bluuebunny/crossref_metadata_2025 huggingface dataset:
COMPARATIVE ANALYSIS OF AIRFOIL SELECTION FOR MINIATURE AIR VEHICLE
Authors: Marathe Mayur , Deshmukh Samadhan ,   Mukesh Patel School of Technology Management and Engineering
Published: September 2023

This article outlines factors to take into account when choosing an MAV airfoil (Miniature Air Vehicle). A MAV is mostly used in hazardous and defense regions that are inaccessible to humans. The MAV has some specified range of speed in which it has travel, i.e.: - 9 to 20m/s. Here, a few airfoils are chosen, and after doing a comparison analysis, the airfoil that produces the best results is chosen. The airfoil is chosen with a flat lower surface for comparative examination. In order to choose the right airfoil, "ANSYS FLUENT" is used to analyze the airfoil and calculate the lift to drag ratio. The reason for this criterion is that the MAV should have a stable flight. This article provides guidance on choosing the ideal airfoil for gliding. The airfoil with the maximum lift to drag ratio is being selected. According to the study of the data, NACA-2205 would be the ideal for MAV since it has a high lift to drag ratio at a high angle of attack and a high capability of gliding.
Learning Graph Databases: Neo4j an overview
Authors: Meher Dr. Dipali , Bulakh Dr. Pallawi , Jabde Prof. Meena ,   Modern College of Arts, Science and Commerce
Published: September 2023

As the internet is growing day by day, the amount of data being generated is huge. This data includes structured data and unstructured data. The data along with its relationship with other data makes the most powerful and meaningful information. Maximum data exists in the form of the relationship between different or same objects and the noticeable thing is the relationship between the data is more important than the data itself. These relationships are handled efficiently by Relational databases that store data having structures and which have several records. The important point to be noted here is that these Relational database management Systems use tables with normalization concept. If the amount of data in such tables is huge, then handling such a large amount of data with its relationships is a tedious task. Here, Graph Databases come into picture. Entities and their relationships in relational databases will be reflected with nodes and relationships in graph databases. Graph databases provide very simple data model than databases with Online Transaction Processing systems. Graph databases provide features such as transactional integrity and operational availability. This paper introduces the idea of graph database systems in conjunction with Neo4j encompassing its query features, consistency, transactions, availability, and scaling.
A REVIEW ON ROLE OF AI IN DAMAGE ASSESSMENT INLAMINATED COMPOSITE STRUCTURES
Authors: Pratap Singh Abhendra , Asgar Md Ehsan , Ranjan Rajeev , Kaushik Yatharth , k Reji Justin , Tyagi Tarun ,   HMRITM
Published: September 2023

Composite structures are susceptible to various forms of non-linear failures, such as delamination,voids, and matrix cracks, during their operational life. Detecting such damages early is crucial to ensuring the structural integrity and reliability of these materials. As a result, researchers are continuously exploring more accurate and efficient methods for structural health monitoring of composite plates. In recent years, Artificial Intelligence (AI) techniques have shown immense potential as versatile tools for assessing damages in these materials.The present work provides a comprehensive review of the feasible methodologies utilized for delamination and crack observations in laminated composites, with a particular emphasis on machine learning techniques. The objective ofthe present article is to demonstrate a comprehensive perspective on the present state-of-the-art of health monitoring of laminated composite structures. Such insights are invaluable, given the escalating usage of laminated composites in various product engineering industries like automotive, aviation and aerospace, where critical quality, presence and location of damages/cracks is critical for improving their structural integrity. Furthermore, this review provides a critical analysis of thestrengths and limitations of wide damage detection techniques and offers insights into potential future research directions.
MACHINE LEARNING MODEL FOR HEART DISEASE PREDICITIONUSING TKINTER FOR GRAPHIC USER INTERFACE
Authors: Kumari Rekha , . Gurpreet , Khanna Anand , Miglani Rahul ,   HMRITM
Published: September 2023

- One of the biggest causes of death in the globe is heart disease. Accurate cardiac disease prediction can aid in early detection and prevention. Heart disease has been accurately predicted using machine learning models. In this study, we investigated 6 machine learning models for predicting heart disease [1]. To train and assess these models, we used the Cleveland HeartDisease dataset, a publically accessible dataset. Age, sex, the type of chest discomfort, blood pressure, cholesterol levels, and other characteristics were among the features used to train the models. To determine the most reliable model for heart disease prediction, the outcomesfrom various models' tests were compared.
ANALYSIS OF TRANSFORMER-DEEP NEURAL NETWORK USING DEEP LEARNING
Authors: Kumari Rekha , Kaur Gurpreet , Rawat Aditya , Chauhan Harshit , Singh Negi Kartik , Mishra Rishi ,   HMRITM
Published: September 2023

Transformers were first used for natural language processing (NLP) tasks, but they quickly spread to other deep learning fields, including computer vision. They assess the interdependence of pairs. Attention is a part that enables to dynamically highlight relevant features of the input data (words in the case of text strings, parts of images in the case of visual Transformers). The cost grows continually with the number of tokens. The most common Trans- former Architecture for image classification uses only the Transformer Encoder to transform the various input tokens. However, the decoder component of the traditional Transformer Architecture is also used in a variety of other applications. In this section, we first introduce the Attention Mechanism (Section 1), followed by the Basic Transformer Block, which includes the Vision Transformer (Section 2).
SARS-COV-2: THE 2019 NOVEL CORONAVIRUS
Authors: Gahlot Amit , . Rakhi
Published: September 2023

The Nationwide Lockdown has been a major part of the planning of government to overcome the pandemic COVID -19 which includes complete shutdown of businesses, disrupted food supply chains, extended limits of time slots and terminated contacts. This pandemic leads to unorganized economic sector with loss at its peak. There has been a total shutdown in all the areas, leaving individuals who are most adversely affected with few or no legal options. On the other hand, the lockdown has assisted in reducing the disease's transmission throughout the society while allowing for a legal and legislative examination of this action that has thus far escaped scrutiny. In the seventh week of the lockdown, it was crucial and appropriate that we assessed the overall legality of the lockdown as well as all the actions the Indian government has taken to combat COVID-19. According the Laws governing this lockdown, it is well known that the State governments and district authorities have implemented a lockdown in accordance with instructions from the Union Ministry of Home Affairs under the Disaster Management Act of 2005whose intentions were “to provide for the effective management of disasters and for the matters which are connected there with incidental thereto”. On March 24, 2020, the NDMA (National Disaster Management Authority) and NEA (National Executive Committee) which were established at the direction of the Prime Minister and chaired by the Home Secretary respectively, they issued orders and guidelines to Union Ministers. To prevent the spread of COVID-19, state governments and relevant authorities should take appropriate, lawful action. They should also follow any instructions that specify which businesses should be closed and which services should be discontinued during this lockdown period. The government issued instructions to impose “social distancing” and the isolation measures to remain “under strict home quarantine” and people to “stay at home and come out only when it is necessary for basic necessities and essential services while following social distancing norms”.
VIRTUAL ASSISTANT USING ARTIFICIAL INTELLIGENCE
Authors: Raj Mayank , Devang Ashish , Chanchal Satya ,   School of Computer Science and Engineering
Published: September 2023

Voice assistants are programs on digital devices that listen and respond to verbal commands. A user can say, “What’s the weather?” and the voice assistant will answer with the weather report for that day and location. They could say, “Tell me a story,” and the assistant will jump into a tale. Many devices are becoming smarter in their own way to interact with human in an easy language. The Desktop based voice assistant are the programs that can recognize human voices and can respond via integrated voice system. Voice assistants are the great innovation in the field of AI that can change the way of living of the people in a different manner. The voice assistant was first introduced on smartphones and after the popularity it got. We use artificial intelligence python as a programming language because it have a major libraries which is use to execute commands. By using python installer packages our personal virtual assistant recognize the user voice and process on it. It takes voice as input. The system is being designed in such a way that all the services provided by the mobile devices are accessible by the end user on the user's voice commands. We reviewed studies that used voice assistants for various tasks in this context. Our study highlighted the usability measures currently used for voice assistants. This paper will define the working of a voice assistants, their main problems and limitations. In this paper it is described that the method of creating a voice assistant without using cloud services, which will allow the expansion of such devices in the future.
Mountain Bike Frame Innovation Using Thermplastic Composites - A Case Study
Authors: Giaraffa Matt , Howell D. DeWayne
Published: September 2023

For over 20 years the bike industry has been using composite materials to make mountain bike frames and other components, becoming the default high end material in the past 5-10 years. Thermoset based carbon fiber composites have traditionally led the way, but recently the next generation technology of thermoplastic infused carbon fiber composites have entered the market as recyclability, impact toughness, and vibration damping become more important. In particular, a new class of mountain bike frames has hit the trails as produced by Revved Industries for their in-house brand, Guerrilla Gravity. Increased impact toughness and vibration damping of thermoplastic composites offer attractive performance advantages that are ideal for applications such as mountain bike frames and components. Several thermoplastic composite material options were investigated and PA6/carbon fiber produced by Toray Advanced Composites was selected. A significant breakthrough in thermoplastic composite part forming, co-molding, and fusing has led to a durable and robust design that sets thermoplastic frames apart from their thermoset counterparts. This paper will review the material selection, design and analysis, fabrication, and testing of a mountain bike frame that has proven itself in the market today.
Analisis kegagalan metakognitif siswa dalam pemecahan masalah matematis
Authors: Cesario Rd. Muhamad Ridwan , Huda Nizlel , Zurweni Zurweni
Published: September 2023

Penelitian ini bertujuan untuk menjelaskan aktivitas metakognitif dan kegagalan metakognitif yang muncul pada siswa selama proses pemecahan masalah matematis. Subjek penelitian ini ialah siswa SMK Yadika Jambi, pemilihan sampel dilakukan melalui teknik purposive sampling untuk memilih 1 orang siswa yang dapat mewakili populasi. Data dikumpulkan menggunakan teknik tes berupa 1 soal uraian yang bersifat HOTS dan wawancara untuk menggali pemahaman siswa mengenai jawaban yang dikerjakan dengan menggunakan pedoman wawancara tak terstruktur. Teknik analisis data menggunakan analisis deskriptif kualitatif dan penarikan kesimpulan. Hasil penelitian menyimpulkan bahwa terjadi kegagalan metakognitif pada aktivitas metakognitif siswa. Kegagalan metakognitif siswa didasari oleh beberapa indikator, yaitu metakognitif mirage yang merupakan keadaan dimana siswa mengacuhkan strategi yang bermanfaat, mengubah perhitungan yang sudah benar dan menolak jawaban benar tersebut, metakognitif vandalism yang merupakan keadaan dimana siswa menerapkan struktur konseptual secara tidak tepat, dan metakognitif blindness yang merupakan keadaan dimana siswa mengabaikan adanya kesalahan perhitungan.
Long-term effects of COVID-19 on the endocrine system – a pilot case-control study
Authors: Szczerbiński Łukasz , Okruszko Michał Andrzej , Szabłowski Maciej , Sołomacha Sebastian , Sowa Paweł , Kiszkiel Łukasz , Gościk Joanna , Krętowski Adam Jacek , Moniuszko-Malinowska Anna , Kamiński Karol
Published: September 2023

Background

Coronavirus disease 2019 (COVID-19) has permanently changed the world. Despite having been a pandemic for nearly 3 years, the mid- and long-term complications of this disease, including endocrine disorders, remain unclear. Our study aimed to evaluate the lasting effects of COVID-19 on the endocrine system 6 months after initial infection.

Methods

We compared patients who underwent COVID-19 to age- and sex-matched subjects from a population-based study conducted before the pandemic. We evaluated differences in multiple parameters related to metabolism and the endocrine system including fasting glucose, insulin, lipids, body composition, thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), anti-thyroglobulin (aTG) and anti-thyroid peroxidase (aTPO) antibodies, prolactin, cortisol, testosterone, and estradiol.

Results

We found significantly lower levels of fT3 and fT4, accompanied by higher levels of TSH and aTPO antibodies, in COVID-19 survivors. Moreover, we found that patients who underwent SARS-CoV2 infection had higher levels of prolactin and lower levels of testosterone than controls. Interestingly, differences in testosterone levels were observed only in male subjects. We did not detect significant differences in body composition or metabolic and glycemic parameters between cases and controls, except for significantly higher values of the HOMA2-B index in COVID-19 survivors.

Conclusion

Our study indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection might have long-term consequences on the endocrine system, including the suppressed function of the thyroid gland, prolactin, and male sex hormone secretion. Moreover, we showed that in a 6-month follow-up, COVID-19 had no consequences on glycemic parameters, lipid profiles, liver function, body composition, cortisol levels, and estradiol levels.
Exploring the synergy of blockchain technology and low-carbon innovation for enterprise sustainability for unlocking a sustainable energy
Authors: A. ZiYa , Guo XiaoChuan
Published: September 2023

Along with further implementation of the policy strategy of carbon peaking and carbon neutralization in our country, the development idea of realizing the “dual carbon” goal with emphasis on environmental protection and low-carbon technology development has been preliminary established. At present, Chinese energy enterprises urgently need to break the dilemma between system and efficiency through technological innovation, so as to achieve the goal of sustainable development. Based on the legitimacy theory and stakeholder theory, this paper discusses the internal mechanism and boundary conditions of low-carbon technology innovation affecting the sustainable development of energy enterprises. Based on the data of listed Chinese energy companies from 2015 to 2021, the empirical study found that the level of low-carbon technology innovation of energy enterprises has an inverted U-shaped positive impact on their sustainable development performance, and the dual legitimacy (political legitimacy, market legitimacy) plays a part of the intermediary role. The degree of market competition positively moderates the relationship between low-carbon technology innovation and political legitimacy, and positively moderates the mediating effect of political legitimacy between low-carbon technology innovation and sustainable development performance. However, the degree of market competition has no significant moderating effect on the relationship between low-carbon technology innovation and market legitimacy, nor can it significantly regulate the mediating effect of market legitimacy. The constraint strength of “dual carbon” targets positively moderates the relationship between low-carbon technology innovation and political legitimacy, and positively moderates the mediating effect of market legitimacy between low-carbon technology innovation and sustainable development performance. On the contrary, the “dual carbon” target constraint intensity negatively moderates the relationship between low-carbon technology innovation and market legitimacy, and negatively moderates the mediating effect of market legitimacy. This article not only provides a new perspective for the integration of low-carbon innovation and legitimacy theory, but also provides theoretical reference and guidance for the practice of low-carbon technology innovation in energy enterprises.
Adaptive VSG control strategy considering energy storage SOC constraints
Authors: Han Jinglin , Feng Xichun , Zhao Hui , Hu Ping , He Chunguang
Published: September 2023

The virtual synchronous generator (VSG) control strategy is proposed to mitigate the low inertia problem in the power system brought about by the high percentage of distributed generation connected to the grid and the application of power electronic devices. In order to maximize the effectiveness of the advantages of the flexible and adjustable parameters of VSG control, an adaptive VSG control strategy considering SOC constraint of the energy storage unit is proposed in this paper. Considering the significant loss of service life by operating the energy storage unit at its limit state, based on the rate and degree of change in system frequency, the adaptive control strategy realizes the online adaptive adjustment of the inertia factor and damping factor under different perturbation conditions by adaptively adjusting the control parameters when the system frequency oscillates. Finally, the effects of this adaptive VSG control method and conventional VSG control method are compared by simulation in PLECS. Hardware-in-the-loop (HIL) experimental platforms and semi-physical simulation experiments are constructed on RTBOX, and the feasibility and validity of this adaptive VSG control strategy are verified.
Y chromosome evidence confirms northeast Asian origin of Xinjiang Kazakhs and genetic influence from 18th century expansion of Kerey clan
Authors: Wang Bangyan , Liang Jiayu , Allen Edward , Chang Xin , Jiang Zixi , Yu Yao , Shi Meisen , Wen Shaoqing
Published: September 2023

The Kazakhs of Xinjiang province are characterized by their nomadic lifestyle and patrilineal clan system. However, compared to Central Asian Kazakhs, a lack of Y chromosomal high-resolution analysis has hindered our understanding of the paternal history of modern Xinjiang Kazakhs.

Methods

In this study, we present the analysis of 110 Y-SNP data from 209 Altay Kazakhs and 201 Ili Kazakhs in Xinjiang, along with their previously reported 24 Y-STR loci data.

Results and discussion

We found that the Y chromosome haplogroups exhibit greater diversity in Altay Kazakhs compared to Kazakhs in Kazakhstan, Russia, and other regions of China. Y-SNP-based PCA plots reveal that both the Altay and Ili Kazakhs are situated between the Turkic, Mongolia, and Tibeto-Burman clusters. The dominant haplogroup C2a1a3-F1918, which originated in northeast Asia during the Neolithic Age, accounts for nearly half of the Altay and Ili Kazakhs. The Y lineage network of C2a1a3-F1918 contained two subclusters. Approximately 60.6% of the Altay Kazakhs belong to the DYS448-23 subcluster, indicating their Kerey-Abakh ancestry. On the other hand, around three-quarters of the Ili Kazakhs belong to the DYS448-22 subcluster, suggesting their Kerey-Ashmaily heritage. Notably, the TMRCA ages of the DYS448-23 subcluster were calculated to be 289.4 ± 202.65 years, which aligns with the historical immigration of the Kerey clan back to the Altay Mountains after the defeat of the Dzungar by the Qing dynasty in the mid-18th century.
Over-the-counter emergency contraception in Italy: ethical reflections and medico-legal issues
Authors: Scendoni Roberto , Cingolani Mariano , Cembriani Fabio , Fedeli Piergiorgio , Tambone Vittoradolfo , Terranova Corrado , De Micco Francesco
Published: September 2023

Although more than ten years have passed since the marketing of Ulipristal acetate in Europe, emergency contraception remains a complex issue with many scientific, legal, ethical and social implications. The topic is an example of the differences that can exist between scientific evidence, the certainties on which law is based, and social implications. This paper shows the incompleteness of the scientific reconstruction on the effects of emergency hormonal contraceptives and the dangerousness of the decision to alienate the supply of over-the-counter drugs from the general rules of health care. This report shows the incompleteness of the scientific reconstruction on the effects of emergency hormonal contraceptives and the dangerousness of the decision to alienate the supply of over-the-counter drugs from the general rules of health care. Various ethical and medico-legal issues will be addressed, also focusing attention on underage women whose sexual and reproductive health requires not abandoning them, but actually taking charge of them without medicalizing their choices.
Single-cell transcriptome sequencing reveals tumor heterogeneity in family neuroblastoma
Authors: Zhang Yunlong , Ma Yue , Liu Qingqing , Du Yifei , Peng Liang , Zhou Jianwu , Zhao Zhenzhen , Li Changchun , Wang Shan
Published: September 2023

Neuroblastoma(NB) is the most common extracranial solid tumor in childhood, and it is now believed that some patients with NB have an underlying genetic susceptibility, which may be one of the reasons for the multiplicity of NB patients within a family line. Even within the same family, the samples show great variation and can present as ganglioneuroblastoma or even benign ganglioneuroma. The genomics of NB is still unclear and more in-depth studies are needed to reveal its key components. We first performed single-cell RNA sequencing(sc-RNAseq) analysis on clinical specimens of two family neuroblastoma(FNB) and four sporadic NB cases. A complete transcriptional profile of FNB was constructed from 18,394 cells from FNB, and we found that SDHD may be genetically associated with FNB and identified a prognostic related CAF subtype in FNB: Fib-4. Single-cell flux estimation analysis (scFEA) results showed that malignant cells were associated with arginine spermine, oxaloacetate and hypoxanthine, and that malignant cells metabolize lactate at lower levels than T cells. Our study provides new resources and ideas for the development of the genomics of family NB, and the mechanisms of cell-to-cell interactions and communication and the metabolic landscape will provide new therapeutic targets.
Identification of lactate regulation pattern on tumor immune infiltration, therapy response, and DNA methylation in diffuse large B-cell lymphoma
Authors: Wang Jinghua , Wang Yanjun , Wan Li , Chen Xinyuan , Zhang Han , Yang Shuo , Zhong Liye
Published: September 2023

Background

Lactate, produced through glycolytic metabolism in the tumor microenvironment (TME), is implicated in tumorigenesis and progression in diverse cancers. However, the impact of lactate on the remodeling of the TME in diffuse large B-cell lymphoma (DLBCL) and its implications for therapy options remain unclear.

Method

A lactate-related (LAR) scoring model was constructed in DLBCL patients using bioinformatic methods. CIBERSORT, XCELL, and ssGSEA algorithms were used to determine the correlation between LAR score and immune cell infiltration. Tumor Immune Dysfunction and Exclusion (TIDE), rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) cohorts, and Genomics of Drug Sensitivity in Cancer (GDSC) were utilized to predict the therapeutic response of DLBCL patients. The impact of the hub gene STAT4 on tumor biological behavior and DNA methylation was experimentally validated or accessed by the TSIDE database.

Results

The LAR scoring model was developed based on 20 prognosis-related lactate genes, which enabled the division of DLBCL patients into high- and low-risk groups based on the median LAR score. Patients with high-risk DLBCL exhibited significantly worse survival outcomes in both the training cohorts (GSE181063) and the validation cohorts (GSE10846, GSE32918, and GSE69053), as indicated by statistically significant differences (all P<0.05) and area under the curve (AUC) values exceeding 0.6. Immune analyses revealed that low-risk DLBCL patients had higher levels of immune cell infiltration and antitumor immune activation compared to high-risk DLBCL patients. Furthermore, DLBCL patients with high LAR scores were associated with a lower TIDE value and poor therapeutic efficacy of the R-CHOP regimen. GDSC analysis identified 18 drugs that exhibited significant response sensitivity in low-risk DLBCL patients. Moreover, in vitro experiments demonstrated that overexpression of the lactate key gene STAT4 could suppress proliferation and migration, induce cell cycle arrest, and promote cell apoptosis in DLBCL cells. Transcriptional expression and methylation of the STAT4 gene were found to be associated with immunomodulators and chemokines.

Conclusion

The lactate-based gene signature effectively predicts the prognosis and regulates TME in DLBCL. Our study underscores the role of lactate gene, STAT4, as an important tumor suppressor in DLBCL. Modulating STAT4 could be a promising strategy for DLBCL in clinical practice.
Can immunotherapy reinforce chemotherapy efficacy? a new perspective on colorectal cancer treatment
Authors: He Xing , Lan Huanrong , Jin Ketao , Liu Fanlong
Published: September 2023

As one of the main threats to human life (the fourth most dangerous and prevalent cancer), colorectal cancer affects many people yearly, decreases patients’ quality of life, and causes irreparable financial and social damages. In addition, this type of cancer can metastasize and involve the liver in advanced stages. However, current treatments can’t completely eradicate this disease. Chemotherapy and subsequent surgery can be mentioned among the current main treatments for this disease. Chemotherapy has many side effects, and regarding the treatment of this type of tumor, chemotherapy can lead to liver damage, such as steatohepatitis, steatosis, and sinus damage. These damages can eventually lead to liver failure and loss of its functions. Therefore, it seems that other treatments can be used in addition to chemotherapy to increase its efficiency and reduce its side effects. Biological therapies and immunotherapy are one of the leading suggestions for combined treatment. Antibodies (immune checkpoint blockers) and cell therapy (DC and CAR-T cells) are among the immune system-based treatments used to treat tumors. Immunotherapy targets various aspects of the tumor that may lead to 1) the recruitment of immune cells, 2) increasing the immunogenicity of tumor cells, and 3) leading to the elimination of inhibitory mechanisms established by the tumor. Therefore, immunotherapy can be used as a complementary treatment along with chemotherapy. This review will discuss different chemotherapy and immunotherapy methods for colorectal cancer. Then we will talk about the studies that have dealt with combined treatment.
Digoxin protects against intervertebral disc degeneration via TNF/NF-κB and LRP4 signaling
Authors: Meng Qunbo , Liu Kaiwen , Liu Zhenchuan , Liu Jinbo , Tian Ziyu , Qin Shanshan , Wei Jianlu , Cheng Lei
Published: September 2023

Background

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain (LBP). The pathological process of IVDD is associated with inflammatory reactions and extracellular matrix (ECM) disorders. Digoxin is widely used for treating heart failure, and it has been reported to have anti-inflammatory effects.

Objective

This study is to investigate the role of digoxin in the pathogenesis of intervertebral disc degeneration as well as the involved molecular mechanism, particularly the potential target protein.

Methods

We exploited a rat needle model to investigate digoxin’s role in intervertebral disc degeneration in vivo. Safranin O staining was used to measure cartilaginous tissue in the intervertebral disc. The morphological changes of intervertebral discs in animal models were determined by Hematoxylin-Eosin (H&E) staining and the pathological score. Primary nucleus pulposus cells (NP cells) from intervertebral discs of patients and murine were used in the present study. Western-Blotting assay, Real-time PCR assay, immunofluorescence staining, and immunochemistry were used to detect the role of digoxin in anti-TNF-α-induced inflammatory effects in vitro. Transfection of siRNA was used to regulate low-density lipoprotein receptor-related protein 4 (LRP4) expression in NP cells to investigate the potential protein target of digoxin.

Results

Digoxin protected against intervertebral disc degeneration in rat needle models. Digoxin was found to exert its disc-protective effects through at least three different pathways by a) suppressing TNF-α-induced inflammation, b) attenuating ECM destruction, c) significantly promoting ECM anabolism. Additionally, LRP4 was found to be the downstream molecule of digoxin in NP cells for anti-inflammation and regulation of ECM metabolism. The knockdown of LRP4 downregulated the protective effect of digoxin in NP cells.

Conclusion

These findings suggest that digoxin may be a potential therapeutic agent for intervertebral disc degeneration through anti-catabolism and pro-anabolism. Digoxin might also work as an alternative for other inflammation-related diseases.
A systematic review and meta-analysis of neopterin in rheumatic diseases
Authors: Mangoni Arduino A. , Zinellu Angelo
Published: September 2023

Introduction

Novel biomarkers of inflammation and oxidative stress might enhance the early recognition, management, and clinical outcomes of patients with rheumatic diseases (RDs). We assessed the available evidence regarding the pathophysiological role of neopterin, the oxidation product of 7,8-dihydroneopterin, a pteridine generated in macrophages activated by interferon-γ, by conducting a systematic review and meta-analysis of studies reporting its concentrations in biological fluids in RD patients and healthy controls.

Methods

We searched electronic databases for relevant articles published between inception and 31 August 2023. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and the Grades of Recommendation, Assessment, Development and Evaluation Working Group system, respectively.

Results

In 37 studies, when compared to healthy controls, RD patients had significantly higher concentrations of neopterin both in plasma or serum (standard mean difference, SMD=1.31, 95% CI 1.01 to 1.61; p<0.001; moderate certainty of evidence) and in the urine (SMD=1.65, 95% CI 0.86 to 2.43, p<0.001; I2 = 94.2%, p<0.001; low certainty of evidence). The results were stable in sensitivity analysis. There were non-significant associations in meta-regression and subgroup analysis between the effect size and age, male to female ratio, year of publication, sample size, RD duration, C-reactive protein, erythrocyte sedimentation rate, specific type of RD, presence of connective tissue disease, analytical method used, or biological matrix investigated (plasma vs. serum). By contrast, the effect size was significantly associated with the geographical area in studies assessing serum or plasma and with the type of RD in studies assessing urine.

Discussion

Pending additional studies that also focus on early forms of disease, our systematic review and meta-analysis supports the proposition that neopterin, a biomarker of inflammation and oxidative stress, can be useful for the identification of RDs. (PROSPERO registration number: CRD42023450209).

Systematic review registration

PROSPERO, identifier CRD42023450209
Plateau pika fecal microbiota transplantation ameliorates inflammatory bowel disease manifestations in a mouse model of colitis
Authors: Yang Yayuan , Cui Baiqiang , Lv Yanan , Lu Xiangnan , Shen Wenxiang , Feng Min , Ding Xuezhi , Dong Pengcheng , Wang Yu
Published: September 2023

Inflammatory bowel disease (IBD) is a serious global public health concern. Although the pathogenesis of the disease is currently unknown, it has been reported to be associated with both intestinal microbiota and inflammatory mediators. There is evidence suggesting that the feces of the Plateau pika is useful for treating gastrointestinal injuries and pain. Although fecal microbiota transplantation is highly efficacious intervention for IBD prevention, however, potential the transfer of pathogenic microbes or toxic substances is potentially hazardous. Fortunately, micropore filtering of the donor feces can minimize the risk of bacterial infection allowing retention of the therapeutic effects of the residual bacteriophages. Here, we demonstrated that Plateau pika feces not only alleviated the IBD symptoms but also promoted optimal structure and composition of the intestinal microbiota. Additionally, Plateau pika feces transfer also enhanced phenotypic features, such as, body-weight, disease activity index, and histological scores. In conclusion, Plateau pika feces was found to protect mice against colitis induced by dextran sodium sulfate by reducing inflammation and regulating microbial dysbiosis. These findings suggest the potential of Plateau pika feces as an alternative therapy for IBD.
Using personal narrative to promote person-centered values in aging, dementia, and caregiving
Authors: Merrilees Jennifer , Mayotte Cliff , Vong Erin , Matice Mindy , Prioleau Caroline
Published: September 2023

Personal narrative is a powerful way to include people in their care and to understand their values that drive their needs. In this paper, we describe a program designed to teach oral history to clinicians and trainees in the field of aging, dementia and caregiving. The training uses empathic listening, open-ended interviewing, and the discovery of individual values and experience to breakdown stigma and preconceptions of what it means to age with cognitive impairment. Sharing these stories of aging, dementia, and caregiving becomes an important tool to break down stereotypes, promote person-centered care, and advocate for the unheard. The profound impact of the oral history process is felt by the narrator, the interviewer and the listener. Human beings are wired for stories, and oral history taps into that power to connect us and provide better care through better understanding.
Visualizing risky situations induces a stronger neural response in brain areas associated with mental imagery and emotions than visualizing non-risky situations
Authors: Zaleskiewicz Tomasz , Traczyk Jakub , Sobkow Agata , Fulawka Kamil , Megías-Robles Alberto
Published: September 2023

In an fMRI study, we tested the prediction that visualizing risky situations induces a stronger neural response in brain areas associated with mental imagery and emotions than visualizing non-risky and more positive situations. We assumed that processing mental images that allow for “trying-out” the future has greater adaptive importance for risky than non-risky situations, because the former can generate severe negative outcomes. We identified several brain regions that were activated when participants produced images of risky situations and these regions overlap with brain areas engaged in visual, speech, and movement imagery. We also found that producing images of risky situations, in contrast to non-risky situations, was associated with increased neural activation in the insular cortex and cerebellum–the regions involved, among other functions, in emotional processing. Finally, we observed an increased BOLD signal in the cingulate gyrus associated with reward-based decision making and monitoring of decision outcomes. In summary, risky situations increased neural activation in brain areas involved in mental imagery, emotional processing, and decision making. These findings imply that the evaluation of everyday risky situations may be driven by emotional responses that result from mental imagery.
Utilizing risk-controlling prediction calibration to reduce false alarm rates in epileptic seizure prediction
Authors: Segal Galya , Keidar Noam , Lotan Roy Maor , Romano Yaniv , Herskovitz Moshe , Yaniv Yael
Published: September 2023

Introduction

Epilepsy is a neurological disease characterized by sudden, unprovoked seizures. The unexpected nature of epileptic seizures is a major component of the disease burden. Predicting seizure onset and alarming patients may allow timely intervention, which would improve clinical outcomes and patient quality of life. Currently, algorithms aiming to predict seizures suffer from a high false alarm rate, rendering them unsuitable for clinical use.

Methods

We adopted here a risk-controllingprediction calibration method called Learn then Test to reduce false alarm rates of seizure prediction. This method calibrates the output of a “black-box” model to meet a specified false alarm rate requirement. The method was initially validated on synthetic data and subsequently tested on publicly available electroencephalogram (EEG) records from 15 patients with epilepsy by calibrating the outputs of a deep learning model.

Results and discussion

Validation showed that the calibration method rigorously controlled the false alarm rate at a user-desired level after our adaptation. Real data testing showed an average of 92% reduction in the false alarm rate, at the cost of missing four of nine seizures of six patients. Better-performing prediction models combined with the proposed method may facilitate the clinical use of real-time seizure prediction systems.
Lightfield hyperspectral imaging in neuro-oncology surgery: an IDEAL 0 and 1 study
Authors: MacCormac Oscar , Noonan Philip , Janatka Mirek , Horgan Conor C. , Bahl Anisha , Qiu Jianrong , Elliot Matthew , Trotouin Théo , Jacobs Jaco , Patel Sabina , Bergholt Mads S. , Ashkan Keyoumars , Ourselin Sebastien , Ebner Michael , Vercauteren Tom , Shapey Jonathan
Published: September 2023

Introduction

Hyperspectral imaging (HSI) has shown promise in the field of intra-operative imaging and tissue differentiation as it carries the capability to provide real-time information invisible to the naked eye whilst remaining label free. Previous iterations of intra-operative HSI systems have shown limitations, either due to carrying a large footprint limiting ease of use within the confines of a neurosurgical theater environment, having a slow image acquisition time, or by compromising spatial/spectral resolution in favor of improvements to the surgical workflow. Lightfield hyperspectral imaging is a novel technique that has the potential to facilitate video rate image acquisition whilst maintaining a high spectral resolution. Our pre-clinical and first-in-human studies (IDEAL 0 and 1, respectively) demonstrate the necessary steps leading to the first in-vivo use of a real-time lightfield hyperspectral system in neuro-oncology surgery.

Methods

A lightfield hyperspectral camera (Cubert Ultris ×50) was integrated in a bespoke imaging system setup so that it could be safely adopted into the open neurosurgical workflow whilst maintaining sterility. Our system allowed the surgeon to capture in-vivo hyperspectral data (155 bands, 350–1,000 nm) at 1.5 Hz. Following successful implementation in a pre-clinical setup (IDEAL 0), our system was evaluated during brain tumor surgery in a single patient to remove a posterior fossa meningioma (IDEAL 1). Feedback from the theater team was analyzed and incorporated in a follow-up design aimed at implementing an IDEAL 2a study.

Results

Focusing on our IDEAL 1 study results, hyperspectral information was acquired from the cerebellum and associated meningioma with minimal disruption to the neurosurgical workflow. To the best of our knowledge, this is the first demonstration of HSI acquisition with 100+ spectral bands at a frame rate over 1Hz in surgery.

Discussion

This work demonstrated that a lightfield hyperspectral imaging system not only meets the design criteria and specifications outlined in an IDEAL-0 (pre-clinical) study, but also that it can translate into clinical practice as illustrated by a successful first in human study (IDEAL 1). This opens doors for further development and optimisation, given the increasing evidence that hyperspectral imaging can provide live, wide-field, and label-free intra-operative imaging and tissue differentiation.
Opposite trends in incidence of breast cancer in young and old female cohorts in Hungary and the impact of the Covid-19 pandemic: a nationwide study between 2011–2020
Authors: Kiss Zoltán , Kocsis Judit , Nikolényi Alíz , Horváth Zsolt , Knollmajer Kata , Benedek Angéla , Várnai Máté , Polányi Zoltán , Kovács Krisztina Andrea , Berta Andrea , Köveskuti István , Karamousouli Eugenia , Szabó Tamás Géza , Rokszin György , Fábián Ibolya , Bartókné Tamás Renáta , Surján Orsolya , Fürtős Diána , Surján György , Kenessey István , Weber András , Barcza Zsófia , Berki Tamás , Vokó Zoltán , Dózsa Csaba , Dank Magdolna , Boér Katalin
Published: September 2023

Background

This nationwide study examined breast cancer (BC) incidence and mortality rates in Hungary between 2011–2019, and the impact of the Covid-19 pandemic on the incidence and mortality rates in 2020 using the databases of the National Health Insurance Fund (NHIF) and Central Statistical Office (CSO) of Hungary.

Methods

Our nationwide, retrospective study included patients who were newly diagnosed with breast cancer (International Codes of Diseases ICD)-10 C50) between Jan 1, 2011 and Dec 31, 2020. Age-standardized incidence and mortality rates (ASRs) were calculated using European Standard Populations (ESP).

Results

7,729 to 8,233 new breast cancer cases were recorded in the NHIF database annually, and 3,550 to 4,909 all-cause deaths occurred within BC population per year during 2011-2019 period, while 2,096 to 2,223 breast cancer cause-specific death was recorded (CSO). Age-standardized incidence rates varied between 116.73 and 106.16/100,000 PYs, showing a mean annual change of -0.7% (95% CI: -1.21%–0.16%) and a total change of -5.41% (95% CI: -9.24 to -1.32). Age-standardized mortality rates varied between 26.65–24.97/100,000 PYs (mean annual change: -0.58%; 95% CI: -1.31–0.27%; p=0.101; total change: -5.98%; 95% CI: -13.36–2.66). Age-specific incidence rates significantly decreased between 2011 and 2019 in women aged 50–59, 60–69, 80–89, and ≥90 years (-8.22%, -14.28%, -9.14%, and -36.22%, respectively), while it increased in young females by 30.02% (95%CI 17,01%- 51,97%) during the same period. From 2019 to 2020 (in first COVID-19 pandemic year), breast cancer incidence nominally decreased by 12% (incidence rate ratio [RR]: 0.88; 95% CI: 0.69–1.13; 2020 vs. 2019), all-cause mortality nominally increased by 6% (RR: 1.06; 95% CI: 0.79–1.43) among breast cancer patients, and cause-specific mortality did not change (RR: 1.00; 95%CI: 0.86–1.15).

Conclusion

The incidence of breast cancer significantly decreased in older age groups (≥50 years), oppositely increased among young females between 2011 and 2019, while cause-specific mortality in breast cancer patients showed a non-significant decrease. In 2020, the Covid-19 pandemic resulted in a nominal, but not statistically significant, 12% decrease in breast cancer incidence, with no significant increase in cause-specific breast cancer mortality observed during 2020.
Kisspeptin-mediated improvement of sensitivity to BRAF inhibitors in vemurafenib-resistant melanoma cells
Authors: Guzzetti Carlotta , Corno Cristina , Vergani Elisabetta , Mirra Luca , Ciusani Emilio , Rodolfo Monica , Perego Paola , Beretta Giovanni L.
Published: September 2023

Metastatic dissemination is still one of the major causes of death of melanoma’s patients. KiSS1 is a metastasis suppressor originally identified in melanoma cells, known to play an important physiological role in mammals’ development and puberty. It has been previously shown that expression of KiSS1 could be increased in lung cancer cells using epigenetic agents, and that KiSS1 could have a pro-apoptotic action in combination with cisplatin. Thus, the aim of the present study was to examine in human melanoma vemurafenib sensitive- and -resistant BRAF mutant cells characterized by different mutational profiles and KiSS1, KiSS1 receptor and KiSS1 drug-induced release, if peptides derived from KiSS1 cleavage, i.e., kisspeptin 54, could increase the sensitivity to vemurafenib of human melanoma, using cellular, molecular and biochemical approaches. We found that kisspeptin 54 increases vemurafenib pro-apoptotic activity in a statistically significant manner, also in drug resistant cellular models. The efficacy of the combination appears to reflect the intrinsic susceptibility of each cell line to PLX4032-induced apoptosis, together with the different mutational profile as well as perturbation of proteins regulating the apoptotic pathway, The results presented here highlight the possibility to exploit KiSS1 to modulate the apoptotic response to therapeutically relevant agents, suggesting a multitasking function of this metastasis suppressor.
Prediabetes and the risk of breast cancer: a meta-analysis
Authors: Lin Jing , Tu Rongzu , Lu Zhai’e
Published: September 2023

Background

Diabetes has been related to a higher risk of breast cancer (BC) in women. However, it remains unknown whether the incidence of BC is increased in women with prediabetes. A systematic review and meta-analysis was therefore performed to evaluate the relationship between prediabetes and risk of BC.

Methods

Observational studies with longitudinal follow-up relevant to the objective were found via searching Medline, Embase, Cochrane Library, and Web of Science. A fixed- or random-effects model was used to pool the results depending on heterogeneity.

Results

Eight prospective cohort studies and two nest case-control studies were included. A total of 1069079 community women were involved, and 72136 (6.7%) of them had prediabetes at baseline. During a mean duration follow-up of 9.6 years, 9960 (0.93%) patients were diagnosed as BC. Pooled results with a fixed-effects model showed that women with prediabetes were not associated with a higher incidence of BC as compared to those with normoglycemia (risk ratio: 0.99, 95% confidence interval: 0.93 to 1.05, p = 0.72) with mild heterogeneity (p for Cochrane Q test = 0.42, I2 = 3%). Subgroup analyses showed that study characteristics such as study design, menopausal status of the women, follow-up duration, diagnostic criteria for prediabetes, methods for validation of BC cases, and study quality scores did not significantly affect the results (p for subgroup analyses all > 0.05).

Conclusion

Women with prediabetes may not be associated with an increased risk of BC as compared to women with normoglycemia.