bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Kat2b impairs intraflagellar transport and the Hedgehog signaling pathway in primary cilia
Authors: Cha Hwayeon , Jun Jae Hee , Ko Je Yeong , Kim Ho-Shik , Yoo Kyung Hyun , Park Jong Hoon
Published: September 2024

Primary cilia are sensory organelles that regulate various signaling pathways. For this, microtubules work as a highway, and they are tuned with post-translational modifications, such as acetylation. However, the role of acetylation in the regulation of primary cilia remains uncertain. Here, we identified K (lysine) acetyltransferase 2B (Kat2b) as a novel regulator of primary cilia. Kat2b localizes to the cytosol, centrosome, and the cilium basal body. Also, the basal expression of Kat2b gradually increases during ciliogenesis. Kat2b regulates the rate of cilia assembly and the acetylation of α-tubulin via its catalytic activity. The loss of Kat2b reduces the recruitment of intraflagellar transport (IFT) components to the ciliary axoneme and impairs Hedgehog signaling activation. In addition, Kat2b-knockout mice show mild abnormalities and ciliary IFT defect in kidneys. Thus, our new findings establish a link between acetylation regulated by Kat2b and its relevance to ciliary assembly and function.
Decoding Synthetic News: An Interpretable Multimodal Framework for the Classificationof News Articles in a Novel News Corpus
Authors: Schlee Michael , Kant Gillian , Ehrling Christoph , Säfken Benjamin , Kneib Thomas
Published: September 2024

Recent advancements in Artificial Intelligence (AI), notably the development of Large Language Models (LLMs)and text-to-image diffusion models, have facilitated the creation of realistic textual content and images. Specifically, platformslike ChatGPT and Midjourney have simplified creation of high-quality text and visuals with minimal expertise and cost. Theincreasing sophistication of Generative AI presents challenges in ensuring the integrity of news, media, and information quality,making it increasingly difficult to distinguish between real and artificially generated textual and visual content. Our workaddresses this problem in two ways. First, by means of ChatGPT and Midjourney we create a comprehensive novel multimodalnews corpus named SyN24News based on the N24News corpus, on which we evaluate our model. Second, we develop a novelexplainable synthetic news detector for discriminating between real and synthetic news articles. We leverage a Neural AdditiveModel (NAM) like network structure that ensures effect separation by handling input data in separate subnetworks. Complexstructures and patterns are extracted by deep features from unstructured data, i.e. images and texts, using fine-tuned VGGand DistilBERT subnetworks. We ensure further explainability by individually processing carefully chosen handcrafted textand image features in simple Multilayer Perceptrons (MLPs), allowing for graphical interpretation of corresponding structuredeffects. Our findings indicate that textual information are the main drivers in the decision finding process. Structured textualeffects, particularly Flesch-Kincaid reading ease and sentiment, have a much higher influence on the classification outcomethan visual features such as dissimilarity and homogeneity.
Single-cell RNA sequencing of murine limbal epithelia reveals Gas1 as a novel stem/progenitor cell marker for the corneal epithelium
Authors: Richardson Alexander , Corley Susan , Delic Naomi , Li Hue , Lloyd Andrew , Girolamo Nick
Published: September 2024

The corneal epithelium is endowed with a rare population of stem cells that reside within the limbus, a circumferential transition zone that partitions the cornea from the conjunctiva, thus referred to as limbal epithelial stem cells (LESC). Despite the surge in investigations using single-cell RNA sequencing (scRNA-seq) of the ocular surface, a unifying marker(s) that distinguish these cells from their progeny is yet to be identified. We used a keratin (K)-14-driven lineage-tracing system and SmartSeq-2 single-cell transcriptomics in 5-60-week-old mice to interrogate the identity of limbal epithelia. Four cell clusters were identified, derived from both Confetti+ and Confetti− cells (clusters 0–3), with cluster 3 designated to harbor progenitor cells. We found one gene of interest in cluster 3, growth arrest-specific gene 1 (Gas1) coding for a cell-surface protein. PCR, flow cytometry and immunofluorescence disclosed this gene to be rarely expressed in limbal epithelial cells. Gas1 was also co-expressed with K14 in both young and old mice and upregulated following a mild mechanical debridement injury to the central cornea. The cell-surface expression of this antigen can be used to identify, extract and enrich progenitor cells for downstream molecular investigations and for generating better-quality cell-based grafts to treat severe corneal disease.
Neural Representation and Semantic Segmentation for Enhanced Underwater Imaging
Authors: Song Jinhao , Wang Chenli , Song Xiaoqiang
Published: September 2024

Underwater images are often plagued by low brightness, contrast, and blurred vision due to sediment and light scattering, hindering effective feature extraction. This paper proposes SGNeR, a novel underwater image enhancement model leveraging semantic segmentation and implicit neural representation. SGNeR combines real and augmented scenes to retain more image details, utilizing semantic segmentation as supervision to improve image quality and segmentation accuracy. To reduce dependence on paired training data, a triple-closed-loop constraint module enables self-supervised learning. Thorough experiments demonstrate that SGNeR outperforms state-of-the-art methods, achieving superior visual and quantitative results on various benchmarks. Our approach offers a robust, data-driven solution for underwater image enhancement, with promising applications in marine exploration and research. The dataset we used and the example code are publicly available at this link : https://github.com/ssssxw/SGNeR
Dual Inhibition of AChE and MAO-B in Alzheimer's Disease: Machine Learning Approaches and Model Interpretations
Authors: Hou Qinghe , Li Yan
Published: September 2024

Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases. Given the multifactorial pathophysiology of AD, monotargeted agents can only alleviate symptoms but not cure AD. Acetylcholinesterase (AChE) and Monoamine oxidase B (MAO-B) are two key targets in the treatment of AD, molecules that inhibiting both targets are considered promising avenue to develop more effective AD therapies. In the present work, a dual inhibition dataset containing 449 molecules was established, based on which six machine-learning algorithms (KNN, SVM, RF, GBDT, LGBM and DNN) four fingerprints (MACCS, ECFP4, RDKitFP, PubChemFP) and DRAGON descriptors were combined to develop 30 classification models in which GBDT model paired with MACCS and especially ECFP4, achieved the best performance across multiple metrics (Accuracy = 0.89, Precision = 0.88, Recall = 0.92, F1 Score = 0.90, MCC = 0.70). Moreover, based on the curated bioactivity datasets of AChE and MAO-B, regression models were developed to predict pIC50 values. For the AChE inhibition task, GBDT and SVM demonstrated the best performance (MSE = 0.43, MAE = 0.47, R2 = 0.75). The SVM algorithm emerged as the most effective for MAO-B inhibition (MSE = 0.35, MAE = 0.45, R2 = 0.77). The SHAP algorithm was used to interpret the optimal models, identifying and analyzing the key substructures and properties for both dual-target and single-target inhibitors. The interactions of these structural fragments with both targets were further validated using molecular docking.
Effective Supervision in Doctoral Studies through Constructive and Motivational Feedback: The CoMFeS Model
Authors: Singh Manvender Kaur Sarjit
Published: September 2024

This study investigates the critical role of effective supervision in the successful completion of doctoral studies, with a focus on constructive and motivational feedback. By examining both personal and professional dynamics between students and supervisors, the research emphasizes the importance of sustainable relationships throughout the doctoral journey. Drawing from qualitative data through semi-structured interviews and observations, this study highlights the significance of timely, specific, and supportive feedback in fostering student motivation, enhancing research skills, and improving academic performance. The findings suggest that effective feedback leads to higher student satisfaction, better research outcomes, and stronger supervisor-student relationships. Practical recommendations for supervisory training and feedback delivery are offered, aiming to enhance supervisory practices and inform institutional policies in doctoral education globally, particularly in the Malaysian context.
Fetal and Neonatal Outcomes in Booked vs. UnBooked Deliveries: A Systematic Review and Meta-analysis of the Global Literature
Authors: Mansoor Javeria , Hafeez Uffaira , Khan Noor Ullah , Ali Ahtisham , Zubair Rooja , Swathi N. L. , Nadeem Abdullah , Mansoor Faareah
Published: September 2024

Purpose
A booked case is an indicator of antenatal care (ANC), embodying a proactive approach to pregnancy care, whereas unbooked deliveries describe scenarios in which pregnant women delay seeking ANC, which may cause adverse fetal outcomes and lead to neonatal morbidity and mortality. Despite extensive exploration of the effects of ANC on maternal and fetal health, a detailed review comparing fetal outcomes in booked versus unbooked cases was lacking. Our study aimed to quantify the effects of ANC on fetal and neonatal outcomes through a comprehensive meta-analysis of booked and unbooked cases.
Methodology
This review was registered in PROSPERO (Registration No: CRD42024526568). Two databases were systematically searched, PubMed and Google Scholar, with a time filter of 2003–2023. Quality was assessed on the basis of the Newcastle‒Ottawa scale for cohort studies and the modified version for cross-sectional studies. The main outcomes were neonatal mortality, low Apgar scores, low birth weight (LBW), macrosomia, meconium aspiration and birth asphyxia. The secondary outcomes were neurological symptoms, neonatal intensive care unit (NICU) admissions, congenital anomalies, jaundice and neonatal sepsis. A random-effects model was used to evaluate the pooled effect size of the odds ratio (OR).
Results
In total, 28 studies were included in the final review, with the majority (n = 24) originating from low to middle-income countries. For the majority of the outcomes, being booked was found to be protective on the basis of pooled ORs, i.e., neonatal mortality (OR 0.30; 95% CI 0.15–0.63, I² = 96%), low APGAR scores at 1 minute (OR 0.33; 95% CI 0.29–0.38, I2 = 92% and 5 minutes (OR 0.16; 95% CI 0.08–0.32, I2 = 91%), LBW (OR 0.36; 95% CI 0.30–0.43, I2 = 46%), jaundice (OR 0.48; 95% CI 0.19–1.25, I2 = 74%), MAS (OR 0.36; 95% CI 0.18–0.70, I2 = 64%), neurological symptoms (OR 0.34; 95% CI 0.13–0.85, I²=20%), neonatal sepsis (OR 0.56; 95% CI 0.37–0.86, I2 = 17%), asphyxia (OR 0.39; 95% CI: 0.32–0.49; I2 = 0%) and however, we did not find any difference between booked and unbooked deliveries in terms of macrosomia (OR 0.99; 95% CI: 0.53–1.83, I² = 32%) and congenital anomalies (OR 0.09; 95% CI 0.35–2.29 I2 = 83%). The publication bias was minimal.
Conclusion
This meta-analysis provides substantial evidence that booked deliveries have significantly better fetal outcomes across a broad spectrum than unbooked deliveries do; therefore, interventions that improve ANC coverage need to be implemented to reduce adverse fetal outcomes.
Optimizing Pretraining Datasets for Large Language Models Through Recursive Perplexity Correlations
Authors: Audrad Samuel , Sullivan James , Bennett Olivia , Rossi Xavier
Published: September 2024

The exponential expansion of textual data has catalyzed the development of sophisticated language models, enabling unprecedented levels of language comprehension and generation. Introducing perplexity correlations as a mechanism for optimizing pretraining datasets constitutes a groundbreaking and substantial advancement, significantly enhancing the quality and effectiveness of the data employed in language model training. Through the careful analysis of perplexity scores in relation to various dataset attributes, this novel approach facilitates the identification and refinement of high-quality data segments, thereby constructing a more coherent and representative training corpus. The application of this methodology to the Mistral Large Language Model resulted in notable reductions in perplexity scores and marked improvements in performance across standard benchmarking evaluations. These enhancements demonstrate the critical importance of data quality in the training of language models and demonstrate that strategic dataset optimization via perplexity correlations can substantially elevate model performance and reliability. Consequently, this study provides a robust framework for ongoing advancements in language model development, emphasizing the significant role of data refinement in achieving superior natural language processing capabilities.
Сборник статей по материалам научно-технической конференции института технологических машин и транспорта леса по итогам научно-исследовательских работ 2017
Authors: Орлов В.В. , Бачериков И.В. , Соколова В.А.
Published: September 2024

В сборнике представлены материалы докладов научно-технической конференции по итогам научно-исследовательских работ 2017 года, которая проходила с 26 января по 2 февраля 2018 года в Институте технологических машин и транспорта леса Санкт-Петербургского государственного лесотехнического университета. Тематика конференции охватывает широкий круг вопросов лесопромышленного комплекса. Сборник предназначен для работников лесной и деревообрабатывающей промышленности, аспирантов, студентов и преподавателей ВУЗов. Опубликовано в редакции авторов с незначительными техническими правками. Сборник не рецензируемый.
Biological gene therapy for psoriasis: more than just skin clearance
Authors: Zhukova О. V. , Artemyeva S. I.
Published: September 2024

Psoriasis is recognized as a systemic inflammatory disease, significantly affecting all major aspects of patients’ health, requiring a timely comprehensive approach to treatment. This approach should improve the overall well-being of patients and consider the psychosocial aspects of their lives. Special attention in modern research is given to psoriatic arthritis (PsA), which affects up to 30% of patients with psoriasis. There is growing interest in the possibility of stopping the progression of the psoriatic process and preventing the manifestation of PsA. Recent studies have shown that timely treatment with genetically engineered biological agents (biologics) can halt disease progression and prevent the development of disabling complications. The article discusses key clinical and immunological markers that can predict the development of PsA, opening pathways for earlier and targeted therapy. Special attention is given to the role of guselkumab, a monoclonal antibody targeting interleukin-23, in preventing the development of PsA in high-risk patients. Clinical observations of three patients with psoriasis treated with guselkumab showed not only complete skin clearance (PASI 0) but also positive changes in all major parameters of psoriasis severity, sustained remission of the skin process, and positive dynamics of manifestations of psoriatic onychodystrophy, which is currently considered the main predictor of PsA. These results indicate suppression of systemic inflammation and control of disease progression risk. The significant overall improvement in patient condition, along with the key indicator of therapy effectiveness – improved quality of life emphasizes the importance and efficacy of timely initiation of targeted therapy in patients with psoriasis with certain aggravating factors.
Neuralink: Entre o desenvolvimento e os neurodireitos
Authors: Cassiani Arthur Gonçales , Marchetto Patrícia Borba
Published: September 2024

Os implantes de chips cerebrais produzidos pela empresa Neuralink, do bilionário Elon Musk, prometem conectar o cérebro humano a computadores, com objetivos diversos, entre eles: combater a paralisia cerebral, a cegueira e, até mesmo, permitir a telepatia humana. Referido equipamento trata-se se uma sonda com mais de 3.000 eletrodos, inserida diretamente no córtex cerebral do paciente, e promete representar a próxima geração de estimulação cerebral profunda. Contudo, os riscos inerentes à usabilidade de tais modelos precisam ser analisados, pois, em caso de sucesso da empreitada, grandes corporações teriam acesso irrestrito até mesmo ao cérebro dos indivíduos sujeitos ao implante. Dessa forma, uma ampla gama de Direitos Humanos poderia ser colocada em xeque, sendo necessário um crítico debate acerca do uso desse tipo de tecnologia no corpo humano. Foi adotada como metodologia de pesquisa a análise bibliográfica, com o levantamento e a análise de produções acadêmicas existentes acerca das questões suscitadas. As conclusões alcançadas indicam que, conquanto haja um potencial transformador médico e terapêutico, a partir do aludido implante cerebral em pessoas paralisadas ou com determinadas doenças, deve-se ter em conta um padrão ético e responsável, de modo a evitar o uso indiscriminado de referida tecnologia para a invasão de privacidade dos sujeitos envolvidos, especialmente a respeito da interpretação de pensamentos, geolocalização e segurança das informações. Portanto, esse contexto complexo e transformador exige uma análise aprofundada das motivações e implicações da prótese cerebral, à medida que são desenvolvidas novas tecnologias disruptivas, que agora dependem do aperfeiçoamento de um novo padrão neuroético.
A CONTRIBUIÇÃO DA SAÚDE PARA O FORTALECIMENTO DAS REDES: O AVANÇO NA GESTÃO PÚBLICA
Authors: Cardoso Juliana Aparecida Fialho , Milagres Clarice Santana , Tavares Bruno , Silva Edson Arlindo
Published: September 2024

A administração pública brasileira passou por grandes mudanças ao longo dos séculos, essas mudanças acompanharam uma nova forma de pensar sobre as organizações (racionalidade instrumental e substantiva), isso refletiu em novos formatos de gestão pública. Nesse contexto, o Sistema Único de Saúde (SUS), a partir da Constituição Federal de 1988 (CF/88), contribuiu para uma descentralização da gestão pública e fortaleceu os sistemas de redes. O questionamento necessário se faz. De que forma a reorganização do Governo Federal (através da Constituição de 1988) aconteceu e quais os principais benefícios alcançados no que tange as temáticas SUS e sistemas de rede? Este trabalho propõe que, apesar dos avanços dos modelos de administração pública, o que se observa hoje, é um sistema híbrido em que ainda prevalece um sistema patrimonialista, no qual as prefeituras e os processos de corrupção acabam por impedir a real efetivação do SUS, prejudicando assim um avanço efetivo dos sistemas de redes de saúde, assim como toda economia pertencente a esse sistema. Ademais, a cultura do “jeitinho” brasileiro acaba fortalecendo essa forma de agir.
CAPITALISMO FINANCEIRO, GLOBALIZAÇÃO E TRANSFORMAÇÕES NO MUNDO DO TRABALHO
Authors: Ferreira Oséias Soares , Vicente Zuleica Cristina Mizael
Published: September 2024

Nossa intenção neste texto é descrever a partir da financeirização da economia e da globalização os efeitos do capitalismo financeiro no mundo do trabalho. Nesse sentido, destacamos as características do capitalismo em sua fase atual e sua influência nas relações trabalhistas. A sustentação teórica do presente texto está embasada principalmente nos estudos de Antunes (2010), Boltanski (2009), Gorz (2005), Harvey (2010) e Leite (1994/2004/2014). Optamos por utilizar o recorte espaço – temporal, entendendo o capitalismo a partir da crise econômica do final dos anos de 1960 e inicio dos anos de 1970, sua transformação a partir daí, bem como as implicações no mundo do trabalho.
CRESCIMENTO E QUALIDADE DE GIRASSOL ORNAMENTAL TRATADOS COM PACLOBUTRAZOL
Authors: Pêgo Rogério Gomes , Mozar Ana Paula de Souza , Veigas Hugo Berçot
Published: September 2024

O girassol é uma planta ornamental cultivada para mercado de flor de corte ou flor de vaso; no entanto, para a sua comercialização como planta envasada, é necessário o controle do seu crescimento em altura, que pode ser realizado com o paclobutrazol. Dessa forma, o objetivo do trabalho foi avaliar o crescimento e a qualidade do girassol ornamental, cultivado em vasos, sob diferentes doses de paclobutrazol. Para isso, foi utilizada a variedade de girassol ‘Anão de Jardim’, que foi tratada com 5 doses paclobutrazol (0; 1; 2; 3; 4 mg L-1) em 5 repetições. Conclui-se que a dose de 3,4 mg L-1 e 2,0 mg L-1 de paclobutrazol possibilita a produção de plantas de girassol de primeira classe e segunda classe, respectivamente, de acordo com os critérios de qualidade Veiling Holambra. O paclobutrazol não afetou o desenvolvimento das plantas para a variável diâmetro do disco floral, diâmetro da flor, número de folhas e diâmetro do caule, o que permitiu melhor equilíbrio da planta com o vaso utilizado para cultivo.
Green and Effective: Chitosan Blends with Fish Collagen and Aloe vera Exudate
Authors: R. L. C. Gonçalves Pâmella , S. Penha Rosiane , J. F. Cardoso Jaciene , R. Guimarães Amanda , B. Bezerra Cícero Wellington
Published: September 2024

Chitosan (CS) blends with collagen (CL) and Aloe vera (AV) have gained significant attention in the biomedical field due to their biocompatibility, biodegradability, and potential for wound healing applications. In this study, we investigated the preparation and characterization of CS/CL and CS/AV blends using selective precipitation and co-precipitation techniques. The synthesis processes were analyzed for yield and 4-hydroxyproline content (in CS/CL blends). The materials were characterized using bromatological analyses, viscosity measurements, Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), and scanning electron microscopy (SEM). These eco-friendly methods effectively promoted interactions between the biopolymers, resulting in homogeneous blends with tunable properties. Besides, they are simple, fast, safe, and require minimal infrastructure. This study demonstrated that selective precipitation and co-precipitation are effective methods for producing chitosan/collagen and chitosan/Aloe vera blends. These methods foster interactions and miscibility between the biopolymers, as confirmed by FTIR, XRD, viscosity, and 4-Hy content analyses. They also align with green chemistry principles by avoiding organic solvents, reducing environmental risks, and minimizing waste. The high yields achieved, especially for CS/AV blends (exceeding 96%), make these materials compatible with lyophilization procedures. The absence of segregated phases after appropriate washing underscores their suitability for pharmaceutical formulations and other applications.
Inclusion of water age in conjunctive optimal operation of water and power networks
Authors: Shmaya Tomer , Ostfeld Avi
Published: September 2024

Water distribution systems (WDSs) are vital infrastructures designed to deliver water safely to consumers. This complex system necessitates continuous operational decisions, often optimized for efficiency. WDSs rely on power grids (PGs) to operate pumps and treatment facilities. PGs, likewise crucial, require strategic management to meet demand and environmental standards. Integrating the operation of both systems has garnered attention for its potential cost, energy, and environmental benefits. By leveraging the interconnection, trade-offs can be assessed, leading to improved solutions. Past research primarily focused on cost or carbon emissions as well as on hydraulic and voltage constraints. However, this study examines the impact of power systems on water quality, particularly water age, a key operational concern. Incorporating PGs into the optimal operation problem may alter flow directions, thereby influencing water age. Through mathematical modelling, this study evaluates these effects and applies them to simple case studies, demonstrating the influence of PG operation on water quality. Results demonstrate how tank constraints affect water age and show that a conjunctive operation approach, although beneficial for reduction of cost and energy consumption, can be damaging for water quality.
Nanomedicine in Management of Cerebral Infarction and Brain Cancer: Role of Inflammation
Authors: Kumar Vikas , Al-Abbasi Fahad , Anwar Firoz , Lal Jonathan A.
Published: September 2024

Introduction:

Cerebral infarction, the blockage of blood vessels in the brain,
is generally an age-related illness. Factors such as unhealthy diets, stressful behaviours
and decreased environmental consistency with physiological barriers also contribute to
increased casualties. Long-term brain function reconstruction and successful drug therapy
are needed. The most frequent malignant brain tumour, glioblastoma, has been linked
to variations in mitochondrial ROS, chaperone-mediated autophagy, and the interaction
between lncRNA (BC200) and miRNA. Glioblastoma stem cells express high levels of
ATP/P2X7 receptors, promoting survival by activating M2 muscarinic receptors.

Areas Covered:

This expert opinion provides an overview of the latest experimental
drug therapies aimed at protecting against and restoring cerebral stroke.

Expert Opinion:

Nanomedicine overcomes the challenges associated with traditional
therapy and physiological obstacles in the treatment of cerebral infarction by improving
stroke management, including diagnosis, imaging, and treatment, addressing a diverse
range of associated factors.
Trends in the Treatment of Chronic Wounds
Authors: Sharma Rohit , Hruska Jan , Peter Lukas , Randlova Kristina , Kuca Kamil
Published: September 2024

Chronic wounds remain one of the significant burdens to health across the
world, mainly in view of diabetes and its natural consequences. This category of lesions
includes pressure ulcers, vascular diseases, and surgery-related wounds, which affect
millions and pose a major challenge to the healthcare industry. The paper reviews the
various physiological mechanisms of wound healing, factors that impede it, and some
new treatments emerging at this moment. In contrast, current developments include surgical
and non-surgical alternatives like topical dressings, medicated formulations, and
skin substitutes. Advanced wound care today covers tissue-engineered skin substitutes,
3D-printed wound dressings, topical medicated formulations, and growth factor-based
therapies. These are non-invasive, biocompatible methods that are cost-effective, userfriendly,
and more conducive to natural healing than traditional therapies. Hydrogel
dressings have high water content to create a moist environment that encourages healing.
They also reflect excellent physicochemical and biological properties, which enhance
autolytic debridement and reduction of pain due to the moisture retention, biocompatibility,
and non-toxicity conferred. Tissue-engineered skin substitutes, comprising allogeneic
or autologous cells, wound-healing enhancement bioengineered allogeneic cellular
therapies are like the natural skin and encourage regeneration. 3D printing allows
the production of customized dressings to aid in better treatment. Newer therapies, including
bioengineered allogeneic cellular therapies and fish skin grafting, require more
clinical trials to confirm safety and efficacy. With such innovations in wound healing
technologies and therapies, the future looks quite promising in managing chronic
wounds, enhancing healing, reducing healthcare expenditure, and promoting a better
quality of life for patients.
NDSRIs Crisis in Pharmaceuticals; Insights on Formation Pathways, Root Causes, Risk Management, and Novel Analytical Techniques
Authors: P.R. Hemanth Vikram , Kandula Dilipkumar Reddy , Gunta Upendra , Kumar Gunjan , Deka Rajashree , Chiriki Devi Sri , Chethan K.S. , Bannimath Namitha , Yadav Thirumalesh , Beeraka Narasimha Murthy , Gurupadayya B.M.
Published: September 2024

The discovery of a new class of nitrosamine impurities called nitrosamine
drug substance related impurities (NDSRIs) in pharmaceuticals has emerged as a significant
challenge for the pharmaceutical sector due to their significant genotoxic and mutagenic
effects. Regulatory bodies globally in active collaboration with all the concerned
stake holders, are taking effective measures to prevent and control NDSRIs. This comprehensive
review on NDSRIs discusses formation pathways, root cause analysis, acceptable
intake limits, case studies, control strategies and regulatory responses pertaining to
recent NDSRI incidents. This review discusses the novel liquid chromatographic techniques
(LC-MS/MS, GC-MS/MS) used to identify and quantify of NDSRIs. This review
would aid pharmaceutical professionals, R&D analytical and formulation scientists, and
regulatory bodies in gaining deeper insights into the NDSRIs crisis, controlling NDSRIs
in drug products, and ensuring their sensitive detection with accurate risk evaluation.
Analysis of the Mechanism Underlying Radiotherapy Resistance
Caused by Oligodendroglia Cells in Glioblastoma by Applying the
Single-cell RNA Sequencing Technology
Authors: Yuan Qinghua , Gao Weida , Guo Mian , Liu Bo
Published: September 2024

Background:

Glioblastoma (GBM) is an aggressive malignancy. The inherent resistance of GBM to radiotherapy poses great challenges for clinical treatment

Objectives:

The primary objective of this study is to explore the molecular mechanisms
of radiotherapy resistance in GBM and identify the key influencing factors that contribute to this phenomenon.

Methods:

The single-cell RNA sequencing (scRNA-seq) data of GBM were downloaded from the Gene Expression Omnibus (GEO) database. Cells were clustered using the
Seurat R package, and the clusters were annotated using the CellMarker database. Pseudotime analysis was conducted using Monocle2. Marker scores were calculated based
on the RNA-seq data of GBM from the UCSC database, and the enrichment of Hallmark
gene sets was measured with the AUCell package. Furthermore, the most frequently mutated genes were identified using the simple nucleotide variation data from The Cancer
Genome Atlas (TCGA) applying the maftools package.

Results:

This study identified two oligodendrocyte subsets (ODC3 and ODC4) as radiotherapy-resistant groups in GBM. Enrichment and Pseudotime analysis revealed that the
inflammatory response and immune activation pathways were enriched in ODC3, while
the cell division and interferon response pathways were enriched in ODC4. The enrichment scores of hallmark gene sets further confirmed that ODC3 and ODC4 subpopulations developed radiotherapy resistance via distinct molecular mechanisms. Analysis of
gene mutation frequencies showed that TP53 exhibited the most significant change in
mutation frequency, indicating that it was an important risk factor involved in radiotherapy resistance in GBM.

Conclusion:

We identified two ODC subpopulations that exhibited resistance to radiotherapy, providing a new perspective and potential targets for personalized treatment
strategies for GBM.
DeepLCRmiRNA: A Hybrid Neural Network Approach for Identifying
Lung Cancer-Associated miRNAs
Authors: Cheng Nitao , Chen Chen , Liu Junliang , Wang Xuanchun , Gao Ziqi , Mao Ming , Huang Jingyu
Published: September 2024

Introduction:

Lung cancer stands as one of the most prevalent malignant neoplasms,
with microRNAs (miRNAs) playing a pivotal role in the modulation of gene expression, impacting
cancer cell proliferation, invasion, metastasis, immune escape, and resistance to therapy.

Method:

The intricate role of miRNAs in lung cancer underscores their significance as biomarkers
for early detection and as novel targets for therapeutic intervention. Traditional approaches for the
identification of miRNAs related to lung cancer, however, are impeded by inefficiencies and complexities.

Results:

In response to these challenges, this study introduced an innovative deep-learning strategy
designed for the efficient and precise identification of lung cancer-associated miRNAs. Through
comprehensive benchmark tests, our method exhibited superior performance relative to existing
technologies.

Conclusion:

Further case studies have also confirmed the ability of our model to identify lung cancer-associated miRNAs that have undergone biological validation.
The Efficacy and Safety Analysis of the Bendamustine, Pomalidomide, and Dexamethasone (BPD) Combination Treatment for Patients with Proteasome Inhibitor Intolerance and/or Relapsed Multiple Myeloma
Authors: Zhao Yiming , Tian Wanlu , Jin Feng bo , Jiang Lei , Zhang Rui , Qian Wei , Xia Leiming , Yang Ming zhen
Published: September 2024

Background:

Multiple Myeloma (MM) is a hematologic malignancy that often progresses
to a refractory relapse, posing significant treatment challenges due to prior treatments,
drug response duration, clinical and molecular characteristics, comorbidities, and adverse reactions.

Methods:

This single-center and single-arm study assessed the BPD regimen, which includes bendamustine,
pomalidomide, and dexamethasone, for its efficacy and safety in 21 patients with Relapsed
and Refractory Multiple Myeloma (RRMM), including those who were intolerant to prior
bortezomib treatment.

Results:

The Overall Response Rate (ORR) after 1-8 cycles of BPD treatment was 58.8%. The 6--
month Progression-Free Survival (PFS) was 70.5%, and the 12-month PFS was 52.9%. The 1-year
Overall Survival (OS) rate was 82.35%. Hematologic toxicities were the main adverse reactions,
with grade 3 or higher adverse events mainly linked to hematologic toxicity and infections.

Conclusion:

The BPD regimen has shown to be highly effective, with a favorable ORR and survival
rate in RRMM patients, indicating it a relatively safe and well-tolerated treatment option.
Influence of Surgical Mask on Exertion Perception and Select Physiological Parameters During an Incremental Test in Healthy Subjects
Authors: Piñeros-Alvarez Jose Luis , Portuguez-Jaramillo Nelson Esteban , Rosero- Carvajal Hamilton Elias , Pizarro-Loaiza Mayra Liliana , Murillo-Ortiz Monica Andrea , Tonguino-Rosero Stefanie
Published: September 2024

Background:

During cardiac or pulmonary rehabilitation exercises, the use of a surgical
mask may not be well tolerated by patients, especially those experiencing dyspnea during certain
activities due to their underlying health conditions. The purpose of this study was to describe
the influence of a surgical mask on exertion perception and some physiological parameters during
an incremental test in healthy subjects.

Methods:

A descriptive study involving 16 healthy adult individuals was conducted. The BRUCE
incremental protocol was performed twice, with and without the use of a surgical mask.

Results:

No significant changes were found in vital signs, such as heart rate (p: 0.8684), mean arterial
pressure (p: 0.2781), and peripheral oxygen saturation (p: 0.5314). However, the respiratory
rate showed a significant difference (p: 0.023). Furthermore, significant differences were observed
in the distance covered (p: 0.0005), duration (p: 0.0003), and measured intensity (METs)
(p: 0.0117). Metabolic acidosis (p: 0.032), hypocapnia (p: 0.238), and hyperlactatemia (p: 0.024)
were detected in the analysis of arterial gases. Oxygenation parameters, such as PaO2 (p: 0.038)
and PaO2/FiO2 ratio (p: 0.038), were higher in the mask-off trial.

Conclusion:

Surgical masks induce negative changes in METs, distance covered, and duration
during an incremental treadmill test. Although no significant impact on vital signs was observed,
the use of a surgical mask resulted in statistically significant but not clinically relevant decreases
in oxygenation parameters. The stages of the Bruce protocol were achieved differently when participants
wore a surgical mask.

conclusion:

During a treadmill incremental test, surgical masks induce negative changes in MET, distance covered, and duration. Although no significant impact was observed on vital signs, wearing a surgical mask resulted in statistically significant but not clinically relevant decreases in oxygenation parameters. The stages of the Bruce protocol were achieved differently when participants wore a surgical mask.
Thermal Spray Nanostructured Coatings Integrated with Artificial Intelligence: A Sustainable Approach in Industry for Corrosion Applications
Authors: Prashar Gaurav , Vasudev Hitesh
Published: September 2024

Coatings are the most common method for protecting metals from corrosion. The use
of nano-sized coating materials can enhance the strength and decrease the porosity level of the
developed coatings. The nano-coatings have shown improved mechanical properties, corrosion
resistance, and wear resistance in recent studies. As a result, the use of nano-sized coatings can
provide the benefit to the Industrial machinery components for longer operational periods. This
review article covers the corrosion behavior of nano-structured coatings in the initial section
followed by the role of artificial intelligence in predicting the corrosion rate of nanostructured
coatings.
Biochemical Sources of Fulvic Acid and its Application in Agriculture
Authors: Chen Yu-He , Liu Jialei , Liu Yang , Liu Zun-Qi
Published: September 2024

:

The demand for crop yields is increasing in modern society. The challenges to agricultural
cultivation, nevertheless, are posed by soil degradation, pollution, and the increasing number
of extreme weather events due to climate change. All these factors can threaten crop yield and quality.
However, fulvic acid can effectively alleviate these problems. It’s a type of humus with multiple
agricultural values, is produced through biomass fermentation, and has various mechanisms that
promote crop growth. It plays a significant role in mitigating various adverse factors affecting crop
growth. Fulvic acid contains more carboxyl and hydroxyl groups but also the presence of ether
bonds and ester bonds, due to the special structure of xanthic acid, which also allows it to closely
bond with many metal ions and substances. This paper provides an in-depth study of the mechanism
and molecular structure of fulvic acid production and describes a variety of application scenes of
fulvic acid in agricultural production. This paper makes a general conclusion on the improvement
of yield and quality of yellow rot crops and analyzes the resistance of yellow rot to the adverse environment,
including heavy metal hazards, salt stress hazards, drought hazards, pests, and diseases.
Through the analysis by many scholars, yellow rot acid can play a significant role in the improvement
of the adverse environment growing plants.

:

Furthermore, the combined use of fulvic acid and modern drip irrigation techniques is receiving
increased attention due to the significant benefits it offers in terms of water management and enhanced
fertilizer efficiency. More studies should be conducted on the mechanism of xanthate in
plants. The characterization of fulvic acid properties is indispensable in practical agricultural applications.
Moreover, the development of effective fulvic acid derivatives according to the actual situation
is essential to promote the sustainable development of agriculture.
In Silico Evaluation of Novel Quinoline Derivatives Targeting Hepatocyte Growth Factor Receptors as Anticancer Agents
Authors: Mhaske Ganesh , Rokade Siddhesh , Rokade Chaitrali , Sonkusare Diksha , Mane Divyani , Mane Poonam , Shinde Aishwarya
Published: September 2024

Background:

Numerous methods for computer-aided drug design (CAAD) have made
it possible to create and synthesize new chemical entities. The utilization of in silico techniques
and structure-based drug design (SBDD) facilitate the visualization of the ligand-target binding
process, in addition to allowing the prediction of receptor affinities and important binding pocket
locations.

Objective:

The current research work was carried out to recognize novel quinoline derivatives designed
specifically to bind with hepatocyte growth factor (HGF) receptors.

Materials and Methods:

For the formation of quinolines derivatives, ChemAxon Marvin Sketch
5.11.5 was utilized. SwissADME and the admetSAR online web tools were exploited to predict
the pharmacokinetic properties and the toxicity of compounds. Numerous software, including Autodock
1.5.7, MGL Tools 1.5.7, Biovia Discovery Studio Visualizer v20.1.0.19295, Procheck,
Protparam tool, and PyMOL, were also used to determine the ligand-receptor interactions of derivatives
of quinoline with the target receptor (PDB -1R0P).

Results:

Based on in silico research, it was found that all compounds were less toxic, orally bioavailable,
and had the proper pharmacokinetic properties. When compared to the commonly used
drug gefitinib, the docking scores of all newly created derivative compounds were higher.

Conclusion:

An increased binding energy, the number of H-bonds generated, and interactions
with quinoline analogues are significant parameters to be considered while constructing compounds
that are most appropriate for additional investigation. The favorable pharmacokinetic profile
of quinoline moiety was found to enhance its potential as a novel lung cancer treatment alternative
and may help medicinal chemists to carry out more thorough in vitro, in vivo, chemical, and
pharmacological research studies.
Protective Role of Ovothiol-A against Muscle and Kidney Injuries in Obese Rats
Authors: Arafa Nada Hussien , Shehata Mohamed Refaat , Mohamed Ayman Saber
Published: September 2024

Background:

Obesity is a serious chronic metabolic disease impairing health damaging
many organs such as kidneys and muscles. Ovothiol-A (Ovo-A) has been found to keep the redox
balance normal in sea urchins indicating its antioxidant characteristics.

Aim:

This study aims to investigate the protective effects of Ovo-A on kidneys and muscles in
obese rats.

Methods:

In-silco studies were performed on lactate dehydrogenase (LDH) and creatine kinase
(CK) with Ovo-A to compute their binding affinities. Obesity was induced by high-fat diet (HFD)
for 4 weeks. Wistar rats were used in this study as 6 rats per group as control, HFD, Ovo-A (200
and 400 mg/Kg, p.o) groups.

Results:

Docking results have revealed that Ovo-A has affinities to bind to LDH (-8.5 kcal/mol)
and CK (-17.7 kcal/mol). Ovo-A reduced the levels of uric acid, urea, creatinine, LDH, CK,
malondialdehyde (MDA), and nitric oxide (NO), while increasing the levels of glutathione (GSH),
catalase (CAT), and glutathione-S-transferase (GST). Histopathological investigations have revealed
that Ovo-A restored the renal and muscular structure.

Conclusion:

The current study showed that Ovo-A has a protective effect on kidneys and muscles
in obese rats. Ovo-A enhances renal and muscular functions by inhibiting LDH and CK activities
and improving the antioxidant system. Ovo-A is more effective in the high dose.
Unveiling The Potential of Microwave Plasma Treated Char For Sustainable Automotive Shredder Residue (ASR) Management and Reduced Ecological Risk Of Cadmium
Authors: Ngo Thi-Huyen-Tran , Wang Ya-Fen , Chang Tien-Chin , You Sheng-Jie
Published: September 2024

Introduction:

This study explores the effectiveness of microwave plasma pyrolysis in reducing
heavy metal concentrations, specifically cadmium, in automobile shredder residue (ASR).
METHOD: The ASR was subjected to plasma pyrolysis at microwave power levels ranging from
800 to 1000W, resulting in a significant decrease in heavy metal concentration in the char. Utilizing
the Bureau Communautaire de Référence (BCR) sequential extraction method, a standardized procedure
developed by the European Commission, we assessed the chemical speciation and matrix
properties of the char. The results indicated that microwave plasma treatment effectively decreased
the bioavailable forms of cadmium. After 6 minutes of pyrolysis at 1000W, the exchangeable and
acid-soluble fractions (F1) dropped to 10%, while the reducible fraction (F2) fell to 12%. RESULT:
This treatment resulted in a substantial increase in the oxidizable (F3) and residue (F4) fractions,
which reached 27% and 51%, respectively. Importantly, the potential ecological risk of cadmium
decreased significantly, with the risk index (Er) dropping from 164.91 to 28.45, aligning with Taiwan's
regulatory standards for non-hazardous waste.CONCLUSION: These findings suggest that
microwave plasma pyrolysis is a promising and sustainable approach for the disposal of ASR, offering
an environmentally friendly alternative for waste management. This study provides valuable
insights for policymakers, environmental scientists, and industries seeking effective solutions for
ASR treatment.
ПРИХОВАНІ РАДІОЙОДЧУТЛИВІ ТА РАДІОЙОДРЕЗИСТЕНТНІ МЕТАСТАЗИ ПАПІЛЯРНОЇ КАРЦИНОМИ ЩИТОПОДІБНОЇ ЗАЛОЗИ: КЛІНІЧНІ АСПЕКТИ
Authors: Гуда Богдан , Остафійчук Мар’ян
Published: September 2024

Актуальність. Резистентність метастазів до радіойоду становить значну клініко-онкологічну проблему при проведенні цільової радіойодтерапії у хворих, які перенесли тиреоїдектомію з приводу папілярної карциноми щитоподібної залози (ПК ЩЗ). Існування прихованих лімфовузлів, які уражені метастазами ПК, особливо якщо вони є радіойодрезистентними (РЙР), подвоює проблему, бо становить загрозу подальшого широкого метастазування карцином, виникнення рецидивів після проведення хірургічного лікування, низької ефективності радіойодного лікування.
Мета роботи. Проаналізувати низку клініко-онкологічних характеристик захворювання, які могли б, у певній мірі, передбачити наявність радіойодрезистентних метастазів у хворих, пухлини яких на основі результатів доопераційної діагностики мали статус N0.
Матеріали та методи. Когортне дослідження частоти РЙР метастазів у лімфовузлах шиї пацієнтів трьох груп – без метастазів, з радіойодчутливими (РЙЧ) і РЙР метастазами – в залежності від низки клінічних параметрів (вік і стать пацієнтів, розмір пухлини та її інвазійні характеристики, наявність супутнього автоімунного тиреоїдиту). Визначали частку уражених лімфовузлів до кількості видалених. Статистичну обробку даних проводили за використання критерію узгодженості розподілів χ2 Пірсона, а також критерію Стьюдента.
Результати. Вікові та гендерні характеристики хворих не пов’язані з прогнозом існування РЙР метастазів ПК, хоча тенденція щодо більшого розміру пухлин, метастази яких були РЙР, простежена у групі жінок, але не чоловіків. Розмір карцином корелює з підвищенням частоти РЙР метастазів лише у випадках пухлин, які не виходять за межі ЩЗ і діаметр яких не перевищує 4 см (категорії Т1-Т2). Найнижчу частоту РЙР метастазів порівняно з частотою РЙЧ метастазів спостерігали за пухлин категорії Т1а, найвищу – за ПК категорії Т2. Не виявили зв’язок частоти РЙР метастазів з такими характеристиками ПК як інвазія у капсулу пухлини, інтратиреоїдна чи екстратиреоїдна інвазія, а також мультифокальний ріст пухлинних клітин, хоча частота пухлин як з РЙЧ, так і з РЙР метастазами була вищою порівняно з такою за інвазійних карцином, які не метастазували. Встановлений чіткий зв’язок частоти РЙР метастазів з наявністю у хворих тиреоїдиту: за асоціації з ПК автоімунного захворювання РЙР метастази зустрічаються значно рідше. Частка метастатичних лімфовузлів була найвищою серед видалених лімфовузлів центрального компартменту.
Висновки. Частота радіойодрезистентних метастазів папілярної карциноми у хворих з доопераційним статусом пухлини N0 не залежить від віку пацієнтів, їх статі, а також інвазійних характеристик пухлин. Найрідше приховані радіойодрезистентні метастази зустрічаються в хворих з мікрокарциномою і на фоні асоційованого з папілярною карциномою автоімунного тиреоїдиту. Визначення частки метастатичних лімфовузлів серед усіх видалених при лімфодисекції може бути корисним для прогнозу виникнення у післяопераційний період рецидиву захворювання.