bluuebunny/crossref_metadata_2025 huggingface dataset:
The unequivocal case for net zero green growth
Authors: Fankhauser Sam
Published: November 2024

This paper makes the case for net zero (or, more broadly, green) growth. It argues that net zero green growth is the most realistic strategy for halting global warming and meeting the objectives of the Paris Agreement. Net zero growth is feasible technologically, economically and behaviourally. Credible decarbonisation paths have been modelled and the leading countries have already broken the link between emissions and gross domestic product. Green growth, which emphasises economic opportunities, is the best way to mobilise the clean innovation and investment that net zero requires, and it is the best strategy to secure public support for rapid decarbonisation.
Extracellular vesicles from microglial cells activated by abnormal heparan sulfate oligosaccharides from Sanfilippo patients impair neuronal dendritic arborization
Authors: Dias Chloé , Ballout Nissrine , Morla Guillaume , Alileche Katia , Santiago Christophe , Guerrera Ida Chiara , Chaubet Adeline , Ausseil Jerome , Trudel Stephanie
Published: November 2024

Background

In mucopolysaccharidosis type III (MPS III, also known as Sanfilippo syndrome), a pediatric neurodegenerative disorder, accumulation of abnormal glycosaminoglycans (GAGs) induces severe neuroinflammation by triggering the microglial pro-inflammatory cytokines production via a TLR4-dependent pathway. But the extent of the microglia contribution to the MPS III neuropathology remains unclear. Extracellular vesicles (EVs) mediate intercellular communication and are known to participate in the pathogenesis of adult neurodegenerative diseases. However, characterization of the molecular profiles of EVs released by MPS III microglia and their effects on neuronal functions have not been described.

Methods

Here, we isolated EVs secreted by the microglial cells after treatment with GAGs purified from urines of Sanfilippo patients (sfGAGs-EVs) or from age-matched healthy subjects (nGAGs-EVs) to explore the EVs’ proteins and small RNA profiles using LC–MS/MS and RNA sequencing. We next performed a functional assay by immunofluorescence following nGAGs- or sfGAGs-EVs uptake by WT primary cortical neurons and analyzed their extensions metrics after staining of βIII-tubulin and MAP2 by confocal microscopy.

Results

Functional enrichment analysis for both proteomics and RNA sequencing data from sfGAGs-EVs revealed a specific content involved in neuroinflammation and neurodevelopment pathways. Treatment of cortical neurons with sfGAGs-EVs induced a disease-associated phenotype demonstrated by a lower total neurite surface area, an impaired somatodendritic compartment, and a higher number of immature dendritic spines.

Conclusions

This study shows, for the first time, that GAGs from patients with Sanfilippo syndrome can induce microglial secretion of EVs that deliver a specific molecular message to recipient naive neurons, while promoting the neuroinflammation, and depriving neurons of neurodevelopmental factors. This work provides a framework for further studies of biomarkers to evaluate efficiency of emerging therapies.

Graphical Abstract
Reduction of neck pain severity in patients with medication-overuse headache
Authors: Hong Yooha , Park Hong-Kyun , Kang Mi-Kyoung , Oh Sun-Young , Kang Jin-Ju , Moon Heui-Soo , Song Tae-Jin , Lee Mi Ji , Chu Min Kyung , Cho Soo-Jin
Published: November 2024

Background

Neck pain and primary headache disorders are highly prevalent in populations and clinical cohorts. Medication-overuse headache (MOH) is a treatable secondary headache, mainly developing in migraine sufferers, that accounts for the majority of patients presenting to headache clinics. Nevertheless, the association between neck pain and MOH has not been reported. This study evaluated the prevalence and clinical course of neck pain in patients with MOH before and after MOH treatment.

Methods

We analyzed 635 MOH patients enrolled in a nationwide, prospective, multicenter MOH registry. Demographics and clinical data were collected at baseline and 3 months to evaluate changes in the status and severity of neck pain and headache. Severity of neck pain was graded into 4 groups, and severe neck pain was defined as grade 3 or 4.

Results

Among 635 patients with MOH, 366 (57.6%) reported neck pain at baseline. MOH patients with neck pain had an earlier onset of their primary headache disorder (23.4 ± 12.7 vs. 26.2 ± 13.3 years, p = 0.007). Although monthly headache days were comparable between the patients with neck pain and those without neck pain, the neck pain group had higher levels of anxiety (7.4 ± 5.8 vs. 6.4 ± 5.4, p = 0.017), more severe cutaneous allodynia (2.4 ± 3.3 vs. 1.8 ± 3.0, p = 0.038), and poorer quality of life (171.7 ± 70.4 vs. 184.0 ± 68.9, p = 0.029). At 3 months, 456 (71.8%) were followed-up, and 257 (56.4%) were recovered from MOH. Compared to the baseline, the proportion of severe neck pain (40.4% vs. 19.4%, p < 0.001) was decreased. The proportion of severe neck pain was much lower in patients with recovery from MOH compared to those without (4.7% vs. 15.1%, p < 0.001).

Conclusions

Neck pain in MOH patients was associated with earlier onset of headache, higher levels of anxiety and allodynia, and poorer quality of life. Improvement in neck pain improvement was linked to recovery from MOH. These findings suggest the potential importance of integrating and management of neck pain into clinical practice for MOH.
PangeBlocks: customized construction of pangenome graphs via maximal blocks
Authors: Avila Cartes Jorge , Bonizzoni Paola , Ciccolella Simone , Della Vedova Gianluca , Denti Luca
Published: November 2024

Background

The construction of a pangenome graph is a fundamental task in pangenomics. A natural theoretical question is how to formalize the computational problem of building an optimal pangenome graph, making explicit the underlying optimization criterion and the set of feasible solutions. Current approaches build a pangenome graph with some heuristics, without assuming some explicit optimization criteria. Thus it is unclear how a specific optimization criterion affects the graph topology and downstream analysis, like read mapping and variant calling.

Results

In this paper, by leveraging the notion of maximal block in a Multiple Sequence Alignment (MSA), we reframe the pangenome graph construction problem as an exact cover problem on blocks called Minimum Weighted Block Cover (MWBC). Then we propose an Integer Linear Programming (ILP) formulation for the MWBC problem that allows us to study the most natural objective functions for building a graph. We provide an implementation of the ILP approach for solving the MWBC and we evaluate it on SARS-CoV-2 complete genomes, showing how different objective functions lead to pangenome graphs that have different properties, hinting that the specific downstream task can drive the graph construction phase.

Conclusion

We show that a customized construction of a pangenome graph based on selecting objective functions has a direct impact on the resulting graphs. In particular, our formalization of the MWBC problem, based on finding an optimal subset of blocks covering an MSA, paves the way to novel practical approaches to graph representations of an MSA where the user can guide the construction.
Postnatal care after gestational diabetes – a systematic review of clinical practice guidelines
Authors: Ohene-Agyei Phyllis , Iqbal Ariba , Harding Jane E. , Crowther Caroline A. , Lin Luling
Published: November 2024

Background

Gestational diabetes mellitus (GDM) is the most common metabolic disorder in pregnancy and later is associated with an increased risk of type 2 diabetes and other metabolic disorders. Consistent and evidence based postnatal care is key to improving maternal long-term health. We therefore aimed to review and compare recommendations of national and international clinical practice guidelines (CPG) for postnatal care after GDM and identify any evidence gaps in recommendations needing further research.

Methods

We searched five databases and forty professional organization websites for CPGs providing recommendations for postnatal care after GDM. CPGs which had full versions in English, endorsed, prepared, or authorized by a professional body, and published between 2013 and 2023 were eligible for inclusion. Two reviewers independently screened the articles, extracted the recommendations, and appraised the included CPGs using the Appraisal of Guidelines, Research, and Evaluation (AGREE) II tool.

Results

Twenty-six CPGs from 22 countries were included. Twelve CPGs (46%) were appraised as low quality with the lowest scoring domains being rigor of development and editorial independence. We found little high certainty evidence for most recommendations and few recommendations were made for maternal mental health and postpartum metabolic screening. Evidence gaps pertained to postpartum glucose screening, including frequency, tests, and ways to improve uptake, evaluation of effective uptake of lifestyle interventions, and ongoing long-term follow up care.

Conclusions

Most of the postnatal care recommendations in GDM guidelines are not based on high certainty evidence. Further efforts are needed to improve the global evidence base for postnatal care after GDM to improve long-term maternal health.

Protocol Registration

This review was registered in PROSEPRO (CRD42023454900).
Osteosarcoma cells depend on MCL-1 for survival, and osteosarcoma metastases respond to MCL-1 antagonism plus regorafenib in vivo
Authors: Ji Yanhao , Harris Michael A. , Newton Lucas M. , Harris Tiffany J. , Fairlie W. Douglas , Lee Erinna F. , Hawkins Christine J.
Published: November 2024

Osteosarcoma is the most common form of primary bone cancer, which primarily afflicts children and adolescents. Chemotherapy, consisting of doxorubicin, cisplatin and methotrexate (MAP) increased the 5-year osteosarcoma survival rate from 20% to approximately 60% by the 1980s. However, osteosarcoma survival rates have remained stagnant for several decades. Patients whose disease fails to respond to MAP receive second-line treatments such as etoposide and, in more recent years, the kinase inhibitor regorafenib. BCL-2 and its close relatives enforce cellular survival and have been implicated in the development and progression of various cancer types. BH3-mimetics antagonize pro-survival members of the BCL-2 family to directly stimulate apoptosis. These drugs have been proven to be efficacious in other cancer types, but their use in osteosarcoma has been relatively unexplored to date. We investigated the potential efficacy of BH3-mimetics against osteosarcoma cells in vitro and examined their cooperation with regorafenib in vivo. We demonstrated that osteosarcoma cell lines could be killed through inhibition of MCL-1 combined with BCL-2 or BCL-xL antagonism. Inhibition of MCL-1 also sensitized osteosarcoma cells to killing by second-line osteosarcoma treatments, particularly regorafenib. Importantly, we found that inhibition of MCL-1 with the BH3-mimetic S63845 combined with regorafenib significantly prolonged the survival of mice bearing pulmonary osteosarcoma metastases. Together, our results highlight the importance of MCL-1 in osteosarcoma cell survival and present a potential therapeutic avenue that may improve metastatic osteosarcoma patient outcomes.
Expected benefits and concerns regarding virtual reality in caring for terminally ill cancer patients – a qualitative interview study
Authors: Greinacher Anja , Alt-Epping Bernd , Gerlach Christina , Wrzus Cornelia
Published: November 2024

Background

Many palliative cancer patients require inpatient hospital treatment for medical reasons, which contrasts their frequent desire to be at home. Virtual reality (VR) could be a way of bringing the home environment closer to them. First observations have shown benefits from VR for inpatients in palliative care. The aim of this qualitative, descriptive study was to explore the expectations of in-patients suffering from incurable cancer and their relatives about VR, in particular individualized VR images of the patients’ own home.

Methods

Semi-structured interviews with inpatients suffering from incurable cancers and their relatives in three medical settings (palliative care, hematology, radiotherapy) of a German university hospital. Qualitative content analysis about expected benefits and concerns regarding VR-videos showing their private home; defining the main topics deductively and the subcategories inductively. We also assessed the patients’ subjective perspective on their remaining time to live to estimate the impact of double awareness on the results. The Patient Advisory Board informed the study protocol and conduct.

Results

We interviewed 15 patients (8 men; age M = 63.4, SD = 11.34; range 39–82) under palliative care, and four relatives. We organized the interview content in 6 themes (general interest, desired content, non-desired content, expected benefits, concerns, and irregularities) and 26 sub-themes. Most patients and relatives were interested in using VR during hospital treatment. They often preferred viewing nature or tourist sites over seeing their home or family. Reasons could be linked to privacy concerns and the general desire for distraction from the current situation that they specified with their expectation of well-being, a break from the patient-experience, the pursue of curiosity, and the VR evoking fond memories.

Conclusion

VR seems to be of interest for palliative cancer patients, especially as distraction and relief from their illness. The desired content can be very different, so a choice from a selection of VR-content should be made available. If patients want to see videos of their own home, recordings by relatives instead of study or hospital staff seem to meet the need for privacy.

Trial registration

Registered at Deutsches Register Klinischer Studien; registration number: DRKS00032172; registration date: 11/07/2023. https://drks.de/search/de/trial/DRKS00032172.
A powerful and versatile new fixation protocol for immunostaining and in situ hybridization that preserves delicate tissues
Authors: Guerrero-Hernández Carlos , Doddihal Viraj , Mann Frederick G. , Sánchez Alvarado Alejandro
Published: November 2024

Background

Understanding how genes function to heal wounds and restore lost tissue is essential for studying regeneration. Whole-mount in situ hybridization (WISH) is a powerful and widely used technique to visualize the expression patterns of genes in different biological systems. Yet, existing methods to permeabilize samples for WISH can damage or destroy fragile regenerating tissues, thereby preventing such experiments.

Results

Here, we describe a new protocol for in situ hybridization (ISH) and immunostaining in the highly regenerative planarian Schmidtea mediterranea. This new Nitric Acid/Formic Acid (NAFA) protocol is compatible with both the assays and prevents degradation of the epidermis and regeneration blastema. The NAFA protocol achieves this without the use of proteinase K digestion which likely leads to better preservation of antigen epitopes. We show that the NAFA protocol successfully permits development of chromogenic and fluorescent signals in situ, while preserving the anatomy of the animal. Furthermore, the immunostaining of different proteins was compatible with the NAFA protocol following fluorescent in situ hybridization. Additionally, the tissue fixation protocol was easily adapted for regenerating killifish tail fin, which yielded better ISH signal with minimal background.

Conclusions

Thus, the NAFA protocol robustly preserves the delicate wounded tissues while also facilitating probe and antibody penetration into internal tissues. Furthermore, the fixation protocol is compatible for WISH on regenerating teleost fins suggesting that it will be a valuable technique for studying the processes of wounding response and regeneration in multiple species.
Dental pulp mesenchymal stem cell (DPSCs)-derived soluble factors, produced under hypoxic conditions, support angiogenesis via endothelial cell activation and generation of M2-like macrophages
Authors: Barone Ludovica , Cucchiara Martina , Palano Maria Teresa , Bassani Barbara , Gallazzi Matteo , Rossi Federica , Raspanti Mario , Zecca Piero Antonio , De Antoni Gianluca , Pagiatakis Christina , Papait Roberto , Bernardini Giovanni , Bruno Antonino , Gornati Rosalba
Published: November 2024

Background

Cell therapy has emerged as a revolutionary tool to repair damaged tissues by restoration of an adequate vasculature. Dental Pulp stem cells (DPSC), due to their easy biological access, ex vivo properties, and ability to support angiogenesis have been largely explored in regenerative medicine.

Methods

Here, we tested the capability of Dental Pulp Stem Cell-Conditioned medium (DPSC-CM), produced in normoxic (DPSC-CM Normox) or hypoxic (DPSC-CM Hypox) conditions, to support angiogenesis via their soluble factors. CMs were characterized by a secretome protein array, then used for in vivo and in vitro experiments. In in vivo experiments, DPSC-CMs were associated to an Ultimatrix sponge and injected in nude mice. After excision, Ultimatrix were assayed by immunohistochemistry, electron microscopy and flow cytometry, to evaluate the presence of endothelial, stromal, and immune cells.

For in vitro procedures, DPSC-CMs were used on human umbilical-vein endothelial cells (HUVECs), to test their effects on cell adhesion, migration, tube formation, and on their capability to recruit human CD14+ monocytes.

Results

We found that DPSC-CM Hypox exert stronger pro-angiogenic activities, compared with DPSC-CM Normox, by increasing the frequency of CD31+ endothelial cells, the number of vessels and hemoglobin content in the Ultimatrix sponges. We observed that Utimatrix sponges associated with DPSC-CM Hypox or DPSC-CM Normox shared similar capability to recruit CD45− stromal cells, CD45+ leukocytes, F4/80+ macrophages, CD80+ M1-macrophages and CD206+ M2-macropages. We also observed that DPSC-CM Hypox and DPSC-CM Normox have similar capabilities to support HUVEC adhesion, migration, induction of a pro-angiogenic gene signature and the generation of capillary-like structures, together with the ability to recruit human CD14+ monocytes.

Conclusions

Our results provide evidence that DPSCs-CM, produced under hypoxic conditions, can be proposed as a tool able to support angiogenesis via macrophage polarization, suggesting its use to overcome the issues and restrictions associated with the use of staminal cells.
The molecular consequences of FOXF1 missense mutations associated with alveolar capillary dysplasia with misalignment of pulmonary veins
Authors: Edel G. G. , van Kempen M. , Munck A. Boerema-de , Huisman C. N. , Naalden C. A. P. , Brouwer R. W. W. , Koornneef S. , van IJcken W. F. J. , Wijnen R. M. H. , Rottier R. J.
Published: November 2024

Background

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACD/MPV) is a fatal congenital lung disorder strongly associated with genomic alterations in the Forkhead box F1 (FOXF1) gene and its regulatory region. However, little is known about how FOXF1 genomic alterations cause ACD/MPV and what molecular mechanisms are affected by these mutations. Therefore, the effect of ACD/MPV patient-specific mutations in the FOXF1 gene on the molecular function of FOXF1 was studied.

Methods

Epitope-tagged FOXF1 constructs containing one of the ACD/MPV-associated mutations were expressed in mammalian cell lines to study the effect of FOXF1 mutations on protein function. EMSA binding assays and luciferase assays were performed to study the effect on target gene binding and activation. Immunoprecipitation followed by SDS‒PAGE and western blotting were used to study protein‒protein interactions. Protein phosphorylation was studied using phos-tag western blotting.

Results

An overview of the localization of ACD/MPV-associated FOXF1 mutations revealed that the G91-S101 region was frequently mutated. A three-dimensional model of the forkhead DNA-binding domain of FOXF1 showed that the G91-S101 region consists of an α-helix and is predicted to be important for DNA binding. We showed that FOXF1 missense mutations in this region differentially affect the DNA binding of the FOXF1 protein and influence the transcriptional regulation of target genes depending on the location of the mutation. Furthermore, we showed that some of these mutations can affect the FOXF1 protein at the posttranscriptional level, as shown by altered phosphorylation by MST1 and MST2 kinases.

Conclusion

Missense mutations in the coding region of the FOXF1 gene alter the molecular function of the FOXF1 protein at multiple levels, such as phosphorylation, DNA binding and target gene activation. These results indicate that FOXF1 molecular pathways may be differentially affected in ACD/MPV patients carrying missense mutations in the DNA-binding domain and may explain the phenotypic heterogeneity of ACD/MPV.
Exploring paraptosis as a therapeutic approach in cancer treatment
Authors: Chang Ling-Chu , Chiang Shih-Kai , Chen Shuen-Ei , Hung Mien-Chie
Published: November 2024

A variety of cell death pathways play critical roles in the onset and progression of multiple diseases. Paraptosis, a unique form of programmed cell death, has gained significant attention in recent years. Unlike apoptosis and necrosis, paraptosis is characterized by cytoplasmic vacuolization, swelling of the endoplasmic reticulum and mitochondria, and the absence of caspase activation. Numerous natural products, synthetic compounds, and newly launched nanomedicines have been demonstrated to prime cell death through the paraptotic program and may offer novel therapeutic strategies for cancer treatment. This review summarizes recent findings, delineates the intricate network of signaling pathways underlying paraptosis, and discusses the potential therapeutic implications of targeting paraptosis in cancer treatment. The aim of this review is to expand our understanding of this unique cell death process and explore the potential therapeutic implications of targeting paraptosis in cancer treatment.
Efficacy of 8-week daclatasvir-sofosbuvir regimen in chronic hepatitis C: a systematic review and meta-analysis
Authors: Farrag Ahmed N. , Kamel Ahmed M.
Published: November 2024

Background

The high rates of the sustained virologic response 12 weeks after treatment (SVR12) in real world settings provoked the adoption of shortened courses of the costly direct-acting antivirals (DAAs) regimens. This study provides, to our knowledge, the first systematic review and meta-analysis for the efficacy of the shortened 8-week course of sofosbuvir (SOF) plus daclatasvir (DCV), the most accessible DAAs in the low-middle income countries (LMICs).

Methods

We performed a proportion meta-analysis to determine a reliable rate of SVR12 by pooling all studies that evaluated the results of the 8-week regimen of DCV + SOF. In addition, we applied sensitivity analyses using two imputation paradigms: a conservative approach, and a pragmatic approach to avoid overestimating the efficacy of the 8-week regimen in studies that followed a response-guided treatment (RGT) approach.

Results

Six studies with a total of 159 patients were included. The pooled SVR12 rate ranged from 91 to 97% in the included scenarios. The pragmatic scenario showed that the pooled SVR12 was 97% (95% confidence interval (CI) 91%; 100%) with lower variability as assessed by the prediction interval. The conservative approach revealed an SVR12 of 93% (95% CI 84%; 95%).

Conclusion

The 8-week course of 60 mg DCV with SOF provided a comparable SVR12 to the standard 12-week regimen in treatment-naïve, non-HIV co-infected patients with a minimum estimated efficacy of 90%.
Advanced presentation of cardiac hemangioma
Authors: Rattenni Francesco , Arlati Francesco Giuseppe , Galanti Andrea , Sansone Fabrizio , Clerici Alberto , Triggiani Michele , Muneretto Claudio
Published: November 2024

Cardiac hemangioma is a rare, benign vascular primary tumor. Clinical presentation is either asymptomatic or with symptoms due to its location and spatial interaction with adjacent structures. The authors present a case of right cardiac hemangioma whose clinical diagnosis was triggered by symptoms of anasarca status, hepatic damage with ascites, pleural effusion and right heart failure. The 79 years-old patient has been treated with complete resection of the tumor by means of cardiopulmonary bypass, without complications. The mid-term outcome (12 months) was favorable. The aim of this study is to report a case of cardiac hemangioma with relevant dimensions, in a rare location (tricuspid valve) with acute onset and interesting aspects of clinical presentation.
Whole-body MRI-based long-term evaluation of pediatric NF1 patients without initial tumor burden with evidence of newly developed peripheral nerve sheath tumors
Authors: Schmalhofer Marie-Lena , Farschtschi Said , Kluwe Lan , Mautner Victor Felix , Adam Gerhard , Well Lennart , Ristow Inka
Published: November 2024

Background

Patients with neurofibromatosis type 1 (NF1) can develop plexiform neurofibromas (PN). Large tumor burden is a predictor for the development of malignant peripheral nerve sheath tumors. Whole-body magnetic resonance imaging (WB-MRI) is the recommended imaging method for the evaluation of PN. WB-MRI is recommended for NF1 patients at transition from adolescence to adulthood. In the absence of internal PN further follow-up WB-MRI is not considered necessary. PN are often detected in early childhood, leading to the assumption that they may be congenital lesions. It remains unclear whether this invariably applies to all patients or whether patients who initially displayed no tumors can still develop PN over time. Therefore, we retrospectively reviewed WB-MRI scans of pediatric patients with NF1 without initial tumor burden and compared these with long-term follow-up scans for presence of newly developed PN.

Methods

We retrospectively reviewed WB-MRI scans of 17 NF1-children (twelve male; median age at initial scan: 9 [IQR 6.1–11.9] years) who initially displayed no PN. MRI scans with a follow-up interval of at least 6 years (median follow-up interval: 9 [IQR 5.6–12.4] years) were reviewed in consensus by two radiologists regarding the development of new PN over time.

Results

New PN were identified in two out of 17 children without initial tumor burden in follow-up examinations. One of these two patients developed two larger distinct PN of 4.5 cm on the right upper arm and of 2.5 cm on the left thoracic wall between the age of ten and twelve. The second child developed multiple smaller PN along the major peripheral nerves between the age of eleven and 16. In addition, 15 of the children without initial tumor burden did not develop any distinct tumors for a period of at least 6 years.

Conclusion

Our results indicate that PN can be newly detected in pediatric patients over time, even if no PN were detected on initial MRI scans. Therefore, it seems reasonable to perform at least a second MRI in pediatric NF1 patients at transition to adulthood, even if they did not display any tumor burden on initial MRI, and when the MRI was performed significantly under the age of 18. With this approach, tumors that may have developed between scans can be detected and patients at risk for complications can be identified.
Pre-hospital care for children: a descriptive study from Central Norway
Authors: Myhre Martine , Eide Næss Lars , Skogvoll Eirik , Haugland Helge
Published: November 2024

Background

Pre-hospital incidents involving pediatric and neonatal patients are infrequent, and clinical characteristics and care for these patients differ from the adult population. Lack of knowledge, guidelines, and experience can make pre-hospital pediatric care challenging, and there is limited research on the epidemiology and best practice of care for this population. We examined the pre-hospital pediatric population in the county of Sør-Trøndelag, Norway, to improve our understanding of this population in our region.

Methods

We conducted a retrospective observational cohort study of emergency incidents involving children under twelve years of age with dispatch of Emergency Medical Services (EMS) in Sør-Trøndelag between 2018 and 2022. Incidents and patient characteristics were extracted from the Emergency Medical Communication Center (EMCC) database. In addition, data on patient characteristics and interventions for more serious incidents seen by the Helicopter Emergency Medical Service (HEMS) were included from the database LABAS. We provided descriptive statistics and estimated population incidences using Poisson regression.

Results

The catchment area of EMCC Sør-Trøndelag has a population of approximately 43,000 children under the age of twelve years. During the five-year study period, there were 7005 emergency calls concerning this patient population, representing 6% of all emergency calls (total no. 108,717). Of these, 3500 (50%) resulted in the dispatch of an ambulance and/or HEMS, yielding an annual incidence of EMS dispatches of 17 per 1000 children. The three most common primary medical problems were respiratory distress, altered consciousness, and trauma. Among the 309 HEMS patients, 131 (42%) received advanced interventions from the HEMS physician. Assisted ventilation was the most frequent intervention.

Conclusions

Pediatric and neonatal patients make up a small proportion of pre-hospital patient dispatches in Sør-Trøndelag. Consequently, each EMS provider infrequently encounters children in the pre-hospital environment, resulting in less experience with pediatric advanced medical interventions. This study identifies some clinical characteristics and interventions regarding pediatric and neonatal patients that have been pointed out as focus areas for pediatric pre-hospital research.
Controlled release of hydrogel-encapsulated mesenchymal stem cells-conditioned medium promotes functional liver regeneration after hepatectomy in metabolic dysfunction-associated steatotic liver disease
Authors: Kasahara Naoya , Teratani Takumi , Doi Junshi , Yokota Shinichiro , Shimodaira Kentaro , Kaneko Yuki , Ohzawa Hideyuki , Sakuma Yasunaru , Sasanuma Hideki , Fujimoto Yasuhiro , Urahashi Taizen , Yoshitomi Hideyuki , Yamaguchi Hironori , Kitayama Joji , Sata Naohiro
Published: November 2024

Background

Globally, prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing, and there is an urgent need to develop innovative therapies that promote liver regeneration following hepatectomy for this disease. Surgical excision is a key therapeutic approach with curative potential for liver tumors. However, hepatic steatosis can lead to delayed liver regeneration and higher post-operative complication risk. Mesenchymal stem cells-conditioned medium (MSC-CM) is considered a rich source of paracrine factors that can repair tissues and restore function of damaged organs. Meanwhile, hydrogels have been widely recognized to load MSC secretome and achieve sustained release. This study aimed to evaluate the therapeutic effect of hydrogel-encapsulated MSC-CM on liver regeneration following partial hepatectomy (PHx) in a rodent model of diet-induced hepatic steatosis.

Methods

Male Lewis rats were fed with a methionine and choline–deficient diet. After 3 weeks of feeding, PHx was performed and rats were randomly allocated into two groups that received hydrogel-encapsulated MSC-CM or vehicle via the intra-mesenteric space of the superior mesenteric vein (SMV).

Results

The regeneration of the remnant liver at 30 and 168 h after PHx was significantly accelerated, and the expressions of proliferating cell nuclear antigen were significantly enhanced in the MSC-CM group. MSC-CM treatment significantly increased hepatic ATP and β-hydroxybutyrate content at 168 h after PHx, indicating that MSC-CM fosters regeneration not only in volume but also in functionality. The number of each TUNEL- and cleaved caspase-3 positive nuclei in hepatocytes at 9 h after PHx were significantly decreased in the MSC-CM group, suggesting that MSC-CM suppressed apoptosis. MSC-CM increased serum immunoregulatory cytokine interleukin-10 and interleukin-13 at 30 h after PHx. Additionally, mitotic figures and cyclin D1 expression decreased and hepatocyte size increased in the MSC-CM group, implying that this mode of regeneration was mainly through cell hypertrophy rather than cell division.

Conclusions

MSC-CM represents a novel therapeutic approach for patients with MASLD requiring PHx.
Crotalaria madurensis flavonol glycosides’ antibacterial activity against Staphylococcus aureus
Authors: Mohammed Hala Sh. , Abu El Wafa Salwa A. , Ibrahim Mona H. , Fathy Rasha Mohammad , Seif-Eldein Noha A.
Published: November 2024

Methicillin-resistant Staphylococcus aureus (MRSA) infections are prevalent in hospitals and often lead to significant health complications. This study aimed to explore the chemical composition of the aerial part of Crotalaria madurensis and evaluate its antioxidant and antibacterial properties. The impact of gamma irradiation on the antibacterial properties of the plant extract and metabolite 1 against MRSA was also examined. Fourier-transform infrared (FTIR) analysis was conducted on the filtrates of untreated MRSA and MRSA treated with the plant extract and metabolite 1. Four flavonol glycosides were identified as gossypetin 8-methoxy, 3-O-β-D-xylopyranoside (metabolite 1), gossypetin 8-O-β-D-glucopyranoside (metabolite 2), kaempferol 3-O-β-D-glucpyranoside (Astragalin, metabolite 3), and herbacetin 7-methoxy-3-O-β-D-glucopyranoside (metabolite 4). All metabolites exhibited significant antioxidant properties using different assays. The antibacterial efficacy of the extract and metabolite 1, which showed substantial antioxidant properties compared to the other isolated metabolites, was evaluated. Both the plant extract and metabolite 1 significantly reduced the viability and cell count of MRSA at concentrations of 1.0 and 0.5 mg/ml. The antibacterial activity of the plant extract and metabolite 1 was assessed after gamma irradiation at 50 and 100 Gy, which did not significantly affect the antibacterial efficiency. FTIR analysis indicated that the plant extract and metabolite 1 significantly altered the band frequency values, bandwidth, and peak intensity % of the treated MRSA filtrate. Molecular docking studies suggested that metabolite 1 exhibited the highest antioxidant and anti-MRSA activity, with strong binding scores like the ligand, indicating an effective interaction and high affinity between metabolite 1 and the target molecule.
Nuclear porcupine mediates XRCC6/Ku70 S-palmitoylation in the DNA damage response
Authors: Chen Yang , Xiao Mingming , Mo Yaqi , Ma Jinlu , Han Yamei , Li Qing , Zeng Qinghua , Boohaker Rebecca J. , Fried Joshua , Li Yonghe , Wang Han , Xu Bo
Published: November 2024

Background

The activation of the DNA damage response (DDR) heavily relies on post-translational modifications (PTMs) of proteins, which play a crucial role in the prevention of genetic instability and tumorigenesis. Among these PTMs, palmitoylation is a highly conserved process that is dysregulated in numerous cancer types. However, its direct involvement in the DDR and the underlying mechanisms remain unclear.

Methods

CRISPR-Cas9 technology was used to generate the PORCN KO and PORCN NLS KO cell lines. The effects of PORCN NLS in the DDR were verified by colony formation assays, MTT assays, the DR/EJ5 homologous recombination/non-homologous end-joining reporter system, xenograft tumor growth and immunofluorescence. Mechanisms were explored by mass spectrometry, acyl-biotin exchange (ABE) palmitoylation assay, Click-iT assay, cell subcellular fractionation assay, Western blot analysis, and in vivo and in vitro co-immunoprecipitation.

Results

In this study, we introduce evidence that Porcupine (PORCN) is an integral component of and plays a critical role in the DDR. PORCN deficiency hampers nonhomologous end joining (NHEJ) and highly sensitizes cells to ionizing radiation (IR) both in vitro and in vivo. We also provide evidence that PORCN possesses a nuclear fraction (nPORCN) with S-acyltransferase activity, unlike its membrane-bound O-acyltransferase in the endoplasmic reticulum. Furthermore, we show that nPORCN is necessary for the successful activation of NHEJ. Using mass spectrometry, we reveal the existence of an nPORCN complex and show that nPORCN mediates the S-palmitoylation of XRCC6/Ku70 at five specific cysteine sites in response to IR. Mutation of these sites causes a substantial increase in radiosensitivity and delays NHEJ. Additionally, we present evidence that nPORCN-dependent Ku70 palmitoylation is required for DNA-PKcs/Ku70/Ku80 complex formation.

Conclusion

Our findings underscore the crucial role of nPORCN-dependent Ku70 S-palmitoylation in the DDR.
The double-edged role and therapeutic potential of TREM2 in atherosclerosis
Authors: Zhu Botao , Liu Yuxuan , Peng Daoquan
Published: November 2024

Atherosclerosis is a chronic lipid-driven inflammatory disease characterized by infiltration of large numbers of macrophages. The progression of the disease is closely related to the status of macrophages in atherosclerotic plaques. Recent advances in plaque analysis have revealed a subpopulation of macrophages that express high levels of triggering receptor expressed on myeloid cells 2 (TREM2). Although TREM2 is known to play a critical role in inflammation, lipid metabolism, and tissue repair, its role in atherosclerosis is still not fully understood. Recent studies have shown that TREM2 promotes macrophage cholesterol uptake and efflux, enhances efferocytosis function, regulates inflammation and metabolism, and promotes cell survival, all of which are significant functions in atherosclerosis. In early plaques TREM2 promotes lipid uptake and increases lesion size. In advanced plaques TREM2 promotes macrophage survival and increases plaque stability. The dualistic nature of TREM2 in atherosclerosis, where it can exert both protective effect and a side effect of increased lesion size, presents a complex but crucial area of study. Understanding these dual roles could help in the development of new therapeutic strategies to modulate TREM2 activity and utilize its atheroprotective function while mitigating its deleterious effects. In this review, we discuss the roles and mechanisms of TREM2 during different stages of atherosclerotic plaques, as well as the potential applications of TREM2 in the diagnosis and treatment of atherosclerosis.
Segmentation and visualization of the Shampula dragonfly eye glass bead CT images using a deep learning method
Authors: Liao Lingyu , Cheng Qian , Zhang Xueyan , Qu Liang , Liu Siran , Ma Shining , Chen Kunlong , Liu Yue , Wang Yongtian , Song Weitao
Published: November 2024

Micro-computed tomography (CT) of ancient Chinese glass dragonfly eye beads has enabled detailed exploration of their internal structures, contributing to our understanding of their manufacture. Segmentation of these CT images is essential but challenging due to variation in grayscale values and the presence of bubbles. This study introduces a U-Net-based model called EBV-SegNet, which enables efficient and accurate segmentation and visualization of these beads. We developed, trained, and tested the model using a dataset comprising four typical Shampula dragonfly eye beads, and the results demonstrated high-precision segmentation and precise delineation of the beads’ complex structures. These segmented data were further analyzed using the Visualization Toolkit for advanced volume rendering and reconstruction. Our application of EBV-SegNet to Shampula beads suggests the likelihood of two distinct manufacturing techniques, underscoring the potential of the model for enhancing the analysis of cultural artifacts using three-dimensional visualization and deep learning.
Advances in materials and technologies for digital light processing 3D printing
Authors: Nam Jisoo , Kim Miso
Published: November 2024

Digital light processing (DLP) is a projection-based vat photopolymerization 3D printing technique that attracts increasing attention due to its high resolution and accuracy. The projection-based layer-by-layer deposition in DLP uses precise light control to cure photopolymer resin quickly, providing a smooth surface finish due to the uniform layer curing process. Additionally, the extensive material selection in DLP 3D printing, notably including existing photopolymerizable materials, presents a significant advantage compared with other 3D printing techniques with limited material choices. Studies in DLP can be categorized into two main domains: material-level and system-level innovation. Regarding material-level innovations, the development of photocurable resins with tailored rheological, photocuring, mechanical, and functional properties is crucial for expanding the application prospects of DLP technology. In this review, we comprehensively review the state-of-the-art advancements in DLP 3D printing, focusing on material innovations centered on functional materials, particularly various smart materials for 4D printing, in addition to piezoelectric ceramics and their composites with their applications in DLP. Additionally, we discuss the development of recyclable DLP resins to promote sustainable manufacturing practices. The state-of-the-art system-level innovations are also delineated, including recent progress in multi-materials DLP, grayscale DLP, AI-assisted DLP, and other related developments. We also highlight the current challenges and propose potential directions for future development. Exciting areas such as the creation of photocurable materials with stimuli-responsive functionality, ceramic DLP, recyclable DLP, and AI-enhanced DLP are still in their nascent stages. By exploring concepts like AI-assisted DLP recycling technology, the integration of these aspects can unlock significant opportunities for applications driven by DLP technology. Through this review, we aim to stimulate further interest and encourage active collaborations in advancing DLP resin materials and systems, fostering innovations in this dynamic field.

Graphical abstract
Cellular oxygen consumption in patients with diabetic ketoacidosis
Authors: Vine Jacob , Lee John H. , Balaji Lakshman , Grossestreuer Anne V. , Morton Andrea , Peradze Natia , Antony Nivedha , Berlin Noa , Kravitz Max S. , Leland Shannon B. , Berg Katherine , Moskowitz Ari , Donnino Michael W. , Liu Xiaowen
Published: November 2024

Background

Diabetic ketoacidosis (DKA) is a potentially life-threatening disorder associated with severe alterations in metabolism and acid–base status. Mitochondrial dysfunction is associated with diabetes and its complications. Thiamine and coenzyme Q10 (CoQ10) are important factors in aerobic metabolism. In this study, we measured cellular oxygen consumption rates (OCRs) and the effects of in vitro administration of thiamine and CoQ10 on OCRs in patients with DKA versus healthy controls.

Methods

Blood samples were collected from a prospective cohort of patients with DKA and from controls. Cellular OCRs were measured in peripheral blood mononuclear cells (PBMC) without treatment and after treatment with thiamine, CoQ10, or both. The mitochondrial profile was measured using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). A linear quantile mixed model was used to compare OCRs and estimate treatment effects.

Results

A total of 62 patients with DKA and 48 controls were included in the study. The median basal and maximal OCRs were lower in the DKA group than in the control group (basal: 4.7 [IQR: 3.3, 7.9] vs. 7.9 [5.0, 9.5], p = 0.036; maximal: 16.4 [9.5, 28.1] vs. 31.5 [20.6, 46.0] pmol/min/µg protein, p < 0.001). In DKA samples, basal and maximal OCRs were significantly increased when treated with thiamine, CoQ10, or both. In controls, basal and maximal OCR were significantly increased only with thiamine treatment.

Conclusion

Mitochondrial metabolic profiles of patients with DKA demonstrated lower cellular oxygen consumption when compared to healthy controls. Oxygen consumption increased significantly in cells of patients with DKA treated with thiamine or CoQ10. These results suggest that thiamine and CoQ10 could potentially have therapeutic benefits in DKA via their metabolic effects on mitochondrial cellular respiration.
The influence of suturing and or gluing of perforated Schneiderian membrane during sinuslift procedure on the outcome: a retrospective study
Authors: Khoury Fouad , Schmidt Christoph , Jackowski Jochen
Published: November 2024

The sinus lift procedure has become the most common method for maxillary bone augmentation. The most frequently observed intraoperative complication is the perforation of the Schneiderian membrane. Various treatment options have been proposed for managing these perforations, including the use of resorbable membranes, centrifugated blood products as PRF, or PRGF, suturing, and fibrin glue application. While long-term studies exist for the use of resorbable membranes to close perforations, there is limited data on the long-term outcomes of suturing or gluing the perforated sinus membrane. The aim of this retrospective study is to evaluate the long-term outcomes of suturing and/or applying fibrin glue to repair perforated sinus mucosa during sinus floor elevation procedures. Between 2005 and 2009, a total of 692 patients underwent 923 sinus lift surgeries, and Schneiderian membrane perforation occurred in 202 sinus floor elevations (21.98%) across 168 patients. The main documented causes of perforations, which ranged from 2 to 10 mm in diameter, were the presence of septa, followed by thin and adherent membranes. Of the perforations, 100 (49.5%) were treated with microsurgical suturing combined with fibrin glue, 78 (38.6%) were treated with fibrin glue alone, and 24 (11.9%) were treated exclusively with suturing. Sinus grafting was performed using autogenous bone in combination with a biomaterial, following the layering technique. All surgeries resulted in primary healing without complications, enabling all patients to undergo restoration as planned. The long term clinical and radiological evaluations of 44 randomly selected patients who followed the recall program up to 10 years post operative confirmed the effectiveness of this treatment approach.
Egyptian patients with cleft lip: our experience with primary rhinoplasty
Authors: Mabrouk Adel , Badawy Mohamed Samir , Hammad Mai Raafat , Mabrouk Amr
Published: November 2024

Background

Controversy exists regarding the timing of rhinoplasty for patients with cleft lip as some surgeons shy away from primary correction for fear of causing harm to the growth of the nose and the maxilla.

We present our favorable experience with primary rhinoplasty with repair of unilateral cleft lip in Ain Shams University plastic surgery department, providing insights into the specific management of patients of middle eastern descent.

Methods

Prospective study of 32 patients, ages 3 months- 1 year with unilateral CL presenting to Ain Shams University hospitals between January 2019 and July 2022. Primary rhinoplasty was performed at the time of lip repair. Lip repair was done by Tennison-Randall technique. Evaluation of results was done by expert analysis of photographs, anthropometric measurements, and parents’ satisfaction.

Results

Over-all concordance rate was 93% and inter-observer concordance was 89%. Non-significant differences were found between cleft and noncleft sides regarding nostril dome height, columellar length, and alar width 6 months post-operatively. 81.25% of the parents were very satisfied with the results.

Conclusion

Our study targeted a cohort of Egyptian patients with unilateral cleft lip, who underwent primary rhinoplasty and the time of lip repair, showing favorable results, supporting the literature advocating for this timing, but limited by relatively short follow up period. To the best of the authors’ knowledge, this is the first study in Egypt to highlight the outcomes and direct experience for primary rhinoplasty with cleft lip repair in an Egyptian population.