A case study of lean digital transformation through robotic process automation in healthcare.

Under Taiwan's National Health Insurance (NHI) system, it's crucial for all healthcare providers to accurately submit medical expense claims to the National Health Insurance Administration (NHIA) to avoid incorrect deductions. With changes in healthcare policies and adjustments in hospital management strategies, the complexity of claiming rules has resulted in hospitals expending significant manpower and time on the medical expense claims process. Therefore, this study utilizes the Lean Six Sigma DMAIC (Define, Measure, Analyze, Improve, Control) management approach to identify wasteful and non-value-added steps in the process. Simultaneously, it introduces Robotic Process Automation (RPA) tools to replace manual operations. After implementation, the study effectively reduces the process time by 380 min and enhances Process Cycle Efficiency (PCE) from 69.07 to 95.54%. This research validates a real-world case of Lean digital transformation in healthcare institutions. It enables human resources to be allocated to more valuable and creative tasks while assisting hospitals in providing more comprehensive and patient-centric services.

Single-stranded pre-methylated 5mC adapters uncover the methylation profile of plasma ultrashort Single-stranded cell-free DNA.

Whole-genome bisulfite sequencing (BS-Seq) measures cytosine methylation changes at single-base resolution and can be used to profile cell-free DNA (cfDNA). In plasma, ultrashort single-stranded cfDNA (uscfDNA, ∼50 nt) has been identified together with 167 bp double-stranded mononucleosomal cell-free DNA (mncfDNA). However, the methylation profile of uscfDNA has not been described. Conventional BS-Seq workflows may not be helpful because bisulfite conversion degrades larger DNA into smaller fragments, leading to erroneous categorization as uscfDNA. We describe the '5mCAdpBS-Seq' workflow in which pre-methylated 5mC (5-methylcytosine) single-stranded adapters are ligated to heat-denatured cfDNA before bisulfite conversion. This method retains only DNA fragments that are unaltered by bisulfite treatment, resulting in less biased uscfDNA methylation analysis. Using 5mCAdpBS-Seq, uscfDNA had lower levels of DNA methylation (∼15%) compared to mncfDNA and was enriched in promoters and CpG islands. Hypomethylated uscfDNA fragments were enriched in upstream transcription start sites (TSSs), and the intensity of enrichment was correlated with expressed genes of hemopoietic cells. Using tissue-of-origin deconvolution, we inferred that uscfDNA is derived primarily from eosinophils, neutrophils, and monocytes. As proof-of-principle, we show that characteristics of the methylation profile of uscfDNA can distinguish non-small cell lung carcinoma from non-cancer samples. The 5mCAdpBS-Seq workflow is recommended for any cfDNA methylation-based investigations.

Zwitterionic modified and freeze-thaw reinforced foldable hydrogel as intraocular lens for posterior capsule opacification prevention.

Posterior capsule opacification (PCO) is a predominant postoperative complication, often leading to visual impairment due to the aberrant proliferation and adhesion of lens epithelial cells (LECs) and protein precipitates subsequent to intraocular lens (IOL) implantation. To address this clinical issue, a foldable and antifouling sharp-edged IOL implant based on naturally-derived cellulose hydrogel is synthesized. The mechanical strength and transparency of the hydrogel is enhanced via repeated freeze-thaw (FT) cycles. The incorporated zwitterionic modifications can remarkably prevent the incidence of PCO by exhibiting proteins repulsion and cell anti-adhesion properties. The graft of dopamine onto both the haptic and the periphery of the posterior surface ensures the adhesion of the hydrogel to the posterior capsule and impedes the migration of LECs without compromising transparency. In in vivo study, the zwitterionic modified foldable hydrogel exhibits uveal and capsular biocompatibility synchronously with no signs of inflammatory response and prevent PCO formation, better than that of commercialized and PEG-modified IOL. With foldability, endurability, antifouling effect, and adhesive to posterior capsule, the reported hydrogel featuring heterogeneous surface design displays great potential to eradicate PCO and attain post-operative efficacy after cataract surgery.

Evaluating Recurrence Risk in Patients Undergoing Breast-conserving Surgery Using E-cadherin Staining as a Biomarker.

BACKGROUND/AIM: Following the National Comprehensive Cancer Network guidelines, radiotherapy is administered after breast-conserving surgery (BCS) in patients with more than four positive lymph nodes. Four positive lymph nodes are typically considered an indicator to assess disease spread and patient prognosis. However, the subjective counting of positive axillary lymph nodes underscores the need for biomarkers to improve diagnostic precision and reduce the risk of unnecessary treatments. Loss of E-cadherin expression is associated with cancer metastasis, but its potential as a predictive marker for cancer treatment remains uncertain. This study aimed to investigate the validity of E-cadherin as a reference for adjuvant radiotherapy in breast cancer patients with positive lymph nodes post-mastectomy. MATERIALS AND METHODS: Immunohistochemistry was performed on 60 clinical tissue specimens to assess these implications. RESULTS: Although no significant result was found in a single E-cadherin subgroup (low, medium, and high subgroups according to the X-tile algorithm), the proposed multivariate model, including the E-cadherin category, breast cancer subtype, and tumor size, yielded satisfactory recurrence risk estimation results for patients undergoing BCS. Patients with a low E-cadherin category, triple-negative breast cancers, and tumor size over 5 cm could have an increased risk of recurrence. CONCLUSION: Our study proposed a multivariate model that serves as a candidate prognostic factor for recurrence-free survival in patients undergoing BCS and radiotherapy. Utilizing this model for patient stratification in high-risk diseases and as a standard for assessing postoperative intensified therapy can potentially improve patient outcomes.

Developmental Differences in Reaching-and-Placing Movement and Its Potential in Classifying Children with and without Autism Spectrum Disorder: Deep Learning Approach.

Autism Spectrum Disorder (ASD) is among the most prevalent neurodevelopmental disorders, yet the current diagnostic procedures rely on behavioral analyses and interviews and lack objective screening methods. This study seeks to address this gap by integrating upper limb kinematics and deep learning methods to identify potential biomarkers that could be validated in younger age groups in the future to enhance the identification of ASD. Forty-one school-age children, with and without an ASD diagnosis (Mean age ± SE = 10.3 ± 0.4; 12 Females), participated in the study. A single Inertial Measurement Unit (IMU) was affixed to the child's wrist as they engaged in a continuous reaching and placing task. Deep learning techniques were employed to classify children with and without ASD. Our findings suggest delays in motor planning and control in school-age children compared to healthy adults. Compared to TD children, children with ASD exhibited poor motor planning and control as seen by greater number of movement units, more movement overshooting, and prolonged time to peak velocity/acceleration. Compensatory movement strategies such as greater velocity and acceleration were also seen in the ASD group. More importantly, using Multilayer Perceptron (MLP) model, we demonstrated an accuracy of ~ 78.1% in classifying children with and without ASD. These findings underscore the potential use of studying upper limb movement kinematics during goal-directed arm movements and deep learning methods as valuable tools for classifying and, consequently, aiding in the diagnosis and early identification of ASD upon further validation in younger children.

Therapeutic Options Targeting the Ataxia-Telangiectasia Mutated (ATM)-mediated DNA Damage Response, Macropinocytosis, and Adaptive Immunity in Ovarian Cancer.

Ataxia-telangiectasia mutated (ATM) is a pivotal protein with versatile kinase activity that responds to DNA damage. While its well-established role as a DNA repair protein is widely recognized, the understanding of its noncanonical functions in ovarian cancer remains limited. Numerous studies have investigated the potential of targeting ATM for ovarian cancer treatment. In addition to its involvement in homologous recombination repair (HRR), an increasing body of research suggests that ATM plays a role in cellular metabolism and adaptive immunity. This review focuses on the current evidence and provides a perspective on how targeting ATM in ovarian cancer can address HRR-deficient genotypes, influence macropinocytosis, and enhance immune checkpoint blockade (ICB) therapy. It underscores the diverse avenues through which targeting ATM is a potential tailored treatment for ovarian cancer.

Association between non-steroidal anti-inflammatory drug use and development of age-related macular degeneration-A 10-year retrospective cohort study.

PURPOSE: To analyze the associations between development of age-related macular degeneration (AMD) and regular use of aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs). METHODS: We retrospectively recruited individuals who received ≥28-day prescriptions of aspirin or NA-NSAIDs exclusively between 2008 and 2017 in one tertiary center as regular users. Non-regular users were free from regular use of any anti-inflammatory drugs and were matched to regular users in terms of age, sex, and visit date at a ratio of 1-4:1. The aspirin cohort included 36,771 regular users and 110,808 matched non-regular users, while the NA-NSAID cohort included 59,569 regular users and 179,732 matched non-regular users. Stratified multivariate Cox regression analyses with adjustment for systemic confounding factors were performed for the development of AMD and neovascular AMD. RESULTS: In the aspirin cohort, the adjusted hazard ratios of aspirin use for AMD in the whole cohort, individuals without cardiovascular diseases (CVDs), and those with CVDs were 0.664, 0.618, and 0.702, respectively (P < 0.0001 for all), while those of aspirin use for neovascular AMD were 0.486, 0.313, and 0.584 (P < 0.05 for all), respectively. In the NA-NSAID cohort, regular use of NA-NSAIDs was associated with a decreased risk of AMD (hazard ratio = 0.823, P < 0.0001) and neovascular AMD (hazard ratio = 0.720, P = 0.040) only in people without arthritis. CONCLUSIONS: Regular use of aspirin or NA-NSAIDs had protective effects on AMD and neovascular AMD. The effect of aspirin was observed in all patients, while the effect of NA-NSAIDs was observed only in people without arthritis.

Comorbidity of Ocular and Facial Demodicosis.

PURPOSE: To determine the association between ocular and facial demodicosis, and the effect of facial treatment on ocular demodicosis. DESIGN: Prospective clinical cohort study. METHODS: Ocular demodicosis outpatients from a tertiary medical center were enrolled from April to December 2020. The diagnosis was based on epilation of 4 eyelashes from each upper eyelid. High ocular Demodex load (ODL) was defined as ≥8 mites per eye. Facial infestation was assessed by direct microscopic examination, with facial Demodex overgrowth (FDO) defined as a density >5 mites/cm2. All patients were prescribed 3 months of ocular treatment, and FDO patients received dermatologic treatment. RESULTS: Eighty-nine patients were enrolled. Among those that completed the treatment course, 39 presented high ODL. Lower cylindrical sleeve counts were found in low ODL patients (low ODL vs high ODL: 8 vs 14, P = .009). FDO was less prevalent in this group (49% vs 77%, P = .012). The Ocular Surface Disease Index score decreased in patients without FDO (20.0 ± 17.1 to 14.0 ± 16.6, P = .027) after 3 months of topical tea tree oil treatment. Topical ivermectin treatment on the facial skin provided a higher ocular Demodex eradication rate in FDO patients (76% vs 16%, P < .001). CONCLUSION: Concurrence of ocular and facial demodicosis is common, especially in cases of severe ocular demodicosis. Although ocular treatment alone is effective for patients with ocular demodicosis only, cotreatment with topical ivermectin on the facial skin enhances ocular Demodex eradication in patients with comorbid facial Demodex overgrowth.

Tenon excision with fibrin glue-assisted reattachment of conjunctiva flap (T.E.F.A.R.C) for the treatment of conjunctivochalasis.

To observe the surgical outcome of "Tenon Excision with Fibrin Glue-Assisted Reattachment of Conjunctiva Flap" (T.E.F.A.R.C.) for the treatment of symptomatic conjunctivochalasis (CCH). This is a retrospective case series of CCH patients undergoing T.E.F.A.R.C. from January 2017 to December 2020 were reviewed. Seven patients (14 eyes) with symptomatic CCH received T.E.F.A.R.C. in both eyes. The symptoms before and after the procedures were compared and surgical complication was evaluated. The mean follow-up time was 13.7 ± 2.14 months. After the operation, resolution of the symptoms was reported in 12 eyes (86%). The grade of CCH decreased from 3 to 0 in all 14 eyes, and the restoration of inferior conjunctival surface and fornix within 1 day was also observed in all eyes. Most patients had localized injection and mild chemosis after the operation, which mostly recovered within 3 weeks. No complication or recurrence of CCH was reported after 1 year of follow-up. In conclusion, T.E.F.A.R.C. is a simple and effective treatment option for CCH with less surgical complication. Future larger studies are needed to confirm its clinical applicability.

Corneal structural alterations in autism spectrum disorder: An in vivo confocal microscopy study.

Individuals with autism spectrum disorder (ASD) often exhibit joint hypermobility and connective tissue disorders. However, it remains unclear if ASD individuals also have structural alterations in the connective tissue of the cornea. This study aims to determine whether the Kobayashi structure (K-structure) characteristics differ between adults with ASD and typically developing controls (TDC) and explore the clinical correlates of the K-structure abnormality. We recruited 30 ASD adults and 35 TDC. Corneal structures, particularly the K-structure in the Bowman's layer, of the participants were examined using in vivo confocal microscopy (IVCM), and a K-grading ranging from 1 to 4 was given to each eye based on the level of morphological mosaicism. The ASD participants' eyes received a significantly higher single-eye K-grading than that of the TDC eyes (p < 0.001), and the medians [25th, 75th percentile] of bilateral-eye summed K-grading were 8 [7, 8] and 5 [4, 6] in ASD and TDC, respectively (p < 0.001). A significantly higher K-grading in the ASD participants' eyes was still observed after adjusting for the within-subject inter-eye correlation (p < 0.001). Youden Index showed the optimal cutoffs to differentiate ASD from TDC by bilateral-eye summed K-grading and single-eye K-grading was >6 and >3, respectively. Additionally, a higher K-grading was associated with fewer visual sensation seeking in ASD (Spearman's correlation coefficient ρ = -0.518, p = 0.008) and low visual registration (i.e., higher sensory threshold) in TDC (ρ = 0.446, p = 0.023). This study provided novel evidence of corneal structural alterations in ASD by IVCM. Our findings may not only support the prior hypothesis of the association between ASD and connective tissue abnormalities but also shed light on the relationship between connective tissue disorder and neurodevelopmental disorders.

SUV39H1 Expression as a Guideline for Omitting Radiotherapy in Lymph Node-positive Triple-negative Breast Cancer Patients.

BACKGROUND/AIM: The role of postoperative radiotherapy (RT) combined with chemotherapy (CT) for lymph node-positive (LN+) triple-negative breast cancer (TNBC) remains controversial. SUV39H1-mediated epigenetic regulation is associated with cancer cell migration, invasion, metastasis, and treatment resistance. This study aims to identify the role of SUV39H1 in TNBCs. MATERIALS AND METHODS: Overall, 498 TNBCs with SUV39H1 RNA-seq profiles were retrieved from TCGA-BRCA and analyzed; the X-tile algorithm was used to stratify the population into low, intermediate, and high SUV39H1. Furthermore, we performed an in vitro clonogenic cell survival assay using the MDA-MB-231 cell line to assess the effects of SUV39H1 on cellular responses. RESULTS: The results showed that SUV39H1 was significantly higher in TNBC than normal tissue and luminal subtype breast cancer. Notably, SUV39H1 is significantly expressed in the basal-like 1 (BL1) and immunomodulatory (IM) subgroups, compared to other subtypes. Compared to patients with a low or medium expression of SUV39H1, omitting RT only worsens disease-free survival (DFS) in those with high SUV39H1 expression. The experimental results showed SUV39H1 was suppressed by si-SUV39H1, and SUV39H1 knockdown in MDA-MB-231-IV2-1 cells enhanced the cellular toxicity of doxorubicin and paclitaxel. CONCLUSION: Targeting SUV39H1 may provide a potential guiding indication of omitting RT to avoid over-treatment and chemosensitivity for TNBC.

Distinct Features of Plasma Ultrashort Single-Stranded Cell-Free DNA as Biomarkers for Lung Cancer Detection.

BACKGROUND: Using broad range cell-free DNA sequencing (BRcfDNA-Seq), a nontargeted next-generation sequencing (NGS) methodology, we previously identified a novel class of approximately 50 nt ultrashort single-stranded cell-free DNA (uscfDNA) in plasma that is distinctly different from 167 bp mononucleosomal cell-free DNA (mncfDNA). We hypothesize that uscfDNA possesses characteristics that are useful for disease detection. METHODS: Using BRcfDNA-Seq, we examined both cfDNA populations in the plasma of 18 noncancer controls and 14 patients with late-stage nonsmall cell lung carcinoma (NSCLC). In comparison to mncfDNA, we assessed whether functional element (FE) peaks, fragmentomics, end-motifs, and G-Quadruplex (G-Quad) signatures could be useful features of uscfDNA for NSCLC determination. RESULTS: In noncancer participants, compared to mncfDNA, uscfDNA fragments showed a 45.2-fold increased tendency to form FE peaks (enriched in promoter, intronic, and exonic regions), demonstrated a distinct end-motif-frequency profile, and presented with a 4.9-fold increase in G-Quad signatures. Within NSCLC participants, only the uscfDNA population had discoverable FE peak candidates. Additionally, uscfDNA showcased different end-motif-frequency candidates distinct from mncfDNA. Although both cfDNA populations showed increased fragmentation in NSCLC, the G-Quad signatures were more discriminatory in uscfDNA. Compilation of cfDNA features using principal component analysis revealed that the first 5 principal components of both cfDNA subtypes had a cumulative explained variance of >80%. CONCLUSIONS: These observations indicate that the distinct biological processes of uscfDNA and that FE peaks, fragmentomics, end-motifs, and G-Quad signatures are uscfDNA features with promising biomarker potential. These findings further justify its exploration as a distinct class of biomarker to augment pre-existing liquid biopsy approaches.

Application of a Perovskite NIR-LED with Highly Stable FAPbI3@SiO2 Core-Shell Nanocomposites in a SPR Sensing Platform.

In recent years, the demand for detection and diagnostic methods has consistently risen due to the aging of the population and the increase in the number of patients with chronic diseases. Label-free biomedical detection techniques have emerged as indispensable instruments for diagnosing a variety of diseases. The development of label-free and highly sensitive near-infrared (NIR) biomedical detection technology has attracted considerable attention. As a label-free, swift, and cost-effective analytical technique, it has demonstrated immense potential for a wide range of applications. We successfully assembled FAPbI3 near-infrared perovskite quantum dots (NIPQDs) into SiO2 shells using a rapid room-temperature atmospheric synthesis method, obtaining monodisperse FAPbI3@SiO2 nanocomposites (NCs) with a high photoluminescence quantum yield (PLQY) of 72%. Additionally, the incorporation of hydrophobic multi-branched trioctylphosphine oxide effectively passivated the surface defects of FAPbI3 NIPQDs and suppressed the hydrolysis rate of tetraethoxysilane, enabling the formation of a highly stable and high PLQY nanoscale-particle level within the FAPbI3@SiO2 core-shell structure. Notably, we successfully incorporated FAPbI3@SiO2 core-shell NCs onto InGaN blue chip as NIR excitation light sources for surface plasmon resonance sensing platforms, providing a novel platform for bioanalytical detection. With a detection sensitivity of 6302.5 nm/RIU, the system demonstrated high sensitivity, stability, and dependability. This achievement expands the biomedical research field's capacity for diagnosis, monitoring, and treatment.

Skin Lesion Correspondence Localization in Total Body Photography.

Longitudinal tracking of skin lesions - finding correspondence, changes in morphology, and texture - is beneficial to the early detection of melanoma. However, it has not been well investigated in the context of full-body imaging. We propose a novel framework combining geometric and texture information to localize skin lesion correspondence from a source scan to a target scan in total body photography (TBP). Body landmarks or sparse correspondence are first created on the source and target 3D textured meshes. Every vertex on each of the meshes is then mapped to a feature vector characterizing the geodesic distances to the landmarks on that mesh. Then, for each lesion of interest (LOI) on the source, its corresponding location on the target is first coarsely estimated using the geometric information encoded in the feature vectors and then refined using the texture information. We evaluated the framework quantitatively on both a public and a private dataset, for which our success rates (at 10 mm criterion) are comparable to the only reported longitudinal study. As full-body 3D capture becomes more prevalent and has higher quality, we expect the proposed method to constitute a valuable step in the longitudinal tracking of skin lesions.

Spectroscopic analyses of particle and energy aggregations at the interface of silver nanoparticles and fluorescent carbon nanodots.

We study the change in the surface electromagnetic field provided by photoexcited silver nanoparticles as the field is disturbed by fluorescent carbon nanodots. Fluorescent carbon nanodots with an appropriate quantity and quality of surface functional groups are used to mediate the aggregation of silver nanoparticles of matching size and shape to form available nano-size conical structures. Carbon nanodots in the composite absorb and transfer additional photoenergy to the silver surface, resulting in energy aggregation within the cone structure and enhancement of the electromagnetic field in proximity to the silver surface. This elevated energy state is manifested in the strengthening of the SERS signal of the analytical probe 4-aminophenyl disulfide and the mechanism involved is elucidated by additional molecular spectroscopy studies.

A cost-effective transperineal prostate biopsy method utilizes the original transrectal setting.

PURPOSE: Transperineal prostate biopsy (TPB) offers an alternative to transrectal prostate biopsy (TRB) for prostate cancer diagnosis. However, TPB may result in additional disposable and capital equipment costs, which can limit implementation within urology practice. Herein, we report the initial experience of a novel TPB technique within a tertiary referral center in Taiwan. MATERIALS AND METHODS: A retrospective review of all men undergoing prostate biopsy January to October in 2021 was performed. Both biopsy techniques were performed with the same setting using the convex-convex array ultrasound probe under local anesthesia alone or with the addition of sedation using double free-hand technique. Complications within 30 days and cancer detection rate (CDR) were compared between the groups. RESULTS: A total of 118 biopsies were included for final analysis. Eleven patients received systematic biopsy with additional MRI-targeted biopsy (TB) cores with all performed via a transperineal approach. The TPB group (n = 47) and TRB group (n = 58) had similar CDR after excluding TB cores (46.8% vs. 44.8%, p = 0.675). General complication rates for TPB were significantly lower than in the TRB group (27.7% vs. 46.6%, p = 0.047). No patients undergoing TPB had infectious complications, where five episodes were recorded in the TRB group (p = 0.114). CONCLUSIONS: TPB performed with convex-convex ultrasound probe and double free-hand technique is safe, feasible, cost-effective, and demonstrates equivalent CDR to TRB. Its use may eliminate infectious hospitalizations while minimizing the need for additional capital in the adoption of TPB.

Nanopore Third-Generation Sequencing for Comprehensive Analysis of Hemoglobinopathy Variants.

BACKGROUND: Oxford Nanopore Technology (ONT) third-generation sequencing (TGS) is a versatile genetic diagnostic platform. However, it is nonetheless challenging to prepare long-template libraries for long-read TGS, particularly the ONT method for analysis of hemoglobinopathy variants involving complex structures and occurring in GC-rich and/or homologous regions. METHODS: A multiplex long PCR was designed to prepare library templates, including the whole-gene amplicons for HBA2/1, HBG2/1, HBD, and HBB, as well as the allelic amplicons for targeted deletions and special structural variations. Library construction was performed using long-PCR products, and sequencing was conducted on an Oxford Nanopore MinION instrument. Genotypes were identified based on integrative genomics viewer (IGV) plots. RESULTS: This novel long-read TGS method distinguished all single nucleotide variants and structural variants within HBA2/1, HBG2/1, HBD, and HBB based on the whole-gene sequence reads. Targeted deletions and special structural variations were also identified according to the specific allelic reads. The result of 158 α-/ß-thalassemia samples showed 100% concordance with previously known genotypes. CONCLUSIONS: This ONT TGS method is high-throughput, which can be used for molecular screening and genetic diagnosis of hemoglobinopathies. The strategy of multiplex long PCR is an efficient strategy for library preparation, providing a practical reference for TGS assay development.

A modified surgical technique of fibrin glue-assisted double bipedicle conjunctival flaps for patients with ocular surface diseases.

This study aimed to describe and investigate the surgical outcome and complications of fibrin glue-assisted double bipedicle conjunctival flaps (CFs) (FADCOF), an alternative surgical technique that restores a stable ocular surface in patients with painful blinding ocular surface disease combined with a shortage of bulbar conjunctiva. Six eyes of six patients with painful blinding ocular surface disease were enrolled in this study. All patients had inadequate superior or inferior conjunctiva tissue to cover the whole corneal surface owing to previous surgeries or ocular surface diseases. These patients received FADCOF between 2009 and 2019. The main outcome included surgical success rate, visual analog scale (VAS) pain score, ocular inflammation score, and postoperative complications. Surgical success was defined as resolution of initial ocular complaints and restoration of a stable ocular surface with no flap melting, retraction, or dehiscence resulting in re-exposure of the corneal surface. All of the six eyes (100%) achieved surgical success. All patients reported significant improvement in subjective symptoms and complete resolution of ocular pain after the surgery (VAS pain score: 6.5 ± 0.5 preoperatively to 0.0 ± 0.0 at 1 month). Ocular inflammation score decreased significantly from a presurgical value of 1.83 ± 0.69 to 0.33 ± 0.47 1 month after the surgery. No postoperative complication was found during the long-term follow-up (range: 12-82 months). FADCOF is a reliable alternative for patients with painful blinding ocular surface diseases unsuitable for single total CF surgery. This surgical technique yields fast ocular surface stabilization, satisfactory recovery, and low complication rates.

Concise nanotherapeutic modality for cancer involving graphene oxide dots in conjunction with ascorbic acid.

Cancer cells tend to have higher intracellular reactive oxygen species (ROS) levels and are more vulnerable to ROS-generating therapies such as ascorbic acid (H2Asc) therapy, whose potency has been explored by several clinical trials. However, its efficiency is restricted by the requirement of pharmacologically high local H2Asc concentrations. Here, we show that nitrogen-doped graphene oxide dots (NGODs), which are highly crystalline and biocompatible, can serve as a catalytic medium for improving H2Asc cancer therapy at orally achievable physiological H2Asc concentrations. NGODs catalyze H2Asc oxidation for H2O2 and dehydroascorbic acid generation to disrupt cancer cells by consuming intracellular glutathione (GSH) and inducing ROS damage. This is the first study to demonstrate the direct consumption of GSH using a carbon-based nano-catalyst (NGODs), which further expedites tumor killing. In addition, as in our previous study, NGODs can also serve as a highly efficient photosensitizer for photodynamic therapy. Under illumination, NGODs produce a considerable amount of H2O2 in the presence of physiological levels of H2Asc as a hole scavenger and further enhance the therapeutic efficiency. Thus, a concise nanotherapeutic modality could be achieved through the conjunction of multifunctional NGODs and H2Asc to selectively eliminate deep-seated and superficial tumors simultaneously (under 65% of normal cell viability, it kills almost all cancer cells). Note that this level of therapeutic versatility generally requires multiple components and complex manufacturing processes that run into difficulties with FDA regulations and clinical applications. In this study, the concise NGOD-H2Asc nanotherapeutic modality has demonstrated its great potential in cancer therapy.