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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.

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: 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.

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.

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.

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.

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.

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.

High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients (BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy. Therefore, there is an urgent need to identify the substantial risk factors for both predisposed and low-risk populations of women, as well as to create an economically and clinically justified screening program. This paper reviews the classic and novel risk factors for HGSOC and methods of diagnosis and prediction, including serum biomarkers, the liquid biopsy of circulating tumor cells or circulating tumor DNA, epigenetic markers, exosomes, and genomic and proteomic biomarkers. The novel future complex approach to ovarian cancer diagnosis should be devised based on these findings, and the general outcome of such an approach is proposed and discussed in the paper.

(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.

Our objective was to overview the most recent data on primary hyperparathyroidism (PHP) in children and teenagers from a multidisciplinary perspective. Methods: narrative review based on full-length, English-language papers (from PubMed, between January 2020 and July 2023). Results: 48 papers (14 studies of ≥10 subjects/study, and 34 case reports/series of MEN1, followed by CDC73, CASR, RET, and CDKN1B, as well as one case of VHL. Symptomatic PHP: 70–100% of all cases. Asymptomatic PHP: 60% of genetic PHP cases. Renal involvement: 10.5% of a cohort with genetic PHP, 71% of sporadic PHP cases; 50% (in a cohort with a mean age of 16.7), 29% (in a cohort with a mean age of 15.2); 0% (in infancy) to 50–62% (in teenagers). Bone anomalies: 83% of the children in one study and 62% of those in two other studies. Gastrointestinal issues: 40% of one cohort, but the data are heterogeneous. Cure rate through parathyroidectomy: 97–98%. Recurrent PHP: 2% of sporadic PHP cases and 38% of familial PHP cases. Hungry bone syndrome: maximum rate of 34–40%. Case reports identified another 7/41 subjects with the same post-parathyroidectomy condition; a potential connection with ectopic presentation or brown tumors is suggested, but there are limited data. Minimally invasive thoracoscopic approaches for ectopic tumors seemed safe. The current level of statistical evidence on pediatric PHP qualifies our study- and case-sample-based analysis (n = 48, N = 534) as one of the largest of its kind. Awareness of PHP is the key factor to benefit our young patients.

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.

Background: Low back pain (LBP) has a high economic burden and is strongly related to the degenerative process of the spine, especially in the intervertebral disc and of the facet joints. Numerous treatment modalities have been proposed for the management of LBP, and the use of platelet-rich plasma (PRP) has emerged as an innovative therapeutic option for degenerative disease of the spine. The present study aims to evaluate the efficacy of PRP injections in managing low back pain. Methods: We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations, a registered at PROSPERO Systematic Reviews Platform, under number CRD42021268491. The PubMed, Web of Science, and Scopus databases were searched to identify relevant articles, along with hand searching to identify gray literature articles, with no language restrictions. Randomized clinical trials (RCTs), nonrandomized trials (NRTs), and case series (CSs) with more than 10 patients were considered eligible. The quality assessment and the risk of bias of the randomized clinical trials were evaluated using the RoB II tool. An evaluation of the description of the preparation methods was performed using an adapted version of the MIBO checklist. Results: An electronic database search resulted in 2324 articles, and after the exclusion of noneligible articles, 13 RCTs and 27 NRTs or CSs were analyzed. Of the 13 RCTs, 11 found favorable results in comparison to the control group in pain and disability, one showed no superiority to the control group, and one was discontinued because of the lack of therapeutic effect at eight-week evaluation. Description of the PRP preparation techniques were found in almost all papers. The overall risk of bias was considered high in 2 papers and low in 11. An adapted MIBO checklist showed a 72.7% compliance rate in the selected areas. Conclusions: In this systematic review, we analyzed articles from English, Spanish and Russian language, from large databases and grey literature. PRP was in general an effective and safe treatment for degenerative LPB. Positive results were found in almost studies, a small number of adverse events were related, the risk of bias of the RCTs was low. Based on the evaluation of the included studies, we graded as level II the quality of the evidence supporting the use of PRP in LBP. Large-scale, multicenter RCTs are still needed to confirm these findings.

The COVID-19 pandemic caused much illness, many deaths, and profound disruption to society. The production of ‘safe and effective’ vaccines was a key public health target. Sadly, unprecedented high rates of adverse events have overshadowed the benefits. This two-part narrative review presents evidence for the widespread harms of novel product COVID-19 mRNA and adenovectorDNA vaccines and is novel in attempting to provide a thorough overview of harms arising from the new technology in vaccines that relied on human cells producing a foreign antigen that has evidence of pathogenicity. This first paper explores peer-reviewed data counter to the ‘safe and effective’ narrative attached to these new technologies. Spike protein pathogenicity, termed ‘spikeopathy’, whether from the SARS-CoV-2 virus or produced by vaccine gene codes, akin to a ‘synthetic virus’, is increasingly understood in terms of molecular biology and pathophysiology. Pharmacokinetic transfection through body tissues distant from the injection site by lipid-nanoparticles or viral-vector carriers means that ‘spikeopathy’ can affect many organs. The inflammatory properties of the nanoparticles used to ferry mRNA; N1-methylpseudouridine employed to prolong synthetic mRNA function; the widespread biodistribution of the mRNA and DNA codes and translated spike proteins, and autoimmunity via human production of foreign proteins, contribute to harmful effects. This paper reviews autoimmune, cardiovascular, neurological, potential oncological effects, and autopsy evidence for spikeopathy. With many gene-based therapeutic technologies planned, a re-evaluation is necessary and timely.

Acne vulgaris presents multifactorial pathogenesis, which may include insulin resistance. To investigate whether insulin resistance is a causative factor in acne vulgaris development, this cohort study and a systematic review were conducted. A cohort of 41 acne vulgaris patients and 47 healthy BMI-matched controls were recruited. Glucose and insulin fasting serum levels were obtained and the HOMA-IR was calculated; insulin resistance was diagnosed in cases with a HOMA-IR value over 2.1. The mean ± SD values for glucose fasting serum level were as follows: 94.88 ± 7.731 (mg/dL) in the study group and 79.51 ± 7.175 (mg/dL) in the controls (p < 0.001). The mean ± SD insulin fasting serum levels were 14.47 ± 6.394 (µIU/mL) and 11.83 ± 4.309 (µIU/mL) (p = 0.059), respectively. The HOMA-IR mean ± SD value calculated for the study group was 3.4 ± 1.49 and, in the control group, it was 2.34 ± 0.909 (p < 0.001). Out of 41 patients, 32 were diagnosed with insulin resistance (78%), and 26 of the 47 controls were diagnosed with IR (55%) (p = 0.026). An insulin resistance diagnosis was statistically more common among the acne patients, compared to the controls. In the articles reviewed in this paper, insulin resistance was found to be more frequent in acne vulgaris patients. Both our study and the papers analyzed in the review indicate that insulin resistance might be an independent factor in acne vulgaris development and should be considered when diagnosing and treating acne.

Exosomes have shown promising potential as a therapeutic approach for wound healing. Nevertheless, the translation from experimental studies to commercially available treatments is still lacking. To assess the current state of research in this field, a systematic review was performed involving studies conducted and published over the past five years. A PubMed search was performed for English-language, full-text available papers published from 2018 to June 2023, focusing on exosomes derived from mammalian sources and their application in wound healing, particularly those involving in vivo assays. Out of 531 results, 148 papers were selected for analysis. The findings revealed that exosome-based treatments improve wound healing by increasing angiogenesis, reepithelization, collagen deposition, and decreasing scar formation. Furthermore, there was significant variability in terms of cell sources and types, biomaterials, and administration routes under investigation, indicating the need for further research in this field. Additionally, a comparative examination encompassing diverse cellular origins, types, administration pathways, or biomaterials is imperative. Furthermore, the predominance of rodent-based animal models raises concerns, as there have been limited advancements towards more complex in vivo models and scale-up assays. These constraints underscore the substantial efforts that remain necessary before attaining commercially viable and extensively applicable therapeutic approaches using exosomes.

This paper is part II of the review on metabolism and chemical degradation of new antidiabetic drugs from glutides, gliflozins and gliptins. It is well known that metabolism data can be helpful for deriving safe levels of degradation impurities and their qualifying as far as toxicological aspects are concerned. As a result, it could link the quality of respective pharmaceutical products to clinical practice and patients. Some overlapping pathways of transformations of these important drugs of different chemical structures and different mechanisms of action were discussed. At the same time, the paper summarized interesting analytical tools for conducting modern drug metabolism as well as drug degradation experiments. The methods described here include liquid chromatography (LC) and liquid chromatography coupled with mass spectrometry (LC-MS or LC-MS/MS), which are widely used for detection and quantitative measurements of the drugs, their metabolites and degradants, as well as radiometric methods that are suitable for pharmacokinetic experiments. Special attention was paid to dedicated types of packing in chromatographic columns, as well as to special solutions in the LC-MS procedures. The present part addresses the analytical approaches elaborated for examining the metabolism and degradation pathways of gliptins that are dipeptidyl peptidase 4 (DPP-4) inhibitors.

Tumors of the parathyroid glands, when associated with PTH (parathyroid hormone) excess, display a large area of complications; in addition to the classical clinical picture of primary hyperparathyroidism (PHP), a complex panel of other symptoms/signs can be identified, including memory and cognitive impairment, chronic asthenia/fatigue, reduced muscle functionality, depressive mood, non-specific bone pain, and loss of sleep quality. The perception of quality of life (QoL) can be supplementarily enhanced by their progressive onset, which makes many patients not be fully aware of them. Their improvement was reported very early after parathyroidectomy (PTx), yet the level of statistical evidence does not qualify these non-classical elements as standalone indications for PTx. Our objective is introducing an up-to-date on QoL scores with regards to the patients diagnosed with PHP, particularly taking into consideration PHP management from baseline to post-operatory outcome, including in cases with multiple endocrine neoplasia. This is a narrative review of literature. We revised full-length papers published in English through PubMed research conducted between January 2018 and May 2023 by using the key words “quality of life” and “primary hyperparathyroidism”. We particularly looked at data on self-reported QoL (through questionnaires). We excluded from the search the studies focused on non-PTH related hypercalcemia, secondary, and/or renal/tertiary hyperparathyroidism, and vitamin D supplementation. Overall, we identified 76 papers and selected for the final analysis 16 original studies on QoL and PHP (a total of 1327 subjects diagnosed with syndromic and non-syndromic PHP). The studies with the largest number of individuals were of 92, 104, 110, 134, 159, as well as 191. A few cohorts (n = 5) were of small size (between 20 and 40 patients in each of them). Concerning the study design, except for 2 papers, all the mentioned studies provided longitudinal information, particularly the timeframe from baseline (before PTx) and after surgery. The post-operatory follow-up was of 3–6 months, but mostly between 1 and 3 years (maximum a decade of surveillance). The age of the patients varies between medians of 56, 62, 64, and 68 years. Most frequent questionnaires were SF-36, PHPQoL, and PAS. Despite not being unanimously similar, an overall reduced score of QoL in patients with PHP versus controls was registered, as well as general improvement following PTx. Variations of QoL results might have a multifactorial background from different comorbidities, studied populations, technical aspects of collecting the data, etc. QoL scores in PHP represents a complex heterogeneous picture, from their correlation with clinical features and lab assays (e.g., the level of serum calcium), the associated comorbidities (such as multiple endocrine neoplasia syndromes), up to the assessment of the QoL improvement after parathyroidectomy (PTx). While current studies do not unanimously agree on each QoL domain, the assessment of QoL might represent a supplementary argument to consider when deciding for PTx, especially in asymptomatic cases and in patients who do not fit into well-known categories of surgery candidates, according to current guidelines, thus assessing QoL in PHP is part of a current research gap. QoL evaluation in PHP remains an open issue, towards which awareness should be cultivated by both endocrinologists and surgeons. The introduction of a routine evaluation of the QoL scores in patients, as well as the selection of the most appropriate questionnaire(s), represents an open chapter thus awareness in mandatory.

The development of polymer matrices as dental drug carriers takes into account the following technological aspects of the developed formulations: the composition and the technology used to manufacture them, which affect the properties of the carriers, as well as the testing methods for assessing their behavior at application sites. The first part of this paper characterizes the methods for fabricating dental drug carriers, i.e., the solvent-casting method (SCM), lyophilization method (LM), electrospinning (ES) and 3D printing (3DP), describing the selection of technological parameters and pointing out both the advantages of using the mentioned methods and their limitations. The second part of this paper describes testing methods to study the formulation properties, including their physical and chemical, pharmaceutical, biological and in vivo evaluation. Comprehensive in vitro evaluation of carrier properties permits optimization of formulation parameters to achieve prolonged retention time in the dynamic oral environment and is essential for explaining carrier behavior during clinical evaluation, consequently enabling the selection of the optimal formulation for oral application.

Oral cavity squamous cell carcinoma (OCSCC) represents a serious health and socio-economic problem in different geographical areas of the world. It is characterized by a high rate of mortality, recurrence and metastasis. Despite the therapeutic strategies implemented for its management and resolution, currently the survival estimate for locally advanced disease is about 50%. The available therapeutic options comprise surgery and pharmacological treatment. Recently, an increased emphasis has been placed on the drugs that might be of benefit in this life-threatening disease. Therefore, the aim of this present review was to offer a general survey of the current available pharmacological treatment for OCSCC. The PubMed database was used to retrieve the papers using “OCSCC” as the search terms. We limited our search to the last 5 years to give a more updated and recent picture of the state of the art, including preclinical and clinical investigations. We found that 77 out of 201 papers were on the surgical treatment of OCSCC, 43 out of 201 focused on the radiotherapy and 81 out of 201 underwent evaluation for the aim of our review. We excluded the case reports, editorial letters, observational studies and papers written in languages other than English. A total of 12 articles were included in the final review. Our results showed that nanotechnologies use to enhance the efficacy of anticancer drugs such as: cisplatin, paclitaxel, cetuximab, EGFR antagonists, MEK1/2 and immune check inhibitors combination could have promising anti-cancer activity. However, the paucity of available data on drugs suggests the urgent need to improve the pharmacological armamentarium for OCSCC treatment.

In recent years, lung cancer prediction is an essential topic for reducing the death rate of humans. In the literature section, some papers are reviewed that reduce the accuracy level during the prediction stage. Hence, in this paper, we develop a Multi-Process Remora Optimized Hyperparameters of Convolutional Neural Network (MPROH-CNN) aimed at lung cancer prediction. The proposed technique can be utilized to detect the CT images of the human lung. The proposed technique proceeds with four phases, including pre-processing, feature extraction and classification. Initially, the databases are collected from the open-source system. After that, the collected CT images contain unwanted noise, which affects classification efficiency. So, the pre-processing techniques can be considered to remove unwanted noise from the input images, such as filtering and contrast enhancement. Following that, the essential features are extracted with the assistance of feature extraction techniques such as histogram, texture and wavelet. The extracted features are utilized to classification stage. The proposed classifier is a combination of the Remora Optimization Algorithm (ROA) and Convolutional Neural Network (CNN). In the CNN, the ROA is utilized for multi process optimization such as structure optimization and hyperparameter optimization. The proposed methodology is implemented in MATLAB and performances are evaluated by utilized performance matrices such as accuracy, precision, recall, specificity, sensitivity and F_Measure. To validate the projected approach, it is compared with the traditional techniques CNN, CNN-Particle Swarm Optimization (PSO) and CNN-Firefly Algorithm (FA), respectively. From the analysis, the proposed method achieved a 0.98 accuracy level in the lung cancer prediction.

The impact of primary arterial hypertension (HTN) in myeloproliferative neoplasms (MPNs) remains unclear, with scant literature available, mostly focusing on cardiovascular risk factors as a singular entity or on organ-specific HTN. Furthermore, available studies reporting findings on drug-induced HTN in MPNs report varying and contradictory findings. In consideration of the above, this study set out to systematically review the available literature and shed light on the occurrence of HTN in MPNs, its association with thrombosis, as well as the drugs used in MPN management that could increase blood pressure. The literature search yielded 598 potentially relevant records of which 315 remained after the duplicates (n = 283) were removed. After we screened the titles and the abstracts of these publications, we removed irrelevant papers (n = 228) and evaluated the full texts of 87 papers. Furthermore, 13 records did not meet the inclusion criteria and were excluded from the systematic review. Finally, a total of 74 manuscripts were entered into the qualitative synthesis and included in the present systematic review. Our systematic review highlights that HTN is the most common comorbidity encountered in MPNs, with an impact on both the occurrence of thrombosis and survival. Moreover, drug-induced HTN remains a challenge in the management of MPNs. Further research should investigate the characteristics of patients with MPNs and HTN, as well as clarify the contribution of HTN to the development of thrombotic complications, survival and management in MPNs. In addition, the relationship between clonal hematopoiesis of indeterminate potential, HTN, cardiovascular disease and MPNs requires examination in upcoming assessments.

Frontotemporal dementia (FTD) is a rare neurodegenerative disease, characterized by behavioral and language impairments. Primary progressive aphasia (PPA) is the linguistic variant of this heterogeneous disorder. To date, there is a lack of consensus about which interventions are effective in these patients. However, several studies show that music-based interventions are beneficial in neurological diseases. This study aims, primarily, to establish the state of the art of music-based interventions designed for PPA due to FTD and, secondarily, to inform the planning of PPA-dedicated future interventions for Italian neurological institutions. The first aim is fulfilled by a review which critically screens the neurological studies examining the effects of music- and/or rhythm-based interventions, especially, on language rehabilitation in aphasic FTD. We found that only two papers fulfilled our criteria and concerned specifically aphasic patients due to FTD. Of those, one paper reported a study conducted in an Italian institution. Most of the reviewed studies focused, instead, on aphasia in post-stroke patients. The results of our review invite further studies to investigate the role of music as a valuable support in the therapy for neurodegenerative patients with language problems and in particular to PPA due to FTD. Moreover, based on this initial work, we can delineate new music-based interventions dedicated to PPA for Italian institutions.

Background and Objectives: Insulin and oral hypoglycemic agents are drugs widely used in the world population due to their therapeutic effects on diabetes mellitus. Despite these benefits, they can also cause accidental or voluntary drug overdose. This review aims to evaluate post-mortem investigations in cases of suspected hypoglycemic drug overdose. Materials and Methods: We performed a comprehensive search using the Preferred Reporting Items for Systematic Review (PRISMA) standards; we systematically searched the PubMed, Science Direct Scopus, Google Scholar, and Excerpta Medica Database (EM-BASE) databases from the point of database inception until August 2022. The following inclusion criteria were used: (1) original research articles, (2) reviews and mini-reviews, (3) case reports/series, (4) and only papers written in English. Results: Thirty-three scientific papers, including original research articles, case reports, and case series, fulfilled the inclusion criteria. A total of 109 cases of insulin or hypoglycemic drug overdose were found. There were 71 cases of suicide (65%), 25 cases of accidental poisoning (23%), and 13 cases of homicide (12%). The most commonly used drug was insulin (95.4%). Autopsy and post-mortem examinations were performed in 84 cases, while toxicological investigations were performed in 79 cases. The most common gross findings in the autopsy were pulmonary edema (55.7%) and congestion (41.8%), while the most common histological finding was neuronal depletion or necrosis (29.1%). Conclusions: In the suspicion of death from insulin or overdose from oral hypoglycemic agents, autopsy findings may be nonspecific, and the search for injection marks can be positive at the external examination. Significant post-mortal alterations can interest biological samples and an early autopsy investigation is recommended.

Traumatic brain injury (TBI) can produce temporary biochemical imbalance due to leaks through cell membranes or disruption of the axoplasmic flow due to the misalignment of intracellular neurofilaments. If untreated, TBI can lead to Alzheimer’s, Parkinson’s, or total disability. Mild TBI (mTBI) accounts for about about 90 percent of all TBI cases. The detection of TBI as soon as it happens is crucial for successful treatment management. Neuroimaging-based tests provide only a structural and functional mapping of the brain with poor temporal resolution. Such tests may not detect mTBI. On the other hand, the electroencephalogram (EEG) provides good spatial resolution and excellent temporal resolution of the brain activities beside its portability and low cost. The objective of this paper is to provide clinicians and scientists with a one-stop source of information to quickly learn about the different technologies used for TBI detection, their advantages and limitations. Our research led us to conclude that even though EEG-based TBI detection is potentially a powerful technology, it is currently not able to detect the presence of a mTBI with high confidence. The focus of the paper is to review existing approaches and provide the reason for the unsuccessful state of EEG-based detection of mTBI.

Oral squamous cell cancer (OSCC) is the most common type of oral cancer (about 80–90% of cases) and various research is being done to cure the disease. This paper aims to verify whether treatment with no-ozone cold plasma (NCP), which is designed for safe usage of the plasma on oral cavities, in combination with gold nanoparticles conjugated with p-FAK antibody (p-FAK/GNP) can trigger the selective and instant killing of SCC-25 cells both in vitro and in vivo. When SCC25 and HaCaT cells are exposed to p-FAK/GNP+NCP, the instant cell death was observed only in SCC25 cells. Such p-FAK/GNP+NCP-mediated cell death was observed only when NCP was directly treated on SCC25 harboring p-FAK/GNP. During NCP treatment, the removal of charged particles from NCP using grounded electric mesh radically decreased the p-FAK/GNP+NCP-mediated cell death. This p-FAK/GNP+NCP-mediated selective cell death of OSCC was also observed in mice xenograft models using SCC25 cells. The mere treatment of p-FAK/GNP and NCP on the xenograft tumor slowly decreased the size of the tumor, and only about 50% of the tumor remained at the end of the experiment. On the other hand, 1 week of p-FAK/GNP+NCP treatment was enough to reduce half of the tumor size, and most of tumor tissue had vanished at the end. An analysis of isolated tissues showed that in the case of individual treatment with p-FAK/GNP or NCP, the cancer cell population was reduced due to apoptotic cell death. However, in the case of p-FAK/GNP+NCP, apoptotic cell death was unobserved, and most tissues were composed of collagen. Thus, this paper suggests the possibility of p-FAK/GNP+NCP as a new method for treating OSCC.

Numerous studies have highlighted the role of the gastrointestinal system in Parkinson disease pathogenesis. It is likely triggered by proinflammatory markers produced by specific gut bacteria. This review’s aim is to identify gut bacterial biomarkers of Parkinson disease. A comprehensive search for original research papers on gut microbiota composition in Parkinson disease was conducted using the PubMed, Embase, and Scopus databases. Research papers on intestinal permeability, nasal and oral microbiomes, and interventional studies were excluded. The yielded results were categorized into four groups: Parkinson disease vs. healthy controls; disease severity; non-motor symptoms; and clinical phenotypes. This review was conducted in accordance with the PRISMA 2020 statement. A total of 51 studies met the eligibility criteria. In the Parkinson disease vs. healthy controls group, 22 bacteria were deemed potentially important. In the disease severity category, two bacteria were distinguished. In the non-motor symptoms and clinical phenotypes categories, no distinct pathogen was identified. The studies in this review report bacteria of varying taxonomic levels, which prevents the authors from reaching a clear conclusion. Future research should follow a unified methodology in order to identify potential biomarkers for Parkinson disease.

A large volume of high-dimensional genetic data has been produced in modern medicine and biology fields. Data-driven decision-making is particularly crucial to clinical practice and relevant procedures. However, high-dimensional data in these fields increase the processing complexity and scale. Identifying representative genes and reducing the data’s dimensions is often challenging. The purpose of gene selection is to eliminate irrelevant or redundant features to reduce the computational cost and improve classification accuracy. The wrapper gene selection model is based on a feature set, which can reduce the number of features and improve classification accuracy. This paper proposes a wrapper gene selection method based on the slime mould algorithm (SMA) to solve this problem. SMA is a new algorithm with a lot of application space in the feature selection field. This paper improves the original SMA by combining the Cauchy mutation mechanism with the crossover mutation strategy based on differential evolution (DE). Then, the transfer function converts the continuous optimizer into a binary version to solve the gene selection problem. Firstly, the continuous version of the method, ISMA, is tested on 33 classical continuous optimization problems. Then, the effect of the discrete version, or BISMA, was thoroughly studied by comparing it with other gene selection methods on 14 gene expression datasets. Experimental results show that the continuous version of the algorithm achieves an optimal balance between local exploitation and global search capabilities, and the discrete version of the algorithm has the highest accuracy when selecting the least number of genes.

Background. Increased attention has been paid to the gut–brain axis recently, but little is known so far regarding how this translates into pain susceptibility. Aim. The aim of this review is to determine whether gastroenterological disorders and sleep disorders (directly or indirectly) contribute to an increased susceptibility to depression and chronic orofacial pain. Method. A search was performed in the U.S. National Library of Medicine (PubMed) database in order to find studies published before 19 December 2021. We used the following terms: gut microbiome, OR sleep quality, OR melatonin, OR GERD, OR IBS, AND: depression OR chronic pain, in different configurations. Only papers in English were selected. Given the large number of papers retrieved in the search, their findings were described and organized narratively. Results. A link exists between sleep disorders and gastroenterological disorders, which, by adversely affecting the psyche and increasing inflammation, disturb the metabolism of tryptophan and cause excessive microglial activation, leading to increased susceptibility to pain sensation and depression. Conclusions. Pain therapists should pay close attention to sleep and gastrointestinal disorders in patients with chronic pain and depression.

Background/Objectives: Endometriosis and inflammatory bowel disease (IBD) share some epidemiological, clinical and pathogenetic features. A differential diagnosis between pelvic endometriosis and IBD may be challenging, even for expert clinicians. In the present review, we aimed to summarize the currently available data regarding the relationship between endometriosis and IBD and their possible association. Methods: The PubMed and Scopus database were considered, by searching the following terms: “Crohn’s Disease”, “Ulcerative Colitis”, “Endometriosis”, “Adenomyosis”, and “Inflammatory Bowel Disease”, individually or combined. Full-text papers published in English with no date restriction were considered. Results: Few studies have researched the possible association between endometriosis and IBD. Both conditions are characterized by chronic recurrent symptoms, which may be shared (abdominal pain, fatigue, infertility, menstrual irregularities, diarrhea, constipation). Deep infiltrating endometriosis (DIE) can cause bowel symptoms. In a large Danish study, a 50% increased risk of IBD was observed in women with endometriosis. A missed diagnosis of endometriosis and an increased risk of endometriosis has been reported in IBD. Current evidence does not support an association between endometriosis and IBD characteristics. However, IBD may be associated with DIE, characterized by pelvic symptoms (dyschezia, dyspareunia). Preliminary observations suggest an increased IBD risk in patients with endometriosis treated with hormonal therapy. Conclusions: Current findings suggest that a careful search is needed for concomitant endometriosis in subgroups of patients with IBD showing compatible symptoms and vice versa. A multidisciplinary approach including dedicated gastroenterologists and gynecologists is required for a proper search for IBD and endometriosis in subgroups of patients. This approach may avoid diagnostic delays or overtreatments for these conditions.

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.

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.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common inflammatory disorder whose complex immunopathogenesis has yet to be fully elucidated. Endotype-2 CRSwNP is the most common form of disease where eosinophils are the main drivers of inflammation. Traditional treatments for CRSwNP have centered around intranasal or systemic corticosteroids and endoscopic sinus surgery (ESS). However, recent advancements in targeted therapies have introduced novel biological agents that specifically target key inflammatory mediators such as IL-4, IL-5, and IL-13. These biologics offer promising options for patients with CRSwNP, particularly those who do not respond adequately to conventional treatments. Nonetheless, some patients do not satisfactorily respond to these drugs because of an insufficient blockade of the inflammatory process. The mast cell (MC) is another important (and somehow neglected) actor in the pathogenesis of CRSwNP, and the latest clinical and translational evidence in this field has been reviewed in the present paper.

Hypoxia represents the temporary or longer-term decrease or deprivation of oxygen in organs, tissues, and cells after oxygen supply drops or its excessive consumption. Hypoxia can be (para)-physiological—adaptive—or pathological. Thereby, the mechanisms of hypoxia have many implications, such as in adaptive processes of normal cells, but to the survival of neoplastic ones, too. Ischemia differs from hypoxia as it means a transient or permanent interruption or reduction of the blood supply in a given region or tissue and consequently a poor provision with oxygen and energetic substratum-inflammation and oxidative stress damages generating factors. Considering the implications of hypoxia on nerve tissue cells that go through different ischemic processes, in this paper, we will detail the molecular mechanisms by which such structures feel and adapt to hypoxia. We will present the hypoxic mechanisms and changes in the CNS. Also, we aimed to evaluate acute, subacute, and chronic central nervous hypoxic-ischemic changes, hoping to understand better and systematize some neuro-muscular recovery methods necessary to regain individual independence. To establish the link between CNS hypoxia, ischemic-lesional mechanisms, and neuro-motor and related recovery, we performed a systematic literature review following the” Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA”) filtering method by interrogating five international medical renown databases, using, contextually, specific keywords combinations/”syntaxes”, with supplementation of the afferent documentation through an amount of freely discovered, also contributive, bibliographic resources. As a result, 45 papers were eligible according to the PRISMA-inspired selection approach, thus covering information on both: intimate/molecular path-physiological specific mechanisms and, respectively, consequent clinical conditions. Such a systematic process is meant to help us construct an article structure skeleton giving a primary objective input about the assembly of the literature background to be approached, summarised, and synthesized. The afferent contextual search (by keywords combination/syntaxes) we have fulfilled considerably reduced the number of obtained articles. We consider this systematic literature review is warranted as hypoxia’s mechanisms have opened new perspectives for understanding ischemic changes in the CNS neuraxis tissue/cells, starting at the intracellular level and continuing with experimental research to recover the consequent clinical-functional deficits better.

Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are some of the biggest public health challenges due to their spread and increasing incidence around the world. NAFLD is characterized by intrahepatic lipid deposition, accompanied by dyslipidemia, hypertension, and insulin resistance, leading to more serious complications. Among the various causes, drug administration for the treatment of numerous kinds of diseases, such as antiarrhythmic and antihypertensive drugs, promotes the onset and progression of steatosis, causing drug-induced hepatic steatosis (DIHS). Here, we reviewed in detail the major classes of drugs that cause DIHS and the specific molecular mechanisms involved in these processes. Eight classes of drugs, among the most used for the treatment of common pathologies, were considered. The most diffused mechanism whereby drugs can induce NAFLD/NASH is interfering with mitochondrial activity, inhibiting fatty acid oxidation, but other pathways involved in lipid homeostasis are also affected. PubMed research was performed to obtain significant papers published up to November 2021. The key words included the class of drugs, or the specific compound, combined with steatosis, nonalcoholic steatohepatitis, fibrosis, fatty liver and hepatic lipid deposition. Additional information was found in the citations listed in other papers, when they were not displayed in the original search.

Cisplatin is one of the most widely used chemotherapeutic drugs in the treatment of a wide range of pediatric and adult malignances. However, it has various side effects which limit its use. Cisplatin mouse models are widely used in studies investigating cisplatin therapeutic and toxic effects. However, despite numerous promising results, no significant improvement in treatment outcome has been achieved in humans. There are many drawbacks in the currently used cisplatin protocols in mice. In the paper, the most characterized cisplatin protocols are summarized together with weaknesses that need to be improved in future studies, including hydration and supportive care. As demonstrated, mice respond to cisplatin treatment in similar ways to humans. The paper thus aims to illustrate the complexity of cisplatin side effects (nephrotoxicity, gastrointestinal toxicity, neurotoxicity, ototoxicity and myelotoxicity) and the interconnectedness and interdependence of pathomechanisms among tissues and organs in a dose- and time-dependent manner. The paper offers knowledge that can help design future studies more efficiently and interpret study outcomes more critically. If we want to understand molecular mechanisms and find therapeutic agents that would have a potential benefit in clinics, we need to change our approach and start to treat animals as patients and not as tools.

(1) Background: Long-term health effects after SARS-CoV-2 infections can manifest in a plethora of symptoms, significantly impacting the quality of life of affected individuals. (2) Aim: The present paper aimed to assess the effects of an individualized and controlled exercise intervention on fatigue and exercise capacity among Long-COVID (LC) patients in an ambulatory setting. (3) Methods: Forty-one (n = 41) LC patients performed an exercise protocol with an individualized control of the patients’ training intensity during the study period based on the individual’s ability to achieve the target criteria. The program was carried out two to three times a week, each session lasted 30 min, and the study parameters were recorded at the beginning of the program, as well as after 6 and 12 weeks, respectively. These included both patient-reported (PCFS questionnaire, FACIT–Fatigue questionnaire) and objective (one-minute sit-to-stand test (1MSTST), workload) outcomes. (4) Results: The exercise training intervention resulted in significant improvements in the FACIT–Fatigue (F(2, 80) = 18.08, p < 0.001), 1MSTST (χ2(2) = 19.35, p < 0.001) and workload scores (χ2(2) = 62.27, p < 0.001), while the PCFS scores remained unchanged. Changes in the workload scores were dependent on the frequency of the completed exercise sessions and were higher in the LC patients with a moderate Post COVID Syndrome Score (PCS) compared to a severe PCS. (5) Conclusions: The individualized and controlled training approach demonstrated efficacy in reducing fatigue and enhancing exercise capacity among outpatient LC patients. However, for complete regeneration, a longer, possibly indefinite, treatment is required, which in practice would be feasible within the framework of legislation.

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.

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.