bluuebunny/crossref_metadata_2025 huggingface dataset:
CGRPβ suppresses the pathogenesis of ulcerative colitis via the immunoproteasome
Authors: Shibao Tatsuya , Hase Hiroaki , Mizokami Kodai , Usui Atsushi , Kitae Kaori , Ueda Yuko , Jingushi Kentaro , Tsujikawa Kazutake
Published: December 2024

Various factors have been implicated in the pathogenesis of ulcerative colitis (UC), with immune system failure being the most important one. Calcitonin gene-related peptide (CGRP), a neuropeptide with two isoforms, CGRPα and CGRPβ, has been reported to regulate the immune system. In this study, we investigated the role of CGRP isoforms in UC pathogenesis. We induced UC-like symptoms in CGRPα and CGRPβ knockout (KO) mice using dextran sulphate sodium. Compared to wild-type and CGRPα KO mice, CGRPβ-deficient mice exhibited severe symptoms with increased blood in the stool and diarrhoea. Proteome analysis revealed significant up-regulation of immune-related proteins and immunoproteasome components in CGRPβ-deficient mice, suggesting that an enhanced immune response contributes to the severity of this disease. Treatment with ONX-0914, an immunoproteasome inhibitor, markedly improved these symptoms, highlighting the role of the immunoproteasome in exacerbating UC. This study provides the first evidence that CGRPβ protects against UC by modulating immune responses, particularly those mediated by the immunoproteasome. Our findings suggest that functional differences in CGRP isoforms may influence the severity and management of UC. This insight into the neuro-immune mechanism of UC opens avenues for novel therapies that address both the neural and immune aspects of this disease.
A latent profile analysis of the EPSI: Mapping anxiety, distress tolerance, and anxiety sensitivity with disordered eating symptomatology among university students
Authors: Claydon Elizabeth , Ward Rose Marie , Geyer Rachel , Weekley Donovan
Published: December 2024

OBJECTIVE: Disordered eating (DE) is associated with a plethora of psychosocial risk factors, including anxiety and substance use disorders. The Eating Pathology Symptoms Inventory (EPSI) is a validated questionnaire to assess DE. There are no latent profile analyses (LPA) of the EPSI that also examines these profiles with regards to important psychosocial risk factors. The purpose of this study was to fill that gap by connecting latent profiles of the EPSI subscales with anxiety, distress tolerance (DT), anxiety sensitivity (AS), and alcohol use (AU).
METHODS: The sample comprised of 1,362 college students from a midwestern university who participated in an online health survey. The EPSI scale profiles were identified using LPA with robust maximum likelihood estimation, and ANOVAs were run to determine if the classes differed across anxiety, AS, DT, and AU.
RESULTS: A four-class solution was found to be optimal (entropy>.96). Class 1 (49.4%) had the lowest levels of DE and alcohol problems; Class 2 (10.6%) had the highest scores for excessive exercise and along with Class 4, the highest beliefs on alcohol centrality; Class 3 (31.4%) comprised of participants who endorsed body dissatisfaction, restriction, and moderately high anxiety; and Class 4 (8.1%) had the highest EPSI scores across all subscales, as well as the highest levels of anxiety and problems with alcohol.
CONCLUSIONS: Several latent profiles were found for the EPSI subscales and Class 4 represented the most problematic levels. Identifying this subgroup of college students may help develop interventions and treatment to address these interrelated behaviors.
Antifungal activity of mycogenic selenium nanoparticles conjugated with fungal nano chitosan against three important phytopathogenic fungi
Authors: Gharieb Mohamed M. , Omara Mohamed S. , Soliman Azza. M.
Published: December 2024

The management of phytopathogenic fungal diseases in an ecofriendly way is an important agricultural challenge. This study evaluates the antifungal activity of mycogenic selenium nanoparticles (SeNPs), chitosan nanoparticles (NCT), and their composite against three phytopathogenic fungi: Alternaria alternata, Fusarium oxysporum and Fusarium verticilliodes. SeNPs were prepared by a previous biosynthesis method. Exposure to SeNPs altered fungal morphogenesis, significantly reducing biomass and sporulation. Transmission electron microscopy revealed SeNPs interactions with cell walls and damage to organelles, with intracellular SeNPs localization. Chitosan was produced from Rhizopus arrhizus yielding 0.52 g/L at 79.5% deacetylation. Fourier transform infrared and scanning electron microscopy characterized NCT and the SeNPs-NCT composite. SeNPs exhibited the strongest antifungal effects, completely inhibiting A. alternata and F. oxysporum growth at 12 ppm and F. verticilliodes at 25 ppm. NCT showed antifungal properties but lower efficacy, requiring 1000 ppm for complete inhibition. The SeNPs-NCT composite reduced activity versus SeNPs alone. This study demonstrates the antifungal potential of SeNPs and NCT against important plant pathogens. SeNPs interactions with fungal cells are also elucidated, providing insights into potential mechanisms of action such as cell wall embedment and organelle disruption.
lncRNA CHAF1B-2 contributes to the tumorigenesis of gastric cancer via activating the Wnt/β-catenin pathway
Authors: Tian Shao-Qi , Shen Jun-Jie , Sun Dao-Ping , Chen Wen-Ming
Published: December 2024

Lnc-CHAF1B-2, a newly unearthed long non-coding RNA (lncRNA), plays a significant role in the evolution and prognosis of diverse neoplasms. However, its role in the development of gastric cancer is not yet fully understood. Utilizing bioinformatics analysis on gastric cancer RNA-seq sequencing data from The Cancer Genome Atlas (TCGA) database, we delved into the expression of lnc-CHAF1B-2 within gastric carcinoma and its implicated molecular signaling pathways. Verification through an array of in vivo and in vitro experiments—namely, EdU incorporation, flow cytometry, Trans-well migration and invasion assays, subcutaneous tumor formation in nude mice, and Western blot analysis—were conducted. We uncovered a notable upregulation of lnc-CHAF1B-2 in gastric cancer tissues. Furthermore, a positive correlation was discerned between lnc-CHAF1B-2 levels and the occurrence of distant metastases in patients, inversely related to their prognostic outlook and survival rates. Moreover, our findings confirmed that lnc-CHAF1B-2 enhances proliferation, invasiveness, and migration of gastric cancer cells, whilst inhibiting apoptosis both in vitro and in vivo. Mechanistically, it was revealed that lnc-CHAF1B-2 promotes the progression of gastric cancer through activating the Wnt/β-catenin signaling pathway. Thus, lnc-CHAF1B-2 and its regulated Wnt/β-catenin signaling pathway emerge as prospective therapeutic targets in gastric cancer management.
A Medial Habenula Neural Circuit Controlling Anxiety-Like Behaviors in Response to Acute Stress
Authors: He Zi-Xuan , Wang Yao , Qiao Jiu-Ye , Lv Xin-Yue , Yue Mei-Hui , Yang Qian-Qian , Wang Si-Ran , Kang Han-Yun , Yu Hua-Li , He Xiao-Xiao , Zhu Xiaojuan
Published: December 2024

Anxiety is characterized by worried thoughts and an aversion to immediate threats. While the neural circuits underlying anxiety have been studied, however, the underlying circuit mechanisms remain largely unknown. Here, we report that the activity of tachykinin-expressing (Tac1) neurons in the medial habenula (MHb) is decreased and excitatory projections from these neurons are inhibited in response to acute stress in mice. Activation of interfascicular nucleus (IF)GLUT→MHbTac1 projections ameliorates anxiety-like behaviors in stressed mice. Moreover, MHbTac1 neurons send excitatory projections to the lateral part of the interpeduncular nucleus (IPL), regulating the activity of Tac1-projecting IPL neurons and anxiety-like behaviors in stressed mice. In summary, these findings delineate the circuit involving Tac1 neurons in the MHb that mediates anxiety-like behaviors in response to acute stress in mice.
The atlas of the tertiary lymphoid structure with omics data from breast cancer patients
Authors: Fan Xiaokai , Feng Daqin , Yu Yongjia , Liang Lun
Published: December 2024

The tertiary lymphoid structure (TLS) is considered a potential prognosis factor for breast cancer, and it has a high correlation with the response of immune therapy. Inducing TLS neogenesis can improve the immunogenicity of cancers and immune therapy efficiency. But it is still poorly known of the TLS, hence, we use high-resolution ways that include single-cell RNA sequencing and spatial transcriptome to explore the tertiary lymphoid structure of breast cancer. We find eighteen types of cells in TLS and calculate the differential expression genes compared the TLS regions with other regions. And the macrophages in the TLS region have lineage transformation, from the immune activation to facilitating the tumor cell growth. For the cell-cell communication in the TLS region, KRT86+ CD8+ T cell, HISTIH4C+ cycling CD8+ T cell, IFNG+ CD8+ T cell, and IGKV3-20+ B strongly communicate with other cells. We also find that APOD+ fibroblast and CCL21+ fibroblast mainly through CXCL12-CXCR4 ligand-receptor to recruit T/B cells.
Determination of the ED 50 of intravenous lidocaine for pain on awakening after pediatric tonsillectomy: A randomized controlled trial
Authors: Hu Yang , Du Ming-Cheng , Chen Yi , Long Xiang , Jiang Jing-Jing , Gong Yuan
Published: December 2024

Background: We investigated the potential of intravenous lidocaine to reduce pain on awakening in a dose-dependent manner and aimed to determine the median effective dose (ED50) of lidocaine in 200 children aged 3–12 years (American Society of Anesthesiologists physical status I–II) who underwent elective tonsillectomy with or without adenoidectomy at Yichang Central People’s Hospital.
Methods: The patients were randomized into four dose groups (A–D: 0.0, 1.0, 1.5, and 2.0 mg/kg, respectively) and underwent the same anesthetic induction and maintenance protocols. The primary outcome was pain on awakening, whereas secondary outcomes included pain scores at 1, 4, 12, and 24 h after awakening; incidences of laryngospasm, bronchospasm, or perioperative stridor; and time to extubation. Intraoperative cardiac events were classified as safety events.
Results: Our findings indicated that intravenous lidocaine dose-dependently reduced pain on awakening. The ED50 of intravenous lidocaine for pain on awakening was 1.75 mg/kg. Significant differences were observed between groups A and D (P ≤ 0.001). No incidents of laryngospasm, bronchospasm, or perioperative stridor were observed. Furthermore, there were significant between-group differences in time to extubation (P ≤ 0.05).
Conclusion: In conclusion, our study demonstrated that lidocaine dose-dependently reduced pain on awakening in children undergoing tonsillectomy with or without adenoidectomy (ED50 = 1.75 mg/kg), with no severe adverse events.
Trial registration: This study was approved by the Institutional Review Board of Yichang Central People’s Hospital (HEC-KYJJ-2020-038-02), The trial was registered at www.chictr.org.cn (ChiCTR2100053006).
Wind Network Fluctuation and Complementary Ventilation Caused by Differences in Wind Demand of The Double-hole Tunnel Construction
Authors: Xiaoming Wang , Yu Zhao , Guang Yang , Xinyu Zhao , Dong Liu , Hongliang Wei , Shiqiang Chen , Huan Deng
Published: December 2024

The realization of two-bore complementary ventilation in construction tunnels is a new challenge. This paper takes two-way four-lane, six-lane and eight-lane tunnel as the research object, and studies the possibility of two-bore complementary construction ventilation and the influence of construction parameters on the effect of complementary ventilation when when there is a difference in wind demand of double-bore. The results show that: two-bore six-lane tunnel is in line with the characteristics of the complementary construction ventilation, when the distance from the wind pipe outlet to the working surface is 20m, the height of the upper step is 3.5m, and the safety distance between the working face of the twin holes is 50m, the ventilation effect of double-hole complementary construction is enhanced. This kind of ventilation can introduce the surplus airflow from the tunnel with small air demand to the tunnel with large air demand, reduce the energy consumption of the tunnel ventilator in the tunnel with large air demand, and enrich the theory of the tunnel construction of the long double-cavity construction.
Nanoparticle Counting for PTI - the Dirty Tail Paradigm
Authors: Mayer Andreas , Czerwinski Jan , Lutz Thomas , Legerer Friedrich , Wyser Max , Comte Pierre , Larsen Hans-Christian , Rubino Lauretta , Vasilatou Konstantina , Engelmann Danilo , Knoll Markus , Burtscher Heinz
Published: December 2024

Using solid particle number (PN) measurements in the European Periodic Technical Inspection (PTI) of diesel engines equipped with particulate filters was proposed by VERT in 2016 during the Dieselgate Hearing of the Federal Republic of Germany. An international working group developed the standards and instruments for this method over three years under the leadership of TNO and VERT, which were next implemented in four countries, Belgium, the Netherlands, Germany and Switzerland, starting in 2022. PN measurement is now state of the art, enabling rapid and reliable detection of possible failures in particulate filters and the need for their immediate restoration. This paper expands on that successful experience, recommending that PN-counting be used for control of PN emissions from all vehicles during PTI. Five large vehicle fleets, Diesel and Gasoline, Heavy Duty Engines (HDE), Light Duty Vehicles (LDV) and Non-Road Mobile Machinery (NRMM), with and without emission aftertreatment were analyzed. It was observed that, while most vehicles in working fleets are clean (i.e., meet or are below their corresponding emission limits), every fleet however, contains some high emitters, about 4–8% of the fleet hereby termed “dirty tail”. This small fraction dominates the PN emission of the entire fleet and may increase the overall PN emission of its corresponding fleet by up to ten fold over the level of the complient vehicles! Experience indicates that PN emission may be a strong indicator of many different deteriorations in a combustion engine, and thus can be used as a highly sensitive diagnostic signal to detect various engine or emission faults quickly and reliably. This is a new understanding of emission control of vehicle fleets: not by regulations which apply for all vehicles but by selecting the high emitters and consequently repair or replace these relatively few vehicles to the extent desired in terms of emissions policy. Most countries have already implemented strong Periodic Technical Inspection systems. We suggest to expand such tests by additionally measuring the particle number concentration in the exhaust gas of all vehicles for just one minute, thereby detecting the high emitters. With consistent annual monitoring, this procedure will reduce urban particle pollution from combustion engines to one fifth or lower, a significant contribution to reducing local health risks.
Comparison of Ventriculoperitoneal Shunt and Lumboperitoneal Shunt for Post- hemorrhagic Hydrocephalus: A Retrospective Analysis of Long-term outcomes
Authors: Sun Tong , Chen Xiaofeng , Yuan Yikai , You Chao , Wu Ke , Guan Junwen
Published: December 2024

Background
Ventriculoperitoneal shunt (VPS) implantation stands as the prevailing therapy for individuals afflicted with post-hemorrhagic hydrocephalus (PHH). This study aims to meticulously scrutinize and juxtapose the enduring effectiveness and safety profiles of VPS and lumboperitoneal shunts (LPS) in addressing PHH.
Materials and Methods
We conducted a retrospective analysis of adult PHH patients who underwent shunt surgery at two centers from 2014 to 2018. The primary outcome was the shunt failure rate at 3 years after surgery. The secondary outcomes included postoperative complications, Evans index, and mRS score. In this study, positive response was defined as an improvement of 1 point or more in the postoperative mRS score, and a favorable outcome was defined as an mRS score of ≤3 points.
Results
A total of 273 patients were included: 177 patients receiving VPS and 96 patients receiving LPS surgery. The study showed that the VPS and LPS groups were at a similar baseline. At 3 years after surgery, the shunt failure rate in the VPS group was 15.3%, lower than that in the LPS group (27.1%) with a statistically significant difference (P=0.018). 138 patients (78.0%) in the VPS group and 60 patients (62.5%) in the LPS group had positive response, with a statistically significant difference between the two groups (P=0.007). The incidence of over-drainage in the VPS group was lower than that in the LPS group (P=0.028).
Conclusion
These discernments unequivocally advocate for VPS as the preferred therapeutic modality over LPS in managing PHH.
Development of a robust and efficient virus-induced gene silencing system for reverse genetics in recalcitrant Camellia drupifera capsules
Authors: Shen Hongjian , Chen Huajie , Li Weimeng , He Shan , Liao Boyong , Xiong Wanyu , Shen Yang , Li Yongjuan , Gao Yanru , Li Yongquan , Zhang Bipei
Published: December 2024

Background
Virus-induced gene silencing (VIGS) is a rapid and powerful method for gene functional analysis in plants that pose challenges in stable transformation. Numerous VIGS systems based on Agrobacterium infiltration has been widely developed for tender tissues of various plant species, yet none is available for recalcitrant perennial woody plants with firmly lignified capsules, such as tea oil camellia. Therefore, there is an urgent need for an efficient, robust, and cost-effective VIGS system for recalcitrant tissues.
Results
Herein, we initiated the Tobacco rattle virus (TRV)-elicited VIGS in Camellia drupifera capsules with an orthogonal analysis including three factors: silencing target, virus inoculation approach, and capsule developmental stage. To facilitate observation and statistical analysis, two genes predominantly involved in pericarp pigmentation were selected for silencing efficiency: CdCRY1 (coding for a key photoreceptor affecting light-responsive perceivable anthocyanin accumulation in exocarps) and CdLAC15 (coding for an oxidase catalyzing the oxidative polymerization of proanthocyanidins in mesocarps, resulting in unperceivable red-hued mesocarps). The infiltration efficiency achieved for each gene was ~ 93.94% by pericarp cutting immersion. The optimal VIGS effect for each gene was observed at early (~ 69.80% for CdCRY1) and mid stages (~ 90.91% for CdLAC15) of capsule development.
Conclusions
Using our optimized VIGS system, CdCRY1 and CdLAC15 expression was successfully knocked down in Camellia drupifera pericarps, leading to fading phenotypes in exocarps and mesocarps, respectively. The established VIGS system may facilitate functional genomic studies in tea oil camellia and other recalcitrant fruits of woody plants.
Verifying clinical benefit of new anticancer drugs after regulatory approval based on exploratory studies
Authors: Ito Akira , Narukawa Mamoru
Published: December 2024

Background: In Japan, anticancer drugs are often approved based on the Objective Response Rate (ORR) when the conduct of a confirmatory study is difficult or expected to take a considerably long time. However, it remains unclear how frequently post-marketing confirmatory studies are conducted and for which indications they are implemented. We aimed to understand the status of post-marketing confirmatory studies for approved anticancer drugs.
Methods: We investigated the status of post-marketing confirmatory studies on anticancer drug indications approved based on ORR in Japan between 2015 and 2022.
Results: We found that 60% of the indications did not have planned confirmatory studies, with many receiving “orphan drug” designations. This observation is consistent with the Japanese regulations thatallow the approval of anticancer drugs based on the ORR, for which confirmatory studies are difficult to conduct or expected to take a long time. Post-marketing confirmatory studies were less commonly requested from the regulatory authority in Japan than in the US. Although the results of post-marketing confirmatory studies were often utilized in regulatory actions in Japan (including modifications to approved indications), no indications were found where these results led to withdrawal of approval or additional confirmatory study requirements, and the evaluations of the results were not disclosed when they did not lead to regulatory actions.
Conclusions: To enhance transparency in the regulatory review process and facilitate smoother regulatory actions based on the results of post-marketing confirmatory studies, it may be beneficial to require the submission of the results of postmarketingconfirmatory studies if it is feasible following the approval based on ORR.
Phase distribution and lattice coherency for Li-rich zero-deformation cathode design
Authors: Jung Sung-Kyun , Nam Hyeong-Jun , Lee Daeyeon , Moon Jiye , Song Seok Hyun , Kim Kyoung Sun , Jo Hyoi , Choi Jingyu , Ha Jeeho , Kang Seok Ju , Kim Hyungsub
Published: December 2024

Chemo-mechanical degradation accompanying anisotropic lattice strain and stress is one of the critical failure modes of layered cathode materials, leading to capacity loss. While “zero-strain” or “zero-volume” advanced cathode materials have shown potential in addressing this issue, design principles and rational strategies for achieving a zero-deformation property still remain elusive. Here, we demonstrate that phase distribution and lattice coherency are key factors in controlling lattice changes and isotropy at phase boundaries within layered-rocksalt intergrown Li-rich cathode materials. These parameters are influenced by kinetics of transition metal ordering from rocksalt to layered phase, as well as atomic intermixing between two phases. Our findings reveal that higher lattice coherency, enhanced by cation intermixing between layered and rocksalt phases, effectively suppresses the lattice and volume changes, promoting isotropic lattice change behavior. Consequently, we successfully designed a zero-deformation cathode with lattice and volume changes of less than 1 %, which is further validated through solid-state battery operation under low stack pressure (~1 MPa). This work introduces phase boundary design strategies for developing zero-deformation cathode materials for next-generation Li-ion and solid-state batteries.
What can be learnt from the catastrophic failure of a check dam system? A forensic analysis of a cascading natural-anthropogenic hazard
Authors: Dallan Eleonora , Marchi Lorenzo , Rosatti Giorgio , Zugliani Daniel , Cavalli Marco , Crema Stefano , Valentinotti Ruggero , Borga Marco
Published: December 2024

Check dams may be effective structures for reducing debris flow hazard, but their failure often results in serious consequences for people and infrastructures. The examination of these failures embracing a forensic engineering approach, still rather poorly represented in the scientific literature, would lead to important improvements in how residual risk is planned and managed.
In this study, we developed a framework for the forensic analysis of check dam systems failures in terms of cascading natural-anthropogenic hazards, and we applied such framework to the catastrophic event occurred in October 2018 in the Rotian creek catchment (Eastern Italian Alps).
The post-event survey and analysis gathered observations about rainfall, peak discharges, morphological impacts, and damaged check dams. Based on these data, we applied a newly developed coupled hydrologic-hydraulic debris flow model and we assessed the failure mode of the check dam system. Our results highlight important practical implications for improving residual risk management, namely: i) development of debris flow models capable of simulating the role of check dams and their failure in the debris flow dynamics, ii) the call for extensive datasets of check dam system failures, and iii) the necessity to develop methodologies for the prioritisation of field inspection and maintenance of existing check dam systems.
Financial Inclusion Status, Measurement, Determinants and Gender Gap: an Empirical Analysis of Punjab State in India
Authors: Kaur Lavneet , Bansal Deepty
Published: December 2024

Access to finance connotes the supply of affordable and high-quality financial products and services, along with demand at the individual level. This research study provides a comprehensive analysis of financial inclusion, with a primary focus on measuring its level in the rural areas of Punjab state of India. The research aims to find the role of financial inclusion in sustainable economic development, elaborates the status of financial inclusion and finds out the financial inclusion indicators to measure the level of financial inclusion. Gender gap in the level of financial inclusion is determined and the impact of different demographic and socio-economic variables on the level of financial inclusion is also explored. A Financial Inclusion Index is developed to assess the extent of financial inclusion. The research highlights significant issues regarding financial inclusion and gender disparities, leading to policy recommendations aimed at enhancing financial inclusion. Ultimately, this study provides valuable insights into the varied aspects of financial inclusion and will be useful for researchers, financial institutions and government policy makers.
KarXT Combines the Partial Benefits of Haloperidol for Positive Symptoms and Sulpiride for Negative Symptoms: Evidence from Computational Biology
Authors: Zhuo Chuanjun , Li Chao , Ma Xiaoyan , Li Ranli , Chen Ximing , Li Yachen , Zhang Qiuyu , Yang Lei , Tian Hongjun , Wang Lina
Published: December 2024

The new drug KarXT is a combination of xanomeline and trospium. KarXT is a unique antipsychotic that targets muscarinic receptors to reduce the positive and negative symptoms of schizophrenia. Haloperidol affects the positive symptoms and sulpiride affects the negative symptoms of schizophrenia. The shared and distinct molecular mechanisms of these three drugs are unclear. The objective of this study is to identify the potential molecular mechanisms underlying the effects of KarXT on schizophrenia and determine if the mechanism for KarXT overlaps with the benefits of haloperidol for positive symptoms and sulpiride for negative symptoms. The putative target genes for haloperidol, sulpiride, and KarXT were identified using PharmMapper, SwissTargetPrediction, GeneCards, CTD, and SuperPred. Targets associated with positive and negative symptoms of schizophrenia were selected from GeneCards and OMIM. A protein-protein interaction (PPI) network was constructed to identify core targets and GO and KEGG pathway enrichment analyses of the top 20 core targets were conducted using DAVID. A drug-pathway-target-disease network was constructed using Cytoscape. The search yielded 179 common targets for haloperidol against positive symptoms, 96 targets for sulpiride against negative symptoms, and 99 targets for KarXT against schizophrenia. Based on the PPI network and KEGG enrichment analyses, haloperidol affects positive symptoms by targeting the IL-17 signaling pathway via TNF, IL6, IL1B, MAPK3, and CASP3, and sulpiride affects negative symptoms by targeting the PI3K-AKT signaling pathway via BDNF, INS, AKT1, IGF1, and BCL2. KarXT affects schizophrenia by targeting the MAPK signaling pathway via AKT1, FOS, CASP3, NFKB1, and IGF1. Molecular docking revealed good binding affinities between the drugs and the potential core targets. This study provides insights into the distinct molecular mechanisms by which haloperidol and sulpiride affect distinct symptoms of schizophrenia. KarXT integrates the partial effects of both drugs, including CASP3 with haloperidol and AKT1 and IGF1 with sulpiride. Our results provide a theoretical basis for clinical applications and new directions for drug development.
The influence of lead brass alloys sampling parameters on the surface properties and mechanical responses
Authors: Hammi Maryama , Bourakadi Khadija El , Dahhou Mohammed , Lazrak Charaf , Eddaoui Abderrahim , Haimeur Amine El
Published: December 2024

Leaded brass alloys are widely used in mechanical applications, making the examination of their surface and mechanical characteristics crucial. This study aims to assess the resistance and mechanical response of leaded brass alloys cast in thermally conductive molds, with a focus on the β’-phase formation during casting.To investigate the mechanical properties, the samples undergo hardness testing, with von Mise stress calculation employed for mechanical visualization. X-ray diffraction (XRD) analysis is conducted to validate the observations and refine the impact of lead content. The study employs chill molds made of steel, iron, silica sand, marble, and clay to achieve a homogeneous, stress-free alloy. Mechanical preparation involves fine particle size (SiC1000) and chemical surface treatment, including electrolytic polishing and metallographic etching.Surface analysis reveals the presence of an α + β’ dual phase in all samples. The microstructure is found to be controllable through cooling speed, influenced by the thermal conductivity and heat transfer rate at the material/mold interface. Micro-hardness calculation indicates a correlation between hardness and microstructure, particularly an increase in the β’ phase. The findings suggest that controlling the cooling speed during casting can significantly influence the microstructure and mechanical properties of leaded brass alloys. This insight can inform the optimization of casting processes to achieve desired material characteristics, enhancing the performance and durability of brass components in mechanical applications.
An Optimization Protocol for MRI Examination Resource Allocation Based on Demand Forecasting and Linear Programming
Authors: Zhou Zhongbin , Zhou Hanyu , Qiao Yuanyuan , Gao Zhihan , Yang Ying
Published: December 2024

Objective: The accessibility of medical services in Mainland China had been on the rise, leading to a surge in the number of Magnetic Resonance Imaging (MRI) scans. This increase had caused substantial delays in MRI examination queues at large hospitals. With MRI equipment and exams being costly, over-purchasing machines could lead to underutilization of resources. It was, therefore, crucial to devise a comprehensive method that could shorten patient wait times and optimize the use of medical resources within hospitals.
Method: The research had utilized daily MRI examination application data from a hospital covering the period from July 1, 2017, to November 30, 2022. The Autoregressive Integrated Moving Average (ARIMA) model and the AutoRegressive Integrated Moving Average with exogenous (ARIMAX) model were developed using SAS (version 9.3) software. Moreover, Non-AutoRegressive (NAR) and Non-AutoRegressive with exogenous (NARX) models were built using MATLAB (version R2015b) to forecast future MRI examination demands. The predictive accuracy of these models was then assessed and compared. Based on the prediction outcomes, an Integer Linear Programming model was employed to calculate the optimal number of MRI examinations per machine per day, targeting cost reduction. An optimization flowchart for MRI examination resource allocation was developed by integrating critical process components, thus streamlining and systematizing the optimization process to improve efficiency.
Results: Analysis of the data revealed a weekly cyclical trend in MRI examination applications. Among the ARIMA, ARIMAX, NAR, and NARX models evaluated for their predictive skills, the NARX model emerged as the most accurate for forecasting. An Integer Linear Programming (ILP) model was utilized to plan the number of examinations for each MRI machine, effectively reducing costs. An optimization flowchart was developed to integrate key factors in MRI examination resource allocation, streamlining and systematizing the optimization process to enhance work efficiency.
Conclusion: This study offers a comprehensive protocol for optimizing MRI examination resource allocation, combining the predictive power of the NARX model, the planning capabilities of the Integer Linear Programming model, and the integration of other relevant factors via an optimization flowchart.
Clinical trial number: not applicable.
Evaluation of yeast extract, chitosan, and pectin as easy and cost-effective applications to increase indirubin and indigotin accumulation in Isatis tinctoria root cultures
Authors: CESSUR Alper , Baydar Nilgün Göktürk
Published: December 2024

This study was carried out to determine the effects of yeast extract, chitosan, and pectin as simple and cost-effective biotic elicitors on root growth and the accumulation of indigotin and indirubin in the root of Isatis tinctoia. For this purpose, different concentrations of yeast extract (1, 2, 3, and 4 g L− 1), chitosan (100, 150, 200, and 250 mg L− 1), and pectin (0.5, 1, 2, and 3%) were applied to 21 days old roots for 7 days. After harvest, roots were evaluated regarding fresh root weight, root growth index, dry root weight, and contents of indigotin and indirubin. As a result of the study, it was determined that yeast extract showed positive effects on root growth while chitosan inhibited. On the other hand, pectin had no positive or negative impact on root growth parameters. Yeast extract and chitosan increased indigotin accumulation in roots compared to control roots while indigotin amounts decreased with the pectin. Within yeast extract applications, the highest indirubin contents were obtained from the roots applied with 3 and 4 g L− 1 of yeast extract. All chitosan applications enhanced the indirubin accumulation compared to control. The effect of pectin on indirubin accumulation was changed depending on its concentrations. Pectin at 0.5 and 1% increased indirubin contents compared to control. In conclusion, 1 g L− 1 of yeast extract for root growth and 100 mg L− 1 of chitosan for indigotin and indirubin contents were selected as the most appropriate applications supplying the highest values.
Synchronous activation of striatal cholinergic interneurons induces local serotonin release
Authors: Matityahu Lior , Hobel Zachary B. , Berkowitz Noa , Malgady Jeffrey M. , Gilin Naomi , Plotkin Joshua L. , Goldberg Joshua A.
Published: December 2024

Striatal cholinergic interneurons (CINs) activate nicotinic acetylcholine receptors on dopamine axons to extend the range of dopamine release. Here we show that synchronous activation of CINs induces and extends the range of local serotonin release via a similar mechanism. This process is exaggerated in the hypercholinergic striatum of a mouse model of OCD-like behavior, implicating CINs as critical regulators of serotonin levels in the healthy and pathological striatum.
The Impact of Regional Integration Policies on Innovation Efficiency--The Case of the Yangtze River Delta Urban Agglomeration
Authors: Xie Wengjing , Xiao chengyou , Zhong Hong
Published: December 2024

Can regional integration policies enhance the efficiency of urban innovation? To this end, this study employs a multi-period PSM-DID approach based on data from 285 prefecture-level cities in China from 2004 to 2020 and a quasi-natural experiment on regional integration in the Yangtze River Delta (YRD) region to assess the impact of the implementation of regional integration policies on the innovation efficiency of cities. The results show that (1) the impact of regional integration policies on urban innovation efficiency (TE) is positively facilitated.(2) This paper further discusses the impact of regional integration policies on innovation efficiency by taking into account the upgrading of industrial structure in Chinese regions and using industrial structure upgrading as a moderating variable, and the results show that upgrading of urban industrial structure enhances the impact of regional integration policies on urban innovation efficiency.(3) Based on the perspective of heterogeneity, in cities with smaller population size, lower economic development level and weaker transportation accessibility, regional integration policy has a more significant effect on the enhancement of urban innovation efficiency, which shows that regional integration policy can effectively bring into play the technological diffusion effect of the central cities such as Shanghai, Hangzhou and Nanjing.
Efficient Remote Sensing Image Classification using the Novel STConvNeXt Convolutional Network
Authors: Liu Bo , Zhan Chenmei , Guo Cheng , Liu Xiaobo , Ruan Shufen
Published: December 2024

Remote sensing image classification poses significant challenges due to complex spatial organization, high inter-class similarity, and large intra-class variance. To address these issues, we propose STConvNeXt, a novel pure convolutional neural network specifically tailored for efficient remote sensing image classification. STConvNeXt integrates a split-based mobile convolutional module, a tree structure, and a fast pyramid pooling module to achieve residual connectivity. Additionally, we introduce a threshold loss function to stabilize model training and improve classification accuracy. Comprehensive experiments on multiple remote sensing datasets demonstrate that STConvNeXt achieves a 56.49% reduction in parameters and a 49.89% decrease in computational load compared to ConvNeXt, while maintaining state-of-the-art classification accuracy. Our results highlight the effectiveness of STConvNeXt in extracting robust features from remote sensing images, advancing the frontiers of deep learning-based remote sensing analysis.
Study on the Destruction Resistance of Collaborative Innovation Networks in City Clusters under Subject Failure Scenarios: Simulation Analysis Based on Network Cascade Failure Models
Authors: Du Danli , Wang Jiahe , Ding Kaixing , Jin Yufeng , Wang Xinyi
Published: December 2024

As the interdependence within inter-city collaborative innovation networks intensifies, the threat posed by subject failures triggered by external shocks to the effective functioning of these networks becomes increasingly critical. This paper delves into the impact of various types of subject failures on the resilience of city cluster collaborative innovation networks. By categorizing subject failures into nine distinct modes, this study integrates two pivotal aspects of innovation network resilience—structure and function—into a unified research framework. Structural resilience is assessed through the maximum connectivity subgraph, while functional resilience is gauged using network efficiency. The findings reveal notable variations in the structure of collaborative innovation networks across different fields, alongside differing sensitivities to the network’s resistance to destruction due to subject failures. Moreover, it was observed that random subject failures associated with high city clustering coefficients exert minimal impact on the network's structural and functional destructiveness, whereas those linked to larger city degree centrality significantly disrupt both network structure and function. Furthermore, the V index is employed to compare the effects of subject failure indicators across nine modes, indicating that cities with higher degrees of centrality have the most profound impact on network resilience. Significantly, when subject failures reach a threshold of 10%, both the structural and functional aspects of the city cluster collaborative innovation network approach a collapse threshold. The outcomes of this research highlight the destructive characteristics of city cluster collaborative innovation networks and offer a theoretical foundation for developing targeted risk management strategies to ensure the network's sustainable development.
Heat tolerance and thermal scope are evolutionarily constrained in Greenlandic terrestrial arthropods
Authors: Wesseltoft Jonas , Ørsted Michael , Jonge Nadieh , Hansen Michael , Høye Toke , Kristensen Torsten
Published: December 2024

Temperatures in the Arctic currently rise at four times the global average, making it of utmost importance to understand the thermal biology of species in these sensitive environments. For arctic ectotherms in particular, thermal tolerance limits and adaptive potential are mostly unknown. Such knowledge is urgently needed to predict climate change impacts on future distributions of biodiversity in these rapidly changing environments. Here, we provide new data on upper and lower thermal limits of 93 Greenlandic species of insects, arachnids, and collembolans identified using barcode sequencing representing ~8% of described terrestrial Greenlandic arthropod species. We found pronounced differences in heat and cold tolerance among species and a strong phylogenetic signal for both heat tolerance and thermal scope (difference between upper and lower thermal limits), suggesting that terrestrial Greenlandic arthropods are evolutionarily constrained in their capacity to cope with increasing and more variable future temperatures. Further, with projected future increases in microclimatic temperatures induced by climate change, we reveal a marked increase in the number of species that will experience potentially stressful temperatures for prolonged periods of time. Together, our results suggest that climate change will likely result in substantial changes in distributions and abundances of Greenlandic terrestrial arthropods.
Vagal AF Induction Test (VAFIT): A New Endpoint for Optimizing Atrial Fibrillation Ablation through Cardioneuroablation
Authors: Pachon-M JC , Pachon-M Enrique I , santillana-P Tomas G , Lobo Tasso J , Cunha-P Carlos T , Pachon-M Juan Carlos , Cunha-P Maria Zelia , Clark John
Published: December 2024

Introduction Currently, there is no reliable endpoint for the conclusion of atrial fibrillation (AF) ablation. Atrial burst pacing and/or isoproterenol challenge are poor diagnostic tools. A newly proposed Vagal AF Induction Test(VAFIT) uses effective atrial refractory period measurement, simultaneously with extra-cardiac vagal stimulation(ECVS) to study AF inducibility pre and post-ablation. This is a prospective study in patients submitted to radiofrequency catheter pulmonary vein isolation(PVI) plus cardioneuroablation(CNA) evaluating the VAFIT result before and at the end of the procedure with AF recurrence. Methods Prospective study of 142 patients, 57.5[48.9–70.2] years-old, 71% males, with symptomatic AF (79.6% paroxysmal/20.4% persistent), left atrium diameter of 38.0[35.0-41.2] mm, and left ventricular ejection fraction of 63.0 [62.0-68.2]. VAFIT was considered positive or negative depending on whether AF induction occurred. It was performed at baseline and after PVI + CNA, with a single atrial extra stimulus during ECVS (5s/50Hz/1V/kg up to 70V/Pulse Width = 50 µs). Patients were followed for a median of 15.0[7.0–20.0] months. The association of VAFIT-positive status at the end of the procedure with AF recurrence was investigated by univariate and multivariate Cox regression analysis. Results Pre-ablation VAFIT was positive in all cases and became negative in 62.9% of patients. AF recurrence: 18.7% in VAFIT-positive and 5.6% in VAFIT-negative patients(p = 0.012). VAFIT-positivity was associated with AF recurrence (HR: 4.56(1.37–15.23,p = 0.014). Conclusion A VAFIT-positive status following PVI + CNA was strongly and independently associated with AF recurrence. It remains to be investigated in randomized studies whether achieving VAFIT-negativity at the end of the procedure, as demonstrated in this study, would lead to better clinical outcomes.
Evaluation of Er,Cr:YSGG laser activation, manual dynamic and conventional irrigation for smear layer removal using different sodium hypochlorite irrigating solutions
Authors: Abaza Muhammad Mahmoud , Harhash Tarek Abd ElHamid
Published: December 2024

Background
The purpose of the present study was to microscopically evaluate the influence of Er,Cr:YSGG laser, manual dynamic, and conventional methods on smear layer removal of different NaOCl solutions at the apical, middle, and coronal regions of root canal walls.
Methods
One hundred & eight freshly extracted human single-canal anterior teeth were enrolled in this study. The teeth were decapitated & their canals were instrumented to size X4, 0.06 taper using rotary files of ProTaper Next® system. According to type of agitation technique, the teeth were classified into three groups (36 teeth each); no activation (traditional), manual dynamic, & Er,Cr:YSGG laser-activated techniques. Each group were further subdivided into four subgroups based on the irrigant type & concentration (n = 9); saline and 1%, 2.5%, and 5.25% NaOCl. Samples were gently split, longitudinally for SEM evaluation. Kruskal-Wallis and Mann-Whitney tests were used for statistical analysis.
Results
Regardless the irrigant type & concentration, Er,Cr:YSGG Laser-activated & manual dynamic groups showed better smear layer removal values than that of conventional group.
Conclusion
Er,Cr:YSGG laser-activated irrigation can eliminates more smear layer compared manual dynamic, & conventional techniques which increasing the cleaning capacity of different root canal irrigants.
Accumulation and distribution of mercury in cacao (Theobroma cacao) grown in artisanal small-scale gold mining areas, Ashanti Region, Ghana
Authors: Poku patrick Adu Adu , Margaret Boohene , Sylvester Addai-Arhin , Elwaleed Ahmed , Tia Agustiani , Jeong Huiho , Agusa Tetsuro , Ishibashi Yasuhiro , Kobayashi Jun
Published: December 2024

Cacao is an important agricultural crop in Ghana, but is grown even in artisanal small scale gold mining (ASGM) area using mercury (Hg) during the amalgamation process. This study investigated Hg concentration in agricultural soil and cacao plant in three ASGM communities in the Ashanti Region of Ghana to evaluate transfer of Hg from soil to cacao and health risk by ingesting of cacao beans. As for the soil samples, the mean Hg concentration was 76 ± 36 µg/kg dw (n = 42), corresponding to moderate contamination by the contamination factor. As for the cacao samples (n = 12 each), the highest mean Hg concentration was found in roots (211 µg/kg dw) and followed by leaves (138 µg/kg dw), pods (40 µg/kg dw) and beans (27 µg/kg dw). Significant correlations were observed between the cacao samples (p < 0.05), but not with the soil samples. indicating accumulation does not only depend on contaminated soil but also the type of plant, its ability to absorb and atmospheric deposition. Data analysis using the bioaccumulation factor (BAF) and the transfer factor (TF) indicated that Hg was highly accumulated from the soil to the root of cacao (BAF = 3.1) but did not highly transfer from the root to the aerial parts (TF < 1). The health risk assessment for ingestion of cacao beans showed that the hazard quotient was less than 1, indicating that there is no possibility of non-carcinogenic health effect.