bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluate the Efficacy of Endodontic Microsurgery on Teeth Having Undeveloped Root Apex Failed in Non-surgical Treatment with Periapical Inflammation
Authors: Tang Yumu , Xu Ke , Chen Yumao , Lu Le
Published: March 2023

Background: To evaluate the efficacy of endodontic microsurgery on teeth with undeveloped root apex and periapical inflammation caused by an abnormal central cusp fracture due to failed nonsurgical treatment.
Methodology: We performed endodontic microsurgery on 80 teeth in 78 patients with undeveloped root apex and periapical inflammation caused by an abnormal central cusp fracture due to failed nonsurgical treatment. All patients were clinically and radiologically examined 1 year after surgery, and the data were statistically analyzed using the SPSS 27.0 software package.
Results: Of 80 teeth in 78 patients, periapical lesions disappeared in 77 teeth at the 1-year postoperative follow-up, with a success rate of approximately 96.3% (77/80). Sex, age, extent of periapical lesions, and the presence of the sinus tractdid not affect the efficacy of endodontic microsurgery. The differences between groups were not statistically significant (P > 0.05).
Conclusions: On failure of nonsurgical treatment in teeth with undeveloped root apexand periapical inflammation caused by an abnormal central cusp fracture, endodontic microsurgery may be a good clinical treatment option.
The impact of the COVID-19 pandemic on the residential aged care sector, responses and recommendations: A systematic scoping review
Authors: Battams Samantha , Martini Angelita
Published: March 2023

Objective:This systematic scoping review sought to identify the impact of the COVID-19 pandemic on the residential aged care (RAC) sector, its system components, and the range of COVID-19 response strategies across the sector.Methods: ProQuest, PubMed, CINAHL, Google Scholar and Cochrane Central were searched April-August 2022 for peer reviewed articles and grey literature. One hundred and forty six articles on the impact of the COVID-19 pandemic on the RAC sector and sector interventions/policy responses are included in this review.Results:The World Health Organization’s (WHO) six building blocks of health systems were used to categorise impacts and interventions. The COVID-19 pandemic generally highlighted poor resourcing of the RAC sector and exacerbated workforce shortages; led to increased workload, changes in job demand and declines in worker mental health; revealed poor integration across health and aged care sectors and reduced advance care and palliative care planning. Social restriction measures led to declines in the physical, mental health and cognitive decline of residents in RACFs, in particular those with cognitive impairment. Innovative care models included the introduction of outreach teams and primary care models for RACFs and increased use of telehealth and videoconferencing for social engagement, although there was mixed evidence on the use of telehealth for people with cognitive impairment.Discussion:Additional funding of the RAC sector is required to boost workforce numbers and training, and support worker mental health, along with policies which attract, maintain and support workers from culturally and linguistically diverse (CALD) backgrounds. COVID-19 response strategies in RACFs need to ensure that all residents have access to resources such as telehealth for health and social engagement, including residents with cognitive impairment. Clear guidelines and additional resourcing are required for utilisation of telehealth during a pandemic. Additional research on appropriate COVID-19 responses for residents with cognitive impairment is required, along with a balance between infection prevention and control and social engagement strategies.
Supportive care and information needs of men following prostate cancer treatment: a qualitative study
Authors: Blackmore Tania , Chepulis Lynne , Burrett Vanessa , Akapita Teresa , Kidd Jacquie , Devcich Glen , Holmes Michael , Lawrenson Ross
Published: March 2023

Purpose

To assess the psychosocial and informational needs of prostate cancer survivors who had attended an information session designed to help men better understand their diagnosis and treatment options.

Methods

We thematically analysed the qualitative interviews of 12 prostate cancer survivors and identified emerging themes related to psychosocial and informational needs following treatment.

Results

The most common source of psychosocial distress was side effects related to androgen deprivation therapy. Young men exhibited higher levels of distress than older men. All men were reluctant to seek psychosocial support, and despite attending the information session, still expressed a desire for more information and clarity around their diagnosis and treatment options.

Conclusions

A minority of prostate cancer survivors experience ongoing psychosocial needs associated with treatment side effects. These men often expressed treatment regret, but did not seek support for their distress, highlighting a barrier that prevents male help-seeking.

Implications for Cancer Survivors

The provision of an additional information session offers a vital service to patients and has the potential to help bridge the difficult period between initial diagnosis and treatment, when prostate cancer patients must make important health decisions. Further investment in information sessions is needed to meet the informational needs of prostate cancer patients.
An in-depth analysis of perinatal related mortality among women of South Asian ethnicity in Aotearoa New Zealand, compared to other ethnic groups
Authors: de Graaff Esti , Sadler Lynn , Lakhdhir Heena , Simon-Kumar Rachel , Peiris-John Roshini , Burgess Wendy , Okesene-Gafa Karaponi , Cronin Robin , McCowan Lesley , Anderson Ngaire
Published: March 2023

Background: International and national New Zealand (NZ) research has identified women of South Asian ethnicity at increased risk of perinatal mortality, in particular stillbirth, with calls for increased perinatal research among this ethnic group. We aimed to analyse differences in pregnancy outcomes and associated risk factors between South Asian, Māori, Pacific, and New Zealand European women in Aotearoa NZ, with a focus on women of South Asian ethnicity, to ultimately understand the distinctive pathways leading to adverse events.
Methods: Clinical data from perinatal deaths between 2008 and 2017 were provided by the NZ Perinatal and Maternal Mortality Review Committee (PMMRC), while national maternity and neonatal data, and singleton birth records from the same decade were linked using the Statistics NZ Integrated Data Infrastructure for all births. Pregnancy outcomes and risk factors for stillbirth and neonatal death were compared between ethnicities with adjustment for pre-specified risk factors.
Results: Women of South Asian ethnicity were at increased risk of stillbirth (aOR 1.51, 95%CI 1.29-1.77), and neonatal death (aOR 1.51, 95%CI 1.17-1.92), compared to NZ European. The highest perinatal related mortality rates among South Asian women were between 20-22 weeks gestation (at 1.3 and 1.1/1,000 ongoing pregnancies; p<0.01 compared to NZ European) and at term, although differences by ethnicity at term were not apparent until ≥41 weeks (p<0.01 compared to NZ European). No major differences in known and collected risk factors for stillbirth and neonatal death were observed between ethnicities. Among perinatal deaths, South Asian women were overrepresented in a range of metabolic-related disorders, such as gestational diabetes, pre-existing thyroid disease, or maternal red blood cell disorders (all p<0.05 compared to NZ European).
Conclusions: Women of South Asian ethnicity in Aotearoa NZ were at increased risk of stillbirth and neonatal death compared to NZ European women. Metabolic-related factors may contribute to adverse pregnancy outcomes in South Asian mothers.
Considering Costs in Health Professions Education: A Scoping Review Protocol
Authors: Yaros J.K. , Mortier C.A. , Egbrink M.G.A. oude , Evers S.M.A.A. , Paulus A.T.G.
Published: March 2023

Background
Profound changes in the healthcare sector and the global shortage of healthcare workers are driving the demand to update and scale-up health professions education (HPE). At the same time, educational institutions are contending with resource scarcity and the decision of where and how to allocate resources must be made conscious of cost. To improve rigor in the economic evidence generated for such decisions, it is necessary to have a better understanding of which costs and costing methods are relevant to HPE. Therefore, this protocol has been developed to outline the rationale and methods for a scoping review of the literature intended to map the current state of cost evidence for HPE.
Methods
This protocol is developed in accordance with the Joanna Briggs Institute Manual for Evidence Synthesis and PRISMA-ScR guidelines. PubMed, ERIC, CINAHL and PsycInfo will be scoped for all types of English language publications from 2012 onward that investigate costs associated with the education of health professionals. Two independent reviewers will assess publications for eligibility. Data will be extracted on the topic of investigation, educational setting, level of education, type of economic evaluation, methods for cost identification, stakeholder perspective and individual cost components.
Discussion
This protocol presents the initial concept for an exploratory review of the costs associated with HPE. This format was chosen for its iterative nature, which allows this relatively unexplored topic to be broadly scoped from multiple educational and economic databases and simultaneously narrowed in focus in response to the discovery of evidence. The results from this planned investigation will provide an overview of the existing evidence on costs and costing methods in HPE, which can be used to set a research agenda on economics of HPE and contribute to cost conscious HPE in practice.
Trial Registration
This protocol was prospectively registered on Open Science Framework (OSF) on June 13, 2022 and is available at https://doi.org/10.17605/OSF.IO/ET4XB.
The neuromorphic Mosaic: in-memory computing and routing for small-world graphical networks
Authors: Dalgaty Thomas , Moro Filippo , Demirağ Yiğit , De Pra Alessio , Indiveri Giacomo , Vianello Elisa , Payvand Melika
Published: March 2023

The connectivity in the brain is locally dense and globally sparse - giving rise to a small-world graph. This is a principle that has persisted during the evolution of many species - indicating a universal solution to the efficient routing of information. However, existing circuit architectures for artificial neural networks neither leverage this organization nor do they efficiently support small-world neural network models. Here, we propose the neuromorphic Mosaic: a non-von Neumann systolic architecture that uses distributed memristors, not only for in-memory computing, but also for in-memory routing, to efficiently implement small-world graph topologies. We design, fabricate, and experimentally demonstrate the building blocks of this architecture, using integrated memristors with 130 nm CMOS technology. We demonstrate that neural networks implemented following this approach can achieve competitive accuracy figures compared to equivalent unconstrained and full-precision networks, for three real-time benchmarks: classification of electrocardiography signals, keyword spotting and motor control via reinforcement learning. The Mosaic shows improvements between one and four orders of magnitude, compared to other event-based neuromorphic architectures for routing events across the network. The Mosaic opens up a new scalable approach for designing edge AI systems based on distributed computing and in-memory routing, offering a natural platform onto which architectures inspired by biological nervous systems can be readily mapped.
Enhancement in ionic conductivity of liquid crystals by graphene/metal-oxide-nanocomposite
Authors: Khodaee M. , Dalir N. , Feghhi F. , Ansari N. , Mohammadimasoudi M. , Goudarzi A. , Nasiri A. Faghih , Kolahdouz M. , Mohseni S. M.
Published: March 2023

Enhancing the ionic conductivity of liquid crystal (LC) circumvents challenges for application in advanced electronic components. Toward this, using additives made of different nanostructures that could result in functional LCs is suggested. In this paper, various concentrations of graphene (Gr)/metal-oxide (Fe3O4) nanocomposite (GMN) (0.0001-1 w%) were added to E7 nematic LC. We found that the role of anisotropic Gr flakes, their edges as well as surface-decorated-metal-oxide-additives have significant impact on electrical properties of E7. A range of appropriate additives of such a nanocomposite enhances the electrical conductivity of LCs. This effect can be traced through the decrease in the formation of GMN aggregates in the E7 and increase in the electrostatic field at the edges of the Gr sheets. Moreover, the presence of metal-oxide nanoclusters due to the presence of oxygen vacancies and defects facilitates the construction of conductive network for improving the charge transfer pathways and contributes to a stronger interaction of the Gr surface with charged species. These factors can provide Gr layers as dipole moments and lead to signal propagation in the dielectric medium. Our finding conveys a pathway toward significant enhancement of ionic conductivity in the LC family which can be useful for functional applications.
Individual differences in knowledge network navigation
Authors: Zhu Manran , Yasseri Taha , Kertész János
Published: March 2023

As online information accumulates at an unprecedented rate, it is becoming increasingly important and difficult to navigate the web efficiently. To create an easily navigable cyberspace for individuals across different age groups, genders, and other characteristics, we first need to understand how they navigate the web differently. Previous studies have revealed individual differences in spatial navigation, yet very little is known about their differences in knowledge space navigation. To close this gap, we conducted an online experiment where participants played a navigation game on Wikipedia and filled in questionnaires about their personal information. Our analysis shows that participants' navigation performance in the knowledge space declines with age and increases with foreign language skills. The difference between male and female performance is, however, not significant in our experiment. Participants' characteristics that predict success in finding routes to the target do not necessarily indicate their ability to find innovative routes.
Comparative study of antennal sensilla in irradiated male and female fall armyworm, Spodoptera frugiperda with gamma radiation
Authors: Zahran Nagwan , Hamza Ali , Kandil Mervat
Published: March 2023

Morphology of the Fall Armyworm (FAW) Spodoptera frugiperda adult antenna was photographed by Scanning Electron Microscope (SEM). The type of the antenna is filiform, and consists of three main segments: the scape, pedicel and flagellum. Scanning of antennae revealed the presence of eight types of sensilla in male and seven in female which are Sensillum Squamiformia, Scales, Sensillum Styloconica, Sensillum Trichodea, Sensillum Chaetica lateral and central, Sensillum Coeloconica, Sensillum Auricillica and Sensillum Basiconica which are distributed among the antennal segments. These types of sensilla found in both sexes except Sensillum Styloconica. The effect of four doses of gamma radiation (50, 100, 150 and 200 Gy) on the antennal sensilla were studied. These studies revealed that these higher doses in both sexes have certain malformation features in the sensilla. The magnitude of these malformations was dose dependent as they increased by increment of the doses applied. These malformations in the sensilla and its role in courtship and mating inhibition were discussed.
Popularization of Science in Colleges and Universities in the New Network Media Environment Based on Artificial Intelligence
Authors: Sheng Lin
Published: March 2023

By introducing new network media and artificial intelligence technology into the field of science popularization in colleges and universities, this research strives to solve the practical problems of science popularization websites that are large but not distinctive in the current era, and tries to improve the social impact and economic benefits of such science popularization platforms, so as to promote platform innovation and break away from the stereotyped system design form. Through the establishment of a science popularization system for colleges and universities, the mainstream content management can be achieved, and the differentiation management between the main station and the sub station can be completed. The platform design is implemented by Java EE technology, carrying multi-functional module components, completing the componentized configuration of the system, which can be developed sustainably and has good security. The university science popularization system can operate stably in most environments, and the security management measures are strict. It can take multiple means to effectively protect the security of information, and it is simple and easy to implement. It can be seen from the design of simulation experiment that this promotion system, through the design of hybrid recommendation strategy, can_ UserCF and SBBRM_ Based on the advantages of Doc2Vec algorithm, the accuracy and coverage of system recommendations are improved, making it more universal. And the hybrid recommendation results can be compared with the main recall model to prove the efficiency of the system. This paper introduces artificial intelligence technology into the field of science popularization in colleges and universities, so as to realize the system design and improvement based on the new network media environment.
An empirical analysis of dynamic network model of international trade by using enterprise sample simulation and improved ANN algorithm
Authors: Liu Ruiqian , Chen Xiaofei
Published: March 2023

With the support of enterprise intelligence system, an intelligent modeling method based on synthesizing various data sources and complex metabolic networks is adopted to provide technical support for the practical application of complex large-scale dynamic models. Academic research on international trade networks relies to a large extent on network models based on macro-national data and static analysis of international trade patterns, which are usually based on charts for trade flows and economic globalization. In this paper, we analyze the complex dynamic meta-network model of international trade based on improved neural network algorithm. Because BP neural networks run through the best neural network model that is constantly adjusted according to weighted values, the adjustment of neural network value is reduced, which may be an effective means to improve the efficiency of intrusion testing applications. The simulation results show that the model has good explanatory power. The internationalization of enterprise market as the main body of international business activities affects the establishment and development of a national or regional international trade network. Therefore, there is a need to study international trade networks using data at the micro level. This paper suggests an interdisciplinary approach to the study of international trade networks and a micro-level study of international trade networks. The model based on complex meta-network dynamic model elements, introduce the dynamic network representation, use temporary labels to define the network boundary characteristics.
Internet financial forecasting and digital economy development by using machine learning algorithm in the New Consumption Environment
Authors: Huang Peng
Published: March 2023

DPDK (Data Plane Development Kit) provides an effective solution for the rapid processing of general multi-core processor platforms. Research based on DPDK on a general-purpose multi-core processor platform can use CPU cache to improve packet forwarding and processor core performance, as well as network function virtualization performance. In the parallel development of finance and network, people find that complex financial problems can be well solved through big data network. The rapidly changing financial market is affected by economic and political factors, and the generation of financial data is also highly uncertain. However, financial forecast analysis and forecast modeling are of great significance. As a whole, this trend could help inform policy; from a meso level, it can be insightful The changes in financial data are conducive to the planning of business strategies for enterprises and gaining market competitive advantages; from a micro level, individual investors will pay attention to historical data changes and the development of industries or companies before making investment decisions in order to obtain benefits. Internet technology can strengthen the accuracy of financial forecasting, so as to effectively avoid risks, but also can promote the development of digital economy, reduce labor costs, improve the breadth and depth of financial services in digital economy.
Campus IoT system and students’ Employment Education Innovation based on mobile edge computing
Authors: Xie Tian
Published: March 2023

With the rapid development of Internet of things, more and more computing intensive applications are running on the Internet of things terminals. These computing intensive applications usually need strong computing power. It requires high energy consumption to process these applications locally through Internet of things terminals. At the same time, the computing capacity and battery capacity of the Internet of things terminals are limited. To solve this problem, computing tasks can be transferred from single Internet (IOT) terminals to cloud computing with powerful computing functions. However, cloud computing has inherent limitations. That is, the distance from user terminal to remote cloud center server is very long, and the application delay time is too long. Mobile edge computing, as a new computing technology, is introduced to the network edge, which provides computing services that can generate enough capacity by obtaining a large number of free computing capacity and scattered storage space on the edge. This is a task that is used in mobile terminal or Internet of things terminal to perform computationally intensive and wait time important tasks. Unlike traditional cloud computing, mobile edge computing can be extended to wireless access points. This paper uses mobile edge computing Internet of things technology to study campus system innovation and student employment education. The high quality employment guidance education for college students is not only an important way to promote the external output of talents, but also an important link to realize the connection between universities and enterprises, and also an important means for universities to provide services to the society.
Factors influencing visual acuity in patients with active polypoidal choroidal vasculopathy and imaging parameters changes
Authors: Xia Fan , Hua Rui , Xing Peiyu , Zhang Hao , Niu Tongtong
Published: March 2023

We performed a retrospective, observational study for 51 eyes of 51 treatment-naive patients with polypoidal choroidal vasculopathy (PCV), whose lesion ranged within the 6x6mm scope of optical coherence tomography angiography (OCTA). Patients were divided into two groups based on the pattern of branching vascular network (BVN) on OCTA: ill-defined group and well-defined group. BVN morphology was not related to baseline best-corrected visual acuity (BCVA). But the improvement of BCVA had a significant positive relationship with the pattern of BVN on OCTA (r = 0.306, p = 0.031). The BCVA in the ill-defined BVN group (-0.18 [interquartile range: -0.40 to 0.00]) was significantly improved after anti-vascular endothelial growth factor (VEGF) injections, compared with that (0.00 [interquartile range: -0.18 to 0.00]) in the well-defined group (z = 2.143, p = 0.032). Multiple logistic regression analysis showed that male sex, smaller number of injections, and presence of polypoidal lesions on OCTA images at baseline predicted a poor prognosis of polypoidal lesions on OCTA images after anti-VEGF therapy (all p < 0.05). Finally, BCVA at baseline and the number of injections were protective factors for BCVA after anti- VEGF therapy (all p < 0.05). In contrast, history of hypertension and macular edema at baseline were risk factors for BCVA after anti-VEGF injections (all p < 0.05).
Giant electromechanical response from defective non-ferroelectric epitaxial BaTiO3 integrated on Si (100)
Authors: Vura Sandeep , Parate Shubham , Pal Subhajit , Khandelwal Upanya , Rai Rajeev , Molleti Sri Harsha , Kumar Vishnu , Ventrapragada Rama , Patil Girish , Jain Mudit , Mallya Ambresh , Ahmadi Majid , Kooi Bart , Avasthi Sushobhan , Ranjan Rajeev , Raghavan Srinivasan , Chandorkar Saurabh , Nukala Pavan
Published: March 2023

Lead-free, silicon compatible materials showing large electromechanical responses comparable to, or better than conventional relaxor ferroelectrics, are desirable for various nanoelectromechanical devices and applications. Defect-engineered electrostriction has recently been gaining popularity to obtain enhanced electromechanical responses at sub 100 Hz frequencies. Here, we report record values of electrostrictive strain coefficients (M31) at frequencies as large as 5 kHz (1.04×10− 14 m2/V2 at 1 kHz, and 3.87×10− 15 m2/V2 at 5 kHz) using A-site and oxygen-deficient barium titanate thin-films, epitaxially integrated onto Si. The effect is robust and retained even after cycling the devices > 5000 times. Our perovskite films are non-ferroelectric, exhibit a different symmetry compared to stoichiometric BaTiO3 and are characterized by twin boundaries and nano polar-like regions. We show that the dielectric relaxation arising from the defect-induced features correlates very well with the observed giant electrostrictive response. These films show large coefficient of thermal expansion (2.36 ⋅ 10− 5/K), which along with the giant M31 implies a considerable increase in the lattice anharmonicity induced by the defects. Our work provides a crucial step forward towards formulating guidelines to engineer large electromechanical responses even at higher frequencies in lead-free thin films.
The impact of dyslipidemia on lumbar intervertebral disc degeneration and vertebral endplate modic changes: a cross-sectional study of 1035 citizens in China
Authors: Yuan Liang , Huang Zhengqi , Han Weitao , Chang Ruiming , Sun Bo , Zhu Mingxi , Li Chenjing , Yan Jiansen , Liu Bin , Yin Haidong , Ye Wei
Published: March 2023

Background: Intervertebral disc degeneration (IDD) and vertebral endplate Modic changes (MCs) are common lumbar degenerative phenotypes related to low back pain (LBP). Dyslipidemia has been linked to LBP but its associations with IDD and MCs have not been fully elucidated. The present study aimed to address the possible link between dyslipidemia, IDD and MCs in the Chinese population.
Methods: 1035 citizens were enrolled in the study. The levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were collected. IDD was evaluated based on the Pfirrmann grading system and subjects with an average grade ≥3 were defined as having degeneration. MCs were classified into typical types 1, 2 and 3. Covariables, including age, sex, BMI and fasting plasma glucose, were included for the adjustment of the logistic analyses.
Results: The degeneration group included 446 subjects while the nondegeneration group included 589 subjects. The degeneration group had significant higher levels of TC and LDL-C (p<0.001) whereas TG and HDL-C were not significant different between the two groups. TC and LDL-C concentrations were significantly positively correlated with average IDD grades (p<0.001). Multivariate logistic regression revealed that high TC (≥6.2 mmol/L, adjusted OR=1.775, 95% CI=1.209-2.606) and high LDL-C (≥4.1 mmol/L, adjusted OR=1.818, 95% CI=1.123-2.943) were independent risk factors for IDD. Type 1 MC presented in 84 (8.12%) subjects, type 2 MC presented in 244 (23.57%) subjects, type 3 MC presented in 27 (2.61%) subjects and no MC was observed in the remaining 680 (65.70%) subjects. The type 2 MC group demonstrated a higher level of TC, but the association between serum lipids and MCs could not be confirmed in further multivariate logistic regression.
Conclusions: High TC (≥6.2 mmol/L) and LDL-C (≥4.1 mmol/L) concentrations were recognized as independent risk factors for IDD for citizens in China. However, the epidemiological association between dyslipidemia and MCs could not be determined. The biomolecular effect of excess serum cholesterol may play a vital role in the development of IDD. Hypolipidemic treatment, especially when targeting cholesterol, may provide new opportunities in the management of lumbar disc degenerative diseases.
SASH3 is an unfavorable prognostic immune biomarker in patients with acute myeloid leukemia(AML).
Authors: Qiu Zhengqi , Wang Lin , Jia Xueyuan , Yang Yanru
Published: March 2023

Background:
Acute myeloid leukemia(AML) is a malignant clonal disease. As the most common type of leukaemia, it is characterised by poor treatment outcomes and a poor prognosis in both the paediatric and adult populations. Improving anti-tumour responses through immunomodulators is a promising strategy or a new avenue for AML treatment.
Methods:
Using publicly available data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx), we examined the association between SAM And SH3 Domain Containing 3(SASH3) and AML. Wilcoxon signed-rank test and logistic regression were used to analyze the relationship between clinical pathologic features and SASH3. Cox regression and Kaplan-Meier methods were used to determine the clinical characteristics associated with overall survival in patients with AML. Then the relationship between immune infiltration and SASH3 was also analyzed. The research finding was validated by data from the Gene Expression Omnibus (GEO) database.
Results:
Compared to normal patients, SASH3 expression in AML patients was significantly higher (p = 3.05e-34) and strongly associated with survival. In addition, SASH3 expression was significantly correlated with survival outcome (p = 5.3E-03) and cytogenetic risk (p = 3E-04) in AML. SASH3 expression was correlated with the expression of the genes HCK, SYK, FYN, ITGB2, PIK3CD, FGR, PIK3R5, VAV1, LCP2, and GRB2. Our study suggests that SASH3 expression is strongly associated with AML development and survival outcomes as well as multiple cancer-related genes and pathways, such as the HCK(Hematopoietic cell kinase) and regulation of small GTPase-mediated signal transduction.
Conclusion:
Our study revealed that SASH3 expression is closely associated with AML development and survival outcome, as well as multiple cancer-related genes and pathways, thus highlighting SASH3 as a potential therapeutic marker of AML.
Angelman Syndrome causing UBE3A ligase displays predominantly synaptic ubiquitination activity in the mouse brain
Authors: Mayor Ugo , Alduntzin Unai , Lectez Benoit , Presa Natalia , Osinalde Nerea , Fernandez Marta , Elu Nagore , Ramirez Juanma , Garcia-Barcena Cristina , Aloria Kerman , Frick Andreas , Peñagarikano Olga
Published: March 2023

Angelman Syndrome (AS) is a neurodevelopmental disorder with complex symptomatology caused by the loss of maternal allele expression of one single gene in the brain, the ubiquitin E3 ligase UBE3A. The underlying genetic basis of AS, and the phenotypes observed in both humans and in animal models of AS, have previously been extensively described. However, the molecular mechanisms regulated by UBE3A ubiquitination in the brain remain highly elusive. Previous studies have reported a number of proteins whose abundance or activity are altered in AS models, implicating various signalling pathways in the physiopathology of AS. However, the identified pathways could well be altered further downstream of UBE3A ubiquitination events. We provide the first proteomic report of UBE3A-mediated ubiquitination events in a mammalian brain. For this we have combined the bioUb mouse model with a new mouse strain moderately increasing UBE3A levels. Several proteins known to be involved in the trafficking and maintenance of neurotransmitter receptors as well as proteins relaying the signals of these synaptic receptors are shown here to be ubiquitinated by UBE3A. The identified proteins have roles in higher mental function, long term potentiation, seizures and neurodevelopmental disorders, being involved in the BDNF, RAS/ERK and TSC/mTOR signalling pathways. A reduced ubiquitination of these proteins is expected when UBE3A levels are lower, so their identification could be key to opening novel therapeutic strategies for treating Angelman Syndrome. Further work will be required to characterize how UBE3A timely orchestrates each of these multiple regulatory events in different neuronal subtypes within the human brain.
Molecular reframing of fibroblasts during resolution of arthritis
Authors: Ramming Andreas , Rauber Simon , Mohammadian Hashem , Schmidkonz Christian , Atzinger Armin , Soare Alina , Treutlein Christoph , Kemble Samuel , Mahony Christopher , Geisthoff Manuel , Angeli Mario , Raimondo Maria , Xu Cong , Yang Kai-Ting , Lu Le , Labinsky Hannah , Saad Mina , Gwellem Charles , Kampylafka Eleni , Knitza Johannes , Distler Jörg , Hanlon Megan , Fearon Ursula , Veale Douglas , Roemer Frank , Bäuerle Tobias , Maric Hans , Maschauer Simone , Buckley Christopher , Croft Adam , Kuwert Torsten , Prante Olaf , Cañete Juan , Schett Georg
Published: March 2023

Fibroblasts are key orchestrators of inflammation. Little is known whether these cells change phenotype during resolution of inflammation. We adopted a method to visualise fibroblast activation during inflammation in humans in vivo, which is based on a fibroblast activation protein (FAP) tracer detected by positron emission tomography (PET). While tracer accumulation was high in active arthritis, it decreased significantly after TNF- and IL-17A inhibition. Biopsy-based scRNA-seq analyses in experimental arthritis demonstrated that FAP signal reduction reflected a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalisation) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalisation). Spatial transcriptomics of human joints revealed that pro-resolving niches of CD200+DKK3+ fibroblasts clustered with innate lymphoid cells (ILC)2, whereas MMP3+/IL6+ fibroblasts were co-localised with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilised the ILC2 phenotype and induced resolution of arthritis via CD200/CD200R1 pathway. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.
Association of Suicidal Status, Inflammation Markers and Resting State Functional Connectivity in Patients with Major Depressive Disorder
Authors: Olié Emilie , CLAIN Guillaume , Malestroit Manon , FIEDOS Dimitri , COGNASSE Fabrice , DEVERDUN Jérémy , Bars Emmanuelle Le , Courtet Philippe
Published: March 2023

Suicidal ideation and attempt might have distinct neural underpinnings. Identifying the neural substrates of suicide behaviors might help to reduce suicide rates. This study wanted to identify i) neural markers of suicide attempt using resting-state functional magnetic resonance imaging (rs-fMRI), and ii) associations between rs-fMRI metrics, suicidal phenotype and peripheral blood inflammation markers. We measured inflammation markers [C-reactive protein (CRP), interleukin (IL)-1b, IL-2, IL-6, TNF-a) and rs-fMRI metrics in 20 healthy controls (HCs) and 42 patients with unipolar depression [n=21 suicide attempters (SAs) in the last 8 days and n=21 affective controls (ACs) without lifetime history of suicide]. Amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo) and Voxel-Mirrored Homotopic Connectivity (VMHC) were estimated in prefrontal cortex, anterior cingulate cortex and insula. Participants were mainly women (66.7% of HCs, 71.4% of ACs and 85% of SAs; age range 40 to 48 years). CRP (but not IL) concentration was higher in SAs than ACs and HCs. ALFF values were decreased in the pars opercularis of the inferior frontal gyrus in SAs vs. ACs and HCs, even after controlling for suicidal ideation intensity and CRP level. Suicidal ideation intensity was negatively correlated with all rs-fMRI metrics (except ReHo of left side) of this region in SAs and ACs. Inflammation markers were not correlated with the rs-fMRI metrics. Resting-state dysfunctional connectivity in regions involved in language and cognitive control is associated with suicide intensity and attempts, but not with inflammation markers.
Enhancing reliability of particulate matter sensing by multivariate Tobit model using weather and air quality data
Authors: Won Wan-Sik , Noh Jinhong , Oh Rosy , Lee Woojoo , Lee Jong-Won , Park Edward , Su Pei-Chen , Yoon Yong-Jin
Published: March 2023

Low-cost particulate matter (PM) sensors have been widely used following recent sensor-technology advancements; however, inherent limitations of low-cost monitors (LCMs), which operate based on light scattering without an air-conditioning function, still restrict their applicability. We propose a regional calibration of LCMs using a multivariate Tobit model with historical weather and air quality data to improve the accuracy of ambient air monitoring, which is highly dependent on meteorological conditions, local climate, and regional PM properties. Weather observations and PM2.5 (fine inhalable particles with diameters ≤ 2.5 µm) concentrations from two regions in Korea, Incheon and Jeju, and one in Singapore were used as training data to build a visibility-based calibration model. To validate the model, field measurements were conducted by an LCM in Jeju and Singapore, where R2 and the error after applying the model in Jeju improved (from 0.85 to 0.88) and reduced by 44% (from 8.4 to 4.7 µg m-3), respectively. The results demonstrated that regional calibration involving air temperature, relative humidity, and other local climate parameters can efficiently correct bias of the sensor. Our findings suggest that the proposed post-processing using the Tobit model with regional weather and air quality data enhances the applicability of LCMs.
Preparation of Bilayered Matrix Type of Transdermal Patches of a Classical Antihypertensive Drug: Assesment of Ex-vivo Permeation and in-vivo Pharmacokinetics
Authors: SUDDALA.SHIRISHA  , Sahoo Sunit Kumar , Seema Keerthana , Adluri Phanindra , Rao Yamsani Madhusudan
Published: March 2023

Objective
Felodipine (FD) is a calcium channel blocker used to treat hypertension and angina pectoris. Because of first-pass hepatic metabolism, it is less soluble, and its oral bioavailability is low (15%). To address the aforementioned drawbacks and maintain a consistent plasma concentration for optimal therapeutic efficacy, new methods, such as transdermal drug administration, must be developed. The goal of this study is to create bilayered transdermal films containing FD and test their efficacy using ex-vivo flux, and in-vivo pharmacokinetics studies.
Methods
Patches were made utilizing a solvent casting approach with both hydrophobic and hydrophilic polymers. The prepared films were thoroughly examined for ex-vivo permeation, and in-vivo pharmacokinetic tests on rabbits. The flux value for the formulation without the permeation enhancer (F4) was 14.585 g/cm2/h, but the flux increased in the formulation with the permeation enhancer lemongrass oil (F9) (1% v/v) was 30.4 g/cm2/h. In-vivo bioavailability findings in New Zealand white rabbits and blood samples were examined using HPLC and UV-visible spectrophotometer detector.
Results
When compared to FD with the transdermal patch system (F9) versus oral suspension administration, the bilayered transdermal films mean area under the curve values revealed an almost 1.2 times improvement in bioavailability (p < 0.05).
Conclusion
With a flux value of 30.4 g/cm2/h, the bilayered transdermal therapeutic system F9 containing lemongrass oil (1% v/v) as a permeation enhancer and a drug: polymer ratio (1:6) demonstrated good physicochemical and mechanical features. Formulation F9 may be deemed the best formulation for hypertension control based on above evaluation metrics.
Bcl-3 regulates T cell function through energy metabolism
Authors: Liu Hui , Zeng Lin , Pan Mengmeng , Huang Liwenhui , Li Hanying , Liu Mengxia , Niu Xinqing , Zhang Chenguang , Wang Hui
Published: March 2023

Background: Bcl-3 is a member of the IκB protein family and an essential nuclear factor NF-κB activity modulator. It is well established that Bcl-3 is critical for the normal development, survival and differentiation of adaptive immune cells, especially T cells. However, the regulation of immune cell function by Bcl-3 through metabolic pathways has rarely been studied.
Results: In this study, we explored the role of Bcl-3 on the metabolism and function of T cells through the mTOR pathway. We verified that the proliferation of Bcl-3-deficient Jurkat T cells was inhibited, but its activation was promoted, and Bcl-3 depletion regulated the cellular energy metabolism by reducing intracellular ATP and ROS production levels and mitochondrial membrane potential. Bcl-3 also regulates cellular energy metabolism in naive CD4+ T cells. In addition, the knockout of Bcl-3 altered the expression of mTOR, Akt, and Raptor, genes related to metabolism in Jurkat cells.
Conclusions: This finding indicates that Bcl-3 may mediate the energy metabolism of T cells through the mTOR pathway, thereby affecting their function. Overall, we provide novel insights into the regulatory role of Bcl-3 on T-cell energy metabolism for prevention and treatment strategies of immune diseases.
The effect of alcohol consumption on all-cause mortality in 70-year-olds in the context of other lifestyle risk factors: Results from the Gothenburg H70 Birth Cohort study
Authors: Ahlner Felicia , Erhag Hanna Falk , Johansson Lena , Samuelsson Jessica , Wetterberg Hanna , Fässberg Madeleine Mellqvist , Waern Margda , Skoog Ingmar
Published: March 2023

Background The relationship between alcohol consumption and health is not fully understood. In this study, we examined the effect of alcohol as well as the combined effect of seven lifestyle factors on all-cause mortality in older adults (baseline age 70 years).
Methods Data was derived from the population-based Gothenburg H70 Birth Cohort study, including 1124 participants from the 2014-16 examination. Risk consumption was defined as >98 grams and hazardous drinking based on the Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) questionnaire. Cox regression models were used to examine the individual effect of alcohol consumption, as well as the combined effect of seven lifestyle risk factors (high alcohol consumption, lifetime smoking, unhealthy Body Mass Index, insufficient physical activity, sedentary behavior, insufficient/prolonged sleep, unhealthy dietary pattern) on all-cause mortality.
Results During a mean follow-up of 7.7 years, 81 (7.2%) participants died. Neither risk consumption nor hazardous drinking were associated with elevated mortality, but hazardous drinking was associated with an increased risk of mortality in those with insufficient physical activity. Those with at least five lifestyle risk factors had an increased all-cause mortality compared to those fulfilling criteria for maximum one lifestyle risk factor, and high alcohol consumption contributed least to this risk, while physical activity and unhealthy dietary pattern had an independent effect on mortality.
Conclusions In this population study on 70-year-olds, neither risk consumption nor hazardous drinking were associated with 8-year all-cause mortality. Among seven life styles factors studied, risk or hazardous drinking of alcohol contributed least to mortality. It may be that high alcohol consumption is less important for mortality among older adults, especially in those with higher physical activity. However, it has to be emphasized that high alcohol consumption may have other adverse health effects among older adults.
Efficacy of hydroxyapatite-based skull base reconstruction for intraoperative high-flow cerebrospinal fluid leakage performed by less-experienced surgeons: a two-institution study
Authors: Hong Inseo , Kim Kyung Hwan , Seo Youngbeom , Choo Yoon-Hee , Lee Han-Joo , Kim Seon-Hwan
Published: March 2023

Cerebrospinal fluid (CSF) leakage after endoscopic skull base surgery remains a challenge despite multilayer reconstruction including nasoseptal flap (NSF) has become a standard technique. Injectable hydroxyapatite (HXA) has shown promising results to prevent CSF leakage. This study aimed to validate the efficacy of HXA-based skull base reconstruction performed by less-experienced neurosurgeons who had short-term clinical experiences as independent surgeons. Between March 2018 and November 2022, 41 patients who experienced intraoperative high-flow CSF leakage following endoscopic endonasal surgery at two independent tertiary institutions were enrolled. Skull base reconstruction was performed using conventional multilayer techniques combined with or without HXA. The primary outcome was postoperative CSF leakage. The surgical steps and nuances were described in detail. The most common pathology was craniopharyngioma. Injectable HXA was used in 22 patients (HXA group) and conventional techniques were performed in 19 patients (control group). The HXA group achieved a significantly lower incidence of postoperative CSF leakage than the control group (0% vs. 26.3%, p = 0.016). No HXA-related complications were observed. The use of injectable HXA in skull base reconstruction was highly effective and safe. This technique and its favorable results might be readily reproduced by less-experienced neurosurgeons.
Fine tuning expression levels of α-mannosidase II (MANII) and β-1,4-N-acetylglucosaminyl- transferase III (GNTIIII) in CHO cells for production of IgG1 antibody with tailored Fc-mediated effector functions
Authors: Nguyen Ngan T.B. , Leung Hau Wan , Pang Zach K. T. , Walsh Ian , Yang Yuansheng
Published: March 2023

Monoclonal antibodies (mAbs) eliminate cancer cells via various effector mechanisms including antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), which are determined by the structures of N-glycans on the Fc region of mAbs. Controlling the glycan structures on mAbs enables improving the therapeutic benefits of different effector functions. Traditional gene deletion or overexpression, which often result in only all-or-nothing changes, are not able to modulate the expression of multiple genes to defined ratios and levels. In this work, we developed a CHO cell engineering platform that allows precise modulation of multiple genes’ expression to custom design N-glycan profiles of mAbs for optimizing effector functions. A CHO targeted integration system with two independent landing pads was constructed, which allows expression of multiple genes at two pre-determined genomic sites. This platform was combined with internal ribosome entry site (IRES)-based polycistronic vectors to simultaneously fine-tuning the expression of α-mannosidase II (MANII) and chimeric β-1,4-N-acetylglucosaminyl-transferase III (cGNTIII) genes in CHO cells to produce mAbs carrying N-glycans with various levels of bisecting and non-fucosylated structures. These mAbs were confirmed to feature different degrees of ADCC and CDC, allowing mAbs with optimal effector functions to be identified. This platform was demonstrated as a powerful tool for producing antibody therapeutics with tailored effector functions via precise engineering of N-glycan profiles.