Current Status Of Clinical Trials Research Articles

Chimeric antigen receptor-natural killer cell therapy: current advancements and strategies to overcome challenges.

Chimeric antigen receptor-natural killer (CAR-NK) cell therapy is a novel immunotherapy targeting cancer cells via the generation of chimeric antigen receptors on NK cells which recognize specific cancer antigens. CAR-NK cell therapy is gaining attention nowadays owing to the ability of CAR-NK cells to release potent cytotoxicity against cancer cells without side effects such as cytokine release syndrome (CRS), neurotoxicity and graft-versus-host disease (GvHD). CAR-NK cells do not require antigen priming, thus enabling them to be used as "off-the-shelf" therapy. Nonetheless, CAR-NK cell therapy still possesses several challenges in eliminating cancer cells which reside in hypoxic and immunosuppressive tumor microenvironment. Therefore, this review is envisioned to explore the current advancements and limitations of CAR-NK cell therapy as well as discuss strategies to overcome the challenges faced by CAR-NK cell therapy. This review also aims to dissect the current status of clinical trials on CAR-NK cells and future recommendations for improving the effectiveness and safety of CAR-NK cell therapy.

Why are clinical trials of deep brain stimulation terminated? An analysis of clinicaltrials.gov

BackgroundAlthough deep brain stimulation (DBS) has established uses for patients with movement disorders and epilepsy, it is under consideration for a wide range of neurologic and neuropsychiatric conditions. ObjectiveTo review successful and unsuccessful DBS clinical trials and identify factors associated with early trial termination. MethodsThe ClinicalTrials.gov database was screened for all studies related to DBS. Information regarding condition of interest, study aim, trial design, trial success, and, if applicable, reason for failure was collected. Trials were compared and logistic regression was utilized to identify independent factors associated with trial termination. ResultsOf 325 identified trials, 79.7% were successful and 20.3% unsuccessful. Patient recruitment, sponsor decision, and device issues were the most cited reasons for termination. 242 trials (74.5%) were interventional with 78.1% successful. There was a statistically significant difference between successful and unsuccessful trials in number of funding sources (p = 0.0375). NIH funding was associated with successful trials while utilization of other funding sources (academic institutions and community organizations) was associated with unsuccessful trials. 83 trials (25.5%) were observational with 84.0% successful; there were no statistically significant differences between successful and unsuccessful observational trials. ConclusionOne in five clinical trials for DBS were found to be unsuccessful, most commonly due to patient recruitment difficulties. The source of funding was the only factor associated with trial success. As DBS research continues to grow, understanding the current state of clinical trials will help design successful future studies, thereby minimizing futile expenditures of time, cost, and patient engagement.

CRISPR/Cas9-Mediated Customizing Strategies for Adoptive T-Cell Therapy.

Clustered regularly interspaced short palindromic repeat-associated protein Cas9 (CRISPR/Cas9) technology is at the forefront of cancer immunotherapy innovation, offering precise and personalized treatment strategies. In this review, we discuss CRISPR/Cas9's ability to precisely edit the genome, its impact on immune checkpoint control, and its application in immune cell engineering, where it surpasses traditional gene editing techniques. Originally inspired by bacterial defense mechanisms, this technology has made great strides in cancer immunotherapy as a mechanism to specifically target the PD-1/PD-L1 pathway in immune checkpoint blockades. In addition, CRISPR/Cas9 plays an important role in cancer treatment by facilitating genetic modifications to enhance the properties of adoptive cell therapy, optimizing the therapeutic potential of this approach. This review provides an overview of the development of CRISPR/Cas9, its important role in immune checkpoint control, applications in immune cell engineering, and the current status of clinical trials. However, safety concerns related to off-target effects and unintended mutations require continued research and caution. Continued advances in CRISPR technology hold the promise of revolutionizing the cancer treatment paradigm, providing personalized and effective therapies for patients with various types of cancer.

A Recent Update on the Potential Use of Catechins in Cosmeceuticals

Catechins are a type of flavonoid known for their beneficial functions as antioxidants and antibacterials. Recent research indicates the antioxidant potential of catechins on the skin. Catechin and epigallocatechin are reported to have significant potential in preventing ageing. Epigallocatechin gallate, gallocatechin gallate, and epigallocatechin can inhibit hyperpigmentation processes. Additionally, catechins exhibit potential in UV protection and inflammation inhibition in acne. Consequently, catechins are now being used in the cosmetics industry, with formulations containing catechins as the active ingredient developed to produce various products such as soap, sunscreen, creams, etc. Herein, this paper reviews the antioxidant potential of catechins for use in cosmetic formulations and the current status of clinical trials of catechins in cosmetics.

The current status of clinical trials on cancer and age disparities among the most common cancer trial participants

ObjectiveTo illustrate the status of all cancer clinical trials and characterize clinical trial enrollment disparities in the most common cancer.MethodsClinical trial data were extracted from ClinicalTrials.gov website. All searched clinical trials were included in the current status analysis of clinical trials on cancer. Among all the clinical trials, only trials addressing single disease sites of breast, prostate, colorectal, or lung (BPCRL) cancer were included in the age disparities analysis. The difference in median age (DMA) between the trial participant median age and the population-based disease-site-specific median age was calculated for each trial.ResultsA total of 7747 clinical trials were included in the current status analysis of clinical trials on cancer. The number of registered trials had been increasing from 2008 to 2021 (AAPC = 50.60, 95% CI 36.60, 66.00, P < 0.05). Of the 7747 trials, 1.50% (116) of the studies were clinical trials for the elderly aged 60 years or older. 322 trials were included in the age disparities analysis. For all trials, the median DMA was − 8.15 years (P25, P75, − 10.83 to − 2.98 years, P < 0.001). The median DMA were − 9.55 years (P25, P75, − 11.63 to − 7.11 years), − 7.10 years (P25, P75, − 9.80 to − 5.70 years), − 9.75 years (P25, P75, − 11.93 to − 7.35 years), 3.50 years (P25, P75, 0.60 to 4.55 years), respectively, for breast cancer, colorectal cancer, lung cancer and prostate cancer.ConclusionThe numbers of registered clinical trials show an upward trend. Age disparities between trial participants and diagnosed disease population are present in BPCRL cancer trials and appear to be increasing over time. Equitable participation in clinical trials on the basis of age is crucial for advancing medical knowledge and evaluating the safety and efficacy of new treatments that are generalizable to aging populations.

Current State of Clinical Trials Regarding Alveolar Bone Grafting.

Alveolar ridge defects develop because of surgery, trauma, infection, or congenital malformations. Alveolar ridge defects can be resolved using an osseous replacement. The primary outcomes of osseous replacement are the maintenance of contour; the elimination of dead space, the reduction of postoperative infection; and the increase in bony and soft tissue healing. Recent research shows promising developments in dental bone grafts. This review presents the results of several clinical trials and provides updates on current alveolar bone grafting. In May 2023, we searched Clinicaltrials.gov for interventional clinical trials related to alveolar bone grafting. A total of 66 clinical trials were included using Boolean Operators AND, OR, NOT we used the “advanced search” option with the search terms [Alveolar Bone Grafting] OR [Ridge Preservation] OR [Dental Bone Grafting] OR [Ridge Augmentation]. Reviewed publications are summarized. 28 out of the 66 trials were successfully completed. None of the trials had offered an invitation to enroll, and only one was terminated. Autograft was the most prevalent kind of grafting, at 28 out of 66, more than twice as prevalent as allograft, which ranked second at 12 out of 66. this study shows a lack of variety in location, low results provided, and low clinical trials regarding bone rejection. The focus of published trials was mainly on cleft palate rehabilitation using secondary alveolar bone grafting, and the usage of L-prf, rh-FGF-2, rhBMP2, and hyaluronic acid in association with alveolar bone grafting showed remarkable results concerning bone's osteoconduction, osteoinduction, and osteogenesis.

Anti-PD-1/PD-L1 for nasopharyngeal carcinoma: a comprehensive analysis of registered trials on ClinicalTrials.gov.

Objective: Clinical trials play an important role in the development of healthcare. However, the current status of clinical trials on anti-PD-1/PD-L1 for nasopharyngeal carcinoma remains unclear. Therefore, this study aims to provide a comprehensive analysis of the registered trials related to anti-PD-1/PD-L1 for nasopharyngeal carcinoma on ClinicalTrials.gov. Methods: A search was conducted on the ClinicalTrials.gov database to identify all registered trials related to anti-PD-1/PD-L1 for nasopharyngeal carcinoma up to 26 February 2023. The characteristics of the trials were examined, and the studied drugs, disease conditions, as well as details of trials with available results were analyzed. Publication status was assessed by a PubMed search using the ClinicalTrials.gov NCT number. Results: A total of 112 interventional clinical trials registered between 2015 and 2023 were included. Of the trials, 90 were carried out in Asia, 72 were in phase 2, and 31 trials had either companies or universities as sponsors/collaborators. The sample sizes across the trials varied greatly, with a median of 71.5 participants per trial. The majority of trials were recruiting participants, with only 6 had posted results. PD-1 inhibitors were preferred over PD-L1, and Toripalimab emerged as the most extensively studied drug. About one-third (33.9%) of the studies looked into recurrent/metastatic nasopharyngeal cancer. Conclusion: This study provides an overview of all registered trials of anti-PD-1/PD-L1 for NPC. It is needed to improve the completeness, outcome selection, randomization and masking of trials and to be transparent and timely in reporting of results.

Clinical relevance of sentinel lymph node biopsy in early ovarian cancer.

The first-line treatment for early ovarian cancer typically involves primary debulking surgery aimed at maximal cytoreduction, alongside adjuvant chemotherapy if clinically indicated. Nodal assessment involving pelvic and para-aortic lymph node dissection is typically performed during the primary debulking surgery. However, the survival benefit of lymphadenectomy in patients with early ovarian cancer has not been well established, and the procedure is associated with longer operation time and higher perioperative complications. With the emergence of minimally invasive surgery as a potential alternative to laparotomy for early ovarian cancer, sentinel lymph node biopsy has been evaluated in this setting. In this review, we summarized the current literature regarding sentinel lymph node biopsy in patients with early ovarian cancer, focusing on the clinical relevance of this method, including its detection rate and diagnostic accuracy. Additionally, we discuss the current status of clinical trials investigating sentinel lymph node biopsy in early ovarian cancer cases.

Human Stem Cells for Cardiac Disease Modeling and Preclinical and Clinical Applications-Are We on the Road to Success?

Cardiovascular diseases (CVDs) are pointed out by the World Health Organization (WHO) as the leading cause of death, contributing to a significant and growing global health and economic burden. Despite advancements in clinical approaches, there is a critical need for innovative cardiovascular treatments to improve patient outcomes. Therapies based on adult stem cells (ASCs) and embryonic stem cells (ESCs) have emerged as promising strategies to regenerate damaged cardiac tissue and restore cardiac function. Moreover, the generation of human induced pluripotent stem cells (iPSCs) from somatic cells has opened new avenues for disease modeling, drug discovery, and regenerative medicine applications, with fewer ethical concerns than those associated with ESCs. Herein, we provide a state-of-the-art review on the application of human pluripotent stem cells in CVD research and clinics. We describe the types and sources of stem cells that have been tested in preclinical and clinical trials for the treatment of CVDs as well as the applications of pluripotent stem-cell-derived in vitro systems to mimic disease phenotypes. How human stem-cell-based in vitro systems can overcome the limitations of current toxicological studies is also discussed. Finally, the current state of clinical trials involving stem-cell-based approaches to treat CVDs are presented, and the strengths and weaknesses are critically discussed to assess whether researchers and clinicians are getting closer to success.

신경섬유종증 2형에서 표적치료: 임상시험의 현황

Neurofibromatosis type 2 (NF2) is a rare autosomal dominant disorder characterized as bilateral vestibular schwannoma (VS), various brain and spinal tumors. Therapeutic options for NF2 patients have been limited to surgery and radiation. However, outcomes are not effective for NF2-related VSs. Understanding the molecular mechanisms driving NF2 pathogenesis holds promise for the potential use of targeted therapy. Many targeted therapies have been evaluated in preclinical models. Several clinical trials have been conducted to stop tumor growth and, in some cases, to improve cer-tain signs and symptoms of NF2, such as hearing loss. We review the current state of clinical trials of NF2.

Current state of clinical trials on xenograft.

Xenotransplantation is a worth investing branch of science, since it aims to fulfil the demand on human cells, tissues and organs. Despite decades of consistent work in preclinical assessments, clinical trials on xenotransplantation are far from reaching the targeted goal. Our study aims to track the characteristics, assess the content and summarize the plan of each trial on skin, beta-island, bone marrow, aortic valve and kidney xenografts, leading to a clear sorting of efforts made in this field. In December 2022, we searched clinicaltrial.gov for interventional clinical trials related to xenograft of skin, pancreas, bone marrow, aortic valve and kidney. A total of 14 clinical trials are included in this study. Characteristics on each trial were gathered. Linked publications were searched using Medline/PubMed and Embase/Scopus. Content of trials was reviewed and summarized. Only 14 clinical trials met our study's criteria. The majority were completed, and most of the trials' enrolment was between 11 and 50 participants. Nine trials used a xenograft of porcine origin. Six trials targeted skin xenotransplantation, four targeted β-cells, two targeted bone marrow and one trial targeted each of the kidney and aortic valve. The average length of trials was 3.38 years. Four trials were conducted in the United States and two trials in each of Brazil, Argentina and Sweden. Of all the included trials, none had any results provided and only three had published work. Phases I, III, and IV had only one trial each. A total of 501 participants were enrolled in these trials. This study sheds the light on the current state of clinical trials on xenograft. Characteristically, trials on this field are of low number, low enrolment, short duration, few related publications and no published results. Porcine organs are the most used in these trials, and skin is the most studied organ. An extension of the literature is highly needed due to the variety of conflicts mentioned. Overall, this study sheds the light on the necessity of managing research efforts, leading to the initiation of more trials targeting the field of xenotransplantation.

Peptide cargo administration: current state and applications

Effective delivery of drug molecules to the target site is a challenging task. In the last decade, several innovations in the drug delivery system (DDS) have tremendously improved the therapeutic efficacy of drug molecules. Among various DDS, cell-penetrating peptides (CPPs)based DDS have gathered notable attention owing to their safety, efficacy, selectivity, specificity, and ease of synthesis. CPPs are emerging as anefficient and effective pharmaceutical nanocarriers-based platforms for successful management of various important human health disorders. Failure of several current chemotherapeutic strategies is attributed to low solubility, reduced bioavailability, and off-target delivery of several anti-cancer drugs. Similarly, development of therapeutics for vision-threatening disorders is challenged by the anatomical as well as physiological complexity of the eye. Such therapeutic challenges in cancer and ocular disease management can be overcome by developing cell-penetrating peptide (CPP)based peptide drug conjugates (PDCs). CPPs can be used to deliver various types of cargo molecules including nucleic acids, small molecules, and peptides/proteinaceous agents. In this review, we have briefly introduced CPPs and the linker strategies employed for the development of PDCs. Furthermore, recent studies employing CPP-based PDCs for cancer and ocular disease management have been discussed in detail highlighting their significance over conventional DDS. Later sections of the review are focused on the current status of clinical trials and future implications of CPP-based PDCs in vaccine development. KEY POINTS: • Cell-penetrating peptides (CPPs) can deliver a variety of cargo macromolecules via covalent and non-covalent conjugation. • CPP-based peptide drug conjugates (PDCs) can overcome drawbacks of conventional drug delivery methods such as biocompatibility, solubility, stability, and specificity. • Various PDCs are in clinical trial phase for cancer and ocular therapeutics.

Current landscape of clinical trials for HPV-positive head and neck squamous cell carcinoma (HNSCC).

This study aims to determine the current state of clinical trials regarding HPV-positive head and neck squamous cell carcinoma (HNSCC). Clinical trials were filtered to fit the study's aim using Clinicaltrials.gov: trials concerning HNSCC specifically those related to HPV done between January 2005 and December 2020 were extracted and information regarding location, duration, phases, patient recruitment, trial status, results, primary outcome, type of intervention and publication status were collected and analysed. As a result, 123 trials were included. North American countries (USA and Canada) conducted more than two-thirds of the trials (72.4%) compared to European countries and the rest of the world. Trials in phase II constituted more than half of those included in this study (53.7%). From the 123 trials included in this study, only 30 had their NCT identification number linked to publications, but less than half (46.7%) of the publications stemmed from trials with results. Drug combination was the most widely studied treatment modality. Despite falling in the middle of the spectrum with respect to the number of trials when compared to other diseases, our research highlights the need for even more trials tackling multiple aspects of HPV-positive HNSCC.

Clinical trials for renal allograft tolerance induction through combined hematopoietic stem cell transplantation: A narrative review.

During the last four decades, development of effective immunosuppressants has significantly improved short-term results of organ transplantation. However, long-term results have not been satisfactory due to chronic rejection or complications caused by immunosuppressive drugs. Therefore, induction of immunological tolerance of the transplanted organ is considered essential to improve the long-term results. Despite numerous tolerance strategies that have been successful in murine models, inducing hematopoietic chimerism through donor hematopoietic stem cell transplantation is the only method that reproducibly induces kidney allograft tolerance in nonhuman primates or humans. Combining kidney and hematopoietic stem cell transplantation to achieve allograft tolerance has now been attempted with different chimerism strategies. This review summarizes the status of current clinical trials on the induction of allograft tolerance. We also summarize recent studies to extend the chimerism approach to deceased donor transplant recipients.

Topical ophthalmic administration: Can a drug instilled onto the ocular surface exert an effect at the back of the eye?

Topical ophthalmic instillation is an appealing strategy to deliver drugs to the back of the eye to treat retinal diseases such as neovascular age-related macular degeneration, diabetic retinopathy, retinal vein occlusion, and glaucomatous optic neuropathy. It has several advantages such as being non-invasive and user-friendly, e.g., allowing self-administration. However, the main obstacle has been how to achieve therapeutic drug concentrations in the retina due to the eye’s protective mechanisms, flows, and barriers. Less than 4% of the instilled drug dose enters the anterior chamber, and much less is expected to reach the posterior segment. It is crucial to understand a drug’s topical pharmacokinetics in humans and how one can extrapolate data from rabbits to humans. In this review, the available data on the retina and vitreous drug concentrations from pharmacokinetics studies conducted in human patients and rabbits have been compiled, together with the critical physiological factors to be considered for this route of administration. Improvements in the design of preclinical studies are suggested to increase their translatability to the treatment of human patients. Finally, the current status of clinical trials with topical ophthalmic formulations intended to treat the back of the eye is depicted. At present, no topical ophthalmic formulations to treat neovascular age-related macular degeneration or other retinal neurodegenerative illnesses have reached the market.

Current state of clinical trials regarding lung transplant rejection

BackgroundOver the last several decades, the field of lung transplantation has made significant advances. Despite these advancements, morbidity and mortality rates are still high when compared to other solid organ transplants. Clinical trials have a significant role bringing new medications with better effects than their predecessors. Our study is critical in evaluating and tracking clinical trials involving rejection of lung transplant, with a focus on interventional therapeutic trials. MethodsOn November 3, 2021, we searched clinicaltrial.gov for interventional clinical trials related to lung transplant rejection. A total of 39 clinical trials are included in this study. Characteristics on each trial were gathered. Linked publications were searched using Medline/PubMed and Embase/Scopus, and their content reviewed and summarized. ResultsThe majority of trials were divided into completed (15 out of 39) and recruiting (12 out of 39). 17 trials had between 11 and 50 participants, and 8 had above 100. Only 1 trial lasted >10 years, and the average length of all trials was 3.6 years. The majority of trials were conducted in Europe/UK/Russia and the United States/Canada (17 and 18 trials, respectively). The results were provided in 3 trials, and also published in 3, showing a decrease in the rate of patients reaching an endpoint after chronic rejection with liposomal aerosol cyclosporine, a decrease in their cytokines level, and an increase in their 5-year-survival rate compared to the oral conventional immunosuppressant, the benefit of sirolimus in decreasing the acute rejection rate and severity in comparison to azathioprine, and its efficacy against cytomegalovirus infections. Other trials revealed the benefits of azithromycin in remarkably decreasing airways and systemic inflammation, with a concomitant decline in the risk of both BOS and CLAD; highlighting the deleterious effects of air pollution after transplantation surgery; and using the grading biopsy as a post-transplantation assessment tool. ConclusionThis study is a descriptive analysis of clinical trials targeting lung transplant rejection. This study shows the low number of trials, lack of variety in location and low publishing rates. Although focus of published trials was mainly towards azithromycin, bronchiolitis obliterans syndrome, air pollution, and biopsy in grading, a remarkable progress was realized concerning therapies, leading to less complications with a delay of chronic rejection onset, and an increase in overall survival. This sheds the light on the need for managing research efforts to fulfill any lack in specific domain, leading to new, effective therapies, and providing thereby much more benefit.

Comprehensive Analysis Of Clinical Trials In Pakistan From September 1992 To February 2019.

Clinical trials are conducted to evaluate interventions (drugs, medical devices, surgical methods and radiation treatment) for treating diseases or conditions. They may also be done to prevent the development or prevent recurrence or determining risk factors. We wanted to review the current status of clinical trials in Pakistan. On searching ClinicalTrials.gov, registered clinical trials conducted in Pakistan from September 1992 to February 2019 were reviewed. The analysis evaluated the characteristics of the clinical studies including the type of intervention, geographic distribution of studies, anticipated enrolment and number of participants, blinding, allocation status, lead sponsors, age group, study type, recruitment status, gender, study results, study phase, primary purpose and subject distribution. The results were tabulated with frequencies and percentages provided by category. There were 508 registered clinical trials conducted in Pakistan from September 1992 to February 2019. Interventional clinical trials were conducted more often than observational trials (77.2% and 22.8% respectively), with drugs (41.4%) as the most common intervention. The majority of registered trials had participants ranging between 101-1000 (47.2%) with most having no blinding in their methodology (34.1%). Most of the trials conducted were randomized (66.5%) while few (5.3%) were non-randomized. Among the sponsor categories, 66.5% of the trials belong to the 'Other' (non-governmental, non-industry) category. Although 59.6% of the registered trials have been completed, most of them (91.3%) did not report their results. Treatment intervention trials in Internal Medicine were the most common primary purpose. An increasing trend in the frequency of clinical trials was also evident. The number of clinical trials in Pakistan showed an increasing trend over the time period studied, which may reflect on the general outlook of clinical research in the country. Most clinical trials were sponsored by universities, hospitals and non-profit organizations but less than 10% of studies reported results.

Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities.

Vitamin K2-7, also known as menaquinone-7 (MK-7) is a form of vitamin K that has health-beneficial effects in osteoporosis, cardiovascular disease, inflammation, cancer, Alzheimer’s disease, diabetes and peripheral neuropathy. Compared to vitamin K1 (phylloquinone), K2-7 is absorbed more readily and is more bioavailable. Clinical studies have unequivocally demonstrated the utility of vitamin K2-7 supplementation in ameliorating peripheral neuropathy, reducing bone fracture risk and improving cardiovascular health. We examine how undercarboxylated osteocalcin (ucOC) and matrix Gla protein (ucMGP) are converted to carboxylated forms (cOC and cMGP respectively) by K2-7 acting as a cofactor, thus facilitating the deposition of calcium in bones and preventing vascular calcification. K2-7 is beneficial in managing bone loss because it upregulates osteoprotegerin which is a decoy receptor for RANK ligand (RANKL) thus inhibiting bone resorption. We also review the evidence for the health-beneficial outcomes of K2-7 in diabetes, peripheral neuropathy and Alzheimer’s disease. In addition, we discuss the K2-7-mediated suppression of growth in cancer cells via cell-cycle arrest, autophagy and apoptosis. The mechanistic basis for the disease-modulating effects of K2-7 is mediated through various signal transduction pathways such as PI3K/AKT, MAP Kinase, JAK/STAT, NF-κB, etc. Interestingly, K2-7 is also responsible for suppression of proinflammatory mediators such as IL-1α, IL-1β and TNF-α. We elucidate various genes modulated by K2-7 as well as the clinical pharmacometrics of vitamin K2-7 including K2-7-mediated pharmacokinetics/pharmacodynamics (PK/PD). Further, we discuss the current status of clinical trials on K2-7 that shed light on dosing strategies for maximum health benefits. Taken together, this is a synthetic review that delineates the health-beneficial effects of K2-7 in a clinical setting, highlights the molecular basis for these effects, elucidates the clinical pharmacokinetics of K2-7, and underscores the need for K2-7 supplementation in the global diet.

MicroRNA Networks in Cognition and Dementia.

The change from viewing noncoding RNA as “junk” in the genome to seeing it as a critical epigenetic regulator in almost every human condition or disease has forced a paradigm shift in biomedical and clinical research. Small and long noncoding RNA transcripts are now routinely evaluated as putative diagnostic or therapeutic agents. A prominent role for noncoding microRNAs in the central nervous system has uncovered promising new clinical candidates for dementia-related disorders, treatments for which currently remain elusive even as the percentage of diagnosed patients increases significantly. Cognitive decline is a core neurodegenerative process in Alzheimer’s Disease, Frontotemporal Dementia, Lewy body dementia, vascular dementia, Huntington’s Disease, Creutzfeldt–Jakob disease, and a significant portion of Parkinson’s Disease patients. This review will discuss the microRNA-associated networks which influence these pathologies, including inflammatory and viral-mediated pathways (such as the novel SARS-CoV-2 virus implicated in COVID-19), and their current status in clinical trials.

Human papillomavirus-related oropharyngeal carcinoma.

It was not until around 2000 that human papillomavirus-related oropharyngeal carcinoma was recognized as carcinoma with clinical presentations different from nonrelated head and neck carcinoma. Twenty years after and with the revision of the tumor-node-metastasis classification in 2017, various clinical trials focused on human papillomavirus-related oropharyngeal carcinoma to improve the prognosis and quality of life of patients with this disease. However, the incidence of human papillomavirus-related cancers is increasing, which is expected to be particularly prominent in Japan, where human papillomavirus vaccination is not widely available. In this review, we describe the current status of clinical trials (mainly focused on initial surgery and radiation dose reduction) for, primary and secondary prevention of, and the present status of human papillomavirus-related oropharyngeal carcinoma in Japan.