Bone-Targeting Exosome Mimetics Engineered by Bioorthogonal Surface Functionalization for Bone Tissue Engineering.

Extracellular vesicles have received a great interest as safe biocarriers in biomedical engineering. There is a need to develop more efficient delivery strategies to improve localized therapeutic efficacy and minimize off-target adverse effects. Here, exosome mimetics (EMs) are reported for bone targeting involving the introduction of hydroxyapatite-binding moieties through bioorthogonal functionalization. Bone-binding ability of the engineered EMs is verified with hydroxyapatite-coated scaffolds and an ex vivo bone-binding assay. The EM-bound construct provided a biocompatible substrate for cell adhesion, proliferation, and osteogenic differentiation. Particularly, the incorporation of Smoothened agonist (SAG) into EMs greatly increased the osteogenic capacity through the activation of hedgehog signaling. Furthermore, the scaffold integrated with EM/SAG significantly improved in vivo reossification. Lastly, biodistribution studies confirmed the accumulation of systemically administered EMs in bone tissue. This facile engineering strategy could be a versatile tool to promote bone regeneration, offering a promising nanomedicine approach to the sophisticated treatment of bone diseases.

Transcriptome analysis of the endangered dung beetle Copris tripartitus (Coleoptera: Scarabaeidae) and characterization of genes associated to immunity, growth, and reproduction.

BACKGROUND: Dung beetles recycle organic matter through the decomposition of feces and support ecological balance. However, these insects are threatened by the indiscriminate use of agrochemicals and habitat destruction. Copris tripartitus Waterhouse (Coleoptera: Scarabaeidae), a dung beetle, is listed as a class-II Korean endangered species. Although the genetic diversity of C. tripartitus populations has been investigated through analysis of mitochondrial genes, genomic resources for this species remain limited. In this study, we analyzed the transcriptome of C. tripartitus to elucidate functions related to growth, immunity and reproduction for the purpose of informed conservation planning. RESULTS: The transcriptome of C. tripartitus was generated using next-generation Illumina sequencing and assembled de novo using a Trinity-based platform. In total, 98.59% of the raw sequence reads were processed as clean reads. These reads were assembled into 151,177 contigs, 101,352 transcripts, and 25,106 unigenes. A total of 23,450 unigenes (93.40%) were annotated to at least one database. The largest proportion of unigenes (92.76%) were annotated to the locally curated PANM-DB. A maximum of 5,512 unigenes had homologous sequences in Tribolium castaneum. Gene Ontology (GO) analysis revealed a maximum of 5,174 unigenes in the Molecular function category. Further, in Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, a total of 462 enzymes were associated with established biological pathways. Based on sequence homology to known proteins in PANM-DB, representative immunity, growth, and reproduction-related genes were screened. Potential immunity-related genes were categorized into pattern recognition receptors (PRRs), the Toll-like receptor signaling pathway, the MyD88- dependent pathway, endogenous ligands, immune effectors, antimicrobial peptides, apoptosis, and adaptation-related transcripts. Among PRRs, we conducted detailed in silico characterization of TLR-2, CTL, and PGRP_SC2-like. Repetitive elements such as long terminal repeats, short interspersed nuclear elements, long interspersed nuclear elements and DNA elements were enriched in the unigene sequences. A total of 1,493 SSRs were identified among all unigenes of C. tripartitus. CONCLUSIONS: This study provides a comprehensive resource for analysis of the genomic topography of the beetle C. tripartitus. The data presented here clarify the fitness phenotypes of this species in the wild and provide insight to support informed conservation planning.

Therapeutic potential of FLT4-targeting peptide in acute myeloid leukemia.

Previously, we found that dysfunctional natural killer (NK) cells with low interferon gamma (IFN-γ) were restored in acute myeloid leukemia (AML) by the FLT4 antagonist MAZ51. Here, we developed 12 peptides targeting FLT4 for clinical application and examined whether they restored the frequency of lymphocytes, especially T cells and NK cells, and high IFN-γ expression, as MAZ51 treatment did in our previous study. Although clinical data from using peptides are currently available, peptides targeting FLT4 to modulate immune cells have not been fully elucidated. In this study, we focus on novel peptide 4 (P4) from the intracellular domain of FLT4 because it had dominant negative activity. Similar to MAZ51, high IFN-γ levels were expressed in AML-mononuclear cells exposed to P4. Additionally, T and NK cell levels were restored, as were high IFN-γ levels, in a leukemic environment when P4 was treated. Interestingly, the regulatory T cells were significantly decreased by P4, implying the role of peptide in tumor niche. Overall, we demonstrated the therapeutic value of functionally modulating lymphocytes using a peptide targeting FLT4 and proposed the development of advanced therapeutic approaches against AML by using immune cells.

Engineering Rhodosporidium toruloides for production of 3-hydroxypropionic acid from lignocellulosic hydrolysate.

Microbial production of valuable bioproducts is a promising route towards green and sustainable manufacturing. The oleaginous yeast, Rhodosporidium toruloides, has emerged as an attractive host for the production of biofuels and bioproducts from lignocellulosic hydrolysates. 3-hydroxypropionic acid (3HP) is an attractive platform molecule that can be used to produce a wide range of commodity chemicals. This study focuses on establishing and optimizing the production of 3HP in R. toruloides. As R. toruloides naturally has a high metabolic flux towards malonyl-CoA, we exploited this pathway to produce 3HP. Upon finding the yeast capable of catabolizing 3HP, we then implemented functional genomics and metabolomic analysis to identify the catabolic pathways. Deletion of a putative malonate semialdehyde dehydrogenase gene encoding an oxidative 3HP pathway was found to significantly reduce 3HP degradation. We further explored monocarboxylate transporters to promote 3HP transport and identified a novel 3HP transporter in Aspergillus pseudoterreus by RNA-seq and proteomics. Combining these engineering efforts with media optimization in a fed-batch fermentation resulted in 45.4 g/L 3HP production. This represents one of the highest 3HP titers reported in yeast from lignocellulosic feedstocks. This work establishes R. toruloides as a host for 3HP production from lignocellulosic hydrolysate at high titers, and paves the way for further strain and process optimization towards enabling industrial production of 3HP in the future.

Stem Cell-Derived Extracellular Vesicles for Cancer Therapy and Tissue Engineering Applications.

Recently, stem cells and their secretomes have attracted great attention in biomedical applications, particularly extracellular vesicles (EVs). EVs are secretomes of cells for cell-to-cell communication. They play a role as intercellular messengers as they carry proteins, nucleic acids, lipids, and therapeutic agents. They have also been utilized as drug-delivery vehicles due to their biocompatibility, low immunogenicity, stability, targetability, and engineerable properties. The therapeutic potential of EVs can be further enhanced by surface engineering and modification using functional molecules such as aptamers, peptides, and antibodies. As a consequence, EVs hold great promise as effective delivery vehicles for enhancing treatment efficacy while avoiding side effects. Among various cell types that secrete EVs, stem cells are ideal sources of EVs because stem cells have unique properties such as self-renewal and regenerative potential for transplantation into damaged tissues that can facilitate their regeneration. However, challenges such as immune rejection and ethical considerations remain significant hurdles. Stem cell-derived EVs have been extensively explored as a cell-free approach that bypasses many challenges associated with cell-based therapy in cancer therapy and tissue regeneration. In this review, we summarize and discuss the current knowledge of various types of stem cells as a source of EVs, their engineering, and applications of EVs, focusing on cancer therapy and tissue engineering.

Prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT in pancreatic neuroendocrine neoplasms.

OBJECTIVES: We aimed to evaluate the prognostic value of tumor-to-parenchymal contrast enhancement ratio on portal venous-phase CT (CER on PVP) and compare its prognostic performance to prevailing grading and staging systems in pancreatic neuroendocrine neoplasms (PanNENs). METHODS: In this retrospective study, data on 465 patients (development cohort) who underwent upfront curative-intent resection for PanNEN were used to assess the performance of CER on PVP and tumor size measured by CT (CT-Size) in predicting recurrence-free survival (RFS) using Harrell's C-index and to determine their optimal cutoffs to stratify RFS using a multi-way partitioning algorithm. External data on 184 patients (test cohort) were used to validate the performance of CER on PVP in predicting RFS and overall survival (OS) and compare its predictive performance with those of CT-Size, 2019 World Health Organization classification system (WHO), and the 8th American Joint Committee on Cancer staging system (AJCC). RESULTS: In the test cohort, CER on PVP showed C-indexes of 0.83 (95% confidence interval [CI], 0.74-0.91) and 0.84 (95% CI, 0.73-0.95) for predicting RFS and OS, respectively, which were higher than those for the WHO (C-index: 0.73 for RFS [p = .002] and 0.72 for OS [p = .004]) and AJCC (C-index, 0.67 for RFS [p = .002] and 0.58 for OS [p = .002]). CT-Size obtained C-indexes of 0.71 for RFS and 0.61 for OS. CONCLUSIONS: CER on PVP showed superior predictive performance on postoperative survival in PanNEN than current grading and staging systems, indicating its potential as a noninvasive preoperative prognostic tool. KEY POINTS: • In pancreatic neuroendocrine neoplasms, the tumor-to-parenchymal enhancement ratio on portal venous-phase CT (CER on PVP) showed acceptable predictive performance of postoperative outcomes. • CER on PVP showed superior predictive performance of postoperative survival over the current WHO classification and AJCC staging system.

Striatal Subregion Analysis Associated with REM Sleep Behavior Disorder in Parkinson's Disease.

BACKGROUND AND PURPOSE: REM sleep behavior disorder (RBD) in Parkinson's disease (PD) is associated with characteristic clinical subtypes and prognosis. In addition, nigrostriatal pathway, the most vulnerable anatomical area in PD, formed neuronal network interplaying with cortical and subcortical structures, and which may cause PD clinical phenotype. We evaluated the regional selectivity of presynaptic striatal dopaminergic denervation associated with RBD in PD. METHODS: We compared two groups (n = 16) of PD patients with and without RBD in terms of specific binding ratios (SBR) in subregions of the striatum, which were measured using positron emission tomography with 18F-FP-CIT. SBRs of the anterior and posterior caudate, ventral striatum, and posterior and ventral putamen regions were measured in more or less affected side, and right or left side, or bilateral sum of the striatum. RESULTS: Age, disease duration, and severity of parkinsonism were not significantly different between groups. Although group differences in all areas were not significant with multiple comparison corrections, SBR of the ventral striatum and anterior caudate in sum of both sides was significantly less in the RBD than in the non-RBD group without correction (p < 0.05). In the right anterior caudate and left ventral striatum, SBR was also lower in the RBD than in the non-RBD group without correction (p < 0.05). Attention function was impaired in the RBD group compared with the non-RBD group (p < 0.05). However, these statistical significances were not definite after correction of multiple comparisons (p > 0.05). CONCLUSIONS: There is a possibility that RBD in early PD may be associated with presynaptic dopaminergic denervation in the ventral striatum and anterior caudate, which may explain decreased attention in our RBD group. RBD in PD may imply a distinct pathological progression. However, further study using large numbers of participants or longitudinal observation is necessary for the statistical conclusion because of small sample size.

Therapies from Thiopeptides.

The first part of this contribution describes solutions that were developed to achieve progressively more efficient syntheses of the thiopeptide natural products, micrococcins P1 and P2 (MP1-MP2), with an eye toward exploring their potential as a source of new antibiotics. Such efforts enabled investigations on the medicinal chemistry of those antibiotics, and inspired the development of the kinase inhibitor, Masitinib®, two candidate oncology drugs, and new antibacterial agents. The studies that produced such therapeutic resources are detailed in the second part. True to the theme of this issue, "Organic Synthesis and Medicinal Chemistry: Two Inseparable Partners", an important message is that the above advances would have never materialized without the support of curiosity-driven, academic synthetic organic chemistry: a beleaguered science that nonetheless has been-and continues to be-instrumental to progress in the biomedical field.

Diversity-oriented routes to thiopeptide antibiotics: total synthesis and biological evaluation of micrococcin P2.

We report the first total synthesis of micrococcin P2 (MP2, 1) by a diversity-oriented route that incorporates a number of refinements relative to earlier syntheses. Biological data regarding the activity of 1 against a range of human pathogens are also provided. Furthermore, we disclose a chemical property of MP2 that greatly facilitates medicinal chemistry work in the micrococcin area and describe a method to obtain MP2 by fermentation in B. subtilis.

Micrococcin P2 Targets Clostridioides difficile.

Clostridioides difficile infection is a global public health threat. Extensive in vitro assays using clinical isolates have identified micrococcin P2 (MP2, 1) as a particularly effective anti-C. difficile agent. MP2 possesses a mode of action that differs from other antibiotics and pharmacokinetic properties that render it especially promising. Its time-kill studies have been investigated using hypervirulent C. difficile ribotype 027. DSS (dextran sulfate sodium)-induced in vivo mouse studies with that strain indicate that 1 is better than vancomycin and fidaxomicin. Thus, micrococcin P2 is a valuable platform to be exploited for the development of new anti-C. difficile antibiotics.

Clinico-radiological characteristics of anti-myelin oligodendrocyte glycoprotein antibody-associated autoimmune encephalitis in children.

AIM: To investigate the clinical characteristics and prevalence of paediatric anti-myelin oligodendrocyte glycoprotein (MOG) antibody-associated autoimmune encephalitis. METHOD: A total of 94 paediatric patients (46 males, 48 females, median age 9 years 5 months, range: 8 months-17 years 8 months) with autoimmune encephalitis were recruited at Seoul National University Children's Hospital. We evaluated autoantibody status and identified patients with anti-MOG antibody-associated autoimmune encephalitis. Retrospective reviews of medical records were performed to describe clinical presentations, laboratory findings, treatments, and outcomes. RESULTS: Eight patients (five males, three females, median age 11 years 9 months) with anti-MOG antibody-associated encephalitis were identified (8.5% of those with autoimmune encephalitis), one of whom was copositive for anti-N-methyl-d-aspartate receptor (NMDAR) antibodies. Anti-NMDAR antibodies were identified in 23 patients (23 out of 94, 24.5%). Unilateral or bilateral cortical involvement was identified in five patients. Focal contrast enhancement was also identified in three of the five patients with cortical lesions. All patients showed favourable response to immunotherapy with a Modified Rankin Scale ≤2 at the last follow-up. Relapse was found in one patient and clinico-radiological remission was achieved with cyclic intravenous immunoglobulin therapy. INTERPRETATION: Anti-MOG antibody-associated encephalitis accounts for a significant proportion of clinically defined paediatric patients with autoimmune encephalitis. Anti-MOG antibody-associated encephalitis should be included in the clinical spectrum of anti-MOG-associated diseases.

Examining the adoption and implementation of behavioral electronic health records by healthcare professionals based on the clinical adoption framework.

BACKGROUND: While various quantitative studies based on the Unified Theory of Acceptance and Use of Technology (UTAUT) and Technology Acceptance Models (TAM) exist in the general medical sectors, just a few have been conducted in the behavioral sector; they have all been qualitative interview-based studies. OBJECTIVE: The purpose of this study is to assess the adoption dimensions of a behavioral electronic health record (EHR) system for behavioral clinical professionals using a modified clinical adoption (CA) research model that incorporates a variety of micro, meso, and macro level factors. METHODS: A questionnaire survey with quantitative analysis approach was used via purposive sampling method. We modified the existing CA framework to be suitable for evaluating the adoption of an EHR system by behavioral clinical professionals. We designed and verified questionnaires that fit into the dimensions of the CA framework. The survey was performed in five US behavioral hospitals, and the adoption factors were analyzed using a structural equation analysis. RESULTS: We derived a total of seven dimensions, omitting those determined to be unsuitable for behavioral clinical specialists to respond to. We polled 409 behavioral clinical experts from five hospitals. As a result, the ease of use and organizational support had a substantial impact on the use of the behavioral EHR system. Although the findings were not statistically significant, information and service quality did appear to have an effect on the system's ease of use. The primary reported benefit of behavioral EHR system adoption was the capacity to swiftly locate information, work efficiently, and access patient information via a mobile app, which resulted in more time for better care. The primary downside, on the other hand, was an unhealthy reliance on the EHR system. CONCLUSIONS: We demonstrated in this study that the CA framework can be a useful tool for evaluating organizational and social elements in addition to the EHR system's system features. Not only the EHR system's simplicity of use, but also organizational support, should be considered for the effective implementation of the behavioral EHR system. TRIAL REGISTRATION: The study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (IRB No.: B-1904-534-301).

The mitochondrial genome of Faughnia haani (Stomatopoda): novel organization of the control region and phylogenetic position of the superfamily Parasquilloidea.

BACKGROUND: Stomatopod crustaceans are aggressive marine predators featuring complex compound eyes and powerful raptorial appendages used for "smashing" or "spearing" prey and/or competitors. Among them, parasquilloids (superfamily Parasquilloidea) possess eyes with 2-3 midband rows of hexagonal ommatidia and spearing appendages. Here, we assembled and analyzed the complete mitochondrial genome of the parasquilloid Faughnia haani and explored family- and superfamily-level phylogenetic relationships within the Stomatopoda based on mitochondrial protein coding genes (PCGs). RESULTS: The mitochondrial genome of F. haani is 16,089 bp in length and encodes 13 protein coding genes (PCGs), 22 transfer RNA genes, 2 ribosomal RNA genes, and a control region that is relatively well organized, containing 2 GA-blocks, 4 poly-T stretches, various [TA(A)]n-blocks, and 2 hairpin structures. This organized control region is likely a synapomorphic characteristic in the Stomatopoda. Comparison of the control region among superfamilies shows that parasquilloid species are more similar to gonodactyloids than to squilloids and lysiosquilloids given the presence of various  poly-T stretches between the hairpin structures and [TA(A)]n-blocks. Synteny is identical to that reported for other stomatopods and corresponds to the Pancrustacea ground pattern. A maximum-likelihood phylogenetic tree based on PCGs revealed that Parasquilloidea is sister to Lysiosquilloidea and Gonodactyloidea and not to Squilloidea, contradicting previous phylogenetic studies. CONCLUSIONS: The novel phylogenetic position of Parasquilloidea revealed by our study indicates that 'spearing' raptorial appendages are plesiomorphic and that the 'smashing' type is either derived (as reported in previous studies) or apomorphic. Our results raise the possibility that the spearing raptorial claw may have independently evolved twice. The superfamily Parasquilloidea exhibits a closer relationship with other stomatopod superfamilies with a different raptorial claw type and with dissimilar numbers of midband rows of hexagonal ommatidia. Additional studies focusing on the assembly of mitochondrial genomes from species belonging to different genera, families, and superfamilies within the order Stomatopoda are warranted to reach a robust conclusion regarding the evolutionary history of this iconic clade based on mitochondrial PCGs.

Extremely Foldable and Highly Porous Reduced Graphene Oxide Films for Shape-Adaptive Triboelectric Nanogenerators.

Here, a thin and foldable porous reduced graphene oxide (rGO) fabricated by a solvent casting method (SC-rGO) is introduced. The SC-rGO is superior to aluminum as a positive triboelectric material in triboelectric nanogenerators (TENGs), significantly enhancing TENG output performance. The film shows extremely foldable features, where it could be folded by 1/16 size. The electrical properties and device performance of SC-rGO are optimized varying thicknesses from 5 to 30 µm. A 30 µm thick TENG with a non-annealed SC-rGO film (STENG) shows the highest output of about 255 µW cm-2 due to its high carrier concentration, low work function, and high surface area. After annealing, STENG performance is optimized with a 10 µm thick SC-rGO because their work functions decreases, while the corresponding carrier concentrations decrease according to the thickness of the SC-rGO films. The SC-rGO films are highly durable and stable, where their output and conductivity show negligible changes after 100 000 cycles of mechanical deformation. A large SC-rGO with a size of 13 × 3 cm2 is fabricated and is attached inside a person's arm to demonstrate the shape-adaptive characteristics. Consequently, 170 V is obtained and it turns on 19 green light emitting diodes by simply touching the STENG.

Blood Vessel Invasion Predicts Postoperative Survival Outcomes and Systemic Recurrence Regardless of Location or Blood Vessel Type in Patients with Lung Adenocarcinoma.

BACKGROUND: Presence of blood vessel invasion (BVI) is one of the prognostic indicators for lung cancer patients with surgical resection. However, prognostic roles of the location and the type of the involved blood vessel have not been fully evaluated yet. PATIENTS AND METHODS: We retrieved the data of 217 cases of surgically resected lung adenocarcinoma from Asan Medical Center. Clinicopathologic features, including BVI, were reassessed. The location (tumor center and/or periphery) and involved blood vessel types (large and/or small vessels; arteries and/or veins) of BVI were separately examined on standard hematoxylin-eosin slides and confirmed by van Gieson elastic staining. RESULTS: BVI was identified in 35% of cases (76/217), with the tumor center (intratumoral) as the location in more than half of the cases (42/76, 55.3%). The presence of BVI was significantly associated with higher pathologic stage, increased size of invasive components, frequent pleural invasion, lymphatic permeation, and spread through alveolar spaces. BVI was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS) both in univariate and multivariate survival analyses [for OS, hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.06-3.48, P = 0.031; for RFS, HR 2.65, 95% CI 1.64-4.28; P < 0.001]. BVI subgroups, according to location and type of the involved blood vessels, invariably displayed significantly poor RFS; however, the results for OS varied. CONCLUSION: Regardless of their location or blood vessel type, presence of BVI is a useful predictor for postoperative survival outcomes, which should be carefully evaluated on pathologic examination.

Prognostic Molecular Indices of Resectable Hepatocellular Carcinoma: Implications of S100P for Early Recurrence.

BACKGROUND: Although hepatocellular carcinomas (HCCs) often recur in patients undergoing hepatectomy, there are no reliable biomarkers of this undesirable event. Recent RNA-based efforts have developed valuable genetic indices prognostic of cancer outcomes. We aimed to identify molecular predictors of early recurrence after resection of HCC, and reveal the genomolecular structure of the resected tumors. METHOD: Based on the transcriptomic and genomic datasets of 206 HCC samples surgically resected in the Asan Medical Center (AMC), we performed a differential gene expression analysis to identify quantitative markers associated with early recurrence and used the unsupervised clustering method to classify genomolecular subtypes. RESULTS: Differential gene expression profiling revealed that S100P was the highest-ranked overexpressed gene in HCCs that recurred within 2 years of surgery. This trend was reproduced in immunohistochemical studies of the original cohort and an independent AMC cohort. S100P expression also independently predicted HCC-specific mortality post-resection (adjusted hazard ratio 1.09, 95% confidence interval 1.01-1.19; p = 0.042). Validation in a Chinese cohort and in in vitro experiments confirmed the prognostic value of S100P in HCC. We further identified five discrete molecular subtypes of HCC; a subtype with stem cell features ('AMC-C4') was associated with the worst prognosis, both in our series and another two Asian datasets, and S100P was most strongly upregulated in that subtype. CONCLUSION: We identified a promising prognostic biomolecule, S100P, associated with early recurrence after HCC resection, and established the genomolecular architecture of tumors affecting clinical outcomes, particularly in Asian patients. These new insights into molecular mediators should contribute to effective care for affected patients.

Genetic diagnosis of infantile-onset epilepsy in the clinic: Application of whole-exome sequencing following epilepsy gene panel testing.

This study aimed to evaluate the clinical utility of whole-exome sequencing in a group of infantile-onset epilepsy patients who tested negative for epilepsy using a gene panel test. Whole-exome sequencing was performed on 59 patients who tested negative on customized epilepsy gene panel testing. We identified eight pathogenic or likely pathogenic sequence variants in eight different genes (FARS2, YWHAG, KCNC1, DYRK1A, SMC1A, PIGA, OGT, and FGF12), one pathogenic structural variant (8.6 Mb-sized deletion on chromosome X [140 994 419-149 630 805]), and three putative low-frequency mosaic variants from three different genes (GABBR2, MTOR, and CUX1). Subsequent whole-exome sequencing revealed an additional 8% of diagnostic yield with genetic confirmation of epilepsy in 55.4% (62/112) of our cohort. Three genes (YWHAG, KCNC1, and FGF12) were identified as epilepsy-causing genes after the original gene panel was designed. The others were initially linked with mitochondrial encephalopathy or different neurodevelopmental disorders, although an epilepsy phenotype was listed as one of the clinical features. Application of whole-exome sequencing following epilepsy gene panel testing provided 8% of additional diagnostic yield in an infantile-onset epilepsy cohort. Whole-exome sequencing could provide an opportunity to reanalyze newly recognized epilepsy-linked genes without updating the gene panel design.

Progressive fibrosing interstitial lung disease: prevalence and clinical outcome.

BACKGROUND: The progressive fibrosing (PF) phenotype of interstitial lung disease (ILD) is characterised by worsening respiratory symptoms, lung function, and extent of fibrosis on high-resolution computed tomography. We aimed to investigate the prevalence and clinical outcomes of PF-ILD in a real-world cohort and assess the prognostic significance of the PF-ILD diagnostic criteria. METHODS: Clinical data of patients with fibrosing ILD other than idiopathic pulmonary fibrosis (IPF) consecutively diagnosed at a single centre were retrospectively reviewed. A PF phenotype was defined based on the criteria used in the INBUILD trial. RESULTS: The median follow-up duration was 62.7 months. Of the total of 396 patients, the mean age was 58.1 years, 39.9% were men, and rheumatoid arthritis-ILD was the most common (42.4%). A PF phenotype was identified in 135 patients (34.1%). The PF-ILD group showed lower forced vital capacity and total lung capacity (TLC) than the non-PF-ILD group. The PF-ILD group also showed poorer survival (median survival, 91.2 months vs. not reached; P < 0.001) than the non-PF-ILD group. In multivariable Cox analysis adjusted for age, DLCO, HRCT pattern, and specific diagnosis, PF phenotype was independent prognostic factor (hazard ratio, 3.053; P < 0.001) in patients with fibrosing ILD. Each criterion of PF-ILD showed similar survival outcomes. CONCLUSIONS: Our results showed that approximately 34% of patients with non-IPF fibrosing ILD showed a progressive phenotype and a poor outcome similar to that of IPF, regardless of the diagnostic criteria used.

Impact of mobile health application on data collection and self-management of epilepsy.

Recent advances in mobile health have enabled health data collection, which includes seizure and medication tracking and epilepsy self-management. We developed a mobile epilepsy management application, integrated with a hospital electronic health record (EHR). In this prospective clinical trial, we assessed whether the mobile application provides quality healthcare data compared to conventional clinic visits, and enhances epilepsy self-management for patients with epilepsy. The study population includes patients with epilepsy (ages 15 years and older) and caregivers for children with epilepsy. Participants were provided access to the application for 90 days. We compared healthcare data collected from the mobile application with data obtained from clinic visits. The healthcare data included seizure records, seizure triggering factors, medication adherence rate, profiles of adverse events resulting from anti-seizure medication (ASM), and comorbidity screenings. In addition, we conducted baseline and follow-up questionnaires after the 90-day period to evaluate how this mobile application improved epilepsy knowledge and self-efficacy in seizure management. Data of 99 participants (18 patients with epilepsy and 81 caregivers) were analyzed. Among 24 individuals who had seizures, we obtained detailed seizure records from 13 individuals through clinic visits and for 18 from the application. Aside from the 6 individuals who reported their medication adherence during clinic visitation, half of the study participants had adherence rates of over 70%, as monitored through the application. However, the adherence rates were not reliable due to high variability. Twenty-three individuals reported 59 adverse reactions on the application, whereas 21 individuals reported 24 adverse reactions during clinic visits. We collected comorbidity data from 4 individuals during clinic visits. In comparison, 64 participants underwent comorbidity self-screening on the application, and 2 of them were referred to neuropsychiatric services. Compared to rare/non-users, app users demonstrated significant improvement in epilepsy knowledge score (p < 0.001) and self-efficacy score (p = 0.038). In conclusion, mobile health technology would help patients and caregivers to record their healthcare data and aid in self-management. Mobile health technology would provide an influential clinical validity in epilepsy care when users engage and actively maintain records on the application.

Effects of an activity tracker with feedback on physical activity in women after midline laparotomy: A randomized controlled trial.

PURPOSE: To investigate whether the use of an activity tracker with feedback increases physical activity and is safe in patients who underwent a midline laparotomy for gynecologic disorders. METHODS: Patients who were planned to undergo a midline laparotomy for gynecologic diseases wore an activity tracker at baseline and from postoperative days 1-6. Patients in the experimental arm could monitor their step counts and were encouraged to achieve the individualized step-count goal daily. In contrast, patients in the control arm did not monitor their step-counts and received the usual encouragement for ambulation. The primary endpoint was the percentage of the average step-count at postoperative days 4-5 divided by the baseline activity count. RESULTS: Seventy-three patients were randomized; 63 patients underwent a surgery and wore an activity tracker; 53 patients were evaluable for primary endpoint. The activity recovery rate was significantly higher in the experimental arm compared to the control arm (71% vs 41%, p < 0.01). However, the study arm was not significantly associated with the activity recovery rate in multivariate analysis. The brief pain inventory score, brief fatigue inventory score, day of first flatus, day of soft blend diet initiation, ileus incidence, and length of postoperative hospital stay were similar between arms. The incidence of wound dehiscence and other adverse events were similar between arms. There were no grade 3 of 4 adverse events. CONCLUSION: The use of an activity tracker with feedback is safe and may increase physical activity in patients who have undergone major gynecologic surgery.