bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced CAD Detection Using Novel Multi-Modal Learning: Integration of ECG, PCG, and Coupling Signals
Authors: Sun Chengfa , Liu Xiaolei , Liu Changchun , Wang Xinpei , Liu Yuanyuan , Zhao Shilong , Zhang Ming
Published: October 2024

Early and highly precise detection is essential for delaying the progression of coronary artery disease (CAD). Previous methods primarily based on single-modal data inherently lack sufficient information that compromises detection precision. This paper proposes a novel multi-modal learning method aimed to enhance CAD detection by integrating ECG, PCG, and coupling signals. A novel coupling signal is initially generated by operating the deconvolution of ECG and PCG. Then, various entropy features are extracted from ECG, PCG, and its coupling signals, as well as recurrence deep features also encoded by integrating recurrence plots and a parallel-input 2-D CNN. After feature reduction and selection, final classification is performed by combining optimal multi-modal features and support vector machine. This method was validated on simultaneously recorded standard lead-II ECG and PCG signals from 199 subjects. The experimental results demonstrate that the proposed multi-modal method by integrating all signals achieved a notable enhancement in detection performance with best accuracy of 95.96%, notably outperforming results of single-modal and joint analysis with accuracies of 80.41%, 86.51%, 91.44%, and 90.42% using ECG, PCG, coupling signal, and joint ECG and PCG, respectively. This indicates that our multi-modal method provides more sufficient information for CAD detection, with the coupling information playing an important role in classification.
Perceptual Response Training for Reduction of Injury Risk Among High School Girls’ Soccer Players
Authors: Wilkerson Gary B. , Mether Kyle S. , Perrin Zoë A. , Emberton Samuel L. , Carlson Lynette M. , Hogg Jennifer A. , Acocello Shellie N.
Published: October 2024

Background/Objectives: Neural processes involved in visual detection, decision-making, and motor plan execution are believed to play a key role in the avoidance of sport-related injuries, but very little evidence exists to guide the development of training activities for the optimization of brain function. Immersive virtual reality provides a means to precisely measure the amount of time that elapses from visual stimulus presentation to the initiation of a motor response (i.e., perceptual latency) or its completion (i.e., response time). Methods: The median value of a metric quantifying both the speed and accuracy (i.e., the rate correct per second of response time) of 50 high school female soccer players was used to assign those who exhibited suboptimal performance to a training program. Training sessions required less than 5 min and the number of sessions completed over a 7-week period ranged from 3 to 13 (median = 5). Results: Among 42 players available for follow-up assessment at 8 weeks after the first practice session (training n = 19; comparison n = 23), the results of regression-discontinuity analyses demonstrated statistically significant differences (p < 0.05) for metrics representing fast/accurate movement initiation (i.e., the rate correct score for perceptual latency, p = 0.016) and across-trial consistency (i.e., perceptual latency variability, p = 0.027). From the first practice session to the end of the soccer season, 12 injuries were sustained by 10 players (four concussions and eight musculoskeletal injuries). A time-to-event analysis demonstrated strong associations with perceptual latency variability ≥ 0.143 (Hazard Ratio = 15.43, p = 0.011) and a lifetime history of at least one concussion (Hazard Ratio = 8.84, p = 0.008). Conclusions: The strong association of movement initiation consistency with the avoidance of concussion or musculoskeletal injury suggests that the training program may have a highly beneficial far-transfer effect.
Engineering and Technological Advancements in Repetitive Transcranial Magnetic Stimulation (rTMS): A Five-Year Review
Authors: Tubbs Abigail , Vazquez Enrique Alvarez
Published: October 2024

In the past five years, repetitive transcranial magnetic stimulation (rTMS) has evolved significantly, driven by advancements in device design, treatment protocols, software integration, and brain-computer interfaces (BCIs). This review evaluates how these innovations enhance the safety, efficacy, and accessibility of rTMS while identifying key challenges such as protocol standardization and ethical considerations. A structured review of peer-reviewed studies from 2019 to 2024 focused on technological and clinical advancements in rTMS, including AI-driven personalized treatments, portable devices, and integrated BCIs. AI algorithms have optimized patient-specific protocols, while portable devices have expanded access. Enhanced coil designs and BCI integration offer more precise and adaptive neuromodulation. However, challenges remain in standardizing protocols, addressing device complexity, and ensuring equitable access. While recent innovations improve rTMS’s clinical utility, gaps in long-term efficacy and ethical concerns persist. Future research must prioritize standardization, accessibility, and robust ethical frameworks to ensure rTMS’s sustainable impact.
Metacontrol Regulates Creative Thinking: An EEG Complexity Analysis Based on Multiscale Entropy
Authors: Qi Hang , Liu Chunlei
Published: October 2024

Previous studies have shown that creative thinking is associated with metacontrol, but its neural basis is unknown. The present study explored the neural basis of both by assessing EEG complexity through multiscale entropy. Subjects were engaged in a metacontrol task and an Alternative Uses Task, grouped according to task performance, and the EEG was analysed by multiscale entropy. The results showed that EEG complexity was significantly higher in the high-metacontrol and high-creativity groups than in the low-metacontrol and low-creativity groups, respectively, at high time scales. The metacontrol adaptability score and multipurpose task score were significantly and positively correlated with the EEG complexity at multiple electrode sites. It suggests that metacontrol and creativity are dependent on the activation of long-duration neural networks.
Combined Effect of tDCS and Motor or Cognitive Activity in Patients with Alzheimer’s Disease: A Proof-of-Concept Pilot Study
Authors: Fonte Cristina , Rotundo Giorgia , Varalta Valentina , Filosa Angelica , Muti Ettore , Barletta Cosimo , Evangelista Elisa , Venturelli Massimo , Picelli Alessandro , Smania Nicola
Published: October 2024

(1) Background: Alzheimer’s disease (AD) accounts for 70% of dementia cases and with no effective pharmacological treatments, new rehabilitation methods are needed. Motor and cognitive activities and transcranial direct current stimulation (tDCS) have shown promise in stabilizing and enhancing cognitive functions. Objective: we want to investigate the effects of tDCS combined with motor or cognitive activity on cognitive functions in AD patients. (2) Methods: Patients with mild or moderate AD were randomized between anodic tDCS groups (MotA or CogA) and sham tDCS groups (MotS or CogS). They received two weeks of treatment (45 min, five days/week), with the first 15 min using tDCS stimulation on the dorsolateral prefrontal cortex. Cognitive assessments were conducted pre-treatment (T0), post-treatment (T1), and one week after (T2). (3) Results: Twenty-three patients were included. Statistical analysis showed significant differences between anodic tDCS groups (MotA + CogA) and sham tDCS groups (MotS + CogS) with advantages for the first in improving global cognitive status (p = 0.042), selective attention (p = 0.012), and sustained attention (p = 0.012). Further analysis indicated no differences between the two anodic tDCS groups between T0 and T1. (4) Conclusions: combined anodal tDCS with motor or cognitive activity could improve global cognitive state and attention, slowing cognitive decline in AD patients. The trial was registered on Clinical Trials: NCT06619795.
Delayed Recovery After Exercise-Induced Pain in People with Chronic Widespread Muscle Pain Related to Cortical Connectivity
Authors: Bishop Mark D. , Alappattu Meryl J. , Rana Priyanka , Staud Roland , Boissoneault Jeff , Blaes Shelby , Joffe Yonah , Robinson Michael E.
Published: October 2024

Background/Objectives: There is a subset of patients with pain who become worse after exercise. To explore this, we examined the responses of people with chronic primary pain to a standardized high intensity exercise protocol used to induce delayed onset muscle soreness (DOMS). Methods: Ten participants with a diagnosis of chronic widespread muscle pain (CWMP) were matched by age and reported gender to ten participants without muscle pain (i.e., no pain (NP)). Participants completed a standardized DOMS protocol. Pain intensity in the arm at rest and with movement was assessed using daily electronic diaries. Peak pain, the timing of peak pain, and the time to recovery were compared between groups. Associations of pain variables with the functional connectivity of the sensorimotor (SMN), cerebellum, frontoparietal control (FPN), and default mode network (DMN) both within network nodes and the rest of the brain was assessed. Results: Significant differences in peak pain, the time to peak pain, and the time to recovery were noted between groups for both pain at rest and pain with movement after controlling for catastrophizing and pain resilience. Connectivity across the SMN, FPN, and DMN was associated with all pain-related variables. Significant group differences were identified between groups. Conclusions: A standardized muscle “injury” protocol resulted in more pain, a longer time to peak pain, and a longer time to resolve pain in the patient group compared to the NP group. These differences were associated with differences in connectivity across brain regions related to sensorimotor integration and appraisal. These findings provide preliminary evidence of the dysregulation of responses to muscle (micro)trauma in people with chronic pain.
Interactive Effects of Built Environment and Parking Policy on Car Use: Examining Differences Between Work and Non-Work Trips
Authors: Wang Xiaoquan , Zhang Yunlong , Sun Jing , Liu Erjian
Published: October 2024

Considerable interest has been shown in decreasing car use through planning and policy-making efforts. However, little is known about the interactive effects of built environment (BE) and parking policy on car use, and it is unclear whether and how these effects differ across trip purposes. We conducted a web-based survey in Beijing and collected data from 1036 respondents, including 517 male and 519 female respondents. This study estimates the interactive effects of BE and parking policy on car use for home-based work and non-work trips by employing multilevel logit models. The results show that BE variables at trip origins and destinations are important for shaping car use for both home-based work and non-work trips. Specifically, land use mixture (Coeff. = −0.121), bus stop density (Coeff. = −0.006), and population density (Coeff. = −0.009) at residential locations are negative factors affecting car use for work trips, whereas distance to local center (Coeff. = 0.012) and distance to the city center (Coeff. = 0.019) at residential locations are positive factors. Land use mixture (Coeff. = −0.323), bus stop density (Coeff. = −0.008), road density (Coeff. = −0.002), and population density (Coeff. = −0.007) at residential locations are negative factors of car use for non-work trips. Among BE factors at destinations, land use mixture (Coeff. = −0.319), bus stop density (Coeff. = −0.015), road density (Coeff. = −0.008), distance to the local center (Coeff. = −0.018), and population density (Coeff. = −0.012) are negative factors for car use for work trips, whereas the negative factors for non-work trips are land use mix (Coeff. = −0. 218), bus stop density (Coeff. = −0.038), road density (Coeff. = −0.003), distance to the city center (Coeff. = −0.121), and population density (Coeff. = −0.009). The effects of BE variables can be strengthened or weakened by free parking and parking convenience. Moreover, the results identify significant differences in the effects between work and non-work trips. These findings inform planners and policymakers of how to coordinate the BE and parking policies to decrease car dependence.
Low-Intensity Focused Ultrasound-Responsive Phase-Transitional Liposomes Loaded with STING Agonist Enhances Immune Activation for Breast Cancer Immunotherapy
Authors: Hu Cong , Jiang Yuancheng , Chen Yixin , Wang Ying , Wu Ziling , Zhang Qi , Wu Meng
Published: October 2024

Background: Pharmacologically targeting the STING pathway offers a novel approach to cancer immunotherapy. However, small-molecule STING agonists face challenges such as poor tumor accumulation, rapid clearance, and short-lived effects within the tumor microenvironment, thus limiting their therapeutic potential. To address the challenges of poor specificity and inadequate targeting of STING in breast cancer treatment, herein, we report the design and development of a targeted liposomal delivery system modified with the tumor-targeting peptide iRGD (iRGD-STING-PFP@liposomes). With LIFU irradiation, the liposomal system exploits acoustic cavitation, where gas nuclei form and collapse within the hydrophobic region of the liposome lipid bilayer (transient pore formation), which leads to significantly enhanced drug release. Methods: Transmission electron microscopy (TEM) was used to investigate the physicochemical properties of the targeted liposomes. Encapsulation efficiency and in vitro release were assessed using the dialysis bag method, while the effects of iRGD on liposome targeting were evaluated through laser confocal microscopy. The CCK-8 assay was used to investigate the toxicity and cell growth effects of this system on 4T1 breast cancer cells and HUVEC vascular endothelial cells. A subcutaneous breast cancer tumor model was established to evaluate the tumor-killing effects and therapeutic mechanism of the newly developed liposomes. Results: The liposome carrier exhibited a regular morphology, with a particle size of 232.16 ± 19.82 nm, as indicated by dynamic light scattering (DLS), and demonstrated low toxicity to both HUVEC and 4T1 cells. With an encapsulation efficiency of 41.82 ± 5.67%, the carrier exhibited a slow release pattern in vitro after STING loading. Targeting results indicated that iRGD modification enhanced the system’s ability to target 4T1 cells. The iRGD-STING-PFP@liposomes group demonstrated significant tumor growth inhibition in the subcutaneous breast cancer mouse model with effective activation of the immune system, resulting in the highest populations of matured dendritic cells (71.2 ± 5.4%), increased presentation of tumor-related antigens, promoted CD8+ T cell infiltration at the tumor site, and enhanced NK cell activity. Conclusions: The iRGD-STING-PFP@liposomes targeted drug delivery system effectively targets breast cancer cells, providing a new strategy for breast cancer immunotherapy. These findings indicate that iRGD-STING-PFP@liposomes could successfully deliver STING agonists to tumor tissue, trigger the innate immune response, and may serve as a potential platform for targeted immunotherapy.
Analysis of Swallowing Functional Preservation by Surgical Versus CRT After Induction Chemotherapy for Oropharyngeal Cancer
Authors: Tsou Yung-An , Chang Wen-Dien , Meng Nai-Hsin , Hua Chun-Hung
Published: October 2024

Objectives: This retrospective observational study investigated to determine whether surgery or chemoradiation therapy after induction chemotherapy leads to better swallow function for oropharyngeal cancer patients. Methods: We documented the treatment paths and results of 267 patients with oropharyngeal squamous cell cancer (OPSCC). By quantifying nasogastric (NG) tube usage, surgery after induction chemotherapy (IC–surgery), and chemoradiation therapy after induction chemotherapy (IC-CRT) could be compared to determine the effectiveness of each. Cancer stages were also recorded concerning treatment options. The differences in NG tube usage IC–surgery and IC-CRT groups were compared. The NG tube dependence rates were also presented. Results: The prognosis and tube dependence differed significantly between the two groups. The IC–surgery had a better prognosis compared to IC-CRT for oropharyngeal cancer. The findings indicated that NG tube dependence was greater in advanced tumor stage 4 compared to stages 1–3, and NG tube dependence rates were higher for patients who underwent chemoradiation therapy after induction chemotherapy. Swallowing function was better in the IC–surgery group compared to the IC-CRT group. Conclusions: Higher NG tube retention rates and NG dependence are found in OPSCC patients who choose CRT as their treatment and also in the advanced-stage group.
Enhancer of Zeste Homolog 2 Protects Mucosal Melanoma from Ferroptosis via the KLF14-SLC7A11 Signaling Pathway
Authors: Du Haizhen , Hou Lijie , Yu Huan , Zhang Fenghao , Tong Ke , Wu Xiaowen , Zhang Ziyi , Liu Kaiping , Miao Xiangguang , Guo Wenhui , Guo Jun , Kong Yan
Published: October 2024

Background: Mucosal melanoma (MM) is epidemiologically, biologically, and molecularly distinct from cutaneous melanoma. Current treatment strategies have failed to significantly improve the prognosis for MM patients. This study aims to identify therapeutic targets and develop combination strategies by investigating the mechanisms underlying the tumorigenesis and progression of MM. Methods: We analyzed the copy number amplification of enhancer of zeste homolog 2 (EZH2) in 547 melanoma patients and investigated its correlation with clinical prognosis. Utilizing cell lines, organoids, and patient-derived xenograft models, we assessed the impact of EZH2 on cell proliferation and sensitivity to ferroptosis. Further, we explored the mechanisms of ferroptosis resistance associated with EZH2 by conducting RNA sequencing and chromatin immunoprecipitation sequencing. Results: EZH2 copy number amplification was closely associated with malignant phenotype and poor prognosis in MM patients. EZH2 was essential for MM cell proliferation in vitro and in vivo. Moreover, genetic perturbation of EZH2 rendered MM cells sensitized to ferroptosis. Combination treatment of EZH2 inhibitor with ferroptosis inducer significantly inhibited the growth of MM. Mechanistically, EZH2 inhibited the expression of Krüpple-Like factor 14 (KLF14), which binds to the promoter of solute carrier family 7 member 11 (SLC7A11) to repress its transcription. Loss of EZH2 therefore reduced the expression of SLC7A11, leading to reduced intracellular SLC7A11-dependent glutathione synthesis to promote ferroptosis. Conclusion: Our findings not only establish EZH2 as a biomarker for MM prognosis but also highlight the EZH2-KLF14-SLC7A11 axis as a potential target for MM treatment.
Ex Vivo Intestinal Organoid Models: Current State-of-the-Art and Challenges in Disease Modelling and Therapeutic Testing for Colorectal Cancer
Authors: Randall-Demllo Sarron , Al-Qadami Ghanyah , Raposo Anita E. , Ma Chenkai , Priebe Ilka K. , Hor Maryam , Singh Rajvinder , Fung Kim Y. C.
Published: October 2024

Despite improvements in participation in population-based screening programme, colorectal cancer remains a major cause of cancer-related mortality worldwide. Targeted interventions are desirable to reduce the health and economic burden of this disease. Two-dimensional monolayers of colorectal cancer cell lines represent the traditional in vitro models for disease and are often used for diverse purposes, including the delineation of molecular pathways associated with disease aetiology or the gauging of drug efficacy. The lack of complexity in such models, chiefly the limited epithelial cell diversity and differentiation, attenuated mucus production, lack of microbial interactions and mechanical stresses, has driven interest in the development of more holistic and physiologically relevant in vitro model systems. In particular, established ex vivo patient-derived explant and patient-derived tumour xenograft models have been supplemented by progress in organoid and microfluidic organ-on-a-chip cultures. Here, we discuss the applicability of advanced culturing technologies, such as organoid systems, as models for colorectal cancer and for testing chemotherapeutic drug sensitivity and efficacy. We highlight current challenges associated with organoid technologies and discuss their future for more accurate disease modelling and personalized medicine.
Effects of Open-Label Placebos on Visual Food Cue Reactivity in Children and Adolescents
Authors: Schienle Anne , Polz Alice , Haslacher Katharina , Osmani Florian , Kogler Wolfgang
Published: October 2024

Background: A high level of food cue reactivity (FCR) is a risk factor for overeating and weight gain. This randomized trial investigated whether open-label placebos (OLPs: placebos honestly administered) can reduce FCR (reported appetite) in children and adolescents. Method: Children (n = 73; 8–12 years old) and adolescents (n = 187; 16–18 years old) were randomly assigned to either an OLP group or a control group (without OLP). Participants viewed images depicting food (sweets and fruits) and non-food items. Before viewing, the OLP group received a placebo for appetite reduction. Participants rated their desire to eat the depicted food items (0–100) and the perceived effectiveness of the OLP intervention. Results: The OLP exhibited a large effect in children, leading to a general reduction in appetite (group difference OLP vs. no OLP: M = −20.8; ηp2 = 0.20). This general effect was absent in adolescents, whose appetite reduction was restricted to fruits (OLP vs. no OLP: M = −8.1; ηp2 = 0.03). Additionally, children perceived the OLP as more effective than adolescents. Conclusion: The reduced response and skeptical attitudes of adolescents towards OLP treatment require further investigation.
Predictable Full Digital Workflow Using Stackable Surgical Templates for Complete Dental Arch Rehabilitation with Implant-Supported Fixed Restorations—Case Series and Proof of Concept
Authors: Cristache Corina Marilena , Burlacu Vatamanu Oana Elena , Butnarasu Cristian Corneliu , Mihut Tamara , Sgiea Eliza Denisa
Published: October 2024

Background: In recent years, advancements in digital dentistry have provided new opportunities for more predictable and efficient treatment options, particularly in patients with failing dentition. This study aimed to evaluate the effectiveness and accuracy of a fully digital workflow using stackable surgical templates for complete dental arch rehabilitation with implant-supported fixed restorations. Methods: Four patients, comprising two males and two females with a mean age of 66 years, were included in this case series. Each patient underwent meticulous digital planning, including CBCT and intraoral scanning, to create a virtual patient for preoperative assessment and virtual treatment planning. The assessment of the trueness of implant positioning was conducted in Geomagic Control X software (version 2017.0.3) by referencing anatomical landmarks from both the preoperative and one-year postoperative CBCT scans. Results: A total of 25 dental implants were placed in the maxilla, followed by the installation of long-term provisional restorations. The results showed minimal deviation between the planned and actual implant positions, with mean 3D coronal, apical, and angular discrepancies of 0.87 mm, 2.04 mm, and 2.67°, respectively. All implants achieved successful osseointegration, and no failures were recorded, resulting in a 100% survival rate at the one-year follow-up. Patients reported high satisfaction with both the esthetic and functional outcomes based on their subjective feedback. Conclusions: The findings suggest that the use of a fully digital workflow with stackable surgical templates is a reliable and effective approach for immediate implant placement and prosthetic rehabilitation, enhancing treatment precision and patient comfort.
Regulation of Cultivation Temperature on Biomass and Activity of Bifidobacterium breve B2798
Authors: Liu Kailong , Liu Yiting , Yang Zhan , Yu Jie , Yao Guoqiang
Published: October 2024

Bifidobacterium is among the dominant flora in the healthy intestine of the human body. It has many probiotic effects such as lowering cholesterol, inhibiting tumors, and regulating immunity. However, fluctuations in culture conditions during cultivation will lead to a decrease in the number of active bacteria. Therefore, more precise control of culture conditions is required to reduce the activity damage caused by environmental fluctuations. Based on this, this study utilized a fully automatic intelligent fermentation tank to develop a cultivation technique suitable for improving the activity and biomass of Bifidobacterium breve B2798. The results show that, under a cultivation temperature of 38.0 °C, the highest viable cell count, which is (2.56 ± 0.04) × 1010 CFU/mL, can be achieved in the culture medium, with the conclusion that the fermentation endpoint should be controlled at the end period of bacteria logarithmic growth when there is the highest viable cell count and bacterial activity in the culture medium. This study has elucidated the influences of different temperatures on the biomass, viable cell count, and activity of Bifidobacterium breve B2798, providing basic data for the later development of industrialized processing techniques for this bacteria strain.
The Activation of Endogenous Proteases in Shrimp Muscle Under Water-Free Live Transport
Authors: Li Jia , Liu Yuxin , Yang Huanhuan , Cai Luyun , Nong Wenqian , Guan Weiliang
Published: October 2024

Water-free transportation (WFT) causes shrimp (Penaeus vannamei) flesh quality deterioration. However, the roles of endogenous protease-induced protein hydrolysis have been neglected in the research. In the present study, calpain zymography, gelatinase zymography, the hematoxylin–eosin staining method, and other methods were applied to investigate the response of various endogenous proteases (cathepsin, calpain, and gelatinase), the myofibril fragmentation index (MFI), and the microscopic morphology of shrimp muscle during WFT in comparison with the shrimp under the conventional water transportation strategy (WT). The results showed that the total activity of proteases in shrimp muscle increased significantly (p ≤ 0.05) after simulated transportation. Cathepsins and gelatinases were activated during WFT. No significant (p > 0.05) changes of the activity of caspase-3 and the muscle cell apoptosis rate were detected in shrimp muscle cells after WFT. In addition, the MFI increased and the gap among muscle fiber bundles enlarged after WFT. Compared with WFT, no significant (p > 0.05) effect on the activities of calpain, gelatinase, and caspase-3 in the muscle of shrimp was found after WT, and only the activity of cathepsin L significantly increased (p ≤ 0.05). Based on the findings, we concluded that the activation of various endogenous proteases was induced during WFT.
Effect of Probiotics on Gastrointestinal Health Through the Aryl Hydrocarbon Receptor Pathway: A Systematic Review
Authors: De la Rosa González Adrián , Guerra-Ojeda Sol , Camacho-Villa María Alejandra , Valls Alicia , Alegre Eva , Quintero-Bernal Ronald , Martorell Patricia , Chenoll Empar , Serna-García Marta , Mauricio Maria D. , Serna Eva
Published: October 2024

Probiotics are living microorganisms recognized for conferring health benefits on the host by modulating the gut microbiota. They interact with various signaling pathways, including the aryl hydrocarbon receptor (AhR), which plays a crucial role in maintaining intestinal homeostasis and immune function. The activation of AhR by probiotics has been associated with benefits such as improved intestinal barrier function, reduced inflammation, and modulation of immune responses. This systematic review aims to summarize current knowledge on the signaling of AhR, mediated by probiotics in physiological conditions and gastrointestinal pathologies. We conducted a comprehensive search across databases, including PubMed and Embase, up until July 2024. Out of 163 studies screened, 18 met the inclusion criteria. Our findings revealed in healthy populations that probiotic consumption increases the production of AhR ligands promoting intestinal immune tolerance. Furthermore, in populations with gastrointestinal pathologies, probiotics ameliorated symptoms through AhR activation by Trp metabolites, leading to the upregulation of the anti-inflammatory response.
Reply to Elgoyhen et al. Comment on “De Rosa et al. Hearing Loss: Genetic Testing, Current Advances and the Situation in Latin America. Genes 2024, 15, 178”
Authors: Walz Katherina
Published: October 2024

First, thanks to Elgoyhen et al [...]
Mitigating the Adverse Effects of Salt Stress on Pepper Plants Through Arbuscular Mycorrhizal Fungi (AMF) and Beneficial Bacterial (PGPR) Inoculation
Authors: Dere Sultan
Published: October 2024

This study investigates arbuscular mycorrhizal fungi (AMF), plant growth-promoting rhizobacteria (PGPR), and their combined application under salt stress (200 mM NaCl), emphasizing their synergistic potential to enhance plant resilience. Conducted in a controlled climate chamber, key parameters such as plant height, biomass, SPAD values, ion leakage, relative water content (RWC), osmotic potential, and mineral uptake were assessed. Salt stress significantly reduced plant growth, chlorophyll content, and nutrient absorption. However, AMF and PGPR improved plant performance, with co-inoculation showing the highest efficacy in increasing RWC, nutrient uptake, and maintaining membrane stability. AMF and PGPR treatments enhanced potassium retention and reduced sodium and chloride accumulation, mitigating ionic imbalances. The improved chlorophyll content and water relations under co-inoculation demonstrate the potential of these biostimulants to boost photosynthesis and plant resilience. These findings highlight AMF and PGPR as eco-friendly solutions for sustainable agriculture, promoting crop productivity and stress tolerance under saline conditions.
Cigar-Specific Health Warnings: Attention, Recall, and Perceived Effectiveness Among Young Adult Users and Non-Users
Authors: Klein Elizabeth G. , Driscoll Anne E. , Shoben Abigail B. , Macisco Joseph M. , Pike Moore Stephanie , Quisenberry Amanda J. , Trapl Erika S.
Published: October 2024

Limited research has examined attention to these cigar-specific health warnings and their perceived effectiveness among young people. The objective of our study was to evaluate the attention to and perceptions of a set of cigar-specific health warnings among young adult tobacco users and non-users. Methods: Young adults ages 18–24 in Columbus, Ohio, were recruited into an eye-tracking experiment examining cigarillo packaging between May 2022 and February 2023. Participants (n = 124) were shown 12 unique, branded cigarillo packages featuring a rotation of four of the Food and Drug Administration’s mandated health warnings: (1) Cigar smoking can cause lung cancer and heart disease (“disease”); (2) tobacco smoke increases the risk of lung cancer and heart disease, even in nonsmokers (“nonsmokers”); (3) cigar smoking can cause cancers of the mouth and throat, even if you do not inhale (“inhale”); and (4) cigars are not a safe alternative to cigarettes (“alternative”). Software captured visual attention to each product package, including the health warning. Participants also ranked the most effective message to motivate people to quit; one week later, the participants (n = 118) self-reported unaided recall of the experiment. Results: Study participants were an average of 21.2 years old, 54.2% were female, 73.7% were White, 65.3% had some college education, and 26.3% reported tobacco use in the previous month. The health warning, “Cigar smoking can cause cancers of the mouth and throat, even if you do not inhale” was ranked the most effective cigar warning (41.5%) and drew the greatest proportion of visual attention (26.1%). More than half (52.5%) recalled details regarding the health warning messages one week following the experiment, with few recalling (17.7%) specific warning message themes. Conclusions: Understanding the best performing health warnings is a crucial strategy to share accurate information on the risks of tobacco use. Our findings suggest that the warning on cancer risk even without inhaling drew the greatest visual attention and highest rating of perceived effectiveness among this sample of young adult cigarillo users and non-users.
Neurosteroids Alter p-ERK Levels and Tau Distribution, Restraining the Effects of High Extracellular Calcium
Authors: Konsta Vasiliki , Paschou Maria , Koti Nikoleta , Vlachou Maria Evangelia , Livanos Pantelis , Xilouri Maria , Papazafiri Panagiota
Published: October 2024

Neurosteroids are undeniably regarded as neuroprotective mediators, regulating brain function by rapid non-genomic actions involving interference with microtubules. Conversely, hyperphosphorylated Tau is considered responsible for the onset of a plethora of neurodegenerative diseases, as it dissociates from microtubules, leading to their destabilization, thus impairing synaptic vesicle transport and neurotransmission. Consequently, we aimed to investigate the effects of neurosteroids, specifically allopregnanolone (Allo) and dehydroepiandrosterone (DHEA), on the levels of total and phosphorylated at Serine 404 Tau (p-Tau) in C57BL/6 mice brain slices. In total tissue extracts, we found that neurosteroids elevated both total and p-Tau levels without significantly altering the p-Tau/Tau ratio. In addition, the levels of several enzymes implicated in Tau phosphorylation did not display significant differences between conditions, suggesting that neurosteroids influence Tau distribution rather than its phosphorylation. Hence, we subsequently examined the mitochondria-enriched subcellular fraction where, again, both p-Tau and total Tau levels were increased in the presence of neurosteroids. These effects seem actin-dependent, as disrupting actin polymerization by cytochalasin B preserved Tau levels. Furthermore, co-incubation with high [Ca2+] and neurosteroids mitigated the effects of Ca2+ overload, pointing to cytoskeletal remodeling as a potential mechanism underlying neurosteroid-induced neuroprotection.
Cellular and Molecular Pathophysiology of Gestational Diabetes
Authors: Torres-Torres Johnatan , Monroy-Muñoz Irma Eloisa , Perez-Duran Javier , Solis-Paredes Juan Mario , Camacho-Martinez Zaira Alexi , Baca Deyanira , Espino-y-Sosa Salvador , Martinez-Portilla Raigam , Rojas-Zepeda Lourdes , Borboa-Olivares Hector , Reyes-Muñoz Enrique
Published: October 2024

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD’s cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD’s impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD’s complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies.
The Role of Heat Shock Factor 1 in Preserving Proteomic Integrity During Copper-Induced Cellular Toxicity
Authors: Ghai Shruti , Shrestha Rejina , Hegazi Ahmad , Boualoy Vanessa , Liu Shi-He , Su Kuo-Hui
Published: October 2024

Copper is crucial for many physiological processes across mammalian cells, including energy metabolism, neurotransmitter synthesis, and antioxidant defense mechanisms. However, excessive copper levels can lead to cellular toxicity and “cuproptosis”, a form of programmed cell death characterized by the accumulation of copper within mitochondria. Tumor cells are less sensitive to this toxicity than normal cells, the mechanism for which remains unclear. We address this important issue by exploring the role of heat shock factor 1 (HSF1), a transcription factor that is highly expressed across several types of cancer and has a crucial role in tumor survival, in protecting against copper-mediated cytotoxicity. Using pancreatic ductal adenocarcinoma cells, we show that excessive copper triggers a proteotoxic stress response (PSR), activating HSF1 and that overexpressing HSF1 diminishes intracellular copper accumulation and prevents excessive copper-induced cell death and amyloid fibrils formation, highlighting HSF1′s role in preserving proteasomal integrity. Copper treatment decreases the lipoylation of dihydrolipoamide S-acetyltransferase (DLAT), an enzyme necessary for cuproptosis, induces DLAT oligomerization, and induces insoluble DLAT formation, which is suppressed by overexpressing HSF1, in addition to enhancing the interaction between HSF1 and DLAT. Our findings uncover how HSF1 protects against copper-induced damage in cancer cells and thus represents a novel therapeutic target for enhancing copper-mediated cancer cell death.
Are There Non-Invasive Biomarker(s) That Would Facilitate the Detection of Ovarian Torsion? A Systematic Review and Meta-Analysis
Authors: Naylor Meg , Doherty Grace , Draper Hannah , Fletcher Daniel M. , Rigby Alan , Adedipe Tolu , Guinn Barbara-ann
Published: October 2024

Ovarian torsion (OT) is a rare gynaecological emergency that requires a prompt diagnosis for optimal patient management. To determine whether there were any biomarkers suitable for the non-invasive detection of OT, two independent reviewers performed systematic searches of five literature databases (PubMed, Medline, Scopus, Cochrane, and CINAHL) from inception until October 1st, 2023. Following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, the search included patients with OT that had quantified biomarker expression with no age, geographical location, publication date, language, or setting restrictions. Articles were excluded if OT was found incidentally, was based on qualitative analyses, or were not primary research articles. Full texts of 23 selected articles were assessed for risk of bias and quality assurance using a modified Newcastle–Ottawa Scale (NOS) for clinical studies and SYRCLE’s risk of bias tool for the assessment of pre-clinical (animal) studies. A total of 11 articles described studies on animals and all described serum biomarkers comparing results between OT versus a sham operation, a control group, or readings before and after OT. Ischaemia-modified albumhumin (IMA), serum D-dimer (s-DD), heat shock protein-70 (hsp-70), Pentraxin-3 (PTX3), and c-reactive protein (CRP) each showed the most promise, with p-values for the difference between OT and control groups achieving ≤ 0.001. In studies of humans, the biomarkers ranged from 16.4 to 92.3% sensitivity and 77–100% specificity. The most promising biomarkers for the early prediction of OT in patients included s-DD, interleukin-6 (IL-6), IMA, and tumour necrosis factor-alpha (TNF-α). Signal peptide, CUB domain, and EGF-like domain-containing 1 (SCUBE1) had a high specificity at 93.3%, second only to s-DD and a positive likelihood ratio (LR) > 10. IMA was the only other biomarker that also had a positive LR > 10, making it a promising diagnostic biomarker. The studies identified by this systematic literature review each analysed small patient groups but IMA, DD, and SCUBE1 nevertheless showed promise as serum biomarkers with a pooled LR > 10. However, further well-designed studies are needed to identify and evaluate individual markers or diagnostic panels to help clinicians manage this important organ-threatening condition.
Predictive Utility of Biochemical Markers for the Diagnosis and Prognosis of Gestational Diabetes Mellitus
Authors: Inthavong Sathaphone , Jatavan Phudit , Tongsong Theera
Published: October 2024

Gestational diabetes mellitus (GDM) is a common complication during pregnancy with an increasing prevalence worldwide. Early prediction of GDM and its associated adverse outcomes is crucial for timely intervention and improved maternal and fetal health. The objective of this review is to provide a comprehensive summary of contemporary evidence on biomarkers, focusing on their potential to predict the development of GDM and serve as predictors of maternal, fetal, and neonatal outcomes in women with GDM. A literature search was conducted in the PubMed database using relevant terms. Original research articles published in English between 1 January 2015, and 30 June 2024, were included. A two-stage screening process was employed to identify studies on biomarkers for GDM diagnosis and prognosis and to evaluate the evidence for each biomarker’s diagnostic performance and its potential prognostic correlation with GDM. Various biochemical markers, including adipokines, inflammatory markers, insulin resistance markers, glycemic markers, lipid profile markers, placenta-derived markers, and other related markers, have shown promise in identifying women at risk of developing GDM and predicting adverse pregnancy outcomes. Several promising markers with high predictive performance were identified. However, no single biomarker has demonstrated sufficient accuracy to replace the current diagnostic criteria for GDM. The complexity of multiple pathways in GDM pathogenesis highlights the need for a multi-marker approach to improve risk stratification and guide personalized management strategies. While significant progress has been made in GDM biomarker research, further studies are required to refine and validate these markers for clinical use and to develop a comprehensive, evidence-based approach to GDM prediction and management that can improve maternal and child health outcomes.
Emotion-Recognition System for Smart Environments Using Acoustic Information (ERSSE)
Authors: Santiago Gabriela , Aguilar Jose , García Rodrigo
Published: October 2024

Acoustic management is very important for detecting possible events in the context of a smart environment (SE). In previous works, we proposed a reflective middleware for acoustic management (ReM-AM) and its autonomic cycles of data analysis tasks, along with its ontology-driven architecture. In this work, we aim to develop an emotion-recognition system for ReM-AM that uses sound events, rather than speech, as its main focus. The system is based on a sound pattern for emotion recognition and the autonomic cycle of intelligent sound analysis (ISA), defined by three tasks: variable extraction, sound data analysis, and emotion recommendation. We include a case study to test our emotion-recognition system in a simulation of a smart movie theater, with different situations taking place. The implementation and verification of the tasks show a promising performance in the case study, with 80% accuracy in sound recognition, and its general behavior shows that it can contribute to improving the well-being of the people present in the environment.
The Influence of Aspergillus fumigatus Fatty Acid Oxygenases PpoA and PpoC on Caspofungin Susceptibility
Authors: Delbaje Endrews , de Castro Patrícia Alves , Calise Dante G. , Mengyao Niu , Horta Maria Augusta Crivelente , Akiyama Daniel Yuri , Pontes João Guilherme , Fill Taícia , Kniemeyer Olaf , Krüger Thomas , Brakhage Axel A. , Wong Koon Ho , Keller Nancy P. , Goldman Gustavo H.
Published: October 2024

Aspergillus fumigatus can cause invasive pulmonary aspergillosis (IPA). Fungicidal azoles and fungistatic caspofungin (CAS) are the first- and second-line therapies, respectively, used to treat IPA. Treatment of A. fumigatus with CAS or micafungin induces the production of the oxylipin 5,8-diHODE by the fungal oxygenase PpoA. For this article, we investigated the influence of ppo genes, which encode the fatty acid oxygenases responsible for oxylipin biosynthesis, on CAS tolerance. The influence of PpoA and PpoC on CAS tolerance is mediated by MpkA phosphorylation and protein kinase A (PKA) activity. RNAseq transcriptional profiling and the label-free quantitative proteomics of the ppoA and ppoC mutants showed that differentially expressed genes and proteins are related to secondary metabolites and carbohydrate metabolism. We also characterized two clinical isolates, CM7555 and IFM61407, which decrease and increase susceptibility to CAS, respectively. CM7555 does not exhibit increased oxylipin production in the presence of CAS but oxylipin induction upon CAS exposure is increased in IFM61407, suggesting that oxylipins are not the only mechanism involved in CAS tolerance in these isolates. Upon CAS exposure, CM7555 has higher MpkA phosphorylation and PKA activity than IFM61407. Our results reveal the different aspects and genetic determinants involved in A. fumigatus CAS tolerance.
The Effects of Cattle Grazing on the Composition of Diatom Assemblages in the Peatland Pools of the Southeastern Alps (Italy, Adamello-Brenta Nature Park)
Authors: Rossi Floriana , Galassi Diana M. P. , Angeli Nicola , Cantonati Marco , Di Cicco Mattia
Published: October 2024

Mires are significant C-sinks and important habitats for biodiversity conservation. Particularly in the Alpine peatlands, grazing and trampling cause mires to degrade, causing changes in plant communities that increase bulk density, peat erosion, and nutrient excesses. We took sixteen samples of epipelic and epiphytic diatoms from mire pools subjected to varying degrees of grazing in the Adamello-Brenta Nature Park (Trento, Italy). We identified >100 diatom species (ca. 70% included in Red List threat categories). We used nMDS to identify groups of diatom species. Their statistical significance was checked with an ANOSIM and, to identify the species that contributed most to the difference between the two groups, a BEST-SIMPER procedure was carried out. The multivariate analyses allowed us to identify significant differences among the most and least grazed sites, and to select the species that contributed most to this distinction. We confirmed that some species were more frequent and abundant in the most grazed sites and behaved as opportunists in the presence of a greater nutrient input, to the detriment of rare and sensitive species, which were more numerous and abundant in the less grazed sites. We provided useful information on grazing effects, underlining the importance of managing and protecting habitats of unique environmental value.