bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monte Carlo simulation of the Varian TrueBeam flattened-filtered beams using a surrogate geometry in PRIMO
Authors: Rodriguez Miguel , Sempau Josep , Brualla Lorenzo 
Published: January 2024

Abstract
Background
Monte Carlo simulation of radiation transport for medical linear accelerators (linacs) requires accurate knowledge of the geometrical description of the linac head. Since the geometry of Varian TrueBeam machines has not been disclosed, the manufacturer distributes phase-space files of the linac patient-independent part to allow researchers to compute absorbed dose distributions using the Monte Carlo method. This approach limits the possibility of achieving an arbitrarily small statistical uncertainty. This work investigates the use of the geometry of the Varian Clinac 2100, which is included in the Monte Carlo system PRIMO, as a surrogate.

Methods
Energy, radial and angular distributions extracted from the TrueBeam phase space files published by the manufacturer and from phase spaces tallied with PRIMO for the Clinac 2100 were compared for the 6, 8, 10 and 15 MV flattened-filtered beams. Dose distributions in water computed for the two sets of PSFs were compared with the Varian Representative Beam Data (RBD) for square fields with sides ranging from 3 to 30 cm. Output factors were calculated for square fields with sides ranging from 2 to 40 cm.

Results
Excellent agreement with the RBD was obtained for the simulations that employed the phase spaces distributed by Varian as well as for those that used the surrogate geometry, reaching in both cases Gamma ($$2\%$$

2
%

, 2 mm) pass rates larger than $$99\%$$

99
%

, except for the 15 MV surrogate. This result supports previous investigations that suggest a change in the material composition of the TrueBeam 15 MV flattening filter. In order to get the said agreement, PRIMO simulations were run using enlarged transport parameters to compensate the discrepancies between the actual and surrogate geometries.

Conclusions
This work sustains the claim that the simulation of the 6, 8 and 10 MV flattening-filtered beams of the TrueBeam linac can be performed using the Clinac 2100 model of PRIMO without significant loss of accuracy.
Zhuifeng Tougu capsules in the treatment of knee osteoarthritis (cold dampness obstruction syndrome): a randomized, double blind, multicenter clinical study
Authors: Zhao Longmei , Zhou Shasha , Wang SiWei , Wu Rui , Meng Qingliang , Li Zhenbin , Peng Jiangyun , Liu Ying , Lu Min , Li Ming , Zhu Caifeng , Sun Yue , He Yanlin , Jin Yue , Gao Jingyue , Zhang Shumin , Li Peihao , Liao Rongjun , Liu Wei , Zhang Guoming 
Published: January 2024

Abstract
Background
In Traditional Chinese Medicine (TCM) theory, cold dampness obstruction is one of the common syndromes of osteoarthritis. Therefore, in clinical practice, the main treatment methods are to dispel wind, remove dampness, and dissipate cold, used to treat knee osteoarthritis (KOA). This report describes a mulitercenter clinical study to assess Zhuifeng Tougu Capsule’s efficacy and safety in the treatment of patients who are cold dampness obstruction syndrome in KOA, and to provide evidence-based medical for the rational use of Zhuifeng Tougu Capsules in clinical practice.

Methods
This randomized, parallel group controlled, double-blind, double dummy trial will include a total of 215 KOA patients who meet the study criteria. 215 patients underwent 1:1 randomisation, with 107 cases assigned the experimental group (Zhuifeng Tougu Capsules + Glucosamine Sulfate Capsules Simulator) and 108 assigned the control group (Glucosamine Sulfate Capsules + Zhuifeng Tougu Capsules Simulator). After enrolment, patients received 12 weeks of treatment. The main efficacy measure is the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) pain score. Visual analogue scale (VAS) pain score, Self-condition assessment VAS score, WOMAC KOA score, TCM syndrome score and TCM syndrome efficacy, ESR level, CRP level, suprapatellar bursa effusion depth, use of rescue drugs, and safety indicators are secondary efficacy indicators.

Results
Compared with before treatment, WOMAC pain score, VAS pain score, Self-condition assessment VAS score, WOMAC KOA score, and TCM syndrome score decreased significantly in both groups (P < 0.01). Also, the experimental group showed significant differences in the above indicators compared to control (P < 0.01). However, after treatment, no significant differences were showed in the ESR level, CRP level, and suprapatellar bursa effusion depth between the two groups (P > 0.05). No any serious adverse effects showed in the experimental group and control group.

Conclusions
Zhuifeng Tougu Capsules can effectively improve knee joint function and significantly alleviate the pain of KOA.
Trial registration: Clinical trial registration was completed with the China Clinical Trial Registration Center for this research protocol (No. ChiCTR2000028750) on January 2, 2020.
Are the European reference networks for rare diseases ready to embrace machine learning? A mixed-methods study
Authors: Iskrov Georgi , Raycheva Ralitsa , Kostadinov Kostadin , Gillner Sandra , Blankart Carl Rudolf , Gross Edith Sky , Gumus Gulcin , Mitova Elena , Stefanov Stefan , Stefanov Georgi , Stefanov Rumen 
Published: January 2024

Abstract
Background
The delay in diagnosis for rare disease (RD) patients is often longer than for patients with common diseases. Machine learning (ML) technologies have the potential to speed up and increase the precision of diagnosis in this population group. We aim to explore the expectations and experiences of the members of the European Reference Networks (ERNs) for RDs with those technologies and their potential for application.

Methods
We used a mixed-methods approach with an online survey followed by a focus group discussion. Our study targeted primarily medical professionals but also other individuals affiliated with any of the 24 ERNs.

Results
The online survey yielded 423 responses from ERN members. Participants reported a limited degree of knowledge of and experience with ML technologies. They considered improved diagnostic accuracy the most important potential benefit, closely followed by the synthesis of clinical information, and indicated the lack of training in these new technologies, which hinders adoption and implementation in routine care. Most respondents supported the option that ML should be an optional but recommended part of the diagnostic process for RDs. Most ERN members saw the use of ML limited to specialised units only in the next 5 years, where those technologies should be funded by public sources. Focus group discussions concluded that the potential of ML technologies is substantial and confirmed that the technologies will have an important impact on healthcare and RDs in particular. As ML technologies are not the core competency of health care professionals, participants deemed a close collaboration with developers necessary to ensure that results are valid and reliable. However, based on our results, we call for more research to understand other stakeholders’ opinions and expectations, including the views of patient organisations.

Conclusions
We found enthusiasm to implement and apply ML technologies, especially diagnostic tools in the field of RDs, despite the perceived lack of experience. Early dialogue and collaboration between health care professionals, developers, industry, policymakers, and patient associations seem to be crucial to building trust, improving performance, and ultimately increasing the willingness to accept diagnostics based on ML technologies.
Mitochondrial CISD1/Cisd accumulation blocks mitophagy and genetic or pharmacological inhibition rescues neurodegenerative phenotypes in Pink1/parkin models
Authors: Martinez Aitor , Sanchez-Martinez Alvaro , Pickering Jake T. , Twyning Madeleine J. , Terriente-Felix Ana , Chen Po-Lin , Chen Chun-Hong , Whitworth Alexander J. 
Published: January 2024

Abstract
Background
Mitochondrial dysfunction and toxic protein aggregates have been shown to be key features in the pathogenesis of neurodegenerative diseases, such as Parkinson’s disease (PD). Functional analysis of genes linked to PD have revealed that the E3 ligase Parkin and the mitochondrial kinase PINK1 are important factors for mitochondrial quality control. PINK1 phosphorylates and activates Parkin, which in turn ubiquitinates mitochondrial proteins priming them and the mitochondrion itself for degradation. However, it is unclear whether dysregulated mitochondrial degradation or the toxic build-up of certain Parkin ubiquitin substrates is the driving pathophysiological mechanism leading to PD. The iron-sulphur cluster containing proteins CISD1 and CISD2 have been identified as major targets of Parkin in various proteomic studies.

Methods
We employed in vivo Drosophila and human cell culture models to study the role of CISD proteins in cell and tissue viability as well as aged-related neurodegeneration, specifically analysing aspects of mitophagy and autophagy using orthogonal assays.

Results
We show that the Drosophila homolog Cisd accumulates in Pink1 and parkin mutant flies, as well as during ageing. We observed that build-up of Cisd is particularly toxic in neurons, resulting in mitochondrial defects and Ser65-phospho-Ubiquitin accumulation. Age-related increase of Cisd blocks mitophagy and impairs autophagy flux. Importantly, reduction of Cisd levels upregulates mitophagy in vitro and in vivo, and ameliorates pathological phenotypes in locomotion, lifespan and neurodegeneration in Pink1/parkin mutant flies. In addition, we show that pharmacological inhibition of CISD1/2 by rosiglitazone and NL-1 induces mitophagy in human cells and ameliorates the defective phenotypes of Pink1/parkin mutants.

Conclusion
Altogether, our studies indicate that Cisd accumulation during ageing and in Pink1/parkin mutants is a key driver of pathology by blocking mitophagy, and genetically and pharmacologically inhibiting CISD proteins may offer a potential target for therapeutic intervention.

Graphical Abstract
Serum levels of PDGF-CC as a potential biomarker for the diagnosis of Kawasaki disease
Authors: Zhang Jing , Yang Penghui , Liu Yihao , Chen Zhuo , Wu Jinhui , Feng Siqi , Yi Qijian 
Published: January 2024

Abstract
Background
Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology that predominantly affects children, and no specific diagnostic biomarkers for KD are available. Platelet-derived growth factor CC (PDGF-CC) is a peptide with angiogenic properties that has been amply demonstrated to play a critical role in the cardiovascular system. This study aimed to investigate the serum expression of PDGF-CC in children with KD and to evaluate the ability of PDGF-CC to diagnose KD.

Methods
A total of 96 subjects, including 59 KD patients, 17 febrile controls (FC), and 20 healthy controls (HC), were enrolled. Serum levels of PDGF-CC were measured via enzyme-linked immunosorbent assay. The associations between PDGF-CC and clinical laboratory parameters were investigated by correlation analysis. The diagnostic performance was assessed by receiver operating characteristic (ROC) curve analysis.

Results
Serum PDGF-CC levels in the KD group were significantly higher than in the FC and HC groups. Serum PDGF-CC levels in the KD group were positively correlated with white blood cell counts, percentage of neutrophils, IL-2, IL-12p70, TNF-α, and IL-1β levels, and negatively correlated with the percentage of lymphocytes. In the analysis of ROC curves, the area under the curve was 0.796 (95% confidence interval 0.688–0.880; P < 0.0001) for PDGF-CC and increased to 0.900 (95% confidence interval 0.808–0.957; P < 0.0001) in combination with white blood cell counts and C-reactive protein.

Conclusions
PDGF-CC is a potential biomarker for KD diagnosis, and the combination with white blood cell counts and C-reactive protein can further improve diagnostic performance.
Current hospital policies on breastfeeding: a survey from Italy
Authors: Davanzo Riccardo , Travan Laura , Giannì Maria Lorella , Giordano Giuseppe , Perugi Silvia , Baldassarre Mariella , Soldi Antonella , Colombo Lorenzo , Mondello Isabella , Pandullo Michela , Ferrara Alessia , Scarpato Elena , Salvatori Guglielmo 
Published: January 2024

Abstract
Background
The availability of an appropriate newborn feeding policy is an essential component of the promotion of breastfeeding in health facilities. The Italian Society of Neonatology (SIN) and the Italian Society of Paediatrics (SIP) have run an online survey among Maternity Hospitals to explore the existing breastfeeding policies and their characteristics.

Methods
Between February and April 2023, an online survey was carried out among 110 Italian maternity hospitals with a Neonatal Intensive Care Unit (NICU).

Results
Forty-nine Maternity Hospitals completed the online questionnaire. Twenty out of 49 (40.8%) reported to have a breastfeeding policy. When a policy is available, its quality appears to be suboptimal because of lack of inclusion of a family representative in the policy working group, limited options for translating breastfeeding policy into minority languages, lack of periodic assessment of their implementation.

Conclusion
Currently, only a limited number of Italian Maternity Hospitals have developed a breastfeeding policy. Additional efforts are needed for their improvement as well as implementation.
Acute otitis media diagnosis in childhood: still a problem in 2023?
Authors: Folino Francesco , Caruso Marco , Bosi Pietro , Aldè Mirko , Torretta Sara , Marchisio Paola 
Published: January 2024

Abstract
Background
Diagnosis of acute otitis media (AOM) in children can be challenging, given that symptoms are often non-specific or absent, and that the direct observation of the tympanic membrane in its entirety through otoscopy can sometimes be difficult. The aim of this study is to assess the diagnostic concordance in detection of AOM episodes between primary care paediatricians and physicians especially trained in paediatric otoscopy, and to characterize the most misleading elements in diagnostic failure.

Methods
Consecutive clinical charts of children regularly followed for recurrent AOM (RAOM, i.e.: >3 episodes in 6 months or > 4 episodes in 1 year) at our Otitis Media paediatric outpatient clinic were retrospectively screened, in order to collect any diagnosis of AOM episode (and the related clinical findings/middle ear complaints) performed by primary care paediatricians/emergency room paediatricians. Diagnosis of AOM episode was validated by the same experienced physician (FF) in case of otoscopic relief of a bulging eardrum with at least one of the following: hyperaemia or yellow-like colour. The diagnostic concordance in detection of AOM episodes between primary care/emergency room paediatricians and our internal validator was expressed as the percentage of matching diagnosis.

Results
One hundred and thirty-four single AOM episodes occurring in 87 children (mean age: 26.9 +/- 18.9 months) were included in the analysis. Diagnostic concordance in detection of AOM episodes between primary care/emergency room paediatricians and our internal validator was reported in 72.4% of cases. The most common pitfall found in our study was the misleading diagnosis of AOM in case of hyperaemic tympanic membrane without bulging (32/37 out of non-validated diagnoses).

Conclusions
AOM diagnosis still represents a relevant issue among paediatricians in our country, and the presence of tympanic membrane hyperaemia without concomitant bulging can be confusing.
Standard vs. targeted oxygen therapy prehospitally for chronic obstructive pulmonary disease (STOP-COPD): study protocol for a randomised controlled trial
Authors: Jensen Arne Sylvester Rønde , Valentin Jan Brink , Mulvad Mathilde Gundgaard , Hagenau Victor , Skaarup Søren Helbo , Johnsen Søren Paaske , Væggemose Ulla , Gude Martin Faurholdt 
Published: January 2024

Abstract
Background
A high concentration of inspired supplemental oxygen may possibly cause hypercapnia and acidosis and increase mortality in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Even so, patients with AECOPD are being treated with high oxygen flow rates when receiving inhalation drugs in the prehospital setting. A cluster-randomised controlled trial found that reduced oxygen delivery by titrated treatment reduced mortality—a result supported by observational studies—but the results have never been reproduced. In the STOP-COPD trial, we investigate the effect of titrated oxygen delivery compared with usual care consisting of high flow oxygen delivery in patients with AECOPD in the prehospital setting.

Methods
In this randomised controlled trial, patients will be blinded to allocation. Patients with suspected AECOPD (n = 1888) attended by the emergency medical service (EMS) and aged > 40 years will be allocated randomly to either standard treatment or titrated oxygen, targeting a blood oxygen saturation of 88–92% during inhalation therapy. The trial will be conducted in the Central Denmark Region and include all ambulance units. The power to detect a 3% 30-day mortality risk difference is 80%. The trial is approved as an emergency trial. Hence, EMS providers will include patients without prior consent.

Discussion
The results will provide evidence on whether titrated oxygen delivery outperforms standard high flow oxygen when used to nebulise inhaled bronchodilators in AECOPD treatment. The trial is designed to ensure unselected inclusion of patients with AECOPD needing nebulised bronchodilators—a group of patients that receives high oxygen fractions when treated in the prehospital setting where the only compressed gas is generally pure oxygen. Conducting this trial, we aim to improve treatment for people with AECOPD while reducing their 30-day mortality.

Trial registration
European Union Clinical Trials (EUCT) number: 2022-502003-30-00 (authorised 06/12/2022), ClinicalTrials.gov number: NCT05703919 (released 02/02/2023), Universal trial number: U1111-1278-2162.
Dysregulated lncRNAs regulate human umbilical cord mesenchymal stem cell differentiation into insulin-producing cells by forming a regulatory network with mRNAs
Authors: Xie Tianqin , Huang Qiming , Huang Qiulan , Huang Yanting , Liu Shuang , Zeng Haixia , Liu Jianping 
Published: January 2024

Abstract
Objective
In recent years, cell therapy has emerged as a new research direction in the treatment of diabetes. However, the underlying molecular mechanisms of mesenchymal stem cell (MSC) differentiation necessary to form such treatment have not been clarified.

Methods
In this study, human umbilical cord mesenchymal stem cells (HUC-MSCs) isolated from newborns were progressively induced into insulin-producing cells (IPCs) using small molecules. HUC-MSC (S0) and four induced stage (S1–S4) samples were prepared. We then performed transcriptome sequencing experiments to obtain the dynamic expression profiles of both mRNAs and long noncoding RNAs (lncRNAs).

Results
We found that the number of differentially expressed lncRNAs and mRNAs trended downwards during differentiation. Gene Ontology (GO) analysis showed that the target genes of differentially expressed lncRNAs were associated with translation, cell adhesion, and cell connection. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the NF-KB signalling pathway, MAPK signalling pathway, HIPPO signalling pathway, PI3K–Akt signalling pathway, and p53 signalling pathway were enriched in these differentially expressed lncRNA-targeting genes. We also found that the coexpression of the lncRNA CTBP1-AS2 with PROX1 and the lncRNAs AC009014.3 and GS1-72M22.1 with JARID2 mRNA was related to the development of pancreatic beta cells. Moreover, the coexpression of the lncRNAs: XLOC_ 050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14- AS1, RP11-148K1.12, and CTD2020K17.3 with p53, regulated insulin secretion by pancreatic beta cells.

Conclusion
In this study, HUC-MSCs combined with small molecule compounds were successfully induced into IPCs. Differentially expressed lncRNAs may regulate the insulin secretion of pancreatic beta cells by regulating multiple signalling pathways. The lncRNAs AC009014.3, Gs1-72m21.1, and CTBP1-AS2 may be involved in the development of pancreatic beta cells, and the lncRNAs: XLOC_050969, LINC00883, XLOC_050981, XLOC_050925, MAP3K14-AS1, RP11-148K1.12, and CTD2020K17.3 may be involved in regulating the insulin secretion of pancreatic beta cells, thus providing a lncRNA catalogue for future research regarding the mechanism of the transdifferentiation of HUC-MSCs into IPCs. It also provides a new theoretical basis for the transplantation of insulin-producing cells into diabetic patients in the future.

Graphical Abstract
Research trends in contemporary health economics: a scientometric analysis on collective content of specialty journals
Authors: Zwack Clara C. , Haghani Milad , de Bekker-Grob Esther W. 
Published: January 2024

AbstractIntroductionHealth economics is a thriving sub-discipline of economics. Applied health economics research is considered essential in the health care sector and is used extensively by public policy makers. For scholars, it is important to understand the history and status of health economics—when it emerged, the rate of research output, trending topics, and its temporal evolution—to ensure clarity and direction when formulating research questions.MethodsNearly 13,000 articles were analysed, which were found in the collective publications of the ten most specialised health economic journals. We explored this literature using patterns of term co-occurrence and document co-citation.ResultsThe research output in this field is growing exponentially. Five main research divisions were identified: (i) macroeconomic evaluation, (ii) microeconomic evaluation, (iii) measurement and valuation of outcomes, (iv) monitoring mechanisms (evaluation), and (v) guidance and appraisal. Document co-citation analysis revealed eighteen major research streams and identified variation in the magnitude of activities in each of the streams. A recent emergence of research activities in health economics was seen in the Medicaid Expansion stream. Established research streams that continue to show high levels of activity include Child Health, Health-related Quality of Life (HRQoL) and Cost-effectiveness. Conversely, Patient Preference, Health Care Expenditure and Economic Evaluation are now past their peak of activity in specialised health economic journals. Analysis also identified several streams that emerged in the past but are no longer active.ConclusionsHealth economics is a growing field, yet there is minimal evidence of creation of new research trends. Over the past 10 years, the average rate of annual increase in internationally collaborated publications is almost double that of domestic collaborations (8.4% vs 4.9%), but most of the top scholarly collaborations remain between six countries only.