Articles

Early-onset neurodegenerative diseases (EO-NDs), such as early-onset Alzheimer’s disease (EOAD), Parkinson’s disease (EOPD), and familial amyotrophic lateral sclerosis (fALS), often stem from monogenic causes and manifest before typical age thresholds. These disorders frequently feature disrupted mitochondrial function and heightened oxidative stress, which together accelerate neuronal damage and degeneration. In this work, the author performs a comprehensive analysis of the literature and data related to mitochondrial dysfunction and redox imbalance in EO-NDs. Bibliometric trends were assessed using R-based tools on PubMed datasets, highlighting keyword networks and publication surges in recent years. Publicly available RNA-seq datasets from GEO and SRA were examined, with example DESeq2 analysis illustrating altered mitochondrial gene expression in EO-ND patient-derived samples. Network modeling of redox pathways using Python’s networkx demonstrates how oxidative stress can propagate through metabolic networks. Together, these computational approaches reinforce that mitochondrial DNA mutations, impaired electron transport chain (ETC) function, and reactive oxygen species (ROS) accumulation play central roles in EO-ND pathogenesis. The discussion further evaluates why antioxidant clinical trials have largely failed and how emerging therapies such as gene replacement, antisense oligonucleotides, and mitochondrial biogenesis modulators may provide more effective interventions.

This paper is a general summary of Neuralink, a revolutionary technology set to elevate human life and neurology. Neuralink itself is a key testimonial to the evolution of neuroscience and even brain-computer interfaces, otherwise known as BCI. The original few BCI experiments were conducted on monkeys in the 1960s and 70s, in which the experiment itself narrowed down and understood brain function as a general concept [3]. More specifically, "Work on these technologies began in the early 1970s, led by computer science professor J.J. Vidal at UCLA" [12]. Science itself progresses day by day, growing rapidly in recent years, especially in neuroscience, something highlighted as a focal point in the previous statement. Moreover, recently we have seen technology go on a rampant rise in terms of popularity, inventions, and changes to the human lifestyle. The interactions humans had with technology initially developed with wearables or wearable technology, such as Apple Watches, AirPods, and Fitbits, and now they have even prompted advancements in brain-computer interfaces. Technology has had the power to advance science, but now it’s capable of changing the human mind. Going back to Neuralink, it’s a startup that began its initiative in 2016 and was approved by the FDA for clinical trials in May of 2023, ready to create a wave of change in the field of neuroscience [6]. The foremost baffling thing is how this chip plans on being placed in the somatosensory system. The somatosensory system is a part of the brain that deals with motor actions, recognition, and perception, and applying Neuralink in this area should supposedly allow for cures and treatment of amyotrophic lateral sclerosis, Parkinson’s disease, spinal cord injuries, epilepsy, autism, depression, schizophrenia, and possibly blindness [9]. Neuralink is deemed to lead to a life-changing future, and with co-founders and investors like Elon Musk, there is a lot to know about this piece of technology.

<b>Objective:</b> This systematic review aimed to identify, synthesize, and critically analyze the available evidence on clinical protocols used for the prevention and treatment of prosthetic joint infection (PJI) in total hip arthroplasty (THA), based on studies published between 2000 and 2025. <b>Methods:</b><b> </b>The review was conducted according to PRISMA guidelines. Electronic searches were performed in PubMed (MEDLINE), Scopus, Web of Science, and Embase between January and April 2025. Eligible studies included clinical trials, cohort studies, case-control studies, systematic reviews, and meta-analyses published in English that addressed either preventive or therapeutic strategies for PJI in THA. Study selection, data extraction, and quality assessment were carried out independently by two reviewers. Due to the heterogeneity of the included studies, a qualitative synthesis was performed. <b>Results:</b><b> </b>A total of 32 studies were included. Preventive measures identified in the literature comprised combined antibiotic prophylaxis (cefazolin and gentamicin), multimodal perioperative protocols such as ACERTO, nasal decolonization for <i>Staphylococcus aureus</i>, silver-impregnated dressings, and structured post-discharge surveillance. Treatment strategies included DAIR (Debridement, Antibiotics, and Implant Retention), the DAPRI technique, one-stage and two-stage revision surgeries, muscle flap reconstructions, and protocols without spacers. These interventions were associated with significantly reduced infection rates and improved clinical outcomes when applied appropriately and in accordance with patient-specific factors. <b>Conclusion:</b><b> </b>Effective prevention and treatment of PJI in total hip arthroplasty require a systematic and evidence-based approach. Integrated protocols—spanning preoperative optimization, meticulous intraoperative techniques, and rigorous postoperative monitoring—have proven effective in reducing infection incidence. In cases of established infection, surgical management must be tailored to the timing of infection, microbial profile, and host conditions. Two-stage revision remains the gold standard for complex infections, while one-stage revision and emerging techniques like DAPRI offer promising results in selected cases. This review contributes to the standardization of clinical practice and supports improved patient outcomes.

This systematic review aimed to evaluate the biomechanical properties, functional performance, and clinical outcomes of different hip prosthesis materials and designs used in total hip arthroplasty (THA). A comprehensive search strategy identified 34 peer-reviewed studies published between 2015 and 2024. The materials investigated included cobalt-chromium-molybdenum (CoCrMo), titanium alloys, PEEK, ceramics, and advanced surface coatings such as polycrystalline diamond (PCD). In addition, dual mobility systems, lattice structures, and additively manufactured and patient-specific implants were assessed. The studies utilized clinical trials, finite element analysis, and biomechanical testing to compare outcomes such as wear resistance, stress distribution, osseointegration, and range of motion. The findings demonstrated that titanium alloys and porous lattice structures reduce stress shielding, while ceramics and CoCrMo provide superior wear resistance. Dual mobility implants improved joint stability and range of motion, particularly in high-risk patients. PEEK and PCD showed promising properties but lacked robust long-term data. The integration of advanced manufacturing technologies and material innovations has led to more personalized and biomechanically efficient solutions for THA. Further longitudinal studies are needed to validate these developments. This review provides a critical synthesis of the biomechanical, functional, and clinical implications of contemporary hip prosthetic systems.

The purpose of this study was to assess different periodontitis groups affected with mild, moderate and severe alveolar bone levels and treated using the Sandwich’s procedures. A total of 53 subjects, who had taken two sets of full-mouth standarized paralleling radiographs with mean observation time was 10.18±3.89 years and (ranges: 5.1 to 18.3 years) were collected for the past 20 years. The radiographic alveolar bone levels (RABL) at mesial and distal aspects of teeth were assessed by measuring the distance between cemento-enamel junction (CEJ) and the bone crest using an electronic digimatic caliper (EDC) under 7.5 magnified radiographs. The patients, who presented with SAP, were between 24 and 84 years of age, with a mean age of 54.8±10.2years. Although, the treatment of angular defects in molars with guided tissue regeneration, emdogain has been reported and has exhibited significant and predictable results, however, afforded very limited and less predictable results in the treatment of advanced class II and III maxillary furcation defects. The majority of root resection procedures are commonly recommended for treating advanced molar furcation, in particular located at molars with class III furcation involvement, there is still some controversy regarding the long-term prognosis after different treatment modalities. In general, the root resection procedure is a surgical approach for simultaneously performing a periodontal flap operation at first and followed by the amputation and/or resection of maxillary root(s). There are some complications and disadvantages, such as post-operative pain and bleeding, swelling, infection, etc. The present report is to describe the combination of therapeutic provisional prosthesis (TPP), fixed prosthesis, non-surgical procedure using root separation and/or resection (RSR) and for the treatment of advanced Class II and III furcation-Involved molars. In addition, evidenced-based clinical trials of retrospective and longitudinal data were also prescribed here. The purpose of this study was to present treatment procedures of Sandwich’s technique and retrospectively to evaluate the long-term clinical trials of this method in treating molar teeth with SAP and molar FI who were diagnosed as guarded and/or hopeless prognosis.

Active Pharmaceutical Ingredients (APIs) serve as the cornerstone of pharmaceutical development, driving therapeutic efficacy and safety in drug formulations. This article provides a comprehensive overview of the lifecycle of APIs, starting from their discovery and development, through to manufacturing processes and regulatory oversight. The development of APIs begins with intensive research and discovery efforts, where medicinal chemists and pharmacologists identify and optimize potential compounds through computational modelling, high-throughput screening, and structure-activity relationship studies. Promising candidates undergo rigorous preclinical testing to assess pharmacological properties, safety profiles, and potential adverse effects in animal models. Upon successful preclinical outcomes, APIs progress to clinical trials, involving phases of testing in human subjects to evaluate efficacy, dosage regimens, and safety profiles under controlled conditions. Clinical trial data are meticulously analyzed to support regulatory submissions, demonstrating the API's therapeutic benefits and safety for eventual patient use. Manufacturing APIs involves complex chemical synthesis or biotechnological methods, ensuring precise control over reaction conditions, purity, and yield. The scale-up from laboratory synthesis to industrial production demands adherence to Good Manufacturing Practices (GMP), where stringent quality control measures verify consistency, potency, and stability throughout production batches. Regulatory oversight by authorities such as the Food and Drug Administration (FDA) in the United States and the European Medicines Agency (EMA) in Europe ensures that APIs meet stringent standards of safety, efficacy, and quality before market approval. Manufacturers must submit comprehensive Chemistry, Manufacturing, and Controls (CMC) data, detailing manufacturing processes, analytical methods, and stability studies to support regulatory filings.

Myeloproliferative neoplasms (MPNs) are hematological disorders affecting myeloid stem cells. They are classified as Philadelphia (Ph) chromosome positive-chronic myeloid leukemia, and Ph-negative polycythemia vera, essential thrombocythemia, primary myelofibrosis, chronic neutrophilic leukemia, chronic eosinophilic leukemia, juvenile myelomonocytic leukemia, and MPN unclassifiable. This review is mainly focused on the Ph-negative MPNs namely, PV, ET, and PMF. These affect both males and females with a slight male predominance, with patients mainly presenting in the seventh decade. Patients often present with thrombotic events resulting in complications that lower survival rates. The major driver mutations that have been identified in MPNs are <i>JAK2 </i>Exon 14, <i>JAK2 </i>Exon 12, <i>MPL </i>Exon 10, and<i> CALR </i>Exon 9. The importance of these driver mutations gives due recognition to their inclusion into the 2022 diagnostic criteria of the MPN WHO Classification. However, other non-driver mutations have also been reported, especially in triple-negative cases. These mutations lead to downstream constitutive activation of the JAK/STAT signaling pathway, as well as the MAPK, and PI3K/Akt pathways. Insights into the molecular pathogenesis of MPN and its association with <i>JAK2</i>, <i>CALR</i>, and <i>MPL</i> mutations have identified JAK2 as a rational therapeutic target. Thus, as an approach to MPN therapy, JAK2 inhibitors, such as ruxolitinib, have been shown to effectively inhibit JAK2, and are currently in clinical trials in combination with other drug classes. This review comprehensively examines the molecular markers of the main Ph-negative MPNs, as well as diagnosis and treatment options.

An increasing number of adverse events are raising concern in the pharmaceutical supply chain due to contaminated active pharmaceutical ingredients (APIs). Most of the active pharmaceutical ingredients are not currently under the scope of environmental regulations, despite their negative impact on human health and the environment. API's life cycle plays a significant role in identifying potential supply chain sources and determining their impact on the environment. The Covid-19 pandemic's intermittent manufacturing interruptions and the increase in the frequency of drug shortages over the past ten years have sparked worries about how resilient the world's drug supply chains are. Many clinical trials were conducted on patients with COVID-19 during the SARS-CoV-2 pandemic and resulted in millions of deaths globally by 2022.

The role of enterprise applications in pharmaceutical industries is driving the digital transformation of various critical processes, and one process benefiting from this innovation is pharmaceutical drug traceability. This industry grapples with challenges like a lack of transparency, difficulties in tracking products, a deficit of trust, and issues related to shipping expired products. To address these concerns, blockchain technology as an enterprise application has been harnessed as a solution. Notably, counterfeit drug prevention emerged as the most prevalent category, aligning with the pharmaceutical industry's primary objective. Blockchain technology is an emerging innovation that is finding enterprise applications in various industries, including healthcare. In the healthcare sector, Blockchain networks are being utilized to securely store and exchange patient data across hospitals, diagnostic laboratories, pharmacies, and medical practitioners. These enterprise applications can effectively identify and mitigate critical errors, including potentially hazardous ones within the realm of healthcare. Consequently, this enterprise technology holds the promise of enhancing the efficiency, security, and transparency of medical data sharing within the healthcare system. Moreover, it offers valuable tools for medical institutions to gain insights and improve the analysis of medical records. It visually represents the diverse capabilities, enablers, and the unified workflow process of Blockchain technology in supporting healthcare on a global scale. Additionally, the paper presents a thorough discussion of fourteen significant applications of Blockchain in healthcare, underscoring its pivotal role in addressing issues like deception in clinical trials.

<b>Background</b>: Coronavirus disease 2019 (COVID-19) is a newly emerging human disease caused by a novel coronavirus, causing a global pandemic crisis<b>.</b> Probiotics and/or colchicine may be considered as options for treatment since they have anti-viral, anti-inflammatory, and immunomodulatory effects. The aim of the current review was to assess the effectiveness of probiotic supplements and colchicine on symptoms, duration, and progression of mild and moderate cases of COVID-19 infection<b>.</b> <b>Re</b><b>view</b><b>:</b> A randomized, double-blind, placebo-controlled trial in the United States with 182 participants who were randomly assigned to receive daily oral probiotic (Lactobacillus rhamnosus) LGG or placebo for 28 days. The study indicated that LGG is well-tolerated and is associated with a delay in the onset of COVID-19 infection, a reduction in the incidence of symptoms, and alterations in the structure of the gut microbiome when administered as post-exposure prophylaxis within seven days of exposure. Colchicine may lessen mortality and the need for mechanical ventilation in mild-to-moderate COVID-19 patients, according to a systematic review and meta-analysis. <b>Conclusion: </b>Probiotics and/or colchicine may be viable treatment options for COVID-19 patients. To examine the efficacy of probiotics and colchicine in the treatment of COVID-19, it is necessary to conduct additional clinical trials and provide clinicians with evidence, as there are currently insufficient studies to support this conclusion.

<b>Background: </b>Recently specific interactions and crosslinks between the gut microbiota and the lungs have been recognized, particularly with regard to respiratory immune and anti-microbial reactions. This is often known as the “gut-lung axis” or “a common mucosal immunological system”.<b> Objective: </b>The aim of the current systematic review was to evaluate evidence, from published clinical trials and cohort studies, if probiotics may have an effect in improving and managing COVID-19 symptoms.<b> Materials and methods: </b>The available studies were searched through a comprehensive search of electronic databases that included PubMed, Science Direct, Scirus, ISI Web of Knowledge, Google Scholar and CENTRAL (Cochrane Central Register of Controlled Trials), using a combination of the following keywords: “COVID-19" OR<i> </i>"SARS-CoV-2" AND "Microbiota" OR "Probiotics” OR “Gut Lung Axis”. The literature was reviewed until August 31, 2022<b>. Results: </b>Only 3 studies were included. One of them evaluated the efficacy of probiotics in COVID-19 patients to obtain complete remission of all signs and symptoms. The clinical trial proves that probiotics have a significant effect on complete remission of all signs and symptoms of COVID-19 patients with statistical significant difference. Only one clinical trial out of the 3 included studies had evaluated the need for O2 therapy during the study between the probiotics and control groups, but without statistical significant difference<b>. </b>No statistical significant difference between the probiotics group and placebo group was observed regarding fatal prognosis during the only clinical trial that measured death as an outcome<b>. Conclusion: </b>We couldn’t judge on these results as they are insufficient data for pooling and meta-analysis. However, what we can say is “Most probably Probiotics have no role in treatment of COVID-19 infection”.

Advances in web-centric cloud computing have facilitated the establishment of an integrated cloud environment connecting a wide variety of clinical trial stakeholders. A web-centric cloud framework is proposed for real-time monitoring and risk prediction during clinical trials. The framework focuses on identifying relevant datasets, developing a data-management interface, and implementing machine-learning algorithms for data analysis. Detailed descriptions of the data-management interface and the machine-learning processes are provided, targeting active clinical trials with therapeutic uses in cancer. Demonstrations utilize publicly available clinical-trial data from the ClinicalTrials.gov repository. The real-time monitoring and risk prediction systems were assessed by developing five supervised-classification-machine-learning models for trial-status prediction and six unsupervised models for patient-safety-profile assessment, each representing a different phase of the clinical-trial process. All supervised models yielded high accuracy and area-under-the-curve values at the testing stage, while the unsupervised models demonstrated practical applicability. The results underscore the advantages of using the trial-status algorithm, the patient-safety-profile model, and the proposed framework for performing real-time monitoring and risk prediction of clinical trials.

Psoriasis is a multi-systemic chronic autoimmune inflammatory disorder affecting 125 million people worldwide. The most common type of psoriasis is plaque psoriasis affecting up to 90% of the patients and is characterized by well-demarcated, symmetric, and erythematous plaques with overlying silvery scales that may be painful or itchy. Psoriasis may also affect the joints; increase the risk of developing metabolic syndrome, diabetes, Crohn’s disease, ulcerative colitis, uveitis, certain cancers and an increase in the risk of cardiovascular diseases. Both the skin and the gut microbiome can modulate the development and progression of psoriasis. A connection between the microbiome and immunological mechanisms are antimicrobial peptides, which regulate the microbiome at interfaces and, as antigens, can trigger psoriasis. Few studies were conducted to demonstrate the effect of probiotics on different diseases, as they are living microorganisms that confer a health benefit when administrated in adequate amounts. The effects of administering probiotics include the stabilization of the gut bacterial community and the restoration of “signature” of bacterial microbiota, which is a result of lowering the pH, producing bacteriocins, altering microRNA (miRNAs), competing with pathogens for certain nutrients and improving the gut barrier function. Probiotics counter weight aggressive commensals in the body and reinforce the barrier function of the epithelium while also contributing to the regulation of innate and adaptive immune responses of the host under healthy or pathogenic conditions. Several clinical trials were conducted based on those findings to examine the role of probiotics in psoriasis, but till now there is no evidence of their efficacy.

Probiotics as an intestinal microbe regulator, not only improve the ability of the gastrointestinal microbiota to modulate immune activity, but also strengthen the body's immune system, inhibit allergic reactions and has a significant role especially in the anti-viral immunomodulation. Therefore, in patients with COVID-19, the intestinal micro-eco-regulator, represented by probiotics, may be a therapeutic choice. However, there is still a lack of evidence-based studies to support probiotic treatment of patients with COVID-19. New cohort studies and randomized controlled clinical trials to assess the effectiveness of probiotics in the management of COVID-19 are strongly and urgently needed.

The pandemic corona virus disease 19 (COVID-19), caused by (SARS-CoV-2) a single stranded-RNA virus, has been spread rapidly worldwide with high rate of morbidity and mortality. Few months after the spread of the pandemic, few medications have proven to be efficient in human clinical trials. Several antiviral drugs have been used outside the scope of their initial medical use, such as lopinavir, hydroxychloroquine or azithromycin. Recent researches were done to show the efficacy of ivermectin in reducing SARS-CoV-2 viral RNA within 2 days. The use of ivermectin in in vitro studies has proven its efficacy against Corona virus. Based on the potency of ivermectin in in vitro studies, various clinical trials including patients infected with COVID-19 have been started; most of them have not been completed yet. Since the way how the virus infects the cells in vitro and in vivo is different, a decisive comment about how the ivermectin could exactly be beneficial to the patients has not been proven yet. Nevertheless, if ivermectin is compared to the other therapeutic treatments available for COVID-19 management, ivermectin has proved to have leverage over them. New randomized controlled clinical trials to assess the effectiveness of ivermectin the management of COVID-19 are strongly and urgently needed.

<b>Objectives:</b> There remains no consensus management for isolated distal deep vein thrombosis (IDDVT), with current data inconclusive and dating back to the warfarin era. In the current direct oral anticoagulant (DOAC) era, optimal management of IDDVT needs to be re-assessed. <b>Methods:</b> A retrospective evaluation of patients treated with therapeutic anticoagulation for IDDVT in the DOAC era (2013-2016) was compared with historically published data from the warfarin era (2011-2012). <b>Results:</b> 247 patients were evaluated, 103 from the DOAC era and 122 from the warfarin era. There were less provoked events in the DOAC cohort (45.6% vs 66.7%, p=<0.01). Overall rate of major bleeding was 1.6% with 1.0% in the DOAC era and 2.1% in the warfarin era (p=0.50). There was no difference in rates of VTE progression on treatment 5.8% vs 4.9% respectively (p=0.91). Overall risk of VTE recurrence post cessation was 5.3% (1.86 per 100 person years) with no difference between groups (5.8% vs 4.9%, p=0.74). <b>Conclusions:</b> Our data shows IDDVT is not always benign, with risk of extension despite treatment and long-term risk of VTE-recurrence. Therapeutic anticoagulation with DOAC in these patients was associated with a major bleeding rate of 1.0% in the DOAC cohort. Further clinical trials into the optimal IDDVT management in the DOAC era are necessary.