bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prioritizing educational initiatives on emerging technologies for Italian pediatricians: bibliometric review and a survey
Authors: Tozzi Alberto Eugenio , Gesualdo Francesco , Pandolfi Elisabetta , Ferro Diana , Cinelli Giulia , Bozzola Elena , Aversa Tommaso , Di Mauro Antonio , Mameli Chiara , Croci Ileana 
Published: September 2023

Abstract
Background
Emerging technologies have demonstrated outstanding potential in improving healthcare, yet their full integration remains a challenge for all medical specialties, including pediatrics. To support the swift implementation of technologies, we identified the current trends through a bibliometric review, and we conducted a survey on Italian pediatricians to gauge educational needs and willingness to integrate technologies into clinical practice.

Methods
A working group of pediatricians representing various backgrounds designed and coordinated the study. To identify relevant topics for educational strategy development, we focused on virtual reality, telehealth, natural language processing, smartphone applications, robotics, genomics, and artificial intelligence. A bibliometric analysis limited to 2018–2023 was performed to identify trends and emerging applications within each topic. Based on the results, a questionnaire was developed and made available online to all Italian pediatricians. The results were analyzed through descriptive analysis and a multivariable logistic regression to explore associations between technology adoption and sociodemographic characteristics.

Results
A total of 3,253 publications were found, with Telehealth and Telemedicine having the highest number of publications and Natural Language Processing the lowest. The number of respondents to the online questionnaire was 1,540, predominantly medical doctors with over 20 years of experience working as family pediatricians. Telehealth had the highest level of knowledge (95.2%), followed by smartphone applications (89.1%) and genomics (63.2%). The greatest potential for increased use through education programs was projected for natural language processing (+ 43.1%), artificial intelligence (+ 39.6%), and virtual and mixed reality (+ 38.1%). Female respondents and older individuals were less likely to use emerging technologies. Hospital pediatricians and residents were more likely to use AI.

Conclusions
We developed a replicable strategy to identify emerging themes in medical technologies relevant to pediatrics and assess the educational needs of pediatricians. A significant gap still exists between current and potential usage of emerging technologies among Italian pediatricians although they showed a positive attitude towards implementing these technologies following specific education programs. The study highlights the need for comprehensive education programs on emerging technologies in pediatrics and recommends addressing gender and age disparities in technology adoption.
Perilipin 5 deficiency aggravates cardiac hypertrophy by stimulating lactate production in leptin-deficient mice
Authors: Jian Lele , Gao Xing , Wang Chao , Sun Xiao , Xu Yuqiao , Han Ruili , Wang Yuying , Xu Shenhui , Ding Lan , Zhou Jingjun , Gu Yu , Zhao Yuanlin , Yang Ying , Yuan Yuan , Ye Jing , Zhang Lijun 
Published: September 2023

Abstract
Background
Perilipin 5 (Plin5) is well known to maintain the stability of intracellular lipid droplets (LDs) and regulate fatty acid metabolism in oxidative tissues. It is highly expressed in the heart, but its roles have yet to be fully elucidated.

Methods
Plin5-deficient mice and Plin5/leptin-double-knockout mice were produced, and their histological structures and myocardial functions were observed. Critical proteins related to fatty acid and glucose metabolism were measured in heart tissues, neonatal mouse cardiomyocytes and Plin5-overexpressing H9C2 cells. 2-NBDG was employed to detect glucose uptake. The mitochondria and lipid contents were observed by MitoTracker and BODIPY 493/503 staining in neonatal mouse cardiomyocytes.

Results
Plin5 deficiency impaired glucose utilization and caused insulin resistance in mouse cardiomyocytes, particularly in the presence of fatty acids (FAs). Additionally, Plin5 deficiency increased the NADH content and elevated the expression of lactate dehydrogenase (LDHA) in cardiomyocytes, which resulted in increased lactate production. Moreover, when fatty acid oxidation was blocked by etomoxir or LDHA was inhibited by GSK2837808A in Plin5-deficient cardiomyocytes, glucose utilization was improved. Leptin-deficient mice exhibited myocardial hypertrophy, insulin resistance and altered substrate utilization, and Plin5 deficiency exacerbated myocardial hypertrophy in leptin-deficient mice.

Conclusion
Our results demonstrated that Plin5 plays a critical role in coordinating fatty acid and glucose oxidation in cardiomyocytes, providing a potential target for the treatment of metabolic disorders in the heart.

Graphic abstract
Evaluation of the safety and immunological effects of Bacillus Calmette–Guérin in combination with checkpoint inhibitor therapy in a patient with neuroendocrine carcinoma: a case report
Authors: Föhse Konstantin , Debisarun Priya A. , Kilic Gizem , van Dodewaard-de Jong Joyce M. , Netea Mihai G. 
Published: September 2023

Abstract
Background
Immune checkpoint inhibitors have revolutionized therapy of advanced and metastatic cancers. However, a significant proportion of patients do not respond to immune checkpoint inhibitors or develop resistance. Therefore, novel therapies or combinations of therapies that may act synergistically are needed. It has been suggested that induction of trained immunity may increase the response to immune checkpoint inhibitor therapy, through reprogramming myeloid cells toward an antitumor phenotype. On the other hand, activation of the immune system also carries the risk of potentially sustaining tumorgenicity and increasing immune- related toxicity.

Case presentation
We report the case of a 37-year-old Dutch male suffering from gastric neuroendocrine carcinoma with liver metastases and high risk for an unfavorable outcome, who was treated with a combination of programmed cell death protein 1 inhibitor nivolumab and the trained immunity-inducer Bacillus Calmette–Guérin vaccine as a salvage therapy. Three doses of BCG vaccine were administered at 3-month intervals, in conjunction with the immune checkpoint inhibitor regimen. At a certain point, radiation therapy was added to the treatment regimen. During the combination of these therapies, the patient developed immune-mediated colitis, which necessitated discontinuation of all treatments. Bacillus Calmette–Guérin vaccination induced a trained immune response with elevated monocyte-derived interleukin-6 and interleukin-1β production capacity. From the first vaccination with Bacillus Calmette–Guérin until 3 months after the last vaccination with Bacillus Calmette–Guérin, the patient displayed only mild progression of the primary tumor and no progression of the metastases.

Conclusion
In this study, we show the feasibility to combine checkpoint inhibitor therapy with inducers of trained immunity in a patient with an aggressive neuroendocrine tumor. Autoimmune side effects are common under programmed cell death protein 1 inhibitor therapy, which was considered the most likely cause of colitis, although an additive effect of Bacillus Calmette–Guérin vaccination or radiotherapy cannot be excluded. The patient displayed only mild progression during the combination therapy, but larger studies are warranted to fully explore the potential benefit of trained immunity inducers as an adjuvant to immune checkpoint inhibitor therapy.
Factors affecting the use of dental services among Arab children in Israel: a qualitative study
Authors: Khatib Mohammad , Ashkenazi Yael , Loeff Yoav , Zusman Shlomo Paul , Natapov Lena 
Published: September 2023

Abstract
Background
In 2010, Israel reformed its hitherto dominantly privately financed dental services and included preventative and restorative dental care for children in the publicly-funded basket of healthcare services. A survey conducted by Brookdale Institute, found that only 67% of low-income Israeli-Arab children were using the new service (compared to 85% of Jewish children) while the majority of others continue using privately funded services. The aim of this study is to explore and explain Israeli-Arab children’s low utilization of publicly-funded preventive and restorative dental care.

Methods
A qualitative study designed to describe and understand the parents’ motivations and choices. As a preliminary stage, eight semi-structured interviews were conducted with directors of HMO dental departments and Israeli-Arab dentists. In the second stage, ten one-on-one interviews with parents, and five focus group discussions with 55 parents held on February–March 2017. All discussions in the focus groups were conducted in Arabic and each group was moderated by one of the research team accompanied by another person who documented and recorded the discussion. All interviews and discussions were recorded, transcribed in full and translated into Hebrew.

Results
The prevalent attitude is that one goes to the dentist only when there is a serious problem. The importance of preventive care is not appreciated. A childhood fear of the drill is very remembered and passed onto the children. Social and cultural factors such as kinship with service providers (GPs and dentists) influence the choice and utilization of health services. Economic barriers are still existing since even the small co-payment is daunting to low-income parents of large families. Provision of the public service is inadequate in some Arab villages.

Conclusions
The extension of Israel's National Health Insurance Law’s basket of services to include dental care for children, while important, is not sufficiently embraced by Israeli Arab children. The remaining barriers include poor living conditions, low educational level that requires very clear sharing of information about the new service, and the resistance of cultural and social traditions. Public dental services providers should focus on conveying relevant oral health messages to the parents too, either through their children or directly.
Antimicrobial stewardship in primary health care programs in humanitarian settings: the time to act is now
Authors: Truppa Claudia , Alonso Beatriz , Clezy Kate , Deglise Carole , Dromer Carole , Garelli Silvia , Jimenez Carolina , Kanapathipillai Rupa , Khalife Mohamad , Repetto Ernestina 
Published: September 2023

AbstractFragile and conflict-affected settings bear a disproportionate burden of antimicrobial resistance, due to the compounding effects of weak health policies, disrupted medical supply chains, and lack of knowledge and awareness about antibiotic stewardship both among health care providers and health service users. Until now, humanitarian organizations intervening in these contexts have confronted the threat of complex multidrug resistant infections mainly in their surgical projects at the secondary and tertiary levels of care, but there has been limited focus on ensuring the implementation of adequate antimicrobial stewardship in primary health care, which is known to be setting where the highest proportion of antibiotics are prescribed. In this paper, we present the experience of two humanitarian organizations, Médecins sans Frontières and the International Committee of the Red Cross, in responding to antimicrobial resistance in their medical interventions, and we draw from their experience to formulate practical recommendations to include antimicrobial stewardship among the standards of primary health care service delivery in conflict settings. We believe that expanding the focus of humanitarian interventions in unstable and fragile contexts to include antimicrobial stewardship in primary care will strengthen the global response to antimicrobial resistance and will decrease its burden where it is posing the highest toll in terms of mortality.
A hypoxia- and lactate metabolism-related gene signature to predict prognosis of sepsis: discovery and validation in independent cohorts
Authors: Peng Yaojun , Wu Qiyan , Ding Xinhuan , Wang Lingxiong , Gong Hanpu , Feng Cong , Liu Tianyi , Zhu Haiyan 
Published: September 2023

AbstractBackgroundHigh throughput gene expression profiling is a valuable tool in providing insight into the molecular mechanism of human diseases. Hypoxia- and lactate metabolism-related genes (HLMRGs) are fundamentally dysregulated in sepsis and have great predictive potential. Therefore, we attempted to build an HLMRG signature to predict the prognosis of patients with sepsis.MethodsThree publicly available transcriptomic profiles of peripheral blood mononuclear cells from patients with sepsis (GSE65682, E-MTAB-4421 and E-MTAB-4451, totaln = 850) were included in this study. An HLMRG signature was created by employing Cox regression and least absolute shrinkage and selection operator estimation. The CIBERSORT method was used to analyze the abundances of 22 immune cell subtypes based on transcriptomic data. Metascape was used to investigate pathways related to the HLMRG signature.ResultsWe developed a prognostic signature based on five HLMRGs (ERO1L,SIAH2,TGFA,TGFBI, andTHBS1). This classifier successfully discriminated patients with disparate 28-day mortality in the discovery cohort (GSE65682,n = 479), and consistent results were observed in the validation cohort (E-MTAB-4421 plus E-MTAB-4451,n = 371). Estimation of immune infiltration revealed significant associations between the risk score and a subset of immune cells. Enrichment analysis revealed that pathways related to antimicrobial immune responses, leukocyte activation, and cell adhesion and migration were significantly associated with the HLMRG signature.ConclusionsIdentification of a prognostic signature suggests the critical role of hypoxia and lactate metabolism in the pathophysiology of sepsis. The HLMRG signature can be used as an efficient tool for the risk stratification of patients with sepsis.
Large-scale proximity extension assay reveals CSF midkine and DOPA decarboxylase as supportive diagnostic biomarkers for Parkinson’s disease
Authors: Paslawski Wojciech , Khosousi Shervin , Hertz Ellen , Markaki Ioanna , Boxer Adam , Svenningsson Per 
Published: September 2023

Abstract
Background
There is a need for biomarkers to support an accurate diagnosis of Parkinson’s disease (PD). Cerebrospinal fluid (CSF) has been a successful biofluid for finding neurodegenerative biomarkers, and modern highly sensitive multiplexing methods offer the possibility to perform discovery studies. Using a large-scale multiplex proximity extension assay (PEA) approach, we aimed to discover novel diagnostic protein biomarkers allowing accurate discrimination of PD from both controls and atypical Parkinsonian disorders (APD).

Methods
CSF from patients with PD, corticobasal syndrome (CBS), progressive supranuclear palsy (PSP), multiple system atrophy and controls, were analysed with Olink PEA panels. Three cohorts were used in this study, comprising 192, 88 and 36 cases, respectively. All samples were run on the Cardiovascular II, Oncology II and Metabolism PEA panels.

Results
Our analysis revealed that 26 and 39 proteins were differentially expressed in the CSF of test and validation PD cohorts, respectively, compared to controls. Among them, 6 proteins were changed in both cohorts. Midkine (MK) was increased in PD with the strongest effect size and results were validated with ELISA. Another most increased protein in PD, DOPA decarboxylase (DDC), which catalyses the decarboxylation of DOPA (L-3,4-dihydroxyphenylalanine) to dopamine, was strongly correlated with dopaminergic treatment. Moreover, Kallikrein 10 was specifically changed in APD compared with both PD and controls, but unchanged between PD and controls. Wnt inhibitory factor 1 was consistently downregulated in CBS and PSP patients in two independent cohorts.

Conclusions
Using the large-scale PEA approach, we have identified potential novel PD diagnostic biomarkers, most notably MK and DDC, in the CSF of PD patients.
Rosemary extract improves egg quality by altering gut barrier function, intestinal microbiota and oviductal gene expressions in late-phase laying hens
Authors: Zhang Lianhua , Ge Junwei , Gao Fei , Yang Min , Li Hui , Xia Fei , Bai Hongtong , Piao Xiangshu , Sun Zhiying , Shi Lei 
Published: September 2023

Abstract
Background
Rosemary extract (RE) has been reported to exert antioxidant property. However, the application of RE in late-phase laying hens on egg quality, intestinal barrier and microbiota, and oviductal function has not been systematically studied. This study was investigated to detect the potential effects of RE on performance, egg quality, serum parameters, intestinal heath, cecal microbiota and metabolism, and oviductal gene expressions in late-phase laying hens. A total of 210 65-week-old “Jing Tint 6” laying hens were randomly allocated into five treatments with six replicates and seven birds per replicate and fed basal diet (CON) or basal diet supplemented with chlortetracycline at 50 mg/kg (CTC) or RE at 50 mg/kg (RE50), 100 mg/kg (RE100), and 200 mg/kg (RE200).

Results
Our results showed that RE200 improved (P < 0.05) Haugh unit and n-6/n-3 of egg yolk, serum superoxide dismutase (SOD) compared with CON. No significant differences were observed for Haugh unit and n-6/n-3 of egg yolk among CTC, RE50, RE100 and RE200 groups. Compared with CTC and RE50 groups, RE200 increased serum SOD activity on d 28 and 56. Compared with CON, RE supplementation decreased (P < 0.05) total cholesterol (TC) level. CTC, RE100 and RE200 decreased (P < 0.05) serum interleukin-6 (IL-6) content compared with CON. CTC and RE200 increased jejunal mRNA expression of ZO-1 and Occludin compared with CON. The biomarkers of cecal microbiota and metabolite induced by RE 200, including Firmicutes, Eisenbergiella, Paraprevotella, Papillibacter, and butyrate, were closely associated with Haugh unit, n-6/n-3, SOD, IL-6, and TC. PICRUSt2 analysis indicated that RE altered carbohydrate and amino acid metabolism of cecal microbiota and increased butyrate synthesizing enzymes, including 3-oxoacid CoA-transferase and butyrate-acetoacetate CoA-transferase. Moreover, transcriptomic analysis revealed that RE200 improved gene expressions and functional pathways related to immunity and albumen formation in the oviductal magnum.

Conclusions
Dietary supplementation with 200 mg/kg RE could increase egg quality of late-phase laying hens via modulating intestinal barrier, cecal microbiota and metabolism, and oviductal function. Overall, RE could be used as a promising feed additive to improve egg quality of laying hens at late stage of production.

Graphical Abstract
68Ga-PSMA PET/CT-based multivariate model for highly accurate and noninvasive diagnosis of clinically significant prostate cancer in the PSA gray zone
Authors: Yang Jinhui , Li Jian , Xiao Ling , Zhou Ming , Fang Zhihui , Cai Yi , Tang Yongxiang , Hu Shuo 
Published: September 2023

Abstract
Background
The prostate-specific antigen (PSA) has been widely used in screening and early diagnosis of prostate cancer (PCa). However, in the PSA grey zone of 4–10 ng/ml, the sensitivity and specificity for diagnosing PCa are limited, resulting in considerable number of unnecessary and invasive prostate biopsies, which may lead to potential overdiagnosis and overtreatment. We aimed to predict clinically significant PCa (CSPCa) by combining the maximal standardized uptake value (SUVmax) based on 68Ga‑PSMA PET/CT and clinical indicators in men with gray zone PSA levels.

Methods
81 patients with suspected PCa based on increased serum total PSA (TPSA) levels of 4 − 10 ng/mL who underwent transrectal ultrasound/magnetic resonance imaging (MRI)/PET fusion-guided biopsy were enrolled. Among them, patients confirmed by histopathology were divided into the CSPCa group and the non-CSPCa group, and data on PSA concentration, prostate volume (PV), PSA density (PSAD), free PSA (FPSA)/TPSA, Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS v2.1) score, 68Ga-PSMA PET/CT imaging evaluation results and SUVmax were compared. Multivariate logistic regression analysis was performed to identify the independent predictors for CSPCa, thereby establishing a predictive model based on SUVmax that was evaluated by analyzing the receiver operating characteristic (ROC) curve and decision curve analysis.

Results
Compared to non-CSPCa, CSPCa patients had smaller PVs (median, 31.40 mL), lower FPSA/TPSA (median, 0.12), larger PSADs (median, 0.21 ng/mL2) and higher PI-RADS scores (P < 0.05). The prediction model comprising 68Ga-PSMA PET/CT maximal standardized uptake value, PV and FPSA/TPSA had the highest AUC of 0.927 compared with that of other predictors alone (AUCs of 0.585 for PSA, 0.652 for mpMRI and 0.850 for 68Ga-PSMA PET/CT). The diagnostic sensitivity and specificity of the prediction model were 86.21% and 86.54%, respectively.

Conclusion
Given the low diagnostic accuracy of regular PSA tests, a new prediction model based on the 68Ga-PSMA PET/CT SUVmax, PV and FPSA/TPSA was developed and validated, and this model could provide a more satisfactory predictive accuracy for CSPCa. This study provides a noninvasive prediction model with high accuracy for the diagnosis of CSPCa in the PSA gray zone, thus may be better avoiding unnecessary biopsy procedures.
Space and atmospheric physics on Svalbard: a case for continued incoherent scatter radar measurements under the cusp and in the polar cap boundary region
Authors: Baddeley Lisa , Lorentzen Dag , Haaland Stein , Heino Erkka , Mann Ingrid , Miloch Wojciech , Oksavik Kjellmar , Partamies Noora , Spicher Andres , Vierinen Juha 
Published: September 2023

Abstract Incoherent scatter radars (ISRs) represent the only instrument (both ground and space based) capable of making high temporal and spatial resolution measurements of multiple atmospheric parameters—such as densities, temperatures, particle velocities, mass flux—over an altitude range covering the entire mesosphere/lower thermosphere/ionosphere (MLTI) system on a quasi-continuous basis. The EISCAT Svalbard incoherent scatter radar (ESR), located just outside Longyearbyen (78.15$$^\circ$$

∘

N) on Svalbard, is the only currently operating facility capable of making such measurements inside the polar cusp—an area of significant energy input into the atmosphere and characterized by heating instabilities and turbulence. The ESR was built in the mid-1990s and has provided valuable data for the international experimental and modelling communities. New radar technologies are now available, in the form of phased array systems, which offer new data products and operational flexibility. This paper outlines the achievements and current research focus of the ESR and provides scientific arguments, compiled from inputs across the international scientific community, for a new phased array ISR facility on Svalbard. In addition to the fundamental scientific arguments, the paper discusses additional benefits of continued ISR observations on Svalbard, building on the key findings of the ESR. Svalbard has a large network of complementary instrumentation both focused on the MLTI system (e.g. the Kjell Henriksen auroral Observatory, the Svalbard SuperDARN radar and the Svalrak sounding rocket launch facility) with synergies to other research fields, such as meteorology and oceanography. As a further holistic system science view of the Earth becomes more important, a new ISR on Svalbard will be important also in this respect with its ability to provide datasets with a wide range of scientific applications. Increased activity in space has highlighted problematic issues such as space debris. A changing Arctic has also seen increased human activity via the opening up of new shipping routes, which are reliant on GNSS technology that is effected by severe turbulence in the MLTI system. As such, societal applications of a future ISR are also presented. The accessibility and logistical support for such a facility is also briefly discussed.