bluuebunny/crossref_metadata_2025 huggingface dataset:
RUVBL1 and RUVBL2 as novel druggable DNA Damage Response regulators in the N-Myc regulatory network in neuroblastoma
Authors: Eynden Jimmy Van den , Siaw Joachim , Claeys Arne , Lai Wei-Yun , Borenäs Marcus , Hilgert Elien , Bekaert Sarah-Lee , Speleman Franki , Durinck Kaat , Hallberg Bengt , Palmer Ruth H
Published: November 2023

High-risk neuroblastoma (NB) accounts for about 50% of all cases. These tumours are characterized by MYCN amplification and high MYC gene expression and patients have a high relapse rate despite intensive therapies, hence the need for safer and more effective drugs. Strategies to develop inhibitors that directly target the MYC proteins have been elusive. Based on in silico molecular signature score and network analyses, we identified RUVBL2 as a key interactor of MYC. Kaplan-Meier survival and multivariate Cox regression analyses using public NB datasets demonstrated that expression of RUVBL2 and its interaction partner RUVBL1 are strong and independent predictors for both overall and event-free survival in NB patients. Using different types of NB cell lines, we experimentally demonstrated that transient knockdown of RUVBL1/2 or pharmacological inhibition using CB-6644 resulted in cell cycle arrest, cell growth arrest and a DNA Damage Response (DDR) through regulation of ATR and ATM. Additionally we confirmed that RUVBL1/2 transcriptionally regulate MYCN and MYC. Our work demonstrates that RUVBL1 and RUVBL2 are novel regulators of the DDR with therapeutic and independent prognostic potential in high-risk NB.
Placental histological differences between COVID19 infected and non-infected mothers during third trimester of pregnancy: a retrospective cohort study.
Authors: meguerian Zarouhi , Irani Jihad , chalhoub elias , samad sara El , Khalifeh Joe , Ghanem Joe , Nassar Jean , Feghali Joe , Hajal Nadim , Snaifer Elie , Anastasiades Elie
Published: November 2023

Background
The aim of this study is to investigate placental histological differences between Covid-19 uncomplicated pregnancies and Covid-19 infected mothers in the 3rd trimester or intrapartum.
METHODS
This was a retrospective cohort study conducted between the 28th of January 2021 and the 31st of June of the same year at Saint George University Medical Hospital. All pregnant women, whether symptomatic or not, were tested for Covid-19 infection via PCR upon presentation for delivery. We randomly collected placentas from Covid-19 uncomplicated gestations and 3rd trimester or intrapartum Covid-19 infected mothers after obtaining an informed consent. Our control population included all previously healthy mothers, singleton, term, and uncomplicated pregnancies regardless of the mode of delivery during the same period of the study. The Covid- 19 infected group had similar medical and obstetrical background only for coronavirus infection during the 3rd trimester or upon admission. Placentas of the two groups were grossly and histologically examined by a single pathologist who was blinded to the placentas of each group. Examination was based on the Amsterdam Consensus Statement guidelines.
RESULTS
A total of 22 Covid-19 positive cases and 21 Covid-19 negative cases were included. The results showed no statistical significance for any of the placental pathologies including maternal vascular malperfusion, amniotic fluid infection including maternal response and fetal response, villitis of unknown etiology, intervillositis and chorangiosis and fetal vascular malperfusion, except for the vascular ectasia, were 5 cases were identified in the Covid-19 positive group (p < 0.05).
CONCLUSION
Covid-19 infection during the 3rd trimester of pregnancy is not a risk factor for the development of placental histopathologies.
TIM-3 on myeloid cells promotes pulmonary inflammation through increased production of galectin-3
Authors: Park Eun Jung , Kim Ki Sun , Lee Chanju , Kim Hyung-Seok , Gu Su Jeong , Yoon Hee Jung , Won Su Bin , Lee Ho , Lee Yong Sun , Kim Sang Soo , Kane Lawrence
Published: November 2023

T cell immunoglobulin and mucin-containing molecule 3 (TIM-3) exhibits unique characteristics and functions that differ by cell type and status, but little is known about the cell-specific properties of TIM-3 in pathophysiological conditions. Here, we report that TIM-3 on myeloid cells plays essential roles in modulating lung inflammation and diseases. We found that myeloid cell-specific TIM-3 knock-in (FSF-TIM3/LysM-Cre+) mice have lower body weight and shorter lifespan than WT mice. Intriguingly, PET/CT analysis and histopathological examination revealed that the lungs of FSF-TIM3/LysM-Cre+ mice display excessive inflammation and features of disease-associated pathology. Similar features were observed in a different myeloid cell-specific TIM-3 knock-in mouse (FSF-TIM3/Cx3cr1-Cre+ mice). Bulk RNA-sequencing and flow cytometry revealed that galectin-3 levels are notably elevated in TIM-3-overexpressing lung-derived myeloid cells. Furthermore, blockade of TIM-3 ameliorated the levels of inflammation and galectin-3 in the lungs of FSF-TIM-3/LysM-Cre+/- mice. Using an LPS-induced lung inflammation model with myeloid cell-specific TIM-3 knock-out mice, we further demonstrated that the level of myeloid cell-expressed TIM-3 is closely associated with both lung inflammation and galectin-3. Collectively, our findings suggest that TIM-3 is an important regulator of myeloid cells in the lungs, and modulation of TIM-3 and galectin-3 could be of therapeutic benefit in inflammation-associated lung diseases.
Experimental investigation of the effect of stratifiers to enhance the performance of the thermal energy storage system
Authors: SELVAM LOKESH , Sivalingam Suyambazhahan , Vis Tharun Sriramalu , Vadivelu Thanigaivelan
Published: November 2023

The performance enhancement of the cascaded thermal energy storage system was investigated using multi-wall carbon nanotubes (MWCNT) in phase change material (PCM) with and without a stratifier at the tank's charging inlet. The circular dispersion introduced by the stratifier into the intake of the charging tank. The experimental tests were conducted with inlet temperatures of 70, 75, and 80 °C and rate of flow 1, 2, and 3 l/min. According to the analysis findings, employing the stratifier in the storage tank resulted in an effective charging time of 37 min and 50 min without the stratifier. Also, a thermogravimetric analysis (TGA) was done to determine the material's stability. In comparison to the cylindrical phase PCM capsule, the spherical phase PCM capsule had higher total energy and enthalpy, and the spherical phase PCM capsule's heat flow contours were uniform.
Investigating the evolution chain of deformation and destabilisation of anti-dip rock slopes
Authors: Ma Wenliang , Li Jinfeng , Wang Hairen , Meng Xiangzhen
Published: November 2023

With the continuous promotion of engineering construction in western China, it is increasingly acknowledged that the frequency and harmfulness of deformation and destabilisation of anti-dip rock slopes are comparable to those of dip rock slopes. Due to the characteristic "no pre-existing weak planes" of anti-dip rock slopes, the cumulative deformation and fracture of rock strata result in slope destabilisation. Focusing on the evolution chain "deformation of rock strata - damage (or fracture) of rock strata - slope destabilisation", this study investigates the mechanisms of deformation and destabilisation of anti-dip rock slopes through a numerical simulation method. For the anti-dip rock slope with a large dip angle of the rock strata, the significant stress characteristic of the rock strata "tension near the upper surface - compression near the lower surface" results in obvious flexural deformation and tensile fracture. The slope undergoes long-term damage and eventually occurs destabilisation. This stress characteristic gradually diminishes and eventually vanishes with decreasing dip angle of the rock strata. The resulting initiation mode of slope destabilisation transitions from tensile fracture to compressive fracture of the rock strata at the slope toe. Meanwhile, the destabilisation mode of slopes transitions from toppling type to sliding type, and the corresponding failure boundary transitions from dual stage toppling-fracture type to multistage sliding type. Moreover, the combined effects of the slope angle and the dip angle of the rock strata are discussed during the process of deformation and destabilisation of anti-dip rock slopes.
The impact of environmental protection tax on green M&As
Authors: Wang Wei , Shi Tingting , Jiang Zhixin
Published: November 2023

This article aims to investigate the impact of The Environmental Protection Tax Law of the People’s Republic of China implemented in 2018 on the decision-making process of green M&As, and incorporates heavy-polluting companies listed on the A-share market in Shanghai and Shenzhen in its study. After collecting data on the green M&As among these firms, the study empirically examines the impact of the environmental protection tax on their decision-making. The findings indicate that: (1)The environmental protection tax offers favorable conditions for enterprises to engage in green M&As.(2)From the perspective of heterogeneity, The environmental protection tax has a particularly evident incentive effect in green M&As of enterprises incorporated in regions with high tax standards, state-owned enterprises, and more heavily-polluting enterprises in central and western China.(3)Green M&As contribute to increased green innovation output by enterprises.(4)The moderating role of regional marketization and corporate legitimacy awareness in the impact of environmental protection taxes on green M&As. Based on these empirical results, several policy recommendations are proposed, including the effective utilization of the environmental protection tax system and the promotion of green transformation among enterprises through price mechanism.
Deep-brain stimulation of the human nucleus accumbens-medial septum enhances memory formation
Authors: Strange Bryan , Treu Svenja , Barcia Juan , Diaz Cristina Torres , Rosa Javier Gonzalez , Nombela Cristina , Pineda Jose , Torres Daniel , Kunz Lukas , Hellerstedt Robin , Avecillas-Chasin Josue , Lara Monica , Navas Marta , Galarza Ana , Garcia Julia , Oliviero Antonio , Seijo Fernando , Horn Andreas , Li Ningfei , Axmacher Nikolai , Canals Santiago , Reneses Blanca , Bierbrauer Anne
Published: November 2023

Deep-brain stimulation (DBS) is a potential novel treatment for memory dysfunction. Current attempts to enhance memory focus on stimulating human hippocampus or entorhinal cortex. However, an alternative strategy is to stimulate brain areas providing modulatory inputs to medial temporal memory-related structures, such as the nucleus accumbens (NAc), which is implicated in enhancing episodic memory encoding. Here, we show that NAc-DBS improves episodic and spatial memory in psychiatric patients. During stimulation, NAc-DBS increased the probability that infrequent (oddball) pictures would be subsequently recollected, relative to periods off stimulation. In a second experiment, NAc-DBS improved performance in a virtual path-integration task. An optimal electrode localization analysis revealed a locus spanning postero-medio-dorsal NAc and medial septum predictive of memory improvement across both tasks. Patient structural connectivity analyses, as well as NAc-DBS-evoked hemodynamic responses in a rat model, converge on a central role for NAc in a hippocampal-mesolimbic circuit regulating encoding into long-term memory. Thus, short-lived, phasic NAc electrical stimulation dynamically improved memory, establishing a critical on-line role for human NAc in episodic memory and providing an empirical basis for considering NAc-DBS in patients with loss of memory function.
Management of Acute Myocardial Infarction in a Liver Transplant Recipient- A rare case report
Authors: Makwana Harsha , Chaudhary Aditi , Dhongani Harshit , Kapadia Parth , Bhut Sumit , Modi Kushal , Chandak Megha
Published: November 2023

Liver transplantation (LT) improves outcomes and quality of life in patients with end-stage liver disease (ESLD). As a result of improved accessibility and recipient survival, transplant candidates are becoming increasingly older, have more co-morbidities, and experience more long-term complications, all of which created new challenges in post-transplantation care. In post-transplant period, a multitude of factors can influence cardiovascular risk in transplant recipients due to aggravation in recipient populations from new-onset dyslipidemia, hypertension, glucose intolerance, and nephrotoxicity as side effects of immunosuppressive agents. Traditional cardiovascular risk factors are becoming increasingly prevalent in the aging population of Liver Transplant candidates, and coronary artery disease is considered to be more common than previously thought. Cardiovascular events are recognized as prominent causes of early and late mortality in liver transplant recipients The most common cardiovascular diseases in transplant candidates are ischemic coronary artery disease (CAD) and cardiomyopathy. We describe a complex case of liver transplant recipient in a 50-year-old male patient with no known history of coronary artery disease who developed progressive acute myocardial infarction within 6 months of liver transplant, ultimately thrombolysed to optimize myocardial perfusion. Management of myocardial ischemia was complicated by high risk of bleeding in the setting of coagulopathy. Once thrombolysed and hemodynamic stability was achieved, the patient immediately shifted for coronary angiography and staged coronary angioplasty was done for triple vessel coronary disease in patient at cardiac institute.
Overcoming the tumor biological barrier: a multistage drug delivery strategy for DDR1-mediated resistant colorectal cancer therapy
Authors: Yan Jun , Cui Guangman , Deng Shaohui , Zhang Biao , Lin Zhousheng , Lan Xinyue , Li Zelong , Yu Meng , Yao Guangyu
Published: November 2023

Chemotherapy resistance remains a significant challenge in the treatment of colorectal cancer (CRC). The roles of discoidin domain receptor 1 (DDR1) in mediating tumor-collagen interactions and promoting cancer progression have been extensively studied. However, the specific mechanisms of DDR1 contribute to matrix-mediated drug resistance (MMDR) remain poorly understood. In this study, we elucidated a novel mechanism in which the interactions between tumor cells and collagen lead to promotion of drug efflux and collagen fiber alignment as well as suppression of immune infiltration, resulting in MMDR in CRC. To address this issue, we employed a multistage drug delivery system carrying Ddr1-siRNA and chemotherapeutic agents to disrupt collagen deposition and alignment by silencing DDR1 in ECM, enhancing chemotherapy drugs diffusion and facilitating immune infiltration. These findings not only revealed a novel role for collagen-rich matrix mediated by DDR1 in tumor resistance, but also introduced a promising CRC treatment strategy.
Validation of the Center for Neurologic Study Bulbar Function Scale–Chinese Version in a Population with Amyotrophic Lateral Sclerosis
Authors: Ye Shan , Chen Lu , Murphy Davan , Wu Jieying , Zhang Hui , Liu Hong , Zou Boliang , Hou Guanghao , Zhang Nan , Yin Tielun , Smith Richard A , Fan Dongsheng
Published: November 2023

Objective
The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-report measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese ALS population.
Methods
A total of 111 ALS patients were included in this study. The CNS-BFSC, the three bulbar function items from the ALSFRS-R, and visual analog scales (VASs) for speech, swallowing and salivation were assessed in the study. Forty-six ALS patients were retested with the same scales 5–10 days after the first evaluation.
Results
CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with VAS subscores (p < 0.001). The CNS-BFSC total, sialorrhea and speech scores were significantly correlated with the ALSFRS-R bulbar subscore (p < 0.001). The CNS-BFSC total score and ALSFRS-R bulbar subscale were highly predictive of clinician diagnosis of impaired bulbar function (area under the receiver operating characteristic curve, 0.947 and 0.911, respectively; p < 0.001). A cutoff value for the CNS-BFSC total score was selected by maximizing Youden's index; this cutoff score was 33, with 86.4% sensitivity and 93.3% specificity. The CNS-BFSC total score and the sialorrhea, speech and swallowing subscores had good–retest reliability (p > 0.05). The Cronbach’s α of the CNS-BFSC was 0.972.
Conclusion
The Chinese version of the CNS-BFSC has acceptable efficiency and reliability for the assessment of bulbar dysfunction in ALS patients.
Altered gut microbiota in hereditary transthyretin amyloidosis with polyneuropathy
Authors: Chen Chieh-Chang , Tseng Ping-Huei , Hsueh Hsueh-Wen , Chiang Ming-Chang , Tzeng Shiou-Ru , Chiang Tsung Hsien , Wu Ming-Shiang , Hsieh Sung-Tsang , Chao Chi-Chao
Published: November 2023

Increasing evidence suggests that gut microbiota alterations are related to development and phenotypes of many neuropsychiatric diseases. Here, we evaluated the fecal microbiota and its clinical correlates in patients with hereditary transthyretin amyloidosis (ATTRv) and polyneuropathy. Fecal microbiota from 38 ATTRv patients and 39 age-matched controls was analyzed by sequencing 16S V3-V4 ribosomal RNA, and its relationships with clinical characteristics of polyneuropathy and cardiomyopathy were explored. The familial amyloidotic polyneuropathy (FAP) stage was stage I, II, and III in 13, 18, and 7 patients respectively. 99mTc-PYP SPECT showed a visual score of 2 in 15 and 3 in 21 patients. The gut microbiota of ATTRv patients showed higher alpha diversity (p = 0.002 for Chao1 index) and dissimilar beta diversity (p = 0.001) compared to controls. Relative abundance of microbiota was dominated by Firmicutes and decreased in Bacteroidetes in ATTRv patients than in controls. Patients with more myocardial amyloid deposition were associated with increased alpha diversity, and the abundance of Clostridia was significantly correlated with pathophysiology of polyneuropathy in ATTRv patients. These findings demonstrated alterations in the gut microbiota, especially Firmicutes, in ATTRv. The association between altered microbiota and phenotypes of cardiomyopathy and polyneuropathy might suggest potential contributions of gut microbiota to ATTRv pathogenesis.
Internet of Things in Medical Education: A Systematic Mapping Review
Authors: Behmanesh Ali , Davarzani Mohammad Hoseeinzadeh , Shams Roshanak , Soleimanpour Samira
Published: November 2023

Context The Internet of Things (IoT) has emerged as a promising technology with the potential to transform medical professional training and education. IoT refers to a network of physical items that are embedded with sensors, software, and connections that exchange data via the Internet. IoT provides the possibility of merging electronic health records, medical devices, and wearable technologies to create an interactive learning environment in medical education. Objectives The current study's goal was to identify and map current IoT advancements in medicine by conducting a systematic mapping review of the existing research on IoT in medical education. It intends to provide answers to major research question, such as trends and activities in IoT development in medical education. Methods Following PRISMA-ScR guidelines, a systematic mapping review was conducted in major online scientific databases such as Web of Science, Scopus, PubMed, and IEEE Xplore up to end of 2022 to identify empirical studies related to IoT and medical education. A total of 199 papers were found, from which 24 were ultimately selected based on particular inclusion/exclusion criteria. Results While the majority of medical IoT research are conducted across a network of twelve different countries, the United States has emerged as the leader in developing IoT systems for medical education. The dynamic potential of IoT devices and sensors in medical education included areas such as activity monitoring, physiological monitoring, data collecting, and simulation. In medical education, IoT applications include surgical training, non-surgical teaching, and resident monitoring. Conclusions The study findings highlight the importance of further research efforts aimed at addressing challenges and unlocking the full array of benefits IoT has to offer in medical education. It is expected that these discoveries will catalyze interest among medical education leaders and policymakers, encouraging them to explore the promising horizons of wearable technology and IoT applications in medical education, ultimately leading to enhanced educational outcomes and practices.
Synergizing Machine Learning and Cybersecurity for Robust Digital Protection.
Authors: Shukla Sameer
Published: November 2023

In today's dynamic digital landscape, cyber threats are growing in sophistication and frequency, challenging traditional cybersecurity methods. This research paper, titled "Fortifying Digital Defenses: Exploring the Synergy of Machine Learning and Cybersecurity," delves into the pivotal role of machine learning in bolstering our cyber defenses. Machine learning, a subset of artificial intelligence, has emerged as a powerful tool in the fight against cyber adversaries. The paper explores how machine learning techniques can significantly enhance threat detection, incident response, and security system adaptability. It showcases real-world applications, such as anomaly detection, behavioral analysis, and predictive threat intelligence, illustrating the symbiotic relationship between machine learning and cybersecurity. By embracing machine learning, organizations can stay ahead of emerging threats, adapt more effectively, and fortify their digital defenses in this ever-evolving digital age.
Role of bridging RT in relapsed/refractory diffuse large B-cell lymphoma undergoing CAR-T therapy: a multicenter study
Authors: Mannina Daniele , Bramanti Stefania , Chiappella Annalisa , Casadei Beatrice , De Philippis Chiara , Giordano Laura , Navarria Pierina , Mancosu Pietro , Taurino Daniela , Scorsetti Marta , Carlo-Stella Carmelo , Zinzani Pier Luigi , Santoro Armando , Corradini Paolo
Published: November 2023

The optimization of bridging regimen before chimeric antigen receptor (CAR)-T cell therapy in diffuse large B-cell lymphoma (DLBCL) may impact CAR-T efficacy and outcome. This retrospective study evaluates CAR-T outcome after bridging with radiotherapy (RT) and other bridging strategies. Among 148 patients with relapsed/refractory DLBCL who underwent leukapheresis for CAR-T manufacturing, 31 received RT-bridging, 84 chemotherapy (CT), 33 no-bridging or steroid-only. CAR-T cell were infused in 96.8% of RT-group. 89.2% of CT-group and 78.8% of no-bridge group (p = 0.079). Response to bridging was generally poor, but patients receiving RT had a significant reduction in LDH levels between pre- and post-bridging (p = 0.05). The one-year PFS was 51.2% in the RT group, 28.2% in the CT group, and 47.6% in the no-bridge group (p = 0.044); 1-year OS was 86.7% in the RT group, 52.7% in the CT group and 69% in the no-bridge group (p = 0.025). We observed a higher incidence of ICANS in patients who received CT than in others (20.0% CT group, 3.3% RT group, 7.7% no-bridge group; p = 0.05).
In conclusion, RT-bridging is associated with lower drop-out rate and CAR-T toxicity, and it might be preferred to other bridging strategies for patients with localized disease or for those with one prevalent symptomatic site.
Optimizing Experiments on the Time Course of Mental Processes: A Novel Method and Application for Measuring Keyboard Switches Bounce-back Time
Authors: Li Jia Qi , Fang Yu , Deng Yi
Published: November 2023

Keyboards, extensively utilized as input devices in reaction time tests, have undergone substantial technological advancements over the past decades. From the Hall Effect Switch introduced in 1965 to the modern Magnet Switches, keyboards based on the Hall Effect have seen innovations not only in hardware architecture but also in key detection mechanisms, notably Rapid Trigger. This has further amplified their advantages in minimizing input latency. Our research introduces an innovative experimental methodology for assessing the rebound time of keyboard switches. Employing this straightforward yet effective approach, we measured and calculated the bottom-out rebound time for three types of keyboard switches. The findings indicate that magnetic switches with Rapid Trigger functionality excel over mechanical keyboards in key actuation, release, and controller latency. The difference in bottom-out rebound time between the two exceeds 20ms. Consequently, we recommend the use of such keyboards in experiments related to the time course of mental processes, as this can mitigate errors induced by input devices and enhance the accuracy of the results.
Research on the Evolution of the Death Psychology of Chinese People in the Context of Lifting COVID-19 Pandemic Restrictions: A hybrid Study of Weibo Big Data
Authors: Li Xiaowen , He Yuanqing
Published: November 2023

Amid the novel coronavirus threat, individuals are compelled to ponder over profound existential matters like life and death.This study employs a hybrid research methodology, merging grounded theory with big data mining techniques, to delve into the psychological adaptation mechanism when individuals confront death threats amidst epidemic deregulation.We fetched texts related to death psychology keywords from the Sina Weibo platform. Post data cleaning, the database incorporated 3868 Weibo texts.Grounded theory forms the basis for data coding and theory formulation. Subsequently, big data mining techniques, including topic mining and semantic network analysis, are employed to validate the formulated codes and theories.The findings demonstrate that within the "Emotion-Cognition-Behavior-Value" framework, the implications of death threats manifest in four aspects: death anxiety, death cognition, coping efficacy, and sense of meaning.As time progresses, the study of death psychology can be segmented into four distinct phases: the tranquil phase prior to lifting pandemic restrictions, the threat phase at lifting pandemic restrictions onset, the coping phase mid-lifting pandemic restrictions, and the reformative phase post-lifting pandemic restrictions.The calculated outcomes of topic mining and semantic network analysis corroborate the coding results and theories derived from the grounded theory. This reaffirms that data mining technology can be a potent tool for validating grounded theory.
Enhancing Elderly Care Services: A Comprehensive Internet+ Community Home Indicator System
Authors: 赵 瑞 , Huo Mingshu , Tan Mingyang , Wang Lei , Liu Qiaoli , Li Jiangxu , Li Hongyu , Wang Ru
Published: November 2023

Background
In the context of the smart city and aging trends, Internet + community home-based care offers a novel approach to elderly care in China. However, limited research has focused on developing a comprehensive indicator system to address the diverse needs of elderly individuals residing at home. Based on existence needs, relationship needs and growth needs abbreviated as "ERG" demand theory. In response, this study leverages the ERG demand theory as a functional framework to establish a demand-oriented Internet + community home-based elderly service indicator system.
Methods
In this study, we adopt the ERG demand theory as the conceptual framework and employ a combination of the Delphi method and Analytic Hierarchy Process (AHP), thereby integrating both qualitative and quantitative research techniques to develop and assign weightings to the demand-orientated indicator system for Internet-based community home healthcare services for the elderly. Our research methodology is based on comprehensive literature reviews and collaborative group meetings.
Results
The study developed a demand-orientated Internet + community home healthy elderly service indicator system, comprising three primary indicators, 10 secondary indicators, and 46 tertiary indicators. These top-level indicators, ranked in descending order of importance, are medical and nursing services (0.493), living care services (0.311), and psychosocial/spiritual support services (0.196).
Conclusion
The indicator system serves the purpose of comprehending the health status and care requirements of elderly individuals confined to their homes while offering personalized services. In addition to addressing the fundamental needs of homebound older people through individualized care and expert medical guidance, this program places a significant emphasis on the spiritual and psychological well-being of these individuals to ensure a holistic approach to their physical and mental needs. This research posits that the indicator system can aid community healthcare workers in discerning the demand distribution for elderly services and optimizing resource allocation. By continuously evaluating and monitoring the indicators, this approach facilitates the enhancement of service quality and the fine-tuning of strategies, ultimately delivering efficient, safe, and high-quality elderly care services.
DNA methylation participates in drought stress memory and response to drought in Medicago ruthenica
Authors: Zi Na , Guo Huiqin , Ren Weibo , Fry Ellen L. , Yuan Feng , Liu Yaling
Published: November 2023

Drought is a serious environmental problem, affecting plant growth and development and resulting in severe yield loss. Many plants exposed to drought stress can generate stress memory, which provides some advantages for resisting recurrent drought. DNA methylation is a mechanism of stress memory formation, and many plants can alter methylation levels to form stress memories; however, it remains unclear whether Medicago ruthenicaexhibits drought stress memory, as the molecular mechanisms underlying this process have not been described in this species. Here, we conducted methylome and transcriptome sequencing to identify gene methylation and expression changes in plants with a history of two drought stress exposures (D2). Methylation analysis showed that drought stress resulted in an approximately 4.41% decrease in M. ruthenica genome methylation levels. CG dinucleotide contexts had the highest methylation levels, followed by CHG contexts, with CHH contexts having the lowest levels. Analysis of associations between methylation and transcript levels showed that most DNA methylation was negatively correlated with gene expression, except for methylation within CHH in gene promoter regions. Genes were divided into four categories according to correlation between methylation and gene expression; demethylated genes expression upregulation accounted for the vast majority (n = 692 genes), and included genes encoding key factors for abscisic acid (ABA) and proline synthesis. Demethylation of the promoter and body regions of these two genes induced increased gene expression levels. In conclusion, DNA methylation may contribute to drought stress memory formation and maintenance in M. ruthenica by increasing transcription levels of genes key for ABA and proline biosynthesis.
PJA2 suppresses colorectal cancer progression by controlling HDAC2 degradation and stability.
Authors: Chen Zhihao , Yang Peng , Jin Chi , Wang Tuo , Wang Ye , Peng Chaofan , Sun Qingyang , Xu Hengjie , Nie Hongxu , Wang Xiaowei , Feng Yifei , Sun Yueming
Published: November 2023

Background
The Praja Ring Finger Ubiquitin Ligase 2 (PJA2), one of the RING ligase family, has been reported to be degrading differential substrates and regulating diverse diseases. However, the E3 ligase function of PJA2 played in cancer development and progression, especially in colorectal cancer, is still almost unknown.
Methods
The correlation between PJA2 and clinical characteristics was explored through the TCGA and GEO data sets. The qRT-PCR and Immunohistochemical assays were employed to assess the expression of PJA2 in CRC tissues and cell lines. The biological functions of PJA2 were verified by cell counting kit-8, colony formation, flow cytometry, cell-derived xenograft, AOM/DSS colorectal tumorigenesis model and other in vivo and in vitro experiments. The RNA-seq, mass spectrometry analysis, GST pull-down, Chromatin Immunoprecipitation and Immunofluorescence were utilized to disclose the underlying molecular mechanisms of PJA2 in CRC proliferation and apoptosis.
Results
Our research discovered that PJA2 was abnormally downregulated in CRC tissues and cell lines, and the lower expression of PJA2 was detected, the poorer prognosis was present. Functionally, further in vivo and in vitro experiments jointly uncovered that PJA2 acted as a tumor suppressor gene via inhibiting tumor proliferation and promoting cancer cell apoptosis in CRC progression. Regarding mechanism, PJA2 could recognize HDAC2 through the RBD domain and bind with the N-terminal of HDAC2 to ubiquitinate and degrade HDAC2 at K90 residue. PJA2-mediated ubiquitination and degradation of HDAC2 could counteract the transcriptional suppression of the IFIT family and PJA2, thus facilitating the transcription of the IFIT family to promote cancer cell apoptosis and inhibit tumor proliferation.
Conclusion
Our data showed that PJA2 interacted with HDAC2, promoted the poly-ubiquitination and degradation of HDAC2, abrogated the transcriptional suppression of the IFIT family and PJA2, constituted a positive feedback loop, and prevented tumor proliferation. Hence, PJA2 might be a potential therapeutic target for CRC, and interruption of this positive feedback loop would be a treatment strategy to slow or restrain the progression of CRC.
Curvularia lingshanensis sp. nov., a New Pathogen Causing stem and leaf rot on Curcuma kwangsiensis and Its Sensitivity to Five Fungicides
Authors: Wang Hanyi , Su Jiali , Liu Ze , Lin Siyu , Guo Jingyi , Gao Qi , Zhou Hao
Published: November 2023

Curcuma kwangsiensis S. G. Lee et C. F. Liang (Zingiberaceae) is a traditional Chinese medicinal plant that is cultivated in the South-West of China. In this study, five fungal strains were isolated from diseased C. kwangsiensis plants in Lingshan County, Guangxi Province. The phylogenetic analyses, based on a combined dataset of ITS, GAPDH, and EF-1α gene sequences, revealed that the strains from this study formed a distinct clade separate from other known Curvularia species. Additionally, these strains were closely related to C. tamilnaduensis, C. radici-foliigena, and C. radicicola. Based on morphological observations, the strains exhibit distinct variations in conidiophore length, conidiogenous cell characteristics, as well as conidial size and shape, distinguishing them from similar species. Consequently, these five strains have been classified as a novel species, C. lingshanensis. Pathogenicity test carried out on the plants confirmed that the new species was pathogenic to C. kwangsiensis. Five fungicides were tested for their toxicity to the pathogen using the mycelial growth rate method. Results indicated that among the studied fungicides, 70% mancozeb, 10% difeno-conazole and 75% trifloxystrobin·tebuconazole had the highest antifungal activity against C. lingshanensis with EC50 values of 1.5233 ± 0.18 mg/L, 0.1748 ± 0.03 mg/L, 0.2557 ± 0.06 mg/L, respectively. This study provides the first report of a severe stem and leaf rot disease on C. kwangsiensis caused by C. lingshanensis and important guidance for preventing and controlling this disease effectively.
The role of HIF-1α silencing in late pregnancy hypoxia-induced autism-like behavior in rat offspring
Authors: Tang Jinghua , Yang Ying , Qu Ping , Chen Jie , Li Tingyu , Dai Ying
Published: November 2023

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that can be caused by a variety of factors. Our previous study indicated that hypoxia-inducible factor 1 alpha (HIF-1α) plays a role in hypoxia-caused autism-like behavior. In this study, we investigated the mechanism by which HIF-1α contributes to prenatal hypoxia-induced autism-like behavior in vivo to provide an experimental basis for the treatment of ASD. We established a prenatal hypoxia model of pregnant rats by placing 17-day pregnant rats into a self-made hypoxia chamber filled with a nitrogen containing 10%±0.5% oxygen. Within 24 h after birth, the lateral ventricles of the prenatal hypoxia offspring rats were injected with a recombinant adeno-associated virus designed to silence HIF-1α expression. The autistic behavior of offspring rats in the HIF-1α silenced group was significantly alleviated compared with that of the prenatal hypoxia group. With the silencing of HIF-1α, the activity of phosphatase and tensin homolog (PTEN) increased and the PI3K/AKT pathway was inhibited by negative feedback. The mRNA expression level of vascular endothelial growth factor (VEGF) was decreased in the Si-HIF-1α silenced group and N-methyl D-aspartate receptor subtype 2 (NR2A) expression was downregulated. Thus, our study indicates that HIF-1α plays a role in hypoxia-induced autism-like behavior, and its regulatory effect may be achieved by inhibiting the activity of PTEN, resulting in activation of the PI3K signaling pathway. Synaptic plasticity regulation may also be involved.
Multi-dimensional comparison of abdominal obesity indices and insulin resistance indicators for assessing NAFLD
Authors: Shi Jiejun , Chen Jianhua , Zhang Zeqing , Qian Guoqing
Published: November 2023

Background The prevalence of non-alcoholic fatty liver disease (NAFLD) keeps increasing annually all around the world. Non-invasive assessment tools for the risk and severity of the disease are still limited. Insulin resistance (IR) and abdominal obesity (ABO) are closely related to NAFLD. Methods A retrospective large-scale, population-based study was conducted based on the data from the 2017–2018 cycle of the National Health and Nutrition Examination Survey (NHANES). Three ABO indexes, namely lipid accumulation product (LAP), visceral obesity index (VAI), waist circumference-triglyceride index (WTI), and three IR indices, including triglyceride glucose index (TyG), homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic score for insulin resistance (METS-IR), were analyzed and compared for their relationships with NAFLD based on weighted multivariable logistic regression, spearman correlation heatmap, smooth curve fittings. Area under the curve (AUC) of receiver-operating characteristic (ROC) curve was used to evaluate the diagnostic capability of these indices for NAFLD. Statistical differences among the AUCs were calculated via Delong test. Results In total, 3095 participants were included in our study among which 1368 adults were diagnosed with NAFLD. Overall, all the six indices presented positive association with NAFLD. There was a claw-shaped curve between HOMA-IR, VAI, LAP and NAFLD while a smooth semi-bell curve was observed in TyG, METS-IR and WTI. Among all the six indices, LAP and HOMA-IR had the best diagnostic capability for NAFLD (for LAP: AUC = 0.8, Youden index = 0.48 and for HOMA-IR: AUC = 0.798, Youden index = 0.472) while VAI (AUC = 0.728, Youden index = 0.361) showed the lowest predictive value. Correlation heat map displayed that all the six indices were positively correlated with liver function, hepatic steatosis and fibrosis severity. Notably, in NAFLD group, IR indicators presented stronger association with alanine aminotransferase (ALT) compared against ABO indexes. Conclusions Based on our study, all the six indices can screen NAFLD among which LAP and HOMA-IR may be optimal predictors. Compared against ABO indexes, IR indices may be more sensitive to identify acute hepatic injure in patients with NAFLD.
The incidence and Risk Factors of fetuses with mirror-image dextrocardia with solitus inversus
Authors: Xu Wenjiao , Wei Yajuan , Gao Xinru , Yang Xiaoxue , Wang Liping , Gao Wenlian , Zhu Xumin , Liu Baomin
Published: November 2023

Objective: This research seeks to ascertain the prevalence and determinants of mirror-image dextrocardia in fetuses
Study Design: With December of 2022 as the reference point , we compiled colleted data on pregnant women who carried fetuses with mirror-image dextrocardia in Xi'an, Shaanxi Province: September-October 2022, November 2022, and December 2022-January 2023 An online questionnaire was distributed to 209 pregnant across china who had contracted COVID-19. The case group comprised women whose final menstrual cycle occurred in November 2022 and who had a fetus with mirror-image dextrocardia. Women with a November 2022 final menstrual period and a fetus without this condition made up the control group. To identify the risk factors associated with fetal mirror-image dextrocardia, both univariate and multivariate logistic regression analyses were employed.
Results: A significant difference was noted in the gestational age at COVID-19 infection women with a September to October 2022 and December 2022 to January 2023 final menstrual period who did not bear a fetus with mirror-image dextrocardia, and those with a November 2022 final menstrual period whose fetus exhibited this condition. The univariate and multivariate analyses conducted on pregnant women with a final menstrual period in November 2022 who had contracted COVID-19 revealed significant differences in the presence and duration of fever between those bearing fetuses with mirror-image dextrocardia and those without (P = 0.000).
Conclusion: The findings suggest two critical factors to the increased prevalence of fetal mirror-image dextrocardia : 1) the infection timing which occurs between the 4th and 6th week of pregnancy; 2) the presence of fever and its prolonged duration.
Automatic Evaluation of EDM Electrode Wear via Integration of Image Segmentation and 3D Registration (IS-3DR)
Authors: Ma Fubin , Zhou Tianfeng , Cui Ying , Uddin Md Nasir , Yao Xiaoqiang , Zeng Jiyong , Guo Weijia , Wang Xibin
Published: November 2023

Electrode wear (EW) during the electrical discharge machining (EDM) process determines surface topography accuracy. In this paper, an automatic evaluation method is proposed by integrating image segmentation and three-dimensional (3D) registration (IS-3DR) to evaluate the EW more accurately. First, the original two-dimensional (2D) image and the 3D point cloud were derived from a laser microscope image, and the 2D worn area was determined by automatic recognition and segmentation. Then, 3D registration between the 3D point cloud and the 2D worn area was utilized to qualitatively define the 3D EW area. Finally, the 3D EW volume was obtained quantitatively through microelement calculation based on the 3D EW area and the shape fitting of the original electrode. The results showed that the intersection over union (IOU) of image segmentation was higher than 97.5%, compared with the manually labeled image segmentation method. The reliability of the proposed IS-3DR evaluation method was confirmed. Additionally, EDM experiments are carried out to verify the proposed IS-3DR evaluation method. The impact of various discharge parameters on EW was illustrated in detail.
Orthotropic transplantation of the bioengineered lung using a mouse-scale perfusion-based bioreactor and human primary endothelial cells
Authors: Suzuki Takaya , Tomiyama Fumiko , Watanabe Tatsuaki , Miyanaga Jun , Suzuki Anna , Murai Sho , Suzuki Yuyo , Niikawa Hiromichi , Oishi Hisashi , Notsuda Hirotsugu , Watanabe Yui , Hirama Takashi , Onodera Ken , Togo Takeo , Noda Masafumi , Waddell Thomas , Karoubi Golnaz , Okada Yoshinori
Published: November 2023

Whole lung engineering and the transplantation of its products is an ambitious goal and ultimately a viable solution for alleviating the donor-shortage crisis for lung transplants. There are several limitations currently impeding progress in the field with a major obstacle being efficient revascularization of decellularized scaffolds, which requires an extremely large number of cells when using larger pre-clinical animal models. Here, we developed a simple but effective experimental pulmonary bioengineering platform by utilizing the lung as a scaffold. Revascularization of pulmonary vasculature using human umbilical cord vein endothelial cells was feasible using a novel in-house developed perfusion-based bioreactor. The endothelial lumens formed in the peripheral alveolar area were confirmed using a transmission electron microscope. The quality of engineered lung vasculature was evaluated using fractal dimension analysis of histological images. The engineered mouse lungs were successfully transplanted into the orthotopic thoracic cavity. The engineered vasculature in the lung scaffold showed blood perfusion after transplantation without significant hemorrhage. The mouse-based lung bioengineering system can be utilized as an efficient ex-vivo screening platform for lung tissue engineering.
Applicability assessment and simplified calculation method of thermal indices in RayMan
Authors: QI CHEN , WANG HUA , MIN JINGJING , DONG YAN
Published: November 2023

Many thermal indices have been proposed for quantitative descriptions of human thermal perception over the past century to meet the strong demand in applied science. Meanwhile, developing the RayMan model provides a great interactive platform to calculate newly developed thermal indices. In this paper, we first used hourly meteorological observation data from national stations in Beijing from 2019 to 2021 to find the thermal indices applicable to the comfort evaluation of Beijing among the RayMan outputs. Using the UTCI and PT output from the RayMan model to evaluate the comfort level in Beijing, the results show that most of the time in winter, dominated by cold thermal perception, hot thermal perception appeared at an increased time in summer, and comfortable level dominated in spring and fall, which is consistent with seasonal changes of thermal perception in Beijing. Second, using the particular observation data from Daxing station in 2022, it is verified that RayMan outputs UTCI are consistent with the results calculated by the globe-thermometer method under most weather conditions. Finally, based on feature engineering and multi-model optimal parameter comparison, we used multi-layer perceptron for regression algorithm to build the UTCI and PT calculation models with reproduction errors less than or equal to 1°C of more than 93% and 95%, respectively. These models can calculate the thermal indices at different locations or time scales in Beijing, using station or grid meteorological observation or forecast data as inputs to meet different demands in applied science.
ARD-Net: Alligator gar real-time detection network model
Authors: Wang Xin , Shi Wei
Published: November 2023

When using advanced detection algorithms to monitor alligator gar in real-time in wild waters, the efficiency of existing detection algorithms is subject to certain limitations due to turbid water quality, poor underwater lighting conditions, and obstruction by other objects. In order to solve this problem, we developed a lightweight real-time detection network model called ARD-Net, from the perspective of reducing the amount of calculation and obtaining more feature map patterns. We introduced a cross-domain grid matching strategy to accelerate network convergence, and combined the involution operator and dual-channel attention mechanism to build a more lightweight feature extractor and multi-scale detection reasoning network module to enhance the network’s response to different semantics. Compared with the yoloV5 baseline model, our method performs equivalently in terms of detection accuracy, but the model is smaller, the detection speed is increased by 1.48 times, and has good real-time performance. Additionally, we created a dataset of alligator gar images for training.