The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

Background: biophysical stimulation therapy, and in particular Pulsed Electromagnetic Fields (PEMFs) and capacitively coupled electric fields (CCEFs) has significantly increased in the last twenty years. For this, it is necessary to have clear information regarding the efficacy, the therapeutic indication and the expected objectives. Methods: we conducted a narrative review taking into consideration different types of studies with different areas of application. The objective was to take into consideration and analyze the different fields of use and the relevant information present in the literature. Results: There is unanimous opinion regarding the usefulness of applying biophysical therapy on the bone compartment both in terms of the tissue healing process and the symptoms associated with this situation. Differently, but no less importantly, in the joint compartment positive opinions were observed mainly on the inflammatory and catabolic process, however, at present,we did not report evidence regarding cartilaginous tissue regeneration. Conclusion: the effectiveness of PEMFs and CCEFs on the bone healing process in the Orthopedic and Traumatology fields is consolidated evidence in the literature. We have also found positive results on symptoms and patient compliance with rehabilitation therapies. Therefore, notable application can be envisaged in the fields of Prosthetic Surgery and Sports Medicine.

Antisense oligonucleotide (ASO)-mediated exon skipping has become a valuable tool for investigating gene function and developing gene therapy. Machine learning-based computational methods such as eSkip-Finder have been developed to predict the efficacy of ASOs via exon skipping. However, these methods are computationally demanding, and the accuracy of predictions remains suboptimal. In this study, we propose a new approach to reduce computational burden and improve prediction performance by using feature selection within machine learning algorithms and ensemble learning techniques. We evaluated our approach using a dataset of experimentally validated exon skipping events, dividing it into training and testing sets. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. Our findings suggest that our approach has the potential to enhance the accuracy and efficiency of predicting ASO efficacy via exon skipping. It could also facilitate the development of novel therapeutic strategies. This study could contribute to the ongoing efforts to improve ASO design and optimize gene therapy approaches.

The extracellular matrix (ECM) is earning an increasingly relevant role in many disease states and the process of aging. Analyzing these disease states is possible with GWAS and PheWAS methodology, and through our analysis, we aimed to explore the relationships between polymorphisms in the compendium of ECM genes (i.e., matrisome genes) in various disease states. A significant contribution on the part of the ECM polymorphisms is evident in many varying types of diseases, particularly those in the core matrisome genes. Our results confirm previous links to connective tissue disorders, but also unearth new and underexplored relationships with neurological, psychiatric, and age-related disease states. Upon analysis of drug indications for gene-disease relationships, we identified numerous targets that may be repurposed for age-related pathology. The identification of ECM polymorphisms and their contribution to disease plays an integral role in future therapeutic developments, drug repurposing, precision medicine, and personalized care.

Antisense oligonucleotide (ASO)-mediated exon skipping has emerged as a powerful tool for examining the function of genes and exons in basic research, as well as gene therapy. Computational methods, such as eSkip-Finder, have been developed to predict the efficacy of ASOs via exon skipping using machine learning. However, these methods can be computationally demanding and the prediction accuracy of the tool is not yet optimal. In this study, we propose an approach to reduce computational burden and improve prediction performance by utilizing feature selection within machine learning algorithms and employing ensemble learning techniques. The method was evaluated using a dataset of genes with experimentally validated exon skipping events. The dataset was divided into training and testing sets to assess the accuracy of the algorithm. Our results demonstrate that using a 3-way voting approach with random forest, gradient boosting, and XGBoost can significantly reduce computation time to under ten seconds while improving prediction performance, as measured by R2 for both 2’-O-methyl nucleotides (2OMe) and phosphorodiamidate morpholino oligomers (PMOs). Additionally, the feature importance ranking derived from our approach is in good agreement with previously published results. These findings suggest that this approach has the potential to enhance the efficiency and accuracy of predicting ASO efficacy via exon skipping, facilitating the development of novel therapeutic strategies.

We are all similar, but a bit different. These differences are partially due to variations in our genomes and are related to the heterogeneity of symptoms and responses to treatments that patients exhibit. Most animal studies are performed in one single strain with one manipulation. However, due to the lack of variability, therapies are not always reproducible when treatments are translated to humans. Panels of already sequenced organisms are valuable tools for mimicking human phenotypic heterogeneities and gene mapping. This review summarizes the current knowledge of mouse, fly and yeast panels with insightful applications for translational research.

In this perspective, we identify emerging frontiers in clinical and basic research of melanocyte biology and its associated biomedical disciplines. We describe challenges and opportunities in clinical and basic research of normal and diseased melanocytes that impact current approaches to research in melanoma and the dermatological sciences. We focus on four themes: (1) clinical melanoma research, (2) basic melanoma research, (3) clinical dermatology, and (4) basic pigment cell research, with the goal of outlining current highlights, challenges, and frontiers associated with pigmentation and melanocyte biology.

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

Breast implant surgery has evolved significantly, yet challenges such as capsular contracture remain a persistent concern. This review presents an in-depth analysis of recent advancements in understanding the immune mechanisms and clinical implications associated with breast implants. The article systematically examines the complex interplay between immune responses and capsular fibrosis, emphasizing the pathophysiological mechanisms of inflammation in the etiology of this fibrotic response. It discusses innovations in biomaterial science, including the development of novel anti-biofilm coatings and immunomodulatory surfaces designed to enhance implant integration and minimize complications. Emphasis is placed on personalized risk assessment strategies, leveraging molecular insights to tailor interventions and improve patient outcomes. Emerging therapeutic targets, advancements in surgical techniques, and the refinement of post-operative care are also explored. Despite notable progress, challenges such as variability in immune responses, long-term efficacy of new interventions, and ethical considerations remain. Future research directions are identified, focusing on personalized medicine, advanced biomaterials, and bridging preclinical findings with clinical applications. As we advance from bench to bedside, this review illuminates the path forward, where interdisciplinary collaboration and continued inquiry weave together to enhance the art and science of breast implant surgery, transforming patient care into a realm of precision and excellence.

Phage therapy, the use of bacteriophages (phages) to treat bacterial infections, is regaining momentum as a promising weapon against the rising threat of multidrug-resistant (MDR) bacteria. This comprehensive review explores the historical context, the modern resurgence of phage therapy, and phage-facilitated advancements in medical and technological fields. It details the mechanisms of action and applications of phages in treating MDR bacterial infections, particularly those associated with biofilms and intracellular pathogens. The review further highlights innovative uses of phages in vaccine development, cancer therapy, and as gene delivery vectors. Despite its targeted and efficient approach, phage therapy faces challenges related to phage stability, immune response, and regulatory approval. By examining these areas in detail, this review underscores the immense potential and remaining hurdles in integrating phage-based therapies into modern medical practices.

The integration of genetic technologies into neurological diagnostics has significantly enhanced our ability to understand and manage neurological disorders. This article discusses the functional analysis of key genetic tests, including microarray analysis, variant sequencing, exome sequencing, RNA sequencing, and whole genome sequencing. Each of these technologies offers unique advantages and challenges, providing a comprehensive toolkit for diagnosing and understanding the genetic basis of neurological conditions. The functional insights gained from these tests not only detect genetic abnormalities but also elucidate their functional consequences, aiding in the diagnosis, prognosis, and management of neurological disorders. As these technologies continue to evolve, they are expected to play an increasingly important role in the field of neurological diagnostics, paving the way for personalized medicine and improved patient outcomes.

Corneal diseases are the third leading cause of blindness worldwide. There are numerous causes of corneal blindness, and the common treatment for this condition often involves corneal tissue transplantation, such as Descemet's Membrane Endothelial Keratoplasty (DMEK). DMEK has been established as the preferred surgical technique for the treatment of corneal endothelial disorders. The success of DMEK depends largely on the quality of the donor endothelial cells and the trans-plantation procedure. However, the scarcity of suitable donor tissue and the sensitivity of endo-thelial cells pose a major challenge. In recent years, tissue engineering has attracted attention as potential solutions to these problems. This review offers an outline of the current landscape of DMEK in the context of bioengineering, exploring various methodologies, advancements, and fu-ture prospects.

The massive amount of human biological, imaging and clinical data produced by multiple and diverse sources, necessitates integrative modeling approaches able to summarize all this information into answers to specific clinical questions. In this paper, we present a hypermodeling scheme able to combine models of diverse cancer aspects regardless of their underlying method or scale. Describing tissue-scale cancer cell proliferation, biomechanical tumor growth, nutrient transport, genomic-scale aberrant cancer cell metabolism, and cell signaling pathways that regulate the cellular response to therapy, the hypermodel integrates mutation, miRNA expression, imaging, and clinical data. The constituting hypomodels as well as their orchestration and links are described. Two specific cancer types, Wilms tumor (nephroblastoma) and non-small cell lung cancer, are addressed as proof of concept study cases. Personalized simulations over the actual anatomy of a patient have been carried out. The hypermodel has also applied to predict tumor control after radiotherapy and the relationship between tumor proliferative activity and response to neoadjuvant chemotherapy. Our innovative hypermodel holds promise as a digital twin based clinical decision support system and the core of future in silico trial platforms, although additional retrospective adaptation and validation is necessary.

The growing dependence on large language models (LLM)s highlights the urgent need to deepen trust in these technologies. Regular, rigorous validation of their expertise, especially in nuanced and intricate scenarios, is essential to ensure their readiness for clinical applications. Our study pioneers the exploration of LLM utility in the field of cardiology. We stand at the cusp of a transformative era where mature AI and LLMs, notably ChatGPT, GPT-4, and Google Bard, are poised to influence healthcare significantly. Recently, we put three available LLMs, OpenAI's ChatGPT-3.5, GPT-4.0, and Google's Bard, to the test against a significant Polish medical special-ization licensing exam (PES). The exams cover the scope of completed specialist training, focusing on diagnostic and therapeutic procedures, excluding invasive medical procedures and interven-tions. In our analysis, GPT-4 consistently outperformed the others, ranking first, with and Google Bard and ChatGPT- 3.5 following, respectively. The performance metrics underscore GPT-4's no-table potential in medical applications. Given a score improvement of over 23.5 % between two AI models released just four months apart, clinicians must stay informed and up-to-date about these rapidly evolving tools and their potential applications to clinical practice. Our results provide a snapshot of the current capabilities of these models, highlighting the nuanced performance dif-ferences when confronted with identical questions

The psychedelic renaissance has reignited interest in the therapeutic potential of psychedelics for mental health and well-being. An emerging area of interest is the potential modulation of psychedelic effects by the gut microbiome - the ecosystem of microorganisms residing in our digestive tract. This review explores the intersection of the gut microbiome and psychedelic therapy, underlining potential implications for personalized medicine and mental health. We delve into the current understanding of the gut-brain axis, its influence on mood, cognition, and behavior, and how the microbiome may affect the metabolism and bioavailability of psychedelic substances. We also discuss the role of microbiome variations in shaping individual responses to psychedelics, along with potential risks and benefits. Moreover, we consider the prospect of microbiome-targeted interventions as a fresh approach to boost or modulate psychedelic therapy's effectiveness. By synthesizing insights from the fields of psychopharmacology, microbiology, and neuroscience, our objective is to advance knowledge about the intricate relationship between the microbiome and psychedelic substances, thereby paving the way for novel strategies to optimize mental health outcomes amid the ongoing psychedelic renaissance.

Age-related macular degeneration (AMD) is a complex multifactorial disease and the primary cause of legal and irreversible blindness among individuals aged >=65 years in developed countries. Globally, it affects 30-50 million individuals, with an estimated increase of approximately 200 million by 2020 and approximately 300 million by 2040. Currently, the neovascular form may be able to be treated with the use of anti-VEGF drugs, while no effective treatments are available for the dry form. Many observational studies, such as AREDS-1 and AREDS 2, have shown a potential role of micronutrient supplementation in lowering the risk of progression of the early stages of AMD. Recently, low-grade inflammation, sustained by dysbiosis and a leaky gut, has been shown to contribute to the development of AMD. Given the ascertained influence of the gut microbiota in systemic low-grade inflammation and its potential modulation by macro- and micro-nutrients, a potential role of diet in AMD has been proposed. This review discusses the role of the gut microbiota in the development of AMD. Using PubMed, Web of Science and Scopus, we searched for recent scientific evidence discussing the impact of dietary habits (high fat and high glucose or fructose diets), micronutrients (vitamins C, E, and D, zinc, beta-carotene, lutein and zeaxanthin) and omega-3 fatty acids on the modulation of the gut microbiota and their relationship with AMD risk and progression.

Stroke remains a major cause of death and disability in the United States and around the world. Solid safety and efficacy profiles of novel stroke therapeutics have been generated in the laboratory, but most failed in clinical trials. Investigations into the pathology and treatment of the disease remain a key research endeavor in advancing scientific understanding and clinical applications. In particular, cell-based regenerative medicine, specifically stem cells transplantation, may hold promise as stroke therapy because grafted cells and their components may recapitulate the growth and function of the neurovascular unit, which arguably represents the alpha and omega of stroke brain pathology and recovery. Recent evidence has implicated mitochondria, organelles with a central role in energy metabolism and stress response, in stroke progression. Recognizing that stem cells offer a source of healthy mitochondria, potentially transferrable into ischemic cells, may provide a new therapeutic tool. To this end, deciphering cellular and molecular processes underlying dysfunctional mitochondria may reveal innovative strategies for stroke therapy. Here, we review recent studies capturing the intimate participation of mitochondrial impairment in stroke pathology, and showcase promising methods of healthy mitochondria transfer into ischemic cells, to critically evaluate the potential of mitochondria-based stem cell therapy for stroke.

The optical complexity of coastal waters is mostly caused by the water discharged from land carrying optical components (such as dissolved and particulate matter) into coastal bays and estuaries, and increasing the attenuation of light. This paper aims to investigate the links between in-water optical properties in four Swedish bays (from the northern Baltic proper up to the Bothnian bay) and the land use and land cover (LULC) and the hydrology in the respective catchment of each bay. The optical properties were measured in situ over the last two decades by various research and monitoring groups while the LULC in each bay was classified using the Copernicus Land Monitoring Service based on Landsat 8 and Sentinel-3 data. The absorption coefficient of coloured dissolve organic matter at 440 nm, aCDOM (440), and its spectral slope factor, SCDOM, were mostly correlated to natural land cover classes (Wetland, Meadow) acting as sources of CDOM, while Agricultural and Urban classes seem to act as sinks. The Agricultural class was also found to be a sink for suspended particulate organic matter (SPOM) whilst Coniferous and Mixed Forests as well as Meadows acted as a sources. SPOM seems to mostly originate from Natural classes, possibly due to the release of pollen and other organic matter. Overall, the methods applied here allow for a better understanding of effects of land used and land cover on the bio-optical properties, and thus coastal water quality, on a macroscopic scale.

Critical and progressive cachexia may be observed in numerous medical disciplines, but in patients with various diseases several pathways overlap (endocrine, inflammatory and kidney diseases, heart failure, cancer). A case-control analysis is presented of patients with initial immune-mediated thyroiditis complicated with cachexia, pulmonary pa-thology coexisting with opportunistic infection, finally diagnosed cancer (thyroid cancer, misdiagnosed as NSCLC). Contrary to other patients with lung cancer the presented pa-tients were not active smokers, exclusively women who developed cachexia with existing autoimmune process in the first phase. Furthermore, coexistence of short overall survival without cancer progression in the most seriously ill patients, correlation with sex (con-trary to history of smoking) and predisposition to mycobacterial disease are very sug-gestive. The unique sequence shed light on immune-mediated thyroid disease as a sub-clinical paraneoplastic process modified by various therapeutic regimens, however, with systemic consequences and a sequel, requiring holistic approach. Differential diagnosis of severe cachexia, adenocarcinoma with pulmonary localization and tuberculosis reac-tivation require analysis of immunological and genetic background. Contrary to highly specialized teams (e.g. lung cancer units) the immunotherapy and general medicine in aging populations require multidisciplinary observation, holistic and inquiring approach. Lack of differentiation, confusing bias as well as discrepancy in literature are the main obstacles in statistical research, that indicate correlation of common factors only. Such time-lapse case studies may be first to build evidence of a pathway and association be-tween immune parameters, comorbidity and cancer.

Solanum indicum Linn, is commonly known as Indian Nightshade or Poison Berry belongs to the family Solanaceae. This review studied the botanical description, traditional uses of its seeds, its chemical composition, pharmacological properties and modern applications in medicinal system. The plant is rich in alkaloids, steroidal saponins, flavonoids and phenolic acids having diverse pharmacological activities and phytochemical profile. It is used in treatment of various respiratory disorders, inflammation, skin problems and gastrointestinal disease since ancient times. Scientific research in modern times also tested many of the traditional uses revealing anti-inflammatory, antioxidant, antimicrobial activities as well as some cytotoxic and even antidiabetic effects. These pharmacological activities show potential future as uses for organic drugs, natural health products, skincare formulations and agricultural advancements.

Background: Studies have tried to identify predictors of functional markers of keratoconus progression, whereas structural outcomes of collagen cross-linking have not been properly investigated. Objective: find and set up a combination of diagnostic modalities and measurements to reliably reflect CXL efficiency. Material and methods: We retrospectively reviewed the medical histories of 107 KC patients (131 eyes) who underwent CXL in a medical center from January 2018 to December 2022. The dataset included preoperative examinations and follow-up results, which provided a total of 796 observations. The cases of other corneal diseases, repeated CXL, pregnancy, and observations without follow-up examinations were excluded. Results: The study findings revealed a significant drop in the central and corneal thickness during 14.01±9.98 months of observations. Linear and polynomial equations suggested different trends in pachymetry change after CXL. The linear model showed corneal thinning, and according to the polynomials, pachymetry findings return to baseline values two years after CXL. Conclusion: The most reliable prognosis of postoperative corneal thickness is achieved with the models trained on keratometry readings and topography indices. BAD indices are also reliable predictors of the corneal thickness after CXL. A combination of the aforementioned structural parameters and their derivatives can reliably predict CXL efficiency.

The aging of the global population has increased the prevalence of neurodegenerative conditions. Bacopa monnieri (BM), an herb with active compounds, such as bacosides A and B, betulinic acid, loliolide, asiatic acid, and quercetin, demonstrates the potential for brain health. Limited research has been conducted on the therapeutic applications of BM in neurodegenerative conditions. This systematic review aims to project BM's beneficial role in brain disorders. BM has anti-apoptotic and antioxidant actions and can repair damaged neurons, stimulate kinase activity, restore synaptic function, improve nerve transmission, and increase neuroprotection. The included twenty-two clinical trials demonstrated that BM can reduce Nuclear Factor-κB phosphorylation, improve emotional function, cognitive functions, anhedonia, hyperactivity, sleep routine, depression, attention deficit, learning problems, memory retention, impulsivity, and psychiatric problems. Moreover, BM can reduce the levels of pro-inflammatory biomarkers and oxidative stress. Here, we highlight that BM provides notable therapeutic benefits and can serve as a complementary approach for the care of patients with neurodegenerative conditions associated with brain disorders. This review adds to the growing interest in natural products and their potential therapeutic applications by improving our understanding of the mechanisms underlying cognitive function and neurodegeneration and informing the development of new therapeutic strategies for neurodegenerative diseases.

The 2022-2023 Mpox multi-country outbreak, identified in over 110 WHO Member States, revealed a predominant impact on cisgender men, particularly those engaging in sex with men, while less frequently affecting women. This disparity prompted a focused investigation into the gender-specific characteristics of Mpox infections, particularly among women, to address a notable knowledge gap. This review systematically gathers and analyzes scientific literature and case reports concerning Mpox infections in women, covering a broad geographical spectrum including regions such as Buenos Aires, Brazil, Northern California, Colombia, Nigeria, Europe, Vietnam, Spain, Switzerland, and the United States. The analysis delves into various aspects of Mpox in women, including clinical features, epidemiology, psychological impacts, preparedness strategies, and case studies, with particular attention to pregnant women and those with underlying health conditions. Empirical data from multiple studies underscore the unique epidemiological and clinical patterns of Mpox in women. In the United States, a small percentage of Mpox cases were reported among cisgender women, with a notable portion involving non-Hispanic Black or African American, non-Hispanic White, and Hispanic or Latino ethnicities. The primary transmission route was identified as sexual or close intimate contact, with the virus predominantly manifesting on the legs, arms, and genital areas. Further, a study in Spain highlighted significant disparities in diagnosis delays, transmission modes, and clinical manifestations between genders, indicating a different risk profile and disease progression in women. Additionally, a case from Vietnam linked to a new Mpox sublineage in women emphasizes the role of women in the transmission dynamics and the importance of genomic monitoring. This review emphasizes the necessity for inclusive surveillance and research to fully understand Mpox dynamics across diverse population groups, including women. Highlighting gender and sexual orientation in public health responses is crucial for an effective approach to managing the spread and impact of the disease. The findings advocate for a gender-diverse assessment in health services and further research to explore the nuances of Mpox transmission, behavior, and progression among different groups, thereby enhancing the global response to Mpox and similar public health challenges.

The fresh bulbs of Stenomesson miniatum, a plant belonging to Amaryllidaceae family with a poorly investigated phytochemical profile, were traditionally employed by Andean healers to treat tumors and abscesses. The aims of this study were to characterize the alkaloid extract from the bulbs of S. miniatum and test its cytotoxic and antibacterial potential. The alkaloid extract was characterized by dereplication using various techniques (CPC, NMR, UPLC-HRMS) and referring to in-home or online databases for spectroscopic data matching. Cytotoxic activities were evaluated on A431 human epidermoid carcinoma cells through a metabolic assay, and on Jurkat human acute T-leukemia cells through a cell-impermeant fluorescent nuclear probe. Antibacterial assays were carried out against Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes by using a standardized microdilution broth method 96-well plate. Eleven known Amaryllidaceae alkaloids were identified together with another compound determined as being an extraction artefact. The alkaloid extract showed good cytotoxic activity against both the tumor cell lines, reaching an IC50 of 3.3 µg/mL against A431 cells and of 10.9 µg/mL against Jurkat cells. The analysis of the fractions allowed the activity to be attributed to the presence of pretazettine and haemathamine. Conversely, no antibacterial activities were recorded for any of the samples.

Additionally, the League’s four observing states, with an additional population of 1.7 billion, if join the group, will form the world’s largest consortium to enhance the accessibility of biotechnology drugs. This effort will also remove the criticism of regulatory agencies that are well-equipped to regulate these products. This should also be a significant economic incentive to consortium states to develop these products, particularly biosimilars, to capture the most critical market anticipated. This plan will also reduce the cost burden on regulatory agencies. The program is divided into two classifications; for products sold in any of the Stringent Regulatory Authority (SRA) states, the registration is automatic but with several requirements that assure ongoing pharmacovigilance; this also applies to copies of reference products or biosimilars. For non-SRA sourcing, a stepwise plan requiring a rapporteur review, as practiced by the EMA and a third-party cGMP audit, is necessary to ensure data and product integrity. However, to reduce the cost burden, approval of these products is based on current scientific findings as presented in this paper.

Adult neural stem and progenitor cells (NSPCs) contribute to learning, memory, maintenance of homeostasis, energy metabolism and many other essential processes. They are highly heterogeneous populations that require input from a regionally distinct microenvironment including a mix of neurons, oligodendrocytes, astrocytes, ependymal cells, NG2+ glia, vasculature, cerebrospinal fluid (CSF), and others. The diversity of NSPCs is present in all three major parts of the CNS, i.e., the brain, spinal cord, and retina. Intrinsic and extrinsic signals, e.g., neurotrophic and growth factors, master transcription factors, and mechanical properties of the extracellular matrix (ECM), collectively regulate activities and characteristics of NSPCs: quiescence/survival, proliferation, migration, differentiation, and integration. This review discusses the heterogeneous NSPC populations in the normal physiology and highlights their potentials and roles in injured/diseased states for regenerative medicine.

In this article, two elliptical-ovel-shaped cylindrical dielectric resonator based wideband Graphene inspired reconfigurable metasurface absorber is designed on diffused quartz substrate having a relative permittivity of 3.75 and conductivity 2200Kg/m3 with height of 25μm. This metasurface having gold plated ground in microstrip with 5μm which is essential by calculating skin depth at 2.0THz frequency. Two elliptical ovel shaped patches with Graphene plated having built in potential varies 0-2.5eV and relaxation time 1.0ps at 290oK. By changing the relaxation time of Graphene 0.1ps-0.3ps its resonance frequency also varies i.e., reconfigurable property they provide without adding any active i.e., PIN diode components. The proposed MS is designed having a dimension of 100×100μm2 is designed on a microstrip. This MS works in the range of 1.6-2.38THz having more than 90% absorbance with two transmission zero at 2.1THz and 2.3THz having high Q ˃ 50 which is used to determine the sensitivity where the proposed MS used as a sensor to determine hemoglobin (Blood Glucose level) and urine (Uric acid) by changing their refractive index from 1.34-1.43. Maximum sensitivity achieved at 2000GHz/RIU and average sensitivity for hemoglobin and urine sensing achieved 833.33GHz/RIU, FOM-8.33 and 4277.7733GHz/RIU, FOM-555.55 respectively.

A Wireless Body Area Sensor Network (WBASN) is combination of numerous sense nodes, positioned onto/close or inside a person body. Wireless Body Area Sensor Networks (WBASN) is a developing automation trend that exploits wireless sensor nodes to put instantaneous wearable well-being of ill person to improve individual’s existence. The sensor nodes might be used outwardly to observe abundant health parameters (like heart activity, blood pressure and cholesterol) of an ill person at a vital site within hospital. Hence the goal of WBASN is much crucial, enhancing the lifetime of nodes is compulsory to sustain many issues such as utility and efficiency. It is essential to evaluate time that when the first node will die it we want to refresh or change the battery reason is that loss of crucial information is not tolerable. The lifetime is termed as the time interval when a first node dies out due to battery exhaustion. In our proposed protocol life time of a network is the main concern as well other protocol related issues such as throughput, path loss, and residual energy. Bio-sensors are used for deployment on human body. Poisson distribution and equilibrium model techniques have been used for attaining the required results. Multi-hop network topology and random network node deployment used to achieve minimum energy consumption and longer network lifetime.

CAR-T cell therapy has emerged as a groundbreaking approach in cancer treatment, leveraging the immune system to target and eliminate cancer cells. While currently focused on hematologic malignancies, the future holds promise for expanding CAR-T cell therapy to diverse cancers, enhancing its efficacy, and improving safety profiles. Recent advances in tumor immunology have propelled CAR-T cell therapy as a game-changer in treating diseases such as relapsed/refractory B-cell acute lymphocytic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and multiple myeloma (MM). Six CAR-T cell products have received FDA approval for treating R/R B cell malignancies. However, challenges persist, including complications like cytokine release syndrome (CRS), coagulopathy, and cytopenias. Strategies to mitigate these complications involve targeting distinct antigens with dual- or multi-targeted CAR-T cells and enhancing immunogenicity. Additionally, γδ CAR-T cells show promise in recognizing antigen- negative leukemia cells in an MHC-independent manner while reducing the risk of inducing graft-versus-host disease (GVHD). As CAR-T cell therapy continues to evolve through innovation and discovery, it holds the potential to revolutionize cancer treatment, offering new hope to patients and reshaping the landscape of oncology with its precision and efficacy.

On April 17, 2019, a coach with tourists from Germany crashed in Madeira requiring repatriation by the German Air Force. The Advance Trauma Life Support (ATLS) concept was the central component of patient care. Data in Madeira were collected through a structured interview. The analysis of the Aeromedical Evacuation was based on intensive care transport records. In Germany all available were reviewed for data collection. Quality of life (HRQoL) was evaluated by the 12-item Short-Form Health Survey (SF-12). Twenty-eight prehospital patients were transported to the Level III Trauma Center in Funchal (Madeira). Five operative procedures were performed. Fifteen patients were eligible for Aeromedical Evacuation (AE). In the second hospital phase in Germany in total 82 radiological images and nine operations were performed. Hospital stay lasted 11 days (median, IQR 10–18). Median Follow-up (14 of 15 patients) was 16 months (IQR 16–21). 80% (8 out of 10) showed an increased risk for post-traumatic stress disorder (PTSD). Six key findings were identified in this study: divergent injury classification, impact of AE mission on health status, lack of communication, need of PTSD prophylaxis, patient identification, media coverage. Those findings may improve AE missions in the future e.g. required after armed conflicts.

Three-dimensional convolutional neural networks (3D CNN) as a type of artificial intelligence (AI) are powerful in image processing and recognition using deep learning to perform generative and descriptive tasks. The advantage of CNN compared to its predecessors is that it automatically detects the important features without any human supervision. 3D CNN are used to extract features in three dimensions where input is a 3D volume or a sequence of 2D pictures e.g., slices in a cone-beam computer tomography scan (CBCT). The main aim of this article was to bridge interdisciplinary cooperation between forensic medical experts and deep learning engineers. With emphasis activating clinical forensic experts in the field with possibly basic knowledge of advanced artificial intelligence techniques with interest in its implementation in their efforts to advance the forensic research further. This paper introduces a novel workflow of 3D CNN analysis of full-head CBCT scans. Authors explore and present 3D CNN method for forensic research design concept in five perspectives: (1) sex determination, (2) biological age estimation, (3) 3D cephalometric landmark annotation, (4) growth vectors prediction, (5) facial soft-tissue estimation from the skull and vice versa. In conclusion, 3D CNN application can be a watershed moment in forensic medicine, leading to unprecedented improvement of forensic analysis workflows based on 3D neural networks.

The objective of the this study was to reduce the benzo[a]pyrene-induced hepatotoxicity method in herbal medicine products and to give proof that neferine, daidzein, genistein possess antihepa-totoxic effects. B[a]P which classified as a group 1 carcinogen and metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) causes mutagenic DNA addition products. The reduc-tion of BPDE-DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE) was derived by benzo[a]pyrene (B[a]P). In HepG2 cells, B[a]P exhibited toxicity and substance treatment of the cells with B[a]P with neferine in lotus and daidzein, genistein in soybean reduced the BPDE-DNA ad-ducts level. The level of B[a]P-metabolites in the substance treatment of the cells was presented that BPDE levels were reduced by neferine in lotus and daidzein, genisten in soybean. These results suggest that neferine in lotus and daidzein, genistein in soybean prevent B[a]P-induced hepato-toxicity for BPDE-DNA adduct formation.

This paper presents a proof-of-concept study on the biocolonization of 3D-printed hydroxyapatite scaffolds with mesenchymal stem cells (MSCs). Three-dimensional (3D) printed biomimetic bone structure made of Calcium Deficient HydroxyApatite (CDHA) intended as future bone graft was made from newly developed composite material for FDM printing. The biopolymer polyvinyl alcohol serves in this material as a thermoplastic binder for 3D molding of the printed object with a passive function and is completely removed during sintering. The study presents the material, the process of fused deposition modeling (FDM) of CDHA scaffolds and its post-processing at three temperatures (1200, 1300, 1400 °C), as well it evaluates the cytotoxicity and biocompatibility of scaffolds with MTT and LDH release assays after 14 days. The study also includes a morphological evaluation of the cellular colonization with scanning electron microscopy (SEM) in two different filament orientations (rectilinear and gyroid). The results of the MTT assay showed that the tested material was not toxic, and cells were preserved in both orientations, with most cells present on the material fired at 1300°C. Results of the LDH release assay showed a slight increase in LDH leakage from all samples. Visual evaluation of SEM confirmed the ideal post-processing temperature of the 3D-printed FDM framework for samples fired at 1300°C and 1400°C, with a porosity of 0.3 mm between filaments. In conclusion, the presented fabrication and colonization of CDHA scaffolds have great potential to be used in the tissue engineering of bones.

The assessment of welfare and disease progression in animal models is critical. Most tools rely on evaluating individual subjects, whereas social behaviors, also sensitive to acute illness, chronic diseases, or mental health, are scarcely monitored because of their complexity, are invasive, and time-consuming. We propose the evaluation of social nesting, a species-typical behavior naturally occurring in standard housing conditions, for such behavioral monitoring. We provide an example of its use to evaluate social deficits and the long-term effects of neonatal sensorial stimulation in male and female adult 3xTg-AD mice for Alzheimer's disease compared to sex- and age-matched NTg counterparts with normal aging. Social nesting was sensitive to genotype (worse in 3xTg-AD mice), sex (worse in males), profile, and treatment (distinct temporal patterns, time to observe the maximum score and incidence of the perfect nest). Since social nesting can be easily included in housing routines, this neuroethological approach can be useful for animal's welfare, monitoring the disease's progress, and evaluating potential risk factors and effects of preventive/therapeutical strategies. Finally, the non-invasive, painless, simple, short time and low-cost features of this home-cage monitoring are advantages that make social nesting feasible to be successfully implemented in most animal department settings.

Crosslinking of proteins for their irreversible immobilization on surfaces is a proven and popular method. However, many protocols lead to random orientation and the formation of undefined or even inactive by-products. Most concepts to obtain a more targeted conjugation or immobilization requires the recombinant modification of at least one binding partner, which is often impractical or prohibitively expensive. Here a novel method is presented, which is based on the chemical preactivation of Protein A or G with selected conventional crosslinkers. In a second step, the antibody is added, which is subsequently crosslinked in the Fc part. This leads to an oriented and covalent immobilization of the immunoglobulin with a very high yield. Protocols for Protein A and Protein G with murine and human IgG are presented. This method may be useful for the preparation of columns for affinity chromatography, immunoprecipitation, antibodies conjugated to magnetic particles, permanent and oriented immobilization of antibodies in biosensor systems, microarrays, microtitration plates or any other system, where the loss of antibodies needs to be avoided, and maximum binding capacity is desired. This method is directly applicable even to antibodies in crude cell culture supernatants, raw sera or protein-stabilized antibody preparations without any purification nor enrichment of the IgG. This new method delivered much higher signals as a traditional method and, hence, seems to be preferable in many applications.

Aim: This study aims to analyze the structure and impact of research collaborations in colonoscopy from 2000 to 2023 by examining co-authorship networks. The goal is to understand the evolution of these networks, identify key contributors, and assess how collaborative relationships influence the field. Method: I conducted a comprehensive network analysis of co-authorship patterns using data from the Web of Science (WoS) Core Collection database. The analysis included 41,213 articles related to colonoscopy published between 2000 and 2023. Using Python (Version 3.10.5) and PyCharm (Software Version 2022.1.3), we evaluated the networks through macro-level indicators (network density, clustering coefficient, number of components, average distance) and micro-level indicators (degree centrality, closeness centrality, betweenness centrality).Result: The analysis revealed a network with increasing but still fragmented collaboration over the years. The network density showed low proportions of realized connections relative to potential ones, with a high clustering coefficient indicating tight-knit groups when collaborations occurred. The number of components remained high, reflecting a fragmented structure. Prominent researchers such as Hassan, Cesare (Italy) and Dekker, Evelien (Netherlands) consistently emerged as central figures across different periods, demonstrating significant roles in facilitating connections between various research clusters.Conclusion: The study highlights a growing but fragmented collaborative landscape in colonoscopy research. Key researchers have played central roles in connecting different parts of the network, yet there remains substantial room for further integration. Strengthening collaborations across isolated groups could enhance the cohesiveness and impact of research in this field.

A single Cancer immunotherapy has ushered in a transformative era in oncology, bringing forth unprecedented promise and opportunities. However, even with its significant breakthroughs, the domain faces the continual issue of treatment resistance. Such resistance not only restricts the broad effectiveness of these pioneering treatments but also highlights the imperative need for further research. Delving into the complex world of cancer immunotherapy resistance, we identify a range of mechanisms, from primary and secondary resistance to the notable effects of genetic and epigenetic variables, and the pivotal importance of the tumor microenvironment (TME). Additionally, we emphasize the need for innovative strategies to mitigate this resistance, including combination treatments, customized immune checkpoints, and instantaneous monitoring. By advocating for these cutting-edge methods, we foresee a direction that incorporates personalized healthcare, enhanced treatment options, and a steadfast dedication to the welfare of patients. Through a comprehensive and diverse approach, we aim to address the hurdles posed by resistance, elevating cancer immunotherapy as a symbol of hope for patients worldwide.

Early reports demonstrated the presence of cells with stem-like properties in bone marrow, with these cells having both hematopoietic and mesenchymal lineages. Over the years, various investigations have purified and characterized mesenchymal stromal/stem cells (MSCs) from different human tissues as cells with multi-lineage differentiation potential under the appropriate conditions. Due to their appealing characteristics and potential, MSCs are leveraged in many applications including medicine, oncology, bioprinting and as recent as treatment of COVID-19. To date, reports indicate mesenchymal stromal/stem cells have varied differentiation capabilities into different cell types and demonstrate immunomodulating and anti-inflammatory properties. Reports indicate that different MSCs microenvironments or niche and the resulting heterogeneity may influence their behavior and differentiation capacity. The potential clinical applications of mesenchymal stromal/stem cells have led to an avalanche of research reports on their properties and hundreds of clinical trials being undertaken. The future looks bright and promising for mesenchymal stem cell research with many clinical trials under way to prove their utility in many applications and in the clinic. This report provides an update on the potential broader use of mesenchymal stromal/stem cells, review early observations of the presence of these cells in the bone marrow and their magnificent differentiation capabilities and immunomodulation.

Placenta-derived mesenchymal stem cells (PD-MSCs) have been highlighted as therapeutic sources in several degenerative diseases. Recently, microRNAs (miRNAs) were mediated one of the therapeutic mechanisms of PD-MSCs in regenerative medicine. To enhance the therapeutic effects of PD-MSCs, we established functionally enhanced PD-MSCs with phosphatase of regenerating liver-1 overexpression (PRL-1(+)). However, the profile and functions of miRNAs induced by PRL-1(+) PD-MSCs in a rat model with hepatic failure prepared by bile duct ligation (BDL) remained unclear. Hence, the objectives of the present study were to analyze the expression of miRNAs and investigate their therapeutic mechanisms for hepatic regeneration via PRL-1(+) in a rat model with BDL. We selected candidate miRNAs based on microarray analysis. Under hypoxic conditions, compared with invaded naïve PD-MSCs, invaded PRL-1(+) PD-MSCs showed improved integrin-dependent migration ability through RHO family-targeted miRNA expression (e.g., hsa-miR-30a-5p, 340-5p, and 146a-3p). Moreover, rno-miR-30a-5p and 340-5p regulated engraftment into injured rat liver by transplanted PRL-1(+) PD-MSCs through the integrin family. Additionally, an increase in PDGFRA by suppressing rno-miR-27a-3p improved vascular structure in rat liver tissues after PRL-1(+) PD-MSCs transplantation. Furthermore, decreased rno-miR-122-5p was significantly correlated with increased proliferation of hepatocytes in liver tissues by PRL-1(+) PD-MSCs by activating IL-6 signaling pathway through the repression of rno-miR-21-5p. Taken together, these findings improve the understanding of therapeutic mechanisms based on miRNA-mediated stem cell therapy in liver diseases.

Aim: This study aims to analyze the structure of the co-authorship network in viral hepatitis research from 2000 to 2023 using data from the Web of Science (WoS) Core Collection. The objective is to identify key researchers, evaluate the collaborative dynamics, and understand the evolution of scientific contributions in this field. Method: This study utilized network analysis techniques to evaluate 60,720 publications related to viral hepatitis research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: The findings reveal that the viral hepatitis research network is characterized by low network density, indicating sparse overall collaboration. However, the clustering coefficient is high, suggesting strong collaborations within small, cohesive groups. Over the years, researchers such as Stefan Zeuzem, Maria Buti, and Fabien Zoulim have played pivotal roles, serving as central figures in the network. A noticeable increase in network density and clustering from 2020-2023 suggests growing collaboration in recent years.Conclusion: This study underscores the importance of international collaboration in advancing viral hepatitis research. Key researchers have emerged as influential contributors, facilitating global research activities. Network analysis provides valuable insight into the structure of these collaborations and helps identify potential areas for future research and partnerships to combat viral hepatitis globally. The results of this study should be used to reduce global healthcare disparities, promote research collaboration, and address viral hepatitis as a global public health problem.

Aim: This study aims to analyze the collaborative networks and identify key players in autoimmune pancreatitis (AIP) research from 2000 to 2023. Using data from the Web of Science (WoS) Core Collection, I assess the structure and evolution of co-authorship networks to understand collaboration trends and influential researchers in the field.Method: I conducted a network analysis of co-authorship patterns in AIP research using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The analysis included macro-level indicators: network density, clustering coefficient, components, and average distance, as well as micro-level indicators: degree centrality, closeness centrality, and betweenness centrality. These metrics were used to evaluate the connectivity, clustering, and key nodes within the network across three distinct periods: 2000-2009, 2010-2019, and 2020-2023.Result: The analysis revealed that the co-authorship network in AIP research evolved from a fragmented structure with limited collaboration in the early 2000s to a more interconnected but still dispersed network in recent years. Despite an increase in network density and a decrease in the number of disconnected components over time, the overall structure remains highly clustered, with many researchers operating within isolated groups. Key figures, such as Kazuichi Okazaki, Terumi Kamisawa, and Shigeyuki Kawa from Japan, consistently ranked high in centrality measures, highlighting their significant influence and leadership in the field. The findings suggest that while local collaborations are strong, broader international connections are still developing.Conclusion: This study provides a comprehensive overview of the collaborative landscape in AIP research, identifying central researchers and highlighting persistent fragmentation within the network. The prominent role of Japanese researchers in shaping the field underscores the importance of fostering greater international collaboration to bridge gaps between research clusters. Enhancing global partnerships could lead to more integrated and impactful research outcomes, ultimately advancing the understanding and management of autoimmune pancreatitis.

Loyalty is one of the greatest intangible assets that any organization can possess and improving client loyalty is a primary marketing goal that can have a significant financial impact on any business. This quantitative study examined the mediating role of communication on the relationship between satisfaction and loyalty (attitudinal and behavioral) in veterinary clinics, along with the moderating roles of trust, commitment, perceived value, and relational characteristics. Responses collected from 351 pet-owners through social media were analyzed using descriptive and inferential statistics. The results show that attitudinal loyalty (AL) has a strong positive relationship with communication at multiple points in a veterinary clinic whereas the relationship with behavioral loyalty was not as clear. Additional findings suggest that AL, which is influenced by trust in the veterinarian, communication from staff members and commitment, has a strong positive relationship with behavioral intentions, increases the number of products and services that a pet-owner consumes at his or her primary veterinary clinic, and attenuates the role of cost in receiving veterinary care. These findings can help veterinary clinic owners and managers in developing and implementing relationship strategies that improve pet-owner loyalty. The article that follows is a synopsis of the author’s dissertation.

The central promise of personalized medicine is individualized treatments that target molecular mechanisms underlying the physiological changes and symptoms arising from disease. We demonstrate a bioinformatics analysis pipeline as a proof-of-principle to test the feasibility and practicality of comparative transcriptomics to classify two of the most popular in vivo diet-induced models of coronary atherosclerosis, apolipoprotein E null mice and New Zealand White rabbits. Transcriptomics analyses indicate the two models extensively share dysregulated genes albeit with some unique pathways. For instance, while both models have alterations in the mitochondrion, the biochemical pathway analysis revealed, Complex IV in the electron transfer chain is higher in mice, whereas the rest of the electron transfer chain components are higher in the rabbits. Several fatty acids anabolic pathways are expressed higher in mice, whereas fatty acids and lipids degradation pathways are higher in rabbits. This reflects the differences between two translational models of atherosclerosis. This study validates transcriptome analysis as a potential method to precisely identify altered cellular and molecular pathways in atherosclerotic disease, which can be used to individualize treatment even in the absence of genetic data.

Aim: This study aims to analyze the structure of the co-authorship network in Budd-Chiari syndrome (BCS) research from 2000 to 2023 using data from the Web of Science (WoS) Core Collection. The objective is to identify key researchers, evaluate the collaborative dynamics, and understand the evolution of scientific contributions in this field. Method: This study utilized network analysis techniques to evaluate 2,877 publications related to BCS research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: The results revealed a highly fragmented network structure in the early years (2000-2009), characterized by low network density (0.0017) and a large number of disconnected components (533). Key researchers such as Aurelie Plessier and Dominique Valla emerged as central figures in terms of degree and closeness centrality. In the 2010-2019 period, the network showed slight improvements, with density decreasing to 0.0016 but an increase in the number of components to 645, indicating persistent fragmentation. From 2020 to 2023, the network demonstrated increased cohesiveness with a density of 0.0032 and a reduction in components to 376. Influential researchers in the final period included Virginia Hernandez-Gea and Valerie Paradis, who played pivotal roles in connecting disparate research clusters.Conclusion: The co-authorship network analysis of BCS research over the past two decades highlights a gradual yet incomplete evolution towards greater collaboration and integration among researchers. While the network's cohesiveness has improved, significant fragmentation remains, suggesting that further efforts are needed to enhance global and interdisciplinary collaboration. Addressing these challenges is crucial for fostering a more connected and productive research community that can advance the understanding and management of BCS.

Aim: This study aims to analyze the evolution of co-author networks in Gastroesophageal Reflux Disease (GERD) research from 2000 to 2023, using data from the Web of Science (WoS) Core Collection. The objective is to provide a structural overview of researcher collaborations in this specialized field, highlighting key contributors and the impact of international cooperation. Method: I conducted a co-author network analysis on 19,463 GERD -related articles indexed in the WoS Core Collection between 2000 and 2023. Using Python (Version 3.10.5) within the PyCharm development environment (Software Version 2022.1.3), I assessed macro-level indicators including network density, clustering coefficient, number of components, and average distance. Micro-level indicators such as degree centrality, closeness centrality, and betweenness centrality were also evaluated to understand the roles of individual researchers in the network.Result: The GERD co-authorship network exhibited a sparse structure with low network density, indicating limited realized collaborations compared to potential connections. The clustering coefficient was consistently high across the analyzed periods, suggesting that researchers frequently formed tight-knit groups. The network was fragmented into numerous components, with significant disconnection between groups. Degree centrality highlighted key researchers such as Dent, J., and Shaheen, N.J., who had extensive collaborative reach. In contrast, closeness and betweenness centrality identified strategic intermediaries like Bredenoord, A.J. and Kahrilas, P.J., who facilitated connections across otherwise isolated segments of the network.Conclusion: The co-authorship network analysis revealed a persistently fragmented landscape in GERD research, with considerable room for enhancing collaboration among researchers. Identifying key contributors and understanding their roles within the network can guide future efforts to foster more integrated and comprehensive research collaborations. This study underscores the importance of strategic networking and partnership development in advancing GERD research and optimizing the field's collaborative potential.

Growth factors, chemokines and cytokines guide tissue regeneration after injuries. However, their applications as recombinant proteins are almost non-existent due to the difficulty of maintaining their bioactivity in the protease-rich milieu of injured tissues in humans. Safety concerns have ruled out their systemic administration. The vascular system provides a natural platform for circumvent the limitations of the local delivery of protein-based therapeutics. Tissue selectivity in drug accumulation can be obtained as organ-specific molecular signatures exist in the blood vessels in each tissue, essentially forming a postal code system (“vascular zip codes”) within the vasculature. These target-specific “vascular zip codes” can be exploited in regenerative medicine as the angiogenic vasculature forming in the regenerating tissues has a unique molecular signature. The identification of vascular homing peptides capable of finding these unique “vascular zip codes” after their systemic administration provides an opportunity for the target-specific delivery of therapeutics to tissue injuries. Therapeutic proteins can be “packaged” together with homing peptides by expressing them as multi-functional recombinant proteins. These multi-functional recombinant proteins provide an example how molecular engineering gives a compound an ability to home to regenerating tissue and enhance its therapeutic potential. Regenerative medicine has been dominated by the locally applied therapeutic approaches despite these therapies are not moving to clinical medicine with success. There might be a time to change the paradigm towards systemically administered, target organ-specific therapeutic molecules in future drug discovery and development for regenerative medicine

The first reports of the acute and often fatal illness known as the “English Sweat” are from 1485 and its last known outbreak was in 1551. During this period, the Sweat produced only five epidemic waves. Except for one outbreak which spread to the northern part of the continent of Europe in 1529, the Sweat was confined almost exclusively to England, with only anecdotal reports of isolated infections in other parts of the British Isles. The Sweat was thus only a minor component in the panorama of infectious disease affecting mediaeval and early modern Europe. Nevertheless, it continues to fascinate both medical historians and modern infectious disease biologists – the latter group now often engaged in competing exercises in retrospective diagnosis. This paper seeks to explore the reasons for such enduring interest, using the Early English Books Online (EEBO) text corpus to analyse the various contexts in which the Sweat was discussed up to 1700. EEBO shows that references to the Sweat occur repeatedly in astrological and religious discourses, especially from the mid-17^th century onwards. Four salient examples are examined in detail. It is proposed that the cultural memory of the Sweat, in the 150 years following its disappearance, was kept disproportionately alive not so much by accounts of its alarming symptoms but more due to its metaphorical and illustrative utility in non-medical discourse.

Aim: This study aims to explore the collaborative networks in Sodium/Glucose Cotransporter 2 (SGLT2) research, covering the period from 2000 to 2023. By conducting a co-authorship network analysis, I investigate the structure and dynamics of scientific collaboration, identifying key researchers, institutions, and trends in the field. This analysis provides insights into how research collaboration has evolved and highlights the influence of international cooperation on the development of SGLT2 research.Method: The data were collected from the Web of Science (WoS) Core Collection and included 6,999 publications on SGLT2 research. Using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3), I analyzed both macro and micro-level network indicators. Macro-level indicators included network density, clustering coefficient, components, and average distance, while micro-level indicators included degree centrality, closeness centrality, and betweenness centrality. These metrics were used to assess the structure of the co-authorship network and identify key contributors.Result: The network analysis revealed significant changes in collaboration patterns over the study period. From 2000 to 2023, the network became more fragmented, with an increase in the number of research clusters and components. However, influential researchers, such as Zinman B. and Heerspink Hiddo J. L., consistently emerged as central figures in terms of both degree and closeness centrality. The analysis also highlighted the rise of international collaboration, particularly involving researchers from the United States, Europe, and Asia, with Japan playing a growing role in recent years.Conclusion: This study demonstrates that SGLT2 research collaboration networks have evolved considerably over the last two decades. The identification of key researchers and institutions provides valuable insights into the field's development, emphasizing the importance of international cooperation in advancing SGLT2 research. These findings may guide future research strategies and promote further collaborative efforts.

The research article provides an in-depth analysis of the European Medicines Agency (EMA) and the Directorate General of Drug Administration (DGDA), focusing on their historical development, organizational structures, and functional roles in ensuring the quality and safety of pharmaceuticals. The study highlights the origins of drug regulation, tracing back to the early 19th century in the United States with the establishment of the Food and Drug Administration (FDA), and discusses the evolution and significance of drug regulatory bodies worldwide. The EMA and DGDA are scrutinized for their efforts in maintaining high standards for drug approval, monitoring clinical trials, and managing post-marketing surveillance to prevent adverse drug reactions (ADRs). The EMA’s role in coordinating with EU member states on pharmacovigilance and the DGDA’s initiatives in Bangladesh, including the implementation of a nationwide drug database and pharmacovigilance system, are explored in detail. The article concludes by emphasizing the essential role of these regulatory bodies in safeguarding public health through stringent regulation and continuous monitoring of pharmaceuticals, thereby ensuring that only safe and effective medicines are available to consumers . It also provides an in-depth analysis of the roles, structures, and historical contexts of the European Medicines Agency (EMA) and the Directorate General of Drug Administration (DGDA). It outlines how these regulatory bodies ensure the safety, efficacy, and quality of medicinal products. The EMA, serving the European Union, and the DGDA, operating in Bangladesh, play critical roles in drug approval processes, pharmacovigilance, and maintaining public health standards. By setting rigorous guidelines and monitoring compliance, these agencies help safeguard the health of millions, ensuring that only safe and effective medications are available in the market. The paper underscores the importance of these regulatory bodies in promoting public health and supporting the pharmaceutical industry's development and innovation.

Aim: This study aims to investigate the global collaboration network among researchers studying Sick Sinus Syndrome (SSS) from 2000 to 2023. Given the syndrome's increasing prevalence in aging populations, understanding the structure of research collaboration is crucial to advancing the field. This analysis explores co-authorship networks to identify key contributors, institutions, and trends in SSS research. Method: This study utilized network analysis techniques to evaluate 1,693 publications related to SSS research indexed in the Web of Science (WoS) Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: The analysis revealed an overall increase in collaboration over time, with rising network density and stronger local clusters, although the network remained fragmented. Key researchers, including Boriani, Giuseppe (Italy), and Glikson, Michael (Australia), emerged as central figures, demonstrating high degrees of centrality in different periods. The results also highlight persistent regional and institutional collaboration patterns, reflecting the growing importance of global partnerships in addressing SSS.Conclusion: This comprehensive network analysis underscores the importance of international collaboration in advancing SSS research. Despite growing collaborative efforts, the field remains somewhat fragmented, suggesting further opportunities for integration. This research has enabled us to identify influential researchers and research institutions, and we will be able to promote research collaboration to further understand and improve treatment methods for SSS as a response to the aging of the world's population.

Aim: This study aims to explore the collaborative networks in Marfan Syndrome (MFS) research by analyzing co-authorship patterns from 2000 to 2023. The objective is to identify key researchers, trends in collaboration, and the extent of interdisciplinary cooperation within the global MFS research community. Understanding these dynamics will inform the future direction of research in this field, emphasizing the need for a more integrated, interdisciplinary approach. Method: This study utilized network analysis techniques to evaluate 6,657 publications related to MFS research indexed in the Web of Science (WoS) Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed. Result: The network analysis revealed a persistent fragmentation within the MFS research community over the past two decades. While network density slightly increased from 0.0012 in the 2000–2009 period to 0.0016 in 2020–2023, the network remained disjointed with numerous disconnected components. Key contributors, such as Harry C. Dietz, Guillaume Jondeau, and Julie De Backer, demonstrated high centrality values, playing pivotal roles in shaping collaboration. The clustering coefficient remained high across all periods, indicating strong intra-group collaboration, yet underscoring the need for broader interdisciplinary partnerships.Conclusion: This study highlights the need for more integrated and cross-disciplinary collaboration in MFS research. Despite the significant contributions of central researchers, the overall fragmentation limits potential advancements. Fostering a more interconnected global network and encouraging interdisciplinary cooperation will be crucial to addressing the complex, multi-systemic nature of Marfan Syndrome and improving patient outcomes.

The term neurodegeneration with brain iron accumulation (NBIA) brings together a broad set of progressive and disabling neurological genetic disorders in which iron is deposited preferentially in certain areas of the brain. Among NBIA disorders, the most frequent subtype is pantothenate kinase-associated neurodegeneration (PKAN) caused by pathologic variants in the PANK2 gene codifying the enzyme pantothenate kinase 2 (PANK2). Nowadays, there are no effective treatments to stop the progression of these diseases. This review discusses the utility of patient-derived cell models as a valuable tool for the identification of commercial pharmacological or natural compounds for implementing polytarget precision medicine in PKAN. In the last years, several studies have described that PKAN patient-derived fibroblasts manifest the main pathological changes associated with the disease including intracellular iron overload. Interestingly, treatment of mutant cell cultures with various supplements such as pantothenate, pantethine, thiamine, L-carnitine, vitamin E, omega 3, and -lipoic acid improved all pathophysiological alterations in PKAN fibroblasts with residual expression of the PANK2 enzyme. The information provided by pharmacological screenings in patient-derived cellular models can help to optimize therapeutic strategies in individual PKAN patients.

The COVID-19 pandemic drew public attention back to the living conditions related to housing, access to green areas in close neighbourhood and nearby recreation. Several studies confirm that visiting green spaces improved the health and wellbeing in times of crisis. This representative study for the metropolitan area of Vienna, Austria’s capital, confirms the high relevance of contact with nature, particularly for citizens to cope with the negative consequences and perceived stress, anxiety, nervousness and many other negative symptoms experienced during the health crisis. It highlights the importance of nearby smaller but also medium to large scale green areas in cities for health and wellbeing of the population. Moreover, it specifically adds novel insights on age effects in use and perception of urban green spaces during COVID-19 pandemic. The online panel survey (n=1012) was conducted in summer 2021. In order to obtain a representative sample reflective of the population’s characteristics, a (stratified) random sample was selected by applying the quota method. The objective was to obtain a sample which represented gender, age and regional distribution of the population of the City of Vienna as well as the immediately surrounding local communities. Interestingly, particularly young people spent more time outside in green areas during the pandemic, discovered novel spaces for the first time and stated a high relevance of contact with nature for their wellbeing. Elderly people above sixty five, on the contrary, stayed more frequently at home. Significant differences are visible between the age groups also with regard to negative symptoms experienced in case of restricted access to green areas due to strict pandemic measures such as lockdowns and quarantine. All age groups, however, similarly acknowledged the importance of green areas for their physical, mental and emotional health in general during the pandemic.

One in 12 babies is born with a rare genetic disease. Sadly, most cases are undetected until later age, missing time for early treatment and opportunity to prevent complications. Humanity has entered a new era where Big Data collected by governments, including 2D and 3D facial scans, are available. Many rare genetic diseases can be identified by artificial intelligence (AI) analysis of the facial photo. Phenotyping AI utilizations facilitate comprehensive and accurate genetic evaluations. AI processing of this Big Data to identify rare genetic diseases could bring unimaginable benefits to healthcare, although this would be a questionable step in terms of citizen privacy and could lead to future "Orwellian" ramifications with government abuse. Going forward, a balance must be found between protecting the privacy of citizens and the enticing use of AI for their health risks and cost savings through prevention. The unimaginable potential of AI early diagnostics from facial photos also raises various ethical and legal concerns. This paper presents concept, protentional methods and legal and other limitations within EU legal framework in contrast with potential benefits. This paper is focused on AI utilization to early diagnostic of rare genetic diseases. Shift of paradigm in the screening for rare genetic diseases in population with AI face analysis is expected to have a significant impact. The potential of AI algorithms utilizations similar to face2gene app in general population or systematically on Big governmental datasets recording facial traits changes in time can have significant impact on public health but at the same time give raise to profound concern as violation of one’s privacy.

Stem/progenitor cell transplantation is a potential novel therapeutic strategy to induce angiogenesis in ischemic tissue, which can prevent major amputation in patients with advanced peripheral artery disease (PAD). Thus, clinicians can use cell therapies worldwide to treat PAD. However, some cell therapy studies did not report beneficial outcomes. Clinical researchers suggested that classical risk factors and comorbidities may adversely affect the efficacy of cell therapy. Some studies have indicated that the response to stem cell therapy varies among patients even in those harboring limited risk factors. This suggested the role of undetermined risk factors, including genetic alterations, somatic mutations, and clonal hematopoiesis. Personalized stem cell-based therapy can be developed by analyzing individual risk factors. These approaches must consider several clinical biomarkers and perform studies (such as genome-wide association studies (GWAS)) on disease-related genetic traits and integrate the findings with those of transcriptome-wide association studies (TWAS) and whole-genome sequencing in PAD. Additional unbiased analyses with state-of-the-art computational methods, such as machine learning-based patient stratification, are suited for predictions in clinical investigations. The integration of these complex approaches into a unified analysis procedure for the identification of responders and non-responders before stem cell therapy, which can decrease treatment expenditure, is a major challenge to increase the efficacy of therapies.

Aim: This study aims to analyze the collaborative structure of Intestinal Behçet’s Disease (IBD) research by examining co-authorship networks in publications indexed in the Web of Science (WoS) Core Collection from 2000 to 2023. The goal is to identify key researchers, institutions, and collaboration patterns that have shaped the field over the past two decades. Method: This study utilized network analysis techniques to evaluate 484 publications related to IBD research indexed in the WoS Core Collection between 2000 and 2023. The analysis was conducted using Python (Version 3.10.5) in the PyCharm development environment (Software Version 2022.1.3). The co-authorship networks were assessed using macro-level indicators such as network density (the ratio of actual to possible connections), clustering coefficient (degree of node clustering), number of components (distinct connected subgroups), and average path length (average distance between nodes). Micro-level indicators including degree centrality (importance based on the number of connections), closeness centrality (proximity to other nodes), and betweenness centrality (frequency of a node on the shortest paths between others) were also analyzed.Result: From 2000 to 2009, the co-authorship network was highly fragmented with a low network density of 0.0114 and 84 distinct components, indicating limited collaboration. Key contributors during this period included Kim, Won Ho, and Cheon, Jae Hee (South Korea), who played central roles in connecting disparate research clusters. In the following decade (2010-2019), network density decreased slightly to 0.0086, and the number of components increased to 113, reflecting continued fragmentation despite growing research output. However, from 2020 to 2023, network density increased to 0.0171, and the number of components decreased to 73, indicating a trend towards greater integration and collaboration. Notable researchers in this period included Emmi, Giacomo (Italy), and Hatemi, Gulen (Turkey), who emerged as central figures, highlighting a shift in research leadership from Asia to Europe..Conclusion: The co-authorship network analysis of IBD research reveals an evolving collaborative landscape with increasing network density and decreasing fragmentation over time, particularly in the most recent period. From 2000 to 2019, Japanese and Korean researchers were prominent contributors, highlighting the significance of Asia in the global research arena. However, since 2020, researchers from Italy and Turkey have gained significant international prominence, suggesting a shift in the research focus from Asia to Europe. This transition may be attributed to changes in the incidence rates of IBD, where rapid increases were observed in Asian countries like Japan, Korea, and China until 2020, followed by stabilization or decline, while incidence rates have been increasing in European countries such as Italy and Turkey. These findings underscore the importance of expanding international collaborations to enhance the understanding of IBD. Fostering global partnerships could further advance the field, promoting more integrated and innovative research efforts, and addressing the shifting dynamics of IBD prevalence across regions.

Type 1 diabetes affects millions of people globally and requires careful management to avoid serious long-term complications, including heart and kidney disease, stroke, and loss of sight. The present standard-of-care for type 1 diabetes is exogenic insulin substitutional therapy. The most advanced stretegies in this area is the development of hybrid-closed loop system and the producing of long-acting insulins. Progresses in stem cell therapies have started to revolutionize the care of patients with type 1 diabetes; however, significant challenges remain including the limited islets availability, difficulties in maintaining the viability, the heterogeneity within a complex pathology and in patients’ responses to treatment. On the way, a considerable amount of efforts in maximizing the islet transplantation effectiveness by controlling the advantageous of different stem cell approaches. With the availability and the use of big data, the concept of precision medicine is gaining wide attention worldwide and could bring the dream of “presonlaized” therapies as a reality in the near future. Here we review the current range of treatments available as well as recent pre-clinical breakthroughs in the field of personlaized medicine for type 1 diabetes.

Aim: This study aims to analyze the evolution of co-author networks in Single-Balloon Enteroscope (SBE) research from 2000 to 2023, using data from the Web of Science (WoS) Core Collection. The objective is to provide a structural overview of researcher collaborations in this specialized field, highlighting key contributors and the impact of international cooperation. Method: I conducted a co-author network analysis on 149 SBE-related articles indexed in the WoS Core Collection between 2000 and 2023. Using Python (Version 3.10.5) within the PyCharm development environment (Software Version 2022.1.3), I assessed macro-level indicators including network density, clustering coefficient, number of components, and average distance. Micro-level indicators such as degree centrality, closeness centrality, and betweenness centrality were also evaluated to understand the roles of individual researchers in the network.Result: The analysis revealed that the co-author networks in SBE research have evolved over the studied period, with varying degrees of connectivity and collaboration. From 2000 to 2009, the network showed moderate clustering but high fragmentation, with a few key researchers like Nista, Enrico C., and Spada, Cristiano playing central roles. In the 2010-2019 period, network density decreased, indicating expansion in the author pool but less frequent co-authorships. However, the clustering coefficient remained high, suggesting localized collaboration. Central figures such as Itoi, Takao emerged as influential in bridging network gaps. In the most recent period (2020-2023), network density moderately increased, reflecting improved collaboration. Key contributors included Tanisaka, Yuki, and Ryozawa, Shomei, who enhanced connectivity within the network. Despite these advancements, the network remained fragmented with isolated components throughout all periods. Conclusion: The co-author networks in SBE research have shown an overall increase in collaboration over the past two decades, with key contributors playing pivotal roles in connecting disparate groups. However, the persistent fragmentation suggests a need for more integrated efforts to enhance international collaboration. Understanding these network dynamics can inform future strategies for fostering global cooperation and advancing SBE research.

Malignant lymphomas, encompassing Hodgkin lymphomas (HL) and non-Hodgkin lymphomas (NHL), represent a significant category of hematological malignancies with diverse presentations and prognoses. This review synthesizes current understanding of malignant lymphomas, focusing on their classification, incidence, epidemiology, staging, histopathology, and evolving treatment strategies. Malignant lymphomas are broadly classified into HL and NHL, with NHL further subdivided into B-cell, T-cell, and NK-cell neoplasms. The emergence of grey zone lymphomas, which exhibit overlapping features and heightened aggressiveness, underscores the complexity of diagnosis and treatment. Epidemiologically, HL predominantly affects younger individuals, while NHL incidence increases with age, reflecting a global rise in both incidence and mortality rates. Advances in diagnostic techniques and treatments have led to improved outcomes, yet challenges persist, particularly in distinguishing between overlapping lymphoma types and managing increasing incidence rates. The management of HL and NHL involves a variety of treatment options tailored to the disease stage and individual patient characteristics. After diagnosis and staging, treatment regimens may include radiotherapy, chemotherapy (either alone or in combination), and immunotherapy. Monitoring patient response is crucial, with adjustments made in cases of therapeutic failure. Achieving remission—either partial or complete—depends on the normalization of biomarkers and imaging results, reduction of lymphoid organ size, and resolution of symptoms. Despite therapeutic advances, treatment complications, including short-term effects like myelosuppression and long-term issues such as cardiomyopathy and secondary cancers, remain significant. The future of HL and NHL treatment lies in refining these approaches, minimizing adverse effects, and enhancing efficacy through innovative therapies and personalized medicine strategies.

We wanted to investigate the current knowledge on the impact of diet on anti-TNF response in inflammatory bowel diseases (IBD), to identify dietary factors that warrant further investigations in relation to anti-TNF treatment response, and, finally, to discuss potential strategies for such investigations. PubMed was searched using specified search terms. One small prospective study on diet and anti-TNF treatment in 56 patients with CD found similar remission rates after 56 weeks among 32 patients with good compliance that received concomitant enteral nutrition and 24 with poor compliance that had no dietary restrictions (78% versus 67%, p = 0.51). A meta-analysis of 295 patients found higher odds of achieving clinical remission and remaining in clinical remission among patients on combination therapy with specialised enteral nutrition and Infliximab (IFX) compared with IFX monotherapy (OR 2.73; 95% CI: 1.73–4.31, p < 0.01, OR 2.93; 95% CI: 1.66–5.17, p < 0.01, respectively). In conclusion, evidence-based knowledge on impact of diet on anti-TNF treatment response for clinical use is scarce. Here we propose a mechanism by which Western style diet high in meat and low in fibre may promote colonic inflammation and potentially impact treatment response to anti-TNF drugs. Further studies using hypothesis-driven and data-driven strategies in observational, animal and interventional studies are warranted.

Abstract: This review addresses the complexities of type 1 diabetes (T1D)and its associated complications, with a par-ticular focus on diabetic retinopathy (DR). This review outlines the progression from non-proliferative to proliferative diabetic retinopathy and diabetic macular edema, highlighting the role of dysglycemia in the pathogenesis of these conditions. A significant portion of the review is devoted to technological advances in diabetes management, particu-larly the use of Hybrid Closed Loop systems (HCLS) and to the potential of open-source HCLS systems, which could be easily adapted to different patiens’needs using big data analytics and machine learning. Personalized HCLS algorithms that integrate factors such as patient lifestyle, dietary habits, and hormonal variations are highlighted as critical to reducing the incidence of diabetes-related complications and improving patient outcomes.

Tandem mass spectrometry (TMS) has emerged as a critical analytical tool in pharmaceutical sciences, playing a pivotal role in ensuring the rational use of medications. This article explores the applications of TMS across various stages of drug development, quality assurance, and patient care, highlighting its precision and reliability in advancing therapeutic efficacy. TMS facilitates the accurate identification and quantification of drug compounds, ensuring that pharmaceutical products meet high standards of purity and potency. By detecting even trace levels of impurities or contaminants, TMS strengthens the quality control processes critical to patient safety. In the realm of pharmacokinetics and pharmacodynamics, TMS enables detailed monitoring of drug absorption, distribution, metabolism, and excretion (ADME), allowing for a better understanding of drug behavior in the human body. It is also instrumental in therapeutic drug monitoring (TDM), ensuring that medication levels remain within therapeutic windows, thus optimizing dosing regimens and minimizing adverse effects. Additionally, TMS supports personalized medicine approaches by assessing drug interactions and tailoring treatments to individual patients. Through its application in drug discovery, development, and therapeutic monitoring, TMS serves as an indispensable tool for fostering rational medication use, contributing to more effective, safe, and personalized pharmaceutical care.

Telemedicine has emerged as a transformative tool in modern healthcare, particularly during the COVID-19 pandemic, which catalyzed its rapid expansion. Despite its demonstrated potential in enhancing remote patient monitoring, AI-driven diagnostics, and telepsychiatry, widespread adoption of telemedicine remains constrained by persistent barriers. This review examines the current state of telemedicine, identifying major advancements alongside key challenges that impede its full integration into global healthcare systems. These barriers include the digital divide, regulatory inconsistencies across regions, and patient concerns about data security and the quality of virtual care. Addressing these issues requires a coordinated multi-sectoral approach, emphasizing infrastructure development, regulatory harmonization, patient education, and the incorporation of emerging technologies such as AI, blockchain, and virtual reality. By overcoming these challenges, telemedicine can be established as a cornerstone of equitable, accessible, and patient-centered healthcare worldwide.

SARS-CoV-2 Omicron variant spike RBD epitopes in complex with spike (S) -protein D614G mutations now predominate globally and increase infectivity by assembling more functional S proteins into the virion. On average, homeopathic medicine contains less than one molecule per dose on average. Single variable SphericalHarmonicY, LaguerreL, WhittakerM, SphericalBesselJ, LegendreP, LegendreQ, LaguerreL, ChebyshevT, and Hypergeometric1F1 Functions pFqarise in connection with the power series solution of the Schrodinger equation or in the summation of perturbation expansions in quantum mechanics. A quantum interpretation of the homeopathic method is presented here through a novel algebraic topology approach to supersymmetry and symmetry breaking in quantum fields and quantum gravity theory with the aim of developing a wide range of physical-based drug design applications in a Small Molecule Quantized Water Memory Network suggesting that the Hidden Black Hole Paradox of Information Loss might be solved under suitable conditions.