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Explore 66,105 preprints on the Authorea Preprint Repository

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Use of optimal fluoroscopic angulation to facilitate effective pulsed field ablation...
Shintaro Yamagami
Shumpei Mori

Shintaro Yamagami

and 6 more

November 11, 2024
Introduction: This case report describes the use of a PulseSelect™ catheter in a patient with atrial fibrillation (AF), using optimal fluoroscopic angulation to ensure tissue-catheter contact during pulsed field ablation (PFA). Methods and Results: A 51-year-old woman with paroxysmal AF underwent PFA using a PulseSelect™ catheter. Preprocedural cardiac computed tomography was used to identify the optimal fluoroscopic angulations for obtaining en face and perpendicular views for pulmonary vein isolation (PVI). Complete PVI was achieved, with no AF recurrence within a 3-month follow-up. Conclusion: This case demonstrates the feasibility of obtaining and applying optimal fluoroscopic angulation during PFA using the PulseSelect™.
High-Precision ECG Signal Classification for Cardiovascular Disease Detection with th...
Nandakumar P
Kotteeswaran C

Nandakumar P

and 2 more

November 11, 2024
BACKGROUND: A critical responsibility in healthcare is the classification of cardiac diseases to facilitate early diagnosis and prevent cardiovascular consequences. Optimizing model performance and managing noisy and high-dimensional datasets are common issues for traditional approaches. OBJECTIVE: Using the MIT-BIH dataset, this paper describes a novel method for analyzing ECG signals in order to detect and classify various types of cardiovascular diseases (CVD). The proposed approach includes a comprehensive workflow that starts with dataset acquisition and progresses to signal buffering to prevent data loss and artifact removal. METHODS: To achieve optimal fusion, signal optimization is performed using Cat Swarm Optimization, and similar signals are clustered using Fuzzy C-Means (FCM). Signal decomposition and feature extraction are achieved using the Stockwell Transform and Empirical Mode Decomposition (EMD), respectively, while texture analysis is accomplished using Local Phase Quantization (LPQ). The classification is carried out using the ALEXIS Model, which combines AlexNet for feature learning, LSTM for temporal analysis, and SVM for final classification. RESULTS: The proposed method was compared to several other approaches, including CNN-LSTM-SE, XGBoost, and traditional machine learning methods. The proposed methodology outperformed all other methods, with an accuracy of 99.432%, sensitivity of 99.271%, specificity of 99.78%, and an F1 score of 99.311%. CONCLUSIONS: These findings demonstrate the integrated approach’s robustness and effectiveness in accurately classifying ECG signals into five types of CVD: congestive heart failure (CHF), valve stenosis, myocardial infarction, vascular disease, and arrhythmia. The high-performance metrics indicate that this methodology has the potential to significantly improve the accuracy and reliability of CVD diagnosis based on ECG signals.
Enhancement of Heat Transfer in Double Pipe Heat Exchangers Using Wavy Edge Twisted T...
Zainab Mahdi Saleh
Riyadh S. Al-Turaihi

Zainab Mahdi Saleh

and 2 more

November 11, 2024
The current study presented numerical simulation for a double pipe heat exchanger (DPHE) with a counter-flow, in order to study the effects of twisting ratio for wavy edge twisted tape and the diameter of the holes it contains. The impact factors, varying Reynolds number (6957-187837), twisted tape ratio (0.5-3) on heat transfer and pressure drop. The inner tube, carrying hot air, incorporates twisted tapes to enhance turbulence and heat transfer. The outer tube, containing cold oil, experiences the effects of the enhanced flow But The Reynolds range is investigated range, and working fluids are on the side of the inner tube and annular space is hot air cold oil . Results demonstrate significant improvements in oil outlet temperature. Nusselt number (Nu) increases with increasing Reynolds numbers and twist ratios, the maximum Nu for enhancement devices with Tr = 0.5 and 3 are 38% and 10.7% higher than for the plain tube. Increasing Reynolds number and twisted tape ratio generally lead to higher heat transfer rates but also increased pressure drop. Optimal configurations of (Tr=2 and hole diameter 30mm)gave a best thermal performance index of 1.11 and 1.24 respectively when balancing heat transfer and pressure drop. The findings provide valuable insights for designing and optimizing heat exchangers in applications demanding efficient heat transfer.
Advancements in misfolded prion protein detection
Ningrui Cao
Meiyi Shou

Ningrui Cao

and 6 more

November 11, 2024
Prion diseases are fatal, progressive, transmissible neurodegenerative conditions that affect both humans and animals. The scrapie prion protein (PrPSc), a misfolded form of prion, is both the cause of prion diseases and gold standard biomarker for diagnosis. Given the infectivity and 100% lethality of prions, new detection methods are urgently needed to enhance the diagnosis and surveillance of prion diseases. In this review, we summarize recent advancements in PrPSc detection. We explore in vitro seeding assays, such as Protein Misfolding Cyclic Amplification and Real-Time Quaking-Induced Conversion, alongside innovative biosensors and imaging techniques developed for prion detection. This review highlights the evolving landscape of PrPSc detection methods and their potential roles in early diagnosis, prion transmission control, and effective treatment development.
Effects of landscape compositional heterogeneity and spatial autocorrelation on envir...
Joseph Tardanico
Thomas Hovestadt

Joseph Tardanico

and 1 more

November 11, 2024
Local adaptation, environmental tolerance, and dispersal mutually influence the evolution of one another and each are in turn influenced by landscape spatial structure. While each of the three have been investigated frequently in isolation in relation to spatial structure, the three have rarely been considered together. In this study, we explored how the magnitude of landscape environmental heterogeneity (compositional heterogeneity), and environmental spatial autocorrelation jointly affect the evolution of environmental niche optima, tolerance, dispersal frequency, and dispersal distance using a spatially explicit individual based model simulating organisms living, reproducing, and dispersing within grid-based fractal landscapes. Compositional heterogeneity tended to have the strongest influence over patterns while spatial autocorrelation typically played a mediating role. We found that niche adaptation and dispersal patterns were driven by a balance between pressure to avoid risk imposed by spatial heterogeneity and pressure to hedge against risk imposed by temporal environmental fluctuations. Dispersal frequency and dispersal distance were affected differently by spatial structure, underscoring the importance of considering the two independently.
Spatial Analysis of Lapwing (Genus: Vanellus) Coexistence in two South Asian Biodiver...
Langtuk Terang
Vivek Chetry

Langtuk Terang

and 3 more

November 11, 2024
Environmental factors play a critical role in shaping species distribution and resource utilization patterns. However, a gap of knowledge exists in understanding the niche dynamics between the two species; the ‘Least Concern’-Vanellus duvaucelii (red-wattled lapwing) and the ‘Near Threatened’-Vanellus indicus (river lapwing), a difference that could prove critical for long-term conservation efforts. Thus, the present study aims to examine V.duvaucelii and V. indicus -wattled) in northeast North-East India. We investigated whether environmental variables influence their spatial patterns and examined the potential impact of niche overlap. The research questions of the present study were: Does environmental factors [1] shape the spatial patterns? and [2] resource utilization patterns? of V. duvaucelii and V.indicus on species persistence. Using primary and secondary species occurrence data, combined with environmental datasets, we modelled suitable habitats for each species with the Dismo and Wallace packages in R. The habitat models performed well, yielding high AUC values of 0.987 for V. indicus and 0.973 for V. duvaucelii. Predicted habitat areas for V. indicus were 3,254 km² (high potential), 6,217 km² (good potential), and 17,057 km² (moderate potential), totaling 255,088 km². For V. duvaucelii, these values were 1,955 km², 7,664 km², and 8,645 km², respectively, also totaling 255,088 km². Niche overlap, measured with Schoener’s D, was 0.55, indicating moderate similarity, with 0.07 and 0.04 representing unique niches for V. duvaucelii and V. indicus, respectively, and 0.96 of the being niches shared. These results underscore the ecological implications of niche sharing between overlap species and highlight potential risks for V. duvaucelii, as overlapping habitats and limited niche exclusivity could increase vulnerability under rapidly changing environmental conditions. These findings further highlight the ecological consequences of niche sharing between the species and point out possible risks for V. duvaucelii, and thus poor niche separation may increase vulnerability under rapid environmental change.
Phylogenetically older oribatid mites of mountain ranges have broader geographic rang...
Xue Pan
Bastian Heimburger

Xue Pan

and 11 more

November 11, 2024
Understanding ecological and evolutionary mechanisms that drive biodiversity patterns is important for comprehending biodiversity. Despite being critically important to the functioning of ecosystems, the mechanisms driving belowground biodiversity are little understood. We here investigated the radiation and trait diversity of soil oribatid mites from two mountain ranges, i.e. the Alps in Austria and Changbai Mountain in China, at similar latitude in the temperate zone differing in orogenesis and exposed to different climates. We collected and sequenced soil oribatid mites from forests at 950 to 1700 m at each mountain and embedded them into the chronogram of species from temperate Eurasia. We investigated the phylogenetic age of oribatid mites and compared the node age of species with the mountain uplift time of the Alps and Changbai Mountain. We then inspected trophic variation, geographical range size and reproductive mode, and identified traits that promote oribatid mite survival and evolution in montane forest ecosystems. We found that oribatid mites on Changbai Mountain are phylogenetically older than species in the Alps. All species on Changbai Mountain evolved long before the mountain uplift, but some species in the Alps evolved after the orogenesis. On Changbai Mountain more species possess broader trophic variation, have larger geographical range sizes and more often reproduce via parthenogenesis compared to species from the Alps. Species on Changbai Mountain survived the mountain uplift or colonized the mountain thereafter supporting the view that generalistic traits promote survival and evolution in phylogenetically old soil animal species. Collectively, our findings highlight that combining species traits and phylogeny allow deeper insight into the evolutionary forces shaping soil biodiversity in montane ecosystems.
A Bibliometric Analysis-Based Review: Macrophages in Oral Diseases From 1994 to 2023
Xuelian Tan
雨乐 郑

Xuelian Tan

and 4 more

November 11, 2024
Aim: Macrophages play a crucial role in the oral immune defense system, which is essential for maintaining oral health. However, they are also implicated in the onset and progression of various oral diseases. This study investigates emerging trends, key research areas, and potential therapeutic strategies related to macrophages in oral diseases, focusing on OSCC, PD, AP and OTM, using the bibliometric method. Methods: Citation data were obtained from Web of Science Core Collections (WOSCC) database. Bibliometric analysis and visualization of countries/regions, institutions, authors and keywords were conducted by VOSviewer and CiteSpace. Results: Included were 1277 articles published between 1994 and 2023. China and the US led in publication volume and citations. Major research institutions were Sichuan University, Wuhan University (China), and Universidade de Sao Paulo (Brazil). Eun Young Choi and In Soon Choi were the most prolific authors, while Fuhua Yan received the most citations, and George Hajishengallis was most co-cited. Keyword clustering analysis identified OSCC, PD, AP, and OTM as active research areas. Specifically, OSCC research focused on macrophage expression, inflammation, TAMs, and polarization. In PD, TNF-α, P. gingivalis, and macrophage differentiation were prominent. For AP, LPS and osteoclast differentiation were significant. In OTM, T cell involvement and bone resorption were notable topics. Conclusion: This study summarizes macrophage research hotspots in OSCC, PD, AP, and OTM using bibliometric analysis. We outline general treatment directions based on findings, highlighting key achievements and identifying research challenges to provide valuable insights and guidance future investigators.
Pulse field ablation of paroxysmal atrial fibrillation complicated with left-side acc...
Hao Li
Liang Xiong

Hao Li

and 4 more

November 11, 2024
We report a case of a patient with paroxysmal atrial fibrillation associated with left-side accessory pathway treated with pulsed field ablation. The patient successfully achieved long-term control of atrial fibrillation, which provides a new therapeutic option for clinical decision-making.
Optimizing ROC Curve for Ensemble Models through Pareto Front Analysis of the Decisio...
Alberto Gutierrez-Gallego
Oscar Garnica

Alberto Gutierrez-Gallego

and 4 more

November 11, 2024
The ROC, Receiver Operating Characteristic, curve is commonly used to evaluate the performance of machine learning ensemble classification models that combine multiple classifiers and use a voting procedure to determine the final classification. Although they have many parameters, their ROC curves usually only explore the voting threshold, limiting their potential for improvement. In this paper we propose a new method, ROC mapping, to improve the performance of the model by re-defining the ROC curve as the Pareto front of a multi-objective optimization problem that maps the multidimensional space of all parameters of the ensemble classifier (Decision space), into the Objective space defined in the two-dimensional unitary interval. We use an algorithm based on NSGA-II to explore the Decision space and validate the proposal on two different classification problems: (1) predicting car insurance claims of a highly imbalanced dataset (Insurance dataset), and (2) predicting obesity risk with a balanced clinical dataset (GenObIA dataset). We compare our method with alternative ensemble optimization methods using the visual assessment, Area Under the Curve, and the Youden Index as figures of merit. In the Insurance dataset, our method shows an average improvement of 46 .4% in Area Under the Curve, and 26 .1% in the Youden Index, both calculated relative to the maximum achievable improvement. In the GenObIA dataset, we achieve an average increase of 29 .7% in Area Under the Curve, and 11 .9% in the Youden Index, again based on the maximum possible improvement. The ROC mapping approach provides a comprehensive and adaptable ROC curve, demonstrating its effectiveness in improving classification performance across different applications.
POWER TRADING SCENARIO IN INDIA: HISTORY, OPERATION AND PERFORMANCE ANALYSIS
SHUVAM MOHAPATRA

SHUVAM MOHAPATRA

November 11, 2024
Power Sector reforms in India were initiated with the ultimate objective of restoring reliability of the power industry, promote competition and efficiency, create an environment conducive to private investment, and facilitate sustainable development of the power sector. With the initiation of the reform process, it was considered essential that the sector be regulated by independent institutions. This led to the introduction of Regulatory Commissions at the Central and State levels through the introduction of the Electricity Regulatory Commissions Act 1998.Thus the enactment of the Electricity Act 2003 strengthened the role of Regulatory Commissions and provided for competition and efficiency in the power sector, quality of supply at reasonable prices to the consumers, promotion of non-conventional sources of energy and power market development.
Clinical presentation of cytomegalovirus meningoencephalitis in adult patients: A 6-y...
Ching-Hao Hsu
Yi-Tien Hsuan

Ching-Hao Hsu

and 3 more

November 11, 2024
Abstract Background: Cytomegalovirus (CMV) is a crucial pathogen in immunocompromised individuals, causing infections such as pneumonitis, colitis, and retinitis. However, research on CMV infections of the central nervous system (CNS) is limited. Objective: This retrospective cohort study enrolled patients with a CMV meningitis or encephalitis diagnosis and analyzed their underlying conditions, clinical manifestations, laboratory findings, treatments, and outcomes. Methods: The study included patients who had positive results in quantitative polymerase chain reaction (PCR) tests of their cerebrospinal fluid (CSF) for CMV at any time between January 2017 and December 2022. Clinical characteristics, laboratory findings, treatment approaches, and outcomes were reviewed and analyzed from electronic medical records. Results: The cohort comprised 12 patients with a median age of 61 years (range, 43–84 years). Stupor and generalized seizures were the most common neurological presentations. Brain imaging in half of the patients revealed nonspecific abnormalities, such as atrophy. CSF protein levels were elevated, with a median of 74.5 mg/dL. CSF pleocytosis was observed in three patients (25%) and was predominantly lymphocytic. The in-hospital mortality rate was 75% (9 out of 12 patients). Conclusions: Although rare, CMV CNS infections are associated with a high mortality rate. CSF pleocytosis is uncommon in such cases, potentially contributing to clinical misdiagnosis or underestimation. CMV meningoencephalitis should be considered in immunocompromised patients who present with unexplained seizures or altered consciousness.
Second wave of the COVID-19 pandemic not as deadly as speculat...
Sushrut Ingawale
Archana Sonawale

Sushrut Ingawale

and 9 more

November 11, 2024
This retrospective multicenter study compared the demographic and clinical characteristics of hospitalized COVID-19 patients across two waves at select public hospitals in Mumbai. A total of 26,405 laboratory-confirmed cases were included, excluding patients transferred to other centers. Data analysis involved chi-square tests and multivariate binomial logistic regression. Both waves showed a male preponderance (64% in wave 1, 63% in wave 2, p=0.131) and a majority of patients over 35 years (77% in wave 1, 76% in wave 2, p=0.273). Despite a higher oxygen requirement in wave 2 (23% vs. 36%, p=0.001), the fatality rate was lower (13% vs. 9%, p=0.001). Symptom burden and comorbidities were significantly lower in wave 2. Kidney involvement (p=0.001) was the strongest predictor of oxygen requirement and death in wave 1, whereas age over 55 (p=0.001) was the most consistent predictor across both waves. Hypertension and/or diabetes (p=0.001) were associated with increased oxygen requirement but not death in both waves. In conclusion, while the age and gender distribution remained similar across both waves, wave 2 had a lower fatality rate and comorbidity burden despite a higher oxygen demand. The lower fatality rate in wave 2 stands out as a striking result in this large population study, contrary to earlier speculations. Age over 55 was a consistent predictor of both oxygen requirement and mortality, while hypertension and diabetes were only predictors of oxygen need.
Novel metal sites revealed by spectroscopic and structural characterization of the Fe...
Yerko Argandoña
Andrea Olivos

Yerko Argandoña

and 6 more

November 11, 2024
Acidithiobacillus ferrooxidans ( Af.) is a microorganism of significant biotechnological interest that thrives in acidic environments with very high concentrations of soluble iron. Understanding the molecular mechanisms that enable its survival in these extreme conditions is of great scientific relevance and practical importance for bioleaching of precious metals. Central to its metabolism is the Ferric Uptake Regulator (Fur), a protein that regulates iron homeostasis and responses to oxidative stress in bacteria. Using a combination of bioinformatics, experimental, and spectroscopic methodologies, this study identified and characterized the metal binding sites and cofactors relevant to AfFur´s function. Three metal-binding sites became evident, two of which are very similar to those found in other members of the superfamily. The third site, formed by four cysteine residues in an configuration (CX 2C-X n-CX 8C), stably binds a iron-sulfur cluster. Site-directed mutagenesis coupled with Electrophoretic Mobility Shift Assays underscored the essentiality of these cysteines for AfFur’s functionality, particularly in DNA binding. Altogether, the findings from this research suggest the presence of an iron-sulfur cluster, which may play a role in fine-tuning iron sensing, particularly adapted to the unique environment of Acidithiobacillus ferrooxidans.
I calcolatori elettronici
Alessio Attilio

Alessio Attilio

November 15, 2024
Architettura di Von NeumannL'architettura di Von Neumann, proposta dal matematico e fisico John Von Neumann nel 1945, rappresenta uno dei fondamenti dell'informatica moderna e ha gettato le basi per la progettazione dei computer digitali. Questo modello è alla base della maggior parte dei computer attuali e descrive un'architettura logica per l'elaborazione delle informazioni, in cui sia i dati che le istruzioni sono memorizzati nella stessa memoria.Contesto StoricoI primi calcolatori erano progettati con una struttura differente. Ad esempio, le macchine analitiche di Charles Babbage e i computer elettromeccanici come l'ENIAC erano configurati per eseguire compiti specifici, e la loro programmazione era statica, spesso realizzata attraverso la modifica manuale dei collegamenti fisici tra i componenti hardware. L'innovazione di Von Neumann risiede nell'introduzione di una memoria condivisa per dati e istruzioni, semplificando così la programmazione e rendendo possibile la realizzazione di macchine programmabili e general-purpose.Principi FondamentaliMemoria UnificataSia i dati che le istruzioni sono memorizzati nella stessa area di memoria.Questo concetto è noto come memoria unificata o memoria condivisa. La memoria è organizzata in celle, ognuna identificata da un indirizzo univocoUnità di Controllo (Control Unit)È il componente del processore responsabile di dirigere l'esecuzione delle istruzioni.interpreta le istruzioni memorizzate in memoria e coordina le operazioni degli altri componenti della macchina.Unità Logico/Aritmetica (ALU) si occupa delle operazioni matematiche e logiche.Esegue calcoli come addizioni, sottrazioni, moltiplicazioni, divisioni e confronti logici (es. AND, OR, NOT).RegistriSono piccole unità di memoria ad accesso rapido presenti all'interno del processore.Sono utilizzati per memorizzare temporaneamente dati e indirizzi durante l'esecuzione delle operazioni.Bus di SistemaÈ l'insieme di linee di comunicazione che permettono lo scambio di dati tra i diversi componenti del computer.Esistono tre tipi principali di bus: Bus dei Dati: Trasporta i dati tra il processore e la memoria.Bus degli Indirizzi: Contiene le informazioni relative agli indirizzi di memoria da cui leggere o scrivere dati. Bus di Controllo: Trasporta segnali di controllo che coordinano le operazioni del sistemaIl Ciclo di EsecuzioneÈ noto come ciclo fetch, decode, execute.Descrive come il processore legge e interpreta le istruzioni.Esso si basa su tre fasi:Fetch:  L'unità di controllo preleva un'istruzione dalla memoria, utilizzando il Program Counter, che indica l'indirizzo della prossima istruzione da eseguireDecode:  L'istruzione prelevata viene decodificata dall'unità di controllo per determinare quale operazione deve essere eseguitaExecute: L'istruzione viene eseguita; se è un'operazione aritmetica o logica, viene effettuata dall'ALU; se è un'operazione di input/output, vengono coinvolti i dispositivi perifericiDopo l'esecuzione, il Program Counter viene aggiornato per puntare alla prossima istruzione e il ciclo riprende.VantaggiSemplicità e FlessibilitàLa memorizzazione unificata di dati e istruzioni consente al computer di essere programmabile e di cambiare facilmente i compiti svolti, adattandosi a nuove esigenze senza modifiche hardware.Riduzione del Tempo di SviluppoGrazie a una struttura standardizzata, la progettazione e la costruzione di computer sono diventate più efficienti.Possibilità di Eseguire Programmi ComplessiLa memorizzazione condivisa permette l'implementazione di programmi sofisticati, inclusi quelli che possono modificare se stessi durante l'esecuzioneLimitiNonostante i suoi vantaggi, l'architettura di Von Neumann presenta anche alcune limitazioniCollo di BottigliaUno dei problemi principali è il cosiddetto "collo di bottiglia", che si verifica quando il bus di sistema diventa un punto di congestione. Poiché sia i dati che le istruzioni devono passare attraverso lo stesso bus, questo può rallentare l'esecuzione, specialmente in applicazioni che richiedono un elevato trasferimento di dati.Vulnerabilità agli AttacchiPoiché i dati e le istruzioni condividono lo stesso spazio di memoria, può essere più facile per un attaccante sovrascrivere le istruzioni con dati malevoli, come avviene in alcuni tipi di exploit di sicurezzaEvoluzioni ModerneNel tempo, quest'architettura è stata affiancata da altri modelli, come l'architettura Harvard, che separa fisicamente la memoria per i dati e quella per le istruzioni. Questo approccio risolve parzialmente il collo di bottiglia, ma introduce complessità aggiuntiva.Inoltre, l'introduzione di cache e l'uso di pipeline nel processore sono soluzioni moderne che cercano di mitigare i limiti dell'architettura di Von Neumann, aumentando la velocità di accesso ai dati e l'efficienza nell'esecuzione delle istruzioni.
One case of advanced lung adenocarcinoma successfully treated by intratumoral injecti...
Huiying Liu
Xuemao Liu

Huiying Liu

and 6 more

November 11, 2024
Nowadays lung cancer is regarded as the leading cause of cancer-related death, leading to a mortality number of nearly 1.8 million annually [1]. Lung adenocarcinoma, as a relatively common pathological type of lung cancer in clinical practice, shows a gradually increasing tendency and ranks top in both morbidity and mortality rate among all malignant tumors[2]. In recent years, rapid progress in tumor immunotherapy and tracheoscopy intervention technology provide more possibilities for the treatment of lung adenocarcinoma. Here we report an 83-year-old patient diagnosed with lung adenocarcinoma stage IV who achieved partial clinical remission after receiving 4 periods of systemic intravenous administration and 2 periods of intratumoral administration of tirellizumab under tracheoscopy. By follow-up on August 24, 2024, the patient’s tumor was still shrinking without any treatment-related adverse reactions. Based on this case, it is suggested that systemic intravenous tirelizumab combined with tracheoscopic intratumoral injection may provide a safe and effective strategy for patients with lung adenocarcinoma, especially for those who cannot tolerate chemotherapy or surgery. However, further prospective studies and more clinical experiments are still needed to confirm our hypothesis.
Unlocking The Potential and Myth of Personalized Vaccines, CRISPR-CAS9, and Bacteriot...
Akmal Zubair
Adil Jamal

Akmal Zubair

and 2 more

November 11, 2024
Recent advancements in cancer treatment, including targeted therapy, personalized vaccines, immunotherapy, and bacteriotherapy have shown promising potential in the curing of many kinds of cancer. The pursuit of innovative therapeutic approaches is impeded by many enduring challenges, such as substantial toxicity towards healthy tissues and cells, limited penetration into cancerous tissue depths, and the risk of tumor cell resistance to drugs. This study examination personalized vaccines, immunotherapy, CRISPR/CAS9, and bacteriotherapy as potential treatments for cancer. The potential use and benefits of a personalized cancer vaccine approach, which can induce a systemic antitumor response, are noteworthy for individuals diagnosed with cancer. Sources were collected through thorough searches of databases PubMed and Embase. The personalized cancer vaccines induce tumor-specific responses against neoantigens specific to each patient. Immunotherapy has reinvigorated the science of tumor immunology. Nevertheless, it is important to note that the efficacy of immunotherapies varies, and only a certain group of individuals with cancer get positive outcomes from interventions such as immune checkpoint inhibitors (ICIs) and adoptive cell transfer (ACT). Immunotherapy enhances the ability of the immune system to detect and destroy cancer. checkpoint inhibitors and cellular immunotherapy are robustly studied and use in various clinical trials. Bacteriotherapy has shown efficacy in promoting tumor regression and inhibiting metastasis. Bacteriotherapy, alone or in combination with traditional techniques, has been demonstrated to reduce tumor growth and metastasis. Using bacteria-assisted tumor-targeted therapy as therapeutic/gene/drug delivery vehicles present promising tumor treatment potential. The use of the CRISPR-Cas9 system for genome editing has shown encouraging outcomes in the pursuit of novel therapeutic approaches. Although CRISPR/Cas9 has shown potential in experimental settings, its use for cancer therapy in human subjects is still in its early stages. A gene-level tumor may be treated using CRISPR/Cas9. CRISPR/Cas9-targeted drugs may change tumor therapy.
DNA synthesis and assembly technologies: from oligonucleotides to complete genomes
Wei Tan
Xuemei Jia

Wei Tan

and 4 more

November 11, 2024
DNA synthesis and assembly technology is the fundamental enabling technology of synthetic biology, providing methods for humans to understand and modify organisms. Oligonucleotide chains and long DNA fragments synthesized through DNA synthesis and assembly technology are becoming increasingly widely used in fields such as biomedicine, energy, new materials, and information storage, with strong application prospects. This review provides a comprehensive and systematic introduction and exposition of current DNA synthesis and assembly technologies, discussing current challenges and future research prospects.
Sensitivity to Negative Stimuli and Psychological Resilience: Perceived Internal Cont...
Linlin Yan
Peng Huini

Linlin Yan

and 4 more

November 11, 2024
Resilience is a critical ability to cope successfully with stressful circumstances. Sensitivity to negative stimuli and perceived control both independently impact stress-related vulnerabilities or resilience. However, the relationships among them remain unclear. This study aimed to examine the association between negative emotion sensitivity and psychological resilience, and whether this association is influenced by perceived internal control. Ninety-one healthy young adults passively viewed negative and neutral pictures while electroencephalogram (EEG) data were recorded. The Late Positive Potential (LPP) was measured as an indicator of sensitivity to negative emotional stimuli. Perceived internal control and psychological resilience were assessed through self-reported questionnaires. Results showed that increased sensitivity to negative stimuli, reflected by larger LPP amplitudes in response to unpleasant versus neutral pictures, was associated with lower psychological resilience after controlling for gender and age. Furthermore, perceived internal control significantly mediated the relationship between LPP amplitudes and psychological resilience, with larger LPP amplitudes linked to lower perceived internal control, which in turn related to lower resilience. These findings suggest that heightened sensitivity to negative stimuli is associated with reduced resilience, with perceived internal control serving as a potential connecting mechanism.
Convergent validity of cortical auditory evoked potential indices of central auditory...
Kenneth Morse
Leah Morse

Kenneth Morse

and 1 more

November 11, 2024
Tinnitus is the perception of a ringing, buzzing, or other sound without the presence of an external stimulus. Reduced central auditory nervous system inhibition is a commonly reported mechanism contributing to a person’s tinnitus perception. Different cortical auditory evoked potential (CAEP) studies have supported the presence of reduced inhibition in people with tinnitus. Although previous CAEPs used to study tinnitus do broadly represent inhibitory function, it is not entirely clear if the different CAEPs present similarly within an individual. To address this gap in knowledge, the current study evaluated the convergent validity between different CAEPs that broadly reflect inhibitory function, called sensory gating and onset-offset CAEPs. Convergent validity between sensory gating and onset-offset CAEPs was evaluated as a function of participant tinnitus status, stimulus frequency, and CAEP quantification approach. The results indicated that sensory gating and onset-offset CAEP responses indicative of inhibitory function did not demonstrate strong convergent validity. Further, the strength of convergent validity did not differ between people with and without tinnitus. However, experimental factors that yielded more robust CAEPs, such as broadband stimuli, and more comprehensive measures of amplitude, such as total response area, resulted in better convergent validity compared to higher frequency stimuli and more isolated measures of amplitude like peak amplitude. Overall, these findings suggest that the specific inhibitory mechanisms represented by sensory gating and onset-offset CAEPs differ. Therefore, each CAEP may be better suited to study distinct populations and/or inhibitory functions.
Hematologic Safety of Siltuximab: A Meta-analysis of Randomized Controlled Trials and...
Zhenghua Wu
Li Wang

Zhenghua Wu

and 5 more

November 11, 2024
Introduction:Siltuximab is a monoclonal antibody approved by the US Food and Drug Administration for interleukin-6 (IL-6). Numerous preclinical and clinical studies have revealed the pathological role of the IL-6 pathway in inflammation, autoimmune diseases, and cancer. The drug was approved in 2014 for the treatment of multicentric Castleman’s disease (MCD) and currently has a wide range of applications in the treatment of hematologic diseases. However, no previous studies have evaluated the safety of this drug in the treatment of hematologic disorders, and therefore the present study primarily reassessed the hematologic safety of this drug. Method:PubMed, EMBASE, and ClinicalTrials.gov were searched per the Preferred Reporting Items for Systematic reviews and Meta-Analyses statements for safety assessment while real-world pharmacovigilance data were mined via OpenVigil. Result:In all, four RCTs with 589 pooled patients were included. The safety evaluation revealed that treatment with siltuximab was associated with a propensity for thrombocytopenia (odds ratio [OR]: 1.67; 95% confidence interval [CI]: 1.16-2.40; p < 0.01), while the incidences of anemia and neutropenia were not significant. Regarding the analysis of real-world pharmacovigilance databases, siltuximab use was associated with a significant proclivity for anemia, neutropenia, and thrombocytopenia. Conclusion: The findings indicate that siltuximab is associated with a relatively high risk of anemia, neutropenia, and thrombocytopenia. Both clinicians and patients should exercise caution regarding these potential adverse events and make wise decisions.
Dynamic Semantic Alignment in Large Language Models for Contextual Vector Transformat...
Wendy Forman

Wendy Forman

and 3 more

November 12, 2024
The evolution of artificial intelligence has introduced models capable of capturing complex linguistic patterns, yet existing architectures often struggle with dynamically adapting to diverse contextual shifts. Addressing this gap, the novel framework of Dynamic Semantic Alignment (DSA) presents a sophisticated approach that enables language models to adjust semantic vectors in real time, thereby achieving precise contextual alignment. DSA integrates seamlessly into model architectures, supporting enhanced adaptability without compromising coherence, making it uniquely suited to handle varied linguistic domains and complex contextual demands. Through an extensive series of experiments comparing DSA-enhanced models with baseline architectures, the empirical findings demonstrate substantial improvements in semantic coherence, contextual relevance, and robustness to noise. Additionally, DSA contributes to more efficient processing across high-volume data environments, confirming its capacity to sustain complex language interactions in practical applications. The implications of this research extend to a wide range of languagebased AI tasks, providing a foundation for models capable of realtime semantic adaptation, thereby enriching human-computer interactions through intelligent, responsive language generation.
Pelvis shape predisposes for pelvic organ prolapse: a geometric morphometric study.
Ekaterina Stansfield
Khoa Phan

Ekaterina Stansfield

and 4 more

November 11, 2024
●        Objective Pelvic floor disorders are frequent in women over the age of 50 years. Assessment of risk factors predisposing to pelvic floor disorders is essential to offer guideline-compliant therapy and to improve patients’ quality of life. This study aimed to identify anatomical risk factors for developing pelvic floor disorders. Specifically, we analysed which aspects of the shape of the bony pelvis were associated with the occurrence of pelvic floor prolapse (POP). ●        Design In this cross-sectional study, we compared the shape of the pelvic floor and bony pelvis between three groups: (1) nulliparous women, (2) parous women with no pelvic organ prolapse (POP) and (3) parous women with POP. ●        Setting USA ●        Population or Sample Nulliparous and parous women with and without POP. The primary sample comprised women around 50 y.a. (mean = 50.3, SD = 1.3), with seven women in each group. Methods Landmarks on the pelvis and the urogenital hiatus were collected on MRIs. Using Geometric morphometrics and principal component analysis, new principal axes of variation were established. ●        Main Outcome Measures Individual scores along the first and second principal components. ●        Results The three groups are different when the soft tissue’s shape is analysed together with the shape of the pelvis. Once pelvis landmarks are considered separately, the difference exists only between parous women with and without POP. The difference is highly significant and generalises to other age groups. ●        Conclusions                 The shape of the pelvis in adult women can be used as a risk factor for post-partum POP development.
New strategy for autoimmune hemolytic anemia during pregnancy: a case report
Wenjing Yong
Xi Yuan

Wenjing Yong

and 7 more

November 11, 2024
New strategy for autoimmune hemolytic anemia during pregnancy: a case reportWenjing Yong1*, MD, Xi Yuan2*, MD, Xiaoe Jiang1, MD, Kuilin Fei1, MD, Yuelan Liu1, MD, Yu Jian1, MD, Caihong Hu1, MD, Ping Li1, MD1Department of Obstetrics, Xiangya Hospital, Central South University, Changsha, Hunan, China2Department of Blood Transfusion, Xiangya Hospital, Central South University, Changsha, Hunan, China*These authors contributed to the work equally and should be regarded as co-first authors.
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