bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Signal Features of Functional Near-Infrared Spectroscopy for Acute Physiological Score Estimation in ECMO Patients
Authors: Chang Hsiao-Huang , Hou Kai-Hsiang , Chiang Ting-Wei , Wang Yi-Min , Sun Chia-Wei
Published: December 2023

Extracorporeal membrane oxygenation (ECMO) is a vital emergency procedure providing respiratory and circulatory support to critically ill patients, especially those with compromised cardiopulmonary function. Its use has grown due to technological advances and clinical demand. Prolonged ECMO usage can lead to complications, necessitating the timely assessment of peripheral microcirculation for an accurate physiological evaluation. This study utilizes non-invasive near-infrared spectroscopy (NIRS) to monitor knee-level microcirculation in ECMO patients. After processing oxygenation data, machine learning distinguishes high and low disease severity in the veno-venous (VV-ECMO) and veno-arterial (VA-ECMO) groups, with two clinical parameters enhancing the model performance. Both ECMO modes show promise in the clinical severity diagnosis. The research further explores statistical correlations between the oxygenation data and disease severity in diverse physiological conditions, revealing moderate correlations with the acute physiologic and chronic health evaluation (APACHE II) scores in the VV-ECMO and VA-ECMO groups. NIRS holds the potential for assessing patient condition improvements.
Improving Sonication Efficiency in Transcranial MR-Guided Focused Ultrasound Treatment: A Patient-Data Simulation Study
Authors: Kim Changsoo , Eames Matthew , Paeng Dong-Guk
Published: December 2023

The potential improvement in sonication efficiency achieved by tilting the focused ultrasound (FUS) transducer of the transcranial MR-guided FUS system is presented. A total of 56 cases of patient treatment data were used. The relative position of the clinical FUS transducer to the patient’s head was reconstructed, and region-specific skull density and porosity were calculated based on the patient’s CT volume image. The total transmission coefficient of acoustic waves emitted from each channel was calculated. Then, the total energy penetrating the human skull—which represents the sonication efficiency—was estimated. As a result, improved sonication efficiency was by titling the FUS transducer to a more appropriate angle achieved in all 56 treatment cases. This simulation result suggests the potential improvement in transcranial-focused ultrasound treatment by simply adjusting the transducer angle.
Are Adenomyosis and Endometriosis Phenotypes of the Same Disease Process?
Authors: Habiba Marwan , Guo Sun-Wei , Benagiano Giuseppe
Published: December 2023

In recent literature reviews, we concluded that the possibility that endometrial molecular aberrations are the sole or a necessary determinant of endometriosis and the Tissue Injury and Repair (TIAR) theory are yet to be convincingly proven. Here, we critically examine the theory that adenomyosis and endometriosis represent different phenotypes of a single disease. A common etiopathology for adenomyosis and endometriosis has been suggested because both conditions entail the presence of endometrial tissue at locations other than the lining of the uterus. There are wide differences in reported disease incidence and prevalence and, consequently, in estimates of the coexistence of both conditions. There are some similarities but also differences in their clinical features and predisposing factors. Each condition has a range of subtypes. These differences alone pose the question of whether subtypes of endometriosis and adenomyosis have different etiopathologies, and, in turn, this raises the question of whether they all share a common etiology. It is debatable whether the recognized differences between the eutopic endometrium in adenomyosis and endometriosis compared to those in unaffected women are the cause or the effect of the disease. The finding of common mutations, particularly of KRAS, lend support to the notion of shared predisposing factors, but this alone is insufficient evidence of causation.
MiR-192-5p Ameliorates Hepatic Lipid Metabolism in Non-Alcoholic Fatty Liver Disease by Targeting Yy1
Authors: Ma Lina , Song Huichen , Zhang Chen-Yu , Hou Dongxia
Published: December 2023

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation in the liver. Clarifying the molecular mechanism of lipid metabolism is crucial for the treatment of NAFLD. We examined miR-192-5p levels in the livers of mice in which NAFLD was induced via a high-fat diet (HFD), as well as in mouse primary hepatocytes and human HepG2 cells treated with free fatty acids (FFAs). MiR-192-5p inhibitor was administered to NAFLD mice and hepatocytes to verify the specific function of miR-192-5p in NAFLD. We validated the target gene of miR-192-5p and further illustrated the effects of this miRNA on the regulation of triglyceride (TG) metabolism. We found that miR-192-5p was significantly increased in the livers of NAFLD mice and FFA-treated hepatocytes. Inhibition of miR-192-5p increased the accumulation of hepatic TGs and aggravated hepatic steatosis in NAFLD mice. In FFA-treated hepatocytes, miR-192-5p inhibitors markedly increased TG content, whereas overexpression of miR-192-5p reduced TG levels. Yin Yang 1 (Yy1) was identified as the target gene of miR-192-5p, which regulates TG synthesis via the YY1/fatty-acid synthase (FASN) pathway. Our results demonstrated that miR-192-5p should be considered a protective regulator in NAFLD that can inhibit hepatic TG synthesis by targeting Yy1.
B-Blockers in Liver Cirrhosis: A Wonder Drug for Every Stage of Portal Hypertension? A Narrative Review
Authors: Karagiannakis Dimitrios S. , Karakousis Nikolaos D. , Androutsakos Theodoros
Published: December 2023

In cirrhotic patients, non-selective b-blockers (NSBBs) constitute the reference treatment of choice as monotherapy or combined with band ligation for the prevention of first variceal bleeding and rebleeding, respectively. Furthermore, the last Baveno VII guidelines recommended carvedilol, a b-blocker with additional anti-a1 receptor activity, in all compensated cirrhotics with clinically significant portal hypertension, to prevent liver decompensation. Interestingly enough, NSBBs have been reported to have a potentially positive impact on the short-term mortality of patients with acute-on-chronic liver failure. However, concerns remain about the use of b-blockers in the presence of severe complications, such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, or established cirrhotic cardiomyopathy. In addition, it has not been verified yet whether carvedilol supersedes all the other NSBBs in every stage of liver disease, even when severe complications have developed. Therefore, this review aims to illustrate recent data regarding the potential role of b-blockers across all stages of liver disease, beyond the primary and secondary prophylaxis of variceal bleeding, and address the authors’ proposals on the use of NSBBs concerning the severity of liver disease and the patient’s performance status.
Machine Learning Combined with Radiomics Facilitating the Personal Treatment of Malignant Liver Tumors
Authors: Sheng Liuji , Yang Chongtu , Chen Yidi , Song Bin
Published: December 2023

In the realm of managing malignant liver tumors, the convergence of radiomics and machine learning has redefined the landscape of medical practice. The field of radiomics employs advanced algorithms to extract thousands of quantitative features (including intensity, texture, and structure) from medical images. Machine learning, including its subset deep learning, aids in the comprehensive analysis and integration of these features from diverse image sources. This potent synergy enables the prediction of responses of malignant liver tumors to various treatments and outcomes. In this comprehensive review, we examine the evolution of the field of radiomics and its procedural framework. Furthermore, the applications of radiomics combined with machine learning in the context of personalized treatment for malignant liver tumors are outlined in aspects of surgical therapy and non-surgical treatments such as ablation, transarterial chemoembolization, radiotherapy, and systemic therapies. Finally, we discuss the current challenges in the amalgamation of radiomics and machine learning in the study of malignant liver tumors and explore future opportunities.
Biodistribution of RNA Vaccines and of Their Products: Evidence from Human and Animal Studies
Authors: Pateev Ildus , Seregina Kristina , Ivanov Roman , Reshetnikov Vasiliy
Published: December 2023

Explosive developments in mRNA vaccine technology in the last decade have made it possible to achieve great success in clinical trials of mRNA vaccines to prevent infectious diseases and develop cancer treatments and mRNA-based gene therapy products. The approval of the mRNA-1273 and BNT162b2 mRNA vaccines against SARS-CoV-2 by the U.S. Food and Drug Administration has led to mass vaccination (with mRNA vaccines) of several hundred million people around the world, including children. Despite its effectiveness in the fight against COVID-19, rare adverse effects of the vaccination have been shown in some studies, including vascular microcirculation disorders and autoimmune and allergic reactions. The biodistribution of mRNA vaccines remains one of the most poorly investigated topics. This mini-review discussed the results of recent experimental studies on humans and rodents regarding the biodistribution of mRNA vaccines, their constituents (mRNA and lipid nanoparticles), and their encoded antigens. We focused on the dynamics of the biodistribution of mRNA vaccine products and on the possibility of crossing the blood–brain and blood–placental barriers as well as transmission to infants through breast milk. In addition, we critically assessed the strengths and weaknesses of the detection methods that have been applied in these articles, whose results’ reliability is becoming a subject of debate.
Feature Selection Problem and Metaheuristics: A Systematic Literature Review about Its Formulation, Evaluation and Applications
Authors: Barrera-García José , Cisternas-Caneo Felipe , Crawford Broderick , Gómez Sánchez Mariam , Soto Ricardo
Published: December 2023

Feature selection is becoming a relevant problem within the field of machine learning. The feature selection problem focuses on the selection of the small, necessary, and sufficient subset of features that represent the general set of features, eliminating redundant and irrelevant information. Given the importance of the topic, in recent years there has been a boom in the study of the problem, generating a large number of related investigations. Given this, this work analyzes 161 articles published between 2019 and 2023 (20 April 2023), emphasizing the formulation of the problem and performance measures, and proposing classifications for the objective functions and evaluation metrics. Furthermore, an in-depth description and analysis of metaheuristics, benchmark datasets, and practical real-world applications are presented. Finally, in light of recent advances, this review paper provides future research opportunities.
An Analysis of Fluid Intake Assessment Approaches for Fluid Intake Monitoring System
Authors: Hsieh Chia-Yeh , Huang Hsiang-Yun , Chan Chia-Tai , Chiu Li-Tzu
Published: December 2023

Monitoring fluid intake is essential to help people manage their individual fluid intake behaviors and achieve adequate hydration. Previous studies of fluid intake assessment approaches based on inertial sensors can be categorized into wrist-worn-based and smart-container-based approaches. This study aims to analyze wrist-worn-based and smart-container-based fluid intake assessment approaches using inertial sensors. The comparison of these two approaches should be analyzed according to gesture recognition and volume estimation. In addition, the influence of the fill level and sip size information on the performance is explored in this study. The accuracy of gesture recognition with postprocessing is 92.89% and 91.8% for the wrist-worn-based approach and smart-container-based approach, respectively. For volume estimation, sip-size-dependent models can achieve better performance than general SVR models for both wrist-worn-based and smart-container-based approaches. The improvement of MAPE, MAD, and RMSE can reach over 50% except MAPE for small sip sizes. The results demonstrate that the sip size information and recognition performance are important for fluid intake assessment approaches.
The Neural Mechanisms of Group Membership Effect on Emotional Mimicry: A Multimodal Study Combining Electromyography and Electroencephalography
Authors: Kuang Beibei , Peng Shenli , Wu Yuhang , Chen Ying , Hu Ping
Published: December 2023

Emotional mimicry plays a vital role in understanding others’ emotions and has been found to be modulated by social contexts, especially group membership. However, the neural mechanisms underlying this modulation remain unclear. We explored whether and how group membership modulated emotional mimicry using a multimodal method combining facial electromyography (fEMG) and electroencephalography (EEG). We instructed participants to passively view dynamic emotional faces (happy vs. angry) of others (in-group vs. out-group) and simultaneously recorded their fEMG and EEG responses. Then, we conducted combined analyses of fEMG-EEG by splitting the EEG trials into two mimicry intensity categories (high-intensity mimicry vs. low-intensity mimicry) according to fEMG activity. The fEMG results confirmed the occurrence of emotional mimicry in the present study but failed to find a group membership effect. However, the EEG results showed that participants mimicked in-group happiness and anger more than out-group. Importantly, this in-group preference involved different neural mechanisms in happiness and anger mimicry. In-group preference for happiness mimicry occurred at multiple neural mechanisms such as N1 (at P7, Pz, and P8), P2 (at Pz and P8), N2 (at P8), and P3 (at P7, Pz, and P8); in-group preference for anger mimicry occurred at P1 (at P7) and P2 (at Pz). Our findings provide new neural evidence for the effect of group membership on emotional mimicry by uncovering the temporal dynamics of this effect.
Efficacy of Transcranial Direct Current Stimulation on Pain Level and Disability of Patients with Fibromyalgia: A Systematic Review of Randomized Controlled Trials with Parallel-Group Design
Authors: Azarkolah Anita , Noorbala Ahmad Ali , Ansari Sahar , Hallajian Amir-Homayun , Salehinejad Mohammad Ali
Published: December 2023

Transcranial direct current stimulation (tDCS) has been increasingly applied in fibromyalgia (FM) to reduce pain and fatigue. While results are promising, observed effects are variable, and there are questions about optimal stimulation parameters such as target region (e.g., motor vs. prefrontal cortices). This systematic review aimed to provide the latest update on published randomized controlled trials with a parallel-group design to examine the specific effects of active tDCS in reducing pain and disability in FM patients. Using the PRISMA approach, a literature search identified 14 randomized controlled trials investigating the effects of tDCS on pain and fatigue in patients with FM. Assessment of biases shows an overall low-to-moderate risk of bias. tDCS was found effective in all included studies conducted in patients with FM, except one study, in which the improving effects of tDCS were due to placebo. We recommended tDCS over the motor and prefrontal cortices as “effective” and “probably effective” respectively, and also safe for reducing pain perception and fatigue in patients with FM, according to evidence-based guidelines. Stimulation polarity was anodal in all studies, and one single-session study also examined cathodal polarity. The stimulation intensity ranged from 1-mA (7.14% of studies) to 1.5-mA (7.14% of studies) and 2-mA (85.7% of studies). In all of the included studies, a significant improvement in at least one outcome variable (pain or fatigue reduction) was observed. Moreover, 92.8% (13 of 14) applied multi-session tDCS protocols in FM treatment and reported significant improvement in their outcome variables. While tDCS is therapeutically effective for FM, titration studies that systematically evaluate different stimulation intensities, durations, and electrode placement are needed.
The Cortical Silent Period and Its Association with Fatigue in Multiple Sclerosis: The Need for Standardized Data Collection
Authors: Strauss Sebastian , Herr Thorsten , Nafz Christina , Seusing Nelly , Grothe Matthias
Published: December 2023

The cortical silent period (CSP), assessed with transcranial magnetic stimulation (TMS), provides insights into motor cortex excitability. Alterations in the CSP have been observed in multiple sclerosis (MS), although a comparison of the sometimes contradictory results is difficult due to methodological differences. The aim of this study is to provide a more profound neurophysiological understanding of fatigue’s pathophysiology and its relationship to the CSP. Twenty-three patients with MS, along with a matched control group, underwent comprehensive CSP measurements at four intensities (125, 150, 175, and 200% resting motor threshold), while their fatigue levels were assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC) and its motor and cognitive subscore. MS patients exhibited a significantly increased CSP duration compared to controls (p = 0.02), but CSP duration was not associated with the total FSMC, or the motor or cognitive subscore. Our data suggest a systematic difference in MS patients compared to healthy controls in the CSP but no association with fatigue when measured with the FSMC. Based on these results, and considering the heterogeneous literature in the field, our study highlights the need for a more standardized approach to neurophysiological data collection and validation. This standardization is crucial for exploring the link between TMS and clinical impairments in diseases like MS.
Psychometric Properties of a Cyberaggression Measure in Mexican Students
Authors: Navarro-Rodríguez Christián Denisse , Bauman Sheri , Vera Noriega José Ángel , Lagarda Lagarda Angel Emigdio
Published: December 2023

Cyberaggression is an important problem today; it can affect adolescents in different ways. Therefore, reliable and valid measures are necessary to better study the phenomenon. The aim of the present study was to generate validity and reliability evidence for a Spanish-language cyberaggression scale from Garaigordobil, (2017) in a population of 1695 adolescents from northwestern Mexico (51.5% female) between 12- and 15-years-of-age. The results of this study contribute to the research and focus on cyberaggression in adolescents in Mexico. The measure used in this paper detects the different roles, including the bystander, rigorously testing the reliability and validity of the measure, providing a solid tool to evaluate cyberaggression in the Mexican context and guide evidence-based interventions and policies in educational settings.
Feature-Centric Approach for Learning-Based Prediction of Pavement Marking Retroreflectivity from Mobile LiDAR Data
Authors: Manasreh Dmitry , Nazzal Munir D. , Abbas Ala R.
Published: December 2023

Given the crucial importance of pavement marking retroreflectivity in ensuring visibility for road safety, this research investigates the correlation between pavement marking reflectivity and LiDAR data. Empirical data were collected from eight road sections using both a handheld retroreflectometer and a mobile LiDAR. The approach proposed focuses on extracting important features from pavement marking regions of the LiDAR point cloud. A comprehensive feature extraction and feature selection process was employed. In addition, a well-rounded selection of learning algorithms was evaluated. A rigorous hold-out evaluation was incorporated, ensuring that the reported performance metrics were robustly generalizable. The best performing model was able to achieve an R2 of 0.824 on unseen data. The findings of this study illuminate the potential for leveraging relatively inexpensive mobile LiDAR sensors in combination with machine learning techniques in conducting efficient pavement marking assessments, not only to detect completely degraded markings, but to accurately estimate retroreflective properties.
Enhancing Thermal Efficiency through the Use of Graphite-Infused Phase Change Materials in Roof Structures to Reduce Building Cooling Demand
Authors: Mano Chanita , Fazlizan Ahmad , Thongtha Atthakorn
Published: December 2023

This research focuses on the thermal properties of three distinctive paraffin waxes—PCMA, PCMB, and PCMC—each characterized by a specific melting point. The crucial phase transition temperature intervals and latent heat values were examined using differential scanning calorimetry (DSC) in the temperature range of 0 °C to 80 °C. These parameters are pivotal for the effective application of these phase change materials (PCMs) in building envelopes, influencing the overall heat storage performance. The study delved into the development and encapsulation of blends containing both the phase change material (PCM) and graphite. This involves combining the chosen PCM with graphite powder and examining the weight ratios of 10% and 20%. The thermal characteristics of these blends revealed that a 10% ratio of graphite powder proved effective in improving the PCM with graphite. This resulted in a reduced range of melting and solidification temperatures while maintaining the essential chemical structure of the PCM without additives. Furthermore, the practical application of PCM–graphite composites within a building’s envelope was explored, revealing a substantial reduction in heat transfer from the exterior to the interior of the building. This underscores the potential for energy-efficient building designs.
Insights on the Mortars of Ancient Roman Aqueducts: Aqua Virgo and Aqueduct Y, Rome (Italy)
Authors: Calzolari Laura , Amadasi Maria Elisa , Medeghini Laura , Mignardi Silvano
Published: December 2023

Despite the archaeological importance of Aqua Virgo, a Roman aqueduct built in 19 BC and still functioning nowadays, there is a lack of information about the mortars coming from the inner duct. This work aims to investigate the mortars from Aqua Virgo and Aqueduct Y, an unidentified aqueduct running under the first one in the La Rinascente area (between Via del Nazareno and Via dei Due Macelli, Rome, IT) through Optical Microscopy (OM), X-ray Powder Diffraction (XRPD) and Scanning Electron Microscopy with Energy Dispersive Spectroscopy (SEM-EDS). The aim is to understand which materials guarantee such longevity and differentiate between different intervention phases. Local natural materials with pozzolanic behaviour—in particular, Pozzolane Rosse—and ceramic fragments are widely employed, mixed or not, for the realisation of the hydraulic mortars under investigation, independently of the intervention phase. Of particular interest is the discovery of an amorphous binder composed of Si, Al, Ca, K and Mg in some samples characterised by the absence of calcite.
Carbon and Greenhouse Gas Emissions from Electricity Consumption in European Union Buildings
Authors: Balaras Constantinos A. , Dascalaki Elena G. , Patsioti Matina , Droutsa Kalliopi G. , Kontoyiannidis Simon , Cholewa Tomasz
Published: December 2023

The buildings sector is the single most important end-user of final energy in the European Union and a significant contributor to carbon and greenhouse gas emissions. This work focuses on a review of available data that are used to calculate the annual emissions from electricity generation in the European Union and quantify indirect emissions from the use of electricity in the buildings sector. Historical data since 1990 are used to derive simple empirical correlations for the time evolution of emissions factors related to electricity production in each Member State of the European Union. More recent trajectories using data from the last ten years are also presented. The derived correlations can be easily integrated in building stock modeling and national studies to facilitate forward-looking projections of emissions from electricity use in buildings. The EU-27 averages 0.2883 kgCO2-eq/kWhel, ranging from 0.0456 kgCO2-eq/kWhel in Sweden up to 1.0595 kgCO2-eq/kWhel in Poland. As a case study, the derived coefficients are then used to quantify the indirect emissions from the electricity consumption attributed to the building stock in each EU Member State. The calculated total EU-27 GHG indirect emissions attributed to electricity consumption amounted to 215 MtCO2-eq for residential buildings and 201 MtCO2-eq for non-residential buildings. In addition, the proposed correlations are used to demonstrate how they can be used for more realistic future projections of emissions towards the national targets in Greece and Poland.
High Energy Density Primary Lithium Battery with Fluorinated S-Doped Graphene
Authors: Colin Marie , Farhat Hani , Chen Sam , Petit Elodie , Flahaut Emmanuel , Guérin Katia , Dubois Marc
Published: December 2023

Sulphur-doped graphene was fluorinated using molecular fluorine (F2). First, the fluorination conditions were adapted in order to be mild enough to maintain S in the carbon lattice and form S-F bonds. An unusually weakened C-F bonding for an F/C ratio of 0.71 was then achieved, which allowed enhanced performances when used as a cathode in primary lithium batteries. The material prepared at a moderate fluorination temperature of 70 °C for a period of 60 min exhibits a high mid-discharge reduction potential of 3.11 V at 10 mA/g and a power density of 3605 W/kg at a discharge rate of 2C. These electrochemical properties make the fluorine/sulfur co-doped graphene a promising material.
CEP-1347 Dually Targets MDM4 and PKC to Activate p53 and Inhibit the Growth of Uveal Melanoma Cells
Authors: Togashi Keita , Suzuki Shuhei , Mitobe Yuta , Nakagawa-Saito Yurika , Sugai Asuka , Takenouchi Senri , Sugimoto Masahiko , Kitanaka Chifumi , Okada Masashi
Published: December 2023

Uveal melanoma (UM) is among the most common primary intraocular neoplasms in adults, with limited therapeutic options for advanced/metastatic disease. Since UM is characterized by infrequent p53 mutation coupled with the overexpression of MDM4, a major negative regulator of p53, we aimed to investigate in this study the effects on UM cells of CEP-1347, a novel MDM4 inhibitor with a known safety profile in humans. We also examined the impact of CEP-1347 on the protein kinase C (PKC) pathway, known to play a pivotal role in UM cell growth. High-grade UM cell lines were used to analyze the effects of genetic and pharmacological inhibition of MDM4 and PKC, respectively, as well as those of CEP-1347 treatment, on p53 expression and cell viability. The results showed that, at its clinically relevant concentrations, CEP-1347 reduced not only MDM4 expression but also PKC activity, activated the p53 pathway, and effectively inhibited the growth of UM cells. Importantly, whereas inhibition of either MDM4 expression or PKC activity alone failed to efficiently activate p53 and inhibit cell growth, inhibition of both resulted in effective activation of p53 and inhibition of cell growth. These data suggest that there exists a hitherto unrecognized interaction between MDM4 and PKC to inactivate the p53-dependent growth control in UM cells. CEP-1347, which dually targets MDM4 and PKC, could therefore be a promising therapeutic candidate in the treatment of UM.
Correction: Gallus et al. Immunotherapy Approaches in Isocitrate-Dehydrogenase-Mutant Low-Grade Glioma. Cancers 2023, 15, 3726
Authors: Gallus Marco , Kwok Darwin , Lakshmanachetty Senthilnath , Yamamichi Akane , Okada Hideho
Published: December 2023

It has come to our attention that the previously published manuscript contained an outdated iteration of Table 1 [...]
ONCOBREAST-TEST Is a Quick Diagnostic, Prognostic and Predictive Method of Response to Systemic Treatment
Authors: Tankiewicz-Kwedlo Anna , Lobacz Tomasz , Kozlowski Leszek , Czartoryska-Arlukowicz Bogumila , Koda Mariusz , Pawlak Krystyna , Czarnomysy Robert , Borkowska Magdalena Joanna , Pawlak Dariusz
Published: December 2023

ONCOBREAST-TEST is a diagnostic and therapeutic procedure that is part of the comprehensive care of a patient with breast cancer.: Chemosensitivity of cancer cells was assessed using the MTT test, morphological assessment of cells, LDH activity in the culture medium, and flow cytometry technique (apoptosis, proliferation, CD24, CD44, GATA3, cytokeratin, Ki-67). Diagnostic tools included panels of simple tests which could be used to accurately predict the chemosensitivity of tumor cells previously isolated from a patient, even before actual chemotherapy. The proposed procedure allows for a simple (based on MTT results, cell morphology, LDH concentration), minimally invasive, quick, and accurate assessment of the sensitivity of breast cancer cells to the drugs used and, to select the most effective treatment plan as part of personalized therapy. In a patient with NOS G3, the most promising therapy will be docetaxel with cyclophosphamide and in the case of a patient with NOS G1, paclitaxel alone and in combination with trastuzumab. The implementation of such a procedure would undoubtedly increase the effectiveness of chemotherapy, reduce side effects by excluding drugs that are ineffective before using them, protect the patient’s health, and shorten the treatment time, bringing economic and social benefits.
Intraoperative Assessment of Resection Margin in Oral Cancer: The Potential Role of Spectroscopy
Authors: Vlocskó Máté , Piffkó József , Janovszky Ágnes
Published: December 2023

In parallel with the increasing number of oncological cases, the need for faster and more efficient diagnostic tools has also appeared. Different diagnostic approaches are available, such as radiological imaging or histological staining methods, but these do not provide adequate information regarding the resection margin, intraoperatively, or are time consuming. The purpose of this review is to summarize the current knowledge on spectrometric diagnostic modalities suitable for intraoperative use, with an emphasis on their relevance in the management of oral cancer. The literature agrees on the sensitivity, specificity, and accuracy of spectrometric diagnostic modalities, but further long-term prospective, multicentric clinical studies are needed, which may standardize the intraoperative assessment of the resection margin and the use of real-time spectroscopic approaches.
SIRT1 Promotes Cisplatin Resistance in Bladder Cancer via Beclin1 Deacetylation-Mediated Autophagy
Authors: Sun Yan , Liu Xudong , Tong Hang , Yin Hubin , Li Tinghao , Zhu Junlong , Chen Junrui , Wu Linfeng , Zhang Xiaoyu , Gou Xin , He Weiyang
Published: December 2023

Autophagy-dependent cisplatin resistance poses a challenge in bladder cancer treatment. SIRT1, a protein deacetylase, is involved in autophagy regulation. However, the precise mechanism through which SIRT1 mediates cisplatin resistance in bladder cancer via autophagy remains unclear. In this study, we developed a cisplatin-resistant T24/DDP cell line to investigate this mechanism. The apoptosis rate and cell viability were assessed using flow cytometry and the CCK8 method. The expression levels of the relevant RNA and protein were determined using RT-qPCR and a Western blot analysis, respectively. Immunoprecipitation was utilized to validate the interaction between SIRT1 and Beclin1, as well as to determine the acetylation level of Beclin1. The findings indicated the successful construction of the T24/DDP cell line, which exhibited autophagy-dependent cisplatin resistance. Inhibiting autophagy significantly reduced the drug resistance index of these cells. The T24/DDP cell line showed a high SIRT1 expression level. The overexpression of SIRT1 activated autophagy, thereby further promoting cisplatin resistance in the T24/DDP cell line. Conversely, inhibiting autophagy counteracted the cisplatin-resistance-promoting effects of SIRT1. Silencing SIRT1 led to increased acetylation of Beclin1, the inhibition of autophagy, and a reduction in the cisplatin resistance of the T24/DDP cell line. Introducing a double mutation (lysine 430 and 437 to arginine, 2KR) in Beclin-1 inhibited acetylation and activated autophagy, effectively reversing the decreased cisplatin resistance resulting from SIRT1 silencing. In summary, our study elucidated that SIRT1 promotes cisplatin resistance in human bladder cancer T24 cells through Beclin1-deacetylation-mediated autophagy activation. These findings suggest a potential new strategy for reversing cisplatin resistance in bladder cancer.
LGR5+ Intestinal Stem Cells Display Sex-Dependent Radiosensitivity
Authors: Zitter Ryan C. , Chugh Rishi Man , Bhanja Payel , Kimler Bruce F. , Saha Subhrajit
Published: December 2023

Tissue radiosensitivity plays a critical role in the overall outcome of radiation therapy. Identifying characteristics that predict how a patient may respond to radiotherapy enables clinicians to maximize the therapeutic window. Limited clinical data have suggested a difference in male and female radiotherapy outcomes. Radiotherapy for gastrointestinal malignancy is still a challenge due to intestinal sensitivity to radiation toxicity. In this manuscript, we demonstrated sex-specific differences in intestinal epithelial radiosensitivity. In a mouse model of abdominal irradiation, we observed a significant increase in oxidative stress and injury in males compared to females. Lgr5+ve intestinal stem cells from male mice showed higher sensitivity to radiation-induced toxicity. However, sex-specific differences in intestinal radiosensitivity were not dependent on sex hormones, as we demonstrated similar sex-specific radiosensitivity differences in pre-pubescent mice. In an ex vivo study, we found that patient-derived intestinal organoid (PID) from males showed higher sensitivity to radiation compared to females as evident from loss of budding crypts, organoid size, and membrane integrity. Transcriptomic analysis of human Lgr5+ intestinal stem cells suggested radiation-induced upregulation of mitochondrial oxidative metabolism in males compared to females, a possible mechanism for radiosensitivity differences.
The Emerging Role of SIRT7 in Glucose and Lipid Metabolism
Authors: Yamagata Kazuya , Mizumoto Tomoya , Yoshizawa Tatsuya
Published: December 2023

Sirtuins (SIRT1–7 in mammals) are a family of NAD+-dependent lysine deacetylases and deacylases that regulate diverse biological processes, including metabolism, stress responses, and aging. SIRT7 is the least well-studied member of the sirtuins, but accumulating evidence has shown that SIRT7 plays critical roles in the regulation of glucose and lipid metabolism by modulating many target proteins in white adipose tissue, brown adipose tissue, and liver tissue. This review focuses on the emerging roles of SIRT7 in glucose and lipid metabolism in comparison with SIRT1 and SIRT6. We also discuss the possible implications of SIRT7 inhibition in the treatment of metabolic diseases such as type 2 diabetes and obesity.
Choroidal Mast Cells and Pathophysiology of Age-Related Macular Degeneration
Authors: Malih Sara , Song Yong-Seok , Sorenson Christine M. , Sheibani Nader
Published: December 2023

Age-related macular degeneration (AMD) remains a leading cause of vision loss in elderly patients. Its etiology and progression are, however, deeply intertwined with various cellular and molecular interactions within the retina and choroid. Among the key cellular players least studied are choroidal mast cells, with important roles in immune and allergic responses. Here, we will review what is known regarding the pathophysiology of AMD and expand on the recently proposed intricate roles of choroidal mast cells and their activation in outer retinal degeneration and AMD pathogenesis. We will focus on choroidal mast cell activation, the release of their bioactive mediators, and potential impact on ocular oxidative stress, inflammation, and overall retinal and choroidal health. We propose an important role for thrombospondin-1 (TSP1), a major ocular angioinflammatory factor, in regulation of choroidal mast cell homeostasis and activation in AMD pathogenesis. Drawing from limited studies, this review underscores the need for further comprehensive studies aimed at understanding the precise roles changes in TSP1 levels and choroidal mast cell activity play in pathophysiology of AMD. We will also propose potential therapeutic strategies targeting these regulatory pathways, and highlighting the promise they hold for curbing AMD progression through modulation of mast cell activity. In conclusion, the evolving understanding of the role of choroidal mast cells in AMD pathogenesis will not only offer deeper insights into the underlying mechanisms but will also offer opportunities for development of novel preventive strategies.
Tsc1 Loss in VIP-Lineage Cortical Interneurons Results in More VIP+ Interneurons and Enhanced Excitability
Authors: Hu Jia Sheng , Malik Ruchi , Sohal Vikaas S. , Rubenstein John L. , Vogt Daniel
Published: December 2023

The mammalian target of rapamycin (mTOR) signaling pathway is a powerful regulator of cell proliferation, growth, synapse maintenance and cell fate. While intensely studied for its role in cancer, the role of mTOR signaling is just beginning to be uncovered in specific cell types that are implicated in neurodevelopmental disorders. Previously, loss of the Tsc1 gene, which results in hyperactive mTOR, was shown to affect the function and molecular properties of GABAergic cortical interneurons (CINs) derived from the medial ganglionic eminence. To assess if other important classes of CINs could be impacted by mTOR dysfunction, we deleted Tsc1 in a caudal ganglionic eminence-derived interneuron group, the vasoactive intestinal peptide (VIP)+ subtype, whose activity disinhibits local circuits. Tsc1 mutant VIP+ CINs reduced their pattern of apoptosis from postnatal days 15–20, resulting in increased VIP+ CINs. The mutant CINs exhibited synaptic and electrophysiological properties that could contribute to the high rate of seizure activity in humans that harbor Tsc1 mutations.
4,4-Bis(isopropylthio)-1,1-diphenyl-2-azabuta-1,3-diene Adducts with Cadmium(II), Mercury(II) and Copper(I) Iodides: Crystal, Molecular and Electronic Structures of d10 Transition Metal Chelate Complexes
Authors: Kinghat Rodolphe , Khatyr Abderrahim , Knorr Michael , Strohmann Carsten , Kubicki Marek M.
Published: December 2023

The thioether-functionalized 2-azabutadiene (iPrS)2C=C(H)-N=CPh2 L ligates to CdI2 and HgI2 to form the chelate compounds [CdI2{(iPrS)2C=C(H)-N=CPh2] (1) and [HgI2(iPrS)2C=C(H)-N=CPh2] (2). Their crystal structures were solved via X-ray diffraction. Both crystallize in the non-centrosymmetric space groups: monoclinic P21 (1) and orthorhombic P212121 (2), respectively. The closed-shell d10 metal centers are four-coordinated (two iodides and S and N coordinating atoms from the ligand L) in both complexes. The geometrical indexes τ indicate that a highly distorted trigonal pyramidal is adopted for 1 and a seesaw geometry for 2. The comparative nature of metal–ligand bonds is discussed on the basis of metric parameters and of QT-AIM (quantum theory of atoms in molecules) calculations. L was also treated with CuI to obtain the dinuclear species [LCu(μ2-I2)CuL] (3), in which the two Cu(I) centers are linked by a short metal–metal bond. The geometric and electronic properties of 3 are compared with those of 1 and 2.
Near-Perfect Infrared Transmission Based on Metallic Hole and Disk Coupling Array for Mid-Infrared Refractive Index Sensing
Authors: Xu Lingyi , Lai Jianjun , Meng Qinghua , Chen Changhong , Gao Yihua
Published: December 2023

Nanostructured color filters, particularly those generated by the extraordinary optical transmission (EOT) resonance of metal–dielectric nanostructures, have been intensively studied over the past few decades. In this work, we propose a hybrid array composed of a hole array and a disk array with the same working period within the 3–14 μm mid-infrared band. Through numerical simulations, near-perfect transmission (more than 99%) and a narrower linewidth at some resonance wavelengths were achieved, which is vital for highly sensitive sensing applications. This superior performance is attributed to the surface plasmon coupling resonance between the hole and disk arrays. A high tunability of the near-perfect transmission peak with varying structural parameters, characteristics of sensitivity to the background refractive index, and angle independence were observed. We expect that this metallic hole and disk coupling array is promising for use in various applications, such as in plasmon biosensors for the high-sensitivity detection of biochemical substances.
Research on Cleft Lip and Palate: What Is New?
Authors: Ambrosio Eloá Cristina Passucci , Jorge Paula Karine , Carrara Cleide Felício Carvalho , Machado Maria Aparecida Andrade Moreira , Oliveira Thais Marchini
Published: December 2023

Craniofacial development begins during the fourth week of intrauterine life (IUL) [...]
Intrainstitutional Changes of the Treatment of Supracondylar Humerus Fracture in Children over a Period of 9 Years
Authors: Wagner Ferdinand , Boeriu Amalia , Eberz Pascal , Weigert Annabelle , Holzapfel Boris Michael , Böcker Wolfgang , Hubertus Jochen , Muensterer Oliver , Bergmann Florian , Ziegler Christian Max
Published: December 2023

To assess changes in treatment modalities for supracondylar humerus fractures (SCHFs) at a large pediatric university hospital, we analyzed patient data from 2014 to 2022. A total of 233 SCHFs treated surgically at our hospital were included. To evaluate postoperative outcome and quality of life, DASH and EuroQol-5D-Y questionnaires were sent to patients. In addition to a significant fluctuation in fracture severity, we found an increase in training interventions (more surgeries were performed by trainees) and a significant decrease in surgery times after 2016. From 2020, there was a significant shift in the type of surgical method away from closed reduction with elastic stable intramedullary nailing (ESIN) and towards closed reduction and crossed K-wire osteosynthesis (CRK). Surgeries performed in the morning and evening hours increased, while those performed in the afternoon and after midnight decreased. After a mean follow-up of 4 years, there was no difference in elbow function between ESIN and open reduction and K-wires (ORK). Treatment with ESIN was equivalent to ORK in terms of function, at least in the medium-term follow-up. In summary, the combination of shifting treatment from SCHF to daytime hours, increasing trainee participation and using cross K-wire fixation instead of ESIN had no negative impact on surgery times. In our setting, these measures have reduced resource utilization and increased efficiency without compromising patient care.
Qualitative Study on the Voices of Adolescents Living with Perinatally Acquired HIV in Selected Clinics in the Limpopo Province of South Africa
Authors: Mabasa Rirhandzu Austice , Muthelo Livhuwani , Skaal Linda , Mothiba Tebogo Maria
Published: December 2023

The disclosure of HIV status among adolescents living with perinatally acquired HIV (APHIV) has become one of the core challenges in the management of APHIV. Disclosure is a challenge that undermines positive advances and achievements in HIV management. There is limited literature on the voices of APHIV on disclosure of their status. This study aims to explore the current disclosure process and how it affects APHIV. A qualitative exploratory design was employed to conduct one-on-one in-depth interviews using a semi-structured interview guide. Purposive sampling was used to sample 21 APHIV in 16 selected health facilities in the Vhembe district of Limpopo Province, South Africa. Data were analyzed using Tesch’s qualitative data method. The findings of this study reflect the gaps in the current disclosure process and guidelines while acknowledging the importance of disclosure to APHIV. A notable finding in this study is that most APHIV, especially those in early adolescence, did not want to know their HIV status due to the stigma attached to an HIV-positive diagnosis. This study suggests that proper training and support of parents and/or guardians in the disclosure process are needed, as they are the primary caregivers of APHIV. The disclosure of HIV status must be a comprehensive part of the management and care of HIV for APHIV. Furthermore, dedicated support programs should be developed and implemented to improve their lives post-disclosure.
Antitumor Immunity: Role of NK Cells and Extracellular Vesicles in Cancer Immunotherapy
Authors: Prokopeva Angelina E. , Emene Charles C. , Gomzikova Marina O.
Published: December 2023

The immune system plays a crucial role in recognizing and eliminating altered tumor cells. However, tumors develop mechanisms to evade the body’s natural immune defenses. Therefore, methods for specifically recognizing/targeting tumor cells, for instance, through the activation, directed polarization, and training of immune cells, have been developed based on the body’s immune cells. This strategy has been termed cellular immunotherapy. One promising strategy for treating tumor diseases is NK cell-based immunotherapy. NK cells have the ability to recognize and destroy transformed cells without prior activation as well as tumor cells with reduced MHC-I expression. A novel approach in immunotherapy is the use of extracellular vesicles (EVs) derived from NK cells. The main advantages of NK cell-derived EVs are their small size and better tissue penetration into a tumor. The aim of this review is to systematically present existing information on the mechanisms of antitumor immunity and the role of NK cells and extracellular vesicles in cancer immunotherapy. Clinical and preclinical studies utilizing NK cells and extracellular vesicles for anticancer therapy currently underway will provide valuable insights for researchers in the field of cancer.
Comparative Transcriptome Analyses Provide New Insights into the Evolution of Divergent Thermal Resistance in Two Eel Gobies
Authors: Liu Jing , Liu Tianwei , Liu Yantao , Wang Yuzhen , Liu Liqin , Gong Li , Liu Bingjian , Lü Zhenming
Published: December 2023

Adaptation to thermal conditions in tidal mudflats always involves tolerating frequent fluctuations and often extreme environmental temperatures. Regulation of gene expression plays a fundamental role in the evolution of these thermal adaptations. To identify the key gene regulatory networks associated with the thermal adaptation, we investigated the capability of cold tolerance, as well as the transcriptomic changes under cold stress in two mudflat inhabitants (Odontamblyopus lacepedii and O. rebecca) with contrasting latitude affinity. Our results revealed a remarkable divergent capacity of cold tolerance (CTmin: 0.61 °C vs. 9.57 °C) between the two gobies. Analysis of transcriptomic changes under cold stress unveiled 193 differentially expressed genes exhibiting similar expression profiles across all tissues and species, including several classic metabolic and circadian rhythm molecules such as ACOD and CIART that may represent the core cold response machinery in eel gobies. Meanwhile, some genes show a unique expression spectrum in the more cold-tolerant O. lacepedii suggesting their roles in the enhanced cold tolerance and hence the extreme thermal adaptations. In addition, a weighted gene co-expression network analysis (WGCNA) revealed a subset of metabolic hub genes including MYH11 and LIPT2 showing distinct down-regulation in O. lacepedii when exposed to cold stress which highlights the role of reduced energy consumption in the enhanced cold tolerance of eel gobies. These findings not only provide new insights into how mudflat teleosts could cope with cold stress and their potential evolutionary strategies for adapting to their thermal environment, but also have important implications for sound management and conservation of their fishery resources in a scenario of global climate warming in the marine realm.