Validation of a dermatoscopy-based algorithm for the diagnosis of acral melanoma.

INTRODUCTION: Diagnosis of acral melanocytic lesions can be challenging. The BRAAFF checklist was introduced as a tool to help differentiate between acral nevi and melanoma but has not been validated. METHODS: We asked raters with varying expertise in dermatoscopy to diagnose dermatoscopic images of 533 acral nevi and 144 melanomas via an online platform with and without use of the BRAAFF checklist. From the ratings we calculated sensitivity, specificity, and interrater agreement. Additionally, a new simplified version of the checklist was also tested. RESULTS: We collected 6880 ratings from 175 readers. The BRAAFF checklist achieved a sensitivity of 92.5% and a specificity of 65.0%, which was similar to diagnosis from pattern recognition (sensitivity 90.0%, specificity: 72.1%). Interrater agreement for the BRAAFF criteria ranged from fair to moderate, with lowest agreement for parallel ridge and fibrillar pattern (alpha=0.31) and highest for asymmetry of colors and structures (alpha=0.46). Agreement and diagnostic accuracy were higher for more experienced readers. A simplified version with only two criteria achieved similar sensitivity (95.0%) and lower specificity (60.0%) as the original BRAAFF checklist. Conclusion: The BRAAFF checklist is a useful tool for the diagnosis of melanocytic acral lesions with acceptable sensitivity and reasonable specificity but is not superior to pattern recognition. A simplified version of the checklist could be easier to use with equal sensitivity while exhibiting a modest reduction in specificity.

Polyploid QTL-seq revealed multiple QTLs controlling steamed tuber texture and starch gelatinization temperature in sweetpotato.

Sweetpotato (Ipomoea batatas) includes diverse cultivars with flesh textures ranging from dry to moist. Moist-fleshed cultivars often contain starch with a lower gelatinization temperature (GT). To elucidate the genetic determinants of flesh texture and starch GT, we conducted a QTL analysis using F1 progenies obtained from a cross between dry-fleshed and moist-fleshed cultivars, 'Benikomachi' (BK) and 'Amahazuki' (AH), by using an updated polyploid QTL-seq pipeline. Flesh texture was assessed based on the wet area ratio (WAR) observed on the cut surface of steamed tubers, as progenies with dry and moist flesh exhibited low and high WAR values, respectively, demonstrating a strong correlation. Three QTLs were found to regulate the WAR. Notably, two AH-derived alleles at 4.30 Mb on Itr_chr05 and 21.01 Mb on Itr_chr07, along with a BK-derived allele at 2.89 Mb on Itr_chr15, were associated with increased WAR. Starch GT, which displayed no correlation with either flesh texture or WAR, was distinctly influenced by two QTLs: a GT-increasing BK-derived allele at 1.74 Mb on Itr_chr05 and a GT-decreasing AH-derived allele at 30.16 Mb on Itr_chr12. Consequently, we developed DNA markers linked to WAR, offering a promising avenue for the targeted breeding of sweetpotato with the desired flesh textures.

A Stealthiness Evaluation of Main Chain Carboxybetaine Polymer Modified into Liposome.

Background: Acrylamide polymers with zwitterionic carboxybetaine (CB) side groups have attracted attention as stealth polymers that do not induce antibodies when conjugated to proteins. However, they induce antibodies when modified onto liposomes. We hypothesized that antibodies are produced against polymer backbones rather than CB side groups. Objectives: In this study, we designed and synthesized a polymer employing CB in its main chain, poly(N-acetic acid-N-methyl-propyleneimine) (PAMPI), and evaluated the blood retention of PAMPI-modified liposomes in mice. Results: The non-fouling nature of PAMPI-modified liposomes estimated from serum protein adsorption was found to be not inferior to PCB- and PEG-modified liposomes. However, to our surprise, the PAMPI-modified liposomes showed an instantaneous clearance less than 1 h post-injection, comparable to the naked liposomes. Conclusions: The extent of the blood retention of polymer-modified liposomes cannot be predicted by their susceptibility to serum protein adsorption and semi-flexible conformation.

Non-invasive SARS-CoV-2 RNA detection and human transcriptome analysis using skin surface lipids.

There have been several reports of skin manifestations in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA can be detected on the skin surface, including the sebum, of these patients. In this study, SARS-CoV-2 RNA was detected using real-time reverse-transcription polymerase chain reaction (RT-PCR) assay of skin surface lipids (SSLs) collected using an oil-blotting film from the faces of hospitalized patients with COVID-19. Human transcriptome analysis was also performed using the same samples. In facial SSLs of patients with COVID-19, the RT-PCR positivity rate was 84.6% (11/13 samples) within 5 days and 30.4% (7/23 samples) by 6-10 days of symptom onset. In the transcriptome analysis, the most characteristic SSL-RNA profile was the upregulation of interferon-stimulated gene (ISG)-related genes, such as ISG15, IFITM1, and MX1. This study presents an alternative technique using SSLs for non-invasive SARS-CoV-2 RNA detection and simultaneous analysis of human molecular pathogenesis in patients with COVID-19.

Vascular Impairment, Muscle Atrophy, and Cognitive Decline: Critical Age-Related Conditions.

The triad of vascular impairment, muscle atrophy, and cognitive decline represents critical age-related conditions that significantly impact health. Vascular impairment disrupts blood flow, precipitating the muscle mass reduction seen in sarcopenia and the decline in neuronal function characteristic of neurodegeneration. Our limited understanding of the intricate relationships within this triad hinders accurate diagnosis and effective treatment strategies. This review analyzes the interrelated mechanisms that contribute to these conditions, with a specific focus on oxidative stress, chronic inflammation, and impaired nutrient delivery. The aim is to understand the common pathways involved and to suggest comprehensive therapeutic approaches. Vascular dysfunctions hinder the circulation of blood and the transportation of nutrients, resulting in sarcopenia characterized by muscle atrophy and weakness. Vascular dysfunction and sarcopenia have a negative impact on physical function and quality of life. Neurodegenerative diseases exhibit comparable pathophysiological mechanisms that affect cognitive and motor functions. Preventive and therapeutic approaches encompass lifestyle adjustments, addressing oxidative stress, inflammation, and integrated therapies that focus on improving vascular and muscular well-being. Better understanding of these links can refine therapeutic strategies and yield better patient outcomes. This study emphasizes the complex interplay between vascular dysfunction, muscle degeneration, and cognitive decline, highlighting the necessity for multidisciplinary treatment approaches. Advances in this domain promise improved diagnostic accuracy, more effective therapeutic options, and enhanced preventive measures, all contributing to a higher quality of life for the elderly population.

Leveraging adrenergic receptor blockade for enhanced nonalcoholic fatty liver disease treatment via a biomimetic nanoplatform.

Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive lipid accumulation, steatosis and fibrosis. Sympathetic nerves play a critical role in maintaining hepatic lipid homeostasis and regulating fibrotic progression through adrenergic receptors expressed by hepatocytes and hepatic stellate cells; however, the use of sympathetic nerve-focused strategies for the treatment of NAFLD is still in the infancy. Herein, a biomimetic nanoplatform with ROS-responsive and ROS-scavenging properties was developed for the codelivery of retinoic acid (RA) and the adrenoceptor antagonist labetalol (LA). The nanoplatform exhibited improved accumulation and sufficient drug release in the fibrotic liver, thereby achieving precise codelivery of drugs. Integration of adrenergic blockade effectively interrupted the vicious cycle of sympathetic nerves with hepatic stellate cells (HSCs) and hepatocytes, which not only combined with RA to restore HSCs to a quiescent state but also helped to reduce hepatic lipid accumulation. We demonstrated the excellent ability of the biomimetic nanoplatform to ameliorate liver inflammation, fibrosis and steatosis. Our work highlights the tremendous potential of a sympathetic nerve-focused strategy for the management of NAFLD and provides a promising nanoplatform for the treatment of NAFLD.

Pronounced Cold Crystallization and Hydrogen Bonding Distortion of Water Confined in Microphases of Double Zwitterionic Block Copolymer Aqueous Solutions.

Advanced materials leveraging water control are garnering considerable interest, with the state of water emerging as a critical aspect of material design. This study explored the impact of microphase separation on water using aqueous solutions of double zwitterionic diblock copolymers, specifically poly(carboxybetaine methacrylate) and poly(sulfobetaine methacrylate) (PCB2-b-PSB4). These copolymers form a mesoscale periodic ordered lattice structure consisting of two distinct aqueous phases. Through differential scanning calorimetry and X-ray emission spectroscopy, it was found that water in these PCB2-b-PSB4 aqueous solutions exhibits pronounced cold crystallization and subtle distortions in hydrogen-bonding configurations.

Curcumin: A Golden Approach to Healthy Aging: A Systematic Review of the Evidence.

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2256 documents, leading to the selection of 15 clinical trials for synthesis. Here, we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

Predictors of Postoperative Persistent Low Back Pain Following Lumbar Fusion in Patients Older than 75 Years: An Analysis of a Minimum 2-Year Follow-Up.

OBJECTIVE: This study aimed to evaluate preoperative and perioperative predictors associated with persistent low back pain (LBP) following lumbar fusion in patients aged >75 years. METHODS: This single-center retrospective study examined 310 patients aged >75 years who underwent lumbar fusion for lumbar degenerative disease (104 males, 206 females; mean age, 79 [75-90] years). The visual analog scale (VAS) score for LBP was examined preoperatively and 2-year postoperatively. The persistent LBP group comprised patients with a 2-year postoperative LBP-VAS score ≥3. The demographic and preoperative radiographic parameters were also reviewed. A multivariate stepwise logistic regression analysis was performed of variables with values of P < 0.2 on the univariate analysis. RESULTS: Ninety-nine patients (32%) experienced persistent postoperative LBP. Multivariate logistic regression analysis revealed that age <82 years, history of previous lumbar decompression, and greater preoperative VAS score for LBP were associated with greater postoperative persistent LBP after lumbar fusion, whereas other factors, such as gender, body mass index, osteoporosis, diabetes mellitus, depression, symptom duration, operative time, estimated blood loss, and spinopelvic sagittal parameters, were not. CONCLUSIONS: This study showed that a relatively younger age, history of preoperative lumbar decompression, and greater preoperative VAS score for LBP were preoperative predictors of postoperative persistent LBP following lumbar fusion in elderly patients. In contrast, preoperative spinopelvic sagittal parameters were not associated with persistent postoperative LBP. Although lumbar fusion is expected to improve LBP, surgeons should pay attention to age, surgical history, and preoperative back pain intensity.

Revolutionizing our understanding of Parkinson's disease: Dr. Heinz Reichmann's pioneering research and future research direction.

Millions of individuals around the world are afflicted with Parkinson's disease (PD), a prevalent and incapacitating neurodegenerative disorder. Dr. Reichmann, a distinguished professor and neurologist, has made substantial advancements in the domain of PD research, encompassing both fundamental scientific investigations and practical applications. His research has illuminated the etiology and treatment of PD, as well as the function of energy metabolism and premotor symptoms. As a precursor to a number of neurotransmitters and neuromodulators that are implicated in the pathophysiology of PD, he has also investigated the application of tryptophan (Trp) derivatives in the disease. His principal findings and insights are summarized and synthesized in this narrative review article, which also emphasizes the challenges and implications for future PD research. This narrative review aims to identify and analyze the key contributions of Reichmann to the field of PD research, with the ultimate goal of informing future research directions in the domain. By examining Reichmann's work, the study seeks to provide a comprehensive understanding of his major contributions and how they can be applied to advance the diagnosis and treatment of PD. This paper also explores the potential intersection of Reichmann's findings with emerging avenues, such as the investigation of Trp and its metabolites, particularly kynurenines, which could lead to new insights and potential therapeutic strategies for managing neurodegenerative disorders like PD.

Disentangling the role of gray matter volume and concentration in autism spectrum disorder: A meta-analytic investigation of 25 years of voxel-based morphometry research.

Despite over two decades of neuroimaging research, a unanimous definition of the pattern of structural variation associated with autism spectrum disorder (ASD) has yet to be found. One potential impeding issue could be the sometimes ambiguous use of measurements of variations in gray matter volume (GMV) or gray matter concentration (GMC). In fact, while both can be calculated using voxel-based morphometry analysis, these may reflect different underlying pathological mechanisms. We conducted a coordinate-based meta-analysis, keeping apart GMV and GMC studies of subjects with ASD. Results showed distinct and non-overlapping patterns for the two measures. GMV decreases were evident in the cerebellum, while GMC decreases were mainly found in the temporal and frontal regions. GMV increases were found in the parietal, temporal, and frontal brain regions, while GMC increases were observed in the anterior cingulate cortex and middle frontal gyrus. Age-stratified analyses suggested that such variations are dynamic across the ASD lifespan. The present findings emphasize the importance of considering GMV and GMC as distinct yet synergistic indices in autism research.

Navigating the Neurobiology of Migraine: From Pathways to Potential Therapies.

Migraine is a debilitating neurological disorder characterized by recurring episodes of throbbing headaches that are frequently accompanied by sensory disturbances, nausea, and sensitivity to light and sound [...].

Ginkgo biloba: A Leaf of Hope in the Fight against Alzheimer's Dementia: Clinical Trial Systematic Review.

Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords-GB in AD and dementia-yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.

Baricitinib ameliorates inflammatory and neuropathic pain in collagen antibody-induced arthritis mice by modulating the IL-6/JAK/STAT3 pathway and CSF-1 expression in dorsal root ganglion neurons.

BACKGROUND: Janus kinase (JAK) inhibitors, such as baricitinib, are widely used to treat rheumatoid arthritis (RA). Clinical studies show that baricitinib is more effective at reducing pain than other similar drugs. Here, we aimed to elucidate the molecular mechanisms underlying the pain relief conferred by baricitinib, using a mouse model of arthritis. METHODS: We treated collagen antibody-induced arthritis (CAIA) model mice with baricitinib, celecoxib, or vehicle, and evaluated the severity of arthritis, histological findings of the spinal cord, and pain-related behaviours. We also conducted RNA sequencing (RNA-seq) to identify alterations in gene expression in the dorsal root ganglion (DRG) following baricitinib treatment. Finally, we conducted in vitro experiments to investigate the direct effects of baricitinib on neuronal cells. RESULTS: Both baricitinib and celecoxib significantly decreased CAIA and improved arthritis-dependent grip-strength deficit, while only baricitinib notably suppressed residual tactile allodynia as determined by the von Frey test. CAIA induction of inflammatory cytokines in ankle synovium, including interleukin (IL)-1ß and IL-6, was suppressed by treatment with either baricitinib or celecoxib. In contrast, RNA-seq analysis of the DRG revealed that baricitinib, but not celecoxib, restored gene expression alterations induced by CAIA to the control condition. Among many pathways changed by CAIA and baricitinib treatment, the interferon-alpha/gamma, JAK-signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) pathways were considerably decreased in the baricitinib group compared with the celecoxib group. Notably, only baricitinib decreased the expression of colony-stimulating factor 1 (CSF-1), a potent cytokine that causes neuropathic pain through activation of the microglia-astrocyte axis in the spinal cord. Accordingly, baricitinib prevented increases in microglia and astrocytes caused by CAIA. Baricitinib also suppressed JAK/STAT3 pathway activity and Csf1 expression in cultured neuronal cells. CONCLUSIONS: Our findings demonstrate the effects baricitinib has on the DRG in relation to ameliorating both inflammatory and neuropathic pain.

Innovation at the Intersection: Emerging Translational Research in Neurology and Psychiatry.

Translational research in neurological and psychiatric diseases is a rapidly advancing field that promises to redefine our approach to these complex conditions [...].

A Decade of Dedication: Pioneering Perspectives on Neurological Diseases and Mental Illnesses.

Welcome to Biomedicines' 10th Anniversary Special Issue, a journey through the human mind's labyrinth and complex neurological pathways [...].

Regulating tumor innervation by nanodrugs potentiates cancer immunochemotherapy and relieve chemotherapy-induced neuropathic pain.

Sympathetic nerves play a pivotal role in promoting tumor growth through crosstalk with tumor and stromal cells. Chemotherapy exacerbates the infiltration of sympathetic nerves into tumors, thereby providing a rationale for inhibiting sympathetic innervation to enhance chemotherapy. Here, we discovered that doxorubicin increases the density and activity of sympathetic nerves in breast cancer mainly by upregulating the expression of nerve growth factors (NGFs) in cancer cells. To address this, we developed a combination therapy by co-encapsulating small interfering RNA (siRNA) and doxorubicin within breast cancer-targeted poly (lactic-co-glycolic acid) (PLGA) nanoparticles, aiming to suppress NGF expression post-chemotherapy. Incorporating NGF blockade into the nanoplatform for chemotherapy effectively mitigated the chemotherapy-induced proliferation of sympathetic nerves. This not only bolstered the tumoricidal activity of chemotherapy, but also amplified its stimulatory impact on the antitumor immune response by increasing the infiltration of immunostimulatory cells into tumors while concurrently reducing the frequency of immunosuppressive cells. Consequently, the combined nanodrug approach, when coupled with anti-PD-L1 treatment, exhibited a remarkable suppression of primary and deeply metastatic tumors with minimal systematic toxicity. Importantly, the nanoplatform relieved chemotherapy-induced peripheral neuropathic pain (CIPNP) by diminishing the expression of pain mediator NGFs. In summary, this research underscores the significant potential of NGF knockdown in enhancing immunochemotherapy outcomes and presents a nanoplatform for the highly efficient and low-toxicity treatment of breast cancer.

Rotational Dynamics of Water near Osmolytes by Molecular Dynamics Simulations.

The behavior of water molecules around organic molecules has attracted considerable attention as a crucial factor influencing the properties and functions of soft matter and biomolecules. Recently, it has been suggested that the change in protein stability upon the addition of small organic molecules (osmolytes) is dominated by the change in the water dynamics caused by the osmolyte, where the dynamics of not only the directly interacting water molecules but also the long-range hydration layer affect the protein stability. However, the relation between the long-range structure of hydration water in various solutions and the water dynamics remains unclear at the molecular level. We performed density-functional tight-binding molecular dynamics simulations to elucidate the varying rotational dynamics of water molecules in 15 osmolyte solutions. A positive correlation was observed between the rotational relaxation time and our proposed normalized parameter obtained by dividing the number of hydrogen bonds between water molecules by the number of nearest-neighbor water molecules. For the 15 osmolyte solutions, an increase or a decrease in the value of the normalized parameter for the second hydration shell tended to result in water molecules with slow and fast rotational dynamics, respectively, thus illustrating the importance of the second hydration shell for the rotational dynamics of water molecules. Our simulation results are anticipated to advance the current understanding of water dynamics around organic molecules and the long-range structure of water molecules.