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The early stage of wound infection is always non-specific. Prompt intervention may help to prevent the wound from worsening. We developed a new protocol, based on previous research, that employs a paper-based IL-6 test strip used in combination with a spectrum-based optical reader to detect IL-6 in normal tissue (n = 19), acute wounds (n = 31), and chronic wounds (n = 32). Our data indicated the presence of significantly higher levels of IL-6 in acute wound tissues, but no significant difference in serum CRP. Receiver operating characteristics were used to determine clinical sensitivity and specificity of tissue IL-6 and systemic CRP. The area under the curve values were 0.87 and 0.63, respectively. The cut-off value of 30 pg/mL for IL-6 provided good sensitivity (75.0%) and superior specificity (88.9%). We found a high correlation between the IL-6 test strip and conventional ELISA results (R2 = 0.85, p < 0.001), and good agreement was also observed according to Bland-Altman analysis. We showed a promising role of tissue IL-6 to help early diagnosis of wound infection when clinical symptoms were non-specific. The advantages of this wound detection protocol included minimal invasiveness, small sample requirements, speed, sample preparation ease, and user-friendliness. This methodology could help care providers quickly clarify wound infection status and implement timely, optimal management.

Paper-based analytical devices (PADs) have emerged as a promising approach to point-of-care (POC) detection applications in biomedical and clinical diagnosis owing to their advantages, including cost-effectiveness, ease of use, and rapid responses as well as for being equipment-free, disposable, and user-friendly. However, the overall sensitivity of PADs still remains weak, posing a challenge for biosensing scientists exploiting them in clinical applications. This review comprehensively summarizes the current applicable potential of PADs, focusing on total signal-amplification strategies that have been applied widely in PADs involving colorimetry, luminescence, surface-enhanced Raman scattering, photoacoustic, photothermal, and photoelectrochemical methods as well as nucleic acid-mediated PAD modifications. The advances in signal-amplification strategies in terms of signal-enhancing principles, sensitivity, and time reactions are discussed in detail to provide an overview of these approaches to using PADs in biosensing applications. Furthermore, a comparison of these methods summarizes the potential for scientists to develop superior PADs. This review serves as a useful inside look at the current progress and prospective directions in using PADs for clinical diagnostics and provides a better source of reference for further investigations, as well as innovations, in the POC diagnostics field.

Spinal cord injury (SCI) represents an urgent unmet need for clinical reparative therapy due to its largely irreversible and devastating effects on patients, and the tremendous socioeconomic burden to the community. While different approaches are being explored, therapy to restore the lost function remains unavailable. Olfactory ensheathing cell (OEC) transplantation is a promising approach in terms of feasibility, safety, and limited efficacy; however, high variability in reported clinical outcomes prevent its translation despite several clinical trials. The aims of this position paper are to present an in-depth analysis of previous OEC transplantation-based clinical trials, identify existing challenges and gaps, and finally propose strategies to improve standardization of OEC therapies. We have reviewed the study design and protocols of clinical trials using OEC transplantation for SCI repair to investigate how and why the outcomes show variability. With this knowledge and our experience as a team of biologists and clinicians with active experience in the field of OEC research, we provide recommendations regarding cell source, cell purity and characterisation, transplantation dosage and format, and rehabilitation. Ultimately, this position paper is intended to serve as a roadmap to design an effective clinical trial with OEC transplantation-based therapy for SCI repair.

Heart disease can be life-threatening if not detected and treated at an early stage. The electrocardiogram (ECG) plays a vital role in classifying cardiovascular diseases, and often physicians and medical researchers examine paper-based ECG images for cardiac diagnosis. An automated heart disease prediction system might help to classify heart diseases accurately at an early stage. This study aims to classify cardiac diseases into five classes with paper-based ECG images using a deep learning approach with the highest possible accuracy and the lowest possible time complexity. This research consists of two approaches. In the first approach, five deep learning models, InceptionV3, ResNet50, MobileNetV2, VGG19, and DenseNet201, are employed. In the second approach, an integrated deep learning model (InRes-106) is introduced, combining InceptionV3 and ResNet50. This model is developed as a deep convolutional neural network capable of extracting hidden and high-level features from images. An ablation study is conducted on the proposed model altering several components and hyperparameters, improving the performance even further. Before training the model, several image pre-processing techniques are employed to remove artifacts and enhance the image quality. Our proposed hybrid InRes-106 model performed best with a testing accuracy of 98.34%. The InceptionV3 model acquired a testing accuracy of 90.56%, the ResNet50 89.63%, the DenseNet201 88.94%, the VGG19 87.87%, and the MobileNetV2 achieved 80.56% testing accuracy. The model is trained with a k-fold cross-validation technique with different k values to evaluate the robustness further. Although the dataset contains a limited number of complex ECG images, our proposed approach, based on various image pre-processing techniques, model fine-tuning, and ablation studies, can effectively diagnose cardiac diseases.

Spinal cord injury (SCI) represents an urgent unmet need for clinical reparative therapy due to its largely irreversible and devastating effects on patients, and the tremendous socioeconomic burden to the community. While different approaches are being explored, therapy to restore the lost function remains unavailable. Olfactory ensheathing cell (OEC) transplantation is a promising approach in terms of feasibility, safety, and limited efficacy; however, high variability in reported clinical outcomes prevent its translation despite several clinical trials. The aims of this position paper are to present an in-depth analysis of previous OEC transplantation-based clinical trials, identify existing challenges and gaps, and finally propose strategies to improve standardization of OEC therapies. We have reviewed the study design and protocols of clinical trials using OEC transplantation for SCI repair to investigate how and why the outcomes show variability. With this knowledge and our experience as a team of biologists and clinicians with active experience in the field of OEC research, we provide recommendations regarding cell source, cell purity and characterisation, transplantation dosage and format, and rehabilitation. Ultimately, this position paper is intended to serve as a roadmap to design an effective clinical trial with OEC transplantation-based therapy for SCI repair.

Heart disease can be life-threatening if not detected and treated at an early stage. The electrocardiogram (ECG) plays a vital role in classifying cardiovascular diseases, and often physicians and medical researchers examine paper-based ECG images for cardiac diagnosis. An automated heart disease prediction system might help to classify heart diseases accurately at an early stage. This study aims to classify cardiac diseases into five classes with paper-based ECG images using a deep learning approach with the highest possible accuracy and the lowest possible time complexity. This research consists of two approaches. In the first approach, five deep learning models, InceptionV3, ResNet50, MobileNetV2, VGG19, and DenseNet201, are employed. In the second approach, an integrated deep learning model (InRes-106) is introduced, combining InceptionV3 and ResNet50. This model is developed as a deep convolutional neural network capable of extracting hidden and high-level features from images. An ablation study is conducted on the proposed model altering several components and hyperparameters, improving the performance even further. Before training the model, several image pre-processing techniques are employed to remove artifacts and enhance the image quality. Our proposed hybrid InRes-106 model performed best with a testing accuracy of 98.34%. The InceptionV3 model acquired a testing accuracy of 90.56%, the ResNet50 89.63%, the DenseNet201 88.94%, the VGG19 87.87%, and the MobileNetV2 achieved 80.56% testing accuracy. The model is trained with a k-fold cross-validation technique with different k values to evaluate the robustness further. Although the dataset contains a limited number of complex ECG images, our proposed approach, based on various image pre-processing techniques, model fine-tuning, and ablation studies, can effectively diagnose cardiac diseases.

The early stage of wound infection is always non-specific. Prompt intervention may help to prevent the wound from worsening. We developed a new protocol, based on previous research, that employs a paper-based IL-6 test strip used in combination with a spectrum-based optical reader to detect IL-6 in normal tissue (n = 19), acute wounds (n = 31), and chronic wounds (n = 32). Our data indicated the presence of significantly higher levels of IL-6 in acute wound tissues, but no significant difference in serum CRP. Receiver operating characteristics were used to determine clinical sensitivity and specificity of tissue IL-6 and systemic CRP. The area under the curve values were 0.87 and 0.63, respectively. The cut-off value of 30 pg/mL for IL-6 provided good sensitivity (75.0%) and superior specificity (88.9%). We found a high correlation between the IL-6 test strip and conventional ELISA results (R2 = 0.85, p < 0.001), and good agreement was also observed according to Bland-Altman analysis. We showed a promising role of tissue IL-6 to help early diagnosis of wound infection when clinical symptoms were non-specific. The advantages of this wound detection protocol included minimal invasiveness, small sample requirements, speed, sample preparation ease, and user-friendliness. This methodology could help care providers quickly clarify wound infection status and implement timely, optimal management.

Coagulation Factor IX-rich protrhombin complex concentrate (FIX-PCC) is a therapeutic biologic product that consists of a mixture of several human plasma-derived proteins, useful for treating hemophilia B. Due to its complex composition, FIX-PCC is very challenging to bioprocess through virus removing nanofilters in order to ensure its biosafety. This article describes a two-step filtration process of FIX-PCC using a nanocellulose-based filter paper with tailored porosity. The filters were characterized with scanning electron microscopy (SEM), cryoporometry with differential scanning calorimetry, and nitrogen gas sorption. Furthermore, in order to probe the filter’s cut-off size rejection threshold, removal of small- and large-size model viruses, i.e., ΦX174 (28 nm) and PR772 (70 nm), was evaluated. The feed, pre-filtrate, and permeate solutions were characterized with mass-spectrometric proteomic analysis, dynamic light scattering (DLS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and analytical size-exclusion high-performance liquid chromatography (SEHPLC). By sequential filtration through 11 μm pre-filter and 33 μm virus removal filter paper, it was possible to achieve high product throughput and high virus removal capacity. The presented approach could potentially be applied for bioprocessing other protein-based drugs.

This study is dedicated to the rapid removal of protein aggregates and viruses from plasma-derived human serum albumin (HSA) product to reduce the risk of viral contamination and increase biosafety. A two-step filtration approach was implemented to first remove HSA aggregates and then achieve high model virus clearance using a nanocellulose-based filter paper of different thicknesses, i.e., 11 μm (prefilter) and 22 μm (virus filter) at pH 7.4 and room temperature. The pore size distribution of these filters was characterized by nitrogen gas sorption analysis. Dynamic light scattering (DLS) and size-exclusion high performance liquid chromatography (SE-HPLC) were performed to analyze the presence of HSA aggregates in process intermediates. The virus filter showed high clearance of a small-size model virus, i.e., log10 reduction value (LRV) > 5, when operated at 3 and 5 bar, but a distinct decrease in LRV was detected at 1 bar, i.e., LRV 2.65–3.75. The throughput of HSA was also dependent on applied transmembrane pressure as was seen by Vmax values of 110 ± 2.5 L m−2 and 63.6 ± 5.8 L m−2 at 3 bar and 5 bar, respectively. Protein loss was low, i.e., recovery > 90%. A distribution of pore sizes between 40 nm and 60 nm, which was present in the prefilter and absent in the virus filter, played a crucial part in removing the HSA aggregates and minimizing the risk of virus filter fouling. The presented results enable the application of virus removal nanofiltration of HSA in bioprocessing as an alternative to virus inactivation methods based, e.g., on heat treatment.

One of the main challenges of newborn screening programs, which screen for inherited metabolic disorders, is cutting down on false positives (FPs) in order to avoid family stresses, additional analyses, and unnecessary costs. False positives are partly caused by an insubstantial number of robust biomarkers in evaluations. Another challenge is how to distinguish between diseases which share the same primary marker and for which secondary biomarkers are just as highly desirable. Focusing on pathologies that involve butyrylcarnitine (C4) elevation, such as short-chain acylCoA dehydrogenase deficiency (SCADD) and isobutyrylCoA dehydrogenase deficiency (IBDD), we investigated the acylcarnitine profile of 121 newborns with a C4 increase to discover secondary markers to achieve two goals: reduce the FP rate and discriminate between the two rare diseases. Analyses were carried out using tandem mass spectrometry with whole blood samples spotted on filter paper. Seven new biomarkers (C4/C0, C4/C5, C4/C5DC\C6OH, C4/C6, C4/C8, C4/C14:1, C4/C16:1) were identified using a non-parametric ANOVA analysis. Then, the corresponding cut-off values were found and applied to the screening program. The seven new ratios were shown to be robust (p < 0.001 and p < 0.01, 0.0937 < ε2 < 0.231) in discriminating between FP and IBDD patients, FP and SCADD patients, or SCADD and IBDD patients. Our results suggest that the new ratios are optimal indicators for identifying true positives, distinguishing between two rare diseases that share the same primary biomarker, improving the predictive positive value (PPV) and reducing the false positive rate (FPR). [ABSTRACT FROM AUTHOR]

Paper-based analytical devices (PADs) have emerged as a promising approach to point-of-care (POC) detection applications in biomedical and clinical diagnosis owing to their advantages, including cost-effectiveness, ease of use, and rapid responses as well as for being equipment-free, disposable, and user-friendly. However, the overall sensitivity of PADs still remains weak, posing a challenge for biosensing scientists exploiting them in clinical applications. This review comprehensively summarizes the current applicable potential of PADs, focusing on total signal-amplification strategies that have been applied widely in PADs involving colorimetry, luminescence, surface-enhanced Raman scattering, photoacoustic, photothermal, and photoelectrochemical methods as well as nucleic acid-mediated PAD modifications. The advances in signal-amplification strategies in terms of signal-enhancing principles, sensitivity, and time reactions are discussed in detail to provide an overview of these approaches to using PADs in biosensing applications. Furthermore, a comparison of these methods summarizes the potential for scientists to develop superior PADs. This review serves as a useful inside look at the current progress and prospective directions in using PADs for clinical diagnostics and provides a better source of reference for further investigations, as well as innovations, in the POC diagnostics field.

This study is dedicated to the rapid removal of protein aggregates and viruses from plasma-derived human serum albumin (HSA) product to reduce the risk of viral contamination and increase biosafety. A two-step filtration approach was implemented to first remove HSA aggregates and then achieve high model virus clearance using a nanocellulose-based filter paper of different thicknesses, i.e., 11 μm (prefilter) and 22 μm (virus filter) at pH 7.4 and room temperature. The pore size distribution of these filters was characterized by nitrogen gas sorption analysis. Dynamic light scattering (DLS) and size-exclusion high performance liquid chromatography (SE-HPLC) were performed to analyze the presence of HSA aggregates in process intermediates. The virus filter showed high clearance of a small-size model virus, i.e., log 10 reduction value (LRV) > 5, when operated at 3 and 5 bar, but a distinct decrease in LRV was detected at 1 bar, i.e., LRV 2.65-3.75. The throughput of HSA was also dependent on applied transmembrane pressure as was seen by Vmax values of 110 ± 2.5 L m -2 and 63.6 ± 5.8 L m -2 at 3 bar and 5 bar, respectively. Protein loss was low, i.e., recovery > 90%. A distribution of pore sizes between 40 nm and 60 nm, which was present in the prefilter and absent in the virus filter, played a crucial part in removing the HSA aggregates and minimizing the risk of virus filter fouling. The presented results enable the application of virus removal nanofiltration of HSA in bioprocessing as an alternative to virus inactivation methods based, e.g., on heat treatment.

Coagulation Factor IX-rich protrhombin complex concentrate (FIX-PCC) is a therapeutic biologic product that consists of a mixture of several human plasma-derived proteins, useful for treating hemophilia B. Due to its complex composition, FIX-PCC is very challenging to bioprocess through virus removing nanofilters in order to ensure its biosafety. This article describes a two-step filtration process of FIX-PCC using a nanocellulose-based filter paper with tailored porosity. The filters were characterized with scanning electron microscopy (SEM), cryoporometry with differential scanning calorimetry, and nitrogen gas sorption. Furthermore, in order to probe the filter's cut-off size rejection threshold, removal of small- and large-size model viruses, i.e., ΦX174 (28 nm) and PR772 (70 nm), was evaluated. The feed, pre-filtrate, and permeate solutions were characterized with mass-spectrometric proteomic analysis, dynamic light scattering (DLS), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), and analytical size-exclusion high-performance liquid chromatography (SEHPLC). By sequential filtration through 11 μm pre-filter and 33 μm virus removal filter paper, it was possible to achieve high product throughput and high virus removal capacity. The presented approach could potentially be applied for bioprocessing other protein-based drugs., Competing Interests: The corresponding author (A.Mi.) is the inventor behind the IP pertaining to virus removal filter paper.

Background: Dental caries is the most common oral disease in the world. When treatable, the drilling method continues to be used. This technique has its disadvantages because it is invasive and nonspecific. Chemomechanical carious tissue removal agents (CCRAs) such as Carisolv™ or Papacarie® are non-invasive products that allow for the specific elimination of infected dentin. On the other hand, cariogenic bacteria are largely responsible for the initiation and development of lesions. Objectives: The aim is to analyze whether CCRAs have a relevant antimicrobial effect on cariogenic bacteria. Methods: A bibliographic search strategy was carried out in online databases using PRISMA 2020. The evaluation of the antibacterial efficacy of CCRAs was carried out through the analysis of the reduction in CFUs of cariogenic bacteria, and the presence of bacterial deposits, TVC, SVC and LVC by comparison with conventional drilling methods. Results: The results showed that the percentage of reduction in TVC, SVC and LVC for each agent is mostly high, but not significantly different from mechanical methods. The best results were found with CCRAs when compared to polymeric drills. The results also showed that there is a lack of methodological standardization. Conclusions: CCRAs have been shown to have a relevant antimicrobial effect on cariogenic bacteria; however, more studies need to be carried out using standardized methodologies. [ABSTRACT FROM AUTHOR]

Knee osteoarthritis (KO) is an important health condition, affecting one third of people aged 65 years or more. Pain is the main cause of disability. Pain management in KO includes pharmacological and non-pharmacological modalities. Patient education, lifestyle changes, physical exercise, and physical agents are prescribed as a first approach for pain control. Laser therapy is part of many therapeutical protocols, with two forms: low-level laser therapy (LLLT) and high-intensity laser therapy (HILT). This paper aimed to stress the advantages of HILT based on a greater wavelength, higher energy delivery, and deeper tissue penetration. Research on 23 published trials revealed that the analgesic effect is rapid, cumulative, and long lasting. Compared to sham, to LLLT, or to other combinations of therapeutical modalities, HILT provided significantly better results on pain reduction and functional improvement. Ultrasound examination showed a reduction in intra-articular inflammation. [ABSTRACT FROM AUTHOR]

The clinical response to classical immunosuppressant drugs (cIMDs) is highly variable among individuals. We performed a systematic review of published evidence supporting the hypothesis that gut microorganisms may contribute to this variability by affecting cIMD pharmacokinetics, efficacy or tolerability. The evidence that these drugs affect the composition of intestinal microbiota was also reviewed. The PubMed and Scopus databases were searched using specific keywords without limits of species (human or animal) or time from publication. One thousand and fifty five published papers were retrieved in the initial database search. After screening, 50 papers were selected to be reviewed. Potential effects on cIMD pharmacokinetics, efficacy or tolerability were observed in 17/20 papers evaluating this issue, in particular with tacrolimus, cyclosporine, mycophenolic acid and corticosteroids, whereas evidence was missing for everolimus and sirolimus. Only one of the papers investigating the effect of cIMDs on the gut microbiota reported negative results while all the others showed significant changes in the relative abundance of specific intestinal bacteria. However, no unique pattern of microbiota modification was observed across the different studies. In conclusion, the available evidence supports the hypothesis that intestinal microbiota could contribute to the variability in the response to some cIMDs, whereas data are still missing for others. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus is an autoimmune condition characterized by the destruction of pancreatic β-cells, necessitating insulin therapy to prevent life-threatening complications such as diabetic ketoacidosis. Despite advancements in glucose monitoring and pharmacological treatments, managing this disease remains challenging, often leading to long-term complications and psychological burdens, including diabetes distress. Advanced treatment options, such as whole-pancreas transplantation and islet transplantation, aim to restore insulin production and improve glucose control in selected patients with diabetes. The risk of transplant rejection necessitates immunosuppressive therapy, which increases susceptibility to infections and other adverse effects. Additionally, surgical complications, including infection and bleeding, are significant concerns, particularly for whole-pancreas transplantation. Recently, stem cell-derived therapies for type 1 diabetes have emerged as a promising alternative, offering potential solutions to overcome the limitations of formerly established transplantation methods. The purpose of this scoping review was to: (1) summarize the current evidence on achieved insulin independence following various transplantation methods of insulin-producing cells in patients with type 1 diabetes; (2) compare insulin independence rates among whole-pancreas transplantation, islet cell transplantation, and stem cell transplantation; and (3) identify limitations, challenges and potential future directions associated with these techniques. We systematically searched three databases (PubMed, Scopus, and Web of Science) from inception to November 2024, focusing on English-language, peer-reviewed clinical studies. The search terms used were 'transplantation' AND 'type 1 diabetes' AND 'insulin independence'. Studies were included if they reported on achieved insulin independence, involved more than 10 patients with type 1 diabetes, and had a mean follow-up period of at least one year. Reviewers screened citations and extracted data on transplant type, study population size, follow-up duration, and insulin independence rates. We identified 1380 papers, and after removing duplicates, 705 papers remained for title and abstract screening. A total of 139 English-language papers were retrieved for full-text review, of which 48 studies were included in this review. The findings of this scoping review indicate a growing body of literature on transplantation therapy for type 1 diabetes. However, significant limitations and challenges, like insufficient rates of achieved insulin independence, risks related to immunosuppression, malignant diseases, and ethical issues remain with each of the established techniques, highlighting the need for innovative approaches such as stem cell-derived islet transplantation to promote β-cell regeneration and protection. [ABSTRACT FROM AUTHOR]

Gut health is crucial in many ways, such as in improving human health in general and enhancing production in agricultural animals. To maximize the effect of a healthy gastrointestinal tract (GIT), an understanding of the regulation of intestinal functions is needed. Proper intestinal functions depend on the activity, composition, and behavior of intestinal epithelial cells (IECs). There are various types of IECs, including enterocytes, Paneth cells, enteroendocrine cells (EECs), goblet cells, tuft cells, M cells, and intestinal epithelial stem cells (IESCs), each with unique 3D structures and IEC distributions. Although the communication between IECs and other cell types, such as immune cells and neurons, has been intensively reviewed, communication between different IECs has rarely been addressed. The present paper overviews the networks among IECs that influence intestinal functions. Intestinal absorption is regulated by incretins derived from EECs that induce nutrient transporter activity in enterocytes. EECs, Paneth cells, tuft cells, and enterocytes release signals to activate Notch signaling, which modulates IESC activity and intestinal homeostasis, including proliferation and differentiation. Intestinal immunity can be altered via EECs, goblet cells, tuft cells, and cytokines derived from IECs. Finally, tools for investigating IEC communication have been discussed, including the novel 3D intestinal cell model utilizing enteroids that can be considered a powerful tool for IEC communication research. Overall, the importance of IEC communication, especially EECs and Paneth cells, which cover most intestinal functional regulating pathways, are overviewed in this paper. Such a compilation will be helpful in developing strategies for maintaining gut health. [ABSTRACT FROM AUTHOR]

This document is an editorial from the journal Biomedicines, discussing a special issue on the latest research in post-COVID conditions. The COVID-19 pandemic has led to a significant increase in research, with a focus on managing acute cases and preventing the spread of the virus. However, there is now a growing concern about the development of long-lasting symptoms after the acute infection, known as long-COVID or post-COVID-19 condition. This special issue includes fourteen papers covering topics such as the treatment of post-COVID-19 condition, the impact of SARS-CoV-2 infection on neonates, risk factors for severe COVID-19, and the phenotyping of post-COVID pain. The papers discuss various treatment strategies, the potential transmission of the virus during pregnancy, risk factors for severe disease, and different types of post-COVID pain. Overall, this special issue provides valuable insights into the understanding and management of post-COVID conditions. [Extracted from the article]

(1) Background: Identification of typical behavioral manifestations in patients with DEAD-Box Helicase 3 X-linked gene (DDX3X) variants plays a crucial role in accurately diagnosing and managing the syndrome. The objective of this paper was to carry out a review of medical and public databases and assess the behavioral features of the DDX3X syndrome (DDX3X), with a particular focus on psycho-pathological symptoms. (2) Methods: An extensive computerized search was conducted in various databases, including PubMed, Medline Complete, Science Direct, Scopus, and Web of Science. Specific keywords and Medical Subject Headings were used to ensure the inclusion of relevant studies. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were applied to assess the methodological quality of the manuscripts. (3) Results: Only nine papers out of the 272 assessed met the inclusion criteria. These articles revealed various psycho-pathological manifestations in patients with the DDX3X syndrome. Intellectual disability (ID) or developmental disability (DD), speech delay, autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), generalized anxiety disorder (GAD), self-injurious behaviors (SIBs), sensory symptoms and sleep disturbance were demonstrated to be the most common psycho-pathological behavior manifestations. (4) Conclusions: Patients with the DDX3X syndrome manifest a wide spectrum of psycho-pathological symptoms. A comprehensive investigation of these symptoms in patients is essential for early diagnosis and effective therapy. [ABSTRACT FROM AUTHOR]

Episcopic imaging using techniques such as High Resolution Episcopic Microscopy (HREM) and its variants, allows biological samples to be visualized in three dimensions over a large field of view. Quantitative analysis of episcopic image data is undertaken using a range of methods. In this systematic review, we look at trends in quantitative analysis of episcopic images and discuss avenues for further research. Papers published between 2011 and 2022 were analyzed for details about quantitative analysis approaches, methods of image annotation and choice of image processing software. It is shown that quantitative processing is becoming more common in episcopic microscopy and that manual annotation is the predominant method of image analysis. Our meta-analysis highlights where tools and methods require further development in this field, and we discuss what this means for the future of quantitative episcopic imaging, as well as how annotation and quantification may be automated and standardized across the field. [ABSTRACT FROM AUTHOR]

The editorial in the Biomedicines journal discusses the trends in 3D printing processes for the biomedical field, highlighting opportunities and challenges. The article traces the history of 3D printing, its impact on various disciplines, and its applications in medicine, including 3D bioprinting for biomimetic scaffolds, human implants, and drug testing models. The editorial also presents a summary of research papers included in a Special Issue, covering topics such as cardiac ablation, bone reconstruction, and brain models created using 3D printing technology. [Extracted from the article]

Background: This report focuses on the treatment histories of 21 patients diagnosed with Dravet syndrome (DRVT) under the care of the Mother and Child Institute in Warsaw. This paper aims to present typical treatment schemes for patients with drug-resistant epilepsy, as well as to highlight the influence of genetic diagnosis on pharmacotherapeutic management and to present an economic analysis of hospitalization costs. This paper will also summarize the effectiveness of the latest drugs used in DRVT. Methods: Clinical data were collected retrospectively from available medical records. The effectiveness of anticonvulsant treatment was assessed based on epileptic seizure diaries and observations by caregivers and pediatric neurologists. Results: The study group (n = 21) consisted of patients aged 3–26 years. Orphan drugs dedicated to Dravet syndrome were introduced in all patients due to the genetic diagnosis, which significantly improved the patients' clinical conditions. The breakthrough drugs were stiripentol (in 16/21) and fenfluramine (in 3/21). Conclusions: In recent years, molecular genetics has rapidly developed in Poland, along with a steady increase in knowledge of Dravet syndrome among the medical profession. Early and precise diagnosis provides the opportunity to target treatment with drugs dedicated to Dravet syndrome with high efficacy. [ABSTRACT FROM AUTHOR]

Biomedical information retrieval for diagnosis, treatment and prognosis has been studied for a long time. In particular, image recognition using deep learning has been shown to be very effective for cancers and diseases. In these fields, scaphoid fracture recognition is a hot topic because the appearance of scaphoid fractures is not easy to detect. Although there have been a number of recent studies on this topic, no studies focused their attention on surgical treatment recommendations and nonsurgical prognosis status classification. Indeed, a successful treatment recommendation will assist the doctor in selecting an effective treatment, and the prognosis status classification will help a radiologist recognize the image more efficiently. For these purposes, in this paper, we propose potential solutions through a comprehensive empirical study assessing the effectiveness of recent deep learning techniques on surgical treatment recommendation and nonsurgical prognosis status classification. In the proposed system, the scaphoid is firstly segmented from an unknown X-ray image. Next, for surgical treatment recommendation, the fractures are further filtered and recognized. According to the recognition result, the surgical treatment recommendation is generated. Finally, even without sufficient fracture information, the doctor can still make an effective decision to opt for surgery or not. Moreover, for nonsurgical patients, the current prognosis status of avascular necrosis, non-union and union can be classified. The related experimental results made using a real dataset reveal that the surgical treatment recommendation reached 80% and 86% in accuracy and AUC (Area Under the Curve), respectively, while the nonsurgical prognosis status classification reached 91% and 96%, respectively. Further, the methods using transfer learning and data augmentation can bring out obvious improvements, which, on average, reached 21.9%, 28.9% and 5.6%, 7.8% for surgical treatment recommendations and nonsurgical prognosis image classification, respectively. Based on the experimental results, the recommended methods in this paper are DenseNet169 and ResNet50 for surgical treatment recommendation and nonsurgical prognosis status classification, respectively. We believe that this paper can provide an important reference for future research on surgical treatment recommendation and nonsurgical prognosis classification for scaphoid fractures. [ABSTRACT FROM AUTHOR]

Isothiocyanates (ITCs) belong to a group of natural products that possess a highly reactive electrophilic −N=C=S functional group. They are stored in plants as precursor molecules, glucosinolates, which are processed by the tyrosinase enzyme upon plant tissue damage to release ITCs, along with other products. Isolated from broccoli, sulforaphane is by far the most studied antioxidant ITC, acting primarily through the induction of a transcription factor, the nuclear factor erythroid 2–related factor 2 (Nrf2), which upregulates downstream antioxidant genes/proteins. Paradoxically, sulforaphane, as a pro-oxidant compound, can also increase the levels of reactive oxygen species, a mechanism which is attributed to its anticancer effect. Beyond highlighting the common pro-oxidant and antioxidant effects of sulforaphane, the present paper was designed to assess the diverse anti-inflammatory mechanisms reported to date using a variety of in vitro and in vivo experimental models. Sulforaphane downregulates the expression of pro-inflammatory cytokines, chemokines, adhesion molecules, cycloxyhenase-2, and inducible nitric oxide synthase. The signalling pathways of nuclear factor κB, activator protein 1, sirtuins 1, silent information regulator sirtuin 1 and 3, and microRNAs are among those affected by sulforaphane. These anti-inflammatory actions are sometimes due to direct action via interaction with the sulfhydryl structural moiety of cysteine residues in enzymes/proteins. The following are among the topics discussed in this paper: paradoxical signalling pathways such as the immunosuppressant or immunostimulant mechanisms; crosstalk between the oxidative and inflammatory pathways; and effects dependent on health and disease states. [ABSTRACT FROM AUTHOR]

This document is a summary of a special issue of the journal Biomedicines on translational laboratory and experimental medicine for neurological diseases and mental illnesses. The issue includes 21 papers that explore various topics such as stroke and neuroplasticity, age and behavioral studies, neuropsychiatric disorders and treatments, and mental health and disorders. The papers provide insights into the mechanisms underlying these conditions and offer perspectives on therapeutic strategies and interventions. The goal of the special issue is to improve our understanding of brain function and mental health and to develop real-world applications to benefit individuals affected by these disorders. [Extracted from the article]

Background: In the world, approximately 1% of the population suffers from chronic spontaneous urticaria (CSU), burdening patients' quality of life and challenging clinicians in terms of treatment. Recent scientific evidence has unveiled the potential role of a family of molecules known as "alarmins" in the pathogenesis of CSU. Methods: Papers focusing on the potential pathogenetic role of alarmins in CSU with diagnostic (as biomarkers) and therapeutic implications, in English and published in PubMed, Scopus, Web of Science, as well as clinical studies registered in ClinicalTrials.gov and the EudraCT Public website, were reviewed. Results: The epithelial-derived alarmins thymic stromal lymphopoietin and IL-33 could be suitable diagnostic and prognostic biomarkers and possible therapeutic targets in CSU. The evidence on the role of non-epithelial-derived alarmins (heat shock proteins, S-100 proteins, eosinophil-derived neurotoxin, β-defensins, and acid uric to high-density lipoproteins ratio) is more heterogeneous and complex. Conclusions: More homogeneous studies on large cohorts, preferably supported by data from international registries, will be able to elucidate the intriguing and complex pathogenetic world of CSU. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorders (ASDs), attention-deficit disorder (ADHD), Parkinson's disease (PD), polycystic ovary disease (PCOS), and Alzheimer's disease (AD) have all been linked to exposure to bisphenol A (BPA). Methods: This paper is a review and discussion of the published literature. Results: Animal studies have shown BPA to be a broad-spectrum endocrine disruptor. BPA is metabolized via the glucuronidation pathway, which involves the addition of glucose to the target molecule, and is catalyzed by uridine 5′-diphospho-glucuronosyltransferases (UGTs). Evidence of compromised glucuronidation has been found for ASD, DHD, PD, and PCOS. Genetic polymorphisms that alter the catalytic activity of the UGTs and efflux transporters involved are common. There are two ways to interpret the findings of associations between BPA glucuronidation efficiency and disease, a 'direct' pathway and an 'indirect' pathway. With the 'direct' pathway, free BPA is the actual causative agent. Compromised BPA detoxification leads to higher concentrations of free BPA in vulnerable tissues. Decreased BPA detoxification leads to increased exposure of vulnerable tissues to free BPA, where it can function as an endocrine disruptor. With the 'indirect' pathway, BPA is not the causative agent. BPA serves as a marker for the decreased glucuronidation efficiency of another unknown compound of endogenous origin detoxified by a similar combination of UGTs and efflux transporters as BPA. It is this compound(s), acting as an endocrine disruptor, that leads to a metabolic environment that favors disease development over an extended time period. Conclusion: A review of the existing literature supports the indirect 'marker' hypothesis over the 'direct' hypothesis. [ABSTRACT FROM AUTHOR]

Cancer remains a leading cause of mortality in Japan, yet participation in conventional screening programs is low due to invasiveness, cost, and accessibility. Non-invasive, affordable, and accurate methods for early cancer detection in asymptomatic individuals are urgently needed. This opinion manuscript evaluates nematode cancer testing, a novel urine-based screening test using the nematode Caenorhabditis elegans, for its potential to improve early cancer detection rates, based on real-world data published in a Japanese journal. Nematode cancer testing leverages the nematode's ability to detect cancer-associated volatile compounds in urine, offering a highly sensitive, non-invasive screening approach. We analyzed data from a nationwide survey of PET-equipped medical institutions in Japan, comparing cancer discovery rates between nematode cancer testing-triggered and standard PET screenings. In nematode cancer testing-triggered PET screenings, the cancer discovery rate was 2.96%, significantly higher than the 1.31% observed in standard PET screenings. The apparent positive predictive value (PPV) of nematode cancer testing was calculated at 2.09%; when adjusted for PET/CT sensitivity, the actual PPV increased to approximately 11.7%. This reflects a screening efficiency 14.6 times higher than the general population's cancer incidence. These findings indicate that nematode cancer testing successfully detects cancer in high-risk individuals and may encourage participation in further diagnostic evaluations. The recently published nationwide survey of PET-equipped medical institutions in Japan highlights the good performance of nematode cancer testing in cancer detection. As an opinion-type manuscript based on real-world data from Japan, this paper shows that nematode cancer testing has substantial potential as a cost-effective, minimally invasive primary cancer screening tool for asymptomatic populations. By enhancing early detection rates and screening efficiency, it addresses the limitations of traditional screening methods. Implementing nematode cancer testing could lead to improved cancer outcomes, particularly in populations with low participation in standard screening programs and resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: Inflammation is caused by an excess of Sodium ions inside the cell. This generates a variation in the cell's membrane electric potential, becoming a steady state from a thermodynamic viewpoint. Methods: This paper introduces a thermodynamic approach to inflammation based on the fundamental role of the electric potential of the cell membrane, introducing an analysis of the effect of heat transfer related to the inflammation condition. Results: The direct proportionality between the reduction in temperature and the increase of Na+ outflow may ameliorate the inflammation cascade. Conclusions: Based on these ion fluxes, we suggest the consideration of a 'companion' electromagnetic therapeutic wave concept in support of the present anti-inflammatory treatment. [ABSTRACT FROM AUTHOR]

Human noroviruses (HuNoVs) are the main pathogens that cause acute gastroenteritis and lead to huge economic losses annually. Due to the lack of suitable culture systems, the pathogenesis of HuNoVs and the development of vaccines and drugs have progressed slowly. Although researchers have employed various methods to culture HuNoVs in vitro in the last century, problems relating to the irreducibility, low viral titer, and non-infectiousness of the progeny virus should not be ignored. In 2016, researchers achieved the cultivation and successive passaging of some HuNoV genotypes using human intestinal enteroids, initially demonstrating the potential use of organoids in overcoming this challenge. This paper reviews the efforts made in the last 20 years to culture HuNoVs in vitro and discusses the superiority and limitations of employing human intestinal enteroids/organoids as an in vitro culture model for HuNoVs. [ABSTRACT FROM AUTHOR]

The recent setbacks in the withdrawal and approval delays of antibody treatments of neurodegenerative disorders (NDs), attributed to their poor entry across the blood–brain barrier (BBB), emphasize the need to bring novel approaches to enhance the entry across the BBB. One such approach is conjugating the antibodies that bind brain proteins responsible for NDs with the transferrin molecule. This glycoprotein transports iron into cells, connecting with the transferrin receptors (TfRs), piggybacking an antibody–transferrin complex that can subsequently release the antibody in the brain or stay connected while letting the antibody bind. This process increases the concentration of antibodies in the brain, enhancing therapeutic efficacy with targeted delivery and minimum systemic side effects. Currently, this approach is experimented with using drug-transferring conjugates assembled in vitro. Still, a more efficient and safer alternative is to express the conjugate using mRNA technology, as detailed in this paper. This approach will expedite safer discoveries that can be made available at a much lower cost than the recombinant process with in vitro conjugation. Most importantly, the recommendations made in this paper may save the antibodies against the NDs that seem to be failing despite their regulatory approvals. [ABSTRACT FROM AUTHOR]

This paper presents an in-depth exploration of Post-Traumatic Epilepsy (PTE), a complex neurological disorder following traumatic brain injury (TBI), characterized by recurrent, unprovoked seizures. With TBI being a global health concern, understanding PTE is crucial for effective diagnosis, management, and prognosis. This study aims to provide a comprehensive overview of the epidemiology, risk factors, and emerging biomarkers of PTE, thereby informing clinical practice and guiding future research. The epidemiological aspect of the study reveals PTE as a significant contributor to acquired epilepsies, with varying incidence influenced by injury severity, age, and intracranial pathologies. The paper delves into the multifactorial nature of PTE risk factors, encompassing clinical, demographic, and genetic elements. Key insights include the association of injury severity, intracranial hemorrhages, and early seizures with increased PTE risk, and the roles of age, gender, and genetic predispositions. Advancements in neuroimaging, electroencephalography, and molecular biology are presented, highlighting their roles in identifying potential PTE biomarkers. These biomarkers, ranging from radiological signs to electroencephalography EEG patterns and molecular indicators, hold promise for enhancing PTE pathogenesis understanding, early diagnosis, and therapeutic guidance. The paper also discusses the critical roles of astrocytes and microglia in PTE, emphasizing the significance of neuroinflammation in PTE development. The insights from this review suggest potential therapeutic targets in neuroinflammation pathways. In conclusion, this paper synthesizes current knowledge in the field, emphasizing the need for continued research and a multidisciplinary approach to effectively manage PTE. Future research directions include longitudinal studies for a better understanding of TBI and PTE outcomes, and the development of targeted interventions based on individualized risk profiles. This research contributes significantly to the broader understanding of epilepsy and TBI. [ABSTRACT FROM AUTHOR]

Background: Necrobiosis lipoidica (NL) is a rare granulomatous skin disorder with a predilection for females, often associated with diabetes mellitus (DM). This paper aims to comprehensively review the literature on NL, focusing on its association with DM, thyroid disorders, and the metabolic syndrome. Methods: A systematic search was conducted in English-language literature from inception to October 2023, utilizing PubMed. We identified 530 studies and selected 19 based on clinical significance, statistical support, and relevance to the paper's goals. Results: The coexistence of NL and DM is prevalent, with rates ranging from 11% to 65.71%. NL may precede DM diagnosis and a correlation between NL and increased daily insulin requirements has been observed in such patients. NL is suggested as a potential prognostic marker for DM complications; however, recent studies question this association, highlighting the need for further research. Studies in the context of NL and Thyroid Disease indicate a correlation, especially with autoimmune thyroiditis. Regarding NL and Metabolic Syndrome, the prevalence of metabolic syndrome among NL patients is notably higher than in the general population. Additionally, DM patients with ulcerated NL commonly exhibit hypertension or obesity, raising questions about the potential influence of hypertension and obesity on NL ulcerations. Conclusion: Additional research is required to untangle the complex connections between NL and various comorbidities. [ABSTRACT FROM AUTHOR]

Dyslipidemia is a common metabolic complication in patients undergoing peritoneal dialysis (PD) and has traditionally been viewed primarily in terms of cardiovascular risk. Current guidelines do not recommend initiating lipid-lowering therapy in dialysis patients due to insufficient evidence of its benefits on cardiovascular mortality. However, the impact of dyslipidemia in PD patients may extend beyond cardiovascular concerns, influencing PD-related outcomes such as the peritoneal ultrafiltration rate, residual kidney function, PD technique survival, and overall mortality. This review challenges the traditional perspective by discussing dyslipidemia's potential role in PD-related complications, which may account for the observed link between dyslipidemia and increased all-cause mortality in PD patients. It explores the pathophysiology of dyslipidemia in PD, the molecular mechanisms linking dyslipidemia to peritoneal membrane dysfunction, and summarizes clinical evidence supporting this hypothesis. In addition, this paper examines the potential for therapeutic strategies to manage dyslipidemia to improve peritoneal membrane function and patient outcomes. The review calls for future research to investigate dyslipidemia as a potential contributor to peritoneal membrane dysfunction and to develop targeted interventions for PD patients. [ABSTRACT FROM AUTHOR]

Objectives: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has gained a primary role in prostate cancer (PCa) imaging, overcoming conventional imaging and prostate-specific antigen (PSA) serum levels, and has recently emerged as a promising technique for monitoring therapy response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with novel hormonal therapy, taxanes, and radioligand therapy (RLT). In this review, we aim to provide an overview of the most relevant aspects under study and future prospects related to the prognostic role of PSMA PET/CT in mCRPC. Methods: A systematic literature search was performed in the following databases: MEDLINE, PubMed, and EMBASE databases. The study focused exclusively on English-language studies, excluding papers not pertinent to the topic. Results: PSMA PET imaging offers a higher sensitivity and specificity than conventional imaging and provides accurate staging and efficient diagnosis of distant metastases. The data presented herein highlight the usefulness of PET in risk stratification, with a prognostic potential that can have a significant impact on clinical practice. Several prospective trials are ongoing and will shortly provide more evidence supporting the prognostic potential of PET PSMA data in this clinical scenario. Conclusions: Current evidence proves the prognostic role of PSMA PET/CT in different settings, with raising relevance also in the context of mCRPC. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-related morbidity and mortality. The median survival time for patients with advanced non-small-cell lung cancer before the era of molecular-based personalized treatment was 7.9 months. The discovery of predictive factors and the introduction of molecular diagnostics into daily practice made a breakthrough, enabling several years of survival in patients with advanced disease. The discovery of rearrangements in the ALK gene and ALK tyrosine kinase inhibitors has resulted in a dramatic improvement in the prognosis of patients with this subtype of cancer. Currently, three generations of ALK inhibitors differing in activity, toxicity and degree of penetration into the central nervous system are available in clinical practice. The current state of knowledge on ALK inhibitors used in clinical practice is summarised in this research paper. Methods of diagnosis of abnormalities in ALK have been shown, and the review of research that contributed to the development of the next generation of ALK inhibitors has been presented. [ABSTRACT FROM AUTHOR]

E-skin is a bionic device with flexible and intelligent sensing ability that can mimic the touch, temperature, pressure, and other sensing functions of human skin. Because of its flexibility, breathability, biocompatibility, and other characteristics, it is widely used in health management, personalized medicine, disease prevention, and other pan-health fields. With the proposal of new sensing principles, the development of advanced functional materials, the development of microfabrication technology, and the integration of artificial intelligence and algorithms, e-skin has developed rapidly. This paper focuses on the characteristics, fundamentals, new principles, key technologies, and their specific applications in health management, exercise monitoring, emotion and heart monitoring, etc. that advanced e-skin needs to have in the healthcare field. In addition, its significance in infant and child care, elderly care, and assistive devices for the disabled is analyzed. Finally, the current challenges and future directions of the field are discussed. It is expected that this review will generate great interest and inspiration for the development and improvement of novel e-skins and advanced health monitoring systems. [ABSTRACT FROM AUTHOR]

In the field of clinical testing, the traditional focus has been on the development of large-scale analysis equipment designed to process high volumes of samples with fully automatic and high-sensitivity measurements. However, there has been a growing demand in recent years for the development of analytical reagents tailored to point-of-care testing (POCT), which does not necessitate a specific location or specialized operator. This trend is epitomized using the lateral flow assay (LFA), which became a cornerstone during the 2019 pandemic due to its simplicity, speed of delivering results—within about 10 min from minimal sample concentrations—and user-friendly design. LFAs, with their paper-based construction, combine cost-effectiveness with ease of disposal, addressing both budgetary and environmental concerns comprehensively. Despite their compact size, LFAs encapsulate a wealth of technological ingenuity, embodying years of research and development. Current research is dedicated to further evolving LFA technology, paving the way for the next generation of diagnostic devices. These advancements aim to redefine accessibility, empower individuals, and enhance responsiveness to public health challenges. The future of LFAs, now unfolding, promises even greater integration into routine health management and emergency responses, underscoring their critical role in the evolution of decentralized and patient-centric healthcare solutions. In this review, the historical development of LFA and several of the latest LFA technologies using catalytic amplification, surface-enhanced Raman scattering, heat detection, electron chemical detections, magnetoresistance, and detection of reflected electrons detection are introduced to inspire readers for future research and development. [ABSTRACT FROM AUTHOR]

Background/Objectives: Mycobacterium tuberculosis (M. tb) is a pathogen that causes tuberculosis (TB), an extremely infectious disease which is responsible for millions of deaths worldwide. The severity of this pathogen is further amplified with the emergence of multidrug-resistant strains that are becoming more prevalent at an alarming rate, and novel treatments are needed. Methods: In this paper, we discuss the pathology M. tb infection. We review the literature on the role that mTOR plays in autophagy and the immune system as well as its impact on M. tb infection. Lastly, we discuss the current therapies targeting mTOR and potential routes to explore for future treatments. Results: The mTOR protein acts as a negative regulator of the autophagy pathway and presents as a potent target to establish new treatments for TB. M. tb survival is affected by mTOR, the PI3K/mTOR/AKT pathway, and autophagy. M. tb evades destruction by manipulating host cellular mechanisms, which increases resistance and complicates treatment. Conclusions: Targeting mTOR can enhance autophagy and increase M. tb clearance. Existing drugs such as everolimus, rapamycin + CC214-2, and bazedoxifene are all being currently studied for effectiveness and show positive results. Alternative therapies, including Chinese herbs, baicalin, BTLA, glutathione, and precision medicine can modulate the PI3K/mTOR/AKT pathway and the host's immune response, resulting in increased M. tb clearance, and these may be the future treatments for M. tb infection. [ABSTRACT FROM AUTHOR]

Background: Alzheimer's disease (AD) is the most prevalent kind of dementia and is a long-term degenerative disease. Pathologically, it is defined by the development of extracellular amyloid-β plaques and intracellular neurofibrillary tangles made up of hyperphosphorylated tau protein. This causes neuronal death, particularly in the hippocampus and cortex. Mesenchymal stem cell (MSC)-derived exosomes have been identified as possibly therapeutic and have promise for Alzheimer's disease due to their regenerative characteristics. Methods: A systematic retrieval of information was performed on PubMed. A total of 60 articles were found in a search on mesenchymal stem cells, exosomes, and Alzheimer's disease. A total of 16 ongoing clinical trials were searched and added from clinicaltrials.gov. We added 23 supporting articles to help provide information for certain sections. In total, we included 99 articles in this manuscript: 50 are review articles, 13 are preclinical studies, 16 are clinical studies, 16 are ongoing clinical trials, and 4 are observational studies. Appropriate studies were isolated, and important information from each of them was understood and entered into a database from which the information was used in this article. The clinical trials on mesenchymal stem cell exosomes for Alzheimer's disease were searched on clinicaltrials.gov. Results: Several experimental investigations have shown that MSC-Exo improves cognitive impairment in rats. In this review paper, we summarized existing understanding regarding the molecular and cellular pathways behind MSC-Exo-based cognitive function restoration, with a focus on MSC-Exo's therapeutic potential in the treatment of Alzheimer's disease. Conclusion: AD is a significant health issue in our culture and is linked to several important neuropathological characteristics. Exosomes generated from stem cells, such as mesenchymal stem cells (MSCs) or neural stem cells (NSCs), have been examined more and more in a variety of AD models, indicating that they may be viable therapeutic agents for the treatment of diverse disorders. Exosome yields may be increased, and their therapeutic efficacy can be improved using a range of tailored techniques and culture conditions. It is necessary to provide standardized guidelines for exosome manufacture to carry out excellent preclinical and clinical research. [ABSTRACT FROM AUTHOR]

The identification of significant gene biclusters with particular expression patterns and the elucidation of functionally related genes within gene expression data has become a critical concern due to the vast amount of gene expression data generated by RNA sequencing technology. In this paper, a Conserved Gene Expression Module based on Genetic Algorithm (CGEMGA) is proposed. Breast cancer data from the TCGA database is used as the subject of this study. The p-values from Fisher's exact test are used as evaluation metrics to demonstrate the significance of different algorithms, including the Cheng and Church algorithm, CGEM algorithm, etc. In addition, the F-test is used to investigate the difference between our method and the CGEM algorithm. The computational cost of the different algorithms is further investigated by calculating the running time of each algorithm. Finally, the established driver genes and cancer-related pathways are used to validate the process. The results of 10 independent runs demonstrate that CGEMGA has a superior average p-value of 1.54 × 10−4 ± 3.06 × 10−5 compared to all other algorithms. Furthermore, our approach exhibits consistent performance across all methods. The F-test yields a p-value of 0.039, indicating a significant difference between our approach and the CGEM. Computational cost statistics also demonstrate that our approach has a significantly shorter average runtime of 5.22 × 100 ± 1.65 × 10−1 s compared to the other algorithms. Enrichment analysis indicates that the genes in our approach are significantly enriched for driver genes. Our algorithm is fast and robust, efficiently extracting co-expressed genes and associated co-expression condition biclusters from RNA-seq data. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the head and neck (SCCHN) is among the ten most common cancers worldwide, with advanced SCCHN presenting with a 5-year survival of 34% in the case of nodal involvement and 8% in the case of metastatic disease. Disease-free survival at 2 years is 67% for stage II and 33% for stage III tumors, whereas 12–30% of patients undergo distant failures after curative treatment. Previous treatments often hinder the success of salvage surgery and/or reirradiation, while the standard of care for the majority of metastatic SCCHN remains palliative chemo- and immuno-therapy, with few patients eligible for locoregional treatments. The aim of this paper is to review the characteristics of recurrent SCCHN, based on different recurrence sites, and metastatic disease; we will also explore the possibilities not only of salvage surgery and reirradiation but also systemic therapy choices and locoregional treatment for metastatic SCCHN. [ABSTRACT FROM AUTHOR]

Lower back pain (LBP) is a widely prevalent global health issue, affecting over half a billion people and remaining the leading cause of years lived with disability (YLDs). LBP significantly impacts healthcare systems, with substantial costs related to surgical procedures and lost workdays. Vertebrogenic back pain (VBP), characterized by specific clinical symptoms and associated with Modic changes (MC) in vertebral endplates, best seen on MRI, is a significant subset of LBP. This paper explores the pathophysiology, diagnosis, and current reports and studies focusing on VBP and the role of basivertebral nerve (BVN) ablation as a therapeutic intervention. Multiple studies, including randomized controlled trials (RCTs) and meta-analyses, demonstrate the efficacy of BVN ablation in reducing pain and improving function in patients with chronic LBP associated with MC. [ABSTRACT FROM AUTHOR]

In this study, we investigated von Willebrand factor (VWF)-related parameters in 30 patients with stable coronary artery disease (CAD) and 50 patients without CAD. In both groups, the following were measured: the VWF antigen level (VWF:Ag); the VWF ristocetin cofactor activity (VWF:RCo); the VWF collagen-binding activity (VWF:CB); and VWF-mediated platelet adhesion. Platelet adhesion was measured in whole blood at a shear rate of 1300 s−1 using a microfluidic chamber with a collagen-coated surface. VWF:Ag and VWF:RCo were found to be the same in both groups of patients. However, VWF:CB was found to be lower in patients with CAD compared with patients without CAD, with values of 106.7% (82.1; 131.6) and 160.4% (112.5; 218.1), respectively (p < 0.001). The decrease in platelet adhesion after GPIb inhibition was more pronounced in patients with CAD compared with patients of the control group, with recorded values of 76.0% (60.6; 82.1) and 29.3% (0.0; 60.4), respectively (p < 0.001). After adjusting for traditional risk factors, the odds ratio for CAD was found to be 0.98 (95% CI, 0.97–0.99; p = 0.011) per 1% increase in VWF:CB activity, and 1.06 (95% CI, 1.03–1.09; p < 0.001) per 1% decrease in GPIb-mediated platelet adhesion. The findings presented in this paper indicate a possible critical role played by complex VWF–collagen-platelet interactions in the development of CAD. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains a significant public health concern because of its lethality, underscoring the need for deeper insights into its molecular mechanisms. Recent studies have increasingly highlighted the role of epigenetic modifications as critical players in cancer progression. Despite their importance, research specifically addressing epigenetic factors in GC is relatively scarce. This paper seeks to bridge that gap by examining recent literature that elucidates the epigenetic landscape associated with GC. The investigation of long noncoding RNAs (lncRNAs) has revealed their substantial involvement in gene dysregulation and epigenetic alterations within GC tumors. Notably, lncRNAs such as LINC00853 and LINC01266 have been identified as significant contributors to the epigenetic modulation of gene expression. Furthermore, the overexpression of KAT5 and GPX4 has been shown to mitigate the antiproliferative effects resulting from the depletion of circRHOT1, suggesting a complex interplay between these molecules in GC pathophysiology. Another pivotal aspect of epigenetic regulation in GC involves modifications in N6-methyladenosine (m6A), which play crucial roles in mRNA maturation processes such as splicing, export, degradation, and translation. m6A modifications are known for their influence on various cancer-related pathways, thus presenting a potential avenue for targeted interventions. Our findings indicate that the most pronounced instances of epigenetic dysregulation in GC can be traced back to the effects of long lncRNAs and alterations in m6A modification patterns. This underscores the urgent need for comprehensive investigations into these epigenetic factors, as a deeper understanding could lead to enhanced diagnostic markers and innovative therapeutic strategies. The integration of genetic and epigenetic considerations is essential for advancing the field of GC research. This synthesis of recent findings concerning epigenetic regulation offers valuable insights that could inform future studies and therapeutic developments. There is a critical need for ongoing research to elucidate the complexities of epigenetic modifications in GC, ultimately improving patient outcomes through tailored interventions. [ABSTRACT FROM AUTHOR]

In this study, a physiologically based pharmacokinetic (PBPK) modeling framework was employed to explore infliximab exposure following intravenous (5 mg/kg) and subcutaneous administration (encompassing the approved 120 mg flat-fixed dose as a switching option) in virtual adult and pediatric patients with inflammatory bowel disease (IBD). The PBPK model and corresponding simulations were conducted using the PK-Sim® software platform. The PBPK simulation indicated that a 120 mg subcutaneous flat-fixed dose might not be optimal for heavier adults with IBD, suggesting the need for infliximab dose escalation. For an older virtual pediatric patient (14 years old), subcutaneous administration of a 120 mg flat-fixed dose appears to be a feasible IBD treatment option. In the final exploration scenario, the model was extended to predict hypothetical subcutaneous infliximab doses in a virtual pediatric population (6–18 years old), stratified into three weight bands (20–30 kg, 30–45 kg, and 45–70 kg), that would yield post-switch trough concentrations of infliximab comparable to those seen in adults with the 120 mg flat-fixed subcutaneous dose. The PBPK-model-informed dose suggestions were 40 mg for the 20–30 kg band, 80 mg for the 30–45 kg band, and 120 mg for the 45–70 kg band. As demonstrated in this paper, the PBPK modeling framework can serve as a versatile tool in clinical pharmacology to investigate various clinical scenarios, such as exploring alternative dosing regimens and routes of administration, ultimately advancing IBD treatment across diverse (sub)populations of clinical interest. [ABSTRACT FROM AUTHOR]

Stem cells are widely used in scientific research because of their ability to self-renew and differentiate into a variety of specialized cell types needed for body functions. However, the self-renewal and differentiation of stem cells are regulated by various stimuli, with mechanical stimulation being particularly notable due to its ability to mimic the physical environment in the body. This study systematically collected 2638 research papers published between 1994 and 2024, employing tools such as VOSviewer, CiteSpace, and GraphPad Prism to uncover research hotspots, publication trends, and collaboration networks. The results indicate a yearly increase in global research on the shear stress stimulation of stem cells, with significant contributions from the United States and China in terms of research investment and output. Future research directions include a deeper understanding of the mechanisms underlying mechanical stimulation's effects on stem cell differentiation, the development of new materials and scaffold designs to better replicate the natural cellular environment, and advancements in regenerative medicine. Despite considerable progress, challenges remain in translating basic research findings into clinical applications. [ABSTRACT FROM AUTHOR]

Immunosenescence, the gradual deterioration of immune function with age, holds profound implications for our understanding and management of multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system. Traditionally diagnosed in young adults, advancements in disease-modifying therapies and increased life expectancy have led to a growing number of older individuals with MS. This demographic shift underscores the need for a deeper investigation into how age-related alterations in immune function shape the course of MS, influencing disease progression, treatment effectiveness, and overall patient outcomes. Age-related immunosenescence involves changes such as shifts in cytokine profiles, the accumulation of senescent immune cells, and compromised immune surveillance, collectively contributing to a state known as "inflammaging". In the context of MS, these immunological changes disturb the intricate balance between inflammatory and regulatory responses, thereby impacting mechanisms of central immune tolerance and peripheral regulation. This paper stands out by combining the most recent advancements in immunosenescence with both pathophysiological and treatment perspectives on multiple sclerosis, offering a cohesive and accessible discussion that bridges theory and practice, while also introducing novel insights into underexplored concepts such as therapy discontinuation and the latest senolytic, neuroprotective, and remyelination therapies. Enhancing our understanding of these complexities will guide tailored approaches to MS management, ultimately improving clinical outcomes for affected individuals. [ABSTRACT FROM AUTHOR]

Diabetes is a global epidemic with severe consequences for individuals and healthcare systems. While early and personalized prediction can significantly improve outcomes, traditional centralized prediction models suffer from privacy risks and limited data diversity. This paper introduces a novel framework that integrates blockchain and federated learning to address these challenges. Blockchain provides a secure, decentralized foundation for data management, access control, and auditability. Federated learning enables model training on distributed datasets without compromising patient privacy. This collaborative approach facilitates the development of more robust and personalized diabetes prediction models, leveraging the combined data resources of multiple healthcare institutions. We have performed extensive evaluation experiments and security analyses. The results demonstrate good performance while significantly enhancing privacy and security compared to centralized approaches. Our framework offers a promising solution for the ethical and effective use of healthcare data in diabetes prediction. [ABSTRACT FROM AUTHOR]