement to 2D in the diagnostics of adenomyosis. Our results may further improve the counseling of women scheduled for ART and enables future studies on the impact of different features of adenomyosis on subfertility, ART results and obstetric outcomes.
Validation of the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes in chronic myelomonocytic leukaemia: A novel approach for improved risk stratification
Authors: Mosquera Orgueira Adrian , Perez Encinas Manuel Mateo , Diaz Varela Nicolas , Wang Yu‐Hung , Mora Elvira , Diaz‐Beya Marina , Montoro Maria Julia , Pomares Marin Helena , Ramos Ortega Fernando , Tormo Mar , Jerez Andres , Nomdedeu Josep , de Miguel Sanchez Carlos , Arenillas Leonor , Carcel Paula , Cedena Romero Maria Teresa , Xicoy Cirici Blanca , Rivero Arango Eugenia , Del Orbe Barreto Rafael Andrés , Benlloch Luis , Lin Chien‐Chin , Tien Hwei‐Fang , Pérez Míguez Carlos , Crucitti Davide , Díez Campelo María , Valcárcel David
Published: February 2024

Chronic myelomonocytic leukaemia (CMML) is a rare haematological disorder characterized by monocytosis and dysplastic changes in myeloid cell lineages. Accurate risk stratification is essential for guiding treatment decisions and assessing prognosis. This study aimed to validate the Artificial Intelligence Prognostic Scoring System for Myelodysplastic Syndromes (AIPSS‐MDS) in CMML and to assess its performance compared with traditional scores using data from a Spanish registry (n = 1343) and a Taiwanese hospital (n = 75). In the Spanish cohort, the AIPSS‐MDS accurately predicted overall survival (OS) and leukaemia‐free survival (LFS), outperforming the Revised‐IPSS score. Similarly, in the Taiwanese cohort, the AIPSS‐MDS demonstrated accurate predictions for OS and LFS, showing superiority over the IPSS score and performing better than the CPSS and molecular CPSS scores in differentiating patient outcomes. The consistent performance of the AIPSS‐MDS across both cohorts highlights its generalizability. Its adoption as a valuable tool for personalized treatment decision‐making in CMML enables clinicians to identify high‐risk patients who may benefit from different therapeutic interventions. Future studies should explore the integration of genetic information into the AIPSS‐MDS to further refine risk stratification in CMML and improve patient outcomes.
Freshwater megafauna shape ecosystems and facilitate restoration
Authors: He Fengzhi , Svenning Jens‐Christian , Chen Xing , Tockner Klement , Kuemmerle Tobias , le Roux Elizabeth , Moleón Marcos , Gessner Jörn , Jähnig Sonja C.
Published: February 2024

Freshwater megafauna, such as sturgeons, giant catfishes, river dolphins, hippopotami, crocodylians, large turtles, and giant salamanders, have experienced severe population declines and range contractions worldwide. Although there is an increasing number of studies investigating the causes of megafauna losses in fresh waters, little attention has been paid to synthesising the impacts of megafauna on the abiotic environment and other organisms in freshwater ecosystems, and hence the consequences of losing these species. This limited understanding may impede the development of policies and actions for their conservation and restoration. In this review, we synthesise how megafauna shape ecological processes in freshwater ecosystems and discuss their potential for enhancing ecosystem restoration. Through activities such as movement, burrowing, and dam and nest building, megafauna have a profound influence on the extent of water bodies, flow dynamics, and the physical structure of shorelines and substrata, increasing habitat heterogeneity. They enhance nutrient cycling within fresh waters, and cross‐ecosystem flows of material, through foraging and reproduction activities. Freshwater megafauna are highly connected to other freshwater organisms via direct consumption of species at different trophic levels, indirect trophic cascades, and through their influence on habitat structure. The literature documenting the ecological impacts of freshwater megafauna is not evenly distributed among species, regions, and types of ecological impacts, with a lack of quantitative evidence for large fish, crocodylians, and turtles in the Global South and their impacts on nutrient flows and food‐web structure. In addition, population decline, range contraction, and the loss of large individuals have reduced the extent and magnitude of megafaunal impacts in freshwater ecosystems, rendering a posteriori evaluation more difficult. We propose that reinstating freshwater megafauna populations holds the potential for restoring key ecological processes such as disturbances, trophic cascades, and species dispersal, which will, in turn, promote overall biodiversity and enhance nature's contributions to people. Challenges for restoration actions include the shifting baseline syndrome, potential human–megafauna competition for habitats and resources, damage to property, and risk to human life. The current lack of historical baselines for natural distributions and population sizes of freshwater megafauna, their life history, trophic interactions with other freshwater species, and interactions with humans necessitates further investigation. Addressing these knowledge gaps will improve our understanding of the ecological roles of freshwater megafauna and support their full potential for facilitating the development of effective conservation and restoration strategies to achieve the coexistence of humans and megafauna.
Demographic and evolutionary consequences of hunting of wild birds
Authors: Grzegorczyk Emilienne , Caizergues Alain , Eraud Cyril , Francesiaz Charlotte , Le Rest Kévin , Guillemain Matthieu
Published: February 2024

Hunting has a long tradition in human evolutionary history and remains a common leisure activity or an important source of food. Herein, we first briefly review the literature on the demographic consequences of hunting and associated analytical methods. We then address the question of potential selective hunting and its possible genetic/evolutionary consequences. Birds have historically been popular models for demographic studies, and the huge amount of census and ringing data accumulated over the last century has paved the way for research about the demographic effects of harvesting. By contrast, the literature on the evolutionary consequences of harvesting is dominated by studies on mammals (especially ungulates) and fish. In these taxa, individuals selected for harvest often have particular traits such as large body size or extravagant secondary sexual characters (e.g. antlers, horns, etc.). Our review shows that targeting individuals according to such genetically heritable traits can exert strong selective pressures and alter the evolutionary trajectory of populations for these or correlated traits. Studies focusing on the evolutionary consequences of hunting in birds are extremely rare, likely because birds within populations appear much more similar, and do not display individual differences to the same extent as many mammals and fishes. Nevertheless, even without conscious choice by hunters, there remains the potential for selection through hunting in birds, for example by genetically inherited traits such as personality or pace‐of‐life. We emphasise that because so many bird species experience high hunting pressure, the possible selective effect of harvest in birds and its evolutionary consequences deserves far more attention, and that hunting may be one major driver of bird evolutionary trajectories that should be carefully considered in wildlife management schemes.
Scoring system for diagnosis and pretreatment risk assessment of neuroblastoma using urinary biomarker combinations
Authors: Amano Hizuru , Uchida Hiroo , Harada Kazuharu , Narita Atsushi , Fumino Shigehisa , Yamada Yuji , Kumano Shun , Abe Mayumi , Ishigaki Takashi , Sakairi Minoru , Shirota Chiyoe , Tainaka Takahisa , Sumida Wataru , Yokota Kazuki , Makita Satoshi , Karakawa Shuhei , Mitani Yuichi , Matsumoto Shojiro , Tomioka Yutaka , Muramatsu Hideki , Nishio Nobuhiro , Osawa Tsuyoshi , Taguri Masataka , Koh Katsuyoshi , Tajiri Tatsuro , Kato Motohiro , Matsumoto Kimikazu , Takahashi Yoshiyuki , Hinoki Akinari
Published: February 2024

The urinary catecholamine metabolites, homovanillic acid (HVA) and vanillylmandelic acid (VMA), are used for the adjunctive diagnosis of neuroblastomas. We aimed to develop a scoring system for the diagnosis and pretreatment risk assessment of neuroblastoma, incorporating age and other urinary catecholamine metabolite combinations. Urine samples from 227 controls (227 samples) and 68 patients with neuroblastoma (228 samples) were evaluated. First, the catecholamine metabolites vanillactic acid (VLA) and 3‐methoxytyramine sulfate (MTS) were identified as urinary marker candidates through comprehensive analysis using liquid chromatography–mass spectrometry. The concentrations of these marker candidates and conventional markers were then compared among controls, patients, and numerous risk groups to develop a scoring system. Participants were classified into four groups: control, low risk, intermediate risk, and high risk, and the proportional odds model was fitted using the L2‐penalized maximum likelihood method, incorporating age on a monthly scale for adjustment. This scoring model using the novel urine catecholamine metabolite combinations, VLA and MTS, had greater area under the curve values than the model using HVA and VMA for diagnosis (0.978 vs. 0.964), pretreatment risk assessment (low and intermediate risk vs. high risk: 0.866 vs. 0.724; low risk vs. intermediate and high risk: 0.871 vs. 0.680), and prognostic factors (MYCN status: 0.741 vs. 0.369, histology: 0.932 vs. 0.747). The new system also had greater accuracy in detecting missing high‐risk neuroblastomas, and in predicting the pretreatment risk at the time of screening. The new scoring system employing VLA and MTS has the potential to replace the conventional adjunctive diagnostic method using HVA and VMA.
Harnessing the potential of reverse‐phase protein array technology: Advancing precision oncology strategies
Authors: Masuda Mari , Nakagawa Riko , Kondo Tadashi
Published: February 2024

The last few decades have seen remarkable strides in the field of cancer therapy. Precision oncology coupled with comprehensive genomic profiling has become routine clinical practice for solid tumors, the advent of immune checkpoint inhibitors has transformed the landscape of oncology treatment, and the number of cancer drug approvals has continued to increase. Nevertheless, the application of genomics‐driven precision oncology has thus far benefited only 10%–20% of cancer patients, leaving the majority without matched treatment options. This limitation underscores the need to explore alternative avenues with regard to selecting patients for targeted therapies. In contrast with genomics‐based approaches, proteomics‐based strategies offer a more precise understanding of the intricate biological processes driving cancer pathogenesis. This perspective underscores the importance of integrating complementary proteomic analyses into the next phase of precision oncology to establish robust biomarker‐drug associations and surmount challenges related to drug resistance. One promising technology in this regard is the reverse‐phase protein array (RPPA), which excels in quantitatively detecting protein modifications, even with limited amounts of sample. Its cost–effectiveness and rapid turnaround time further bolster its appeal for application in clinical settings. Here, we review the current status of genomics‐driven precision oncology, as well as its limitations, with an emphasis on drug resistance. Subsequently, we explore the application of RPPA technology as a catalyst for advancing precision oncology. Through illustrative examples drawn from clinical trials, we demonstrate its utility for unraveling the molecular mechanisms underlying drug responses and resistance.
Machine learning identifies fatigue as a key symptom of fibromyalgia reflected in tyrosine, purine, pyrimidine, and glutaminergic metabolism
Authors: Zetterman Teemu , Nieminen Anni I. , Markkula Ritva , Kalso Eija , Lötsch Jörn
Published: February 2024

Fibromyalgia patients vary in clinical phenotype and treatment can be challenging. The pathophysiology of fibromyalgia is incompletely understood but appears to involve metabolic changes at rest or in response to stress. We enrolled 54 fibromyalgia patients and 31 healthy controls to this prospective study. Symptoms were assessed using the Fibromyalgia Impact Questionnaire (FIQ) and blood samples were collected for metabolomics analysis at baseline and after an oral glucose tolerance test and a cardiopulmonary exercise test. We identified key symptoms of fibromyalgia and related them to changes in metabolic pathways with supervised and unsupervised machine learning methods. Algorithms trained with the FIQ information assigned the fibromyalgia diagnosis in new data with balanced accuracy of 88% while fatigue alone already provided the diagnosis with 86% accuracy. Supervised analyses reduced the metabolomic information from 77 to 13 key markers. With these metabolites, fibromyalgia could be identified in new cases with 79% accuracy. In addition, 5‐hydroxyindole‐3‐acetic acid and glutamine levels correlated with the severity of fatigue. Patients differed from controls at baseline in tyrosine and purine pathways, and in the pyrimidine pathway after the stress challenges. Several key markers are involved in glutaminergic neurotransmission. This data‐driven analysis highlights fatigue as a key symptom of fibromyalgia. Fibromyalgia is associated with metabolic changes which also reflect the degree of fatigue. Responses to metabolic and physical stresses result in a metabolic pattern that allows discrimination of fibromyalgia patients from controls and narrows the focus on key pathophysiological processes in fibromyalgia as treatment targets.
Hume and the fiction of the self
Authors: Parrott Matthew
Published: February 2024

In the Treatise, Hume attempts to explain why we all believe that the self is a single unified entity that persists over time, a belief which Hume calls a fiction. In this paper, I demonstrate how Hume uses a type of functional explanation to account for this belief. After explicating Hume's view, I shall argue that it faces two related problems, which constitute a sort of dilemma. In the final section, I show how one of the horns of this dilemma is plausibly what troubles Hume in the famous Appendix passage where he retracts his positive account of personal identity.
Fuzzy logic‐based trusted routing protocol using vehicular cloud networks for smart cities
Authors: Kait Ramesh , Kaur Sarbjit , Sharma Purushottam , Ankita Chhikara , Kumar Tajinder , Cheng Xiaochun
Published: February 2024

Due to the characteristics of vehicular ad hoc networks, the increased mobility of nodes and the inconsistency of wireless communication connections pose significant challenges for routing. As a result, researchers find it to be a fascinating topic to study. Furthermore, since these networks are vulnerable to various assaults, providing an authentication method between the source and destination nodes is crucial. How to route in such networks more efficiently, taking into account node mobility characteristics and accompanying massive historical data, is still a matter of discussion. Fuzzy logic‐based Trusted Routing Protocol for vehicular cloud networks (FTRP) is proposed in this study that determines the secure path for data dissemination. Fuzzy Logic determines the node candidacy value and selects or rejects a path accordingly. The cloud assigns a confidence score to each vehicle based on the data it collects from nodes after each interaction. Our study identifies the secure path on the basis of trust along with factors such as speed, closeness to other nodes, signal strength and distance from the neighbouring nodes. Simulations of the novel protocol demonstrate that it can keep the packet delivery ratio high with little overhead and low delay. FTRP has significant implications for deploying Vehicular Cloud Networks using electric vehicle technologies in smart cities. The routing data is collected with the help of Internet of Technology (IOT) sensors. The information is transmitted between vehicles using IOT gateways.
Children's behavioural and emotional reactions towards living with congenital heart disease in Saudi Arabia: A grounded theory study
Authors: Dahlawi Nada , Milnes Linda , Swallow Veronica
Published: February 2024

Background

A high incidence of children with congenital heart disease (CHD) was found in Saudi Arabia (SA). International literature reports that children with CHD exhibit behavioural and emotional issues due to experiencing hospitalisation and clinical treatments combined with a dearth of qualitative understanding of the experiences of younger children with CHD. Therefore, the aim was to explore the behaviour and emotions of 4–10‐year‐olds with CHD in SA through children's accounts of their own experiences and parental proxy reports of children's behaviour and emotions.

Methods

Charmaz's constructivist grounded theory (GT) approach was used. Twenty single semi‐structured interviews of 10 child/parent dyads were undertaken at a hospital clinic in SA. Children's interviews were combined with an arts‐based approach using drawings, pictures and faces of emotions (emojis). Constant comparison analysis was undertaken. Consolidated Criteria for Reporting Qualitative Research guidelines was followed in reporting this study.

Findings

A substantive GT: children's behavioural and emotional reactions towards stressors related to living with CHD was developed and provides new insights into children's and parents' perceptions of the children's behavioural and emotional reactions to living with CHD in SA. The theory proposes that children's reactions to living with CHD relate to medical treatment stressors, sociocultural stressors and physical change stressors. Several further factors influenced children's responses to these stressors.

Conclusion

Children and parents in SA contributed to a new understanding of the relationship between CHD and children's behavioural and emotional reactions. In addition, findings support the need for early assessment of behaviour and emotions among children with CHD and the application of preventative and supportive measures for the children and their families in SA.

Patient or Public Contribution

Before the research commenced, the developmental appropriateness of the proposed arts‐based data collection tools was tested with three healthy children aged 6–9 years old; the tools were then revised accordingly before the interviews were undertaken.
Whole‐exome sequencing has revealed novel genetic characteristics in intracranial germ cell tumours in the Chinese
Authors: Huang Xiang , Huang Jianhan , Zhou Xiaoyu , Zhang Chao , Ding Xinghua , Wong Peter Jih Cheng , Wang Yang , Zhang Rong
Published: February 2024

Aims

Intracranial germ cell tumour (IGCT) is a type of rare central nervous system tumour that mainly occurs in children and adolescents, with great variation in its incidence rate and molecular characteristics in patients from different populations. The genetic alterations of IGCT in the Chinese population are still unknown.

Methods and Results

In this study, 47 patients were enrolled and their tumour specimens were analysed by whole‐exome sequencing (WES). We found that KIT was the most significantly mutated gene (15/47, 32%), which mainly occurred in the germinoma group (13/20, 65%), and less frequently in NGGCT (2/27, 7%). Copy number variations (CNVs) of FGF6 and TFE3 only appeared in NGGCT patients (P = 0.003 and 0.032, respectively), while CNVs of CXCR4, RAC2, PDGFA, and FEV only appeared in germinoma patients (P = 0.004 of CXCR4 and P = 0.027 for the last three genes). Compared with a previous Japanese cohort, the somatic mutation rates of RELN and SYNE1 were higher in the Chinese. Prognostic analysis showed that the NF1 mutation was associated with shorter overall survival and progression‐free survival in IGCT patients. Clonal evolution analysis revealed an early branched evolutionary pattern in two IGCT patients who underwent changes in the histological subtype or degree of differentiation during disease surveillance.

Conclusion

This study indicated that Chinese IGCT patients may have distinct genetic characteristics and identified several possible genetic alterations that have the potential to become prognostic biomarkers of NGGCT patients.
Genomic analysis of primary epithelial neoplasms of the seminal vesicle identifies a subset of mucinous cystic tumours driven by KRAS mutations
Authors: Collins Katrina , Galea Laurence A , Foroughi Forough , Siegmund Stephanie E , Anderson William J , Appu Sree , Idrees Muhammad T , Ulbright Thomas M , Acosta Andres M
Published: February 2024

Background

Carcinomas of the seminal vesicle are exceedingly rare, with a limited number of cases described in the literature. Reported cases span a relatively wide morphological spectrum, and their genomic features remain unexplored.

Design

In this study, we interrogated five primary epithelial neoplasms of the seminal vesicle using a targeted DNA sequencing platform (OncoPanel, 447 genes).

Results

The tumours included one adenocarcinoma with intestinal phenotype presenting after external beam radiation (for prostatic adenocarcinoma), one carcinoma with Müllerian‐type clear cell phenotype, two mucinous tumours resembling low‐grade mucinous neoplasms of the appendix (LAMN) and one mucinous cystadenoma. The post‐radiation mucinous adenocarcinoma had genomic findings consistent with bi‐allelic inactivation of TP53, as well as multiple copy‐number changes with regional and chromosomal arm‐level copy‐number losses. The Müllerian‐type clear cell carcinoma exhibited a complex copy‐number profile with numerous regional and arm‐level copy‐number changes, as well as focal amplification events, including copy‐number gain of 8q and amplification of a region within 20q13. Both low‐grade mucinous tumours resembling LAMN harboured hot‐spot gain‐of‐function KRAS variants (p.G12V and p.G13D) as the only genomic alteration. No genomic alterations were detected inthe lesion diagnosed as mucinous cystadenoma.

Conclusion

Our results suggest that primary low‐grade mucinous neoplasms of the seminal vesicle may represent a distinct entity equivalent to appendiceal counterparts, driven by gain‐of‐function variants of RAS GTPases. The remaining tumours showed genomic features that closely resembled those of neoplasms with comparable phenotypes and/or biological characteristics arising in other sites, suggesting that they could be managed similarly, with special considerations related to their anatomical location.
STING inhibition alleviates bone resorption in apical periodontitis
Authors: Mao Han‐Qing , Zhou Lu , Li Jia‐Qi , Wen Yuan‐Hao , Chen Zhi , Zhang Lu
Published: February 2024

Aim

The goal of this study was to investigate the potential effects of an immunotherapeutic drug targeting STING to suppress the overreactive innate immune response and relieve the bone defect in apical periodontitis.

Methodology

We established an apical periodontitis mouse model in Sting−/− and WT mice in vivo. The progression of apical periodontitis was analysed by micro‐CT analysis and H&E staining. The expression level and localization of STING in F4/80+ cells were identified by IHC and immunofluorescence staining. RANKL in periapical tissues was tested by IHC staining. TRAP staining was used to detect osteoclasts. To clarify the effect of STING inhibitor C‐176 as an immunotherapeutic drug, mice with apical periodontitis were treated with C‐176 and the bone loss was identified by H&E, TRAP, RANKL staining and micro‐CT. Bone marrow‐derived macrophages (BMMs) were isolated from Sting−/− and WT mice and induced to osteoclasts in a lipopolysaccharide (LPS)‐induced inflammatory environment in vitro. Moreover, WT BMMs were treated with C‐176 to determine the effect on osteoclast differentiation by TRAP staining. The expression levels of osteoclast‐related genes were tested using qRT‐PCR.

Results

Compared to WT mice, the bone resorption and inflammatory cell infiltration were reduced in exposed Sting−/− mice. In the exposed WT group, STING was activated mainly in F4/80+ macrophages. Histological staining revealed the less osteoclasts and lower expression of osteoclast‐related factor RANKL in Sting−/− mice. The treatment of the STING inhibitor C‐176 in an apical periodontitis mice model alleviated inflammation progression and bone loss, similar to the effect observed in Sting−/− mice. Expression of RANKL and osteoclast number in periapical tissues were also decreased after C‐176 administration. In vitro, TRAP staining showed fewer positive cells and qRT‐PCR reflected decreased expression of osteoclastic marker, Src and Acp5 were detected during osteoclastic differentiation in Sting−/− and C‐176 treated BMMs.

Conclusions

STING was activated and was proven to be a positive factor in bone loss and osteoclastogenesis in apical periodontitis. The STING inhibitor C‐176 administration could alleviate the bone loss via modulating local immune response, which provided immunotherapy to the treatment of apical periodontitis.
Structural stability and proton beam irradiation effects on simulated metal fluoride waste–loaded iron phosphate glass
Authors: Joshi Akhilesh C. , Roy Mainak , Dutta Dimple P. , Mishra Raman K. , Meena Sher Singh , Kumar Ravi
Published: February 2024

Next‐generation nuclear reactor technologies such as the molten salt reactor utilize alkali metal fluoride salts as both fuel and coolant. In the present study, the suitability of iron phosphate glass (IPG) as a vitrification matrix for alkali metal fluoride (NaF, CaF2) and simulated fission product loaded fluoride (NdF3, CeF3, SmF3) waste has been explored. The structural change in the metal fluoride–loaded IPG has been analyzed thoroughly using Raman and fourier transform infrared (FTIR) spectroscopy. Thermal analysis showed that the stability and glass forming ability of IPG improved upon loading the same with various mixed metal fluorides. Mössbauer data and X‐ray absorption spectroscopy at Fe K‐edge explored the minute changes in the local structure. The effect of radiation emanating from radioactive wastes in the fluoride‐loaded IPG has been scrutinized via 4.5 MeV proton beam irradiation. Our study firmly establishes the applicability of IPG as suitable vitrification matrix for radioactive metal fluoride–loaded nuclear wastes.
Novel 532‐nm Q‐switched Nd: YAG laser for the treatment of melasma and rejuvenation: a prospective, randomized controlled comparison with 1,064‐nm Q‐switched Nd: YAG laser
Authors: Wu Wenjie , Su Qianya , Zhang Yuezhu , Du Yaxin , Hu Yakun , Wang Fei
Published: February 2024

Background

Melasma is a common pigmentary and photoaging disorder. Although various treatments, including 1,064‐nm Q‐switched neodymium‐doped yttrium aluminum garnet (QS‐Nd: YAG) laser toning, are available for melasma, results are often unsatisfactory.

Objective

We aimed to determine the efficacy and safety of 532‐nm QS‐Nd: YAG laser (shortwave toning) in patients with melasma and facial rejuvenation.

Methods

Fifty‐two patients were recruited to receive either 1,064‐nm QS‐Nd: YAG laser or 532‐nm QS‐Nd: YAG laser every 2 weeks for 8 sessions and a 2‐month follow‐up visit in a randomized controlled double‐blinded study. The primary outcome measure was the Melasma Area and Severity Index (MASI) score. Dermoscope and high‐frequency ultrasound (HFUS) were used to assess the improvement of melasma and photoaging.

Results

532‐nm QS‐Nd: YAG laser achieved significantly higher improvement in the MASI score (P = 0.000). The Dermoscopic melasma score (DMS) displayed significant change and confirmed the improvement. HFUS showed a significant decrease in the thickness of the subepidermal low‐echogenic band (SLEB) and increases in dermal thickness and dermal density in both groups (P = 0.000 for all). The rate of very satisfied responses was significantly higher in the 532‐nm laser group (P = 0.001). There was no significant difference in the visual analog scale pain assessment score (P = 0.248) and recurrence rate (P = 0.734) between the two groups.

Conclusion

532‐nm QS‐Nd: YAG laser (shortwave toning) proved to be an effective and safe treatment for melasma and rejuvenation. Shortwave toning was significantly better for pigmentation clearance, while 1,064‐nm laser showed better improvement in skin rejuvenation.
Examining the benefits of extended patch test series in children: a comprehensive analysis
Authors: Andre Nicolas , Usher Alisa , Ofri Mai , Kilimnik Vitali , Horev Amir
Published: February 2024

Introduction

The growing presence of allergens in materials and scarce data on allergic contact dermatitis in children has increased our need to refine its diagnosis in this population. We aimed to analyze children's specific responsivity to highly reactive subcomponents of Fragrance mix I, Fragrance mix II, and Textile dye mix from the European baseline series.

Methods

We retrospectively analyzed patch test records of children aged 2 to 18 who underwent patch testing with the European baseline series between 2014 and 2022 in Israel.

Results

A total of 367 children were included in the study. In all, 160 children had positive results; 43 patients reacted to one of the mixes, and 20 performed further testing. Eleven of them completed the extended series at the exact same times as the regular European series, which benefited children. Farnesol was the most reactive compound (30.8%).

Conclusions

Performing the extended European series provides a more accurate and time‐efficient allergic contact dermatitis diagnosis. Farnesol reactivity appears prominent in children and may justify tighter product regulations.
Leaving no one behind: A case for inclusive social protection for displaced children
Authors: Kukrety Nupur , Knoppik Daniela
Published: February 2024

The United Nations Convention on the Rights of the Child (UNCRC) outlines the rights for every child, including the right to benefit from social security and the right to a standard of living adequate for their physical, mental, spiritual, moral, and social development. The UNCRC is the most widely ratified human rights treaty to date. However, millions of children continue to be denied their rights and face poverty, vulnerability and social exclusion, merely because they are displaced – internally or across borders. Children bear the heaviest burden of displacement, despite not being responsible for its triggers. This reality underlines that a significant population is being “left behind”, threatening progress to achieve the UN Sustainable Development Goals as part of international efforts to end poverty and ensure all people enjoy peace and prosperity. This article advocates for inclusive social protection systems for displaced children by highlighting the difficulties they encounter, emphasizing the potential benefits of social protection, and assessing the current status of inclusive social protection for this vulnerable group. Drawing on emerging lessons from UNICEF’s experience across several refugee and internal displacement contexts, such as Brazil, Ethiopia, Slovakia, and Türkiye, the article also offers recommendations to strengthen inclusive social protection systems specifically tailored to meet the humanitarian and development needs of displaced children.
Dielectric and mechanical properties of porous Si3N4–Kovar composites prepared by low‐temperature oxidation sintering
Authors: Lin Hong , Xia Zihang , Cao Liangliang , Lin Huixing , Li Hongtao , Meng Fancheng , Peng Haiyi
Published: February 2024

The aim of this study is to investigate the impact of the Kovar glass content on the mechanical and electrical properties of Si3N4–Kovar composites sintering at air atmosphere. To achieve this, Si3N4–Kovar composites were prepared using molding technology with the Kovar glass powder ranging from 20 to 70 wt%. The phase composition, morphology, bulk density, apparent porosity, flexural strength at room temperature, dielectric constant, and dielectric loss of the composites were all examined in relation to changing the Kovar glass content. During the sintering process, the α‐quartz on the surface of Si3N4 particles acted as the crystal nucleus, inducing the crystallization of the glass at the wetting position that the Kovar glass and the surface of the Si3N4 particles. A small amount of the β‐quartz phase was crystallized at 750–850°C, followed by a large amount of the β‐quartz phase crystallizing above 900°C. Additionally, some β‐quartz phase transformed into the metastable β‐cristobalite phase that could exist below 1470°C. During the cooling process, the β‐cristobalite phase transformed into a low‐temperature α‐cristobalite phase, while the β‐quartz phase transformed into a low‐temperature α‐quartz phase. The results indicate that the Si3N4–Kovar glass composite with 60 wt% the Kovar glass content sintered at 900°C exhibits higher density (1.88 g/cm3), lower porosity (25.4%), higher flexural strength (55.34 MPa), lower dielectric constant (3.46), and lower dielectric loss (4.26 × 10−3).
The Allocation of Refugees to Host States: Should Refugees' Interests and Preferences be Considered?
Authors: Hoesch Matthias , Mantel Susanne
Published: February 2024

When states cooperate in refugee protection and implement a scheme with fixed rules allocating refugees to host states, should they consider refugees' interests and preferences regarding where they receive protection? This article briefly examines the kinds of preferences and interests that are relevant to both refugees and states before discussing the moral principles determining the respective weight that should be attributed to them. We conclude that states must adhere to some minimal constraints concerning the consideration of refugees' concerns, and should promote some further moral goals that go beyond these constraints. Finally, we suggest a scheme that meets all the moral demands we argued for and seems feasible without posing serious threats to the destination states.
Tooth loss during supportive periodontal care: A prospective study
Authors: Hasan Fatemah , Magan‐Fernandez Antonio , Akcalı Aliye , Sun Chuanming , Donos Nikos , Nibali Luigi
Published: February 2024

Aim

To assess periodontal stability and the association between tooth‐ and patient‐related factors and tooth loss during supportive periodontal care (SPC).

Materials and Methods

A prospective observational study was carried out on previously treated periodontitis patients followed up for 5 years in SPC. The risk profile (low, moderate, high) of each patient based on periodontal risk assessment (PRA) scoring at baseline was evaluated, and tooth loss rates were analysed.

Results

Two hundred patients were included in the study, and 143 had 5‐year follow‐up data available for analysis. The overall annual tooth loss per patient was 0.07 ± 0.14 teeth/patient/year. Older age, smoking, staging and grading were associated with increased tooth loss rates. Most patients whose teeth were extracted belonged to the PRA high‐risk group. Both PRA and a tooth prognosis system used at baseline showed high negative predictive value but low positive predictive value for tooth loss during SPC.

Conclusions

Overall, the tooth loss rate of periodontitis patients in this prospective cohort study under SPC in private practice was low. Both tooth‐based and patient‐based prognostic systems can identify high‐risk cases, but their positive predictive value should be improved.
Polysensitization in the Spanish Contact Dermatitis Registry (REIDAC): A 2019–2022 prospective study with cluster and network analysis
Authors: Pesqué David , Borrego Leopoldo , Zaragoza‐Ninet Violeta , Sanz‐Sánchez Tatiana , Miquel‐Miquel Francisco Javier , González‐Pérez Ricardo , Silvestre Juan Francisco , Córdoba‐Guijarro Susana , Carrascosa José Manuel , Gatica‐Ortega María Elena , Ruiz‐González Inmaculada , Mercader‐García Pedro , Tous‐Romero Fátima , Ortiz de Frutos Francisco Javier , Serra‐Baldrich Esther , Pastor‐Nieto María Antonia , Rodríguez‐Serna Mercedes , Sánchez‐Pérez Javier , Sánchez‐Gilo Araceli , Melé‐Ninot Gemma , Sánchez‐Pedreño Guillén Paloma , Pujol Ramon Maria , Giménez‐Arnau Ana María
Published: February 2024

Background

There is still limited clinical‐practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS).

Objectives

To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation.

Methods

Prospective multicentric study (January 2019–December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS.

Results

A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24–2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25–2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05–2.25, hands vs. face OR: 1.46, 95% CI:1.15–1.85, arms vs. face OR: 1.49, 95% CI:1.01–2.20, trunk vs. face OR: 1.40, 95% CI:1.06–1.85). Cluster and network analyses revealed specific‐allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides.

Conclusions

This study confirms that PS is structured by discernible patterns of specific‐allergen clusters and reinforces significant allergen associations in PS. Cross‐reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.
Automated first floor height estimation for flood vulnerability analysis using deep learning and Google Street View
Authors: Sorboni Nafiseh Ghasemian , Wang Jinfei , Najafi Mohammad Reza
Published: February 2024

Flood events can cause extensive damage to physical infrastructure, pose risks to human life, and necessitate the reoccupation and rehabilitation of affected areas. A key parameter for flood vulnerability assessment is the first floor height (FFH), which also plays an important role in setting insurance premiums. Traditional methods for FFH estimation rely on ground surveys and site inspections, yet these approaches are both time‐consuming and labor‐intensive. In this study, we propose an alternative approach based on measurements derived from Google Street View (GSV) images and Deep Learning (DL). We employ the YOLOv5s algorithm, which belongs to a family of compound‐scaled object detection models trained on the COCO dataset, for the detection of crucial building elements such as the Front Door (FD), stairs, and overall building extent. Additionally, we utilized the YOLOv5s algorithm to identify basement windows and assess the existence of basements. To validate our methodology, we conducted tests in both the Greater Toronto Area (GTA) and the state of Virginia in the United States. The results demonstrate an achievement of RMSE and Bias values of 81 cm and −50 cm for GTA, and 95 cm and −20 cm for the Virginia region, respectively.
Associations of light exposure patterns with sleep among Dutch children: The ABCD cohort study
Authors: Stefanopoulou Magdalini , Ruhé Naomi , Portengen Lützen , van Wel Luuk , Vrijkotte Tanja G. M. , Vermeulen Roel , Huss Anke
Published: February 2024

Light exposure affects the circadian system and consequently can affect sleep quality. Only few studies examined this relationship in children. We evaluated associations between light exposure patterns and sleep metrics in children. We measured the sleep parameters of 247 Dutch children, aged between 11 and 13 years and recruited from the ABCD cohort, using actigraphy and sleep records for 7 consecutive nights. Personal light exposures were measured with a light meter during the whole day and night. We applied generalized mixed‐effects regression models, adjusted for possible confounders, to evaluate the associations of light exposure patterns on sleep duration, sleep efficiency and sleep‐onset delay. In the models mutually adjusted for potential confounders, we found the amount of hours between the first time of bright light in the morning and going to sleep and the duration of bright light to be significantly associated with decreased sleep duration (in min; β: −2.02 [95% confidence interval: −3.84, −0.25], β: −8.39 [95% confidence interval: −16.70, −0.07], respectively) and with shorter sleep‐onset delay (odds ratio: 0.88 [95% confidence interval: 0.80, 0.97], odds ratio: 0.40 [95% confidence interval: 0.19, 0.87], respectively). Increased light intensities at night were associated with decreased sleep duration (T2 β: −8.54 [95% confidence interval: −16.88, −0.20], T3 β: −14.83 [95% confidence interval: −28.04, −1.62]), while increased light intensities before going to bed were associated with prolonged sleep onset (odds ratio: 4.02 [95% confidence interval: 2.09, 7.73]). These findings further suggest that children may be able to influence their sleep quality by influencing the light exposure patterns during day and night.
Comparison of power spectra from overnight electroencephalography between patients with Down syndrome and matched control subjects
Authors: Talukder Amlan , Yeung Deryck , Li Yuanyuan , Anandanadarajah Nishanth , Umbach David M. , Fan Zheng , Li Leping
Published: February 2024

Electroencephalograms can capture brain oscillatory activities during sleep as a form of electrophysiological signals. We analysed electroencephalogram recordings from full‐night in‐laboratory polysomnography from 100 patients with Down syndrome, and 100 age‐ and sex‐matched controls. The ages of patients with Down syndrome spanned 1 month to 31 years (median 4.4 years); 84 were younger than 12 years, and 54 were male. From each electroencephalogram, we extracted relative power in six frequency bands or rhythms (delta, theta, alpha, slow sigma, fast sigma, and beta) from six channels (frontal F3 and F4, central C3 and C4, and occipital O1 and O2) during five sleep stages (N3, N2, N1, R and W)—180 features in all. We examined differences in relative power between Down syndrome and control electroencephalograms for each feature separately. During wake and N1 sleep stages, alpha rhythms (8.0–10.5 Hz) had significantly lower power in patients with Down syndrome than controls. Moreover, the rate of increase in alpha power with age during rapid eye movement sleep was significantly slower in Down syndrome than control subjects. During wake and N1 sleep, delta rhythms (0.25–4.5 Hz) had higher power in patients with Down syndrome than controls. During N2 sleep, slow sigma rhythms (10.5–12.5 Hz) had lower power in patients with DS than controls. These findings extend previous research from routine electroencephalogram studies demonstrating that patients with Down syndrome had reduced circadian amplitude—the difference between wake alpha power and deep sleep delta power was smaller in Down syndrome than control subjects. We envision that these brain oscillatory activities may be used as surrogate markers for clinical trials for patients with Down syndrome.