bluuebunny/crossref_metadata_2025 huggingface dataset:
Whole-body parametric mapping of tumour perfusion in metastatic prostate cancer using long axial field-of-view [15O]H2O PET
Authors: Jochumsen Mads Ryø , Christensen Nana Louise , Iversen Peter , Gormsen Lars Christian , Sörensen Jens , Tolbod Lars Poulsen
Published: April 2024

Purpose:
Tumour perfusion is nutrient-agnostic biomarker for cancer metabolic rate. Use of tumour perfusion for cancer growth assessment has been limited by complicated image acquisition, image analysis and limited field-of-view scanners. Long axial field-of-view (LAFOV) PET scan using [15O]H2O, allows quantitative assessment of whole-body tumour perfusion. We created a tool for automated creation of quantitative parametric whole-body tumour perfusion images in metastatic cancer.
Methods:
Ten metastatic prostate cancer patients underwent dynamic LAFOV [15O]H2O PET (Siemens, Quadra) followed by [18F]PSMA-1007 PET. Perfusion was measured as [15O]H2O K1 (mL/min/mL) with a single-tissue compartment model and an automatically captured cardiac image-derived input function. Parametric perfusion images were calculated using the basis-function method with initial voxel-wise delay estimation and a leading-edge approach.
Results:
For 8 primary tumours, 64 lymph node metastases, and 85 bone metastases, median tumour perfusion were 0.19 (0.15–0.27) mL/min/mL, 0.16 (0.13–0.27) mL/min/mL, and 0.26 (0.21–0.39), respectively. The correlation between calculated perfusion from time-activity-curves and parametric images was excellent (r = 0.99, p < 0.0001).
Conclusion:
LAFOV PET imaging using [15O]H2O allows creation of truly quantitative parametric images of whole-body tumour perfusion, a potential biomarker for guiding personalized treatment and monitoring treatment response.
Impacts of Pollinator Declines on Agri-Food Systems in Europe and Beyond
Authors: Feuerbacher Arndt , Kempen Markus , Steidle Johannes , Wieck Christine
Published: April 2024

While biodiversity conservation policies often encounter resistance, the potential repercussions of diminished pollination services on the global agri-food system remain underexplored. We leverage a global agricultural sector model with a focused analysis of the European sector to evaluate the possible effects of a worldwide decline in both managed and wild pollinators by 2030. Our findings suggest that such a decline could reduce global average crop yields by 9%, leading to an 6% expansion in cropland area to mitigate the reduction in global crop production to 3%. Global economic welfare would decrease by 302 billion EUR (0.4% of global GDP). The European Union, particularly its Eastern members resistant to biodiversity-friendly policies, would incur disproportionately large economic impacts. Although market responses, including expanded land use and shifts in trade patterns, could alleviate some effects, they risk exacerbating food insecurity and hampering biodiversity conservation efforts, especially in the Global South.
Estimation of nucleic acid mimics (NAMs) diffusion in bacteria with fluorescence recovery after photobleaching (FRAP) and PyFRAP
Authors: Magalhães Beatriz T. , Herrmann Alexander , Santos Rita S. , Azevedo Nuno F.
Published: April 2024

The antibiotic resistance crisis urges novel drugs against bacterial infections. Nucleic acids can serve as such drugs by inhibiting vital bacterial genes, provided their diffusion within bacterial cells is understood. We adapted PyFRAP, originally for eukaryotic cell protein diffusion analysis based on Fluorescence Recovery After Photobleaching (FRAP), to assess nucleic acid diffusion in bacteria. Validating the method, FRAP assays were conducted in E. coli expressing enhanced Green Fluorescent Protein (eGFP), yielding a diffusion coefficient (DC) of 1.25 (0.38) µm²·s⁻¹, consistent with the literature. We then investigated the internalization and diffusion of a 14-mer nucleic acid mimic (NAM) sequence in live bacterial cells, employing four fitting models. NAMs exhibited DCs (1.90 x 10⁻³ – 6.98 x 10⁻³ µm²·s⁻¹) aligning with theoretical values. This study validates PyFRAP for bacterial FRAP analysis, facilitating the understanding of nucleic acid diffusion and bacterial internalization and efflux mechanisms.
Construction of ecological security network in mountainous transitional geospace using morphological spatial pattern analysis and circuit theory: a case study of Taihang Mountain area
Authors: Zhang Ruicong , Hu Maogui , Sheng Anjie , Deng Wei , Zhang Shaoyao , Liu Jintong
Published: April 2024

Context
Since entering the process of industrialization, human activities have interfered with the original ecological environment all the time, and the expansion of cities has also continuously impacted the ecological service function.
Objectives
In order to maintain the balance of the ecosystem and the stability of ecological security, it is very important to establish an ecological security network (ESN), particularly in the composite transitional geospace. To address this, we proposed a framework for mountainous transitional geospace by morphological spatial pattern analysis and circuit theory.
Methods
We take Taihang mountain area as a case, identify sources based on landscape connectivity, establish a suitable evaluation system for the mountainous transitional geospace. Then, using circuit theory to quantitate ecological key nodes and constructing the ESN.
Results
We found 34 ecological sources and use eight factors to form a resistance surface. The corridors primarily run north-south on the east and west, but display a mesh-like layout in the central and southern parts. Additionally, pinch points are primarily in plains or plateaus, while barriers are mainly in basins and mountainous areas. These elements integrated an ESN of "four zones and three lines".
Conclusions
Pay more attention to the key ecological pinch point areas and ecological barrier restoration areas, particularly basin and mountainous area. Furthermore, the protection and resotoration of cultivated land are also important to the advance of ecological security. The study provides recommendations for protection and restoration work in the Taihang Mountain area, which hold both theoretical and practical significance for ecological planning.
Strengthening Antibiotics Stewardship at Mowbray Maternity Hospital– Neonatal Unit.
Authors: Mkony Martha Franklin , VanNiekerk Anika , Shabani Josephine , Engelbrecht Heather , Rhoda Natasha Raygaan
Published: April 2024

Objective To assess antimicrobial usage, prescription practices, sensitivity patterns, hand hygiene (HH) practices and adherence to antibiotic stewardship principles in the neonatal unit at Mowbray Maternity Hospital (MMH).
Study design: A mixed method observational study was performed at MMH. A point of prevalence survey to assess antibiotic stewardship and HH audits was conducted using the WHO tools in two phases, a baseline in December 2020. The findings of this baseline audit were presented to the Health Care Workers (HCW) and small-group HH training was done with all HCWs (day- and night-shift), representing the intervention. This was followed by a post-intervention audit from March to May 2021.
Results: A total of 246 neonatal unit patient folders were reviewed between December 2020 and May 2021. At baseline, compliance with treatment guidelines was 90%, which improved to 100% postintervention. We found that 37 (15.0%) babies were on antibiotics, with 64.9% of those on first-line antibiotics (Access group). Using multivariate logistic regression, extremely preterm infants were more likely to be on antibiotics, with an odds ratio of 11, which was statistically significant. We found eight positive blood cultures (18.9%), which included one carbapenem-resistant enterococci, Klebsiella pneumoniae. For HH, a total of 444 opportunities were observed. Moment 5 had the lowest overall mean compliance of 57.4%, which was statistically significant with a p-value =0.0172.
Conclusion: Strict adherence to treatment guidelines and good HH are essential factors for the good antibiotic stewardship seen at the MMH neonatal unit. This was reflected by low antibiotic usage, good HH compliance and a low HAI rate. Further improvement requires ongoing HH audits and training, especially focusing on HH moment 5, after touching the patient's surroundings.
Future projection of marine heat waves in a global marine hotspot Case of East/Japan Sea
Authors: Deegala Danushka , Chung Eun-Sung
Published: April 2024

The future analysis of the Marine Heat Waves (MHWs) has high uncertainty due to the significant shortcomings of the Global Climate Models (GCMs) in simulating the Sea Surface Temperature (SST) and the MHWs. This study suggests a more systematic approach to do the future projection of MHWs. Our study area is East/Japan Sea which is a large marine ecosystem exposed to rapid warming of the ocean. This study found the models; ACCESS-CM2, BCC-CSM2-MR ACCESS-ESM1, and GFDL-ESM4 from Coupled Model Intercomparison Project sixth phase (CMIP6) are the best performing GCMs in the East Sea by analyzing their grid-wise performance during the historical period (1985–2014). Using the ensemble mean from the selected models, the future MHW metrices of frequency, maximum intensity, and duration during the near future (2041–2070) and far future (2071–2100) was investigated. Following the state-of-art, shifting baseline approach was utilized to identify the MHWs and 30 years were used as the climatology period for each historical and future periods. The time series results from the ensemble mean indicated that high emission scenarios (SSP3-7.0, and SSP5-8.5) would have higher trends than that of low emission scenarios (SSP1-2.6, and SSP2-4.5) as well as that of historical observations. The high emission scenarios would have lower values in the beginning of their respective climatology period when compared to that of low emission scenarios but rather higher values toward the end of the period. The average MHW metrices of near and far futures shows certain shifts compared to that of historical but the numerical values are almost similar to that of historical period.
Polyvinyl Pyrrolidone-Chitosan Blend Membrane for Pervaporation Separation of Trimethyl Borate-Methanol Mixture
Authors: Ozekmekci Mehtap , Copur Mehmet , Unlu Derya
Published: April 2024

Trimethyl borate (TMB) is crucial for applications ranging from organic synthesis to borohydride production, requiring efficient separation from methanol for optimal use. This study examines the effectiveness of pervaporation separation using blend membranes composed of chitosan (CS) and polyvinyl pyrrolidone (PVP) in various ratios in order to enhance pervaporation separation of TMB/methanol mixtures. Comprehensive characterizations of these membranes, addressing aspects like structural morphology, thermal and crystalline nature were carried out using techniques such as Fourier transform infrared spectroscopy (FTIR), Thermogravimetric analysis (TGA), contact angle measurements, Scanning electron microscopy (SEM) and X-ray Diffraction Analysis (XRD). Pervaporation experiment were conducted varying feed compositions, operational temperatures and PVP ratios. Evaluations revealed a noticeable improvement in permeation flux with increased PVP content. Two different blended membranes were subjected to cross-linking procedures in order to carefully evaluate its influence on their separation performance. The crosslinked PVP-CS-1 membrane showed good performance, achieving 146.37 selectivity. The optimal performance was achieved in an experiment utilizing a PVP-CS-2 membrane at 45°C, employing a mixture of 75 wt% TMB-25 wt% methanol, resulting in a recorded value of 335.44 g/m2h. Furthermore, the membrane exhibited excellent stability during 5 run experiment, showcasing robust mechanical and chemical stability.
Elevated resting heart rate is associated with mortality in patients with chronic kidney disease
Authors: Saito Hirotaka , Tanaka Kenichi , Ejiri Hiroki , Kimura Hiroshi , Shimabukuro Michio , Asahi Koichi , Watanabe Tsuyoshi , Kazama Junichiro
Published: April 2024

Background
A higher heart rate is recognized as an independent risk factor for all-cause mortality and cardiovascular events in the general population. However, the association between elevated heart rate and clinical adverse outcomes in patients with non-dialysis-dependent chronic kidney disease (CKD) has not been sufficiently investigated.
Methods
A total of 1,353 participants enrolled in the Fukushima CKD Cohort Study were examined to investigate associations between resting heart rate and clinical adverse outcomes using Cox proportional hazards analysis. The primary outcome of the present study was all-cause mortality, with cardiovascular events as the secondary outcome. Participants were stratified into four groups based on resting heart rate levels at baseline (heart rate < 70/min, ≥ 70 and < 80/min, ≥ 80 and < 90/min, and ≥ 90/min).
Results
During the median observation period of 4.9 years, 123 participants died, and 163 cardiovascular events occurred. Compared with the reference level heart rate < 70/min group, the adjusted hazard ratios (HRs) for all-cause mortality were 1.74 (1.05–2.89) and 2.61 (1.59–4.29) for the heart rate ≥ 80 and < 90/min group and heart rate ≥ 90/min group, respectively. A significantly higher risk of cardiovascular events was observed in the heart rate ≥ 80/min and < 90/min group (adjusted HR 1.70, 1.10–2.62), but not in the heart rate ≥ 90/min group (adjusted HR 1.45, 0.90–2.34).
Conclusion
In patients with non-dialysis-dependent CKD, a higher resting heart rate was associated with increased all-cause mortality.
Promoting active behaviours in schoolchildren using the socio- ecological model in the physical education class: study protocol of ACTIBESE Project
Authors: Rodríguez-Rodríguez Fernando , Cristi-Montero Carlos , Zurita-Corvalán Natalia , Brand Caroline , Mota Jorge , Chillón Palma , Gaya Anelise Reis , Brazo-Sayavera Javier , Aguilar-Farias Nicolás
Published: April 2024

Background.
The correlation between parental and child physical activity levels has been the subject of significant investigation. Existing research has illuminated this association, particularly emphasising its influence during childhood. However, as children transition into adolescence, this relationship appears to weaken. Despite the recognised importance of parental involvement in promoting physical activity among children, scant attention has been directed towards understanding effective strategies and interventions to bolster this relationship. Consequently, there exists a critical gap in the literature concerning actionable measures to enhance parent-child physical activity engagement during the pivotal stage of adolescence.
Methods. The ACTIBESE project aims to assess and intervene in Chilean schoolchildren’s active behaviours by examining the influence of personal, interpersonal, and school factors. This study includes a cross-sectional and intervention study involving schools in the Valparaíso and Araucanía Regions, representing urban and rural areas. Participants, divided into children (8–11 years old) and adolescents (12–16 years old), will undergo a comprehensive evaluation, including sociodemographic characteristics, physical activity (PA) levels, parental and peer support, teaching styles of the teachers, and school environment characteristics. In the intervention study, a 5-month continuous training program for teachers will be implemented, focusing on improving teaching styles and enhancing teaching competencies related to physical education and health classes. The research will use mixed models, ANCOVA, and logistic regressions for data analysis, network analysis, exploratory factors analysis, and structural equation modelling.
Discussion. Through innovative research methods, interventions involving schoolteachers, and a diverse geographical scope, this project aims to make significant contributions to both the scientific understanding of promoting PA and public policy efforts aimed at improving the health and well-being of school-aged children. The ACTIBESE project's multifaceted approach, considering school, family, and peer influences, is well positioned to contribute significantly to promoting AB and addressing the alarming decline in PA levels among Chilean youth.
Electrochemically synthesized Tin micro-nanometer powders for visible light photocatalytic degradation of Rhodamine B dye from polluted water
Authors: Lu Yukun , Zhang Yaojie , Zhang Jiale , Li Zhaoyang , Hu Feiyang , Pan Duo , Melhi Saad , Shi Xuetao , Amin Mohammed A. , El-Bahy Zeinhom M.
Published: April 2024

Tin (Sn) micro-nanoparticles with special pine tree dendritic morphology were synthesized by using tin foil as the anode and titanium as the cathode through simple anodization method. Surprisingly, it is found that the morphology of Sn particles is closely related to factors such as the type of electrolyte, the concentration of the electrolyte, and the different applied voltages, and briefly discussed the influence of various factors on the growth of Sn particles. In addition, Sn particles are calcined under different temperature conditions to obtain Sn/SnO2 hybrid materials with different tin dioxide (SnO2) contents. The changes in morphology and the phase of SnO2 crystal lattices were characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD), respectively, which proved the successful synthesis of Sn/SnO2 mixed materials. Finally, the Sn/SnO2 hybrid material with metal-doped modified semiconductor properties was used to photocatalytic degradation of simulated organic pollutants rhodamine B (RhB). It was found that the photocatalytic degradation efficiency of the Sn/SnO2 hybrid material under simulated sunlight conditions is near 90% in 5 h. Therefore, this work provides a convenient and effective environmental protection approach for the treatment of architecture and industrial dyes.
Novel Pathogenic Variant in a Mild Case of Type B Molybdenum Cofactor Deficiency: Case Report and Literature Review
Authors: Kinsinger Morgan , Mithal Divakar S.
Published: April 2024

Background:
Molybdenum cofactor deficiency (MoCD) is a rare metabolic disorder caused by pathogenic variants in the highly conserved biosynthetic pathway of molybdenum cofactor (MoCo), resulting in sulfite intoxication. MoCD may present in a clinically severe, rapidly fatal form marked by intractable seizures after birth, hyperekplexia, microcephaly and cerebral atrophy, or a later onset form with a more varied clinic course. Three types of MoCD have been described based on the effected gene along the MoCo synthesis pathway: type A (MOCS1); type B (MOCS2 or MOCS3) and type C (GPHN). The MOCS2 gene is bicistronic, encoding the small (MOCS2A) and large (MOCS2B) subunits with an overlapping coding region. This case report describes a patient with the first known variant causative of mild disease in the overlapping bicistronic region (c.263 G>C) and the first ever described in the highly conserved C-terminal glycine-glycine motif of MOCS2A.
Case Presentation:
The patient developed normally until age 12 months when she presented in the setting of acute illness withdevelopmental regression, low serum uric acid, and MRI with bilateral globus pallidus (GP) injury. Whole exome sequencing (WES) identified a homozygous variant of unknown significance in the MOCS2 gene and the diagnosis of MoCD type B was confirmed by the patient’s elevated urine sulfocysteine and low uric acid. Nearly two years after her initial presentation she has demonstrated progress in language and motor domains, consistent with a mild phenotype of MoCD.
Conclusions:
The case emphasizes challenges in identifying atypical forms of rare diseases, the importance of whole exome sequencing (WES) to identify mild cases of MoCD, and the ongoing challenges with understanding the MOCS2 gene. While one FDA approved treatment exists for MoCD type A, further research into the mechanisms of phenotype-genotype differences among this patient population may aid in additional therapeutic options for MoCD.
Prognostic of postoperative systemic inflammatory response for gastric cancer
Authors: Fukushima Naoko , Masuda Takahiro , Tsuboi Kazuto , Yuda Masami , Takahashi Keita , Yano Fumiaki , Eto Ken
Published: April 2024

Purpose
The systemic inflammatory response is a significant prognostic indicator in patients with cancer. Few studies have reported a relationship between postoperative systemic inflammatory responses and prognosis in patients with gastric cancer. This study aimed to clarify the efficacy of postoperative systemic inflammatory response in patients with gastric cancer after gastrectomy and to determine which prognostic scoring system is better.
Methods
Overall, 210 patients with gastric cancer who underwent gastrectomy between February 2013 and July 2022 were included. Systemic inflammatory response markers, including the Glasgow prognostic score, prognostic nutritional index, neutrophil-lymphocyte ratio, and platelet-lymphocyte ratio, were calculated before and 1 month after surgery. The relationship between preoperative and postoperative systemic inflammatory responses and the prognosis of patients with gastric cancer was investigated.
Results
In multivariate analysis, postoperative Glasgow prognostic score of 1or 2 (P = 0.04, P < 0.01, respectively), stage II or III (P < 0.01, P < 0.01, respectively), and R1 or R2 curability (P = 0.03, P < 0.01, respectively) were independent and significant predictors of disease-free survival and overall survival. Eighty-seven patients (41%) were classified as having postoperative Glasgow prognostic scores of 1 or 2. Patients with a postoperative Glasgow prognostic score of 1 or 2 had significantly more advanced tumors, more invasive surgery, and more postoperative complications than those with a postoperative Glasgow prognostic score of 0.
Conclusion
The postoperative Glasgow prognostic score was independently associated with poor prognosis and recurrence in patients who underwent gastrectomy for gastric cancer comparing other pre- and post- operative prognostic scoring markers.
Importance of hospital and clinical factors for early mortality in Takotsubo syndrome: Insights from the Swedish Coronary Angiography and Angioplasty Registry
Authors: Gudmundsson Thorsteinn , Redfors Björn , Råmunddal Truls , Angerås Oskar , Petursson Petur , Rawshani Araz , Hagström Henrik , Alfredsson Joakim , Ekenbäck Christina , Henareh Loghman , Skoglund Kristofer , Ljungman Charlotta , Mohammad Moman , Jernberg Thomas , Fröbert Ole , Erlinge David , Omerovic Elmir
Published: April 2024

Background
Takotsubo syndrome (TTS) is an acute heart failure syndrome with symptoms similar to acute myocardial infarction. TTS is often triggered by acute emotional or physical stress and is a significant cause of morbidity and mortality among patients with acute coronary syndromes. Predictors of mortality in patients with TS are not well understood, and there is a need to identify high-risk patients and tailor treatment accordingly. This study aimed to assess the importance of various clinical factors in predicting 30-day mortality in TTS patients using a machine learning algorithm.
Methods
We analyzed data from the nationwide Swedish Coronary Angiography and Angioplasty Registry (SCAAR) for all patients with TTS in Sweden between 2015–2022. Gradient boosting was used to assess the relative importance of variables in predicting 30-day mortality in TTS patients.
Results
Of 3,180 patients hospitalized with TTS, 76.0% were women. The median age was 71.0 years (interquartile range 62–77). The crude all-cause mortality rate was 3.2% at 30 days. Machine learning algorithms by gradient boosting identified treating hospital as the most important predictor of 30-day mortality. This factor was followed in significance by the clinical indication for angiography, creatinine level, Killip class, and age. Other less important factors included weight, height, and certain medical conditions such as hyperlipidemia and smoking status.
Conclusions
In an analysis of all Swedish patients diagnosed with TTS over seven years, using machine learning with gradient boosting, we found that the treating hospital was the most significant predictor of 30-day mortality.
Plasma exosomal miR-125b-5p and miR-143-3p have potential to diagnose breast cancer
Authors: Fan Lei , Li Yao , Huang Jicheng , Hua Bin
Published: April 2024

Background
Breast cancer (BC) is the most common malignancy in women, posing a serious health risk. Exosomal microRNA (miRNA) has emerged as a promising cancer biomarker. Despite its potential, research on exosomal miRNA in BC remains limited. This study aims to identify plasma exosomal miRNAs for diagnosing BC.
Methods
Firstly, plasma exosomal miRNA sequencing was conducted on 45 BC patients and 5 healthy controls, followed by Differential Expression Analysis to screen for differentially expressed miRNAs. The diagnostic value of these miRNAs was assessed using receiver operating characteristic (ROC) curves. Subsequent analysis of candidate miRNAs was carried out in the TCGA database. Target genes of differentially expressed miRNAs were predicted using online databases, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. Finally, a ceRNA network was constructed using Cytoscape.
Results
Our analysis indicates that, compared to normal controls, plasma exosomal miR-125b-5p and miR-143-3p are significantly downregulated in BC patients. The area under the curve (AUC) for exosomal miR-125b-5p is 0.951 (sensitivity 91.1%, specificity 100%), and the AUC for exosomal miR-143-3p is 0.924 (sensitivity 86.7%, specificity 100%). In the TCGA database, the expression of miR-125b-5p and miR-143-3p is downregulated in BC tissues compared to adjacent normal tissues. Target gene prediction and enrichment analyses reveal pathways closely associated with BC occurrence.
Conclusions
Our results demonstrate that plasma exosomal miR-125b-5p and miR-143-3p can distinguish between BC patients and normal controls. The downregulation of plasma exosomal miR-125b-5p and miR-143-3p may potentially serve as a marker for the occurrence of BC.
Mental health nursing consultations in Brazilian primary care: analysis of proposed competencies for advanced practice nurses
Authors: de Almeida Patricia Aline , de Almeida Letícia Yamawaka , Vesga-Varela Andrea Liliana , Barreto Carla Pereira , Carrer Marília Orlandelli , Reis Keila Gisele Lima , Serranegra Nayara Vilela Farias , Neto Manoel Vieira de Miranda , Martiniano Claudia Santos , Bonfim Daiana
Published: April 2024

Background: Primary Health Care (PHC) is described as a key strategy to identifying, managing and coordinating mental health cases. Considering that nurses stand out as an essential element to integrate mental health care in PHC, initiatives to broaden the discussion and incorporate the role of Advanced Practice Nurses (ANP) in this setting, can contribute to reduce disparities in mental health care. Thus, this study aimed to analyze mental health nursing consultations in PHC and investigate whether nurses have care management skills proposed for ANP.
Methods: multicenter study, with a quantitative and qualitative approach, carried out in 17 Primary Care Health Units, distributed in three regions of Brazil, from May to July 2022. Data collection was carried out in two moments of the nurse's professional practice: nursing consultation (recorded using film, with direct and non-participatory observation) and nursing record. From a quantitative perspective and during the first research stage, consultations with ≥50% compliance with the nursing process were selected so that, in the second qualitative stage, through content analysis, the competencies proposed for ANP in PHC were identified.
Results: a total of 49 mental health nursing consultations were performed by 21 nurses. Of these, seven were selected with a score greater than 50% of compliance with the Nursing Process, carried out by three nurses. The consultations presented few competencies in the care management dimension proposed for the ANP, nevertheless, NC presented 39.68% in the care focus, 38.78% in assessment and diagnosis and 47.62% in the provision of care.
Conclusions: nurses who carry out mental health nursing consultations in PHC present, in a scarce and partial way, the competencies proposed for the ANP regarding the domain of care management.
Design and synthesis of novel EGFR kinase inhibitors for the treatment of EGFR C797S mutation in non-small cell lung cancer
Authors: Nie Wenyan , Wang Mengxuan , Xia Zhenhong , Wang Chunlong , Nie Haoran , Zhang Shuai , Qiu Jiaqi , yang Yang , Yao Cuifang , Li Xingshu , An Baijiao
Published: April 2024

Third-generation cutaneous growth factor receptor tyrosine kinase inhibitors have led to impressive advances in the treatment of non-small cell lung cancer. However, acquired resistance significantly limits the clinical application of these agents, with the epidermal growth factor receptor (EGFR)C797S mutation being the primary resistance mechanism. In this study, a series of novel EGFR kinase inhibitors was designed and synthesized for the treatment of the EGFRC797S mutation in non-small cell lung cancer. Structure activity relationship screening revealed that compound 5d was the most effective inhibitor of the C797S mutation. It strongly inhibited Baf3-EGFRL858R/T790M/C797S and Baf3-EGFR 19del/T790M/C797S cell lines, with IC50 values of 0.01836±0.0065 and 0.025±0.005 μM, respectively. Molecular docking studies showed that 5d binds to the EGFRL858R/T790M/C797S and EGFR19del/T790M/C797S proteins effectively. A mechanistic study showed that 5d induced cell cycle arrest in the G2/M phase. Compound 5d caused cell apoptosis in a dose-dependent manner, accompanied by a significant increase in the level of the apoptotic protein cleaved caspase-3. An in vivo xenograft assay of mice with Baf3-EGFR19del/T790M/C797S cells showed that 5d effectively inhibited tumor growth, with inhibition rates of 45.2% (70 mg/kg) and 55.7% (100 mg/kg) being observed. Therefore, 5d is worthy of further investigation as a fourth-generation EGFR inhibitor.
PCSK9 promotes vascular neointimal hyperplasia through non-lipid regulation of vascular smooth muscle cell proliferation, migration, and autophagy
Authors: Zhang Qian , Miao Mengdan , Cao Shanhu , Chen Lixia , Liu Da , Wei Mei , Sun Shaoguang , Jin Sheng , Dong Lihua , Yin Yajuan , Liu Gang , Zheng Mingqi
Published: April 2024

We aim to explore the impact of Proprotein convertase subtilisin-kexin type 9 (PCSK9) and its inhibitor evolocumab on neointimal hyperplasia. Wild type and PCSK9 knockout (PCSK9-/-) mice were subjected to ligation of the common carotid artery, with or without subcutaneous injection of PCSK9i Evolocumab. Mouse aortic vascular smooth muscle (MOVAS) cells were pretreated with evolocumab or under siRNA-mediated suppression of PCSK9, and then exposed to platelet-derived growth factor type BB(PDGF-BB), a major promoter of MOVAS transformation to a proliferative phenotype. PCSK9 was upregulated in ligated carotid arteries and PDGF-BB-treated MOVAS cells. PCSK9-/- mice showed decreased intimal area and intimal/ media area ratio, downregulation of proliferation and autophagy, which was coincidence with wild-type mice treated with evolocumab. In MOVAS cells fortified with evolocumab or silencing of PCSK9, PCNA, Beclin1, p62, LC3 were downregulated, additionally, EdU-positive cells decreased, cell viability reduced, migration ability was weakened, and the number of autophagosomes and autolysosomes decreased after the treatment. We also identified the PI3K/AKT/mTOR signaling molecules as potential PCSK9 targets mediating proliferative effect in MOVAS cells. To sum up, our results suggest that PCSK9 has intrinsic properties to promote proliferation, migration and autophagy in VSMCs independent of its lipid- regulating role. The proliferative effects of PCSK9 may be mediated by the PI3K/AKT/mTOR signaling pathway. These data provide additional evidence for PCSK9i in cardiovascular disease beyond the low-density lipoprotein (LDL)-lowering benefit.
Characterization of Carbapenem-Resistant Escherichia coli From a Tertiary Hospital in Hangzhou, China
Authors: Zeng Lingyi , Hu Kewang , Zheng Zhibei , Yu Hua , Zheng Wei , Xu Qihao , Yan Jiaqi , Xiang Mengdie , Wu Jun , Li Jun
Published: April 2024

Background: In recent years, with the large-scale use of antibiotics, the detection rate and mortality of carbapenem-resistant Escherichia coli (CR-EC) have gradually increased. This study explores the molecular characteristics and prevalence of CR-EC isolated from a tertiary hospital in Hangzhou.
Methods: A total of 10 non-duplicated CR-EC were collected. The minimal inhibitory concentration was determined by microbroth dilution method. Various drug-resistant genes were detected by polymerase chain reaction. The transferability of plasmid was verified by conjugation test and genetic homology was detected by pulsed-field gel electrophoresis. The whole genome is sequenced using the Illumina MiSeq technology.
Results: The strains were of diverse origin and all showed multidrug resistance. blaNDM was the only detected carbapenem gene with a high carrying rate (80%). The success rate of conjugation was 75%, indicating the horizontal transfer of blaNDM. Homology analysis showed that there was no widespread cloning outbreak of CR-EC in this study, blaNDM-5-ST410 is prevalent in the local area as a dominant group. WGS suggests complex plasmid replicon situations and greater potential risks of drug resistance and virulence.
Conclusions: This is a survey on the prevalence and molecular characteristics of CR-EC in the Hangzhou, blaNDM-like production combined with ESBLs and/or AmpC was the main resistance mechanism of CR-EC. Complex drug resistance, potential virulence risks and the transferability of plasmids have intensified the trend of widespread prevalence of CR-EC, and medical personnel should closely monitor the changes of dominant clone groups (such as ST410) to prevent and control the further spread of CR-EC.
Comparative Clinical Outcomes of Irrigation Techniques in Burr-Hole Craniostomy for Chronic Subdural Hemorrhage: A Multicenter Cohort Study
Authors: Cho Ho Seong , Lee Hyun-Seok , Jeon Yoo Sung , Lee Won Hee , Cho Kyung Rae
Published: April 2024

Background
CSDH is often treated with surgical blood drainage, but concerns about recurrence and outcomes persist. Surgical techniques, including irrigation, vary. This study compares the outcomes of irrigation in cSDH surgery.
Materials and methods
From September 2020 to September 2022, 92 cSDH patients underwent surgery. Two different irrigation methods were used: extensive irrigation (IG) and non-irrigation (NIG). Method of irrigation was selected by each surgeon’s preference. Parameters measured included volume of hematoma changes, midline shifting, complications, and basic demographics. Recurrence was defined as symptomatic or hematoma expansion more than double the volume before surgery. Factors predicting recurrence and irrigation method impact were analyzed.
Results
Eleven patients were excluded because of bilateral or related to other disease. We analyzed 81 patients (44 NIG, 37 IG). Recurrence occurred in 6 IG cases (16.2%) and 1 NIG case (2.3%). Irrigation method significantly affected recurrence (P = 0.043). Age, gender, medication, medical history, and preoperative measurements had no major impact on recurrence. NIG had unexpected cases of intracerebral hemorrhage.
Conclusion
Extensive irrigation may increase recurrence in cSDH drainage. Non-irrigation drainage had fewer recurrences, but unexpected complications arose. Careful drainage in non-irrigated cases is crucial.
Physical Activity and Chronic Diseases: A Cross-sectional Study of 19,084 Middle-aged and Elderly Chinese
Authors: Huang Yongyu , Lu Zuosheng
Published: April 2024

Background: Regular physical activity is beneficial for both physical and mental health, yet studies on the levels of physical activity among the elderly in China are relatively scarce, and the health benefits of different levels of physical activity remain unclear.
Objective: To investigate the levels of physical activity among the elderly in China and to analyze the association between different levels of physical activity and 15 chronic diseases using multinomial logistic regression.
Methods: The participants (N=19084) were drawn from the China Health and Retirement Longitudinal Study data, a nationally representative survey designed to collect high-quality microdata on households and individuals aged 45 and over, covering 28 provinces in China. We used the latest survey data from 2020 to describe the participation in physical activity among the middle-aged and elderly population in China using frequencies and percentages, and to explore the differences in the prevalence of chronic diseases among different levels of physical activity using multinomial logistic regression.
Results: Of the 19084 participants, 8750 (45.8%) met the recommended levels of physical activity guidelines（level3）, 8159 (42.8%) did not meet the recommended levels（level2）, and 2175 (11.4%) did not participate in any form of physical activity（level1）. Compared to those who did not participate in physical activity（level1）, those who participated but did not meet the guidelines（level2） had a reduced risk of 8 types of chronic diseases, including hypertension (OR=0.92, CI: 0.83-1.01) and stroke (OR=0.70, CI: 0.61-0.82). Among those who met the guidelines（level3）, compared to those who did not participate in physical activity（level1）, there was a reduced risk of 11 types of chronic diseases, including hypertension (OR=0.73, CI: 0.66-0.80) and stroke (OR=0.42, CI: 0.36-0.50). Compared to those who did not meet the physical activity guidelines（level1+level2）, those who met the guidelines（level3） had a reduced risk of 10 types of chronic diseases, including hypertension (OR=0.78, CI: 0.73-0.83) and stroke (OR=0.55, CI: 0.48-0.62).
Discussion: More than half of the elderly in China (54.2%) do not meet the physical activity guidelines. Participating in physical activity, even if not meeting the guidelines, can reduce the risk of chronic diseases, but adhering to the guidelines for physical activity offers greater health benefits. It is recommended that the Chinese government create favorable conditions for the elderly to participate in physical activities to further increase the proportion of the elderly population meeting the physical activity guidelines.
Ensemble Machine Learning Approach to Bankruptcy Prediction
Authors: Olatunji Sunday O. , Musleh Dhiaa , Rahman Atta-ur , Salih Ilyas A. , Salem Abdlrhman M. , Dash Sujata , Fares Mahmoud O. , Bokir Ahmed S. , Al-Qahtani Osama , Mallik Saurav , Shah Mohd Asif
Published: April 2024

Bankruptcy is among the biggest threats every company has in terms of its reputation. It can be explained as a situation in which a company is unable to pay back the outstanding debts to banks, lenders, and/or suppliers. An accurate and timely prediction could help the companies avoid and prevent this situation by incorporating remedial actions beforehand. In this regard, current research aims to investigate a combination of techniques to accurately predict bankruptcy. This is achieved by investigating different ensemble techniques to combine the best methods for accuracy enhancement. Comparative analysis has been carried out on the proposed ensemble models using the original but imbalanced dataset as well as the balanced dataset using the oversampling technique. The proposed method of using the balanced dataset on the proposed ensemble models outperformed the models using the original dataset in terms of accuracy and other performance metrics. As an outcome, Balance Bagging exhibits the highest accuracy at 98.77% followed by Random Forest at 98.68% and AdaBoost at 96.9%, respectively. This is considerable in contrast to the state-of-the-art techniques.
“Why shouldn’t I expect a lot from life?” – a qualitative study of what facilitates long-term recovery in first-episode psychosis
Authors: Åsbø Gina , Haavind Hanne , Kruse Sindre Hembre , Wold Kristin Fjelnseth , Hegelstad Wenche ten Velden , Romm Kristin Lie , Slade Mike , Ueland Torill , Melle Ingrid , Simonsen Carmen
Published: April 2024

Background: Qualitative research frequently characterises recovery, but more knowledge on subjective experiences of facilitators of long-termrecovery in psychosis is needed. This interview study aimed to explore what people with first-episode psychosis (FEP) highlight as important for their long-term recovery.
Methods: Interviews with 20 individuals in recovery (personal and/or clinical) participating in two follow-up studies, 10 and 20-years after treatment start for a first episode schizophrenia or bipolar spectrum disorder. Interviews were thematically analysed by the research team that included a peer researcher.
Results: The analysis generated that personal agency was experienced as the overarching facilitator of recovery, with five themes: 1. Doing recovery in everyday life, involving agency in daily life; 2. Re-evaluating risk, involving re-evaluating limitations and stress reduction; 3. Becoming a caregiver, involving development from being cared for to taking care of others; 4. Negotiating normality, involving identity and social inclusion; 5. Owning and sharing your story, involving accepting lived experience and overcoming stigma.
Discussion: All participants described themselves as the main facilitators of their own recovery, and treatment as secondary to their efforts. Gradually testing limitations and taking risks, providing social support to others, as well as owning and sharing your story were crucial for promoting long-term recovery in FEP. Clinical implications include supporting service users’ agency with strength- based interventions and shared-decision making, and refining stress reduction psychoeducation in a long-term perspective.
Evaluation of a youth-focused suicide prevention HOPE aftercare service: protocol for a non-randomized hybrid effectiveness-implementation type 1 design
Authors: Kartal Dzenana , Jaeger Tess , Lamblin Michelle , Richards Hannah , Witt Katrina , Occhipinti Jo-An , Mihalopoulos Cathrine , Chatterton Mary Lou , Chanen Andrew , McGorry Patrick , Skinner Adam , Zbukvic Isabel , Thompson Andrew , Knott Jonathan , Flego Anna , Hamilton Craig , Webb Marianne , Mullen Eddie , Swingler Natasha , Robinson Jo
Published: April 2024

Background: Suicide is the fourth leading cause of death among young people aged 15–29 worldwide. Young people often present to emergency departments (EDs) with self-harm and suicide related behaviors. The period following discharge from the ED is recognized as one of elevated risk for both repeated self-harm and suicide. During this critical time, suicide prevention aftercare services are recommended. Despite their increased popularity, evidence demonstrating the effectiveness of these models is very limited.
Methods: Using a hybrid effectiveness-implementation type I design, this evaluation will assess the effectiveness and implementation of a suicide prevention aftercare (Hospital Outreach Post-suicidal Engagement; HOPE) service designed to reduce risk of self-harm and suicide in young people aged 12–25 who are referred to the service following an ED presentation for self-harm or suicide attempt. Two complementing theoretical frameworks will guide this evaluation, specifically the design, data collection, analysis, and interpretation of results. The RE-AIM evaluation framework will be used to assess Reach, Effectiveness (including cost-effectiveness), Adoption, Implementation and Maintenance of the HOPE aftercare service. The PRISM implementation framework will be used to assess multi-level contextual factors hypothesized to affect the RE-AIM outcomes. Several data sources will be used to assess the changes in primary and secondary outcomes from baseline to post–intervention, and at follow-up, including user and provider self-report surveys, semi-structured interviews, and routinely collected hospital data. An historical control study will also be conducted using data from the Self-Harm Monitoring System for Victoria to examine the impact of the service on rates of self-harm and suicide-related presentations to ED, and compare trends prior to and following commencement of the HOPE aftercare service. In addition, dynamic systems modelling will be used to assess the future scalability of the service.
Discussion: Findings from this evaluation will determine the effectiveness, including cost-effectiveness, of the HOPE aftercare service and describe the implementation context. They will inform the future development and sustainability of this and other similar services across Australia and internationally.
Trial registration: ACTRN12623001332617
The impact of temporal hydrogen regulation on hydrogen exporters and their domestic energy transition
Authors: Schumm Leon , Abdel-Khalek Hazem , Brown Tom , Ueckerdt Falko , Sterner Michael , Fioriti Davide , Parzen Max
Published: April 2024

As global demand for green hydrogen rises, potential hydrogen exporters move into the spotlight. However, the large-scale installation of on-grid hydrogen electrolysis for export can have profound impacts on domestic energy prices and energy-related emissions. Our investigation explores the interplay of hydrogen exports, domestic energy transition and temporal hydrogen regulation, employing a sector-coupled energy model in Morocco. We find substantial co-benets of domestic climate change mitigation and hydrogen exports, whereby exports can reduce domestic electricity prices while mitigation reduces hydrogen export prices. However, increasing hydrogen exports quickly in a system that is still dominated by fossil fuels can substantially raise domestic electricity prices, if green hydrogen production is not regulated. Surprisingly, temporal matching of hydrogen production lowers domestic electricity cost by up to 31% while the effect on exporters is minimal. This policy instrument can steer the welfare (re-)distribution between hydrogen exporting firms, hydrogen importers, and domestic electricity consumers and hereby increases acceptance among actors.
Blockage of BAG2-CHIP Axis Combats Gastric Cancer by Inducing HSP70 Ubiquitination-mediated Apoptosis
Authors: Liu Qian , Wei Hong , Tang Baoyuan , Tian Binbin , Ma Zhijian , Gu Qianlin , Su Xiaolu , Yu Zeyuan , Dong Yuman , Shi Wengui , Luo Changjiang
Published: April 2024

The acquired resistance of cells to apoptosis is strongly correlated with the development of gastric cancer. Bcl-2-associated athanogene 2 (BAG2) functions as an oncogene in numerous tumours by regulating cell apoptosis. However, its functional, clinical importance and underlying mechanism in gastric cancer (GC) remain unclear. Here, we reported BAG2 as a therapeutic target to regulate GC apoptosis through BAG2-CHIP-HSP70-Apaf1-Cytc axis. BAG2 is highly overexpressed in GC and negatively correlated with prognosis of patients with GC. Knockout of BAG2 inhibits GC growth and induces cell apoptosis in vitro and in vivo. Mechanistically, BAG2 interacts with C-terminus of HSP70-inteacting protein (CHIP) to inhibit the ubiquitination degradation of HSP70, resulting in an increase in the binding of HSP70 and Apoptotic protease activating factor (Apaf1), and in turn reduction of mitochondrial Cytochrome C (Cytc) release to block cell apoptosis. In addition, we identified FIIN-2 as an inhibitor of the BAG2-CHIP complex, which induces apoptosis to inhibit GC growth in GC cell lines, organoids and CDX mice models. In conclusion, we characterize that BAG2 drive the GC growth by regulating cell apoptosis through BAG2-CHIP-HSP70-Apaf1-Cytc axis, and blockage of BAG2-CHIP using FIIN-2 as a potential strategy to combat GC.