bluuebunny/crossref_metadata_2025_split huggingface dataset:
Osteointegration of functionalised high-performance oxide ceramics: imaging from micro-computed tomography
Authors: Migliorini Filippo , Eschweiler Jörg , Betsch Marcel , Maffulli Nicola , Tingart Markus , Hildebrand Frank , Lecouturier Sophie , Rath Björn , Schenker Hanno 
Published: July 2024

Abstract
Background
This study evaluated the osseointegration potential of functionalised high-performance oxide ceramics (HPOC) in isolation or coated with BMP-2 or RGD peptides in 36 New Zeeland female rabbits using micro-computed tomography (micro CT). The primary outcomes of interest were to assess the amount of ossification evaluating the improvement in the bone volume/ total volume (BV/TV) ratio and trabecular thickness at 6 and 12 weeks. The second outcome of interest was to investigate possible differences in osteointegration between the functionalised silanised HPOC in isolation or coated with Bone Morphogenetic Protein 2 (BMP-2) or RGD peptides.

Methods
36 adult female New Zealand white rabbits with a minimum weight of three kg were used. One-third of HPOCs were functionalised with silicon suboxide (SiOx), a third with BMP-2 (sHPOC-BMP2), and another third with RGD (sHPOC-RGD). All samples were scanned with a high-resolution micro CT (U-CTHR, MILabs B.V., Houten, The Netherlands) with a reconstructed voxel resolution of 10 µm. MicroCT scans were reconstructed in three planes and processed using Imalytics Preclinical version 2.1 (Gremse-IT GmbH, Aachen, Germany) software. The total volume (TV), bone volume (BV) and ratio BV/TV were calculated within the coating area.

Results
BV/TV increased significantly from 6 to 12 weeks in all HPOCs: silanised (P = 0.01), BMP-2 (P < 0.0001), and RGD (P < 0.0001) groups. At 12 weeks, the BMP-2 groups demonstrated greater ossification in the RGD (P < 0.0001) and silanised (P = 0.008) groups. Trabecular thickness increased significantly from 6 to 12 weeks (P < 0.0001). At 12 weeks, BMP-2 promoted greater trabecular thickness compared to the silanised group (P = 0.07), although no difference was found with the RGD (P = 0.1) group.

Conclusion
Sinalised HPOC in isolation or functionalised with BMP-2 or RGD promotes in vivo osteointegration. The sinalised HOPC functionalised with BMP-2 demonstrated the greatest osseointegration.
Global health diplomacy in humanitarian action
Authors: Falqui Luca , Li Fangfang , Xue Yufeng 
Published: July 2024

AbstractThis commentary explores the intersection of Global Health Diplomacy (GHD) and humanitarian action within Fragility, Conflict, and Violence (FCV) contexts. It aims at addressing the multifaceted challenges faced by communities living in these environments, where a convergence of multiple factors, including over 110 active armed conflicts, creates complex emergencies impact on large populations globally. This commentary holds three primary significances: 1) it scrutinizes the profound and enduring health consequences of major humanitarian crises on last-mile populations, highlighting the pivotal role of health diplomacy for better navigating humanitarian challenges; 2) it advocates for a paradigm shift in humanitarian approaches, recognizing GHD’s potential in shaping international cooperation, building consensus on inclusive global health policies, and enabling more effective interventions; 3) it underscores the operational impact of health diplomacy, both at diplomatic tables and on the frontlines of humanitarian efforts. Through real-world cases such as the cholera outbreak in Yemen and the response to Ebola outbreaks in DRC, the paper illustrates how diplomatic dialogue can impact health outcomes in fragile settings.
The cross-talk between the macro and micro-environment in precursor lesions of pancreatic cancer leads to new and promising circulating biomarkers
Authors: Mottini Carla , Auciello Francesca Romana , Manni Isabella , Pilarsky Christian , Caputo Damiano , Caracciolo Giulio , Rossetta Alessandro , Di Gennaro Elena , Budillon Alfredo , Blandino Giovanni , Roca Maria Serena , Piaggio Giulia 
Published: July 2024

AbstractPancreatic cancer (PC) is a clinically challenging tumor to combat due to its advanced stage at diagnosis as well as its resistance to currently available therapies. The absence of early symptoms and known detectable biomarkers renders this disease incredibly difficult to detect/manage. Recent advances in the understanding of PC biology have highlighted the importance of cancer-immune cell interactions, not only in the tumor micro-environment but also in distant systemic sites, like the bone marrow, spleen and circulating immune cells, the so-called macro-environment. The response of the macro-environment is emerging as a determining factor in tumor development by contributing to the formation of an increasingly immunogenic micro-environment promoting tumor homeostasis and progression. We will summarize the key events associated with the feedback loop between thetumorimmunemicro-environment (TIME) and thetumorimmunemacroenvironment (TIMaE) in pancreatic precancerous lesions along with how it regulates disease development and progression. In addition, liquid biopsy biomarkers capable of diagnosing PC at an early stage of onset will also be discussed. A clearer understanding of the early crosstalk between micro-environment and macro-environment could contribute to identifying new molecular therapeutic targets and biomarkers, consequently improving early PC diagnosis and treatment.
Enzymatic hydrolysis of waste streams originating from wastewater treatment plants
Authors: Zarina Ruta , Mezule Linda 
Published: July 2024

Abstract
Background
Achieving climate neutrality is a goal that calls for action in all sectors. The requirements for improving waste management and reducing carbon emissions from the energy sector present an opportunity for wastewater treatment plants (WWTPs) to introduce sustainable waste treatment practices. A common biotechnological approach for waste valorization is the production of sugars from lignocellulosic waste biomass via biological hydrolysis. WWTPs produce waste streams such as sewage sludge and screenings which have not yet been fully explored as feedstocks for sugar production yet are promising because of their carbohydrate content and the lack of lignin structures. This study aims to explore the enzymatic hydrolysis of various waste streams originating from WWTPs by using a laboratory-made and a commercial cellulolytic enzyme cocktail for the production of sugars. Additionally, the impact of lipid and protein recovery from sewage sludge prior to the hydrolysis was assessed.

Results
Treatment with a laboratory-made enzyme cocktail produced by Irpex lacteus (IL) produced 31.2 mg sugar per g dry wastewater screenings. A commercial enzyme formulation released 101 mg sugar per g dry screenings, corresponding to 90% degree of saccharification. There was an increase in sugar levels for all sewage substrates during the hydrolysis with IL enzyme. Lipid and protein recovery from primary and secondary sludge prior to the hydrolysis with IL enzyme was not advantageous in terms of sugar production.

Conclusions
The laboratory-made fungal IL enzyme showed its versatility and possible application beyond the typical lignocellulosic biomass. Wastewater screenings are well suited for valorization through sugar production by enzymatic hydrolysis. Saccharification of screenings represents a viable strategy to divert this waste stream from landfill and achieve the waste treatment and renewable energy targets set by the European Union. The investigation of lipid and protein recovery from sewage sludge showed the challenges of integrating resource recovery and saccharification processes.
A new magnetic resonance imaging-based PUMCH classification system for congenital cervical malformations: devising a standardised diagnosis pathway
Authors: Yuan Zhi-Lin , Ren Jing , Huang Meng-Lin , Qi Ya-Fei , Gao Xin , Sun Yi-Ying , He Yong-Lan , Zhu Lan , Xue Hua-Dan 
Published: July 2024

Abstract
Objectives
To develop an innovative magnetic resonance imaging (MRI)-based PUMCH (Peking Union Medical College Hospital) classification system aimed at standardising the diagnosis of congenital cervical malformations (CCMs) by identifying their distinctive MRI features.

Methods
Seventy-nine consecutive patients with CCM underwent pre-treatment pelvic MRI; three experienced gynaecological radiologists retrospectively analysed these images. Qualitative assessments included Rock et al’s classification; PUMCH classification; haematometra; cervical signal features; ovarian endometriosis; haematosalpinx; and uterine, vaginal, urinary, and musculoskeletal malformations. Quantitative assessments involved the uterine volume, sagittal cervical length, and maximum ovarian cross-sectional area. The surgical treatment types were also recorded. Statistical methods were used to incorporate differences in clinical features and surgical methods into our classification.

Results
Morphologically, CCMs were categorised into three types: type I (53%) was characterised by the presence of a cervix with visible cervical canals; type II (23%) featured an existing cervix with concealed cervical canals; and type III (24%) indicated cervical aplasia, which involves a blind end in the lower part of the uterine corpus. Haematometra was significantly more prevalent in patients with type I CCM than in those with type II (p < 0.001). There were three cervical signal patterns: no signal (27%), no evident layer differentiation (21%), and multi-layer differentiation with haematocele (52%). Most patients (94%) had complete vaginal atresia. Type I CCM patients had a higher likelihood of regaining normal uterovaginal anatomy compared to types II and III.

Conclusions
Our proposed PUMCH classification system has a high potential for enhancing the efficiency of clinical diagnosis among patients with CCM.

Critical relevance statement
The proposed new PUMCH classification promised to elevate the conventional diagnostic trajectory for congenital cervical malformations, offering a valuable framework to refine the selection and planning of surgical interventions, thereby enhancing overall clinical efficacy.

Key Points

Effective classification of congenital cervical malformations is desirable to optimise the diagnostic process.

We presented a PUMCH classification of congenital cervical malformations using pelvic MRI.

The new classification significantly aids clinical triage for congenital cervical malformations.

Graphical Abstract
Benign and malignant focal liver lesions displaying rim arterial phase hyperenhancement on CT and MRI
Authors: Matteini Francesco , Cannella Roberto , Garzelli Lorenzo , Dioguardi Burgio Marco , Sartoris Riccardo , Brancatelli Giuseppe , Vilgrain Valérie , Ronot Maxime , Vernuccio Federica 
Published: July 2024

Abstract
Rim arterial phase hyperenhancement is an imaging feature commonly encountered on contrast-enhanced CT and MRI in focal liver lesions. Rim arterial phase hyperenhancement is a subtype of arterial phase hyperenhancement mainly present at the periphery of lesions on the arterial phase. It is caused by a relative arterialization of the periphery compared with the center of the lesion and needs to be differentiated from other patterns of peripheral enhancement, including the peripheral discontinuous nodular enhancement and the corona enhancement. Rim arterial phase hyperenhancement may be a typical or an atypical imaging presentation of many benign and malignant focal liver lesions, challenging the radiologists during imaging interpretation. Benign focal liver lesions that may show rim arterial phase hyperenhancement may have a vascular, infectious, or inflammatory origin. Malignant focal liver lesions displaying rim arterial phase hyperenhancement may have a vascular, hepatocellular, biliary, lymphoid, or secondary origin. The differences in imaging characteristics on contrast-enhanced CT may be subtle, and a multiparametric approach on MRI may be helpful to narrow the list of differentials. This article aims to review the broad spectrum of focal liver lesions that may show rim arterial phase hyperenhancement, using an approach based on the benign and malignant nature of lesions and their histologic origin.

Critical relevance statement
Rim arterial phase hyperenhancement may be an imaging feature encountered in benign and malignant focal liver lesions and the diagnostic algorithm approach provided in this educational review may guide toward the final diagnosis.

Key Points

Several focal liver lesions may demonstrate rim arterial phase hyperenhancement.

Rim arterial phase hyperenhancement may occur in vascular, inflammatory, and neoplastic lesions.

Rim arterial phase hyperenhancement may challenge radiologists during image interpretation.

Graphical Abstract
Optimization strategies for mesenchymal stem cell-based analgesia therapy: a promising therapy for pain management
Authors: Zhang Jing , Wu Ping , Wen Qingping 
Published: July 2024

AbstractPain is a very common and complex medical problem that has a serious impact on individuals’ physical and mental health as well as society. Non-steroidal anti-inflammatory drugs and opioids are currently the main drugs used for pain management, but they are not effective in controlling all types of pain, and their long-term use can cause adverse effects that significantly impair patients’ quality of life. Mesenchymal stem cells (MSCs) have shown great potential in pain treatment. However, limitations such as the low proliferation rate of MSCs in vitro and low survival rate in vivo restrict their analgesic efficacy and clinical translation. In recent years, researchers have explored various innovative approaches to improve the therapeutic effectiveness of MSCs in pain treatment. This article reviews the latest research progress of MSCs in pain treatment, with a focus on methods to enhance the analgesic efficacy of MSCs, including engineering strategies to optimize the in vitro culture environment of MSCs and to improve the in vivo delivery efficiency of MSCs. We also discuss the unresolved issues to be explored in future MSCs and pain research and the challenges faced by the clinical translation of MSC therapy, aiming to promote the optimization and clinical translation of MSC-based analgesia therapy.
Graphical Abstract
Mesenchymal stem cells-derived extracellular vesicles ameliorate lupus nephritis by regulating T and B cell responses
Authors: Li Cuifang , Wu Feifeng , Mao Jueyi , Wang Yang , Zhu Junquan , Hong Kimsor , Xie Haotian , Zhou Xin , Tian Jidong , Wen Chuan 
Published: July 2024

Abstract
Background
Human umbilical cord mesenchymal stem cells-derived extracellular vesicles (hUCMSC-EVs) have potent immunomodulatory properties similar to parent cells. This study investigated the therapeutic effects and immunomodulatory mechanisms of hUCMSC-EVs in an experimental lupus nephritis model.

Methods
The hUCMSC-EVs were isolated by using differential ultracentrifugation. In vivo, the therapeutic effects of hUCMSC-EVs in lupus-prone MRL/lpr mice were investigated, and the mechanisms of treatment were explored according to the abnormal T and B cell responses among both the spleen and kidney.

Results
MRL/lpr mice treated with hUCMSC-EVs reduced proteinuria extent, serum creatinine and renal pathological damage; decreased splenic index and serum anti-dsDNA IgG level; and improved survival rate. hUCMSC-EVs lowered the percentage of T helper (Th)1 cells, double-negative T (DNT) cells, and plasma cells among splenocytes; inhibited the infiltration of Th17 cells but promoted regulatory T (Treg) cells in the kidney, followed by a reduction in pro-inflammatory cytokine levels(IFN-γ, IL-2, IL-6, IL-21, and IL-17 A). In addition, hUCMSC-EVs inhibited the activation of STAT3 and down-regulated IL-17 A protein levels in the kidney.

Conclusion
The results of this study demonstrated that hUCMSC-EVs had therapeutic effects on experimental lupus nephritis (LN) by regulating Th1/Th17/Treg imbalance and inhibiting DNT and plasma cells. Additionally, hUCMSC-EVs inhibited Th17 cell differentiation in kidney by regulating the IL-6/STAT3/IL-17 signal pathway, which might be an important mechanism for alleviating renal injury. Taken together, we demonstrated that hUCMSC-EVs regulating T and B cell immune responses might represent a novel mechanism of hUCMSCs in treating LN, thus providing a new strategy for treating LN.
[68Ga]Ga-FAPI versus 2-[18F]FDG PET/CT in patients with autoimmune thyroiditis: a case control study
Authors: Pabst Kim M. , Kessler Lukas , Ferdinandus Justin , Hamacher Rainer , Bartel Timo , Siveke Jens T. , Nader Michael , Brandenburg Tim , Desaulniers Mélanie , Herrmann Ken , Fendler Wolfgang P. 
Published: July 2024

Abstract
Purpose
Radiolabelled fibroblast activation protein inhibitors (FAPIs) are becoming increasingly important for imaging various tumour diseases. However, it is essential to be aware of potential pitfalls. Here, we investigate FAP expression in the thyroid gland in autoimmune thyroiditis (AIT).

Methods
AIT patients with pathological thyroid uptake on [68Ga]Ga-FAPI PET were compared with glucose metabolism on 2-[18F]FDG PET in terms of SUVmax/SUVpeak/SUVmean/tissue-to-background ratio (TBR), and with a healthy control group.

Results
Between September 2019 and July 2021, 6 patients presented with a visually increased thyroid uptake and TBR on [68Ga]Ga-FAPI PET. In the retrospective clinical work-up, all patients had known or newly diagnosed AIT. Compared to a matched healthy control group, FAP expression and glucose metabolism were significantly increased ([68Ga]Ga-FAPI (SUVpeak): 7.0 vs. 1.7; p = 0.004/(TBRbloodpool): 6.8 vs. 1.7; p = 0.002; 2-[18F]FDG (SUVpeak): 3.9 vs. 1.4; p = 0.004/(TBRbloodpool): 4.0 vs. 1.2; p = 0.041). However, there was no significant difference in median uptake between [68Ga]Ga-FAPI and 2-[18F]FDG PET (SUVpeak: 7.3 vs. 5.6; p = 0.104).

Conclusion
Patients with AIT show higher thyroid uptake on [68Ga]Ga-FAPI and 2-[18F]FDG PET. Incidental thyroid uptake is another pitfall in the interpretation of [68Ga]Ga-FAPI PET and should prompt a clinical work-up.
Has China’s hierarchical medical system improved doctor-patient relationships?
Authors: Gao Yang , Yang Yang , Wang Shoupeng , Zhang Wenqian , Lu Jiao 
Published: July 2024

Abstract
Background and objective
Developing harmonious doctor-patient relationships is a powerful way to promote the construction of a new pattern of medical reform in developing countries. We aim to analyze the effects of China’s hierarchical medical system on doctor-patient relationships, thus contributing to China’s medical and health system reform.

Methods
With panel data on prefectural-level cities in China from 2012 to 2019, we used a time-varying difference-in-differences model to evaluate the effect of hierarchical medical treatment policy.

Results
Hierarchical medical treatment policies can significantly improve doctor-patient relationships, and this conclusion is supported by various robustness tests. And improving doctor-patient relationships can be indirectly realized by the optimization of resource allocation and saving of medical costs. In addition, the marginal effect of the pilot policy on doctor-patient relationships decreased with age within the city population. In focal cities and cities with high levels of fiscal spending on health care, the effect of the pilot policy on doctor-patient relationships was stronger.

Conclusion
While reinforcing the literature on the doctor-patient relationship, this study also provides a reference for further exploration of the pilot policy of hierarchical medical treatment and the development of new medical and health system reform in developing countries.
Integrative analysis of bulk and single-cell RNA sequencing reveals the gene expression profile and the critical signaling pathways of type II CPAM
Authors: Li Fengxia , Tan Zheng , Chen Hongyu , Gao Yue , Xia Jie , Huang Ting , Liang Liang , Zhang Jian , Zhang Xianghong , Shi Xucong , Chen Qiang , Shu Qiang , Yu Lan 
Published: July 2024

Abstract
Backgroud
Type II congenital pulmonary airway malformation (CPAM) is a rare pulmonary microcystic developmental malformation. Surgical excision is the primary treatment for CPAM, although maternal steroids and betamethasone have proven effective in reducing microcystic CPAM. Disturbed intercellular communication may contribute to the development of CPAM. This study aims to investigate the expression profile and analyze intercellular communication networks to identify genes potentially associated with type II CPAM pathogenesis and therapeutic targets.

Methods
RNA sequencing (RNA-seq) was performed on samples extracted from both the cystic area and the adjacent normal tissue post-surgery in CPAM patients. Iterative weighted gene correlation network analysis (iWGCNA) was used to identify genes specifically expressed in type II CPAM. Single-cell RNA-seq (scRNA-seq) was integrated to unveil the heterogeneity in cell populations and analyze the communication and interaction within epithelial cell sub-populations.

Results
A total of 2,618 differentially expressed genes were identified, primarily enriched in cilium-related biological process and inflammatory response process. Key genes such as EDN1, GPR17, FPR2, and CHRM1, involved in the G protein-coupled receptor (GPCR) signaling pathway and playing roles in cell differentiation, apoptosis, calcium homeostasis, and the immune response, were highlighted based on the protein-protein interaction network. Type II CPAM-associated modules, including ciliary function-related genes, were identified using iWGCNA. By integrating scRNA-seq data, AGR3 (related to calcium homeostasis) and SLC11A1 (immune related) were identified as the only two differently expressed genes in epithelial cells of CPAM. Cell communication analysis revealed that alveolar type 1 (AT1) and alveolar type 2 (AT2) cells were the predominant communication cells for outgoing and incoming signals in epithelial cells. The ligands and receptors between epithelial cell subtypes included COLLAGEN genes enriched in PI3K-AKT singaling and involved in epithelial to mesenchymal transition.

Conclusions
In summary, by integrating bulk RNA-seq data of type II CPAM with scRNA-seq data, the gene expression profile and critical signaling pathways such as GPCR signaling and PI3K-AKT signaling pathways were revealed. Abnormally expressed genes in these pathways may disrupt epithelial-mesenchymal transition and contribute to the development of CPAM. Given the effectiveness of prenatal treatments of microcystic CPAM using maternal steroids and maternal betamethasone administration, targeting the genes and signaling pathways involved in the development of CPAM presents a promising therapeutic strategy.