bluuebunny/crossref_metadata_2025 huggingface dataset:
Qualitative results and numerical approximations of the $ (k, \psi) $-Caputo proportional fractional differential equations and applications to blood alcohol levels model
Authors: Sudsutad Weerawat , Thaiprayoon Chatthai , Aphithana Aphirak , Kongson Jutarat , Sae-dan Weerapan
Published: December 2024

The initial value problem in Cauchy-type under the $ (k, \psi) $-Caputo proportional fractional operators was our focus in this paper. An extended Gronwall inequality and its properties were analyzed. The existence and uniqueness results were proven utilizing the fixed point theory of Banach's and Leray-Schauder's types. The qualitative analysis included results for Ulam-Mittag-Leffler stability, which was also investigated. Using a decomposition principle, a novel numerical technique was presented for the $ (k, \psi) $-Caputo proportional fractional derivative operator. Finally, theoretical results were supported with numerical examples to demonstrate their practical application, especially to blood alcohol level problems.
“Un cattivo cartigiano”. Pirandello fascista nelle pagine di Giustizia e libertà (1934-1937)
Authors: Frabetti Anna
Published: December 2024

La question des rapports entre Pirandello et le fascisme est depuis longtemps au centre des débats qui visent soit à démontrer l'authenticité de son adhésion au régime, soit à en faire ressortir l’ambiguïté. C'est dans ce contexte que s’inscrivent les articles que Giustizia e Libertà consacre à Pirandello dans les années 1930 et qui sont publiés ici, en annexe. Des pages du journal antifasciste jaillit un portrait du dramaturge, dans la dernière période de sa vie, riche de contradictions et d'incohérences
Creazione e derisione nella poesia di Curzio Malaparte
Authors: Belletti Gabriele
Published: December 2024

L’article analyse la poétique de Curzio Malaparte, en se concentrant sur L’Arcitaliano. Cantate de 1928 et ses relations intertextuelles avec d’autres œuvres du corpus de l’auteur. En particulier, il fait apparaître une évolution thématique et stylistique en comparant le recueil de ‘28 avec Il battibecco de 1949, en mettant en évidence une maturation poétique. De plus, il discute du rôle de la poésie dans la critique sociale et politique de Malaparte, examinant les Cantate comme des exemples de sa capacité à réinterpréter la tradition. Enfin, il analyse la nature critique et satirique de sa poésie et son impact sur ses œuvres en prose.
Dans l’atelier du traducteur : adaptation ou traduction ? Salfi aux prises avec Fénelon ou bien les religieuses de Cambrai de Chénier.
Authors: Leone Evelina
Published: December 2024

L'article propose une analyse de la traduction italienne de la pièce de Marie-Joseph Chénier, Fénelon ou les religieuses de Cambrai, réalisée par Francesco Saverio Salfi. À travers des pistes de lectures, l’étude met en lumière les thèmes principaux de la pièce, les choix lexicaux et d'adaptation du traducteur italien. La traduction se transforme en un instrument de lutte politique par lequel Salfi diffuse de nouvelles idées, éduque le public et éveille les consciences.
Déprédation des cultures par la faune sauvage : comment articuler préservation de la biodiversité et évolution de l’agriculture ?
Authors: Miscopein Aliénor , Giguet-Chevalier Victor , Bassoleil Mary-Anne , Ruault Claire , Atlan Anne
Published: December 2024

L’évolution de l’agriculture depuis l’après-guerre a conduit à une spécialisation des exploitations et une simplification des assolements aujourd’hui remises en cause pour les externalités négatives qui leur sont associées. Diverses initiatives sur l’ensemble du territoire français encouragent la construction d’un tissu agricole diversifié plus adapté aux enjeux sociétaux et environnementaux contemporains. C’est le cas de Belle-Île-en-Mer, territoire insulaire sur lequel plusieurs initiatives locales ont été engagées depuis le début des années 2000 dans le but de maintenir et développer le tissu agricole, améliorer l’autonomie alimentaire et conserver les caractéristiques paysagères (paysage ouvert) faisant la renommée de l’île. Les tentatives de diversification de la production agricole et d’augmentation de l’autonomie des exploitations se heurtent cependant à la déprédation exercée sur les cultures par différentes espèces animales pouvant être regroupées sous le terme générique de « petite faune sauvage ». Cet article présente les résultats de travaux conduits en 2021 visant à mieux comprendre la problématique rencontrée par les agriculteurs et identifier des pistes de solutions. Ils ont permis d’identifier les espèces déprédatrices et les dégâts occasionnés, de mettre en évidence des pertes sur céréales de plein champ à hauteur de 30 % des semis cette année-là ainsi qu’un effet favorable de la présence de zones enfrichées à proximité des cultures sur la déprédation. L’analyse des entretiens menés avec l’ensemble des parties prenantes impliquées dans cette situation a permis d’analyser les dispositifs règlementaires et les jeux d’acteurs entourant la problématique.
Les lisières du Parc national de forêts comme témoin d’une mémoire environnementale
Authors: Guerin Agnès , Barrès Gabriel , Brochet Valentin , Chabroux Ulysse , Muller Capucine Garnier , Reist Amandine , Weingand Emma , Ronsin Gaëlle
Published: December 2024

Les parcs nationaux français cherchent désormais à protéger les interactions sociales et naturelles qui produisent leurs paysages. Les lisières sont un exemple d’entités du paysage mêlant de multiples dimensions. Elles forment une mémoire environnementale de la forêt en révélant des pratiques et usages très divers d’un même espace rural. De façon contemporaine, les lisières sont également un enjeu des politiques de la continuité écologique ou des préoccupations de cohabitation. En s’appuyant sur le terrain du Parc national de forêts, créé en 2019, un atelier d’enquête composé d’étudiants a voulu questionner de façon sensible l’écologie sociale des lisières agroforestières pour les acteurs de la protection de la nature. Premièrement, la sémantique autour des lisières fait apparaître un vocabulaire de l’esthétisme qui révèle des préoccupations et propriétés spécifiques à ces lieux. Deuxièmement, la lisière est paradoxalement un espace remarquable pour certains acteurs mais complètement inexistante et invisible pour d’autres. Enfin, ces lieux ou non-lieux retracent de façon dynamique les mémoires environnementales des forêts et de leurs usages sur ces territoires.
The Intersection of Climate Change and Global Health Security
Authors: Dahri Abdul Samad , Saraih Ummi Naiemah Binti , Memon Salman Bashir , Dahri Abdul Sami , Khan Muhammad Shahzeb , Rehman Junaid , Pahi Munawar
Published: December 2024

This chapter overviews the connection between climate change and the security of the world's health. Malnutrition, waterborne illnesses, and illnesses spread by insects and other animals are just a few of the health problems that are made worse by climate change and pose a serious threat to human health. In addition, the possible direct and indirect effects of climate change are discussed on human health, such as respiratory conditions, heat exhaustion, and issues with mental health. In order to combat impact of climate change on global health security, developed countries must reduce greenhouse gas emissions, offer financial and technical assistance, share their knowledge and expertise and technological resources such as climate monitoring tools and early warning systems.
The Influence of Green Knowledge Management on Digital Transformation, Green Innovation, Energy Efficiency, and Firm Sustainable Development
Authors: Sheikh Adnan Ahmed , Wisal Muhammad , Hassan Bilal , Hassan Nadir Munir , Khan Sajjad
Published: December 2024

This study investigates the rapid development of green knowledge management, digital transformation, green innovation adoption, and improved energy efficiencies that lead to enhanced corporate sustainability developments in light of knowledge management theory and green theory. The authors used a non-probability convenient sampling technique to gather data from 360 manufacturing firms and analyzed using PLS-SEM. The study's findings reveal that green knowledge management positively enhances digital transformation and innovation adoption for improved energy efficiency and a firm's sustainable development. This study provided valuable theoretical and practical enlightenment for managers and policymakers to promote digital transformation and green innovation adoption strategies to improve energy efficiency and sustainable development. The study has added a thoughtful contribution to the existing literature.
The Impact of Board Qualifications on the Complexity of Sustainability Reports
Authors: Merter Abdullah Kürşat , Balcioğlu Yavuz Selim , Çerez Sedat , Özer Gökhan
Published: December 2024

The boards of directors serve as an important control unit in the effective management of sustainability reports. Various characteristics, such as the experience and skills of the board members, the presence of female members on the board, and the size of the board, can affect the company's approach to sustainability issues. Therefore, the boards of directors of companies have a critical role in understanding sustainability reports. The objective of this study is to investigate the correlation between the intricacy of sustainability reports and the attributes of the board. For this purpose, firms listed on the Borsa Istanbul (BIST) between 2014 and 2022 were selected as the sample. The complexity of the reports was evaluated on the basis of the length of pages, words, and characters within the reports. The findings indicate a positive relationship between board size, gender diversity within the board, and the length of sustainability reports. Furthermore, it was found that firms with effective audit committees tend to have shorter sustainability reports.
Green Supply Chain Practices and Environmental Performance
Authors: Shah Adeel , Shah Obaidullah , Ali Saheer
Published: December 2024

Clothing is considered essential for human beings, providing cover and warmth and representing stature in society. The products manufactured by the sector on a global scale are gigantic in size and are categorized as prominent sectors, which are also prominent in terms of economic value in international trade. Billions of products are changing hands across the world and thus require more understanding of the upstream part of the global supply chain, especially the practices used in their ecosystem for production. In a similar pursuit, a study has been conducted on green supply chain management practices and their effect on the environmental performance of the Pakistani textile industry to transform into a chapter for a larger audience. By delving into the supply chain and operational procedures of textile manufacturers in Pakistan, the chapter uncovers their GSCM practices and their effects on environmental performance through empirical testing.
Examine the Adoption of Blockchain Technology Among Tourists
Authors: Sahu Pramendra , Singh Pravin Chandra , Kr Divya , Singh Sujay Vikram , Singh Vishal Kumar , Bakshi Shailja , Neelam Kumari , Kumar Pankaj , Keshari Utkarsh
Published: December 2024

Blockchain technology has become a hot topic of interest and has gained considerable attention in a range of research fields, including the tourism industry. It has completely transformed the way tourists experience things, but there is still ongoing research on its impact in the field of tourism. This study aims to identify the facilitators that help in the adoption of blockchain technology in an emerging economy like India. The study examines various factors that contribute to the ease of use and effectiveness of a system, including expectations of effort, security, availability of resources, social influence, and expectations of performance. Conducted in Raipur, the capital city of Chhattisgarh, with a sample size of 380 using convenience sampling. Findings indicate that all facilitators significantly impact blockchain adoption among tourists. Effort Expectancy was found to be the most influential factor, while Social Influence had the least impact. This study offers valuable insights into the adoption of blockchain technology among tourists, specifically in central India.
The Emergence of Crypto Travel
Authors: Raina Ashish
Published: December 2024

The rapid advancement and growth in adoption of crypto-currencies are revolutionizing the global travel industry. This chapter explores the emergence of “crypto travel,” where digital currencies such as Bitcoin and Ethereum are increasingly used for travel services. The chapter examines how blockchain enhances transparency, reduces transaction fees, and ensures the privacy and security of financial data. Platforms like Travala, alongside major travel companies experimenting with crypto payments, are leading this shift. However, the chapter also discusses challenges, including market volatility, limited merchant adoption, and regulatory uncertainties. As crypto travel evolves, it offers the potential to reshape the tourism landscape, providing tech-savvy travelers with innovative payment options while driving efficiency. The integration of digital currencies and blockchain technology marks a significant milestone in the future of global tourism.
Revolutionizing Air Travel in India
Authors: Seal Partho Pratim , Yadav Nagendra , Konar Rupam
Published: December 2024

Digital technology has transformed various sectors with aviation not being exceptional. Digiyatra a government-promoted app enhances the traveller's experience by streamlining the operation. A blockchain-based identity management system Digiyatra uses a digital identity system which stores travelers' information on a distributed ledger. The airports and the airlines adopt the system to enhance the security of travellers, reduce the waiting queues in airports, and provide seamless travel and great experience. The chapter explores the revolutionary role of Digiyatra in air travel in India. The study uses online reviews of travellers about their experience using the app. The findings of the study state that security, experience, efficiency, and digitization are key factors for adopting digiyatra. The study's results will assist the government in understanding adopting digital technologies which can redefine the Indian aviation industry and make it future-ready
Enhancing Guest Experience and Data Security in Hospitality
Authors: Dambhare Ankit , Rana Varinder Singh
Published: December 2024

This chapter examines how blockchain technology has a significant impact on data security and visitor experience in the hospitality industry. Blockchain provides a transparent and decentralized solution in a time when data security and trust are critical. This chapter clarifies blockchain's significance in transforming visitor interactions and protecting private data by going over its fundamental ideas and features. An unchangeable ledger system in blockchain technology serves as a basis for open and unhackable guest management systems. Hospitality businesses may increase operational efficiency and client happiness by using smart contracts to automate tasks like reservation and feedback gathering. Additionally, guest data security and privacy are guaranteed by blockchain's cryptographic algorithms, which reduce the possibility of breaches and unauthorized access. This chapter demonstrates the benefits and practical implications of blockchain implementation in hospitality environments using case studies and real-world experiences.
Exploring the Growing Threat of Cyber Risks and Vulnerabilities in the Hospitality Industry
Authors: Harit Priya , Singh Amrik , Agrawal Kritika , Verma Devangana , Bathla Gaurav , Raina Ashish
Published: December 2024

This chapter discussed the necessity of strong protective measures and the inherent challenges of cybersecurity in the hospitality sector. As hotels increasingly rely on digital systems to import guest experiences, they become prime targets for cybercriminals. The chapter lists major cyber threats and highlights their influence on customer confidence and financial stability. These threats include malware, phishing, Distributed Denial of Service (DDoS) attacks, and insider threats. It also addresses the human factor in cybersecurity. By examining the case studies of notable breaches impacting companies such as Marriott, IHG, and Hilton, the chapter offers valuable insights into the comprehensive cybersecurity strategies that include risk assessment, employee training, and the adoption of established frameworks. Cybersecurity awareness can strengthen the defence, safeguard sensitive data, and guarantee long term sustainability of the hospitality industry with leveraging cutting edge technologies.
Design and Development of Small-Scale, Industrial Compression Molding Machine for Bamboo Biocomposite Boards
Authors: Martinez Dan William , Tuazon Brian Jumaquio , Moreno Daniel , Obdin Kim Janzel
Published: December 2024

Bamboo production is one of the emerging sectors in the Philippines in terms of socioeconomic value and environmental sustainability. Its versatility in product design and sustainability from production to end-of-life has become popular in the local and foreign markets. However, challenges remain in utilizing bamboo and its potential as a sustainable material. During the post-processing of bamboo products, 33.5% to 70% of bamboo ends up as waste. One solution to the problem is utilizing bamboo wastes in biocomposite materials. However, the technology developed for bamboo-based biocomposite processing is only available in large industries. This project focuses on creating an industrial compression molding machine to efficiently transform bamboo wastes into biocomposite boards. The study employs a comprehensive methodology from computer-aided design and fabrication to machine and product testing and design of experiments. Results demonstrate optimal performance at 180°C and 45% waste content that meets industry standards. Beyond contributing to biocomposite production methodologies, this research addresses the imperative for sustainable practices in the evolving bamboo industry with broad potential applications in the industry.
A novel detection method for heteroduplex DNA using carbodiimide-induced interrupted primer extension
Authors: Tabone Tania , Cotton Richard , Mathew Ninan , Parkin J. Des , Savige Judy
Published: December 2024

Direct sequencing may be problematic in demonstrating mutations where inherited disease results from multiple different heterozygous variants in large genes. We describe here a novel mutation screening method based on the ability of carbodiimide to bind mismatched DNA and interrupt primer extension thereby identifying both a heterozygous variant and its location. This assay detected all four classes of DNA mismatch in 550 bp engineered plasmid fragments and in two dominantly inherited renal diseases. In patients with thin basement membrane nephropathy, the method demonstrated multiple variants within a single amplicon including some close to the primer binding site. This method also detected a complex mutation in medullary cystic kidney disease type 2 (c.278-289 del/insCCGGCTCCT) as multiple termination events and, furthermore, correctly identified five affected and 28 unaffected family members. Carbodiimide-induced interrupted primer extension identifies heterozygous variants in large or multiexonic genes, where the variants differ in each family, their locations are unknown, and even if there are multiple known non-pathogenic variants within the same amplicon. This assay incorporates a “universal” protocol that detects all types of mutations without the need for further optimization, and potentially detects mutations where the proportion of heteroduplex is less than 50%.
The mitochondrial housekeeping gene 16S is inappropriate as an internal standard in comparative studies of rare mitochondrial transcripts using S1-nuclease protection assays
Authors: Ebert Sandra , Breumlund Line , Nau Roland , Michel Uwe
Published: December 2024

The analysis of rare mitochondrial transcripts derived from the L-strand of the mitochondrial genome requires a sensitive method such as the S1-nuclease protection assay. We examined whether the ribosomal mitochon­drial transcript 16S is suitable as an internal standard in a multiplex S1-nuclease protection assay for the measurement of different mitochondrial transcripts. For reliable quantification of rare mitochondrial transcripts with the RNase protection assay, a minimum of 2 μg of total RNA is necessary. Standard curves of 16S RNA produced with total RNA from human kidney, liver, brain, and a human neuroblastoma cell line (SH-SY5Y) revealed dose-response relationships that were saturated already at less than 0.5 μg of total RNA. Therefore, 16S is inappropriate as an internal standard for analyzing mitochondrial transcripts with RNase protection assays when more than 0.5 μg of total RNA have to be analyzed.
Induced pluripotent stem cells: the long-expected revolution in medical science and practice?
Authors: Sorrentino Antonio
Published: December 2024

Within the matter of a few years, development of the somatic reprogramming technology to generate induced pluripotent stem (iPS) cells has contributed enormously to the stem cell research field. We learned that differentiated adult cells possess an unrestricted plasticity that allows them to be driven back to their embryonic or pluripotent state, but owing to the juvenile nature of this novel science chapter, there are many unanswered questions and dilemmas. It is indisputable, however, that iPS cells potentially could represent the jack-of-all-trades remedy in areas of medicine ranging from toxicology screening to regenerative medicine. In this review I will summarize the current strategies employed to reprogram somatic cells and the major promises and hurdles for the future of iPS cells.
Survival of the fittest or best adapted: HLA-dependent tumor development
Authors: Masucci Giuseppe V. , Andersson Emilia , Villabona Lisa , Helgadottir Hildur , Bergfeldt Kjell , Cavallo Federica , Forni Guido , Ferrone Soldano , Choudhury Aniruddha , Seliger Barbara , Kiessling Rolf
Published: December 2024

The major histocompatibility complex (MHC) comprises a set of genes that are critical to immunity and surveillance against neoplastic transformation. There is increasing evidence that the MHC antigens not only regulate antitumor immune responses in experimental animal models but directly correlate with survival and prognosis of patients with diverse types of cancers. MHC antigens may in the future function as potential biomarkers for prognosis and allow selection of cancer patients for intensive therapy.
Cancer immunoediting and dioxin-activating aryl hydrocarbon receptor: a missing link in the shift toward tumor immunoescape?
Authors: Ridolfi Ruggero , Guidoboni Massimo , Ridolfi Laura
Published: December 2024

The aryl hydrocarbon receptor (AhR), a member of the PAS protein family, is found in organisms as diverse as Drosophila melano­gaster, nematodes, and mammals. While several reviews have reported that AhR, once activated by agonist ligands, causes long-term effects such as modification of cell growth through cell cycle control, there is also recent evidence of its decisive role in immunosuppression. The most widely studied AhR agonist is 2,3,7,8-tetrachlorodibenzo-p-dioxin, which binds AhR with the highest known affinity, leading to profound suppression of both humoral and cellular immune responses, with praecox thymus involution, consequent thymocyte loss, and induction of T-cell apoptosis. Dioxin-AhR binding causes a decline in the number of dendritic cells and enhances apoptosis following their inappropriate activation. Dioxin-mediated activation of AhR also has a direct influence on the expansion of regula­tory T-cells CD4+CD25+ FoxP3+ (T-regs) and an adverse affect on CD8+ T-cell responses. Dioxin released from industrial and waste incinerators over the last few decades has caused widespread contamination of food, leading to its accumulation in fatty tissue in animals and humans. The elimination half-life of dioxin in humans (7-10 years) may favor the potentially continuous and long-lasting activation of AhR, leading to perpetual immune suppression and facilitating the onset, growth, and diffusion of tumors, especially in young people. In the cancer immunoediting hypoth­esis, which subdivides the relationship between tumor and immune system into three phases: elimination, equilibrium, and escape, it is thought that dioxin accumulation may cause an inevitable shift toward tumor escape.
Predictive molecular markers for EGFR-TKI in non-small cell lung cancer patients: new insights and critical aspects
Authors: Ulivi Paola , Calistri Daniele , Zoli Wainer , Amadori Dino
Published: December 2024

In recent years, a number of novel agents have been investigated that target specific molecular pathways in non-small cell lung cancer (NSCLC). A great deal of effort has been focused on identifying specific markers that predict treatment response, given that a tailored approach would maximize both the therapeutic index and the cost-effectiveness. The epidermal growth factor receptor (EGFR) pathway has emerged as a key regulator of cancer cell proliferation and invasion, and several specific EGFR inhibitors have been examined. Gefitinib and erlotinib are selective EGFR tyrosine kinase inhibitors (EGFR-TKIs), demonstrating good results in selected cases both in terms of objective response rate and of overall survival. At present, EGFR gene mutations are the best positive predictive factors for TKI therapy, and a number of other potential biomarkers are being investigated as additional positive or negative predictors of response. The correct selection of patients that could benefit from these innovative therapies, based on an accurate molecular characterization, is mandatory to provide the best clinical management. Currently, the main factor limiting the characterization of metastatic NSCLC patients is the small quantity of tumor cells available for molecular analysis. In this paper we provide an overview of the most important molecular predictive markers for EGFR-TKIs therapy in NSCLC patients, and focus attention on biological samples suitable for analysis and alternative sampling approaches such as plasma- or serum-derived DNA.
Development of network inference among LexA/RecA-dependent manner genes in the SOS response
Authors: Aburatani Sachiyo
Published: December 2024

The expression of many genes varies under different conditions. The relationships among genes can be identified from DNA microarray data. To better understand the SOS response, I developed a network model of whole LexA/RecA-dependent manner genes in two genotypes of Escherichia coli from expression data after ultraviolet (UV) irradiation. First, all LexA/RecA-dependent manner genes were estimated by a combination of the Mann-Whitney U test and hierarchical clustering. Second, the relationships between genes were inferred from a graphical Gaussian model combined with hierarchical clustering. Here, I incorporate a step-by-step procedure of the method developed in my previous study to identify interactions within larger clusters. The analysis suggested the presence of a sequential relationship between LexA/RecA-dependent manner gene groups in which the association between neighboring groups was positive while that between non-neighboring groups was negative. I suggest the inferred network provides information on the functional role of poorly defined genes whose expression patterns change according to LexA/RecA. Although relationships in the network require biological validation, the model presented here provides insights into potential LexA/RecA regulation following UV irradiation.
Expression of microRNA during bovine adipogenesis
Authors: Pratt Scott L. , Burns T. Ashley , Curry Erin , Duckett Susan K.
Published: December 2024

Studies have recently indicated that the adipogenic process and the expression of genes involved in lipid metabolism may be regulated in part at the post-transcriptional level by a class of small RNA called microRNA (miRNA). The objectives of this study were to i) determine if miRNAs are differentially expressed, and ii) evaluate expression of known miRNA targets in bovine adipocytes. Bovine adipose samples were collected from castrated males fattened on a high concentrate diet (C) or pasture (PA) and were frozen in liquid nitrogen and stored at -80°C, or used to generate primary stromal-vascular cells (SV). SV cells were cultured to confluence (Control) or differentiated at confluence and harvested 2 (D2), 6 (D6), or 12 (D12) days post-confluence. A 3x3 microarray analysis was performed comparing Control and differentiated samples. miR-21, -221, and -222 (P less than 0.05) were differentially expressed. qRT-PCR was conducted using the in vitro samples, and all three miRNAs were down regulated on D2 (P less than 0.05). miR-221 and -222 were decreased on D6 compared to Control (P less than 0.05), but only miR-222 expression was decreased at D12 (P less than 0.05) compared to Control. miR-21 increased in expression compared to Control on D12 (P less than 0.05). In vivo, only miR-21 expression was affected and it was reduced in PA compared to C fat samples (P less than 0.05). Two targets of miR-21 are Programmed Cell Death Protein 4 (PDCD4) and Phosphatase and Tensin Homolog (PTEN), and neither messenger RNA was differentially expressed in vitro (P greater than 0.05), but both messenger RNAs were elevated for PA compared to C (P less than 0.05). These data show that miRNAs are differentially expressed in adipose cells and tissue, and that miR-21 may be involved in adipocyte function by regulating the translation of PDCD4 and PTEN.
Molecular markers for prediction of risk of radiation-related injury to normal tissue
Authors: Ghilotti Marco , Pierotti Marco Alessandro , Gariboldi Manuela
Published: December 2024

Radiotherapy is one of the most effective methods for the treatment of cancer, but occurrence of adverse reactions developing in the co-irradiated normal tissue can be a threat for patients. Identification of individuals at risk of severe reaction is very difficult and considerable efforts have been made to correlate normal tissue toxicity with cellular responses to ionizing radiation. Genetic markers enabling to identify hyper-sensitive patients prior to treatment would considerably improve its outcome. Gene association studies should help to identify such markers. Expression levels of specific transcripts could be putative markers; in fact, different studies found associations between gene expression profiles in normal cells and the reaction of normal tissues to radiation therapy. The finding that ionizing radiation induces the deregulation of a high number of genes suggests that also microRNAs that affect the expression of a large number of target genes may be involved. This review briefly introduces the mechanisms of radiation-induced normal tissue toxicity and summarizes clinical research focused on the evaluation of molecular biomarkers for predicting risk of injury to normal tissue, mainly describing gene transcripts alterations.
Online resources for microRNA analysis
Authors: Alexiou Panagiotis , Maragkakis Manolis , Hatzigeorgiou Artemis G
Published: December 2024

The use of online tools for bioinformatics analyses is becoming increasingly widespread. Resources specific to the field of microRNAs are available, varying in scope and usability. Online tools are the most useful for casual as well as power users since they need no installation, are hardware independent and are used mostly through graphic user interfaces and links to external sources. Here, we present an overview of useful online resources that have to do with microRNA genomics, gene finding, target prediction and functional analysis.
Unusual 5'-regulatory structure and regulation of the murine Mlc1 gene: lack of promoter-specific functional elements
Authors: Henseler Darja , Turner Jonathan D. , Eckhardt Matthias , Van der Mark Maaike , Revsin Yanina , Lin Michelle K. , Kranz Thorsten , Muller Claude , Meyer Jobst
Published: December 2024

The MLC1 gene is involved in an autosomal recessive neurological disorder, megalencephalic leucoencephalopathy with subcortical cysts (MLC), which is characterized by macrocephaly during the first year of life and swollen white matter (leucoencephaly). Variants of MLC1 have also been associated with psychiatric disorders such as schizophrenia, major depression and bipolar disorder. Currently, little is known about the encoded protein (MLC1). Judging from its similarity to other known proteins, it may serve as a trans-membrane transporter. However, the function of the encoded protein and its gene regulation has not been investigated successfully so far. We investigated the 5’ region of the murine Mlc1 with respect to regulatory elements for gene expression. A promoter search and an in silico analysis were conducted. Luciferase reporter gene constructs with potential promoter regions were created to study promoter activity in vitro. We found two alternative first exons for the murine Mlc1 but were not able to detect any promoter activity for the investigated reporter gene constructs in different cell lines, thus pointing to the presence of essential cis-acting elements far outside of the region. In silico analysis indicated an uncommon promoter structure for Mlc1, with CCAAT-boxes representing the only noticeable elements.
HER2 splice variants and their relevance in breast cancer
Authors: Sasso Marianna , Bianchi Francesca , Ciravolo Valentina , Tagliabue Elda , Campiglio Manuela
Published: December 2024

The HER2 gene amplification occurs in 20-30% of breast cancer and is correlated with a poorer prognosis compared to HER2-negative disease due to increased proliferation and metastatic potential. Two major types of receptor inhibitors have been developed for therapy and one for each categories is currently used in clinic: i) the humanized monoclonal antibody trastuzumab, directed against the HER2 extracellular domain; and ii) the EGFR/HER2 dual tyrosine kinase inhibitor lapatinib. However, patients may develop resistance to drugs and show disease progression. Several resistant mechanisms have been explored and are still under investigation. Here, we focus our attention on the role played by the alternative splicing forms of HER2 in mediating HER2 oncogenic activity and in conditioning the response to HER2 therapies. Three HER2 splice variants have been described so far; the p100 and the herstatin gave raised to two secreted proteins of 100 kd and 68 kd, respectively that act as cell growth inhibitors. Herstatin has been described for its ability to interrupt the constitutive HER2 activation, but also for its capacity to hamper HER2 dimerization with the others HER receptors. Interestingly, herstatin, present as mRNA and protein in non cancerous tissue in areas adjacent to breast carcinoma, is absent as protein in 75% of mammary tumors, which indicates that cancer cells are protected by some intrinsic mechanism against the putative growth-inhibitory effects of this naturally occurring molecule. The third splice form of HER2 gene is the Δ16HER2, encoding for a receptor lacking exon16, whose absence determines a constitutive active dimers with transforming activity in vitro and in vivo. The Δ16HER2 binds to trastuzumab to a less extend, due to conformational changes of the extracellular domain. The Δ16HER2 accounts for almost 9% of the total HER2 transcripts in human breast cancers and, additionally, Δ16HER2 levels are supposed to increase proportionally at the increasing of the HER2 wild-type copy numbers in human primary breast cancers. The availability of a specific assay to determine and quantify the expression levels of this splicing form and the availability of Δ16HER2 transgenic mice models made this variant as the most promising for the development of biodrugs. Finally, HER2 carboxy-terminal fragments (CTFs), generated by alternative initiation of translation, were observed in breast cancer patients. In particular, 611-CTF was described to activate multiple signaling pathways since it is expressed as a constitutively active homodimer. Expression of 611-CTF led to development of aggressive and invasive mammary tumors and it was suggested to be a potent oncogene capable of promoting mammary tumor progression and metastasis.
Silencing of hpv16 e6 and e7 oncogenic activities by small interference RNA induces autophagy and apoptosis in human cervical cancer cells
Authors: Salazar-León Jonathan , Reyes-Román Fabiola , Meneses-Acosta Angélica , Merchant Horacio , Lagunas-Martínez Alfredo , Meda-Monzón Elizabeth , Pita-López María Luisa , Gómez-Cerón Claudia , Bermúdez-Morales Victor Hugo , Madrid-Marina Vicente , Peralta-Zaragoza Oscar
Published: December 2024

Cervical cancer is the second most common form of death by cancer in women worldwide and has special attention for the development of new treatment strategies. Human Papilloma Virus (HPV) persistent infection is the main etiological agent of this neoplasia, and the main cellular transformation mechanism is by disruption of p53 and pRb function by interaction with HPV E6 and E7 oncoproteins. This generates alterations in cellular differentiation and cellular death inhibition. Thus, HPV E6 and E7 oncogenes represent suitable targets for the development of gene therapy strategies against cervical cancer. An attractive technology platform is developing for post-transcriptional selective silencing of gene expression, using small interference RNA. Therefore, in the present study, we used SiHa cells (HPV16+) transiently transfected with specific siRNA expression plasmids for HPV16 E6 and E7 oncogenes. In this model we detected repression of E6 and E7 oncogene and oncoprotein expression, an increase in p53 and hypophosphorylated pRb isoform protein expression, and autophagy and apoptosis morphology features. These findings suggest that selective silencing of HPV16 E6 and E7 oncogenes by siRNAs, has significant biological effects on the survival of human cancer cells and is a potential gene therapy strategy against cervical cancer.
A new entropy model for RNA: part I. A critique of the standard Jacobson-Stockmayer model applied to multiple cross links
Authors: Dawson Wayne , Yamamoto Kenji , Kawai Gota
Published: December 2024

The Jacobson-Stockmayer (JS) model is used in a number of standard programs for calculating the conformational entropy of RNA (and proteins). However, it is shown in this study that, in certain limiting cases, the current form of this model can lead to highly unphysical conclusions. The origin of this behavior can be traced to misunderstandings that occurred during the development of the model as applied to folded, single-stranded RNA. Here we show that an alternative model known as the cross linking entropy (CLE) model can overcome these issues. The principal object that causes entropy loss on a global scale in the CLE model is the stem, the primary measure of structural order in such coarse-grained calculations. The principal objects in the JS-model are various types of loops, and, with the exception of the hairpin loop, they are topologically local in character. To extract experimentally measurable variables, a simplified version of the CLE model is developed that resembles many features of the contact order model used in RNA and protein folding. These modifications are then applied to single molecule force-extension experiments (molecular tweezers) to extract quantitative information. It is further shown that a crude derivative of the CLE model itself can be derived directly from the JS-model when the misunderstandings are examined and corrected.
High mobility group A-interacting proteins in cancer: focus on chromobox protein homolog 7, homeodomain interacting protein kinase 2 and PATZ
Authors: Fedele Monica , Pierantoni Giovanna Maria , Pallante Pierlorenzo , Fusco Alfredo
Published: December 2024

The High Mobility Group A (HMGA) proteins, a family of DNA architectural factors, by interacting with different proteins play crucial roles in neoplastic transformation of a wide range of tissues. Therefore, the search for HMGA-interacting partners was carried out by several laboratories in order to investigate the mechanisms underlying HMGA-dependent tumorigenesis. Three of the several HMGA-binding proteins are discussed in this review. These are the Chromobox family protein (chromobox protein homolog 7, CBX7), the homeodomain interacting protein kinase 2 (HIPK2) and the POZ/domain and Kruppel zinc finger family member, PATZ. All of them play a critical role in tumorigenesis, and may also be independent markers of cancer. Their activities are linked to cell cycle, apoptosis and senescence. In this review, we discuss the properties of each protein, including their effect on HMGA1 functions, and propose a model accounting for how their activities might be coordinated.
Practical strategies for the evaluation of high-affinity protein/nucleic acid interactions
Authors: Altschuler Sarah E. , Lewis Karen A. , Wuttke Deborah S.
Published: December 2024

The quantitative evaluation of binding interactions between proteins and nucleic acids is highly sensitive to a variety of experimental conditions. Optimization of these conditions is critical for obtaining high quality, reproducible data, particularly in the context of very high affinity interactions. Here, we discuss the practical considerations involved in optimizing the apparent binding constant of an interaction as measured by two common quantitative assays, electrophoretic mobility shift assay and double-filter binding when measuring extremely tight protein/nucleic acid interactions with sub-nanomolar binding affinities. We include specific examples from two telomere end-binding protein systems, Schizosaccharomyces pombe Pot1 and Saccharomyces cerevisiae Cdc13, to demonstrate potential experimental pitfalls and some useful strategies for optimization.
Same-day identification and genotypic antibiotic resistance testing of Mycobacterium tuberculosis complex and non-tuberculous mycobacteria from positive blood culture bottles – a proof of principle assessment
Authors: Camaggi Anna , Minisini Rosalba , Tonello Stelvio , Mantovani Monia , Caroppo Maria Simona , Merlo Anna , Cordovana Miriam , Kostrzewa Markus , Frickmann Hagen , Andreoni Stefano
Published: December 2024

Background and Aims: patients suffering from systemic mycobacterial spread are at high risk of unfavorable clinical outcomes. Rapid microbiological diagnosis, however, is complicated due to the very slow cultural growth of mycobacteria. To facilitate the diagnostic workflow, we assessed a workflow allowing mass spectrometry-based identification and molecular resistance testing of mycobacteria directly from blood culture pellets.
Materials and Methods: for this study, 50 blood cultures spiked with n=10 Mycobacterium tuberculosis (MTC) isolates and n=40 isolates belonging to 12 other species of non-tuberculous mycobacteria (n=13 M. abscessus complex, n=5 M. avium, n=3 M. chimaera, n=5 M. fortuitum, n=5 M. intracellulare, n=2 M. lentiflavum and n=2 M. mucogenicum, n=1 for each one of the species M. elephantis, M. hassiacum, M. marseillense, M. nebraskense and M. parascrofulaceum) were used next to two clinical cases of a disseminated infection in HIV patients.
Results: the application of the MBT Sepsityper® kit allowed the correct species level identification by applying mass spectrometry as well as correct molecular resistance testing results as compared to the diagnostic reference approach applied with mycobacterial culture material.
Conclusions: in conclusion, the results provide a proof-of-principle of the suitability of the assessed potential workflow in order to achieve a shortened time-to-result for the diagnosis of systemic mycobacterial infections. Future studies in high endemicity settings are desirable to assess the clinical applicability and impact of such a shortened workflow.
Immune responses to Covid-19 vaccination in cancer patients
Authors: Campagna R. , Dominelli F. , Zingaropoli M. A. , Ciurluini F. , Grilli G. , Amoroso A. , De Domenico A. , Amatore D. , Lia M. S. , Mastroianni C. M. , Ciardi M. R. , De Santis R. , Antonelli G. , Turriziani O.
Published: December 2024

Not available.
Vancomycin variable enterococci (VVE) responsible for two cases of severe bloodstream infections in immunocompromised patients colonized with vancomycin resistant Enterococcus faecium (VRE)
Authors: Giardina A. , Meschiari M. , Venturelli C. , Fortuna S. A. , Conti P. , Venturelli I. , Del Monte M. , Dessilani A. , Mussini C. , Campanile F. , Sarti M.
Published: December 2024

Not available.
Evolution of intestinal microbiota and role of fecal microbiota transplant for Clostridioides difficile recurrent infection management: a one-year experience in a Tertiary regional hospital
Authors: Bottino P. , Gotta F. , Vay D. , Pizzo V. , Ferrara L. , Gota C. , Novi M. L. , Rocchetti A.
Published: December 2024

Not available.
Evaluation of the CMV RNA elite MGB kit for monitoring CMV infections in pediatric solid organ transplant
Authors: Arosio M. , Passera I. , Nicastro E. , Guarneri D. , Fazioli M. , Napolitano G. , D'Antiga L. , Farina C.
Published: December 2024

Not available.
Evaluation of a multiplex real-time PCR panel for the diagnosis of intestinal helminths
Authors: Schillaci N. F. J. , Cuntrò M. , Oliva E. , Clemente L. , Varani S. , Menegotto N. , Besutti V. , Bruno A. , Petrullo L. , Oggioni D. , Carducci A. , Ghia C. , Mirri P. , Farina C. , Raglio A. , CoSP-AMCLI Gdl
Published: December 2024

Not available.
Performance evaluation of a new RT-PCR assay for the screening of carbapenemase-producing enterobacterales (CPE) and Acinetobacter spp.
Authors: Tocci G. , Lepera V. , Palladini G. , Zappavigna A. , Cordini C. , Gorrini C. , La Vergata L. , Schiavo R. , Lo Cascio G.
Published: December 2024

Not available.
Quadriceps Strength Does Not Associate with Gait Adaptation Ability in Individuals with Anterior Cruciate Ligament Reconstruction
Authors: Evans-Pickett Dr. Alyssa , Franz Dr. Jason R. , Padua Dr. Darin A. , Kiefer Dr. Adam , Schwartz Dr. Todd A. , Blackburn Dr. J. Troy , Pietrosimone Dr. Brian
Published: December 2024

Context

Postoperative muscle weakness contributes to the development of aberrant gait biomechanics that persist following traditional anterior cruciate ligament reconstruction (ACLR). However, it is unknown if quadriceps weakness impedes the ability of ACLR patients to modify gait biomechanics using a real-time gait biofeedback (RTGBF) intervention.

Objective

The purpose was to determine if quadriceps strength associates with the ability to modify vertical ground reaction force (vGRF) during a RTGBF intervention.

Design

Cross-Sectional Study

Setting

Research Laboratory

Participants

35 individuals with unliateral ACLR (Time since ACLR= 32 ± 16 months; 22 Females, 13 Males)

Main Outcome Measures

Peak vGRF was evaluated during a baseline walking trial, and three 250-step randomized RTGBF walking trials which cued an increased average peak vGRF of the baseline walking trial by 5%, 10%, or 15%. The ability to modify gait was reported as changes in pvGRF (ΔpvGRF; BW) and root mean square error (RMSE) of the peak vGRF relative to the feedback target (pvGRF RMSE; BW). We also calculated quadriceps strength.

Results

There were no significant associations between strength (Mean: 2.56 ± 0.75 Nm/kg, Range: 0.84-4.6 Nm/kg) and ΔpvGRF (5% ΔpvGRF: 0.04 ± 0.03 BW, 10% ΔpvGRF: 0.10 ± 0.03 BW, 15% ΔpvGRF: 0.15 ± 0.04 BW) nor strength and RMSE (5% RMSE: 0.04 ± 0.02 BW, 10% RMSE: 0.05 ± 0.02 BW, 15% RMSE: 0.08 ± 0.04 BW) for any of the 3 RTGBF trials (R2: 0.003-0.025; P: 0.37-0.77).

Conclusions

The magnitude of quadriceps strength did not influence the ability to modify gait using RTGBF. These data suggest that it may be unnecessary to wait for quadriceps full strength recovery to capitalize on the benefits of RTGBF following ACLR.