bluuebunny/crossref_metadata_2025 huggingface dataset:
Progress in Wound Healing Products based on Natural Compounds, Stem Cells and MicroRNA-based Biopolymers in the European, USA, and Asian Markets: Opportunities, Barriers, and Regulatory Issues
Authors: Srivastava Girish Kumar , Martínez Rodríguez Sofía , Md Fadilah Nur Izzah , Looi Qi Hao Daniel , Markey Gavin , Shukla Priyank , Fauzi Mh Busra , Panetsos Fivos
Published: November 2023

Wounds are breaks in the continuity of the skin and the underlying tissues, due to external causes, such as cuts, blows and impacts, or even, during surgical interventions. Millions of people suffer minor or serious injuries, sometimes ending in death. Today, there are many commercially available products that promote healing from wounds. The high demand from the healthcare industry has created a huge market that continues to grow, fueling research and development of new wound healing products. In the present article, we review recent advances in wound healing products based on natural biopolymers, stem cells, and microRNAs. We analyze the advances of both, the commercial products and the products that are still in research phase, and we also include an overview of the opportunities, barriers, and regulatory issues for the commercialization of these products in the European, American, and Asian markets.
The Breakup of Gas Bubbles by a Shock Wave: Brief Historical Background
Authors: Minin Igor V. , Minin Oleg V.
Published: November 2023

A gas-hydrate method of CO2 gas storage is one of the modern technology for reducing it emissions into the atmosphere. The breakup of gas bubbles by a shock wave is an actual area of scientific and technological research. However, it is little known that such research began in the late 1950s in the USSR. The article presents the main discoveries related to the destruction of gas bubbles in a liquid under the influence of a shock wave, made more than 60 years ago. Looking back: study the past to understand the present.
Restoration of Degraded Landscapes Along the Urban-Rural Gradient of Lubumbashi City (DR Congo) by Acacia auriculiformis Plantations: Spatial Dynamics and Impact on Plant Diversity
Authors: Sikuzani Yannick Useni , Muteya Héritier Khoji , Mleci Jonas Yona , Mukenza Médard Mpanda , Malaisse François , Bogaert Jan
Published: November 2023

With the liberalization of the mining sector, a considerable demographic explosion is witnessed in Lubumbashi city (southeastern of the D.R. Congo). The resulting spatial urban expansion is unplanned, reducing the vegetation cover abundance within and around the city. To address this situation, Acacia auriculiformis, an alien species, has been planted without planning and monitoring. We quantify the spatio-temporal pattern dynamics of A. auriculiformis along the urban-rural gradient from the digitisation of Google Earth images from 2006, 2014 and 2021, and evaluate tree diversity through floristic inventory. Results showed that the plantation of A. auriculiformis, belonging to park, street trees and green spaces-types, increased in patch number and acreage, mostly in urban zone. The values of the patch which were highest in 2006 decreased in 2021, especially in the urban zone. Thirty-nine trees species were founded on A. auriculiformis plantations, with Albizia lebbeck, Albizia alba and Leucaena leucocephala being the most common. However, results showed that 20 species out of 39 species found are exotic, half of which are invasive species. However, 19 trees species are indigenous, mainly found in peri-urban zones. Although most tree species were observed in urban zones, the average diameters were greater in the peri-urban zone. Overall, obtained results appear to suggest that the sustainability of A. auriculiformis within the urban and peri-urban zones of Lubumbashi city appears uncertain since a considerable number of attracted species are found to be alien invasive trees that pose a threat to biodiversity conservation. There is an urgent need for adoption of a master plan for sustainable integration and monitoring of trees plantations for limiting erosion of indigenous phytodiversity and the spread of alien invasive species populations in the adjacent rural area.
Revisiting Classical Controllers Design and Tuning with Genetic Programming
Authors: García Carlos A. , Velasco Manel , Angulo Cecilio , Marti Pau , Camacho Antonio
Published: November 2023

This paper introduces the implementation of a genetic programming (GP)-based procedure to the automatic design and tuning of process controllers. The proposed approach makes a significant contribution to the field of artificial intelligence (AI) in control engineering. Unlike other controller design methods, the GP-based program handles the entire design in the time domain, including differential operations like derivatives and integrals, without the need for intermediate inverse Laplace transformation. This approach not only simplifies the design process but also ensures that all generated controllers are implementable in physical systems. Furthermore, GP’s functions set includes various mathematical operations beyond basic arithmetic operators, such as trigonometric, exponential, and logarithmic operators. The performance and validity of the resulting controllers generated by the proposed GP-based approach are evaluated by verifying whether the generator can replicate the structure and performance of those produced by traditional controller design methods and, in some cases, achieve even better results. As a result, the GP-based approach presents a promising solution for automating the controller design process and addressing control problems in various engineering applications.
Spontaneous Synchronization of Two Bistable Pyridine-Furan Nanosprings Connected by an Oligomeric Bridge
Authors: Markina Anastasia A. , Frolkina Maria A. , Muratov Alexander D , Petrovskii Vladislav S , Valov Alexander F , Avetisov Vladik A.
Published: November 2023

The intensive development of nanodevices acting as two-state systems has motivated the search for nanoscale molecular structures whose long-term conformational dynamics are similar to the dynamics of bistable mechanical systems such as Euler arches and Duffing oscillators. Collective synchrony in bistable dynamics of molecular-sized systems has attracted immense attention as a potential pathway to amplify the output signals of molecular nanodevices. Recently, pyridin-furan oligomers of helical shape that are a few nanometers in size and exhibit bistable dynamics similar to a Duffing oscillator have been identified through molecular dynamics simulations. In this article, we present the case of dynamical synchronization of these bistable systems. We show that two pyridine-furan springs connected by a rigid oligomeric bridge spontaneously synchronize vibrations and stochastic resonance enhances the synchronization effect.
Li on a Ch Divacancy Self-Healed Graphane: A First -Principles Study
Authors: Mapasha Refilwe Edwin , Kgalema Sentserere Phodisho , Mapingire Hezekia , Igumbor Emmanuel
Published: November 2023

The possibility of using graphane monolayer crystals as the electrode material is becoming popular. Graphane is stable at room temperature and has large surface area, but its chemical inertness hinders its direct interactions with Li ions. In this study, we performed density functional theory calculations to study the energetic stability, structural and electronic properties of Li on graphane with various CH divacancy configurations (v12, v13 and v14 ). The results show that adsorption of Li atom reduces the formation

energy of the CH divacancy configurations. The Li-v12 is most stable with the highest binding energy of 3.25 eV/Li and relaxes to in-plane with other C atoms. Altering the Li charge state to have Li−1-v12 or Li+1 -v12 affects the energetic stability and electronic characters of Li-v12 . The Li−1-v12 (Li +1-v 12 ) enhances (reduces) the binding force between Li and v 12 configuration, and furthermore it improves (deteriorates) the conductivity of the structure. Further investigation of graphane with vacancies is encouraged due to these intriguing observations, as it holds promise for potential utilization as an electrode material.
Co-delivery of Novel Synthetic TLR4 and TLR7/8 Ligands Adsorbed to Aluminum Salts Promotes Th1-Mediated Immunity against Poorly Immunogenic SARS-CoV-2 RBD
Authors: Siram Karthik , Lathrop Stephanie K. , Abdelwahab Walid , Tee Rebekah , Davison Clara J. , Partlow Haley A. , Evans Jay T. , Burkhart David J.
Published: November 2023

Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.
Evaluation of Phα1β Interaction on the Kv11.1 Potassium Channel in HEK293 Cells Trans-fected with the Human ERG Channel
Authors: Calixto Joao Batista , Santos Adara Aurea , Ferreira Juliano , Souza Alessandra Hubner , Castro Junior Célio José , Gomez Marcus Vinicius
Published: November 2023

Phα1β a spider peptide, purified from the venom of Phoneutria nigriventer inhibits high voltage calcium channels and is antagonist of TRPA1 receptor two important pain transduction path-ways. In the last 15 years, we have showed, in preclinical tests with Phα1β native and recombi-nant in rodent models of pain the potential of Phα1β to become a new analgesic drug. Evaluation of new drug on human ERG channel is requirement of the regulatory agencies. For the hERG channel inhibition assay it was used the commercial kit FLIPR® Potassium Assay. It was tested the effect of Phα1β and as positive control dofetilide, a well characterized hERG block-er. Phα1β 56, 225, 450 and 900 pMol caused at a higher concentration a very weak inhibition of the hERG channel activity of about 13.47 % with channel inhibition at 50%, IC50 > 900 pMol. Dofetilide (0.0001 - 10 µM), a known hERG inhibitor, caused a well-known, concentra-tion-dependent inhibition of the hERG channel with a mean IC50 of 0.1642 µM (0.1189 – 0.2282 µM. For the cytotoxicity assay, Phα1β concentrations of 56, 225, 450 and 900 pMol incubated for 24 h with HEK293-hERG cells did not alter the viability of the HEK293-hERG cells. It is con-cluded that Phα1β even at high concentrations does not interfere with hERG channels.
Research on the Improvement Path of Total Factor Productivity in Industrial Software Industry: Evidence from Chinese typical firms
Authors: Wang Xiaoxiang , Wu Songling , Zhao Lixiang
Published: November 2023

The high-quality development of the industrial software industry is of strategic significance to enhancing the core competitiveness of the manufacturing industry and promoting the high-quality development of China's industrial economy. By integrating the "capital- technology-environment-human" production factor theory and configuration perspective, this paper constructs a comprehensive analysis framework that drives the total factor productivity (TFP) of the industrial software industry. It uses 40 typical industrial software firms as case samples and uses fuzzy set Qualitative Comparative Analysis (fsQCA) was used to empirically explore the influencing factors and complex mechanisms that achieve high-quality development of the industrial software industry. It is found that: (1) a single industrial factor is hardly a necessary condition to drive industrial software industry; (2) there are four paths to achieve high TFP, which are summarized as "technology-human-environment" balanced driving type, "capital-human-environment" balanced driving type, "technology-capital" dual driving type, and "capital" single driving type. There are four driving mechanisms. There are also four not-high TFP configurations with asymmetric characteristics; (3) under certain conditions, the combination of capital factors, capital factors, environmental factors and human factors can drive TFP in a "all roads lead to Rome". In this process, the government's attention plays a more universal role. The study not only expands the application scenarios of fsQCA, but also provides decision guidelines for the practice of strategic emerging industrialization represented by industrial software industry.
Effects of Physical Exercise and Motor Activity on Depression and Anxiety in Post‐Mastectomy Pain Syndrome
Authors: Calapai Marco , Puzzo Luisa , Bova Giuseppe , Vecchio Daniele Alfio , Blandino Rosario , Barbagallo Alessia , Ammendolia Ilaria , Cardia Luigi , Calapai Fabrizio , Currò Mariaconcetta , Ficarra Giovanni , Esposito Emanuela , Trimarchi Fabio , Di Mauro Debora , Calapai Gioacchino , Mannucci Carmen
Published: November 2023

Background: Chronic post-surgical pain is a condition persisting at least three months after surgery. It is estimated that 25-60% of patients who underwent breast cancer removal surgery suffer from post-mastectomy pain syndrome and occurred anxiety, depression, sleep disturbance and catastrophizing. Physical activity can reduce the risk of chronic diseases and has a good impact on mood and cognitive function. Aim of this study was to evaluate the effects of physical activity on the intensity of pain, depression and anxiety in women underwent mastectomy for breast cancer removal. Methods: A prospective observational unicentric cohort study was performed. Patients were female underwent unilateral or bilateral mastectomy. Numerical Rating Scale (NRS), was used to assess pain intensity, Beck’s Depression Inventory (BDI) for depression and Generalized Anxiety Disorders-7 (GAD-7), for anxiety evaluation. Physical activity was assessed by International Physical activity questionnaire (IPAQ). Interleukin (IL)-17, IL-1β, cortisol, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) were also evaluated in the blood of patients. All the evaluation was assessed 3 and 6 months after the surgery. Results: Adequate physical activity reduced intensity of pain, depression and anxiety symptoms in women affected by post-mastectomy pain syndrome. Moreover, adequate active women, showed a reduction of biomarkers of inflammation, cortisol, ACTH and an increase of BDNF. Conclusions: Our results suggest that physical activity can improve quality of life, reducing intensity of pain, inflammatory markers and it can be useful in the reduction of associated anxiety and depression.
Effects and Interactions of Incubation Time and Preplacement Holding Time on Mortality at Placement, Yolk Sac Utilization, Early Feeding Behavior and Broiler Live Performance
Authors: Elibol Okan , Özlü Serdar , Erkuş Tolga , Nicholson Dinah
Published: November 2023

Effects and interactions of incubation time and chick preplacement holding time on mortality at placement, utilization of yolk sac, crop filling rate, early feeding–drinking behavior and broiler live performance were investigated. Ross 308 broiler hatching eggs from a 39-week-old flock were set in two identical setters in a commercial hatchery,with setting time 12 hours earlier in one machine. At the end of incubation, chicks were removed from the hatchers at the same time. Thus, incubation times were either 504 h (normal incubation time (NIT) treatment) or 516 h (longer incubation time (LIT) treatment). After pull time, chicks from each incubation time group were subjected to either 6, 24, 48, 60 or 72 h preplacement holding times. At placement, chicks were given access to feed and water. In total, 19,200 chicks were randomly assigned to a total of 10 subtreatment groups (2 incubation times × 5 preplacement holding times). Therefore, a total of 1,920 chicks were used in each subtreatment group for the grow-out period in a commercial broiler house. An interaction was found between incubation time and preplacement holding time for residual yolk sac (RYS) weight (g, %) (p < 0.001). RYS weight was greater at pull time and at 6 and 24 h of preplacement holding time in the NIT treatment compared to the LIT treatment, while differences were no longer evident at 48–72 h. The lowest percentage of chicks with full crops and eating activity was observed in the shortest preplacement holding time (6 h) group at 3 h after placement. As expected, the initial BW at placement clearly decreased with increasing duration after the pull time (p < 0.05) with the highest and lowest weights were found in the 6 and 72 h holding time treatments respectively. This BW difference was still evident at 35 d after placement and chicks held for the longest period after the pull time (72 h) showed the lowest BW (p < 0.001). However, there was no significant difference between the 6 and 60 h preplacement holding times. Mortality during the first 7 d after placement increased only when the preplacement holding time was extended to 72 h (p = 0.031). Similar to the 7 d results, chicks held for 72 h exhibited higher 0-35 day mortality compared to those held for 6 or 24 h (p = 0.028). Neither BW nor mortality was affected by incubation time treatment at 35 d after placement (p > 0.05). It can be concluded that there were no significant differences in average BW and mortality, up to and including a 60-h holding time under thermal comfort conditions, but a 72-h preplacement holding time resulted in final BW and mortality being negatively affected. In addition, LIT tended to have a beneficial effect on BW and mortality compared to NIT when the preplacement holding time was shorter (6–24 h) but had a negative effect for extended holding times (48–72 h).
Pengaruh Mathematical Digital Book (MAGIC BOOK) terhadap Keterampilan Berpikir Kritis Siswa Sekolah Dasar
Authors: Eko Sugandi  , Hanim Faizah
Published: November 2023

Abad 21 menuntut setiap orang untuk dapat mengembangkan kompetensinya dan memiliki kemampuan bersaing sesuai dengan tuntutan global. Keterampilan berpikir kritis mampu melatih seseorang dalam menghadapi segala tantangan dan melakukan pemecahan masalah dalam kehidupan sehari hari. Peran teknologi dalam pembelakjaran sangat penting untuk pencapaian proses pembelajaran yang maksimal. Penelitian ini dilakukan dengan tujuan untuk mengetahui pengaruh limplementasi Mathematical Digital Creative Book (MAGIC BOOK) yang telah dikembangkan terhadap keterampilan berpikir kritis siswa sekolah dasar. Metode pengumpulan data menggunakan tes kemampuan berpikir kritis yang telah divalidasikan kepada ahli. Teknik pengambilan sampel menggunakan teknik Cluster Random Sampling. Analisis data menggunakan pendekatan kuantitatif pre-experimental dengan One-shot Study Research Design. Populasi dalam penelitian ini adalah siswa kelas IV di Sidoarjo dan Surabaya. Hasil penelitian menunjukkan bahwa implementasi MAGIC BOOK yang telah dikembangkan dapat memberikan pengaruh positif terhadap kemampuan berpikir kritis siswa sekolah dasar. Sehingga, MAGIC BOOK dapat digunakan sebagai buku pendamping untuk meningkatkan kemampuan berpikir kritis siswa.
Tissue-resident memory T cells in Epicardial adipose tissue comprise transcriptionally distinct subsets that are modulated in Atrial Fibrillation
Authors: Longhi Paula , Vyas Vishal , Sandhar Balraj , Wood Elizabeth , Blythe Hazel , Jones Aled , Shahaj Eriomina , Fanti Silvia , Williams Jack , Metic Nasrine , Efremova Mirjana , Ng Han Leng , Feldhahn Niklas , Marelli-Berg Federica , Tinker Andrew , Finlay Malcolm
Published: November 2023

Atrial fibrillation (AF) is the most common sustained arrhythmia and carries an increased risk of stroke and heart failure. Here, we investigate how the immune infiltrate of human epicardial adipose tissue (EAT), which directly overlies the myocardium, contributes to AF. Flow cytometry analysis revealed an enrichment of tissue-resident memory T (TRM) cells in AF patients. Cellular indexing of transcriptomes and epitopes by sequencing (CITE-Seq) and single-cell TCR sequencing, identified two transcriptionally distinct CD8+ TRM cells that are modulated in AF. Spatial transcriptomic analysis of EAT and atrial tissue identified the border region between the tissues to be a region of intense inflammatory and fibrotic activity, while the addition of TRM populations to atrial cardiomyocytes demonstrated their ability to differentially alter calcium flux as well as activate inflammatory and apoptotic signalling pathways. This study identified EAT as a novel reservoir of TRM cells that can directly modulate vulnerability to cardiac arrhythmia.
Genetic Insights into the 'Sandwich Fusion' Subtype of Klippel-Feil Syndrome: Novel FGFR2 Mutations Identified by 21 cases of Whole-Exome Sequencing
Authors: Hung Kan-Lin , Xu Nanfang , Gong Xiaoli , Fan Dongwei , Tian Yinglun , Yan Ming , Wei Yuan , Wang Shenglin
Published: November 2023

Background
Klippel-Feil syndrome (KFS) is a rare congenital disorder characterized by the fusion of two or more cervical vertebrae during early prenatal development. This fusion results from a failure of segmentation during the first trimester. Although six genes have previously been associated with KFS, they account for only a small proportion of cases. Among the distinct subtypes of KFS, "sandwich fusion" involving concurrent fusion of C0-1 and C2-3 vertebrae is particularly noteworthy due to its heightened risk for atlantoaxial dislocation. In this study, we aimed to investigate novel candidate mutations in patients with "sandwich fusion."
Methods
We collected and analyzed clinical data from 21 patients diagnosed with "sandwich fusion." Whole-exome sequencing (WES) was performed, followed by rigorous bioinformatics analyses. Our focus was on the six known KFS-related genes (GDF3, GDF6, MEOX1, PAX1, RIPPLY2, and MYO18). Suspicious mutations were subsequently validated through in vitro experiments.
Results
Our investigation revealed two novel exonic mutations in the FGFR2 gene, which had not previously been associated with KFS. Notably, the c.1750A > G variant in Exon 13 of FGFR2 was situated within the tyrosine kinase domain of the protein, in close proximity to several established post-translational modification sites. In vitro experiments demonstrated that this certain mutation significantly impacted the function of FGFR2. Furthermore, we identified four heterozygous candidate variants in two genes (PAX1 and MYO18B) in two patients, with three of these variants predicted to have potential clinical significance directly linked to KFS.
Conclusions
This study encompassed the largest cohort of patients with the unique "sandwich fusion" subtype of KFS and employed WES to explore candidate mutations associated with this condition. Our findings unveiled novel variants in PAX1, MYO18B, and FGFR2 as potential risk mutations specific to this subtype of KFS.
A Control Oriented Strategy of Disruption Prediction to Avoid the Configuration Collapse of Tokamak Reactors
Authors: Gelfusa Michela , Murari Andrea , Rossi Riccardo , Craciunescu Teddy , Vega Jesus
Published: November 2023

The objective of thermonuclear fusion consists of producing electricity from the coalescence of light nuclei in high temperature plasmas. The most promising route to fusion envisages the confinement of such plasmas with magnetic fields, whose most studied configuration is the tokamak. Disruptions are catastrophic collapses affecting all tokamak devices and one of the main potential showstoppers on the route to a commercial reactor. Deploying new analysis methods on thousands of JET discharges, covering the isotopic compositions from hydrogen to full tritium and including the last major D-T campaign, the nature of the various forms of collapse is investigated. A new approach to proximity detection has been developed, which allows determining both the probability of and the time interval remaining before an incoming disruption, with adaptive, from scratch, real time compatible techniques. The results indicate that physics based prediction and control tools can be developed, to deploy realistic strategies of disruption avoidance and prevention, meeting the requirements of the next generation of devices.
Spatial-temporal variations of b-values prior to medium to large earthquakes in Taiwan and the feasibility of real-time precursor monitoring
Authors: Chan Chung-Han , Kao Jo-Chen , Chen Da-Yi
Published: November 2023

This study investigates the temporal and spatial variations of the b-values before earthquakes greater than magnitude 6.0 in the Taiwan region and assesses the feasibility of monitoring earthquake precursors through b-values. Using the 2018 Hualien earthquake as an example, the b-value in the vicinity of the region one year before the earthquake was in the 12th percentile of all Taiwan, indicating a relatively low spatial value. Moreover, the b-value near the epicenter noticeably decreased within a year before the earthquake, showing a temporally relative low value. Based on this experience, we examine the temporal and spatial variations of b-values before earthquakes greater than magnitude 6.0 in Taiwan from 1999 to 2021. It was found that the epicenters of many large earthquakes were in regions with relatively low b-values across Taiwan a year prior. However, the b-values around various epicenters did not show significant changes at different times before the earthquakes. To further evaluate the feasibility of real-time monitoring of earthquake precursors using b-values, we analyzed the 2022 Yuli earthquake and the Chihshang earthquake sequence as case studies. Immediate post-event analysis using the rapid earthquake report catalog showed significant anomalies in both time and space for b-values, even though the real-time catalog obtains a larger magnitude of completeness. Specifically, the b-value in the vicinity of the region one year before the earthquake was in the 3rd percentile for the entire Taiwan region; furthermore, the b-value consistently decreased within the four years preceding the earthquake. These results validate the feasibility of evaluating earthquake precursors by analyzing real-time earthquake data. To more precisely predict future earthquake activity characteristics, it is suggested to incorporate other reference factors for a comprehensive evaluation, aiming to reduce cognitive uncertainty.
Multiomics-based causal inference identifies novel therapeutic targets for inflammatory bowel disease in East Asians
Authors: Kim Jung Oh , Lee Sun Yeop , Kim Eun Gyo , Lee Eunbyeol , Lee Jihye , Shim Yu Jeong
Published: November 2023

Multiomics-based efforts to identify therapeutic targets for IBD have been limited to European populations. Prior reports on heterogeneity between East Asians and Europeans in clinical manifestations of IBD and genetic architectures of IBD-related variants warrant a separate investigation in East Asians. Using the East Asian genome and proteome data, we applied two multiomics-based causal inference methods, proteome-wide Mendelian randomization and causal proteome-wide association study. For IBD, Crohn’s disease (CD), and ulcerative colitis (UC), we found 30 potential drug targets with proteomic evidence. IL18R1, IL1RL1, KIR3DL1, and MEP1B had consistent associations with across IBD, CD, and UC. Fifteen targets were CD-specific, while eight were UC-specific. Among the candidate targets, thirteen and eight had supportive MR evidence in the plasma transcriptome data and the multi-tissue transcriptome data of European ancestry, respectively. IL18R1, IL6R, IL16, TNFRSF14 or their direct interactors were currently targeted by drugs being developed to treat IBD. IL1RL1 and PDGFRB had existing drugs that may be repurposed for IBD. Crucially, we identified six previously unreported target genes, opening new avenues for therapeutic interventions in IBD that warrant immediate validation in upcoming experiments and clinical trials.
The 30 Years Of Shifting In Indonesian Cardiovascular Burden -Analysis Of Global Burden Of Disease Study
Authors: Muharram Farizal Rizky , Multazam Chaq El Chaq Zamzam , Mustofa Ali , Harmadha Wigaviola Socha ,   Andrianto3 Andrianto3, Martini Santi , Aminde Leopold , Yi-Li Chung
Published: November 2023

Importance: Cardiovascular disease (CVD) remains the leading cause of mortality and morbidity. Compared with disease burden rates in 1990, significant reductions in Disability-Adjusted Life Years (DALYs) burden rates for CVD have been recorded. However, general DALYs rates have not changed in Indonesia in the past 30 years. Thus, assessing Indonesian CVD burdens will be an essential first step in determining primary disease interventions.
Objective: To determine the national and province-level burden of CVD from 1990 to 2016 in China.
Design, Setting, and Participants: This research used Global Burden Disease (GBD) 2019 Institute of Health Metrics (IHME) data to analyze CVD burden trends, including mortality, morbidity, and prevalence characteristics of 12 underlying CVDs.
Exposures: Residence in Indonesia
Main Outcomes and Measures: Mortality, Incidence, prevalence, death, and DALYs of CVD.
Results: CVD Deaths have doubled from 278 million in 1990 to 651 million in 2019. ALL CVDs recorded increased death rates, except for rheumatic heart disease (RHD) (-69%) and congenital heart disease (CHD) (-37%). Based on underlying diseases, stroke and ischemic heart disease (IHD) are still the leading causes of mortality and morbidity in Indonesia, whereas stroke and peripheral artery disease (PAD) are the most prevalent CVDs. Indonesia has the second worst CVD DALYs rates compared to ASEAN countries after Laos. At provincial levels, the highest CVD DALY rates were recorded in Bangka-Belitung, South Kalimantan, and Yogyakarta. In terms of DALYs rate changes, they were recorded in West Nusa Tenggara (24%), South Kalimantan (18%), and Central Java (11%). Regarding sex, only RHD and PAD burdens were dominated by females.
Conclusions: CVD mortality, morbidity, and prevalence rates increased in Indonesia from 1990-2019. Importantly, these data could provide reference points for policymakers, such as improving risk factor prevention and health care optimization.
We Prevent and Recover as One: Local Responses to Ramp up COVID-19 Vaccination Efforts in the Philippines
Authors: Casimiro Rosemarie , Antonio Olive Chester , Talion Dhick , Ramos Vilma
Published: November 2023

The Philippines is among the pandemic-affected nations globally. The study evaluated COVID-19 vaccination programs in the seven provinces in Region III. The framework for the study was the World Health Organization's Six Building Blocks of Health Systems: Leadership and Governance, Financing, Health Workforce, Information System, Medical Products/Vaccines, and Service Delivery. For implementers, purposeful sampling was used, while for vaccinees, convenience sampling was employed. A self-designed questionnaire, an interview, and focus group discussions (FGD) were used to acquire information from the participants. The mixed sampling design employs both probability random sampling and non-probability sampling to select a sample. The statistics revealed significant variations in the implementation of the COVID-19 vaccination program across the seven provinces of Central Luzon. Identifying practices analyzing reactions to the COVID-19 vaccination distribution are essential components of a successful immunization plan. The findings of this study may aid the government in correcting vaccination misconceptions and deficiencies.
Analysis of Sudan Mpox surveillance data during the recent pandemic, 2022
Authors: Izzoddeen Ahmad , Elbadri Omer , Nageeb Mohammed , Magbol Mustafa
Published: November 2023

Background
Mpox is a zoonosis that is known to be endemic in several Central and West African countries. Recently, in 2022, it has emerged in Europe and the United States, which raises the alarm to be declared in June as a public health event of international concern. This study aimed to analyze Mpox surveillance data at the national level.
Methods
Mpox data was extracted from the disease surveillance line-list at the national level. The data was customized and then analyzed using Epi Info7 software. The analysis was done using frequencies and percentages, and the results were presented in tables and charts. Permission and ethical approval were obtained from the Health Emergency and Epidemic Control Directorate at the Federal Ministry of Health.
Results
From the national line-list 375 records were extracted and analyzed. Males comprised 54.4% of cases. The mean age was 12.90 (SD 14.69), with 50.2% of the cases were children under 15 years old. All cases had a skin rash, and 74.1% reported a fever. Around a third of the cases reported headaches, sore throats, and lymphadenopathy. The majority of the confirmed cases were children under 5 years old. Around half of the cases were either preschool or school children. The states reported 11 cases, with the majority of cases reported from Gadaref, West Darfur, and Khartoum. A history of contact was identified in 5.8% of cases. Specimens were collected for 212 cases, with the disease confirmed in only 18 (4.8%) through RT-PCR. The number of reported cases increased gradually to reach its peak in week 38, with 100 cases reported, and then began to decrease to reach zero cases in late October.
Conclusion
Mpox surveillance is functioning, with suspect cases reported on a daily basis. The infection is more common in males and children. The commonest presentations were rash and fever with a sore throat, and lymphadenopathy was recognized in one-third of cases. The case definition adopted is broad and sensitive to what influenced the specimen’s positivity rate. Carful data collection and complete filling out of the case report form are recommended to have more comprehensive data for analysis.
Establishment of a stem cell administration imaging method in bleomycin- induced pulmonary fibrosis mouse models
Authors: Morita Saho , Iwatake Mayumi , Suga Sakura , Takahashi Kazuomi , Sato Kazuhide , Miyagi-Shiohira Chika , Noguchi Hirofumi , Baba Yoshinobu , Yukawa Hiroshi
Published: November 2023

Pulmonary fibrosis is a progressive disease caused by interstitial inflammation. Treatments are extremely scarce; therapeutic drugs and transplantation therapies are not widely available due to cost and a lack of donors, respectively. Recently, there has been a high interest in regenerative medicine and exponential advancements in stem cell-based therapies have occurred. However, a sensitive imaging technique for investigating thein vivodynamics of transplanted stem cells has not yet been established and the mechanisms of stem cell-based therapy remain largely unexplored. In this study, we administered adipose tissue-derived mesenchymal stem cells (ASCs) labeled with quantum dots (QDs; 8.0 nM) to a mouse model of bleomycin-induced pulmonary fibrosis in an effort to clarify the relationship betweenin vivodynamics and therapeutic efficacy. These QD-labeled ASCs were injected into the trachea of C57BL/6 mice seven days after bleomycin administration to induce fibrosis in the lungs. The therapeutic effects and efficacy were evaluated viain vivo/ex vivoimaging, CT imaging, and H&E staining of lung sections. The QD-labeled ASCs remained in the lungs longer and suppressed fibrosis. The 3D imaging results showed that the transplanted cells accumulated in the peripheral and fibrotic regions of the lungs. These results indicate that ASCs may play a significant role in the therapeutic effects of pulmonary fibrosis. Thus, QD labeling could be a suitable and sensitive imaging technique for evaluatingin vivokinetics in correlation with the efficacy of cell therapy.
D-dimer-based screening for detecting preoperative venous thromboembolism in patients with musculoskeletal tumors: a retrospective study of 756 patients
Authors: Hayashida Kenta , Kawabata Yusuke , Choe Hyonmin , Kato Ikuma , Takeyama Masanobu , Inaba Yutaka
Published: November 2023

Malignant musculoskeletal tumors are considered high risk for venous thromboembolism, but the characteristics of venous thromboembolism in benign musculoskeletal tumors are unclear. We evaluated D-dimer as a screening preoperative test in patients with benign and malignant musculoskeletal tumors to determine the prevalence and risk factors for venous thromboembolism and the utility of D-dimer in the diagnosis of venous thromboembolism. A total of 756 patients, 328 with malignant and 428 with benign, were evaluated for thrombosis by preoperative D-dimer and imaging. Medical data were analyzed retrospectively to determine the prevalence of venous thromboembolism, risk factors and diagnostic accuracy of D-dimer. The prevalence of venous thromboembolism in patients with malignant and benign musculoskeletal tumors was 11.3% and 1.6%, respectively. For malignant tumors, age >60 years, lower extremities, hypertension, and hepatobiliary-pancreatic disease were risk factors for venous thromboembolism, while for benign tumors, pathologic fracture and D-dimer were risk factors for venous thromboembolism. The prevalence of VTE was higher in patients with malignant tumors than in patients with benign tumors, and malignancy was a risk factor for VTE development in musculoskeletal tumors. D-dimer was useful in ruling out VTE in both benign and malignant musculoskeletal tumors, with particularly high diagnostic accuracy in benign tumors.
The Dynamic Instability Analysis of Electrodynamic Tether System
Authors: Li Xialin , Yang Keying , Zhang Jingrui
Published: November 2023

The libration motion of conductive tether in electrodynamic tether system had been demonstrated unstable inherently. This paper conducts a further dynamic analysis of the instability in electrodynamic tether system, specifically investigating the existence of periodic solution and equilibrium point, as well as exploring the condition for rapid instability in libration motion. The dumbbell model is employed to depict the in-plane and out-plane libration motion, and the parameter ε is introduced to incorporate the influences of tether current and inclination. The critical ranges of ε and out-plane angle that determine whether the libration motion will go tumbling quickly are derived analytically based on the existence condition of periodic solution and equilibrium point. The numerical simulations were conducted to demonstrate these analytical critical ranges, and the results show that the libration motion will become unstable quickly if the out-plane angle or ε exceeds the critical range even under control strategy. This critical range of ε and out-plane angle is a general conclusion applicable to any situation (within the limitation of the model considered in this study), which can be utilized in guiding the design of system parameters to avoid rapid instability of electrodynamic tether system.
KMSBOT: Enhancing Educational Institutions with an AI-Powered Semantic Search Engine and Graph Database
Authors: subramanian venkata , J chandra , Ammunuel Ashok , V Rohini
Published: November 2023

In the rapidly evolving field of education, the need for a semantic search engine to efficiently retrieve graph-based data is crucial. Universities and colleges generate vast amounts of educational content research articles, and having a semantic search engine can enhance the accuracy of search results, ensuring that students and staff can access the right information effectively. It's imperative to develop an AI-based smart recommendation system equipped with semantic search capabilities to optimize information retrieval and provide accurate mapping for students or scholars. Such a system can revolutionize how educational content is accessed, offering personalized recommendations that align with the individual learning objectives of students and scholars, thus improving their educational experience. KMSBOT is an innovative academic recommendation system designed to enhance the efficiency of existing models. It effectively summarizes academic data and provides tailored information for students, research scholars, and educational faculty. The system employs a three-module approach, utilizing data structuring, NLP processing, and semantic search engine integration. By leveraging Neo4j, NLTK, and BERT in Python, this proposed work ensures optimal performance metrics such as time, accuracy, and loss value. The proposed solution addresses the limitations of traditional recommendation systems and contributes to improving user satisfaction and engagement in academic environments.
Mendelian Randomization Study Highlights the Role of Haematological Traits on Type-2 Diabetes Mellitus in African Ancestry Individuals
Authors: Fatumo Segun , Soremekun Chisom , Jjingo Daudi , Kateete David , Nashiru Oyekanmi , Nitsch Dorothea , Nyirenda Moffat , Gill Dipender , Zeggini Eleftheria , Grallert Harald , Peters Annette , Chikowore Tinashe , Batini Chiara , Soremekun Opeyemi
Published: November 2023

BackgroundObservational studies have identified associations between haematological traits and type-2 diabetes mellitus (T2D). However, it is difficult to infer causal effects due to the potential of confounding. Our study utilizes the Mendelian randomization (MR) approach to address the above limitation and investigate the causal effect of haematological traits (HT) such as white blood cell (WBC) count, platelet count, haemoglobin (Hb) levels, and red blood cell (RBC) count, on T2D in individuals of African ancestry.MethodsThe participating cohorts included participants of African ancestry in the Blood Cell consortium (n = 15,171) and the Million Veteran Program dataset (N=53,445: Ncases =23,305; Ncontrol = 30,140). We applied a univariable, bidirectional, and multivariable Two-sample MR to estimate the causal relationship between haematological traits and T2D using GWAS summary statistics. Genetic instruments for haematological traits and T2D included only the variants that attained a genome-wide significant level (P ≤ 5 × 10−8) of association with the respective exposure. The inverse-variance weighted MR approach was used in the main analysis, complemented by sensitivity analyses that are more robust to the inclusion of pleiotropic variants, including MR-Egger and MR-PRESSO. We further evaluated the genetic correlation between the hematological traits and T2D using linkage disequilibrium score regression (LDSC).ResultsIn the main inverse-variance weighted (IVW) MR estimates, genetically predicted mean corpuscular hemoglobin concentration (MCHC), mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV) levels were associated with decreased risk of T2D. Genetically predicted higher RBC was significantly associated with an increased risk of T2D. For WBC traits, there was evidence of protective effects of total WBC count and neutrophil count (NEU) on T2D. In the reverse analysis, genetically predicted T2D liability was associated with lower levels of RBC distribution width (RDW) and elevated levels of lymphocyte count (LYM). The multivariable analysis supported direct effects of genetically predicted MCH, MCHC, RDW, MCV, and lower levels of WBC with decreased risk of T2D. Additionally, LDSC showed negative genetic correlation of T2D with haematocrit (HCT) and haemoglobin concentration (HGB), and positive with eosinophil (EOS) and platelet count (PLT), suggesting that there is a genetic basis for the association between T2D and these blood traits.ConclusionThese findings indicate that haematological traits may differentially play a role in the development of T2D and be affected by T2D. However, further research is needed to validate and explore the biological pathways and mechanisms involved in these associations.
Synthesis, spectroscopic and structural characterization of two (2,4,6-tribromophenyl)thiourea
Authors: Arslan N. Burcu , Aydın Fatma
Published: November 2023

Two new compounds N-Benzoyl-N'-tribromophenyl thiourea (C14H9Br3N2OS) (I) and 4-Nitrobenzoyl-N'-tribromophenyl thiourea (C14H8Br3N3O3S) (II) were synthesized and characterized by 1HNMR, 13CNMR, IR, and structural (XRD) techniques. The molecular geometry, vibrational frequencies of the title compound (I, II) in the ground state have been calculated by using the density functional theory (DFT) method with B3LYP / 6–311G(d,p) basis set and compared with the experimental data. The calculated results show that the optimized geometries can well reproduce the crystal structural parameters. A detailed vibrational spectral analysis has been carried out and assignments of observed fundamental bands have been proposed on the basis of peak positions. The scaled theoretical frequencies show very good agreement with experimental values. Frontier molecular orbitals energies (HOMO&LUMO), energy gap (ΔE), global chemical reactivity parameters such as ionization potential (IP), electron affinity (ΔE), chemical hardness (η) and chemical softness (σ), etc. have been calculated, the sites of electrophilic and nucleophilic regions where the molecular interactions likely to happen are identified. Besides, molecular electrostatic potential (MEP) and thermodynamic properties of the title compounds were investigated by theoretical calculations.
Plate manufacturing constraint in topology optimization using anisotropic Helmholtz filter
Authors: Wada Yuji , Shimada Tokimasa , Nishiguchi Koji , Okazawa Shigenobu , Tsubokura Makoto
Published: November 2023

The manufacturing constraint of topology optimization for finding structures composed primarily of plate cross sections with an automatically decided surface normal is discussed. The Helmholtz filter to the sensitivity of the objective function is designed such that the eigenvalue-resolved stress tensor is converted to the anisotropic filter tensor. Plate structure formation and stiffness compliance performance are discussed through three sample problems: a solid bar subjected to torsional loads, an L-shaped member subjected to multiple loads, and a vehicle body frame intended to be a complex frame.