bluuebunny/crossref_metadata_2025 huggingface dataset:
An integrated understanding of the multifaceted impact of Hospital at Home: a mixed-methods study to articulate and test a HaH programme theory
Authors: Chen Hong , Ignatowicz Agnieszka , Skrybant Magdalena , Lasserson Daniel
Published: April 2023

Background: Hospital at Home (HaH) provides intensive, hospital-level care in private or care homes for acute conditions that would normally require an acute hospital bed, using multidisciplinary healthcare teams. As a programme of complex medical-social interventions, a HaH programme theory has not been fully articulated yet, although implicit in the structures, functions, and activities of the existing HaH services. We aimed to unearth the tacit theory from international evidence and test the soundness of the theory by studying UK HaH services.Methods: We conducted a rapid systematic review of 29 articles adopting a ‘realist review’ approach and examined 11 UK-based services by interviewing up to 3 staff members (e.g. doctors, nurses, service leads, therapists) from each service. The review and interview data were analysed using Framework Analysis and Purposive Text Analysis.Results: Our programme theory has three interlinked components: Organisation, Utilisation and Impact. Central to the programme theory is Impact Theory. It shows multifaceted impacts of HaH on patients and carers and at the system level; and reveals multiple, intertwined pathways of change in which certain outputs of the main HaH functions and activities were the instigating causes and certain clinical, health and wellbeing, and system-level benefits were the effects they eventually produced. Our findings also highlight the main features of HaH that created added value for patients and carers: comprehensiveness of assessment leading to individually tailored, situational appropriate interventions; special and more holistic healing effects of home environment; high quality interactions between professionals and patients and carers; and less complexity and fragmentation of care.Conclusions: We have shown that the multifaceted impacts of HaH add value to patient care, carer support and health system performance, making HaH a better option for some patients who would otherwise need hospital admission. Our Impact Theory helps unpack the “black box” to reveal how these impacts can be brought about, informing how HaH services can organise resources and design processes of care to optimise patient satisfaction and outcomes. It can be used as a basis for formulating and prioritising evaluation questions, designing evaluation research, and interpreting evaluation findings in future HaH service evaluations.
Comparison of patient length of stay in care between home-based care and hospitalized covid-19 patients in northern and West Nile regions, Uganda
Authors: Namusoosa Ritah , Tamale Andrew , Baziira Joel , Ssekyanzi Micheal , Nabadda Susan N. , Kungu Joseph M
Published: April 2023

SARS-CoV-2-caused COVID-19 was first detected in Wuhan, China, in December 2019. Uganda reported her first COVID-19 case on March 21, 2020. The pandemic placed an enormous burden on health systems across the world. This retrospective cross-sectional study compared COVID-19 patient length of stay in care and associated factors for hospitalised patients in Regional Referral Hospitals and those who underwent home-based care in Northern and West Nile regions in Uganda. 400 patients were studied (200 inpatient and 200 home-based).
All patients were confirmed COVID-19 cases with a positive real-time PCR test result. Regardless of signs or symptoms development, all individuals with confirmed SARS-COV2 infection were eligible for admission to the hospital during this period.
It was found that hospitalized and home-based care patients were similar. 61.1% died within 14 days and 59.9% recovered under both types of care. Hospitalized patients stayed 14.8 days and home-based patients 15.0.
The difference in the mean length of stay in care among hospitalized patients and patients under home-based was not statistically significant (t=0.28, p=0.38) and there was no association between type of care and length of stay in care (OR: 0.96: 95% CI 0.64 to 1.43: p=0.837).
Symptom Status of patients and their occupation were found to be one of the important factors influencing recovery. It was observed that symptomatic patients were associated with longer stay in care (OR: 1.96, p=0.01). Likewise, law enforcement officers had a higher likelihood of staying longer compared to people involved in health-related work (OR: 3.28, p=0.03).
Covid-19 patient length of stay in care is not dependent on the approach used in case management. Therefore, the decision of whether a patient should be hospitalised or treated at home requires careful consideration of all relevant factors and an individual evaluation of the patient's circumstances.
Negative impacts of social isolation on behavior and neuronal functions are recovered after short-term social reintroduction in zebrafish.
Authors: Müller Talise Ellwanger , Santos Matheus Mulling dos , Ferreira Sabrina Antunes , Claro Mariana Torri , de Macedo Gabriel Teixeira , Fontana Barbara Dotto , Barbosa Nilda Vargas
Published: April 2023

Recently, social isolation measures were crucial to prevent the spread of the coronavirus pandemic. However, the lack of social interactions affected the population mental health and may have long-term consequences on behavior and brain functions. Here, we evaluated the behavioral, physiological, and molecular effects of a social isolation (SI) in adult zebrafish, and whether the animals recover such changes after their reintroduction to the social environment. Fish were submitted to 12 days of SI, and then reintroduced to social context (SR). Behavioral analyses to evaluate locomotion, anxiety-like and social-related behaviors were performed after SI protocol, and 3 and 6 days after SR. Cortisol and transcript levels from genes involved in neuronal homeostasis (c-fos, egr, bdnf), and serotonergic (5-HT) and dopaminergic (DA) neurotransmission (thp, th) were also measured. SI decreased anxiety-related phenotype, and altered social behaviors in zebrafish. Fish submitted to SI also presented changes in the transcript levels of genes related to neural activity, and 5-HT/DA signaling. Interestingly, most of the behavioral and molecular changes induced by SI were not found again 6 days after SR. Thus, we highlight that SR of zebrafish to their conspecifics played a positive role in social behaviors and in the expression of genes involved in different neuronal signaling pathways that were altered after 12 days of SI. This study brings unprecedented data on the effects of SR in the recovery from SI neurobehavioral alterations, and reinforces the role of zebrafish as a translational model for understanding the neurobiological mechanisms adjacent to SI and resocialization.
Microbially synthesised agriculturally useful urea nanoparticles have no phytotoxicity and show enhanced fertilising effects in Kharif (monsoon) paddy
Authors: Priyam Ayushi , Seth Prerna , Shukla Sadhana , Vineetha U. , Manna Palash Kumar , Singh Pushplata Prasad
Published: April 2023

Urea has been used as a conventional nitrogenous fertiliser since long, however, the nutrient use efficiency of the conventional urea is low due to issues related to ammonia volatilisation. Nanotechnology-based fertilisers are now proposed to reduce the dose of conventional fertilisers and enhance nutrient use efficiency. In the present study, we proposed a novel microbial-assisted synthesis approach for urea nanoparticles (TERI NanoUrea: TNU) using a microbial co-culture approach that included two species from the Bacillaceae family. This approach is an eco-friendly method as opposed to the synthesis of conventional urea. In brief, the synthesis reaction was modelled using Monod’s kinetics for bacterial growth in presence of substrate. Two species of Bacilluswere co-cultured and during the algorithmic growth phase were exposed to the bulk substrate (conventional urea: 46% N). Difference in release patterns of organic acids, carbohydrates, lipids, and proteins during microbial culture exposure to bulk substrate was observed, which resulted in the synthesis of urea nanoparticles (TNU) after 24 hr of incubation. Also, biomolecules released during synthesis of nanoparticles contributed to a biomolecular corona over the nanoparticles. The prepared TNU was thoroughly characterised by using various physicochemical and analytical techniques and it was observed that via microbial synthesis approach, 5-15 nm sized spherical particles possessing inherent characteristics of urea were synthesised. Along with the synthesis and characterisation we also investigated the effects of TNU on the early development of seedlings of a monocot (maize) and two dicot (tomato and okra) species. It was found that the novel biogenic TNU did not show any phytotoxicity to the selected monocot and dicot species and resulted in enhanced seed vigour and plant growth. Further, the TNU was used in Kharif (monsoon) field trials on paddy for nitrogen supplementation to the conventional urea fertilisers. The field trial observations showed the agronomic efficiency of replacing 25% of the conventional urea with TNU (TNU + 75% urea along with 100% treatment with recommended doses of phosphorus and potassium fertilisers). These results suggest that biogenic TNU, can be explored further for its application to various crop systems and can aid in supplementation of conventional urea fertilisers.
Determinants of Neural Tube Defect Among Newborns Admitted to Neonatal Intensive Care Units of Teaching Hospitals in Gedeo Zone and Sidama Region, Southern Ethiopia; A Case Control Study
Authors: Getnet Addisu , Figa Zerihun , Gido Rediet , Aschalew Getanew , Gebeyehu Kasse , Destaw Belete , Abebe Mesfin , Girma Bekahegn , Bimer Kirubel , Kebede Daniel
Published: April 2023

Background: A neural tube defect is a form of congenital malformation that can occur in the early embryonic period and result in child morbidity and mortality. Little emphasis is given to congenital anomalies, especially neural tube defects, which are significant causes of child death. Ethiopia is one of the countries with a high estimated prevalence of neural tube defects. So, identifying factors contributing to it would be significant for planning risk reduction and preventive strategies. Therefore this study aimed to identify determinants of neural tube defects among neonates admitted to neonatal intensive care units.
Methods: A hospital-based, unmatched case control study was conducted on 104 cases and 208 controls selected from neonatal intensive care units of teaching hospitals in Gedeo Zone and Sidama Region, southern Ethiopia. All neural tube defect cases admitted at the time of the data collection period were included, and controls were selected using a simple random sampling method. Data analysis was done using SPSS version 25. Binary logistic regression was used, and variables with a P value less than 0.25 in bivariate analysis were entered into the multivariable logistic regression model. An adjusted odds ratio with a 95% confidence interval was estimated, and finally, variables that show a level of P value less than 0.05 in multivariable analysis were declared statistically significant.
Result; after controlling confounders, factors like unplanned pregnancy 2.20(1.20- 4.041), history of abortions 2.09(1.19-3.67), khat chewing 6.67(2.95-15.06), antipyretic and analgesic medications 2.87(1.47-5.56) and, being a female neonate 2.11(1.21-3.67) were significantly associated with a neural tube defect.
Conclusion: In this study, different determinants were identified and linked with neural tube defects .hence, the behavioral, medical, and obstetrical conditions of mothers need serious evaluation in the pre-pregnancy period. So it is highly recommended to improve preconception counseling and prenatal care practices, which could reduce the risk of neural tube defects.
A Framework on Developing an Integrative Medicine Clinical Practice Guideline (CPG) for Systemic Lupus erythematosus (SLE) with Comorbidities Management in Hong Kong
Authors: Chen Yuanyuan , Li Philip Hei , Zhang Cheng , Wang Ning , Feng Yibin , Lau Che-Shing
Published: April 2023

Background: Systemic Lupus erythematosus (SLE) is a heterogeneous autoimmune disease that affects multiple organs. In most patients with SLE, the comorbidity manifests within three years of initial diagnosis. In Hong Kong, SLE with comorbidities significantly affect patients' quality of life and contributes to mortality. Due to the complexity of comorbidities, clinicians require comprehensive suggestions across disciplines. An integrative medicine clinical practice guideline (CPG) must be developed for the management of SLE with comorbidities. Therefore, this framework is designed to address multimorbidity in SLE patients.
Methods & Results: The framework is based on the steps of developing CPGs outlined in the WHO handbook for guideline development, Appraisal of Guidelines for Research and Evaluation II Instrument, Guideline International Network and Reporting Items for Practice Guidelines in Healthcare. The design of CPG for SLE includes nine steps as the followings: topic scoping, establishing a guideline development group, formulating key clinical questions, selecting and rating outcomes, conducting a systematic review of the evidence, assessing the quality of evidence, developing recommendations, drafting and publishing the guideline document, and updating are conducted.
Conclusion: This CPG represents a significant advancement in establishing guidelines for multimorbidity in SLE. It will provide recommendations for the management of comorbidities in SLE. To update and adjust recommendations, further studies with large-scale clinical trials are necessary for the future.
Identification of prognosis-related genes in Burkitt Lymphoma by integrated bioinformatic analysis.
Authors: Xu Yanfeng , Wang Guanyun , Zhang Mingyu , Yang Jigang
Published: April 2023

Background: Burkitt's lymphoma (BL) is a highly aggressive malignant tumor originating from germinal center or post germinal center B cells. The objective of our research was to construct a novel prognostic model of candidate genes based on clinical features.
Methods: Gene expression profile and clinic traits of BL patients were collected from the Gene Expression Omnibus (GEO) database. weighted gene co-expression network analysis (WGCNA) was applied to construct gene co-expression modules, and cytoHub tool was used to find the hub genes. Then, the hub genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and constructed Protein-Protein Interaction (PPI) and Genetic Interaction (GI) Network. By overall survival analysis, prognostic candidate genes were identified. Finally, a nomogram was established to assess the predictive value of hub genes and Drug–Gene interaction were constructed.
Results: In this study, we obtained 8 modules by WGCNA analysis, and there was a significant correlation between the yellow module and age. We identified 10 hub genes (SRC, TLR4, CD40, STAT3, SELL, CXCL10, IL2RA, IL10RA, CCR7 and FCGR2B) by cytoHub tool. Moreover, we found 2 hub genes associated with OS (CXCL10, P = 0.029 and IL2RA, P = 0.0066) by survival analysis. Additionally, we combined the two hub genes and age to build a nomogram. And we also found several potential therapeutic targets for BL with poor prognosis.
Conclusion: From WGCNA and survival analysis, we identified CXCL10 and IL2RA might be prognostic markers for BL.
Isosceles Trapezoidal Spiral Microchannel for Separation of Large particles and Giant Cancer cells
Authors: Park Chanyong , Lim Wanyoung , Song Ryungeun , Han Jeonghun , You Daeun , Kim Sangmin , Lee Jeong Eon , Noort Danny , Mandenius Carl-Fredrik , Lee Jinkee , Hyun Kyung-A , Jung Hyo-Il , Park Sungsu
Published: April 2023

Background: Polyploid giant cancer cells (PGCCs) contribute to the genetic heterogeneity and evolution of tumor cells. To study these cells, they need to be separated from tumor cell populations. However, due to their large size it is challenging to isolate them. Currently used methods, such as fluorescence-activated cell sorting (FACS) require fluorescent labeling which impedes reliable downstream analysis and removal of PGCCs.
Results: This study solves this impediment by separating the PGCCs by applying an isosceles trapezoidal spiral microchannel (ITSμC), which maximizes the Dean drag force (FD) and increases the separation distance between particles through identical vortices. Numerical simulations showed that the ITSμC generated a stronger FD than either rectangular or trapezoidal channels. Experimental results confirmed that the ITSμC aligned large polystyrene (PS) particles (50 μm in average diameter) close to the inner wall, while small PS particles (23 μm in average diameter) were aligned close to the outer wall of the channel. Using the ITSμC, we successfully isolated PGCCs from doxorubicin-resistant triple-negative breast cancer (DOXR-TNBC) cells, including normal-sized cells, with high purity (> 90%), yield (> 90%), and viability (> 90%) at high flow rates (3-4 mL/min) in both cultured and clinical samples.
Conclusion: The ITSμC can be used to separate large rare cells, such as PGCCs, without fluorescent labeling and can be applied to downstream analysis when cells need to be cultured after separation. The generality of the ITSµC methodology makes it a potential method for other heterogeneous cell populations as well as other nano-sized particles.
Placental extracellular vesicles promote cardiomyocyte maturation and fetal heart development
Authors: Renaud Stephen , Jeyarajah Mariyan , Patterson Violet , Bhatttad Gargi Jaju , Zhao Lin , Whitehead Shawn
Published: April 2023

Congenital heart defects are leading causes of neonatal mortality and are often associated with placental abnormalities, but mechanisms are unknown. Herein, we investigated a potential signaling network connecting the placenta and nascent heart in mice. We found that fetal hearts exposed to media conditioned by placental tissue or differentiated wild-type trophoblast stem (TS) cells, but not undifferentiated TS cells, showed increased heart rate and epicardial cell outgrowth. This effect was not observed when hearts were exposed to media from TS cells lacking OVO-like 2, a transcription factor required for trophoblast differentiation and placental development. Trophoblasts released abundant extracellular vesicles into media. These vesicles contained microRNAs such as mmu-miR-1249-3p, which was sufficient to mediate cardio-promoting effects. Our findings provide a potential mechanism whereby the placenta communicates with the fetal heart to promote cardiac morphogenesis, and offers insight into the link between poor placentation and a higher incidence of heart defects.
Early bloomer and future master: getting to the top of the modern badminton world
Authors: Hsu Jen-Hao , Chiang Hung-Chieh Fan , Lee Duan-Shin , Yao Zai-Fu
Published: April 2023

The road to the top is never easy. Here, we tested whether the career progression of elite men's and women's singles badminton players can be predicted by the age of first debut impression on the world stage and the time spent to make it top 150. We extracted and analyzed publicly available data on BWF from October 2009 to October 2022, constructing equivalent fractions to model both time and age to test the predictive linear regression model with Bayesian inference after adjusting for anthropocentric variables. Findings support that the age of first debut impression on the world stage predicts career-high rankings in fluctuating trajectories of over one hundred and twenties world-class elite badminton players. Furthermore, we found that the Matthew effect may not be the case for explaining early-career success in badminton players at a young age, while nature outweighs nurture in future athletic-career success trajectories. The potential relative age effect and early specialization in sports are also discussed.
Comparative Study Between Machine learning algorithms and feature ranking techniques on UI-PRMD dataset
Authors: Zaher Moamen , Ghoneem Amr , Abdelhamid Laila , Ezzat Ayman
Published: April 2023

Rehabilitation exercises reduce the demand for healthcare services over time by decreasing the number of hospital visits, lengths of stay, and readmissions. Since rehabilitation is a continuous process, it is crucial to monitor patient progress. This paper compares various machine learning classifiers which enable patients to perform exercises at home instead of visiting a physiotherapy center. The system assesses the correct performance of the exercises and tracks the patient's improvement, leading to lower rehabilitation costs. A distinct skeletal part, angle, and trajectory are required for each activity to distinguish between the workouts and assess whether they were executed correctly. Data extraction was performed using one Kinect camera, and six feature ranking algorithms were employed to construct the system, with the top features selected. Subsequently, 13 classical machine learning algorithms were implemented to identify the algorithm that produced the most accurate classification results. According to our experiments, Extra Tree Classifier, which employs feature extraction using the ReliefF technique, produces the best classification results, with an accuracy score of 99.94%.
Gut microbial metabolite- PE(0:0/14:0) could inhibit sepsis-induced intestinal injury
Authors: Wang Zetian , Qi Yue , Wang Fei , Ziyao Peng , Han Ruiqin , Wang Xingyun , Jianguo Tang
Published: April 2023

Sepsis causes injury to the intestinal mucosa, bacterial translocation, and worsens intestinal and distant organ injury. Herein, we harvested fecal samples from the sepsis group and the healthy group. Intestinal microbiota 16sRNA sequencing of the fecal samples revealed that sepsis destroyed the imbalance in intestinal microbiota. More recently, there is a growing interest in the link between lipid metabolism and disease. Fecal metabolome analysis has identified four differentially lipid metabolized compounds: PE(O-16:0/0:0), PE(17:0/0:0), PE(0:0/14:0), and PE(12:0/20:5(5Z,8Z,11Z,14Z,17Z)). Subsequently, we found that the relative abundanceof PE(0:0/14:0) was lower in the sepsis group compared with the healthy group. In vitro and in vivoexperimentations were finally used to demonstrated that PE(0:0/14:0) treatment protected against sepsis-induced damage to the intestinal barrier. Collectively, these findings provided new insight into enhanced therapy and/or preventative measures against sepsis-induced damage to the intestinal barrier.
A novel sparse learning method with feature selection for optimizing sensors and predicting structural vibration responses
Authors: Zhang Minzhao , Ding Junliang , Li Bin
Published: April 2023

Monitoring the vibration responses of structures accurately and efficiently is the key point of structural health monitoring (SHM). The monitoring of structural vibration responses depends on the sensor system. Therefore, discovering critical sensor positions is a challenging but beneficial task for SHM. Unfortunately, the predominant approaches only focus on predicting the vibration responses and lack the capability to identify meaningful sensor positions, which inevitably restricts their predictive capabilities. Furthermore, the strong linear correlation between sensors results in instability when selecting sensor locations, which leads to the difficulty of sensor optimization. To bridge this gap, we propose a novel sparse learning method with feature selection (SLMFS) to identify meaningful and interpretable sensor positions. In this method, to facilitate interpretation and stability, we use innovative sparsity-inducing penalties to select the important sensors at both individual and group levels. In addition, we introduce independently regularization term (IR) for stable and consistent feature selection. We also present an efficient iterative optimization algorithm to address the SLMFS, which is guaranteed to converge to the global optimum. Experiments of finite element model are used to validate the effectiveness and accuracy of SLMFS. The results show that the SLMFS could not only predict vibration responses effectively but also identify more accurate and relevant sensor positions that satisfy industrial requirements. Therefore, our learning method could provide a novel and useful methodology for SHM.
Energy consumption analysis for the fine blanking process
Authors: Liu Yanxiong , Zhang Yijun , Ji Kaisheng , Yang Can , Yin Fei , Song Yanli , Hua Lin
Published: April 2023

As an advanced sheet metal processing technology, fine blanking is usually used to produce precision parts for automobiles, aerospace, and other industries, but the forming process consumes huge energy. The previous research on fine blanking has mainly focused on improving the forming quality, but the analysis of process energy consumption is rare. Firstly, the energy consumption of the fine blanking process was analyzed theoretically, and a theoretical model was established. Then, the Ludwik hardening model and Oyane fracture criterion for 16MnCr5 were constructed. Next, the orthogonal experiment was designed to analyze the influence and degree of the main process parameters on surface quality and process energy consumption. Among them, blanking clearance, blank holder type, and blank holder force have the greatest influence on the size of the shear zone, energy consumption of deformation, and total process energy consumption, respectively. Furthermore, the influence mechanism of key process parameters on process energy consumption was deeply revealed from the perspective of deformation area, hydrostatic stress change, and material flow velocity, which provided a theoretical basis for green fine blanking. Finally, the fine blanking experiment was carried out to verify the great difference in surface quality and energy consumption under different process parameter combinations. This paper provides a theoretical direction for the fine blanking process, which can not only get high surface quality but also save energy consumption.
Brewing conditions and low-temperature storage affect the total phenolics, caffeoylquinic acid content, and antioxidant activity of yerba mate infusion
Authors: Khaksar Gholamreza , Chaichana Nantachaporn , Assatarakul Kitipong , Sirikantaramas Supaart
Published: April 2023

Herbal infusions exhibit diverse pharmacological effects, mainly attributed to the high content of phenolics (e.g., caffeoylquinic acids (CQAs)). Herein, we evaluated the content of CQAs in the methanolic extracts of model herbs, namely yerba mate (Ilex paraguariensis), stevia (Stevia rebaudiana), and Pluchea indica, showing that yerba mate had the highest total CQA content (108.05 ± 1.12 mg/g of dry weight). The analysis of yerba mate infusions prepared using different steeping times, dried leaf weights, and water temperature demonstrated that the amount of extracted CQAs was maximized (~ 175 mg per 150 mL) when 6 g of dried leaves were steeped in hot water for 10 min. Ten-day refrigerated storage induced no significant changes in the antioxidant activity and total phenolic and CQA contents of the infusion kept in a brown container but negatively affected the above parameters when kept in a clear container, suggesting the detrimental effect of light exposure. Our findings provide consumers, food scientists, and commercial producers with guidelines for optimizing the preparation and storage conditions of herbal infusions.
WITHDRAWN: A Pyroptosis-Related Gene Signature Predicts Prognosis and Reveals Potential Immunotherapy Targets in Kidney Renal Clear Cell Carcinoma
Authors: Song Mengyu , Zhu Zhipeng , Geng Qilong , Chen Bo , Cao Guodong
Published: April 2023

Background:Kidney renal clear cell carcinoma (KIRC) is a common type of renal cancer with poor prognosis and limited treatment options. Pyroptosis, a non-apoptotic form of cell death, has been shown to regulate tumor microenvironment and impact the prognosis of various cancers, including KIRC. However, the role of pyroptosis-related genes (PRGs) in KIRC remains poorly understood. Therefore, we aimed to construct a PRG signature to predict prognosis and identify potential immunotherapy targets for KIRC patients.
Methods:We utilized transcriptomic data from The Cancer Genome Atlas (TCGA) and identified 27 PRGs with prognostic value in KIRC. We used multivariate Cox regression analysis to identify a 5-gene signature (CASP3, CASP4, CHMP3, CHMP4A, and CHMP4C) and divided patients into high-risk and low-risk groups based on their risk scores. We then performed survival analysis and constructed a nomogram to predict the survival probability of KIRC patients. We also performed functional annotation and pathway enrichment analysis of differentially expressed genes (DEGs) between high-risk and low-risk groups to identify potential immunotherapy targets.
Results:The 5-gene signature had significant prognostic value in KIRC, as patients in the high-risk group had poorer prognosis and shorter survival time compared to those in the low-risk group. The risk score calculated based on the signature was an independent prognostic factor. The prognostic model had excellent predictive ability, as shown by the ROC analysis and cross-validation. The DEGs between high-risk and low-risk groups were enriched in immune-related pathways,suggesting potential immunotherapy targets for KIRC.
Conclusions:We constructed a PRG signature that predicts prognosis and identifies potential immunotherapy targets for KIRC patients. The signature has excellent predictive ability and provides insights into the role of pyroptosis in KIRC. These findings could guide the development of new immunotherapy strategies for KIRC and improve the prognosis of KIRC patients.
Trial registration: Not applicable
Effect of Wnt/β-catenin signaling pathway on repair and regeneration after dentin-pulp injury
Authors: Li Yue , Wu Meiying , Xing Xinyu , Li Xingxing , Shi Congchong
Published: April 2023

The Wnt/β-catenin signaling pathway performs multiple essential functions during tooth development. Several Wnt/β-catenin signaling pathway components are expressed in the dental epithelium and mesenchyme during tooth development in humans and mice. Functional studies and experimental analyses in relevant animal models have confirmed the regulatory role of the Wnt/β-catenin signaling pathway on developing tooth formation and adult dental homeostasis. In this study, we used the adult mouse incisor as a model to explore the effect of the Wnt/β-catenin signaling pathway on the repair and regeneration of dental pulp stem cells after injury. We established the dentin-pulp injury models successfully in two different ways and observed an obvious injury in the proximal region of the adult mouse incisor in each group. Faster repair and regeneration were detected after Wnt/β-catenin signaling activation and vice versa, indicating that Wnt/β-catenin signaling is required for cell proliferation and odontoblast differentiation. The same results were further verified by culturing mouse DPSCs in vitro. In our experiments, we found that Wnt10a also showed significant expression when the Wnt/β-catenin signaling pathway was activated and further demonstrated that Wnt10a-mediated Wnt/β-catenin signaling plays a positive regulatory role to regulate DPSCs proliferation and odontoblast differentiation and promoting the repair process of incisor injury. This study highlights the crucial role of the Wnt/β-catenin signaling pathway in the tooth injury and repair and shed new lights on the discovery of novel molecular mechanisms associated with tooth regeneration.
Profilin 2 regulates pyruvate kinase M2 nuclear translocation and potentiates tumor angiogenesis in non-small cell lung cancer
Authors: Xiaohui Du , Chi Ma , Mingxin Xu , Yingyan Wang , Yanbin Kuang , Mengyun Li , Shuang Wen , Hui Zhao , Qi Wang
Published: April 2023

Profilin 2 (PFN2) is an actin-binding protein important for cancer initiation and progression. However, the function and precise role of PFN2 in non-small cell lung cancer (NSCLC) remain unclear. Here, we assessed the expression levels of PFN2 in tissue from patients with NSCLC; identified binding partners using mass spectrometry, co-immunoprecipitations, and molecular modeling; and studied the angiogenic-promoting function of PFN2 using 3D droplet cultures and tube-formation assays. We found that upregulated PFN2 expression is associated with poor prognosis in patients with NSCLC. Knockdown of PFN2 significantly impaired the proliferation and angiogenesis of NSCLC cells, both in vivo and in vitro. Mechanistically, PFN2 physically interacts with pyruvate kinase M2 (PKM2) and modulates extracellular-signal regulated kinase 1/2 (ERK1/2)-mediated phosphorylation of PKM2 at S37, which substantially increases its nuclear translocation. PFN2 knockdown lead to reduced expression of PKM2, p65-NF-κB, and hypoxia-inducible factor (HIF)-1α and inhibited the nuclear translocation of PKM2. This resulted in impaired formation of the PKM2-HIF-1α-p65-NF-κB transcription complex, leading to decreased expression of its downstream target genes VEGFA, CCND1, and MAP2K5. Moreover, mutations in PFN2 at Y134 or S138 impaired its binding to PKM2, nuclear translocation of PKM2, and functionally inhibited angiogenesis in lung cancer cells. Overall, our data provide insights into the role of PFN2 in the regulation of lung cancer angiogenesis and indicate that PFN2 may serve as a therapeutic target against NSCLC.
Preparation of two-stage microporous layers with gradient pore structure using pore-making agent for improving the performance of fuel cell
Authors: Zhao Chongxue , Zhang Haihang , Huang Zheng , Zhao Meng , Chen Haiming , Lin Guangyi
Published: April 2023

In this paper, a gradient pore size structure gas diffusion layer (GDL) was prepared. The pore structure of microporous layers (MPL) were controlled by pore-making agent ammonium bicarbonate (NH4HCO3). The effects of the two-stage MPL and the different pore size structures in the two-stage MPL on the performance of proton exchange membrane fuel cells (PEMFC) were investigated.
The results of the conductivity and water contact angle tests showed that the GDL had outstanding conductivity and good hydrophobicity. The results of the pore size distribution test indicated that the introduction of a pore-making agent altered the pore size distribution of the GDL as well as increased the capillary pressure difference within the GDL. Specifically, there was an increase in pore size within the 7-20 μm and 20-50 μm ranges, which improved the stability of water and gas transmission within the fuel cell.
The maximum power density of the GDL03 was increased by 37.1% at 40% humidity, 38.9% at 60% humidity, and 40.3% at 100% humidity when compared to the commercial GDL29BC in a hydrogen-air environment. The design of gradient MPL ensured that pore size between carbon paper and MPL changed from an initially abrupt state to a smooth transition state, which greatly improved water and gas management capabilities of proton exchange membrane fuel cell.
Functional Electrostimulation Therapy for Vastus Medialis Decreases Varus Thrust During Gait
Authors: Shimada Noboru , Shimada Masashi , Toriyama Minoru , Ishikawa Masakazu , Hirata Kazuhiko , Kono Yoshifumi , Ushio Kai , Mikami Yukio , Adachi Nobuo
Published: April 2023

Background Varus thrust is known to affect the onset and progression of knee osteoarthritis, and delayed activation of the vastus medialis (VM) muscle has been suggested as a cause of this condition. However, no current reports exist on the effects of physical therapy on delayed activity in the VM. In this study, we investigated whether modifying VM activity delay suppresses varus thrust.Methods Ten participants (Kellgren-Laurence grades I:2, II:6, and III:2) diagnosed with knee osteoarthritis were enrolled. All patients wore a functional electrical stimulation (FES) set to contract the VM before heel contact and practiced walking for 10 min. We evaluated the patients’ varus thrust, maximal knee extension angle, maximal varus moment, and VM onset time before and after intervention. A Vicon Nexus ground reaction force meter and a wireless electromyograph DELSYS were used for the evaluation. The task involved free walking with no specified walking speed on a 10-m walkway, and measurements were taken before and after the intervention.Results Analysis revealed a significant difference in varus thrust before and after intervention (2.7 ± 1.1° vs 2.2 ± 1.3°, p < 0.05). Furthermore the vastus medialis activation time decreased following intervention (-0.06 ± 0.09 vs -0.21 ± 0.1, p < 0.05), as did the knee joint extension angle (8.7 ± 5.1° vs 5.5 ± 5.9°, p < 0.05). Similarly, the knee joint varus moment significantly increased after intervention (0.50 ± 0.20° vs 0.56 ± 0.18°, p < 0.05).Conclusion The vastus medialis muscle stabilizes the knee joint by extending the knee joint and pulling the patella inward. When the knee joint is in a slightly flexed position, the medial and lateral collateral ligaments relax, causing the knee joint to move inward and outward. The results of this study suggest that wearing FES caused the VM to act earlier in response to a heel strike, which improved the knee joint extension angle and suppressed the varus thrust.
Acute/atypical Signs of Budd Chiari Syndrome Secondary to Multi-thrombotic Causes
Authors: Qambar Amna , Zaidi Syeda Mahrukh Fatima , Rangwala Burhanuddin Sohail , Alam Muhammad Tanveer
Published: April 2023

Budd-Chiari syndrome is a rare medical condition that affects one in a million people and can be caused by various thrombotic and non-thrombotic factors. In rare instances, multiple factors may contribute to its development, with coagulation factor deficiencies being a less commonly implicated cause. This case report presents a case of BCS associated with protein C deficiency and antiphospholipid syndrome (APLS). The patient is a 30-year-old woman who was brought in due to sudden abdominal distension. She had a three weeks history of intractable vomiting and loose stools. There was also a history of repeated miscarriages. The laboratory findings revealed slightly elevated liver enzymes, a positive Anti-β2 GPI screening, moderately decreased Protein C level and activated protein C resistance/FV Leiden. The patient was discharged after 21 days of inpatient treatment with symptomatic improvement.
What factors promote the development of technological innovation? An analysis of 286 Chinese cities
Authors: LI Yang , CAI Zhaoyang , CAO Shixiong
Published: April 2023

Scientific discovery and technological innovation are the ultimate forces that promote socioeconomic development. However, researchers are not certain which factors play a leading role in scientific discovery and technological innovation and what differences in these factors exist between regions. In this study, we selected 286 Chinese cities at the same administrative level and developed a coupling model to link them within a comprehensive evaluation framework, then performed multiple-regression analysis and geographically weighted regression to identify the key driving factors for scientific discovery and technological innovation, their contributions to innovation, and their regional differences. We found that marketization (development of a market economy), population density, industrial upgrading, health care, and industrialization most strongly promoted Chinese innovation from 2007 to 2019, whereas the innovation level decreased with increasing environmental pollution. To promote scientific discovery and technological innovation, we should increase marketization, promote market-oriented reform of universities, sustainably increase population density, and upgrade the industrial structure. These results will provide important guidance for the formulation of China's future science and technology policy, but our method will also help other countries improve their own science and innovation by learning from China's experience.
Longitudinal Changes of Refractive Error in Preschool Children with Congenital Ectopia Lentis
Authors: Lian Zhangkai , Hu Yin , Liu Zhenzhen , Young Charlotte Aimee , Liu Siyuan , Zheng Danying , Jin Guangming
Published: April 2023

Background: Congenital ectopia lentis (CEL) is a hereditary eye disease which severely impacts preschool children’s visual function and development. This study aimed to evaluate the longitudinal changes in spherical equivalent (SE) refractive error in preschool children with CEL.
Methods: A retrospective cohort study was conducted at Zhongshan Ophthalmic Center, Guangzhou, China. Medical records of CEL patients under 6-year-old who were diagnosed with Marfan syndrome at the initial visit from January, 2014 to March, 2022 were collected and were divided into surgery and non-surgery groups. Mean change rate of SE in the two groups were evaluated and the potential associated factors of SE change rate were investigated by mixed-effect regression model.
Results: A total of 94 preschool patients from 14 provinces of China were included. Among the 42 children of the surgery group, the mean age with standard deviation (SD) was 5.02±0.81 years and patients experienced a myopic shift of -0.05±0.09 D/month in average. The mean age with SD of the 52 children of the non-surgery group was 4.34±1.02 years and the mean myopic shift was -0.09±0.14 D/month. The mixed-effect regression model identified that higher degree of myopia at baseline was associated with slower myopic shift both in surgery (β= 0.901, 95% CI: 0.822~0.980, P< 0.001) and in non-surgery group (β= 1.006, 95% CI: 0.977~1.034, P< 0.001) in CEL patients. Surgical treatment (β= 2.635, 95% CI: 1.376~3.894, P< 0.001) was associated with slower myopic shift in all participants CEL patients.
Conclusions: Myopic progression was slower in the surgery group than in the non-surgery group of CEL. Preschool CEL patients who met the surgical indication are suggested being performed with timely surgery to slow down the myopic progression.
Association of receiving opioid medication-assisted treatment with sexual identity and mental health/substance use disorder symptoms in a nationally representative sample of adults
Authors: Adzrago David , Evans Gabrielle S , Dias Emanuelle M , Kwentua Victoria , White Grace Elizabeth , Wilkerson J. Michael
Published: April 2023

Background Although the literature suggests that medication-assisted treatment (MAT) is an effective treatment for opioid use disorder, limited studies have assessed the prevalence or the association between MAT use and sexual identity, mental health, or substance use disorder among a nationally representative sample. We assessed the prevalence and association of opioid MAT use between sexual identity, depressive disorder symptoms, alcohol use dependence, and marijuana use dependence in the United States.Methods We used the 2019 National Survey on Drug Use and Health public-use data on adults aged 18–64 years (N = 38,841) to conduct a weighted multivariable logistic regression analysis.Results A total of 4.80% and 2.32% of the population identified as bisexual and lesbian/gay, respectively. About 0.31% (612,750 people) of the population reported receiving opioid MAT, 3.73% had alcohol use dependence, 1.42% had marijuana use dependence, and 9.13% had major depressive episode (MDE) symptoms. Of those who had received opioid MAT, 0.57% were bisexuals and 1.07% were lesbians/gays, 0.65% were people with alcohol use dependence, 2.32% with marijuana use dependence, and 1.59% with MDE symptoms. Lesbian/gay individuals were more likely to receive opioid MAT (AOR = 3.43, 95% CI = 1.42, 8.25) compared to heterosexual individuals. The odds were higher for people with marijuana use dependence (AOR = 3.44, 95% CI = 1.47, 8.06) and MDE symptoms (AOR = 5.22, 95% CI = 3.46, 7.89) than their counterparts.Conclusions In this study, sexual minorities, people with MDE symptoms, and those dependent on marijuana use were more likely to receive opioid MAT, suggesting the need to investigate further opioid use disorder symptoms and their risk factors among these populations.
Multiple-habitat graphs for improving functional connectivity assessment among composite habitat species
Authors: Clauzel céline , Godet Claire , Tarabon Simon , Bailleul Marion , Eggert Christophe , Miaud Claude
Published: April 2023

The authors have requested that this preprint be removed from Research Square.
Livestock wastes-derived capped and bactericidal silver nanoparticles induce immuno-physiological responses in fish for multiple stress resilience – The One Health Approach
Authors: Lamare Sowa o , Krishnani K. K. , Kumar Neeraj , Pathak Madhuri , Upadhyay Ajay , Sarkar Biplab , Verma AK , Chakraborty Puja
Published: April 2023

The present study elucidates the extracellular synthesis of capped silver nanoparticles using processing waste (intestine) of sheep and swine in aqueous media and phosphate buffers incubated with silver nitrate by dispensing with the addition of any capping agent and the advantage of avoiding the agglomeration and loss of nanosized characteristics of AgNPs. The synthesis of Ag-NPs was ascertained by UV-VIS spectrophotometry of the incubated suspension of yellowish-brown at 400-410 nm. The Ag-NPs were further characterized using a High-Resolution Transmission Electron Microscope, which confirmed that the Ag-NPs were primarily spherical and had a size range of 5–100 nm with a maximum frequency fall between 5-20 nm, 21-30 nm, 31-50 nm and a few falls within 51-100 nm. In addition, Ag-NPs synthesized using sheep and pig wastes are characterized by Dynamic Light Scattering, which confirmed the high stability of Ag-NPs with a zeta potential of -27 and -32 mV respectively. Biomolecules and biological extracts of sheep and swine waste act as biogenic reducing and capping agents. Based on the zone of inhibition achieved through the agar well diffusion method, Ag-NPs biosynthesized using sheep waste showed high bactericidal properties against Aeromonas hydrophila, Edwardsiella tarda, and Micrococcus luteus as compared to swine waste-derived AgNPs. The chronic toxicity analysis of biosynthesized Ag-NPs on Pangasianodon hypophthalmus was carried out using stress biomarkers such as an antioxidant enzyme, AChE, and metabolic enzyme activity. Chronic toxicity of synthesized Ag-NPs was found to increase with increased sub-lethal ammonia concentration and temperature. The findings of this study revealed that biosynthesis of capped and non-agglomerated Ag-NPs can be undertaken by using sheep and swine wastes for their potential application in aquaculture based on the properties observed in characterization, bactericidal activity, and physiological responses of the fish.
Parkin promotes airway inflammatory response to interferon gamma
Authors: Dimasuay Kris Genelyn , Berg Bruce , Schaunaman Niccolette , Nichols Taylor , Chu Hong Wei
Published: April 2023

Background Increased type 2 interferon (i.e., IFN-γ) signaling has been shown to be involved in airway inflammation in a subset of asthma patients who often show high levels of airway neutrophilic inflammation and poor response to corticosteroid treatment. How IFN-γ mediates airway inflammation in a mitochondrial dysfunction setting (e.g., Parkin up-regulation) remains poorly understood. The goal of this study was to determine the role of Parkin, an E3 ubiquitin ligase, in IFN-γ-mediated airway inflammation and the regulation of Parkin by IFN-γ.Results Using a mouse model of IFN-γ treatment in wild-type and Parkin knockout mice, and cultured human primary airway epithelial cells with or without Parkin gene deficiency, we found that Parkin was necessary for the production of neutrophil chemokines (i.e., KC and IL-8) and airway neutrophilic inflammation. Mechanistically, Parkin was induced by IFN-γ treatment both in vivo and in vitro, which was associated with less expression of a Parkin transcriptional repressor Thap11. Overexpression of Thap11 inhibited Parkin expression in IFN-γ-stimulated airway epithelial cells.Conclusions Our data suggests a novel mechanism by which IFN-γ induces airway neutrophilic inflammation through the Thap11/Parkin axis. Inhibition of Parkin expression or activity may provide a new therapeutic target for the treatment of excessive neutrophilic inflammation in an IFN-γ high environment.