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Efficacy of derinat as a treatment for murine and androgenetic alopecia (AGA) patients
No full text[[abstract]]Androgenetic alopecia (AGA), one of the most common types of hair loss, is associated with oxidative stress, inflammation and aging. Derinat, a transient receptor potential canonical channels (TRPCs) inhibitor, restrains TRPCs-mediated increase intracellular Ca2+ signaling, which initiates the skin aging process with intracellular reactive oxygen species (ROS) accumulation. This study investigated whether Derinat protected skin from oxidative stress-induced damage and aging, thus inhibiting AGA pathogenesis
Profibrotic subsets of SPP1(+) macrophages and POSTN(+) fibroblasts contribute to fibrotic scarring in acne keloidalis
No full text[[abstract]]Acne keloidalis (AK) is a primary scarring alopecia characterized by longstanding inflammation in the scalp causing keloid-like scar formation and hair loss. Histologically, AK is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in the later stages. To further explore its pathogenesis, bulk RNA-sequencing, single-cell RNA-sequencing, and spatial transcriptomics were applied to occipital scalp biopsy specimens of lesional and adjacent non-lesional skin in patients with clinically active disease. Unbiased clustering revealed 19 distinct cell populations, including two notable populations, POSTN(+) fibroblasts with enriched extracellular matrix signatures and SPP1(+) myeloid cells with a M2 macrophage phenotype. Cell communication analyses indicated that fibroblasts and myeloid cells communicated by SPP1 signaling networks in lesional skin. A reverse transcriptomics in-silico approach identified corticosteroids as possessing the capability to reverse the gene expression signatures of SPP1(+) myeloid cells and POSTN(+) fibroblasts. Intralesional corticosteroid injection greatly reduced SPP1 and POSTN gene expression, as well as AK disease activity. Spatial transcriptomics and immunofluorescence staining verified micro-anatomic specificity of SPP1(+) myeloid cells and POSTN(+) fibroblasts with disease activity. In summary, the communication between POSTN(+) fibroblasts and SPP1(+) myeloid cells by SPP1 axis may contribute to the pathogenesis of AK
Neurocutaneous melanosis with meningeal melanocytosis: A rare case of intracranial hypertension and cutaneous manifestations
No full text[[abstract]]A 50-year-old male presented to the emergency room after experiencing sudden right upper limb facial numbness and dysphasia, followed by full recovery. A brain CT scan showed hyperdense lesions within the left hemispheric sulcus, which raised suspicion of spontaneous subarachnoid hemorrhage. A T1-weighted MRI showed multiple tiny leptomeningeal enhancements in the same area, and a digital subtraction angiography showed no signs of vascular abnormality. Cerebrospinal fluid cytology revealed atypical melanin-containing cells with minimal pleomorphism. One month later, the patient developed sixth nerve palsy, which was determined to be due to intracranial hypertension. Multiple giant nevi on the legs, trunk, and scalp were also observed. A skin biopsy showed well-defined and symmetrical proliferation of melanocytic nevus cell nests in the dermis. An open biopsy was performed due to the suspicious leptomeningeal lesions, which surprisingly revealed diffuse and thick black-colored tissue infiltration of the leptomeninges. Pathology confirmed the diagnosis of meningeal melanocytosis. A ventriculoperitoneal shunt was then placed, and the patient's neurological symptoms gradually improved. Based on the presence of multiple giant nevi on the patient's skin and the finding of diffuse meningeal melanocytosis during the open biopsy, the patient was diagnosed with neurocutaneous melanosis. The patient received 6 cycles triweekly of Ipilimumab and Nivolumab 8 months after initial diagnosis. Unfortunately, the disease progressed and the patient passed away 14 months after initial diagnosis
The burgeoning field of advanced vascular wound management
No full text[[abstract]]In the landscape of modern medical challenges, vascular wound management occupies a critical intersection, where the intricacies of lifestyle diseases meet the advancements in medical devices. The growing prevalence and severity of arterial and venous wounds, primarily due to chronic limb-threatening ischemia (CLTI) and chronic venous insufficiency (CVI), present a significant global healthcare concern. This increase is largely driven by the aging society and lifestyle factors such as the global trend of obesity,1 tobacco use, and the growing prevalence of type 2 diabetes
Unlocking the secrets behind advanced artificial intelligence language models in deidentifying Chinese-English mixed clinical text: Development and validation study
No full text[[abstract]]BACKGROUND: The widespread use of electronic health records in the clinical and biomedical fields makes the removal of protected health information (PHI) essential to maintain privacy. However, a significant portion of information is recorded in unstructured textual forms, posing a challenge for deidentification. In multilingual countries, medical records could be written in a mixture of more than one language, referred to as code mixing. Most current clinical natural language processing techniques are designed for monolingual text, and there is a need to address the deidentification of code-mixed text. OBJECTIVE: The aim of this study was to investigate the effectiveness and underlying mechanism of fine-tuned pretrained language models (PLMs) in identifying PHI in the code-mixed context. Additionally, we aimed to evaluate the potential of prompting large language models (LLMs) for recognizing PHI in a zero-shot manner. METHODS: We compiled the first clinical code-mixed deidentification data set consisting of text written in Chinese and English. We explored the effectiveness of fine-tuned PLMs for recognizing PHI in code-mixed content, with a focus on whether PLMs exploit naming regularity and mention coverage to achieve superior performance, by probing the developed models' outputs to examine their decision-making process. Furthermore, we investigated the potential of prompt-based in-context learning of LLMs for recognizing PHI in code-mixed text. RESULTS: The developed methods were evaluated on a code-mixed deidentification corpus of 1700 discharge summaries. We observed that different PHI types had preferences in their occurrences within the different types of language-mixed sentences, and PLMs could effectively recognize PHI by exploiting the learned name regularity. However, the models may exhibit suboptimal results when regularity is weak or mentions contain unknown words that the representations cannot generate well. We also found that the availability of code-mixed training instances is essential for the model's performance. Furthermore, the LLM-based deidentification method was a feasible and appealing approach that can be controlled and enhanced through natural language prompts. CONCLUSIONS: The study contributes to understanding the underlying mechanism of PLMs in addressing the deidentification process in the code-mixed context and highlights the significance of incorporating code-mixed training instances into the model training phase. To support the advancement of research, we created a manipulated subset of the resynthesized data set available for research purposes. Based on the compiled data set, we found that the LLM-based deidentification method is a feasible approach, but carefully crafted prompts are essential to avoid unwanted output. However, the use of such methods in the hospital setting requires careful consideration of data security and privacy concerns. Further research could explore the augmentation of PLMs and LLMs with external knowledge to improve their strength in recognizing rare PHI
First-in-class dual EZH2-HSP90 inhibitor eliciting striking antiglioblastoma activity in vitro and in vivo
No full text[[abstract]]Structural analysis of tazemetostat, an FDA-approved EZH2 inhibitor, led us to pinpoint a suitable site for appendage with a pharmacophoric fragment of second-generation HSP90 inhibitors. Resultantly, a magnificent dual EZH2/HSP90 inhibitor was pinpointed that exerted striking cell growth inhibitory efficacy against TMZ-resistant Glioblastoma (GBM) cell lines. Exhaustive explorations of chemical probe 7 led to several revelations such as (i) compound 7 increased apoptosis/necrosis-related gene expression, whereas decreased M phase/kinetochore/spindle-related gene expression as well as CENPs protein expression in Pt3R cells; (ii) dual inhibitor 7 induced cell cycle arrest at the M phase; (iii) compound 7 suppressed reactive oxygen species (ROS) catabolism pathway, causing the death of TMZ-resistant GBM cells; and (iv) compound 7 elicited substantial in vivo anti-GBM efficacy in experimental mice xenografted with TMZ-resistant Pt3R cells. Collectively, the study results confirm the potential of dual EZH2-HSP90 inhibitor 7 as a tractable anti-GBM agent
Nitrogen and sulfur doped carbon dots coupled cellulose nanofibers: A surface functionalized nanocellulose membranes for air filtration
No full text[[abstract]]Background: The current study demonstrates a process to produce a hybrid bio-organic cellulose nanofiber (CNF) membrane with high filtration performance and mechanical strength. This was accomplished by 1) tailoring the functional groups of CNFs, notably using the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical oxidation and 2) coupling them with carbon dots (CDs). Methods: The surface chemistry of CNF was modified through TEMPO oxidation. Subsequently, a coupling reaction was conducted with CDs synthesized hydrothermally, as well as synthesized N/S-CDs derived from palm bunch. The impact of these modifications on the formation of air filters was investigated. Modification and coupling of surface modified CNF were evaluated by advanced analytical techniques. The toxicity of pristine and N/S-CDs coupled cellulose nanofibers was studied by cytotoxicity assay. Vacuum filtration and sequential compression molding techniques were applied to fabricate CNF filters, and the particle filtration efficiency of different filters was determined. Significant findings: The coupling of N/S-CDs to CNF significantly enhanced the tensile strength of the membranes. Coupling of N/S-CDs to TEMPO[sbnd]CNF membrane showed the highest tensile strength (9.3 ± 1.9 MPa), while N/S-CDs coupling to CNF membrane exhibited slightly lower tensile strength (9.0 ± 1.3 MPa). The average pore diameter of the filters was slightly reduced after the CNF surface modification, which led to higher differential pressure across the filters. Both the pristine and TEMPO-modified CNF filters displayed high filtration efficiency for 0.3 μm-aerosol particles (∼70–81 %) and 0.1 μm-aerosol model particles (∼50–68 %), which was in a range of bacteria and viruses. This study provided detailed information about the fabrication of modified CNF filters with high air filtration efficiency for micro/nano-sized particles using cost-effective biodegradable raw materials
Long-term PM2.5 exposure is associated with asthma prevalence and exhaled nitric oxide levels in children
No full text[[abstract]]Background: Exhaled nitric oxide concentration (FENO) is a marker of airway inflammation. This study aimed to evaluate the association of air pollution exposure with FENO levels and asthma prevalence with respiratory symptoms in school children. Methods: We analyzed 4736 school children who reside in six townships near industrial areas in central Taiwan. We evaluated asthmatic symptoms, FENO, and conducted the environmental questionnaire. The personal exposure of PM2.5, NO, and SO2 was estimated using land-use regression models data on children’s school and home addresses. Results: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma (OR = 1.595), exercise-induced wheezing (OR = 1.726), itchy eyes (OR = 1.417), and current nasal problems (OR = 1.334) (P < 0.05). FENO levels in the absence of infection were positively correlated with age, previous wheezing, allergic rhinitis, atopic eczema, near the road, and for children with high exposure to PM2.5 (P < 0.05). An increase of 1 μg/m3 PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels for children after adjusting for potential confounding variables, including exposures to NO and SO2. Conclusions: Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children. Impact: Annual exposure to PM2.5 was associated with increased odds of physician-diagnosed asthma and nasal problems and itchy eyes. Long-term exposures to PM2.5 were significantly associated with FENO levels after adjusting for potential confounding variables.This is first study to assess the association between FENO levels and long-term air pollution exposures in children near coal-based power plants.An increase of 1 μg/m3 annual PM2.5 exposure was significantly associated with a 1.0% increase in FENO levels. Long-term exposures to PM2.5 posed a significant risk of asthma prevalence and airway inflammation in a community-based population of children
A biomimetic micropillar wound dressing with flavone and polyphenol control release in vitro and in vivo
No full text[[abstract]]Background: Wound healing is a complex and dynamic process involving the replacement of devitalized and missing cellular structures and tissue layers. Methods: This study involved developing a drug-loaded biomimetic micropillar wound dressing based upon inspiration from witnessing the adhesive ability in a gecko's footpad. The conformal adhesion was set up by applying a soft elastomer thin film on the developed wound dressing surfaces. The results showed that the developed surfaces prepared based on polydimethylsiloxane (PDMS) had low surface free energy, high chemical stability, and good plasticity. Astaxanthin (AST) and curcumin were applied as the patch's bioactive compounds to help accelerate the wound healing process. Results: The results showed that the developed surfaces prepared based on polydimethylsiloxane (PDMS) had low surface free energy, high chemical stability, and good plasticity. Astaxanthin (AST) and curcumin were applied as the patch's bioactive compounds to help accelerate the wound healing process. The results indicate that the developed biomimetic micropillar patches could release the loaded drugs and significantly increase cell viability and collagen content to 20 % ∼ 25 % in vitro and in vivo. Conclusion: In summation, the primary purpose of this study has been to design a novel encapsulated carrier (micropillar patch) for use in adjustable drug release, while combining with the biomimetic microstructure to reach wound healing through percutaneous absorption
Use of leukotriene-receptor antagonists during pregnancy and risk of neuropsychiatric events in offspring
No full text[[abstract]]Background: Leukotriene-receptor antagonists (LTRA) are a class of medications used for treating allergic airway diseases including asthma and allergic rhinitis. The U.S. Food and Drug Administration has monitored postmarketing data about the potential harm of neuropsychiatric events (NEs) with montelukast, the originator remedy of LTRA. However, evidence regarding the risk of NEs associated with LTRA in children have been conflicting. To the best of our knowledge, none studies report in utero effect of LTRA exposure on risk of NEs in offspring. Method: We used data from the entire National Health Insurance Research Database to identify pregnant women and their offspring during 2009 and 2019 in Taiwan. Exposure was defined as having any dispensed prescription for LTRA during pregnancy. Propensity score matching was applied to control for the systematic differences at baseline between LTRA users and non-users. Main outcomes are primary diagnoses of attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD), or Tourette syndrome in offspring. Cox proportional hazards models were constructed to estimate the associations between prenatal LTRA exposure and NEs among offspring with covariate adjustment. Results: A total of 576,157 mother-offspring pairs (1995 LTRA exposed children and 574,162 non-exposed children) was identified in the original study population. After propensity score matching, 1988 LTRA exposed children and 19,880 non-exposed children were included in the subsequent analyses. No significant associations were found between prenatal LTRA exposure and ADHD, ASD and Tourette syndrome among offspring (adjusted hazard ratio (AHR) = 1.10; 95% confidence interval (CI): 0.85–1.42 for ADHD; AHR = 1.25; 95% CI: 0.82–1.89 for ASD; and AHR = 0.98; 95% CI: 0.49–1.93 for Tourette syndrome). In addition to overall LTRA exposure, duration of LTRA use (1–4 weeks vs. more than 4 weeks), and cumulative dose of LTRA (1–170 mg vs. more than 170 mg), separately, was not significantly associated with ADHD, ASD and Tourette syndrome among offspring. Conclusion: The use of LTRA during pregnancy does not pose significant risks of NEs in offspring. Clinicians prescribing LTRA to pregnant women with asthma or allergic rhinitis may be reassured by our findings of no increased risk of NEs, specifically ADHD, ASD and Tourette syndrome, in offspring