bluuebunny/crossref_metadata_2025 huggingface dataset:
AI-Based Nano-Scale Material Property Prediction for Li-Ion Batteries
Authors: Lal Mohit Anil , Singh Akashdeep , Mzik Ryan , Lanjan Amirmasoud , Srinivasan Seshasai
Published: January 2024

In this work, we propose a machine learning (ML)-based technique that can learn interatomic potential parameters for various particle–particle interactions employing quantum mechanics (QM) calculations. This ML model can be used as an alternative for QM calculations for predicting non-bonded interactions in a computationally efficient manner. Using these parameters as input to molecular dynamics simulations, we can predict a diverse range of properties, enabling researchers to design new and novel materials suitable for various applications in the absence of experimental data. We employ our ML-based technique to learn the Buckingham potential, a non-bonded interatomic potential. Subsequently, we utilize these predicted values to compute the densities of four distinct molecules, achieving an accuracy exceeding 93%. This serves as a strong demonstration of the efficacy of our proposed approach.
A Portable, Neurostimulation-Integrated, Force Measurement Platform for the Clinical Assessment of Plantarflexor Central Drive
Authors: Collimore Ashley N. , Alvarez Jonathan T. , Sherman David A. , Gerez Lucas F. , Barrow Noah , Choe Dabin K. , Binder-Macleod Stuart , Walsh Conor J. , Awad Louis N.
Published: January 2024

Plantarflexor central drive is a promising biomarker of neuromotor impairment; however, routine clinical assessment is hindered by the unavailability of force measurement systems with integrated neurostimulation capabilities. In this study, we evaluate the accuracy of a portable, neurostimulation-integrated, plantarflexor force measurement system we developed to facilitate the assessment of plantarflexor neuromotor function in clinical settings. Two experiments were conducted with the Central Drive System (CEDRS). To evaluate accuracy, experiment #1 included 16 neurotypical adults and used intra-class correlation (ICC2,1) to test agreement of plantarflexor strength capacity measured with CEDRS versus a stationary dynamometer. To evaluate validity, experiment #2 added 26 individuals with post-stroke hemiparesis and used one-way ANOVAs to test for between-limb differences in CEDRS’ measurements of plantarflexor neuromotor function, comparing neurotypical, non-paretic, and paretic limb measurements. The association between paretic plantarflexor neuromotor function and walking function outcomes derived from the six-minute walk test (6MWT) were also evaluated. CEDRS’ measurements of plantarflexor neuromotor function showed high agreement with measurements made by the stationary dynamometer (ICC = 0.83, p < 0.001). CEDRS’ measurements also showed the expected between-limb differences (p’s < 0.001) in maximum voluntary strength (Neurotypical: 76.21 ± 13.84 ft-lbs., Non-paretic: 56.93 ± 17.75 ft-lbs., and Paretic: 31.51 ± 14.08 ft-lbs.), strength capacity (Neurotypical: 76.47 ± 13.59 ft-lbs., Non-paretic: 64.08 ± 14.50 ft-lbs., and Paretic: 44.55 ± 14.23 ft-lbs.), and central drive (Neurotypical: 88.73 ± 1.71%, Non-paretic: 73.66% ± 17.74%, and Paretic: 52.04% ± 20.22%). CEDRS-measured plantarflexor central drive was moderately correlated with 6MWT total distance (r = 0.69, p < 0.001) and distance-induced changes in speed (r = 0.61, p = 0.002). CEDRS is a clinician-operated, portable, neurostimulation-integrated force measurement platform that produces accurate measurements of plantarflexor neuromotor function that are associated with post-stroke walking ability.
RETRACTED: Esmaeilzadeh et al. Identify Biomarkers and Design Effective Multi-Target Drugs in Ovarian Cancer: Hit Network-Target Sets Model Optimizing. Biology 2022, 11, 1851
Authors:   Biology Editorial Office
Published: January 2024

The journal retracts the article, (Identify Biomarkers and Design Effective Multi-Target Drugs in Ovarian Cancer: Hit Network-Target Sets Model Optimizing [...]
The Role of Methionine Restriction in Gastric Cancer: A Summary of Mechanisms and a Discussion on Tumor Heterogeneity
Authors: Zou Yonghui , Yuan Yiwu , Zhou Qi , Yue Zhenqi , Liu Jiang , Fan Luojun , Xu Hesong , Xin Lin
Published: January 2024

Gastric cancer is ranked as the fifth most prevalent cancer globally and has long been a topic of passionate discussion among numerous individuals. However, the incidence of gastric cancer in society has not decreased, but instead has shown a gradual increase in recent years. For more than a decade, the treatment effect of gastric cancer has not been significantly improved. This is attributed to the heterogeneity of cancer, which makes popular targeted therapies ineffective. Methionine is an essential amino acid, and many studies have shown that it is involved in the development of gastric cancer. Our study aimed to review the literature on methionine and gastric cancer, describing its mechanism of action to show that tumor heterogeneity in gastric cancer does not hinder the effectiveness of methionine-restricted therapies. This research also aimed to provide insight into the inhibition of gastric cancer through metabolic reprogramming with methionine-restricted therapies, thereby demonstrating their potential as adjuvant treatments for gastric cancer.
Mitochondrial Dysfunction and Protein Homeostasis in Aging: Insights from a Premature-Aging Mouse Model
Authors: Ross Jaime M. , Olson Lars , Coppotelli Giuseppe
Published: January 2024

Mitochondrial dysfunction has been implicated in aging and age-related disorders. Disturbed-protein homeostasis and clearance of damaged proteins have also been linked to aging, as well as to neurodegenerative diseases, cancers, and metabolic disorders. However, since mitochondrial oxidative phosphorylation, ubiquitin–proteasome, and autophagy-lysosome systems are tightly interdependent, it is not understood whether the facets observed in aging are the causes or consequences of one or all of these failed processes. We therefore used prematurely aging mtDNA-mutator mice and normally aging wild-type littermates to elucidate whether mitochondrial dysfunction per se is sufficient to impair cellular protein homeostasis similarly to that which is observed in aging. We found that both mitochondrial dysfunction and normal aging affect the ubiquitin–proteasome system in a tissue-dependent manner, whereas only normal aging markedly impairs the autophagy-lysosome system. Thus, our data show that the proteostasis network control in the prematurely aging mtDNA-mutator mouse differs in certain aspects from that found in normal aging. Taken together, our findings suggest that severe mitochondrial dysfunction drives an aging phenotype associated with the impairment of certain components of the protein homeostasis machinery, while others, such as the autophagy-lysosome system, are not affected or only minimally affected. Taken together, this shows that aging is a multifactorial process resulting from alterations of several integrated biological processes; thus, manipulating one process at the time might not be sufficient to fully recapitulate all changes associated with normal aging.
Understanding the Biological Relationship between Migraine and Depression
Authors: Viudez-Martínez Adrián , Torregrosa Abraham B. , Navarrete Francisco , García-Gutiérrez María Salud
Published: January 2024

Migraine is a highly prevalent neurological disorder. Among the risk factors identified, psychiatric comorbidities, such as depression, seem to play an important role in its onset and clinical course. Patients with migraine are 2.5 times more likely to develop a depressive disorder; this risk becomes even higher in patients suffering from chronic migraine or migraine with aura. This relationship is bidirectional, since depression also predicts an earlier/worse onset of migraine, increasing the risk of migraine chronicity and, consequently, requiring a higher healthcare expenditure compared to migraine alone. All these data suggest that migraine and depression may share overlapping biological mechanisms. Herein, this review explores this topic in further detail: firstly, by introducing the common epidemiological and risk factors for this comorbidity; secondly, by focusing on providing the cumulative evidence of common biological aspects, with a particular emphasis on the serotoninergic system, neuropeptides such as calcitonin-gene-related peptide (CGRP), pituitary adenylate cyclase-activating polypeptide (PACAP), substance P, neuropeptide Y and orexins, sexual hormones, and the immune system; lastly, by remarking on the future challenges required to elucidate the etiopathological mechanisms of migraine and depression and providing updated information regarding new key targets for the pharmacological treatment of these clinical entities.
Bioinformatics Prediction for Network-Based Integrative Multi-Omics Expression Data Analysis in Hirschsprung Disease
Authors: Lucena-Padros Helena , Bravo-Gil Nereida , Tous Cristina , Rojano Elena , Seoane-Zonjic Pedro , Fernández Raquel María , Ranea Juan A. G. , Antiñolo Guillermo , Borrego Salud
Published: January 2024

Hirschsprung’s disease (HSCR) is a rare developmental disorder in which enteric ganglia are missing along a portion of the intestine. HSCR has a complex inheritance, with RET as the major disease-causing gene. However, the pathogenesis of HSCR is still not completely understood. Therefore, we applied a computational approach based on multi-omics network characterization and clustering analysis for HSCR-related gene/miRNA identification and biomarker discovery. Protein–protein interaction (PPI) and miRNA–target interaction (MTI) networks were analyzed by DPClusO and BiClusO, respectively, and finally, the biomarker potential of miRNAs was computationally screened by miRNA-BD. In this study, a total of 55 significant gene–disease modules were identified, allowing us to propose 178 new HSCR candidate genes and two biological pathways. Moreover, we identified 12 key miRNAs with biomarker potential among 137 predicted HSCR-associated miRNAs. Functional analysis of new candidates showed that enrichment terms related to gene ontology (GO) and pathways were associated with HSCR. In conclusion, this approach has allowed us to decipher new clues of the etiopathogenesis of HSCR, although molecular experiments are further needed for clinical validations.
Compensated Advanced Chronic Liver Disease and Steatosis in Patients with Type 2 Diabetes as Assessed through Shear Wave Measurements and Attenuation Measurements
Authors: Barisic-Jaman Mislav , Milosevic Marko , Skurla Viktoria , Dohoczky David , Stojic Josip , Dinjar Kujundzic Petra , Cigrovski Berkovic Maja , Majic-Tengg Ana , Matijaca Ana , Lucijanic Tomo , Kardum-Pejic Mirjana , Pandzic Jaksic Vlatka , Marusic Srecko , Grgurevic Ivica
Published: January 2024

Patients with type 2 diabetes (T2D) are at risk of developing metabolic dysfunction-associated steatotic liver disease (MASLD). We investigated the prevalence of compensated advanced chronic liver disease (cACLD) and steatosis in patients with T2D using the new non-invasive diagnostic methods of shear wave measurements (SWMs) and attenuation (ATT) measurements in comparison with those of vibration-controlled transient elastography (VCTE) and the controlled attenuation parameter (CAP), which served as the reference methods. Among 214 T2D patients, steatosis at any grade and cACLD were revealed in 134 (62.6%) and 19 (8.9%) patients, respectively. SWMs showed a high correlation with VCTE (Spearman’s ρ = 0.641), whereas SWMs produced lower (mean of −0.7 kPa) liver stiffness measurements (LSMs) overall. At a LSM of >11.0 kPa (Youden), SWMs had an AUROC of 0.951 that was used to diagnose cACLD (defined as a LSM of >15 kPa through VCTE) with 84.2% sensitivity and 96.4% specificity. The performance of ATT measurements in diagnosing liver steatosis at any grade (defined as the CAP of ≥274 dB/m) was suboptimal (AUROC of 0.744 at the ATT measurement cut-off of >0.63 dB/cm/MHz (Youden) with 59% sensitivity and 81.2% specificity). In conclusion, the prevalence of liver steatosis and previously unrecognized cACLD in patients with T2D is high and SWMs appear to be a reliable diagnostic method for this purpose, whereas further investigation is needed to optimize the diagnostic performance of ATT measurements.
Design, Characterization, and Preliminary Assessment of a Two-Degree-of-Freedom Powered Ankle–Foot Prosthesis
Authors: Hsieh Tsung-Han , Song Hyungeun , Shu Tony , Qiao Junqing , Yeon Seong Ho , Carney Matthew , Mooney Luke , Duval Jean-François , Herr Hugh
Published: January 2024

Powered ankle prostheses have been proven to improve the walking economy of people with transtibial amputation. All commercial powered ankle prostheses that are currently available can only perform one-degree-of-freedom motion in a limited range. However, studies have shown that the frontal plane motion during ambulation is associated with balancing. In addition, as more advanced neural interfaces have become available for people with amputation, it is possible to fully recover ankle function by combining neural signals and a robotic ankle. Accordingly, there is a need for a powered ankle prosthesis that can have active control on not only plantarflexion and dorsiflexion but also eversion and inversion. We designed, built, and evaluated a two-degree-of-freedom (2-DoF) powered ankle–foot prosthesis that is untethered and can support level-ground walking. Benchtop tests were conducted to characterize the dynamics of the system. Walking trials were performed with a 77 kg subject that has unilateral transtibial amputation to evaluate system performance under realistic conditions. Benchtop tests demonstrated a step response rise time of less than 50 milliseconds for a torque of 40 N·m on each actuator. The closed-loop torque bandwidth of the actuator is 9.74 Hz. Walking trials demonstrated torque tracking errors (root mean square) of less than 7 N·m. These results suggested that the device can perform adequate torque control and support level-ground walking. This prosthesis can serve as a platform for studying biomechanics related to balance and has the possibility of further recovering the biological function of the ankle–subtalar–foot complex beyond the existing powered ankles.
Effect of Bionic Crab Shell Attitude Parameters on Lift and Drag in a Flow Field
Authors: Hu Shihao , Chen Xi , Li Jiawei , Yu Peiye , Xin Mingfei , Pan Biye , Li Sicen , Tang Qinyun , Wang Liquan , Ding Mingxuan , Liu Kaixin , Liu Zhaojin
Published: January 2024

Underwater bionic-legged robots encounter significant challenges in attitude, velocity, and positional control due to lift and drag in water current environments, making it difficult to balance operational efficiency with motion stability. This study delves into the hydrodynamic properties of a bionic crab robot’s shell, drawing inspiration from the sea crab’s motion postures. It further refines the robot’s underwater locomotion strategy based on these insights. Initially, the research involved collecting attitude data from crabs during underwater movement through biological observation. Subsequently, hydrodynamic simulations and experimental validations of the bionic shell were conducted, examining the impact of attitude parameters on hydrodynamic performance. The findings reveal that the transverse angle predominantly influences lift and drag. Experiments in a test pool with a crab-like robot, altering transverse angles, demonstrated that increased transverse angles enhance the robot’s underwater walking efficiency, stability, and overall performance.
Development of a Quantitative Digital Urinalysis Tool for Detection of Nitrite, Protein, Creatinine, and pH
Authors: Siu Vince S. , Lu Minhua , Hsieh Kuan Yu , Wen Bo , Buleje Italo , Hinds Nigel , Patel Krishna , Dang Bing , Budd Russell
Published: January 2024

This paper presents a cost-effective, quantitative, point-of-care solution for urinalysis screening, specifically targeting nitrite, protein, creatinine, and pH in urine samples. Detecting nitrite is crucial for the early identification of urinary tract infections (UTIs), while regularly measuring urinary protein-to-creatinine (UPC) ratios aids in managing kidney health. To address these needs, we developed a portable, transmission-based colorimeter using readily available components, controllable via a smartphone application through Bluetooth. Multiple colorimetric detection strategies for each analyte were identified and tested for sensitivity, specificity, and stability in a salt buffer, artificial urine, and human urine. The colorimeter successfully detected all analytes within their clinically relevant ranges: nitrite (6.25–200 µM), protein (2–1024 mg/dL), creatinine (2–1024 mg/dL), and pH (5.0–8.0). The introduction of quantitative protein and creatinine detection, and a calculated urinary protein-to-creatinine (UPC) ratio at the point-of-care, represents a significant advancement, allowing patients with proteinuria to monitor their condition without frequent lab visits. Furthermore, the colorimeter provides versatile data storage options, facilitating local storage on mobile devices or in the cloud. The paper further details the setup of the colorimeter’s secure connection to a cloud-based environment, and the visualization of time-series analyte measurements in a web-based dashboard.
Investigating the Interplay between Olfaction, Social Behaviour, and Individual Differences: Editorial
Authors: Zou Laiquan , Mahmut Mehmet K.
Published: January 2024

Long-COVID mercilessly brought awareness to what olfaction researchers have known all along; losing your sense of smell changes your experiences with the world around you and can compromise your health and wellbeing [...]
Implementation of the Prevent-Teach-Reinforce Model for Elementary School Students Needing Intensive Behavior Intervention
Authors: Ford Sofia , Blair Kwang-Sun Cho , Iovannone Rose , Kwak Daniel
Published: January 2024

This study evaluated the implementation of the school-based Prevent-Teach-Reinforce (PTR) model for elementary school students who engage in high levels of challenging behavior. Three students (one with speech or language impairment and two without disabilities) and their classroom teachers in two public schools participated in the team-based PTR process, which involved teaming and goal setting, functional behavior assessment, intervention, and evaluation. A multiple-baseline-across-participants design was used to evaluate the impact of PTR on student behaviors. Direct and indirect observations of student behaviors were conducted across target and generalization academic time periods. The findings indicated that the PTR intervention effectively improved the classroom behaviors of all three participating students in both target and generalization academic time periods, decreasing disruptive behavior and increasing on-task behavior. Social validity assessments with the participating teachers and one student indicated high levels of acceptability of and satisfaction with the PTR intervention goals, procedures, and outcomes.
Involvement of Personality and Health Status in the Psychological Wellbeing of Subjects with Chronic Disease
Authors: Rivera-Picón Cristina , Sánchez-González Juan Luis , Rivera-Picón Marta , Rodríguez-Muñoz Pedro Manuel
Published: January 2024

(1) Background: Psychological wellbeing correlates with improved physical and psychological health, as this construct plays a fundamental role in disease recovery and health maintenance. Hence, for healthcare professionals, understanding the factors that predict psychological wellbeing is of great interest. Thus, the objective of this study was to determine whether health status and personality traits influence psychological wellbeing. (2) Methods: The total sample (N = 600) consisted of HIV patients, individuals with diabetes, and healthy subjects from the Salamanca Clinical Hospital. The instruments used for data collection included a sociodemographic questionnaire, Ryff’s Psychological Wellbeing Scale, and the Spanish version of the Big Five Taxonomy to measure personality. (3) Results: Specific personality traits, such as Emotional Stability, Extraversion, Responsibility, and Integrity were significant predictors of different dimensions of psychological wellbeing. Regarding health status, individuals with diabetes and healthy subjects, compared to HIV+ subjects, were associated with higher levels of psychological wellbeing dimensions. (4) Conclusions: Individual differences in personality traits and the diagnosis of a chronic condition may play a fundamental role in psychological wellbeing. These conclusions are of great interest for developing strategies aimed at individuals with chronic illnesses and specific personality traits associated with poorer psychological wellbeing.
Therapies for the Treatment of Advanced/Metastatic Estrogen Receptor-Positive Breast Cancer: Current Situation and Future Directions
Authors: Rej Rohan Kalyan , Roy Joyeeta , Allu Srinivasa Rao
Published: January 2024

The hormone receptor-positive (HR+) type is the most frequently identified subtype of breast cancer. HR+ breast cancer has a more positive prognosis when compared to other subtypes, such as human epidermal growth factor protein 2-positive disorder and triple-negative disease. The advancement in treatment outcomes for advanced HR+ breast cancer has been considerably elevated due to the discovery of cyclin-dependent kinase 4/6 inhibitors and their combination effects with endocrine therapy. However, despite the considerable effectiveness of tamoxifen, a selective estrogen receptor modulator (SERMs), and aromatase inhibitors (AI), the issue of treatment resistance still presents a significant challenge for HR+ breast cancer. As a result, there is a focus on exploring new therapeutic strategies such as targeted protein degradation and covalent inhibition for targeting ERα. This article discusses the latest progress in treatments like oral selective ER degraders (SERDs), complete estrogen receptor antagonists (CERANs), selective estrogen receptor covalent antagonists (SERCAs), proteolysis targeting chimera (PROTAC) degraders, and combinations of CDK4/6 inhibitors with endocrine therapy. The focus is specifically on those compounds that have transitioned into phases of clinical development.
Effects of Ionizing Radiation on Cardiac Implantable Electronic Devices (CIEDs) in Patients with Esophageal Cancer Undergoing Radiotherapy: A Pilot Study
Authors: Uzun Davut D. , Salatzki Janek , Xynogalos Panagiotis , Frey Norbert , Debus Juergen , Lang Kristin
Published: January 2024

(1) Background: The prevalence of cancer patients relying on cardiac implantable electronic device (CIED) is steadily rising. The aim of this study was to evaluate RT-related malfunctions of CIEDs. (2) Methods: We retrospectively analyze sixteen patients with esophageal cancer who were treated with radiotherapy between 2012 and 2022 at the University Hospital Heidelberg. All patients underwent systemic evaluation including pre-therapeutic cardiological examinations of the CIED functionality and after every single irradiation. (3) Results: Sixteen patients, predominantly male (14) with a mean age of 77 (range: 56–85) years were enrolled. All patients received 28 fractions of radiotherapy with a cumulative total dose 58.8 Gy. The mean maximum dose at the CIEDs was 1.8 Gy. Following radiotherapy and during the one-year post-radiation follow-up period, there were no registered events associated with the treatment in this evaluation. (4) Conclusion: The study did not observe any severe CIED malfunctions following each radiation fraction or after completion of RT. Strict selection of photon energy and alignment with manufacturer-recommended dose limits appear to be important. Our study showed no major differences in the measured values of the pacing threshold, sensing threshold and lead impedance after RT.
Safety and Efficacy of Single-Fraction Carbon-Ion Radiotherapy for Early-Stage Lung Cancer with Interstitial Pneumonia
Authors: Aoki Shuri , Ishikawa Hitoshi , Nakajima Mio , Yamamoto Naoyoshi , Mori Shinichiro , Omatsu Tokuhiko , Tada Yuji , Mizobuchi Teruaki , Ikeda Satoshi , Yoshino Ichiro , Yamada Shigeru
Published: January 2024

Patients with lung cancer complicated by interstitial pneumonia (IP) often lose treatment options early owing to acute exacerbation of IP concerns. Carbon-ion radiotherapy (CIRT) can provide superior tumor control and low toxicity at high dose concentrations. We conducted a retrospective analysis of the efficacy and tolerability of a single-fraction CIRT using 50 Gy for IP-complicated lung cancer. The study included 50 consecutive patients treated between April 2013 and September 2022, whose clinical stage of lung cancer (UICC 7th edition) was 1A:1B:2A:2B = 32:13:4:1. Of these, 32 (64%) showed usual interstitial pneumonia patterns. With a median follow-up of 23.5 months, the 3-year overall survival (OS), cause-specific survival, and local control rates were 45.0, 75.4, and 77.8%, respectively. The median lung V5 and V20 were 10.0 and 5.2%, respectively (mean lung dose, 2.6 Gy). The lung dose, especially lung V20, showed a strong association with OS (p = 0.0012). Grade ≥ 2 pneumonia was present in six patients (13%), including two (4%) with suspected grade 5. CIRT can provide a relatively safe and curative treatment for patients with IP-complicated lung cancer. However, IP increases the risk of severe radiation pneumonitis, and further studies are required to assess the appropriate indications.
Phase I/II Trial of Urokinase Plasminogen Activator-Targeted Oncolytic Newcastle Disease Virus for Canine Intracranial Tumors
Authors: Rossmeisl John H. , King Jamie N. , Robertson John L. , Weger-Lucarelli James , Elankumaran Subbiah
Published: January 2024

Neurotropic oncolytic viruses are appealing agents to treat brain tumors as they penetrate the blood–brain barrier and induce preferential cytolysis of neoplastic cells. The pathobiological similarities between human and canine brain tumors make immunocompetent dogs with naturally occurring tumors attractive models for the study of oncolytic virotherapies. In this dose-escalation/expansion study, an engineered Lasota NDV strain targeting the urokinase plasminogen activator system (rLAS-uPA) was administered by repetitive intravenous infusions to 20 dogs with intracranial tumors with the objectives of characterizing toxicities, immunologic responses, and neuroradiological anti-tumor effects of the virus for up to 6 months following treatment. Dose-limiting toxicities manifested as fever, hematologic, and neurological adverse events, and the maximum tolerated dose (MTD) of rLAS-uPA was 2 × 107 pfu/mL. Mild adverse events, including transient infusion reactions, diarrhea, and fever were observed in 16/18 of dogs treated at or below MTD. No infectious virus was recoverable from body fluids. Neutralizing antibodies to rLAS-uPA were present in all dogs by 2 weeks post-treatment, and viral genetic material was detected in post-treatment tumors from six dogs. Tumor volumetric reductions occurred in 2/11 dogs receiving the MTD. Systemically administered rLAS-uPA NDV was safe and induced anti-tumor effects in canine brain tumors, although modifications to evade host anti-viral immunity are needed to optimize this novel therapy.
RenseNet: A Deep Learning Network Incorporating Residual and Dense Blocks with Edge Conservative Module to Improve Small-Lesion Classification and Model Interpretation
Authors: Seo Hyunseok , Lee Seokjun , Yun Sojin , Leem Saebom , So Seohee , Han Deok Hyun
Published: January 2024

Deep learning has become an essential tool in medical image analysis owing to its remarkable performance. Target classification and model interpretability are key applications of deep learning in medical image analysis, and hence many deep learning-based algorithms have emerged. Many existing deep learning-based algorithms include pooling operations, which are a type of subsampling used to enlarge the receptive field. However, pooling operations degrade the image details in terms of signal processing theory, which is significantly sensitive to small objects in an image. Therefore, in this study, we designed a Rense block and edge conservative module to effectively manipulate previous feature information in the feed-forward learning process. Specifically, a Rense block, an optimal design that incorporates skip connections of residual and dense blocks, was demonstrated through mathematical analysis. Furthermore, we avoid blurring of the features in the pooling operation through a compensation path in the edge conservative module. Two independent CT datasets of kidney stones and lung tumors, in which small lesions are often included in the images, were used to verify the proposed RenseNet. The results of the classification and explanation heatmaps show that the proposed RenseNet provides the best inference and interpretation compared to current state-of-the-art methods. The proposed RenseNet can significantly contribute to efficient diagnosis and treatment because it is effective for small lesions that might be misclassified or misinterpreted.
Gender-Specific Genetic Predisposition to Breast Cancer: BRCA Genes and Beyond
Authors: Valentini Virginia , Bucalo Agostino , Conti Giulia , Celli Ludovica , Porzio Virginia , Capalbo Carlo , Silvestri Valentina , Ottini Laura
Published: January 2024

Among neoplastic diseases, breast cancer (BC) is one of the most influenced by gender. Despite common misconceptions associating BC as a women-only disease, BC can also occur in men. Additionally, transgender individuals may also experience BC. Genetic risk factors play a relevant role in BC predisposition, with important implications in precision prevention and treatment. The genetic architecture of BC susceptibility is similar in women and men, with high-, moderate-, and low-penetrance risk variants; however, some sex-specific features have emerged. Inherited high-penetrance pathogenic variants (PVs) in BRCA1 and BRCA2 genes are the strongest BC genetic risk factor. BRCA1 and BRCA2 PVs are more commonly associated with increased risk of female and male BC, respectively. Notably, BRCA-associated BCs are characterized by sex-specific pathologic features. Recently, next-generation sequencing technologies have helped to provide more insights on the role of moderate-penetrance BC risk variants, particularly in PALB2, CHEK2, and ATM genes, while international collaborative genome-wide association studies have contributed evidence on common low-penetrance BC risk variants, on their combined effect in polygenic models, and on their role as risk modulators in BRCA1/2 PV carriers. Overall, all these studies suggested that the genetic basis of male BC, although similar, may differ from female BC. Evaluating the genetic component of male BC as a distinct entity from female BC is the first step to improve both personalized risk assessment and therapeutic choices of patients of both sexes in order to reach gender equality in BC care. In this review, we summarize the latest research in the field of BC genetic predisposition with a particular focus on similarities and differences in male and female BC, and we also discuss the implications, challenges, and open issues that surround the establishment of a gender-oriented clinical management for BC.
The Anticancer Potential of Kaempferol: A Systematic Review Based on In Vitro Studies
Authors: de Morais Everton Freitas , de Oliveira Lilianny Querino Rocha , Farias Morais Hannah Gil de , Souto Medeiros Maurília Raquel de , Freitas Roseana de Almeida , Rodini Camila Oliveira , Coletta Ricardo D.
Published: January 2024

Given the heterogeneity of different malignant processes, planning cancer treatment is challenging. According to recent studies, natural products are likely to be effective in cancer prevention and treatment. Among bioactive flavonoids found in fruits and vegetables, kaempferol (KMP) is known for its anti-inflammatory, antioxidant, and anticancer properties. This systematic review aims to highlight the potential therapeutic effects of KMP on different types of solid malignant tumors. This review was conducted following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Searches were performed in EMBASE, Medline/PubMed, Cochrane Collaboration Library, Science Direct, Scopus, and Google Scholar. After the application of study criteria, 64 studies were included. In vitro experiments demonstrated that KMP exerts antitumor effects by controlling tumor cell cycle progression, proliferation, apoptosis, migration, and invasion, as well as by inhibiting angiogenesis. KMP was also able to inhibit important markers that regulate epithelial–mesenchymal transition and enhanced the sensitivity of cancer cells to traditional drugs used in chemotherapy, including cisplatin and 5-fluorouracil. This flavonoid is a promising therapeutic compound and its combination with current anticancer agents, including targeted drugs, may potentially produce more effective and predictable results.
Age-Associated Differences in Recovery from Exercise-Induced Muscle Damage
Authors: Li Donna Ching Wah , Rudloff Stefan , Langer Henning Tim , Norman Kristina , Herpich Catrin
Published: January 2024

Understanding the intricate mechanisms governing the cellular response to resistance exercise is paramount for promoting healthy aging. This narrative review explored the age-related alterations in recovery from resistance exercise, focusing on the nuanced aspects of exercise-induced muscle damage in older adults. Due to the limited number of studies in older adults that attempt to delineate age differences in muscle discovery, we delve into the multifaceted cellular influences of chronic low-grade inflammation, modifications in the extracellular matrix, and the role of lipid mediators in shaping the recovery landscape in aging skeletal muscle. From our literature search, it is evident that aged muscle displays delayed, prolonged, and inefficient recovery. These changes can be attributed to anabolic resistance, the stiffening of the extracellular matrix, mitochondrial dysfunction, and unresolved inflammation as well as alterations in satellite cell function. Collectively, these age-related impairments may impact subsequent adaptations to resistance exercise. Insights gleaned from this exploration may inform targeted interventions aimed at enhancing the efficacy of resistance training programs tailored to the specific needs of older adults, ultimately fostering healthy aging and preserving functional independence.
A Cataract-Causing Mutation in the TRPM3 Cation Channel Disrupts Calcium Dynamics in the Lens
Authors: Zhou Yuefang , Bennett Thomas M. , Ruzycki Philip A. , Guo Zhaohua , Cao Yu-Qing , Shahidullah Mohammad , Delamere Nicholas A. , Shiels Alan
Published: January 2024

TRPM3 belongs to the melastatin sub-family of transient receptor potential (TRPM) cation channels and has been shown to function as a steroid-activated, heat-sensitive calcium ion (Ca2+) channel. A missense substitution (p.I65M) in the TRPM3 gene of humans (TRPM3) and mice (Trpm3) has been shown to underlie an inherited form of early-onset, progressive cataract. Here, we model the pathogenetic effects of this cataract-causing mutation using ‘knock-in’ mutant mice and human cell lines. Trpm3 and its intron-hosted micro-RNA gene (Mir204) were strongly co-expressed in the lens epithelium and other non-pigmented and pigmented ocular epithelia. Homozygous Trpm3-mutant lenses displayed elevated cytosolic Ca2+ levels and an imbalance of sodium (Na+) and potassium (K+) ions coupled with increased water content. Homozygous TRPM3-mutant human lens epithelial (HLE-B3) cell lines and Trpm3-mutant lenses exhibited increased levels of phosphorylated mitogen-activated protein kinase 1/extracellular signal-regulated kinase 2 (MAPK1/ERK2/p42) and MAPK3/ERK1/p44. Mutant TRPM3-M65 channels displayed an increased sensitivity to external Ca2+ concentration and an altered dose response to pregnenolone sulfate (PS) activation. Trpm3-mutant lenses shared the downregulation of genes involved in insulin/peptide secretion and the upregulation of genes involved in Ca2+ dynamics. By contrast, Trpm3-deficient lenses did not replicate the pathophysiological changes observed in Trpm3-mutant lenses. Collectively, our data suggest that a cataract-causing substitution in the TRPM3 cation channel elicits a deleterious gain-of-function rather than a loss-of-function mechanism in the lens.
Effect of Coating Damage on the Micro Area Corrosion Performance of HDR Duplex Stainless Steel
Authors: Lin Yufeng , Li Zhuying , Wang Xiaoqiang , Liu Xin , Chi Junhan , Zhang Zhenhai
Published: January 2024

In order to determine the effect of damaged insulating enamel on the corrosion of high-chromium (H), duplex (D), and corrosion-resistant (R) duplex stainless steel, the corrosion characteristics of HDR duplex stainless steel in 3.5% NaCl solution were studied by means of local electrochemical impedance spectroscopy (LEIS) and micro-morphology analysis. It was shown that the LEIS impedance was stable at about 7.0 × 103 Ω within 10 days when the HDR duplex stainless steel was not coated. The minimum LEIS impedance of exposed HDR at the damaged area fluctuated around 6.5 × 103 Ω within 15 days when the coating of the self-control insulating enamel damaged area was 1 mm × 10 mm. The coating-damaged area from 1 mm × 10 mm reduced to a circular hole with a diameter of φ1 mm, and the LEIS impedance of the exposed HDR increased at the damaged coating. When extending along the damaged coating to the intact coating area, the impedance rapidly increased, and the further the distance from the damage, the greater the increase in impedance. The impedance of coated HDR increased with the prolongation of immersion time and ultimately stabilized. The thicker the coating, the longer the impedance took to reach a stable state. The stabilized coating had a better effect on improving the corrosion resistance of HDR duplex stainless steel. Within 15 days, the HDR ferrite structure at different areas of coating damage prioritized corrosion. Cl− mainly comes from the solution, and Si and S elements mainly come from elements of the collective itself, with Cl− adsorption, S, and Si element inclusion being the main factors influencing the corrosion of the ferrite structure.
Responses of Natural Microorganisms to Land Reclamation and Applications of Functional Microorganisms in Biorestoration of Coal Mining Area
Authors: Mao Zhen , Harris Jim , Zhang Zheyu
Published: January 2024

Extensive coal mining causes significant ecological and environmental impacts on the local ecosystem, especially on the terrestrial ecosystem. Mining activities induce the degradation of topsoil physico–chemical characteristics and the succession of soil microbial communities. The soil microbial community is sensitive to soil disturbance and restoration practices, being significant in soil reconstruction and land restoration. Microbes could be effective instruments to restore or reclaim disturbed terrestrial ecosystems and indispensable, unambiguous, indicators to assess reclaimed soils. In the present review, we aimed to provide insight into the effects of mining and subsequent land reclamation on soil microorganisms and the importance and application of microorganisms in the reclamation process. We address changes in the diversity and structure of the soil microbial community after reclamation and discuss the main driving factors of the community. We hypothesize that there is a discernible pattern or regularity in the variation of microbial community composition during the process of restoration succession. By employing the life strategy concept, the study attempts to identify and understand how microbial communities evolve during land reclamation. Land reclamation could improve the nutrients in the soil while increasing the proportion of saprotrophic microorganisms. In community succession, vegetation, soil properties, and reclamation time are key determining factors. Whereas bacteria, fungi, and archaea showed different responses to these factors, as they responded differently to varied soil environments, nutrition, and plants, and occupied different biological niches. Finally, we describe the applications of microorganisms as land reclamation monitors or promoters. This knowledge and understanding can provide comprehensive insight into the soil health condition and strong support for forecasting and decision-making in mine land restoration.
A Proposal for Neurography Referral in Patients with Carpal Tunnel Syndrome Based on Clinical Symptoms and Demographic Variables of 797 Patients
Authors: Vázquez-Sánchez Fernando , Gómez-Menéndez Ana Isabel , López-Veloso María , Calvo-Simal Sara , Lloria-Gil María Carmen , González-Santos Josefa , Muñoz-Alcaraz María Nieves , Jiménez-Vilchez Antonio José , González-Bernal Jerónimo J. , García-López Beatriz
Published: January 2024

The clinical manifestation of median nerve entrapment at the carpal tunnel level is known as carpal tunnel syndrome (CTS). Electroneurography (ENG) is considered the gold standard in CTS evaluation. We conducted a retrospective study and analyzed some clinical and demographic variables, relating them to the degree of neuropathy using ENG, to better understand the role of ENG in this very common disease. We studied 816 patients referred to our service for neurographic evaluation. Their symptoms were classified as compatible with CTS (cCTS) (n = 646) and atypical for CTS (aCTS) (n = 170). A blind ENG was performed on 797 patients. Patient characteristics were coded as variables and analyzed to study whether they could predict neuropathy severity (sensory and motor involvement or grade ≥ 3 in our classification). We found a correlation between typical symptomatology, age over 50 years, male gender, positivity of Phalen’s maneuver and Tinel’s sign, and a neuropathy grade ≥ 3. We also found a correlation with CTS in the contralateral hand if the other hand showed neuropathy, despite the lack of symptoms in this hand. We propose a practical algorithm for ENG referral based on clinical symptoms, demographic factors, and neurophysiological variables.
Location, Location, Location: A Pilot Study to Compare Electrical with Echocardiographic-Guided Targeting of Left Ventricular Lead Placement in Cardiac Resynchronisation Therapy
Authors: Chousou Panagiota A. , Chattopadhyay Rahul K. , Matthews Gareth D. K. , Vassiliou Vassilios S. , Pugh Peter J.
Published: January 2024

Introduction: Cardiac resynchronisation therapy is ineffective in 30–40% of patients with heart failure with reduced ejection fraction. Targeting non-scarred myocardium by selecting the site of latest mechanical activation using echocardiography has been suggested to improve outcomes but at the cost of increased resource utilisation. The interval between the beginning of the QRS complex and the local LV lead electrogram (QLV) might represent an alternative electrical marker. Aims: To determine whether the site of latest myocardial electrical and mechanical activation are concordant. Methods: This was a single-centre, prospective pilot study, enrolling patients between March 2019 and June 2021. Patients underwent speckle-tracking echocardiography (STE) prior to CRT implantation. Intra-procedural QLV measurement and R-wave amplitude were performed in a blinded fashion at all accessible coronary sinus branches. Pearson’s correlation coefficient and Cohen’s Kappa coefficient were utilised for the comparison of electrical and echocardiographic parameters. Results: A total of 20 subjects had complete data sets. In 15, there was a concordance at the optimal site between the electrically targeted region and the mechanically targeted region; in four, the regions were adjacent (within one segment). There was discordance (≥2 segments away) in only one case between the two methods of targeting. There was a statistically significant increase in procedure time and fluoroscopy duration using the intraprocedural QLV strategy. There was no statistical correlation between the quantitative electrical and echocardiographic data. Conclusions: A QLV-guided approach to targeting LV lead placement appears to be a potential alternative to the established echocardiographic-guided technique. However, it is associated with prolonged fluoroscopy and overall procedure time.
Proposed Framework for Conducting Clinically Relevant Translational Biomarker Research for the Diagnosis, Prognosis and Management of Sepsis
Authors: Ventura François , Greub Gilbert , Liles W. Conrad , Jacob Shevin T.
Published: January 2024

Although the diagnosis of sepsis requires the identification of the three components of infection, a systemic inflammation response, and organ dysfunction, there is currently no consensus on gold-standard criteria. There are however suggested tools and tests, which have been proposed in international guidelines, including those produced by the Surviving Sepsis Campaign. Biomarkers play an important role in these tools and tests, and numerous heterogeneous studies have been performed to evaluate their respective clinical utility. Our review of the current practice shows that no biomarkers of infection, systemic inflammation response, organ dysfunction and sepsis are currently specifically recommended, which is probably due to the lack of standardization of studies. We therefore propose to define a framework for conducting clinically relevant translational biomarker research and seek to establish ideal criteria that can be applied to an infection, systemic inflammation response, organ dysfunction and sepsis biomarkers, which can enable early screening of sepsis, diagnosis of sepsis at the time of clinical suspicion and monitoring of sepsis treatment efficacy.
Relevance of Territorial Identity in the Rural Development Programs—The Case Study of Tajo-Salor (Extremadura, Spain)
Authors: Castellano-Álvarez Francisco Javier , Robina-Ramirez Rafael
Published: January 2024

Since their origins, rural development programs have considered the county level as the axis on which to implement their development strategies. Taking Tajo-Salor County (Extremadura, Spain) as a reference, this research analyzes the assessment that some of the agents directly involved in the implementation of these programs make of the suitability of the configuration of their territorial scope, as well as the achievement of their objectives. For it, the case study methodology is used, in which fieldwork is carried out where the main source of information will be interviews with promoters of tourism projects. The results show that Tajo-Salor County can be considered as a paradigmatic example of an “artificial” configuration of the territory, showing that, among those interviewed, there is no feeling of county. This has consequences on the assessment that local actors make of the implementation of the development program: those areas that do not feel part of the county have a much more negative assessment of the results obtained than the rest. This is a lesson that this case study offers; the political and technical managers of these programs should bear in mind in the future definition of the territories that apply this type of development strategy.