bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation in Follow-Up after Radical Cystectomy for Bladder Cancer—An Inventory Roundtable and Literature Review
Authors: Contieri Roberto , Pichler Renate , del Giudice Francesco , Marcq Gautier , Gallioli Andrea , Albisinni Simone , Soria Francesco , d’Andrea David , Krajewski Wojciech , Carrion Diego M. , Mari Andrea , van Rhijn Bas W. G. , Moschini Marco , Pradere Benjamin , Mertens Laura S.
Published: April 2024

Background: Follow-up after radical cystectomy (RC) for bladder cancer can be divided into oncological and functional surveillance. It remains unclear how follow-up after RC should ideally be scheduled. The aim of this report was to gain insight into the organization of follow-up after RC in Europe, for which we conducted a roundtable inventory within the EAU Young Academic Urologists Urothelial Cancer working group. Methods: An inventory semi-structured survey was performed among urologists of the EAU Young Academic Urologists Urothelial Cancer working group to describe the organization of follow-up. The surveys were analyzed using a deductive approach. Similarities and differences in follow-up after RC for bladder cancer were described. Results: The survey included 11 urologists from six different European countries. An institutional follow-up scheme was used by six (55%); three (27%) used a national or international guideline, and two (18%) indicated that there was no defined follow-up scheme. Major divergent aspects included the time points of follow-up, the frequency, and the end of follow-up. Six centers (55%) adopted a risk-adapted follow-up approach tailored to (varying) patient and tumor characteristics. Laboratory tests and CT scans were used in all cases; however, the intensity and frequency varied. Functional follow-up overlapped with oncological follow-up in terms of frequency and duration. Patient-reported outcome measures were only used by two (18%) urologists. Conclusions: Substantial variability exists across European centers regarding the follow-up after RC for bladder cancer. This highlights the need for an international analysis focusing on its organization and content as well as on opportunities to improve patients’ needs during follow-up after RC.
Effect of Annoying Sounds on Postural Control
Authors: Błażkiewicz Michalina , Gulatowska Michalina , Hadamus Anna , Kędziorek Justyna , Brzuszkiewicz-Kuźmicka Grażyna
Published: April 2024

Objectives: This study aimed to explore the impact of irritating sounds on the postural control of healthy adults, considering both linear and nonlinear parameters, subjective assessments, and gender differences. Methods: Thirty-four young participants (17 females, 17 males) completed three 30 s bipedal standing stability tests on a balance platform: one with visual control (EO), another without visual control (EC), and a third without visual control but accompanied by irritating sounds (ECS). Additionally, participants filled out a questionnaire evaluating their sound sensitivity. Linear and nonlinear parameters from each balance test were considered for statistical analysis. Results: The findings reveal significant gender-based variations in sensitivity to sound, with women exhibiting higher sensitivity. No statistically significant differences in postural control were observed between males and females, except for a notable increase in irregularity (SampEn values) in the anterior–posterior direction for females in the ECS trial. Correlation analyses revealed a moderate and statistically significant correlation between SampEn values in the AP direction and SE scores. Conclusions: This study highlights the intricate relationship between sensory stimuli, attention, and the body’s ability to maintain balance. The presence of irritating sounds led to increased irregularity in postural control, particularly in the absence of visual control.
Control of Peach Leaf Curl with Foliar Applications of Plant Immunity Inducers and Insights in Elicitation of Defense Responses against Taphrina deformans
Authors: Kavroumatzi Charikleia K. , Matziarli Paschalina , Chatzidimopoulos Michael , Boutsika Anastasia , Tsitsigiannis Dimitrios I. , Paplomatas Epaminondas , Zambounis Antonios
Published: April 2024

Taphrina deformans is the causal agent of leaf curl, a serious peach disease which causes significant losses in peach production worldwide. Nowadays, in order to control plant diseases, it is necessary to adopt novel and low-cost alternatives to conventional chemical fungicides. These promising strategies are targeted at eliciting host defense mechanisms via priming the host through the consecutive application of plant immunity inducers prior to pathogen challenge. In this study, we investigated whether chitosan or yeast cell wall extracts could provide enhanced tolerance against leaf curl in two-season field trials. Furthermore, we addressed the possible molecular mechanisms involved beyond the priming of immune responses by monitoring the induction of key defense-related genes. The efficacy of spraying treatments against peach leaf curl with both inducers was significantly higher compared to the untreated control, showing efficacy in reducing disease severity of up to 62.6% and 73.9% for chitosan and yeast cell wall extracts, respectively. The application of chitosan in combination with copper hydroxide was more efficient in reducing disease incidence and severity, showing efficacy values in the range of 79.5–93.18%. Peach plantlets were also spray-treated with immunity inducers three times prior to leaf inoculation with T. deformans blastospores in their yeast phase. The relative expression levels of nine key defense and priming genes, including those encoding members of pathogenesis-related (PR) proteins and hub genes associated with hormone biosynthesis, were monitored by RT-qPCR across three days after inoculation (dai). The results indicate that pre-treatments with these plant immunity inducers activated the induction of genes involved in salicylic acid (SA) and jasmonate (JA) defense signaling pathways that may offer systemic resistance, coupled with the upregulation of genes conferring direct antimicrobial effects. Our experiments suggest that these two plant immunity inducers could constitute useful components towards the effective control of T. deformans in peach crops.
The Transcription Factors AcuK and AcuM Influence Siderophore Biosynthesis of Aspergillus fumigatus
Authors: Caballero Patricia , Yap Annie , Bromley Michael J. , Haas Hubertus
Published: April 2024

The mold Aspergillus fumigatus employs two high-affinity uptake systems, reductive iron assimilation (RIA) and siderophore-mediated iron acquisition (SIA), for the acquisition of the essential trace element iron. SIA has previously been shown to be crucial for virulence in mammalian hosts. Here, we show that a lack of AcuK or AcuM, transcription factors required for the activation of gluconeogenesis, decreases the production of both extra- and intracellular siderophores in A. fumigatus. The lack of AcuM or AcuK did not affect the expression of genes involved in RIA and SIA, suggesting that these regulators do not directly regulate iron homeostasis genes, but indirectly affect siderophore production through their influence on metabolism. Consistent with this, acetate supplementation reversed the intracellular siderophore production defect of ΔacuM and ΔacuK. Moreover, ΔacuM and ΔacuK displayed a similar growth defect under iron limitation and iron sufficiency, which suggests they have a general role in carbon metabolism apart from gluconeogenesis. In agreement with a potential role of the glyoxylate cycle in adaptation to iron starvation, transcript levels of the malate synthase-encoding acuE were found to be upregulated by iron limitation that is partially dependent on AcuK and AcuM. Together, these data demonstrate the influence of iron availability on carbon metabolism.
HER2 Overexpression in Periampullary Tumors According to Anatomical and Histological Classification—A Systematic Review
Authors: Bodea Ioan Cătălin , Ciocan Andra , Zaharie Florin Vasile , Bodea Raluca , Graur Florin , Ursu Ștefan , Ciocan Răzvan Alexandru , Al Hajjar Nadim
Published: April 2024

Pancreatic cancer is one of the most aggressive, heterogeneous, and fatal types of human cancer; therefore, more effective therapeutic drugs are urgently needed. Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been identified as a cornerstone in this pathology. The aim of this review is to identify HER2 membrane overexpression in relation to pancreatic cancer pathways that can be used in order to develop a targeted therapy. After searching the keywords, 174 articles were found during a time span of 10 years, between 2013 and 2023, but only twelve scientific papers were qualified for this investigation. The new era of biomolecular research found a significant relationship between HER2 overexpression and pancreatic cancer cells in 25–30% of cases. The variables are dependent on tumor-derived cells, with differences in receptor overexpression between PDAC (pancreatic ductal adenocarcinoma), BTC (biliary tract cancer), ampullary carcinoma, and PNETs (pancreatic neuroendocrine tumors). HER2 overexpression is frequently encountered in human pancreatic carcinoma cell lines, and the ERBB family is one of the targets in the near future of therapy, with good results in phase I, II, and III studies evaluating downregulation and tumor downstaging, respectively.
Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy versus Endocrine Therapy Alone for HR-Positive, HER-2-Negative Early Breast Cancer: Meta-Analysis of Phase III Randomized Clinical Trials
Authors: Moraes Francisco Cezar Aquino de , de Oliveira Almeida Gustavo , Alves Vinícius Freire Costa , Priantti Jonathan N. , Gomes Giovanna da Conceição , Carnevalli Sarah Vitória Bristot , Madeira Thiago , Vilbert Maysa , Stecca Carlos , Figueroa Magalhães Maria Cristina , Fernandes Marianne Rodrigues , dos Santos Ney Pereira Carneiro
Published: April 2024

Background: Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors are approved for advanced breast cancer combined with endocrine therapy (ET). The efficacy of CDK4/6 inhibitors plus ET in hormone estrogen-positive, human epidermal growth factor 2-negative (HR+/HER2−) early-stage breast cancer (esBC) is still to be confirmed. Methods: We performed a systematic review and a meta-analysis to investigate the efficacy of CDK4/6i plus ET in esBC. Main outcomes included invasive disease-free survival (iDFS), distant relapse-free survival (DRFS), and overall survival (OS). We included only phase III randomized controlled trials. We used RStudio version 4.2.3, and we considered p < 0.05 to be statistically significant. Results: Four studies were selected, including 14,168 patients, of which 7089 were treated with CDK4/6i plus ET and 7079 received ET monotherapy. Regarding patient characteristics, 6828 (48.2%) were premenopausal. Compared with ET alone, iDFS rates (HR 0.81; 95% CI: 0.67, 0.98; p = 0.034) were significantly in favor of CDK4/6 inhibitors plus ET. However, there were no significant differences in DRFS (HR 0.79; 95% CI: 0.58, 1.07; p = 0.132) nor OS (HR 0.96; 95% CI: 0.69, 1.35; p = 0.829). Conclusions: Our results show that the addition of CDK4/6 inhibitors is associated with a significant benefit for HR+/HER2− esBC patients in iDFS. More studies and longer follow-up are needed to assess overall survival benefits.
A Pathophysiological Approach to Spontaneous Orbital Meningoceles: Case Report and Systematic Review
Authors: Gaudioso Piergiorgio , Biancoli Elia , Battistuzzi Veronica , Concheri Stefano , Saccardo Tommaso , Franchella Sebastiano , Contro Giacomo , Taboni Stefano , Zanoletti Elisabetta , Causin Francesco , Nico Lorena , Gabrieli Joseph Domenico , Maroldi Roberto , Nicolai Piero , Ferrari Marco
Published: April 2024

Background: Spontaneous orbital cephaloceles are a rare condition. The purpose of this study is to provide a description of a clinical case and to carry out a systematic literature review. Methods: A systematic review of the English literature published on the Pubmed, Scopus, and Web of Science databases was conducted, according to the PRISMA recommendations. Results: A 6-year-old patient was admitted for right otomastoiditis and thrombosis of the sigmoid and transverse sinuses, as well as the proximal portion of the internal jugular vein. Radiological examinations revealed a left orbital mass (22 × 14 mm) compatible with asymptomatic orbital meningocele (MC) herniated from the superior orbital fissure (SOF). The child underwent a right mastoidectomy. After the development of symptoms and signs of intracranial hypertension (ICH), endovascular thrombectomy and transverse sinus stenting were performed, with improvement of the clinical conditions and reduction of the orbital MC. The systematic literature review encompassed 29 publications on 43 patients with spontaneous orbital MC. In the majority of cases, surgery was the preferred treatment. Conclusions: The present case report and systematic review highlight the importance of ICH investigation and a pathophysiological-oriented treatment approach. The experiences described in the literature are limited, making the collection of additional data paramount.
Advances in Computational Methods for Modeling Photocatalytic Reactions: A Review of Recent Developments
Authors: Gusarov Sergey
Published: April 2024

Photocatalysis is a fascinating process in which a photocatalyst plays a pivotal role in driving a chemical reaction when exposed to light. Its capacity to harness light energy triggers a cascade of reactions that lead to the formation of intermediate compounds, culminating in the desired final product(s). The essence of this process is the interaction between the photocatalyst’s excited state and its specific interactions with reactants, resulting in the creation of intermediates. The process’s appeal is further enhanced by its cyclic nature—the photocatalyst is rejuvenated after each cycle, ensuring ongoing and sustainable catalytic action. Nevertheless, comprehending the photocatalytic process through the modeling of photoactive materials and molecular devices demands advanced computational techniques founded on effective quantum chemistry methods, multiscale modeling, and machine learning. This review analyzes contemporary theoretical methods, spanning a range of lengths and accuracy scales, and assesses the strengths and limitations of these methods. It also explores the future challenges in modeling complex nano-photocatalysts, underscoring the necessity of integrating various methods hierarchically to optimize resource distribution across different scales. Additionally, the discussion includes the role of excited state chemistry, a crucial element in understanding photocatalysis.
A New Biorthogonal Spline Wavelet-Based K-Layer Network for Underwater Image Enhancement
Authors: Zhou Dujuan , Cai Zhanchuan , He Dan
Published: April 2024

Wavelet decomposition is pivotal for underwater image processing, known for its ability to analyse multi-scale image features in the frequency and spatial domains. In this paper, we propose a new biorthogonal cubic special spline wavelet (BCS-SW), based on the Cohen–Daubechies–Feauveau (CDF) wavelet construction method and the cubic special spline algorithm. BCS-SW has better properties in compact support, symmetry, and frequency domain characteristics. In addition, we propose a K-layer network (KLN) based on the BCS-SW for underwater image enhancement. The KLN performs a K-layer wavelet decomposition on underwater images to extract various frequency domain features at multiple frequencies, and each decomposition layer has a convolution layer corresponding to its spatial size. This design ensures that the KLN can understand the spatial and frequency domain features of the image at the same time, providing richer features for reconstructing the enhanced image. The experimental results show that the proposed BCS-SW and KLN algorithm has better image enhancement effect than some existing algorithms.
Mathematical Model and Analysis of Novel Bevel Gear with High Load-Capacity Based on the Geometric Elements
Authors: Wang Dongyu , Zhang Luhe , Tian Chao , Miao Jiacheng , An Laiqiang , Shi Jia , Chen Bingkui
Published: April 2024

Load-capacity has always been one of the performances that is paid much attention to in the development of bevel gear transmission applications. Consequently, the mathematical model of novel bevel gear with high load-capacity based on geometric elements is proposed in this paper, which could be applied to the aviation, aerospace and other fields. In parallel, the design principle and design method of the novel bevel gear are introduced in detail. Subsequently, the conditions for tooth surface continuity and non-interference are derived. Furthermore, the model of novel bevel gear is established. Finally, the load-bearing characteristics are analyzed, revealing that an increase in the number of contact points could significantly enhance the load capacity of the bevel gear pairs. When the load torque applied to bevel gear II is 100 Nm, the contact pressure endured by the bevel gear pair with five-point contact is decreased by 41.37% compared to the bevel gear pair with single-point contact. When the number of contact points is the same, increasing the distance between the contact points could also reduce the contact stress. This provides strong theoretical support for the application of the bevel gear based on the geometric elements.
Prediction of Myocardial Infarction Using a Combined Generative Adversarial Network Model and Feature-Enhanced Loss Function
Authors: Yu Shixiang , Han Siyu , Shi Mengya , Harada Makoto , Ge Jianhong , Li Xuening , Cai Xiang , Heier Margit , Karstenmüller Gabi , Suhre Karsten , Gieger Christian , Koenig Wolfgang , Rathmann Wolfgang , Peters Annette , Wang-Sattler Rui
Published: April 2024

Accurate risk prediction for myocardial infarction (MI) is crucial for preventive strategies, given its significant impact on global mortality and morbidity. Here, we propose a novel deep-learning approach to enhance the prediction of incident MI cases by incorporating metabolomics alongside clinical risk factors. We utilized data from the KORA cohort, including the baseline S4 and follow-up F4 studies, consisting of 1454 participants without prior history of MI. The dataset comprised 19 clinical variables and 363 metabolites. Due to the imbalanced nature of the dataset (78 observed MI cases and 1376 non-MI individuals), we employed a generative adversarial network (GAN) model to generate new incident cases, augmenting the dataset and improving feature representation. To predict MI, we further utilized multi-layer perceptron (MLP) models in conjunction with the synthetic minority oversampling technique (SMOTE) and edited nearest neighbor (ENN) methods to address overfitting and underfitting issues, particularly when dealing with imbalanced datasets. To enhance prediction accuracy, we propose a novel GAN for feature-enhanced (GFE) loss function. The GFE loss function resulted in an approximate 2% improvement in prediction accuracy, yielding a final accuracy of 70%. Furthermore, we evaluated the contribution of each clinical variable and metabolite to the predictive model and identified the 10 most significant variables, including glucose tolerance, sex, and physical activity. This is the first study to construct a deep-learning approach for producing 7-year MI predictions using the newly proposed loss function. Our findings demonstrate the promising potential of our technique in identifying novel biomarkers for MI prediction.
Petrology and Geochemistry of an Unusual Granulite Facies Xenolith of the Late Oligocene Post-Obduction Koum Granodiorite (New Caledonia, Southwest Pacific): Geodynamic Inferences
Authors: Cluzel Dominique , Trotet Fabien , Paquette Jean-Louis
Published: April 2024

Pressure–temperature estimates of a xenolith found within a post-obduction granodiorite in southern New Caledonia provide evidence for subcrustal, granulite facies, peak crystallisation conditions (ca. 850 °C—8.5 ± 1.0 kbar), followed by isobaric cooling to 700 °C, and final decompression with partial rehydration at ca. 650 °C—3.5 kbar. The xenolith, dated at 24.7 Ma (U-Pb zircon), i.e., the same age as the granodiorite host rock, has low SiO2 (35.5 wt%) and high Al2O3 (33.2 wt%) contents, suggesting that it is the restite of a previous melting episode, while the elevated Ca (Ba and Sr) contents suggest mantle metasomatism. Although the concentrations of Rb, K, Ca, Ba, and Sr have been strongly modified, some geochemical (REE patterns and some “immobile” trace element ratios) and isotopic (Sr and Nd isotopic ratios, U-Pb zircon age) characteristics of the granulite facies xenolith are similar to those of the xenoliths found in other Late Oligocene intrusions in southern New Caledonia; therefore, this rock is interpreted to be related to an early magmatic episode. The rock protolith was emplaced and equilibrated at the base of the crust where it underwent ductile deformation. Younger ascending magma picked it up and they eventually crystallised together at a shallow crustal level, near the tectonic sole of the ophiolite. The recrystallisation and ductile deformation at ~8.5 kbar suggest that a rheological discontinuity existed at about 25–28 km, probably representing the Moho. It is concluded that a continental crust of normal thickness must have existed beneath New Caledonia at about 24 Ma, i.e., 10 Ma after obduction.
Improving the Flotation of Unoxidized and Oxidized Molybdenite Fines Using Dodecylamine as a Collector: Flotation Tests and Interaction Mechanism
Authors: Yang Bingqiao , Wu Jie , Deng Bing , Shao Hui , Song Shaoxian , Quintana Mildred
Published: April 2024

The flotation of unoxidized and oxidized molybdenite fines is a challenging job worldwide. In this work, dodecylamine (DDA) was developed as a potential collector to improve the flotation of molybdenite fines with and without oxidation. The flotation behaviors and interaction mechanisms were probed through flotation tests, contact angle, Zeta potential, Scanning Electron Microscope-Energy Dispersive Spectrometer(SEM-EDS), and X-ray Photoelectron Spectroscopy (XPS). The flotation tests revealed that DDA improved the flotation of unoxidized or oxidized molybdenite fines efficiently. The results of Zeta potential, contact angle, and SEM-EDS uncovered that a substantial number of DDA species adsorbed on both fresh and oxidized molybdenite faces and edges, thus enhancing their hydrophobicity. XPS analysis further manifested that RNH2 and RNH3+ adsorbed on the S atoms of fresh faces through hydrogen bonding. Meanwhile, RNH2 and RNH3+ mainly adsorbed on fresh edges via chemical bonding between amine groups and Mo sites and electrostatic force. For oxidized molybdenite, RNH2 and RNH3+ interacted with oxidized faces through hydrogen bonding while adsorbed on oxidized edges via hydrogen bonding and electrostatic interaction.
Application of Magnetic Materials Combined with Echo® Mass Spectrometry System in Analysis of Illegal Drugs in Sewage
Authors: Yang Feiyu , Ma Kaijun , Cao Yichao , Li Zhiyuan
Published: April 2024

The aim of this study is to solve the problems of the complicated pretreatment and high analytical cost in the detection technology of trace drugs and their metabolites in municipal wastewater. A high-performance magnetic sorbent was fsynthesized for the enrichment of trace drugs and their metabolites in wastewater to develop a magnetic solid-phase extraction pretreatment combined with the acoustic ejection mass spectrometry (AEMS) analytical method. The magnetic nanospheres were successfully prepared by magnetic nanoparticles modified with divinylbenzene and vinylpyrrolidone. The results showed that the linear dynamic range of 17 drugs was 1–500 ng/mL, the recovery was 44–100%, the matrix effect was more than 51%, the quantification limit was 1–2 ng/mL, and the MS measurement was fast. It can be seen that the developed magnetic solid-phase extraction (MSPE) method is a good solution to the problems of the complicated pretreatment and analytical cost in the analysis of drugs in wastewater. The developed magnetic material and acoustic excitation pretreatment coupled with mass spectrometry analysis method can realize the low-cost, efficient enrichment, and fast analysis of different kinds of drug molecules in urban sewage.
Development of the VEGANScreener, a Tool for a Quick Diet Quality Assessment among Vegans in Europe
Authors: Kronsteiner-Gicevic Selma , Bogl Leonie , Wakolbinger Maria , Müller Sandra , Dietrich Joelina , De Keyzer Willem , Bullón-Vela Vanessa , Selinger Eliska , Keller Vanessa , Martínez Tabar Ainara , Asif Tooba , Craig Leone , Kyle Janet , Schlesinger Sabrina , Köder Christian , Ouradova Anna , Henikova Marina , Van Lippevelde Wendy , Cahova Monika , Martínez González Miguel , Willett Walter , Bes-Rastrollo Maira , Gojda Jan , De Henauw Stefaan , Keller Markus , Kuzma Marek , Schernhammer Eva
Published: April 2024

Background: Plant-based diets are not inherently healthy. Similar to omnivorous diets, they may contain excessive amounts of sugar, sodium, and saturated fats, or lack diversity. Moreover, vegans might be at risk of inadequate intake of certain vitamins and minerals commonly found in foods that they avoid. We developed the VEGANScreener, a tool designed to assess the diet quality of vegans in Europe. Methods: Our approach combined best practices in developing diet quality metrics with scale development approaches and involved the following: (a) narrative literature synthesis, (b) evidence evaluation by an international panel of experts, and (c) translation of evidence into a diet screener. We employed a modified Delphi technique to gather opinions from an international expert panel. Results: Twenty-five experts in the fields of nutrition, epidemiology, preventive medicine, and diet assessment participated in the first round, and nineteen participated in the subsequent round. Initially, these experts provided feedback on a pool of 38 proposed items from the literature review. Consequently, 35 revised items, with 17 having multiple versions, were suggested for further consideration. In the second round, 29 items were retained, and any residual issues were addressed in the final consensus meeting. The ultimate screener draft encompassed 29 questions, with 17 focusing on foods and nutrients to promote, and 12 addressing foods and nutrients to limit. The screener contained 24 food-based and 5 nutrient-based questions. Conclusions: We elucidated the development process of the VEGANScreener, a novel diet quality screener for vegans. Future endeavors involve contrasting the VEGANScreener against benchmark diet assessment methodologies and nutritional biomarkers and testing its acceptance. Once validated, this instrument holds potential for deployment as a self-assessment application for vegans and as a preliminary dietary screening and counseling tool in healthcare settings.
The Efficacy of Multivitamin, Vitamin A, Vitamin B, Vitamin C, and Vitamin D Supplements in the Prevention and Management of COVID-19 and Long-COVID: An Updated Systematic Review and Meta-Analysis of Randomized Clinical Trials
Authors: Sinopoli Alessandra , Sciurti Antonio , Isonne Claudia , Santoro Maria Mercedes , Baccolini Valentina
Published: April 2024

This review aims to evaluate the efficacy of any vitamin administration(s) in preventing and managing COVID-19 and/or long-COVID. Databases were searched up to May 2023 to identify randomized clinical trials comparing data on the effects of vitamin supplementation(s) versus placebo or standard of care on the two conditions of interest. Inverse-variance random-effects meta-analyses were conducted to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs) for all-cause mortality between supplemented and non-supplemented individuals. Overall, 37 articles were included: two regarded COVID-19 and long-COVID prevention and 35 records the COVID-19 management. The effects of vitamin D in preventing COVID-19 and long-COVID were contrasting. Similarly, no conclusion could be drawn on the efficacy of multivitamins, vitamin A, and vitamin B in COVID-19 management. A few positive findings were reported in some vitamin C trials but results were inconsistent in most outcomes, excluding all-cause mortality (RR = 0.84; 95% CI: 0.72–0.97). Vitamin D results were mixed in most aspects, including mortality, in which benefits were observed in regular administrations only (RR = 0.67; 95% CI: 0.49–0.91). Despite some benefits, results were mostly contradictory. Variety in recruitment and treatment protocols might explain this heterogeneity. Better-designed studies are needed to clarify these vitamins’ potential effects against SARS-CoV-2.
Therapeutic Implications of Phenolic Acids for Ameliorating Inflammatory Bowel Disease
Authors: Lu Yanan , Han Xue
Published: April 2024

Inflammatory bowel disease (IBD) is a chronic inflammatory intestinal disorder, and its complex etiology makes prevention and treatment challenging. Research on new drugs and treatment strategies is currently a focal point. Phenolic acids are widely present in plant-based diets and have demonstrated the potential to alleviate colitis due to their powerful antioxidant and anti-inflammatory properties. In this review, we provide an overview of the structures and main dietary sources of phenolic acids, encompassing benzoic acid and cinnamic acid. Additionally, we explore the potential of phenolic acids as a nutritional therapy for preventing and treating IBD. In animal and cell experiments, phenolic acids effectively alleviate IBD induced by drug exposure or genetic defects. The mechanisms include improving intestinal mucosal barrier function, reducing oxidative stress, inhibiting excessive activation of the immune response, and regulating the balance of the intestinal microbiota. Our observation points towards the need for additional basic and clinical investigations on phenolic acids and their derivatives as potential novel therapeutic agents for IBD.
The Influence of Probiotic Lactobacilli on COVID-19 and the Microbiota
Authors: Taufer Clarissa , da Silva Juliana , Rampelotto Pabulo
Published: April 2024

This comprehensive review explores the potential of using lactobacilli as a probiotic in the management of COVID-19. Our findings suggest that lactobacilli show promise in reducing the risk of death, gastrointestinal and overall symptoms, and respiratory failure, as well as in lowering cytokines and inflammatory markers associated with the disease. The molecular mechanisms by which lactobacilli protect against COVID-19 and other viral infections may be related to the reduction in inflammation, modulation of the immune response, and direct interaction with viruses to produce antiviral substances. However, the selected studies demonstrate the presence of mixed findings for various clinical, biochemical, hematological, and immunological parameters, which may be attributed to methodological differences among studies. We highlight the importance of clearly describing randomization processes to minimize bias and caution against small sample sizes and inappropriate statistical tests that could lead to errors. This review offers valuable insights into the therapeutic potential of lactobacilli in the context of COVID-19 and identifies avenues for further research and applications. These findings hold promise for the development of novel approaches to managing COVID-19 and warrant further investigation into the potential benefits of lactobacilli in combating the disease.
Effectiveness of Psychobiotics in the Treatment of Psychiatric and Cognitive Disorders: A Systematic Review of Randomized Clinical Trials
Authors: Mosquera Freiser Eceomo Cruz , Lizcano Martinez Santiago , Liscano Yamil
Published: April 2024

In this study, a systematic review of randomized clinical trials conducted from January 2000 to December 2023 was performed to examine the efficacy of psychobiotics—probiotics beneficial to mental health via the gut–brain axis—in adults with psychiatric and cognitive disorders. Out of the 51 studies involving 3353 patients where half received psychobiotics, there was a notably high measurement of effectiveness specifically in the treatment of depression symptoms. Most participants were older and female, with treatments commonly utilizing strains of Lactobacillus and Bifidobacteria over periods ranging from 4 to 24 weeks. Although there was a general agreement on the effectiveness of psychobiotics, the variability in treatment approaches and clinical presentations limits the comparability and generalization of the findings. This underscores the need for more personalized treatment optimization and a deeper investigation into the mechanisms through which psychobiotics act. The research corroborates the therapeutic potential of psychobiotics and represents progress in the management of psychiatric and cognitive disorders.
Effect of Sugar- and Polyphenol-Rich, Diluted Cloudy Apple Juice on the Intestinal Barrier after Moderate Endurance Exercise and in Ultra-Marathon Runners
Authors: Valder Sarah , Staltner Raphaela , Bizjak Daniel Alexander , Esatbeyoglu Tuba , Herdegen Volker , Köpsel Magdalena , Kostov Tihomir , Bergheim Ina , Diel Patrick
Published: April 2024

Background: Exercise and the consumption of sugars result in a dysfunction of the intestinal barrier (IB). Here, we determined the effect of sugar in a natural matrix on the intestinal barrier after moderate (A) and intensive endurance exercise (B). Method: The IB function was determined before (pre) and after running (post), and 120 and 180 min after consuming the drink by measuring serum endotoxin concentrations (lipopolysaccharides—LPS), IL-6, CD14, and i-FABP. In study A, nonspecifically trained participants (n = 24, males and females, age 26 ± 4) ran for one hour at 80% of their individual anaerobic threshold (IAT). After finishing, the runners consumed, in a crossover setup, either 500 mL of water, diluted cloudy apple juice (test drink), or an identical drink (placebo) without the fruit juice matrix (FJM). In study B, the participants (n = 30, males and females, age 50 ± 9) completed an ultra-marathon run, were divided into groups, and consumed one of the above-mentioned drinks. Results: Study A: Exercise resulted in a significant increase in serum LPS, i-FABP, and IL-6, which decreased fast after finishing. No impact of the different drinks on LPS i-FABP, or IL-6 could be observed, but there was an impact on CD14. Study B: The ultra-marathon resulted in a strong increase in serum LPS, which decreased fast after finishing in the water and test drink groups, but not in the placebo group. Conclusions: The consumed drinks did not affect the kinetics of IB regeneration after moderate exercise, but impacted CD14 serum concentrations, indicating possible beneficial effects of the FJM on the immune system. After an ultra-marathon, IB function regenerates very fast. The intake of sugar (placebo) seems to have had a negative impact on IB regeneration, which was diminished by the presence of the FJM.
Differential Activation of TAS2R4 May Recover Ability to Taste Propylthiouracil for Some TAS2R38 AVI Homozygotes
Authors: Nolden Alissa A. , Behrens Maik , McGeary John E. , Meyerhof Wolfgang , Hayes John E.
Published: April 2024

Bitterness from phenylthiocarbamide and 6-n-propylthiouracil (PROP) varies with polymorphisms in the TAS2R38 gene. Three SNPs form two common (AVI, PAV) and four rare haplotypes (AAI, AAV, PVI, and PAI). AVI homozygotes exhibit higher detection thresholds and lower suprathreshold bitterness for PROP compared to PAV homozygotes and heterozygotes, and these differences may influence alcohol and vegetable intake. Within a diplotype, substantial variation in suprathreshold bitterness persists, and some AVI homozygotes report moderate bitterness at high concentrations. A second receptor encoded by a gene containing a functional polymorphism may explain this. Early work has suggested that PROP might activate TAS2R4 in vitro, but later work did not replicate this. Here, we identify three TAS2R4 SNPs that result in three diplotypes—SLN/SLN, FVS/SLN, and FVS/FVS—which make up 25.1%, 44.9%, and 23.9% of our sample. These TAS2R4 haplotypes show minimal linkage disequilibrium with TAS2R38, so we examined the suprathreshold bitterness as a function of both. The participants (n = 243) rated five PROP concentrations in duplicate, interleaved with other stimuli. As expected, the TAS2R38 haplotypes explained ~29% (p < 0.0001) of the variation in the bitterness ratings, with substantial variation within the haplotypes (AVI/AVI, PAV/AVI, and PAV/PAV). Notably, the TAS2R4 diplotypes (independent of the TAS2R38 haplotypes) explained ~7–8% of the variation in the bitterness ratings (p = 0.0001). Given this, we revisited if PROP could activate heterologously expressed TAS2R4 in HEK293T cells, and calcium imaging indicated 3 mM PROP is a weak TAS2R4 agonist. In sum, our data are consistent with the second receptor hypothesis and may explain the recovery of the PROP tasting phenotype in some AVI homozygotes; further, this finding may potentially help explain the conflicting results on the TAS2R38 diplotype and food intake.
Mycobacterium avium paratuberculosis Infection Suppresses Vitamin D Activation and Cathelicidin Production in Macrophages through Modulation of the TLR2-Dependent p38/MAPK-CYP27B1-VDR-CAMP Axis
Authors: Talafha Muna M. , Qasem Ahmad , Naser Saleh A.
Published: April 2024

Background: Vitamin D plays a vital role in modulating both innate and adaptive immune systems. Therefore, vitamin D deficiency has been associated with higher levels of autoimmune response and increased susceptibility to infections. CYP27B1 encodes a member of the cytochrome P450 superfamily of enzymes. It is instrumental in the conversion of circulating vitamin D (calcifediol) to active vitamin D (calcitriol). This is a crucial step for macrophages to express Cathelicidin Anti-microbial Peptide (CAMP), an anti-bacterial factor released during the immune response. Our recent study indicated that a Crohn’s disease (CD)-associated pathogen known as Mycobacterium avium paratuberculosis (MAP) decreases vitamin D activation in macrophages, thereby impeding cathelicidin production and MAP infection clearance. The mechanism by which MAP infection exerts these effects on the vitamin D metabolic axis remains elusive. Methods: We used two cell culture models of THP-1 macrophages and Caco-2 monolayers to establish the effects of MAP infection on the vitamin D metabolic axis. We also tested the effects of Calcifediol, Calcitriol, and SB203580 treatments on the relative expression of the vitamin D metabolic genes, oxidative stress biomarkers, and inflammatory cytokines profile. Results: In this study, we found that MAP infection interferes with vitamin D activation inside THP-1 macrophages by reducing levels of CYP27B1 and vitamin D receptor (VDR) gene expression via interaction with the TLR2-dependent p38/MAPK pathway. MAP infection exerts its effects in a time-dependent manner, with the maximal inhibition observed at 24 h post-infection. We also demonstrated the necessity to have toll-like receptor 2 (TLR2) for MAP infection to influence CYP27B1 and CAMP expression, as TLR2 gene knockdown resulted in an average increase of 7.78 ± 0.88 and 13.90 ± 3.5 folds in their expression, respectively. MAP infection also clearly decreased the levels of p38 phosphorylation and showed dependency on the p38/MAPK pathway to influence the expression of CYP27B1, VDR, and CAMP which was evident by the average fold increase of 1.93 ± 0.28, 1.86 ± 0.27, and 6.34 ± 0.51 in their expression, respectively, following p38 antagonism. Finally, we showed that calcitriol treatment and p38/MAPK blockade reduce cellular oxidative stress and inflammatory markers in Caco-2 monolayers following macrophage-mediated MAP infection. Conclusions: This study characterized the primary mechanism by which MAP infection leads to diminished levels of active vitamin D and cathelicidin in CD patients, which may explain the exacerbated vitamin D deficiency state in these cases.
The Effect of Phenolic-Rich Extracts of Rubus fruticosus, R. ulmifolius and Morus nigra on Oxidative Stress and Caco-2 Inhibition Growth
Authors: Martins Mariana S. , Rodrigues Márcio , Flores-Félix José David , Garcia-Viguera Cristina , Moreno Diego A. , Alves Gilberto , Silva Luís R. , Gonçalves Ana C.
Published: April 2024

Currently, a clear interest has been given to berries due to their richness in active metabolites, including anthocyanins and non-coloured phenolics. Therefore, the main aim of the present work is to investigate the phenolic profile, antioxidant abilities, and antiproliferative effects on normal human dermal fibroblasts (NHDF) and human colon carcinoma cell line (Caco-2) cells of phenolic-rich extracts from three red fruits highly appreciated by consumers: two species of blackberries (Rubus fruticosus and Rubus ulmifolius) and one species of mulberry (Morus nigra). A total of 19 different phenolics were identified and quantified by HPLC-DAD-ESI/MSn and HPLC-DAD, respectively. Focusing on the biological potential of the phenolic-rich extracts, all of them revealed notable scavenging abilities. Concerning the antiproliferative properties, R. fruticosus presented a cytotoxic selectivity for Caco-2 cells compared to NHDF cells. To deeper explore the biological potential, combinations with positive controls (ascorbic acid and 5-fluorouracil) were also conducted. Finally, the obtained data are another piece of evidence that the combination of phenolic-rich extracts from natural plants with positive controls may reduce clinical therapy costs and the possible toxicity of chemical drugs.
The Long-Term Effect of COVID-19 Infection on Body Composition
Authors: Atieh Ornina , Durieux Jared C. , Baissary Jhony , Mouchati Christian , Labbato Danielle , Thomas Alicia , Merheb Alexander , Ailstock Kate , Funderburg Nicholas , McComsey Grace A.
Published: April 2024

Background: The effect of COVID-19 infection versus the indirect effect of the pandemic on body composition remains unclear. This study investigates the long-term changes in body composition in COVID-19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who underwent a pre-pandemic whole-body DXA scan (DXA#1) between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including their medical and COVID-19 history. Inflammation markers and fasting lipids were measured. For those participants who experienced a COVID-19 infection between the two DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n = 80) of the participants experienced a COVID-19 infection between their two DXA scans (COVID-19+ group), and the other half had never had COVID-19. COVID-19-negative participants displayed an increase in annualized trunk fat (g) [922.5 vs. 159.7; p = 0.01], total fat (g) [1564.3 vs. 199.9; p = 0.2], and LBM (g) [974.9 vs. −64.5; p = 0.0002] when compared to the COVID-19+ group. However, among the COVID-19+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p > 0.05). Conclusion: During the pandemic, both the COVID-19 survivors and the COVID-19-negative group exhibited increases in weight, total fat, and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19 survivors displayed a decline in lean body mass over the same period, regardless of PASC symptoms.
Carrageenan as a Potential Factor of Inflammatory Bowel Diseases
Authors: Komisarska Paulina , Pinyosinwat Anan , Saleem Mutaz , Szczuko Małgorzata
Published: April 2024

Carrageenan is a widely used food additive and is seen as a potential candidate in the pharmaceutical industry. However, there are two faces to carrageenan that allows it to be used positively for therapeutic purposes. Carrageenan can be used to create edible films and for encapsulating drugs, and there is also interest in the use of carrageenan for food printing. Carrageenan is a naturally occurring polysaccharide gum. Depending on the type of carrageenan, it is used in regulating the composition of intestinal microflora, including the increase in the population of Bifidobacterium bacteria. On the other hand, the studies have demonstrated the harmfulness of carrageenan in animal and human models, indicating a direct link between diet and intestinal inflammatory states. Carrageenan changes the intestinal microflora, especially Akkermansia muciniphilia, degrades the mucous barrier and breaks down the mucous barrier, causing an inflammatory reaction. It directly affects epithelial cells by activating the pro-inflammatory nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) pathway. The mechanism is based on activation of the TLR4 receptor, alterations in macrophage activity, production of proinflammatory cytokines and activation of innate immune pathways. Carrageenan increases the content of Bacteroidetes bacteria, also causing a reduction in the number of short chain fatty acid (SCFA)-producing bacteria. The result is damage to the integrity of the intestinal membrane and reduction of the mucin layer. The group most exposed to the harmful effects of carrageenan are people suffering from intestinal inflammation, including Crohn disease (CD) and ulcerative colitis (UC).
Huaier Polysaccharide Alleviates Dextran Sulphate Sodium Salt-Induced Colitis by Inhibiting Inflammation and Oxidative Stress, Maintaining the Intestinal Barrier, and Modulating Gut Microbiota
Authors: Tang Yi-Fei , Xie Wen-Yin , Wu Hong-Yu , Guo Hai-Xiang , Wei Fan-Hao , Ren Wen-Zhi , Gao Wei , Yuan Bao
Published: April 2024

The incidence of ulcerative colitis (UC) is increasing annually, and UC has a serious impact on patients’ lives. Polysaccharides have gained attention as potential drug candidates for treating ulcerative colitis (UC) in recent years. Huaier (Trametes robiniophila Murr) is a fungus that has been used clinically for more than 1000 years, and its bioactive polysaccharide components have been reported to possess immunomodulatory effects, antitumour potential, and renoprotective effects. In this study, we aimed to examine the protective effects and mechanisms of Huaier polysaccharide (HP) against UC. Based on the H2O2-induced oxidative stress model in HT-29 cells and the dextran sulphate sodium salt (DSS)-induced UC model, we demonstrated that Huaier polysaccharides significantly alleviated DSS-induced colitis (weight loss, elevated disease activity index (DAI) scores, and colonic shortening). In addition, HP inhibited oxidative stress and inflammation and alleviated DSS-induced intestinal barrier damage. It also significantly promoted the expression of the mucin Muc2. Furthermore, HP reduced the abundance of harmful bacteria Escherichia-Shigella and promoted the abundance of beneficial bacteria Muribaculaceae_unclassified, Anaerotruncus, and Ruminococcaceae_unclassified to regulate the intestinal flora disturbance caused by DSS. Nontargeted metabolomics revealed that HP intervention would modulate metabolism by promoting levels of 3-hydroxybutyric acid, phosphatidylcholine (PC), and phosphatidylethanolamine (PE). These results demonstrated that HP had the ability to mitigate DSS-induced UC by suppressing oxidative stress and inflammation, maintaining the intestinal barrier, and modulating the intestinal flora. These findings will expand our knowledge of how HP functions and offer a theoretical foundation for using HP as a potential prebiotic to prevent UC.