bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhancement of Control Stability Using Double Pulleys for Coupled Tendon-Driven Long-Reach Manipulator “Super Dragon”
Authors: Shizume Yuki ,   Editorial Office, Takata Atsushi , Endo Gen
Published: February 2024

The exploration and inspection of narrow spaces in nuclear facilities require the use of long-reach manipulators. Coupled tendon-driven manipulators can realize lightweight and slender arms by positioning actuators, such as motors, at the base. Currently, we are developing a coupled tendon-driven super long-reach articulated arm, which we name “Super Dragon.” Super Dragon is a robot arm with a total length of 10 m, a maximum arm diameter of 0.2 m, and 10 joints. In this paper, we focused on the elasticity and elongation of ropes. The joint actuation of Super Dragon utilizes synthetic fiber ropes characterized by their high strength and flexible bending. However, when these ropes are used over long lengths, wire elongation occurs, thus causing the joint angles to exhibit unintended and unstable behavior. Therefore, we focused on a specific posture and employ a double pulley as a mechanical solution to suppress unstable behavior. We introduced stability criteria and performed parametric searches to obtain the appropriate double pulley radii. Subsequently, we identified the position and radius of the introduced double pulley that can be analytically stabilized. By installing a double pulley in the actual machine and conducting experiments, we successfully suppressed the unstable behavior.
Распространение вариантов вируса SARS-COV-2, вызывающих интерес (VOI) и находящихся под наблюдением (VUM), на основе количества их геномов, депонированных в базу данных GISAID за неделю с 10 по 16 февраля 2024 г.
Authors: Дмитриева Людмила , Краснов Ярослав , Чумачкова Елена , Гусева Наталья , Осина Наталья , Зимирова Анастасия , Иванова Александра , Карнаухов Игорь , Караваева Татьяна , Щербакова Светлана , Кутырев Владимир
Published: February 2024

В обзоре представлена информация по циркулирующим в настоящее время вариантам вируса SARS-COV-2 Omicron вызывающих интерес (VOI) и находящихся под наблюдением (VUM), геномные последовательности которых размещены в международной базе данных GISAID за неделю с 10 по 16 февраля 2024 г.
Deep learning methods for omics data imputation
Authors: Huang Lei , Song Meng , Shen Hui , Hong Huixiao , Gong Ping , Hong-Wen Deng , Chaoyang Zhang
Published: February 2024

One common problem in omics data analysis is missing values, which can arise due to various reasons, such as poor tissue quality and insufficient sample volumes. Instead of discarding missing values and related data, imputation approaches offer an alternative means of handling missing data. However, the imputation of missing omics data is a non-trivial task. Difficulties mainly come from high dimensionality, non-linear or nonmonotonic relationships within features, technical variations introduced by sampling methods, sample heterogeneity, and the non-random missingness mechanism. Several advanced imputation methods, including deep learning-based methods, have been proposed to address these challenges. Due to its capability of modeling complex patterns and relationships in large and high-dimensional datasets, many researchers have adopted deep learning models to impute missing omics data. This review provides a comprehensive overview of the currently available deep learning-based methods for omics imputation from the perspective of deep generative model architectures such as autoencoder, variational autoencoder, generative adversarial networks, and Transformer, with an emphasis on multi-omics data imputation. In addition, this review also discusses the opportunities that deep learning brings and the challenges that it might face in this field.
Case For Chapbooks
Authors: Rupchan Juliana
Published: February 2024

Collecting contemporary poetry is often a low priority for libraries, but interest in poetry is rising, and many library patrons have the potential to become poetry readers. Building a collection of poetry chapbooks can maximize the impact of a renewed poetry collecting effort because the poetry chapbook is an accessible, high-interest, and often low-cost form that captures the cutting edge of the poetic field. I introduce the poetry chapbook and its creative and social functions and describe various avenues for building a chapbook collection, including acquisition strategies, examples of digital initiatives such as participatory chapbook repository projects, and notes on promoting engagement. The community-building potential and links to higher-level goals such as diverse collecting, local interest, and cultural preservation allow chapbook collections to add unique value to a variety of public, academic, special, and school library contexts.
Apatite (U-Th)/He Thermochronological Constraints on the Landscape Evolution Linked to the Normal Faulting in Taishan Mountain, Eastern China
Authors: Liu Fangbin , Yang Fan , Zheng Dewen , Ding Haiyang , Li Caopeng , Jepson Gilby
Published: February 2024

Taishan Mountain in the eastern China is a normal-fault-controlled range that formed during the Meso-Cenozoic, in response to large-scale extension and lithospheric thinning of the North China Craton. However, constraints on the timing of the polyphase extensional events which formed the Taishan edifice remain poorly resolved, hindering a detailed understanding of the landscape evolution of this prominent mountain. Here, we conducted apatite (U-Th)/He dating on sixteen samples from three profiles perpendicular in the Taishan Mountain, with a major view to control structures in Taishan Mountain and to resolve the Meso-Cenozoic landscape evolution. The newly determined apatite (U-Th)/He ages show a wide variation range of ~113 to 30 Ma, indicating a slow and protracted cooling history. The inverse thermal history modeling results reveal two pulses of enhanced cooling at ~80 to 60 and 55 to 50 Ma, which we interpret as exhumation related to normal fault activity. Furthermore, one-dimensional modeling indicates that the magnitude of tectonic exhumation is constrained at ≥15 m/Myr across the Yunbuqiao, Zhongtianmen, and Taishan Piedmont faults. Integrating this study and published studies, we suggest that Taishan Mountain underwent four-stage evolution since 100 Ma: (1) the whole Taishan Mountain commenced a continuous and slow exhumation under a weaker tensional environment at ~100 to 80 Ma, (2) the joint growth and interactions within a normal fault system resulted in rapid uplift and promoted the formation of the Proto-Taishan Mountain at ~80 to 60 Ma, (3) the Taishan Mountain underwent exhumation at ~55 to 50 Ma, interpreted as a tectonic response to the Taishan Piedmont Fault, and (4) the last stage (~50 to 0 Ma), the Taishan Mountain experienced protracted exhumation related to normal faulting until now. We attribute the extensive normal faulting to the subduction and slab rollback of the Izanagi-Pacific Plates, which shaped the present-day geomorphology of Taishan Mountain.
Proyecto de inversión para un banco de leche materna en Lima Metropolitana
Authors:   , Freitas Chota Melida Rosaura , Huaytalla Arango Jhina Evelin , Polo Cercado José Gonzalo , Zevallos Guzmán Joan Leonardo
Published: February 2024

El presente trabajo de investigación tiene el propósito de plantear y evaluar un proyecto privado de un producto biológico compuesto 100% de leche materna (LM) suministrada por madres de menores hasta dos años de edad. La idea de inversión, consiste en evaluar la factibilidad de la creación de un Banco de Leche Materna (BLM) en Lima Metropolitana, de acuerdo a los estándares de calidad y reglamentación exigido mínimamente a los BLM por el Ministerio de Salud, dirigido particularmente a satisfacer la necesidad de alimento, nutrición y desarrollo de bebés prematuros y/o recién nacidos hasta dos años de edad, que no pueden ser amantados directamente por la madre. El proyecto, no solo busca plasmar la información adquirida en el plano financiero, contable, administrativo y económico; sino que, también demanda que el bien a comercializar sea innovador y, que además se encuentre respaldado por un trabajo de investigación previo. La empresa proyectada, BANLEMA S.A.C. nace como persona jurídica, desde una minuciosa indagación de mercado, pasando por los planes exigidos, los aspectos administrativos hasta llegar a ser sustentado como rentable para la inversión, tomando en cuentas aspectos que ayudan a tomar decisiones de inversión (VA, VAN, TIR, COK) sobre los flujos de caja que se obtiene durante los años de duración del proyecto. Una de las características esenciales de todo proyecto es la determinación del COK (costo de oportunidad), y este trabajo no lo excluye, esta tasa de descuento es esencial para traer al presente los flujos futuros y se regirá de acuerdo a la metodología que aplique al determinar el financiamiento del mismo (mercado financiero, costo de capital de la empresa y rentabilidad esperada): CAPM o WACC.
Nivel de conocimiento de profesionales de salud sobre demencia en Perú
Authors:   , Aguirre Pérez Rafhael Junior
Published: February 2024

Objetivo: Determinar el nivel de conocimiento sobre demencia y la enfermedad de Alzheimer de los profesionales de salud en el Perú. Materiales y métodos: La encuesta se llevó a cabo de manera presencial y virtual en el año 2020, y estuvo dividida en tres partes. Se incluyeron a profesionales de salud de los centros evaluados cuyo proceso de formación haya sido realizado en universidades peruanas. Se analizaron 804 encuestas de las cuales 56 fueron eliminadas por datos incompletos o por no ser profesionales de salud. Se realizó una prueba de chi-cuadrado para valorar las diferencias entre grupos evaluados. Se consideraron como estadísticamente significativos valores con p<0.008 (Corregido Bon Ferroni). Resultados: El 69.4% de los encuestados fueron de centros de Salud en la región Lima. El 41.6% de los encuestados fueron médicos. El 72.8% refirió no estar capacitado para diagnosticar y tratar a un paciente con demencia. Con respecto a la enfermedad de Alzheimer, se obtuvo que el 19.5% de los profesionales de salud refirió que ésta no es un tipo de demencia. Médicos capacitados en postgrado, que se perciben capaces de pacientes con demencia, o que atienden más de cinco pacientes al mes con este diagnóstico, obtuvieron mejores resultados con diferencias estadísticamente significativas. Conclusión: El nivel de conocimiento entre los diferentes profesionales de salud encuestados en nuestro país acerca de demencia y la EA es bajo, con niveles menores fuera de Lima y mayores en profesionales con posgrado.
Investigating the Extent of the Impact of Acetic Acid as Halite Precipitation Reduction Agent for Enhancing CO2 Injectivity in Deep Saline Aquifers
Authors: Darkwah-Owusu Victor , Md Yusof Muhammad Aslam , Sokama-Neuyam Yen Adams , Tackie-Otoo Bennet Nii , Turkson Joshua Nsiah , Kwon Sunil , Hyun Lee Jang , Fjelde Ingebret
Published: February 2024

CO2 sequestration in deep saline aquifers is vital to reduce the global carbon footprint. However, this effort can be hampered due to salt precipitation during CO2 injection, which clogs flow pathways leading to a significant reduction in CO2 injectivity. While freshwater has traditionally been employed as the primary solution to dissolve the precipitated salt, the salt tends to re-precipitate upon CO2 reinjection post-treatment, exacerbating the injectivity damage. The project was divided into two stages: (1) simulating salt precipitation scenarios with varying brine salinities to mimic formation damage during CO2 injection in saline aquifers, and (2) critically assessing the impact and effectiveness of acetic acid as a mitigation fluid under different injection scenarios through core-flooding experiments. The results were compared with freshwater and low salinity water (LSW). Mineralogical and petrographical assessments were carried out on the core samples to characterize the Berea sandstone cores. The core flooding experiments were conducted at 60 °C and 1600 psi for CO2 injection, freshwater, LSW and acetic acid flooding. The experimental results revealed significant reductions in permeability (37% -75% impairment) and porosity (18% to 33%) due to salt precipitation. Among the treatments, LSW exhibited the lowest efficacy, followed by freshwater, possibly due to clay swelling, fines migration, and capillary trapping effects causing pore throat blockages. In contrast to freshwater and LSW, acetic acid treatment demonstrated improved injectivity, showing a high dissolution potential with up to a 137% increase compared to initial permeability. This study provides a preliminary assessment of the potential of acetic acid for CO2 injectivity enhancement and recommends further investigations on the effects of acetic acid and brine concentrations on the process.
Lethal and sublethal heat-exposure of bed bugs (Cimex lectularius L.) causes alarm pheromone emission and elicits a movement response in nearby recipients
Authors: Ashbrook Aaron , Feder Jeffrey , Bennett Gary , Ginzel Matthew , Gondhalekar Ameya
Published: February 2024

Many gregarious insect species use aggregation and alarm pheromones. The bed bug, Cimex lectularius L., emits an alarm pheromone (AP), a 70/30 blend of (E)-2-hexenal and (E)-2-octenal, when threatened. Bed bugs avoid temperatures above 43 °C, which are lethal to bugs and used commercially as spatial heat treatments to manage infestations. However, the interaction of bed bug AP in heat avoidance has not been investigated. The goal of this research was to: 1) determine if bed bugs emit AP as an alarm response to heat exposure, and 2) quantify the behavioral responses of conspecifics to AP emitted by heat-exposed bed bugs. Using a selected ion flow tube mass spectrometer, we found that bed bugs responded to lethal and sublethal heat exposure by emitting AP. The Harlan laboratory population emitted more pheromone than a laboratory adapted field population from Florida (McCall). Harlan females emitted the most AP, followed by Harlan males, McCall females and males. In separate behavioral experiments, we showed that conspecifics (i.e., recipients) reacted to AP released by heat exposed bed bugs (i.e., emitters) by frantically moving within 50 mm and 100 mm test arenas. The Harlan recipients reacted to AP in 100 mm areas, whereas the McCall strain did not, indicating a short area of effectiveness of the AP. Synthetic AP components tested in behavioral experiments caused identical effects as the natural AP blend released by heat-exposed bed bugs.
Mechanisms underlying the therapeutic effects of Gang Huo Qing wen granules in the treatment of influenza based on network pharmacology, molecular docking and molecular dynamics
Authors: Wu Wenyu , Jiao Xin , Lan Wanning , Wu Peng , Wang Kai , Zhan Shaofeng
Published: February 2024

Background:Influenza (Flu) is a severe health, medical, and economic problem, but no medication that has excellent outcomes and lowers the occurrence of these problems is now available. GanghuoQingwenGranules(GHQWG) is a common Chinese herbal formula for the treatment of influenza (flu). However, its methods of action remain unknown. We used network pharmacology, molecular docking, and molecular dynamics simulation techniques to investigate the pharmacological mechanism of GHQWGin flu.
Methods: TCMSP and various types of literature were used to obtain active molecules and targets of GHQWG. Flu-related targets were found in the Online Mendelian Inheritance in Man (OMIM) database, the DisFeNET database, the Therapeutic Target Database (TTD), and the DrugBank database. To screen the key targets, a protein-protein interaction (PPI) network was constructed. DAVID was used to analyze GO and KEGG pathway enrichment. Target tissue and organ distribution was assessed. Molecular docking was used to evaluate interactions between possible targets and active molecules. For the ideal core protein-compound complexes obtained using molecular docking, a molecular dynamics simulation was performed.
Results: In total, 90 active molecules and 312 GHQWG targets were discovered. The PPI network's topology highlighted six key targets. GHQWG's effects are mediated via genes involved in inflammation, apoptosis, and oxidative stress, as well as the TNF and IL-17 signaling pathways, according to GO and KEGG pathway enrichment analysis. Molecular docking and molecular dynamics simulations demonstrated that the active compounds and tested targets had strong binding capabilities.
Conclusions: This analysis accurately predicts the effective components, possible targets, and pathways involved in GHQWG flu treatment. We proposed a novel study strategy for future studies on the molecular processes of GHQWGin flu treatment. Furthermore, the possible active components provide a dependable source for flu drug screening.
Potential anatomical triggers for plan adaptation of cervical cancer external beam radiotherapy
Authors: Brown Rhianna , Holloway Lois , Lau Annie , Lim Karen , Moodaley Pereshin , Metcalfe Peter , Do Viet , Cutajar Dean , Walker Amy
Published: February 2024

This study aimed to identify potential anatomical variation triggers using magnetic resonance imaging for plan adaption of cervical cancer patients to ensure dose requirements were met over an external beam radiotherapy course. Magnetic resonance images (MRIs) acquired before and during treatment were rigidly registered to a pre-treatment computerised tomography (CT) image for 11 retrospective cervix cancer datasets. Target volumes (TVs) and organs at risk (OARs) were delineated on both MRIs and propagated onto the CT. Treatment plans were generated based on the pre-treatment contours and applied to the mid-treatment contours. Anatomical and dosimetric changes between each timepoint were assessed. The anatomical changes included the change in centroid position and volume size. Dosimetric changes included the V30Gy and V40Gy for the OARs, and V95%, V100%, D95% and D98% for the TVs. Correlation with dosimetric and anatomical changes were assessed to determine potential replan triggers. Changes in the bowel volume and position in the superior-inferior direction, and the high-risk CTV anterior posterior position were highly correlated with a change in dose to the bowel and target, respectively. Hence changes in bowel and high-risk CTV could be used as a potential replan triggers.
Molecular Characteristic of High Grade Glioma in Relation to 5-ala Fluorescence Intensity
Authors: Arjona Santiago Garfias , Almunia Mónica Lara , Valentí Ester Antón , Lopetegui Javier Pierola , Escalas Juan Bestard , Barcelo Albert Maimo , Marzese-Parrilli Diego Matías , Íñiguez-Muñoz Sandra , Ensenyat-Mendez Miquel , Doval Marta Brell
Published: February 2024

The intensity of 5-ALA fluorescence used in glioma surgery varies within tumors, and among different patients, several molecular and external factors have been implicated; however, there is no clear evidence analysing the difference in fluorescence according to glioma molecular characteristics. This study aimed to compare the molecular factors of glioma samples with fluorescence intensity to identify potential cofounders and associations with clinically relevant tumor features. Tumor samples from high-grade glioma patients treated with 5-ALA for guided resection were included for comparative analysis of fluorescence intensity and molecular features. The mean fluorescence was compared for each molecular variation. p53, ATRX and Ki67 expression and IDH1 mutation status were assessed via immunohistochemistry. The patients were followed upfor progression-free survival and overall survival. We found that the fluorescence intensity for each specific tumor was independent of the methylation status of the MGMT promoter region, as assessed by pyrosequencing, and that there was no association between fluorescence and p53, ATRX, or IDH1 mutation, as assessed by immunochemistry. Additionally, fluorescence intensity was not related to the duration of tumor recurrence or overall survival. Weargue that many factors are involved in the difference in fluorescence intensity and may be related to the specific metabolic status of the glioma cells analysed, which is likely responsible for the variation in fluorescence.
Concentrating on Sustainable development: The Analysis of China’s Fashion Industry Base on Literatures from 2013 to 2023
Authors: Xie Lin , Li Chaode
Published: February 2024

The purpose of this research is to explore the current industrial status and the possible trend of China’s fashion industry which would be a supplement to previous research on the topic of “current and future sustainability of international fashion industry”. This research applies the unsupervised machine learning technology “Latent Dirichlet Allocation” (LDA) to analyse the researches on the topic “sustainable development and approaches of China’s fashion industry” from China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) from 2013 to 2023, and mine keywords in it so as to clarify what scholars consider as the key elements of China’s fashion industry’s development. There are two findings of this research: firstly, sustainable development would be the main path of China’s fashion industry; Secondly, China’s fashion industry would appear three subdivided directions in the future, which is digitalise, green-system and regional integration. The value of this research lies in offering rational prediction through professional data in order to provide experiences, references, empirical merit for more fashion researcher that concerned about issues of industrial structure optimisation and sustainable development.
A Differentially Private Federated Learning Application in Privacy-Preserving Medical Imaging
Authors: FARES Mohamad HAJ , SERTBAŞ Ahmet
Published: February 2024

This research addresses the escalating concerns surrounding privacy, particularly in the context of safeguarding sensitive medical data within the increasingly demanding healthcare landscape. We undertake an experimental exploration of differentially private federated learning systems, employing three benchmark datasets—PathMNIST, BloodMNIST, and OrganAMNIST—for medical image classification. This study pioneers the application of federated learning with differential privacy in healthcare, closely simulating real-world data distribution across twelve hospitals. Additionally, we introduce a novel deep-learning architecture tailored for differentially private models. Our findings demonstrate the superior performance of federated learning models compared to traditional approaches, with accuracy levels approaching those of non-private settings. By leveraging resilient deep learning models, we aim to enhance privacy, efficiency, and effectiveness in healthcare solutions, benefiting patients, healthcare practitioners, and the overall healthcare system through privacy-protected healthcare.
Baseline Serum Cholinesterase Levels Predict the Outcome of HIV-Related Diffuse Large B-Cell Lymphoma
Authors: Zhou Minghan , Qin Jiaying , Tong Yong , Wang Lingyun , Ye Shasha , Xu Lijun
Published: February 2024

Background
Serum cholinesterase (CHE) has been utilized as a surrogate marker in the context of solid cancers. Nevertheless, its potential association with the prognosis of hematologic malignancies remains unclear.
Methods
Sixty-five patients with new-onset HIV-related diffuse large B-cell lymphoma (DLBCL) were enrolled in this retrospective study. The patients were categorized into a high CHE group (> 5500 U/L) and a low CHE group (≤ 5500 U/L). The demographic details, laboratory test results and clinical outcomes were compared between the high CHE group and the low CHE group. The overall response rate (ORR) at the end of chemotherapy was assessed by logistic regression analysis, and the 1-year overall survival rate (OS) was assessed by a multivariate Cox proportional hazards model.
Results
Compared with patients with high CHE, HIV-related DLBCL patients with low CHE exhibited lower levels of hemoglobin [g/L; 101.0 (81.0-115.0) vs. 123.5 (108.2–141.0), P < 0.001] and serum albumin [g/L; 31.2 ± 5.6 vs. 40.4 ± 4.5, P < 0.001] but higher levels of lactate dehydrogenase (LDH) [U/L; 404.0 (253.0-849.0) vs. 248.0 (178.3–372.0), P = 0.014] and C-reactive protein (CRP) [mg/L; 36.1 (5.8–66.6) vs. 5.1 (0.8–5.1), P < 0.001]. Moreover, HIV-related DLBCL patients with low CHE demonstrated a higher prevalence of Ann Arbor stage III/IV (92.6% vs. 56.8%, P < 0.001) and International Prognostic Index (IPI) ≥ 3 (85.2% vs. 35.1%, P = 0.002) at the time of diagnosis of DLBCL. The 1-year OS of patients was 84.2% in the high CHE group and 40.7% in the low CHE group (log-rank P < 0.001). At the end of chemotherapy, the ORR was 80.0% in the high CHE group and 31.8% in the low CHE group (P < 0.001). In multivariate analysis, CHE > 5500 U/L was independently associated with a higher ORR [adjusted odds ratio (AOR): 4.74 (1.02–22.06), P = 0.047] and lower 1-year mortality [hazard ratio (HR): 0.11 (0.03–0.52), P = 0.005].
Conclusion
Based on our robust data, baseline serum CHE levels show great potential as a surrogate marker for risk stratification and for guiding treatment decisions in HIV-related DLBCL patients.
Use of immune-modulating agents to regulate hyperinflammation in severe COVID-19; the assessment of tocilizumab use in combination with steroids
Authors: Sadeghi Somayeh , Naderi Zohre , Saghaei Mozhdeh , Tavakoli Fereshteh , Abdeyazdan Neda
Published: February 2024

Introduction
COVID-19 infection might lead to hyperinflammatory state in severe cases leading to devastating outcomes. Immune modulation using steroids or other immune modulators can regulate the intensity of inflammatory response; however, this theory has not been adequately assessed in practice. The current study aims to investigate the use of corticosteroids alone or in combination with tocilizumab for the treatment of patients with severe COVID-19.
Methods
The current retrospective cross-sectional study has been conducted on 168 patients with severe COVID-19 infection who were categorized into three treatment groups of A: primary treatment with high-dose methylprednisolone (> 1 mg/kg) continued with tocilizumab; B: primary treatment with low-dose methylprednisolone (< 1 mg/kg) continued with tocilizumab and C: treatment with high-dose methylprednisolone (> 1 mg/kg) only. The parameters including clinical outcome, laboratory parameters, length of hospitalization, intensive care unit (ICU) admission requirement and drug-related adverse events were compared between the groups.
Results
The outcomes were significantly better in group B considering the shorter length of ICU stay, lower CRP, LDH, and higher oxygen saturation and platelet count in group B than the other groups (P-value < 0.05). Logistic regression assessment in crude and adjusted models revealed increased risks of mortality, the incidence of nosocomial infection and the incidence of adverse effects, including hepatic dysfunction, renal dysfunction and GIB in both groups A and C compared with group B (P-value < 0.05).
Conclusion
Based on the findings of this study, low-dose steroid continued with tocilizumab was superior over high-dose steroid alone or in combination with tocilizumab in terms of all evaluated parameters.
Quantum Biochemical Analysis of the TtgR Regulator and Effectors
Authors: Matias Érika G. C. , Bezerra Katyanna. S. , Costa Aranthya H. Lima , Clemente Washington S. , Oliveira Jonas I. N. , Junior Luiz A. Ribeiro , Galvão Douglas S. , Fulco Umberto L.
Published: February 2024

The recent expansion of multidrug-resistant (MDR) pathogens poses significant challenges in treating healthcare-associated infections. Although antibacterial resistance occurs through numerous mechanisms, including enzymatic inactivation of drugs, lack of pro-drug activation, and drug target alteration, increased active efflux of the drugs is a major concern, especially because a single species of efflux pump can produce simultaneous resistance to several drugs. One of the best-studied efflux pumps is the TtgABC, a tripartite RND efflux pump implicated in the intrinsic antibiotic resistance in \textit{Pseudomonas putida} DOT-T1E. Expression of the TtgABC gene is down-regulated by the HTH-type transcriptional repressor TtgR. The association of effectors with the TtgR-DNA complex leads to the dissociation of TtgR from the operator region, allowing transcription. Therefore, studies that evaluate the action of these regulators are important for understanding the peculiarities of the resistance mechanisms promoted by the efflux pumps. In this context, by employing quantum chemistry methods based on density functional theory (DFT) within the MFCC approach, we investigated the coupling profiles of the transcriptional regulator TtgR in complex with quercetin (QUE), a natural polyphenolic flavonoid, tetracycline (TAC), and chloramphenicol (CLM), two broad-spectrum antimicrobial agents. Our quantum biochemical, computational results show the [i] convergence radius, [ii] total binding energy, [iii] relevance (energetically) of the ligands regions, and [iv] most important amino acids residues of the TtgR-QUE/TAC/CLM complexes, pointing out distinctions and similarities among them. These findings improve our understanding of the mechanism of binding of effectors and facilitate the development of new chemicals targeting TtgR, helping in the fight against the rise of resistance to antimicrobial drugs.
Naphthoquinone Derivative ZSW-4B Induces Apoptosis in Triple-negative Breast Cancer via AMPK signal Activation
Authors: Hu Xiyuan , Liu Hongdou , Luo Tiao , Chen Lin , Wen Min , Luo Wensong , Peng Ting , Xie Yuanzhu , Li Mo , Liu Mingquan , Liu Xiaohe , Liu Suyou , Zhu Shuaiwen , Zou Zizheng , Luo Zhiyong
Published: February 2024

Triple-negative breast cancer (TNBC) is the most malignant molecular subtype of breast cancer characterized by its strong aggressiveness, high mortality, significant heterogeneity, and poor prognosis. AMPK plays a critical role in maintain cellular energy balance, and its inactivation is associated with the malignancy breast cancer. Here, we identified the pharmacological mechanism of the 1, 4-naphthoquinone derivative ZSW-4B. The MTT assay, colony formation as-say, and nude mouse xenograft tumor model demonstrated that ZSW-4B selectively inhibits the proliferation of TNBC cells in both vitro and vivo. Flow cytometry and Western blot analysis revealed that ZSW-4B induces apoptosis in TNBC cells. Phosphoproteomics analysis unveiled the activation of the AMPK signaling pathway by ZSW-4B, and the application of the CRISPR-Cas9 system to genetically knockout AMPK in TNBC cell lines markedly reversed the anti-tumor effects elicited by ZSW-4B, both in vitro and in vivo. In summary, ZSW-4B inhibits TNBC by inducing cell apoptosis through the activation of the AMPK.
Hippo pathway in cancer cells modulates tumor microenvironment by inducing immunosuppressive NCAM1+αSMA+ fibroblasts
Authors: Moroishi Toshiro , Thinyakul Chanida , Sakamoto Yasuhisa , Shimoda Mayuko , Liu Yanliang , Thongchot Suyanee , Reda Omnia , Nita Akihiro , Sakamula Romgase , Sampattavanich Somponnat , Maeda Ayato , Niimura Mayumi , Kanamori Yohei , Thuwajit Peti , Nakayama Keiichi , Guan Kun-Liang , Satou Yorifumi , Thuwajit Chanitra
Published: February 2024

Tumor cells adeptly manipulate the tumor microenvironment (TME) to evade host antitumor immunity. However, the role of tumor cell-intrinsic signaling in shaping the immunosuppressive TME remains unclear. Here, we found that the Hippo pathway in tumor cells orchestrated the immunosuppressive TME by influencing the composition of cancer-associated fibroblasts (CAFs). In a 4T1 mouse breast cancer model, Hippo pathway kinases, large tumor suppressor 1 and 2 (LATS1/2), promoted the formation of immunosuppressive neural cell adhesion molecule 1 (NCAM1)+alpha-smooth muscle actin (αSMA)+ CAFs expressing the transforming growth factor-β, thereby contributing to T cell dysfunction. Depletion of LATS1/2 in tumor cells resulted in a less immunosuppressive TME, indicated by the reduced proportions of NCAM1+αSMA+ CAFs and dysfunctional T cells. Notably, similar Hippo pathway-induced NCAM1+αSMA+ CAFs were observed in human breast cancer cells, highlighting the potential of TME-manipulating strategies to reduce immunosuppression in cancer immunotherapy.
Acceleration of bone repairation by BMSCs overexpressing NGF combined with NSA and allograft bone scaffolds
Authors: Ji Ying , Mao Yongkang , Lin Honghu , Wang Ye , Zhao Peishuai , Guo Yong , Gu L.T. , Fu Can , Chen Ximiao , Lv Zheng , Wang Ning , Li Qiang , Bei Chaoyong
Published: February 2024

Background Repairation of bone defects remains a major clinical problem. Constructing bone tissue engineering containing growth factors, stem cells, and material scaffolds to repair bone defects has recently become a hot research topic. Nerve growth factor (NGF) can promote osteogenesis of bone marrow mesenchymal stem cells (BMSCs), but the low survival rate of the BMSCs during transplantation remains an unresolved issue. In this study, we investigated the therapeutic effect of BMSCs overexpression of NGF on bone defect by inhibiting pyroptosis.
Methods The relationship between the low survival rate and pyroptosis of BMSCs overexpressing NGF in localized inflammation of fractures was explored by detecting pyroptosis protein levels. Then, the NGF+/BMSCs-NSA-Sca bone tissue engineering was constructed by seeding BMSCs overexpressing NGF on the allograft bone scaffold and adding the pyroptosis inhibitor necrosulfonamide(NSA). The femoral condylar defect model in the Sprague-Dawley (SD) rat was studied by micro-CT, histological, WB and PCR analyses in vitro and in vivo to evaluate the regenerative effect of bone repair.
Results The pyroptosis that occurs in BMSCs overexpressing NGF is associated with the nerve growth factor receptor (P75NTR) during osteogenic differentiation. Furthermore, NSA can block pyroptosis in BMSCs overexpression NGF. Notably, the analyses using the critical-size femoral condylar defect model indicated that the NGF+/BMSCs-NSA-Sca group inhibited pyroptosis significantly and had higher osteogenesis in defects.
Conclusion NGF+/BMSCs-NSA had strong osteogenic properties in repairing bone defects. Moreover, NGF+/BMSCs-NSA-Sca mixture developed in this study opens new horizons for developing novel tissue engineering constructs.
Precise anti-inflammatory nano-contrast agents to treat Hashimoto thyroiditis by sustainably targeting HLA-DR
Authors: Zhou Xiaoying , Guo Lu , Shi Dandan , Shang Mengmeng , Sun Xiao , Zhao Yading , Wang Xiaoxuan , Meng Dong , Xiao Shan , Li Jie
Published: February 2024

According to previous reports, in vivo precision treatment using nanocarrier systems has proven effective in a variety of diseases. This work aimed to synthesize controlled nano-ultrasound contrast agents loaded with small interfering ribonucleic acid (siRNA) and drugs to target thyroid tissue and to evaluate this non-invasive method’s therapeutic effect on Hashimoto thyroiditis (HT) and the underlying mechanism thereof. In this study, we used high-biocompatibility anti-inflammatory nano-contrast agents (AINAs) with an erythrocyte membrane as the shell; the surface of this membrane was grafted with rapamycin. Its core included mesoporous-silica nanoparticles loaded with class II transactivator (CIITA)–siRNA and Trans-Activator of Transcription (TAT) transduction peptide. As seen under light and electron microscopes, each AINA was a approximately 255nm elliptical nanodroplet. AINAs could achieve long-lasting circulation in the bloodstream and targeted release of CIITA-siRNA and rapamycin into thyroid cells and the thyroid tissue microenvironment, respectively, with the assistance of the ultrasound-targeted microbubble destruction effect and TAT transduction peptide. AINAs could also be clearly visualized on contrast-enhanced ultrasound. They worked against multiple mechanisms to alleviate inflammatory trauma, including downregulation of HLA-DR expression, inhibition of antigen presentation and T-cell activation, reactive oxygen species levels, and anti-apoptosis of thyroid cells. In summary, our results showed that AINAs are a safe, effective treatment for HT.
Near Infrared-spectroscopy in resin transfer molding – determination of the degree of cure
Authors: Salzmann Moritz , Märzinger Wolfgang , Teuchtmann Michael , Ravindran Bharath , Kirschnick Ulrike , Fauster Ewald
Published: February 2024

Near infrared (NIR) spectroscopy is employed to monitor the degree of cure of a composite material directly during the curing phase in the resin-transfer-molding (RTM) process. The composite material used consists of natural fibers and an epoxy/amine resin. The quantitative determination of the degree of cure, α, from the NIR spectra is realized by partial least square (PLS) regression in conjunction with various pre-treatments of the spectral data. As a reference, the degree of cure is also determined by isothermal DSC experiments. The best PLS model that could be obtained for α is characterized by a determination coefficient of prediction (R²P) of 0.980 and root-mean-square error of prediction (RMSEP) of 4.4 %. While for every RTM trial the spectra during curing change corresponding to literature, major differences can be observed between the spectra of different RTM trials. The reasons for this are discussed in detail. The findings show the potential of inline NIR spectroscopy for monitoring α in the RTM process.
Synthesis and radiolabeling of a nitrofuran derivate with 18F for identification of areas of hypoxia in the tumor microenvironment
Authors: Araujo Yasniel Babi , Carneiro Maria Ângela Pepe , Silva Fabio Fernando Alves da , Lapolli André Luis , Bernardes Emerson Soares
Published: February 2024

Background
Positron Emission Tomography (PET) is a non-invasive molecular imaging technique widely known for studying hypoxia mostly employing 2-nitroimidazole-based radiotracers. These probes are based on the oxygen-mimetic chemical sensitizers of hypoxic cells developed for cancer therapy during the 1970s. 5-nitrofuran derivates are more electron affinic than nitroimidazoles, therefore, higher specificity for hypoxic regions is expected for the formers, and new radiotracer probes bearing a 5-nitrofuran ring could be used for imaging hypoxia.
Results
A nitrofuran-based radiotracer for detection of hypoxic areas in the tumor microenvironment, (E)-1-(4-[18F]-fluorophenyl)-3-(5-nitrofuran-2-yl)prop-2-en-1-one, baptized as [18F]FNFP, was obtained. Two copper-mediated nucleophilic radiofluorination procedures were tested and compared using the same pinacol-derived aryl boronic ester precursor: method 1, using K222/K2CO3 and [Cu(OTf)2(py)4] afforded the product in 56 ± 8% (n = 5) RCY after HPLC analysis of the crude reaction mixture; method 2: an azeotropic drying-free [18F]-labelling procedure, using Cu(OTf)2 as [18F]-elution agent and copper source, yielded [18F]FNFP in 88 ± 4% (n = 5) RCY. Method 2 was chosen as the standard for the synthesis of the radiotracer, obtaining the product with an overall radiochemical yield of 38,4 ± 3% (n = 5), high radiochemical purity (> 99%), total synthesis time of 85 minutes and a molar activity of 41.56 GBq/µmol. [18F]FNFP was found to be stable in serum and Phosphate-buffered saline for up to 6h, and lipophilicity measurements concluded that it is more hydrophilic than [18F]FMISO (log10𝑃=2.6), with log10𝑃=1.05.
Conclusion:
The first nitrofuran-based radiotracer to be used as a PET hypoxia imaging agent was efficiently radiolabeled with 18F. In vitro and in vivo studies are being lined up to compare [18F]FNFP with [18F]FMISO and [18F]FAZA.
Research on optimization of Pricing and Replenishment Decision Making Problem Based on LightGBM and Dynamic Programming
Authors: Tao Wenyue , Wu Chaoran , Wu Ting , Chen Fuyuan
Published: February 2024

The fresh-keeping period of vegetable commodities was relatively short, and its sales problem had always been of great concern under the vegetable production and distribution pattern of ”small production and big market” in China. Therefore, it was necessary to establish a systematic and comprehensive mathematical model, and rationally formulate the replenishment plans and pricing strategies for each category and individual product of vegetables. In this paper, we mainly solved the following three questions:
Question One: What was the distribution law and relationship between the sales volume of vegetable categories and single products?
Question Two: What was the relationship between total sales volume and costplus pricing of vegetable categories? Could you give the daily total replenishment and pricing strategy of each vegetable category in the next week, so that the supermarket would have the greatest profit?
Question Three: On the premise of meeting the market demand for various categories of vegetable products, how to further formulate the replenishment plan requirements of single products to maximize the revenue of supermarkets?
For the first question, we used the Pearson correlation coefficient and the Mfuzz package based on fuzzy c-means clustering to analyze the distribution law and correlation between vegetable categories and single products.We found that mosaic leaves, peppers and edible mushrooms accounted for a larger proportion, while cauliflower, aquatic rhizomes and eggplants accounted for a small proportion. And for single items, lettuce, cabbage, green pepper, screw pepper, enoki mushroom and shiitake mushroom accounted for a large proportion of their respective categories. We also found that there was a strong correlation between vegetable categories. And the sales of vegetable items belonging to the same category showed the same change pattern over time. For the second question, we established the LightGBM sales forecasting model to solve it. Combined with previous sales data, we forecasted the daily replenishment volume of each vegetable category in the coming week. And we developed a pricing strategy for vegetable categories to maximize the benefits of the supermarket. For the third question, we built a dynamic programming model to solve it. We developed an optimal replenishment volume and pricing strategy for single items, which let the supermarket maximize its income on the premise of meeting the constraints.
Mathematics Subject Classification (2020) 68M07 · 91B03 · 91B24
Towards a better understanding of idiopathic epilepsy through metabolic fingerprinting of cerebrospinal fluid in dogs.
Authors: Verdoodt Fien , Bhatti Sofie F.M. , Kragic Karla , Ham Luc , Vanhaecke Lynn , Hesta Myriam , Hemeryck Lieselot Y.
Published: February 2024

Cerebrospinal fluid metabolomics is a promising research technology in the elucidation of nervous system disorders. Therefore, in this work, a cerebrospinal fluid (CSF) metabolomics method using liquid chromatography coupled to mass spectrometry was optimized and validated to cover a wide range of metabolites. An acceptable coefficient of variance regarding instrumental, within-lab and intra-assay precision was found for 95, 70 and 96 of 102 targeted metabolites, together with 1256, 676 and 976 untargeted compounds, respectively. Moreover, approximately 75% of targeted metabolites and 50% of untargeted compounds displayed good linearity across different dilution ranges. Consequently, metabolic alterations in CSF of dogs with idiopathic epilepsy (IE) were studied by comparing CSF of dogs diagnosed with IE (Tier II) to dogs with non-brain related disease. Targeted metabolome analysis revealed higher levels of cortisol, creatinine, glucose, hippuric acid, mannose, D-pantothenol, and 2-phenylethylamine (P-values < 0.05) in CSF of dogs with IE, whereas CSF of dogs with IE showed lower levels of spermidine (P-value = 0.02). Untargeted CSF metabolic fingerprints discriminated dogs with IE from dogs with non-brain related disease using Orthogonal Partial Least Squares Discriminant Analysis (R2(Y) = 0.997, Q2(Y) = 0.828), from which norepinephrine was putatively identified as an important discriminative metabolite.
An exploration of Northern Ireland general practice pharmacists’ views on their role in general practice: a cross-sectional survey
Authors: Hassan Abrar H. F. , Barry Heather E. , Hughes Carmel M.
Published: February 2024

Background: There is a lack of research examining the views of general practice pharmacists (GPPs) on their role and their impact in general practice. The aim of this study was to explore GPPs’ views regarding this role and its potential impact within general practice in Northern Ireland (NI).
Methods: A paper-based self-administered questionnaire was mailed to 319 general practices in NI in 2022, directed to the GPP who spent most time at the practice. A variety of closed and open questions were included in six sections. Responses to closed questions were analysed descriptively whilst open question responses were analysed using content analysis. To ascertain associations between variables (e.g. GPP prescribing status, working arrangements and aspects of collaboration with GPPs), Fisher's exact test was employed with an a priorisignificance level of p<0.05.
Results: 155 responses were received equating to a response rate of 48.5%. Most participants (72.3%) were female, independent prescribers (71%), and 64.5% were currently using their independent prescriber qualification. Services that were provided by most GPPs were medication reconciliation (99.4%) and medication reviews (97.4%). The most common method of communication between GPPs and general practitioners (GPs) was face-to-face (89.0%). Telephone was the most common method of communication between GPPs, community pharmacists (97.4%) and patients (98.7%). Most GPPs (>80%) showed positive attitudes towards collaboration with GPs and those who worked in multiple practices were more likely to agree with the Attitudes Towards Collaboration Instrument for pharmacists (ATCI-P) statements compared to those who worked in a single practice (p<0.05). Less than 40% (36.8%) of GPPs agreed that patients were aware of the role they provided. The majority of GPPs (80.6%) expressed positive views on their impact on primary care. Analysis of the free-text comments revealed the need for more GPP patient-facing activities, GPP-specific training, and promotion of the GPP role.
Conclusion: The findings indicated that GPPs had largely positive views about their role and their impact on primary care. The results may be helpful for practices and service commissioners. Further research is necessary to explore the perspectives of patients regarding the role of the GPP and to enhance patients’ awareness of the GPP.
Comprehensive epidemiological analyses of urinary stone diseases in China: a population- based study
Authors: Wang Dawei , Zhan Yongle , Zhang Ning , Huang Da , Huang Jingyi , Huang Jinlun , Zhu Yu , Ho Brian Sze-Ho , Ng Ada Tsui-Lin , Tsu James Hok-Leung , Ruan Xiaohao , Na Rong
Published: February 2024

Backgrounds: Urinary stone disease (USD, or urolithiasis) is common and poses a significant healthcare burden and health economic burden in a working-age population.
We aim to provide epidemiological insights into the prevalence, incidence, trends, and risk factors of USD among the Chinese population.
Methods: A prospective cohort study of 966,481 participants from the CHinese Electronic health Records Research during 2009-2022 in Yinzhou, China (CHERRY). Temporal trends were estimated by annual percentage changes (APC) using Joinpoint regression analyses. A stratified Cox proportional hazards regression and propensity score analyses were used to assess the effect of potential risk factors, population attribution factor (PAF) and number needed to prevent (NNTP).
Results: Between 2014/2015 and 2021, there was an annualized increase in USD incidence by 5.3-6.8% (P<0.05). Tobacco smoking, alcohol drinking, high body mass index, diabetes, hyperlipidemia, hypertension, and heart disease were identified as risk factors while regular exercising was a protective factor of USD. PAF ranged from 22.5% in regular exercising (weekly) to 1.3% in non-drinking behavior. NNTP ranged from 21 in weekly exercising to 182 in non-smoking behavior.
Conclusions: USD is a common disease affecting about 1 in 10 Chinese, and the incidence increased by 5-6% annually over the past 6-7 years. Lifestyle factors and metabolic symptoms are potential risk factors for USD.