Challenges In Interpretation Research Articles

Cracking modes and force dynamics in the insertion of neural probes into hydrogel brain phantom

Objective. The insertion of penetrating neural probes into the brain is crucial for advancing neuroscience, yet it involves various inherent risks. Prototype probes are typically inserted into hydrogel-based brain phantoms and the mechanical responses are analyzed in order to inform the insertion mechanics during in vivo implantation. However, the underlying mechanism of the insertion dynamics of neural probes in hydrogel brain phantoms, particularly the phenomenon of cracking, remains insufficiently understood. This knowledge gap leads to misinterpretations and discrepancies when comparing results obtained from phantom studies to those observed under the in vivo conditions. This study aims to elucidate the impact of probe sharpness and dimensions on the cracking mechanisms and insertion dynamics characterized during the insertion of probes in hydrogel phantoms. Approach. The insertion of dummy probes with different shank shapes defined by the tip angle, width, and thickness is systematically studied. The insertion-induced cracks in the transparent hydrogel were accentuated by an immiscible dye, tracked by in situ imaging, and the corresponding insertion force was recorded. Three-dimensional finite element analysis models were developed to obtain the contact stress between the probe tip and the phantom. Main results. The findings reveal a dual pattern: for sharp, slender probes, the insertion forces remain consistently low during the insertion process, owing to continuously propagating straight cracks that align with the insertion direction. In contrast, blunt, thick probes induce large forces that increase rapidly with escalating insertion depth, mainly due to the formation of branched crack with a conical cracking surface, and the subsequent internal compression. This interpretation challenges the traditional understanding that neglects the difference in the cracking modes and regards increased frictional force as the sole factor contributing to higher insertion forces. The critical probe sharpness factors separating straight and branched cracking is identified experimentally, and a preliminary explanation of the transition between the two cracking modes is derived from three-dimensional finite element analysis. Significance. This study presents, for the first time, the mechanism underlying two distinct cracking modes during the insertion of neural probes into hydrogel brain phantoms. The correlations between the cracking modes and the insertion force dynamics, as well as the effects of the probe sharpness were established, offering insights into the design of neural probes via phantom studies and informing future investigations into cracking phenomena in brain tissue during probe implantations.

Harp literature of Slovenian composers in the 20th century: interpretative challenges and possibilities and parallels with European literature in three Concertos

Harp literature of Slovenian composers in the 20th century: interpretative challenges and possibilities and parallels with European literature in three Concertos

A Report on the Chinese Translation of the Which interventions work best in a pandemic? from the Perspective of Translation as Adaptation

In scientific English texts, there are numerous complex and intricately structured long sentences, primarily used to describe complex and abstract scientific theories, laws, and phenomena. In the practice of scientific translation, accurately translating long and difficult sentences is often a major challenge for translators. Previous research has typically started with an analysis of the syntactic characteristics of long sentences and explored specific translation strategies for these sentences. This article, however, aims to explore the application of seven flexible techniques (amplification, subtraction, rearrangement, elaboration, condensation, combination, and modification) in the translation of long sentences in scientific English from the perspective of translation as adaptation, summarizing different translation strategies into various flexible techniques.

A pH-sensitive closed-loop nanomachine to control hyperexcitability at the single neuron level

Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed. Here, we develop pH-sensitive inhibitory luminopsin (pHIL), a closed-loop chemo-optogenetic nanomachine composed of a luciferase-based light generator, a fluorescent sensor of intracellular pH (E2GFP), and an optogenetic actuator (halorhodopsin) for silencing neuronal activity. Stimulated by coelenterazine, pHIL experiences bioluminescence resonance energy transfer between luciferase and E2GFP which, under conditions of acidic pH, activates halorhodopsin. In primary neurons, pHIL senses the intracellular pH drop associated with hyperactivity and optogenetically aborts paroxysmal activity elicited by the administration of convulsants. The expression of pHIL in hippocampal pyramidal neurons is effective in decreasing duration and increasing latency of pilocarpine-induced tonic-clonic seizures upon in vivo coelenterazine administration, without affecting higher brain functions. The same treatment is effective in markedly decreasing seizure manifestations in a murine model of genetic epilepsy. The results indicate that pHIL represents a potentially promising closed-loop chemo-optogenetic strategy to treat drug-refractory epilepsy.

Rajah dan Spiritualitas Lokal dalam Hukum Islam; Studi Analisis Tafsir Hermeneutik

This study examines the integration of rajah (spiritual chants or incantations) and local spirituality within the context of Islamic law through a hermeneutic interpretative analysis. The research explores how local spiritual practices, particularly the use of rajah, coexist and interact with the principles of Islamic jurisprudence. By employing a hermeneutic approach, the study aims to uncover the deeper meanings and implications of rajah in relation to the spiritual and legal frameworks of Islam. It investigates the cultural and historical significance of rajah, its acceptance and adaptation within various Islamic communities, and the interpretative challenges it presents. The findings reveal a complex interplay between local traditions and Islamic legal thought, highlighting the dynamic nature of religious interpretation and the need for contextual understanding in the application of Islamic law. This study contributes to a broader comprehension of how local spiritual practices can be harmonized with Islamic jurisprudence, offering insights into the evolving relationship between tradition and religion.

Evaluating predictors of kinase activity of STK11 variants identified in primary human non-small cell lung cancers.

Critical evaluation of computational tools for predicting variant effects is important considering their increased use in disease diagnosis and driving molecular discoveries. In the sixth edition of the Critical Assessment of Genome Interpretation (CAGI) challenge, a dataset of 28 STK11 rare variants (27 missense, 1 single amino acid deletion), identified in primary non-small cell lung cancer biopsies, was experimentally assayed to characterize computational methods from four participating teams and five publicly available tools. Predictors demonstrated a high level of performance on key evaluation metrics, measuring correlation with the assay outputs and separating loss-of-function (LoF) variants from wildtype-like (WT-like) variants. The best participant model, 3Cnet, performed competitively with well-known tools. Unique to this challenge was that the functional data was generated with both biological and technical replicates, thus allowing the assessors to realistically establish maximum predictive performance based on experimental variability. Three out of the five publicly available tools and 3Cnet approached the performance of the assay replicates in separating LoF variants from WT-like variants. Surprisingly, REVEL, an often-used model, achieved a comparable correlation with the real-valued assay output as that seen for the experimental replicates. Performing variant interpretation by combining the new functional evidence with computational and population data evidence led to 16 new variants receiving a clinically actionable classification of likely pathogenic (LP) or likely benign (LB). Overall, the STK11 challenge highlights the utility of variant effect predictors in biomedical sciences and provides encouraging results for driving research in the field of computational genome interpretation.

Utilization of SmartNav technology in cochlear implantation: optimizing efficiency in assessment of electrode placement

Objectives Proper electrode placement is essential for favorable hearing outcomes following cochlear implantation. Though often used, traditional intraoperative X-ray imaging is time consuming, exposes patients and staff to radiation, and poses interpretational challenges. The Nucleus® SmartNav System, utilizes electrode voltage telemetry (EVT) to analyze the positioning of the electrode array intraoperatively. This study investigates the efficacy of SmartNav in optimizing the efficiency and accuracy of assessing electrode placement. Methods This prospective clinical study analyzed placement of 50 consecutive Cochlear Corporation cochlear implants conducted at a single institution between March of 2022 and June of 2023. Placement check of electrode array using SmartNav and X-ray was completed and individually assessed. A comparative analysis of SmartNav and X-ray completion times for electrode placement assessment was conducted. Results Subjects included nine ears with abnormal anatomy and three reimplants. SmartNav placement check required a total time of 2.12 min compared to X-ray imaging at 14.23 min (p = 1.6E-16, CI 95%). Both SmartNav and X-ray had excellent sensitivity of 100% in identifying appropriate electrode position (p = 1.0). Tip fold-over was identified using both modalities in 3 cases with noted easier interpretation using SmartNav. Conclusion The Nucleus® SmartNav System significantly outperformed traditional X-ray imaging, offering a faster and more straightforward approach to assessing electrode positioning during cochlear implant surgery, thereby enhancing surgical efficiency and patient safety.

Navigating Disease Management: A Comprehensive Review of the De Ritis Ratio in Clinical Medicine.

The De Ritis ratio, defined as the serum aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, is a widely recognized biochemical marker with significant applications in diagnosing and managing various diseases, particularly liver disorders. This comprehensive review synthesizes current knowledge surrounding the clinical relevance of the De Ritis ratio, examining its historical development, diagnostic utility, and prognostic significance across various medical conditions, including liver diseases, cardiovascular disorders, and muscular pathologies. Through an in-depth analysis of literature spanning several decades, this review highlights the role of the De Ritis ratio not only in differential diagnosis but also as a prognostic indicator for disease progression and patient outcomes. The ratio's ability to distinguish between different types of liver pathology, aid in early disease detection, and its potential use in monitoring treatment response are discussed. Additionally, the review addresses the methodological considerations, such as confounding factors and interpretation challenges, that impact the clinical utility of the De Ritis ratio. Given the evolving landscape of clinical diagnostics and the push toward more personalized medicine, the review concludes with recommendations for further research. These include longitudinal studies to explore the ratio's changes over time, comparative research across diverse populations, and technological integration to enhance diagnostic accuracy and patient care. This review aims to reaffirm the importance of the De Ritis ratio in modern clinical practice and encourages continued exploration into its potential applications and benefits in healthcare.

Iron metabolism in doxorubicin-induced cardiotoxicity: From mechanisms to therapies

Doxorubicin (DOX) is an anti-tumor agent for chemotherapy, but its use is often hindered by the severe and life-threatening side effect of cardiovascular toxicity. In recent years, studies have focused on dysregulated iron metabolism and ferroptosis, a unique type of cell death induced by iron overload, as key players driving the development of DOX-induced cardiotoxicity (DIC). Recent advances have demonstrated that DOX disturbs normal cellular iron metabolism, resulting in excessive iron accumulation and ferroptosis in cardiomyocytes. This review will explore how dysregulated iron homeostasis and ferroptosis drive the progression of DIC. We will also discuss the current approaches to target iron metabolism and ferroptosis to mitigate DIC. Besides, we will discuss the limitations and challenges for clinical translation for these therapeutic regimens.

Saturation genome editing maps the functional spectrum of pathogenic VHL alleles

To maximize the impact of precision medicine approaches, it is critical to identify genetic variants underlying disease and to accurately quantify their functional effects. A gene exemplifying the challenge of variant interpretation is the von Hippel–Lindautumor suppressor (VHL). VHL encodes an E3 ubiquitin ligase that regulates the cellular response to hypoxia. Germline pathogenic variants in VHL predispose patients to tumors including clear cell renal cell carcinoma (ccRCC) and pheochromocytoma, and somatic VHL mutations are frequently observed in sporadic renal cancer. Here we optimize and apply saturation genome editing to assay nearly all possible single-nucleotide variants (SNVs) across VHL’s coding sequence. To delineate mechanisms, we quantify mRNA dosage effects and compare functional effects in isogenic cell lines. Function scores for 2,268 VHL SNVs identify a core set of pathogenic alleles driving ccRCC with perfect accuracy, inform differential risk across tumor types and reveal new mechanisms by which variants impact function. These results have immediate utility for classifying VHL variants encountered clinically and illustrate how precise functional measurements can resolve pleiotropic and dosage-dependent genotype–phenotype relationships across complete genes.

Clinical evaluation on the use of a new accessory device for Fox plane.

Evaluate the assimilation capacity and ease of handling of the Fox plane accessory by dentistry students, through a questionnaire about the experience in using this device compared to the conventional one. Its intention is to minimize possible interpretation errors and challenges that the traditional method determines. After approval by the Research Ethics Committee, registration at Sistema Nacional de Informações sobre Ética em Pesquisa/National Information System on Research Ethics (SISNEP) and signing of the free and informed consent form, 51 undergraduate students treating patients in need of complete dentures at Instituto de Ciência e Tecnologia/Institute of Science and Technology (ICT) Unesp in São José dos Campos completed a questionnaire to evaluate the technical ease of use and provider acceptance. The obtained data were submitted to statistical analysis, evaluating technical ease and acceptance by operators. The results were analyzed using descriptive and inferential statistics using the Jamovi 2.2.5 software. From the responses, the frequency was obtained for each question in the questionnaire, then the weighted mean was calculated, average rating and percentage. With the results of these analyses it was possible to measure the level of satisfaction of the participants in relation to the use of the device. It was concluded that most students have difficulty using the conventional Fox plane and that the accessory facilitated the process of determining the superior orientation plane, and its ease of use.

Difficulties of translating language and ideas in process drama research across cultural contexts: Insight from Sri Lankan experiences

Completing Ph.D. degrees in western or European countries has long been a practice for students and researchers around the world, which contributes to scientific productivity, allows for international recognition and encourages international ties and collaboration between researchers from different countries. Many of these doctoral students conduct data collection for their research projects in their native language in their home country before moving on to the analysis and interpretation stages with the support of language translation. The quality of the translation process and interpretation of data has a huge impact on the ultimate effectiveness and success of proposed interventions. However, conducting data collection in one’s native language, particularly in creative arts such as drama, presents unique challenges for translation and interpretation processes. This article reflects upon the challenges encountered during the translation of data from two original sources – one in Australia and one in Sri Lanka – during an investigation of a process drama intervention. It discusses the cultural and linguistic appropriateness of research methodologies within different educational contexts, emphasizing the importance of considering these factors for ensuring research credibility and validity. By addressing these challenges, educators and researchers can create more inclusive and impactful learning environments for students across diverse cultural and linguistic backgrounds.

Cell-drug conjugates.

By combining living cells with therapeutics, cell-drug conjugates can potentiate the functions of both components, particularly for applications in drug delivery and therapy. The conjugates can be designed to persist in the bloodstream, undergo chemotaxis, evade surveillance by the immune system, proliferate, or maintain or transform their cellular phenotypes. In this Review, we discuss strategies for the design of cell-drug conjugates with specific functions, the techniques for their preparation, and their applications in the treatment of cancers, autoimmune diseases and other pathologies. We also discuss the translational challenges and opportunities of this class of drug-delivery systems and therapeutics.

A Multi-Level Interpretable Sleep Stage Scoring System by Infusing Experts' Knowledge Into a Deep Network Architecture.

In recent years, deep learning has shown potential and efficiency in a wide area including computer vision, image and signal processing. Yet, translational challenges remain for user applications due to a lack of interpretability of algorithmic decisions and results. This black box problem is particularly problematic for high-risk applications such as medical-related decision-making. The current study goal was to design an interpretable deep learning system for time series classification of electroencephalogram (EEG) for sleep stage scoring as a step toward designing a transparent system. We have developed an interpretable deep neural network that includes a kernel-based layer guided by a set of principles used for sleep scoring by human experts in the visual analysis of polysomnographic records. A kernel-based convolutional layer was defined and used as the first layer of the system and made available for user interpretation. The trained system and its results were interpreted in four levels from microstructure of EEG signals, such as trained kernels and effect of each kernel on the detected stages, to macrostructures, such as transitions between stages. The proposed system demonstrated greater performance than prior studies and the system learned information consistent with expert knowledge.

Italy: The updated provisions on the taxation of income distributions from foreign trusts and similar entities residing in ‘privileged tax jurisdictions’

Abstract The article provides an in-depth analysis of Italy’s updated provisions, effective late 2019, on the taxation of income distributions from foreign trusts and similar entities residing in ‘privileged tax jurisdictions’. It highlights the Italian Revenue Agency’s efforts to clarify the tax treatment of these distributions, as well as the challenges posed by the deemed-income-characterization provision whereby any distribution made by such trusts and entities is presumed to be income unless the recipient may document the contrary (ie the characterisation as capital). The article provides a thorough overview of the regulatory landscape, highlighting critical areas and addressing interpretative challenges.

The Role of Image Schemas in Interpreting English Phrasal Verbs: A Philosophical and Linguistic Perspective

Phrasal verbs pose challenges for interpretation due to unpredictable meanings. This study examined how image schemas aid comprehension from linguistic and philosophical viewpoints. A literature review methodology integrated insights from cognitive linguistics, philosophy of language, and related fields to provide a comprehensive understanding. Linguistically, image schemas offer a cognitive framework for processing phrasal verbs by mapping meanings to embodied experiences. Philosophically, schemas reflect how language emerges from and shapes conceptualization. Comparative analysis showed linguistics emphasizes schemas' mental role in comprehension, while philosophy explores their existential significance. Results identified schemas like CONTAINER and PATH that extend metaphorically from physical interactions to abstract phrasal verb meanings. Linguistically, schemas provide a framework for analyzing structures and meanings. Philosophically, schemas reflect language's emergence from embodiment and influence on thought. Teaching implications were to connect phrasal verbs to familiar embodied experiences through schemas. Theoretical implications were that schemas are fundamental to thought and linguistic expressions. By synthesizing perspectives, this study enhanced understanding of the intricate cognitive mechanisms linking schemas to phrasal verbs. It highlighted implications for language education and advances in interdisciplinary inquiry into embodied cognition and communication.

Effects of drug-induced liver injury on the in vivo fate of liposomes

Liposomes represent one of the most extensively studied nano-carriers due to their potential in targeted drug delivery. However, the complex in vivo fate, particularly under pathological conditions, presents challenges for clinical translation of liposomal therapeutics. Liver serves as the most important organ for liposome accumulation and metabolism. Unfortunately, the fate of liposomes under pathological liver conditions has been significantly overlooked. This study aimed to investigate the in vivo pharmacokinetic profile and biodistribution profile of liposomes under drug-induced liver injury (DILI) conditions. Two classic DILI animal models, i.e. acetaminophen-induced acute liver injury (AILI) and triptolide-induced subacute liver injury (TILI), were established to observe the effect of pathological liver conditions on the in vivo performance of liposomes. The study revealed significant changes in the in vivo fate of liposomes following DILI, including prolonged blood circulation and enhanced hepatic accumulation of liposomes. Changes in the composition of plasma proteins and mononuclear phagocyte system (MPS)-related cell subpopulations collectively led to the altered in vivo fate of liposomes under liver injury conditions. Despite liver injury, macrophages remained the primary cells responsible for liposomes uptake in liver, with the recruited monocyte-derived macrophages exhibiting enhanced ability to phagocytose liposomes under pathological conditions. These findings indicated that high capture of liposomes by the recruited hepatic macrophages not only offered potential solutions for targeted delivery, but also warned the clinical application of patients under pathological liver conditions.

Mengoptimalkan Analisis Sifat Mekanik Material Berbasis Data Dengan Pandas Profiling

The analysis of mechanical properties based on data is a method used to analyze the mechanical properties of a material using data, typically obtained from a material database. This process encounters several challenges, such as large volume of data, complexity in data processing, as well as difficulties in data visualization and interpretation. In this study, Pandas Profiling, a Python library designed specifically for automated dataset analysis, was employed. The dataset used consisted of tensile test results for various austenitic stainless steel types such as SUS 304, SUS 316, SUS 321, SUS 347, and NCF 800H. This dataset comprised 1916 samples with attributes related to mechanical properties and factors influencing them. The analysis results using Pandas Profiling indicated a strong negative correlation between heat treatment temperature and Yield Strength (YS) and Ultimate Tensile Strength (UTS). Additionally, a positive correlation was found between chemical elements such as Copper (Cu) and Nickel (Ni) with Elongation (EL). Furthermore, the analysis results revealed that stainless steel treated with water cooling exhibited a higher average UTS value, measuring at 493 MPa, compared to air cooling, which only reached 403 MPa. Pandas Profiling offers an effective solution to overcome common challenges in data-based mechanical property analysis, including dealing with large data volumes, complex data processing, as well as challenges in data visualization and interpretation. By utilizing Pandas Profiling, researchers can easily comprehend the dataset comprehensively, identify patterns, trends, and relationships among variables, and optimize the analysis process of data-based material mechanical properties.

Double strategies for reproducing multimodal puns in interlinguistic translation: Experimental research

The research is dedicated to exposing the specifics of translating multimodal puns based on the retrospective experiment. A multimodal pun is defined as a creolized/ polycoded formation substantiated by a specific type of ambiguity consisting of two inhomogeneous semiotic modes. The material for our research was provided by verbal-visual puns functioning as separate texts. Each multimodal pun results from intersemiotic translation when the signs of one semiotic system are transformed into the signs of another. For the vast majority of multimodal puns, verbal signs are interpreted into pictures, but the opposite cannot be excluded either. The role of the visual component is twofold. It can be creative when the picture is part of the ambiguity mechanism, or it can be amplifying when the picture accentuates the verbal wordplay, not participating directly in the creation of ambiguity. Hence, our first hypothesis is that multimodal puns with an amplifying visual component are a lesser challenge for translators than those with a creative one due to the absence of the necessity to coordinate verbal and visual modes in the target text. The research aims to identify the strategies of interlinguistic translation of multimodal puns and the factors that determine them, particularly the impact of the visual mode on the translator’s decision-making. Hence, our second hypothesis is that multimodal puns require double strategies that would allow to correlate the reproduction of the elements of two different semiotic systems. The analysis of the subjects’ translations, as well as their reports received in the course of the delayed retrospective experiment, confirmed both hypotheses. Disclosure Statement The authors reported no potential conflicts of interest. * Corresponding author: Oleksandr Rebrii, 0000-0002-4912-7489o.v.rebrii@karazin.ua

Effects of multicollinearity and data granularity on regression models of stream temperature

Water temperature is a key factor influencing biota of stream ecosystems. Hence, it is important to comprehend the environmental drivers of stream temperature for robust prediction of conditions and effective management of stream communities. Linear regression models are commonly used for predictive purposes, but their predictive capacity and interpretability can be significantly affected by their complexity and the structure of input data. In some cases, researchers may be obligated to favor prediction power or interpretability while compromising the other. Therefore, insight into relationships between model fit, correlation among predictor variables (i.e., multicollinearity), and level of temporal aggregation of data (i.e., data granularity) may be helpful to reduce such trade-offs. In this paper, we investigated these relationships within a hierarchical set of multiple linear regression (MLR) models examining environmental factors influencing stream temperature dynamics. Our findings showed that as the number of predictor variables (i.e., model complexity) increased, the magnitude of multicollinearity in MLR models increased, but model fit also increased. The results also revealed that using data averaged over longer time frames (i.e., coarser data granularity) yielded high multicollinearity, as indexed by variance inflation factor values (VIF) for all model predictors. This led to higher variance in parameter estimates (i.e., parameter instability) and potential challenges in model interpretation as the sign of parameter estimates changed in many streams examined. Multicollinearity was not the only reason for these changes in the sign of parameter estimates as they were also observed in simple linear regression models across varying levels of data granularity. Based on our findings, we conclude that the selection of data granularity is an important consideration in multiple regression modeling, with profound implications for model interpretability.