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The natural circulation system has been widely studied for use in various applications because of its inherent advantage. However, it has a key weakness called flow instability that makes the system unstable. Through massive previous research, the mechanisms of flow instability were analyzed, but there was an ambiguous aspect related to the effect of experimental parameters on the phenomenon. Particularly, there has been no report on the heat transfer performance of the system when flow instability phenomena were present. In this study, thermal-hydraulic phenomena of a two-phase natural circulation system that functions as a passive containment cooling system (PCCS) was investigated according to experimental parameters, namely, the temperature boundary (120–158 °C) and exit loss coefficient (0–34.5) under atmospheric pressure conditions. The experimental results showed five different flow types in the loop. The flow modes that occurred by the interaction between flashing and boiling were classified by referring to the mass flow rate, void fraction, and visualization data. The system was more unstable when the temperature boundary conditions increased, but it was more stable when the exit loss coefficient increased. These results have only been confirmed in our research. The reason for the results is that the flow conditions are located on the boundary between Density Wave Oscillation I and the stable flow region, and that boundary does not have clear criteria. In addition, comparing the heat transfer performance of a system by heat rate can confirm the effect of flow instability on the thermal performance of the passive cooling system. As a result, the high exit loss coefficient stabilizes the system better than the low case and has similar heat removal performance.

This study represents the first report of the complete mitochondrial genome of a carnivorous stag beetle, Figulus punctatus. The genome is 17,664 bp long with a total of 37 genes including 13 protein-coding genes, 22 tRNA, and 2 rRNA. The nucleotide composition is 37.25% A, 31.71% T, 10.00% G, and 20.99% C (GC contents 30.99%). Our molecular phylogenetic analysis based on the maximum-likelihood method recognizes Figulini and Nigidiini as a monophyletic clade, with a robust support value, and suggests that their carnivorous feeding trait may have evolved once within the family.

This quasi-experimental study investigated the effect of using model texts as a written corrective feedback (WCF) strategy on second language learners' writing, in both rewritten drafts and new drafts. It further examined learners' perceptions of model-based feedback and how those perceptions affected model effectiveness. Sixty-six English learners were equally divided into either a model group (i.e. an experiment group) or a control group. They wrote an argumentative essay, rewrote the same text, and then wrote a new text using a different prompt. Before rewriting their first draft, the model group received model texts with which they compared their initial writing, whereas the control group self-corrected their errors instead. The model group also completed a perception questionnaire on the usefulness of model-based feedback. The model group outperformed the control group, but only in the rewriting task. Furthermore, in the rewriting task there was a significant correlation between learners' perceptions of models and the effectiveness of model-based feedback, but not in the new writing task.

Abstract Background Dual-phase fluorine-18 labeled N-3-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (18F-FP-CIT) positron emission tomography (PET) scans could be used to support disorders like Parkinson’s disease (PD). Dopamine transporter (DAT) binding and cerebral perfusion are associated with ageing and gender. We investigated the effects of age and gender on non-degenerative parkinsonism, using automated quantification in striatum: specific binding ratios (SBRs) for DAT binding in delayed phase PET (dCIT) and standardized-uptake-value ratios (SUVRs) for cerebral perfusion in early phase PET (eCIT). We also examined the correlations between SBR and SUVR. Methods This retrospective study analyzed subjects with dual-phase 18F-FP-CIT PET scans. The eCIT images were acquired immediately post-injection, and dCIT images were taken 120 min later. With Brightonix software, automated quantification of SBRs for dCIT and SUVRs for eCIT were acquired from visually normal scans. The effects of aging and gender were assessed by regressing SBRs and SUVRs on age for both genders. The correlations between SUVRs and SBRs were evaluated. Results We studied 79 subjects (34 males and 45 females). An age-related reduction in SBRs was observed in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for both genders. SUVRs were found to negatively correlate with age in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for males and in the dorsal striatum and caudate nucleus for females. Positive correlations between SBRs and SUVRs in the dorsal striatum, ventral striatum, caudate nucleus, and putamen for male and in the dorsal striatum, caudate nucleus, and putamen for females. Conclusions Using quantified values from dual-phase 18F-FP-CIT PET with a single injection, we demonstrate a negative impact of age on SBRs (DAT binding) in the striatum for both genders and SUVRs (cerebral perfusion) in the dorsal striatum and caudate nucleus for both genders and in the ventral striatum and putamen for males. Additionally, we found positive associations between SBR and SUVR values in the dorsal striatum, caudate nucleus, and putamen for both genders and in the ventral striatum for males.

Abstract Background This study analyzed the genetic traits and fitness costs of vancomycin-resistant Enterococcus faecium (VREfm) blood isolates carrying Tn1546-type transposons harboring the vanA operon. Methods All E. faecium blood isolates were collected from eight general hospitals in South Korea during one-year study period. Antimicrobial susceptibility testing and vanA and vanB PCR were performed. Growth rates of E. faecium isolates were determined. The vanA-positive isolates were subjected to whole genome sequencing and conjugation experiments. Results Among 308 E. faecium isolates, 132 (42.9%) were positive for vanA. All Tn1546-type transposons harboring the vanA operon located on the plasmids, but on the chromosome in seven isolates. The plasmids harboring the vanA operon were grouped into four types; two types of circular, nonconjugative plasmids (Type A, n = 50; Type B, n = 46), and two types of putative linear, conjugative plasmids (Type C, n = 16; Type D, n = 5). Growth rates of vanA-positive E. faecium isolates were significantly lower than those of vanA-negative isolates (P

Abstract Precise genome editing is crucial for establishing isogenic human disease models and ex vivo stem cell therapy from the patient-derived hPSCs. Unlike Cas9-mediated knock-in, cytosine base editor and prime editor achieve the desirable gene correction without inducing DNA double strand breaks. However, hPSCs possess highly active DNA repair pathways and are particularly susceptible to p53-dependent cell death. These unique characteristics impede the efficiency of gene editing in hPSCs. Here, we demonstrate that dual inhibition of p53-mediated cell death and distinct activation of the DNA damage repair system upon DNA damage by cytosine base editor or prime editor additively enhanced editing efficiency in hPSCs. The BE4stem system comprised of p53DD, a dominant negative p53, and three UNG inhibitor, engineered to specifically diminish base excision repair, improves cytosine base editor efficiency in hPSCs. Addition of dominant negative MLH1 to inhibit mismatch repair activity and p53DD in the conventional prime editor system also significantly enhances prime editor efficiency in hPSCs. Thus, combined inhibition of the distinct cellular cascades engaged in hPSCs upon gene editing could significantly enhance precise genome editing in these cells.

Secondary prevention of skin cancer consists in early detection of malignant lesions through patients’ mole self-examination and medical examination. The objective of this study was to assess the self-reported frequency of mole examination in a large, representative sample of the adult general population of 17 countries from all continents. Of a total of 17,001 participants, 4.8% had their moles checked by a dermatologist more than once a year, 11.3% once a year, 8.4% every 2–3 years, 12.4% once in a while, 10.3% once in lifetime, and 52.6% of participants had never performed a mole examination. Egypt was the country with the highest prevalence of people who performed a moles check more than once a year (15.9%), followed by Brazil and the USA. A higher frequency of mole checks was associated with sex (man vs woman), higher education, higher income, fair phototype, history of skin cancer, medical insurance, and sun-protective behaviours. Despite recommendations by health providers, it appears that the frequency of mole checks in the general population is still low. It is necessary for dermatologists to keep informing at-risk populations about the importance of moles check, with particular care regarding categories that less frequently adhere to secondary prevention measures.

Objective: This study aims to investigate the relationship between body mass index (BMI) and molecular subtypes of endometrial carcinoma using an immunohistochemistry (IHC)-based classification approach. Methods: We analyzed a consecutive series of endometrial cancer cases undergoing surgical staging in southern Alberta (2019–2021). Molecular classification was determined through IHC-based molecular typing, incorporating p53 and mismatch repair (MMR), and further characterized with the addition of ER and PR. BMI associations with molecular classification were assessed using t-tests. Hormone receptor status was further examined in a separate cohort of MMRd endometrial cancer patients undergoing surgical staging at Foothills Medical Centre (Alberta, Canada). Results: Among 289 cases, comprising various histological subtypes, the pNSMP subtype exhibited the highest average BMI (33.93 kg/m2) compared to the p53 abnormal subtype (30.40 kg/m2, p = 0.02). The MMRd subtype had an average BMI of 33.22 kg/m2. While there were no significant BMI differences between FIGO grade 1 and grade 2/3 tumours in the pNSMP or MMRd, a trend toward higher BMI in grade 1 tumours versus grade 2/3 tumours in the MMRd was observed (p = 0.13). A separate cohort of 53 MMRd endometrial carcinomas revealed that FIGO grade 1 tumours were associated with higher BMI (p

Abstract Polyhexamethylene guanidine phosphate (PHMG-p) is a major component in humidifier disinfectants, which cause life-threatening lung injuries. However, to our knowledge, no published studies have investigated associations between PHMG-p dose and lung damage severity with long-term follow-up. Therefore, we evaluated longitudinal dose-dependent changes in lung injuries using repeated chest computed tomography (CT). Rats were exposed to low (0.2 mg/kg, n = 10), intermediate (1.0 mg/kg, n = 10), and high (5.0 mg/kg, n = 10) doses of PHMG-p. All rats underwent repeated CT scans after 10 and 40 weeks following the first exposure. All CT images were quantitatively analyzed using commercial software. Inflammation/fibrosis and tumor counts underwent histopathological evaluation. In both radiological and histopathologic results, the lung damage severity increased as the PHMG-p dose increased. Moreover, the number, size, and malignancy of the lung tumors increased as the dose increased. Bronchiolar–alveolar hyperplasia developed in all groups. During follow-up, there was intergroup variation in bronchiolar–alveolar hyperplasia progression, although bronchiolar–alveolar adenomas or carcinomas usually increase in size over time. Thirty-three carcinomas were detected in the high-dose group in two rats. Overall, lung damage from PHMG-p and the number and malignancy of lung tumors were shown to be dose-dependent in a rat model using repeated chest CT scans during a long-term follow-up.

The purpose of this study is to report the clinical application of Hominis Placenta Pharmacopunture for Alopecia areata. Patient was diagnosed as stress-induced Alopecia areata 1 years ago. To reduce symptom, we treated a patient 8 times using Hominis Placenta Pharmacopunture. Hominis Placenta was injected subcutaneously into the lesion of head scalp alopecia. According to photographs, the lesion had been replaced with new terminal hair and the size of the lesion had decreased. This case has shown that stress-induced Alopecia areata patient could be treated by Hominis Placenta Pharmacopunture.

Abstract Given the intricate etiology and pathogenesis of atopic dermatitis (AD), the complete cure of AD remains challenging. This study aimed to investigate if topically applying N-benzyl-N-methyldecan-1-amine (BMDA), derived from garlic, and its derivative [decyl-(4-methoxy-benzyl)-methyl-1-amine] (DMMA) could effectively alleviate AD-like skin lesions in 2,4-dinitrochlorobenzene (DNCB)-treated mice. Administering these compounds to the irritated skin of DNCB-treated mice significantly reduced swelling, rash, and excoriation severity, alongside a corresponding decrease in inflamed epidermis and dermis. Moreover, they inhibited spleen and lymph node enlargement and showed fewer infiltrated mast cells in the epidermis and dermis through toluidine-blue staining. Additionally, they led to a lower IgE titer in mouse sera as determined by ELISA, compared to vehicle treatment. Analyzing skin tissue from the mice revealed decreased transcript levels of inflammatory cytokines (TNF-α, IL-1β, and IL-6), IL-4, iNOS, and COX-2, compared to control mice. Simultaneously, the compounds impeded the activation of inflammation-related signaling molecules such as JNK, p38 MAPK, and NF-κB in the mouse skin. In summary, these findings suggest that BMDA and DMMA hold the potential to be developed as a novel treatment for healing inflammatory AD.

Abstract Seborrheic keratosis (SK) is a common skin disease in the elderly. However, in cases where SK presenting as multiple skin-colored or clustered lesions can be easily misdiagnosed as verruca plana (VP), especially in the young population. This retrospective study investigated the prevalence of SK and VP in the lesions that appear clinically similar to VP according to age. We examined the pathology slides of the skin tissue and photographs of patients who were clinically suspected to have VP. A total of 503 patients were included in the study, out of which 174 patients were finally diagnosed with SK (34.6%) and 132 with VP (26.2%). The mean ages of the SK- and VP-diagnosed group were 39.3 and 35.4 years, respectively. SK had a higher prevalence among individuals older than 30 years, and relative frequency of SK should not be ignored in patients with a grouped distribution in their 20 s and 30 s. Therefore, our study suggests that multiple verrucous skin-colored to brownish plaques are also commonly diagnosed as SK in young people as well as VP, and the prevalence of SK and VP may not always depend solely on chronological aging, and the prevalence of SK among young people may be higher than commonly believed stereotypes suggest.

Alkaline pretreatment stands out as a valuable strategy in biomass conversion to overcome the recalcitrance of biomass by removing lignin and a part of hemicellulose. This enhances enzyme accessibility and promotes saccharification. However, increasing the alkaline concentration to enhance the delignification and improve glucose yield together presents inherent limitations. In this experiment the amount of delignification and glucose yield resulting from surfactant associated with sonication during mild alkaline pretreatment of Eucalyptus pellita was investigated. Also, the effect of various factors (sonication temperature and surfactant immersion time) on delignification and glucose yield were examined. The results demonstrated that surfactant associated with sonication pretreatment could overcome the limitation of alkaline pretreatment and could increase the amount of delignification alongside enzymatic hydrolysis glucose yield of Eucalyptus pellita wood by around 90%. The findings indicated that surfactant-assisted with sonication during mild alkaline pretreatment of Eucalyptus pellita (i.e., hardwood) could be recommended as a supporting pretreatment method for the production of monomeric sugars.

Abstract Mesonephric‐type (or ‐like) adenocarcinomas (MAs) of the ovary are an uncommon and aggressive histotype. They appear to arise through transdifferentiation from Müllerian lesions creating diagnostic challenges. Thus, we aimed to develop a histologic and immunohistochemical (IHC) approach to optimize the identification of MA over its histologic mimics, such as ovarian endometrioid carcinoma (EC). First, we screened 1,537 ovarian epithelial neoplasms with a four‐marker IHC panel of GATA3, TTF1, ER, and PR followed by a morphological review of EC to identify MA in retrospective cohorts. Interobserver reproducibility for the distinction of MA versus EC was assessed in 66 cases initially without and subsequently with IHC information (four‐marker panel). Expression of PAX2, CD10, and calretinin was evaluated separately, and survival analyses were performed. We identified 23 MAs from which 22 were among 385 cases initially reported as EC (5.7%) and 1 as clear cell carcinoma. The interobserver reproducibility increased from fair to substantial (κ = 0.376–0.727) with the integration of the four‐marker IHC panel. PAX2 was the single most sensitive and specific marker to distinguish MA from EC and could be used as a first‐line marker together with ER/PR and GATA3/TTF1. Patients with MA had significantly increased risk of earlier death from disease (hazard ratio = 3.08; 95% CI, 1.62–5.85; p

IntroductionThe use of natural products for the treatment of sleep disturbances is increasing owing to the side effects and limitations of traditional sleep therapy. Moreover, recent studies have shown a significant correlation between sleep quality and gut microbiota composition. This study aimed to assess the impact of LTC-022, a commercially available dietary supplement containing Lactium and L-theanine, on enhancing sleep quality.MethodsForty participants experiencing sleep discomfort were enrolled in a double-blind randomized controlled trial, wherein they received LTC-022 or a placebo orally for 8 weeks. The effects of treatment on sleep quality were assessed using the Pittsburgh Sleep Quality Index and Insomnia Severity Index. To comprehensively evaluate changes in sleep patterns, various parameters were evaluated, including the time in bed (TIB), total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), wake after sleep onset (WASO) counts, and bedtime. These parameters were derived from daily sleep logs recorded over the 8-week study period, categorized into weekdays and weekends. Stool samples were analyzed for microbiome composition. The V4 region of bacterial 16S rRNA genes was amplified using specific primers (515F and 806R) and targeted for analysis. Microbial diversity, including operational taxonomic units, the Shannon and Chao indices, the Firmicutes/Bacteroidetes (F/B) ratio, and the variety of bacterial taxa, was assessed.ResultsNo significant differences were observed in sleep quality and insomnia scale characteristics between the two groups. In-depth analysis using sleep diaries showed that WASO counts after 8 weeks and bedtime after 4 weeks showed significant differences between the LTC-022 and control groups. In the LTC-022 group, significant differences were observed in the increase in TST, decrease in SOL, increase in SE, decrease in WASO counts, and earlier bedtime. Microbiome analysis revealed that the abundance of the genera Blautia and Ruminococcus increased in fecal samples from the LTC-022 group.ConclusionThese results suggest that continuous LTC-022 intake has a beneficial effect on maintaining sleep duration and an appropriate bedtime. Additionally, changes in the gut microbiota may be linked to changes in sleep patterns resulting from the consumption of Lactium and L-theanine.Clinical trial registrationhttps://cris.nih.go.kr/cris/search/detailSearch.do/22841, KCT0007750.

Abstract To evaluate diagnostic efficacy of deep learning (DL)-based automated bone mineral density (BMD) measurement for opportunistic screening of osteoporosis with routine computed tomography (CT) scans. A DL-based automated quantitative computed tomography (DL-QCT) solution was evaluated with 112 routine clinical CT scans from 84 patients who underwent either chest (N:39), lumbar spine (N:34), or abdominal CT (N:39) scan. The automated BMD measurements (DL-BMD) on L1 and L2 vertebral bodies from DL-QCT were validated with manual BMD (m-BMD) measurement from conventional asynchronous QCT using Pearson’s correlation and intraclass correlation. Receiver operating characteristic curve (ROC) analysis identified the diagnostic ability of DL-BMD for low BMD and osteoporosis, determined by dual-energy X-ray absorptiometry (DXA) and m-BMD. Excellent concordance were seen between m-BMD and DL-BMD in total CT scans (r = 0.961/0.979). The ROC-derived AUC of DL-BMD compared to that of central DXA for the low-BMD and osteoporosis patients was 0.847 and 0.770 respectively. The sensitivity, specificity, and accuracy of DL-BMD compared to central DXA for low BMD were 75.0%, 75.0%, and 75.0%, respectively, and those for osteoporosis were 68.0%, 80.5%, and 77.7%. The AUC of DL-BMD compared to the m-BMD for low BMD and osteoporosis diagnosis were 0.990 and 0.943, respectively. The sensitivity, specificity, and accuracy of DL-BMD compared to m-BMD for low BMD were 95.5%, 93.5%, and 94.6%, and those for osteoporosis were 88.2%, 94.5%, and 92.9%, respectively. DL-BMD exhibited excellent agreement with m-BMD on L1 and L2 vertebrae in the various routine clinical CT scans and had comparable diagnostic performance for detecting the low-BMD and osteoporosis on conventional QCT.

Purpose To evaluate whether the image quality of chest radiographs obtained using a camera-type portable X-ray device is appropriate for clinical practice by comparing them with traditional mobile digital X-ray devices. Materials and Methods Eighty-six patients who visited our emergency department and underwent endotracheal intubation, central venous catheterization, or nasogastric tube insertion were included in the study. Two radiologists scored images captured with traditional mobile devices before insertion and those captured with camera-type devices after insertion. Identification of the inserted instruments was evaluated on a 5-point scale, and the overall image quality was evaluated on a total of 20 points scale. Results The identification score of the instruments was 4.67 ± 0.71. The overall image quality score was 19.70 ± 0.72 and 15.02 ± 3.31 (p < 0.001) for the mobile and camera-type devices, respectively. The scores of the camera-type device were significantly lower than those of the mobile device in terms of the detailed items of respiratory motion artifacts, trachea and bronchus, pulmonary vessels, posterior cardiac blood vessels, thoracic intervertebral disc space, subdiaphragmatic vessels, and diaphragm (p = 0.013 for the item of diaphragm, p < 0.001 for the other detailed items). Conclusion Although caution is required for general diagnostic purposes as image quality degrades, a camera-type device can be used to evaluate the inserted instruments in chest radiographs.

Abstract Melasma relapse is almost common after discontinuation of conventional treatment. Recent studies suggesting that photoaging dermis is the main pathomechanism of melasma, emphasize the dermal targeting therapy. We investigated maintenance effect of microneedling radiofrequency (RF) for melasma treatment. Subjects with melasma were administered oral tranexamic acid and triple combination cream for 2 months and a randomly assigned half face was treated with RF. After discontinuation of conventional therapy, the half face RF continued monthly over 6 months. Modified melasma area severity index (mMASI) score and L* value by a chromameter were collected monthly. Fifteen subjects were enrolled and eleven completed the 8-month study. At 2nd month of conventional therapy, all subjects showed improvement with a 64% reduction in mMASI score. With continuous RF treatment, the improvement was well maintained; whereas in untreated side, the Δ L* gradually decreased, returning to the baseline after the conventional therapy ended. The continuous microneedling RF therapy is beneficial in maintaining the conventional therapy of melasma suggesting the protective effect of dermal targeting therapy in melasma development. (Clinical Trial registration number: NCT05710068, date of first registration: 02/02/2023).

Background: With the outbreak of COVID-19, school closures and quarantines following social distancing have brought significant changes to children's lifestyles. Therefore, we aimed to compare the population-adjusted incidence of febrile seizures(FS) and epilepsy before and after the COVID-19 outbreak in Korea and to assess the effects of the COVID-19 outbreak on the incidence by region and age group. Methods: A retrospective cohort study was conducted using nationwide claims data and covid data from January 2019 to December 2020. The incidence of diseases and difference in incidence before (Jan 20 to Dec 30, 2019) and after (Jan 20 to Dec 30, 2020) the COVID-19 outbreak was measured using rate ratio. An Interrupted time series analysis was used to identify the effect of COVID-19 on trends of FS and epilepsy. Subgroup analysis by age, sex, insurance, and risk of coronavirus by area were conducted. Results: Following the onset of the pandemic, the number of newly diagnosed FS cases decreased sharply by 69 % (24,182 to 7238), whereas the incidence of epilepsy, increased to 1.02 times (30,286−29,312), when adjusted in proportion to the population. Notably, a greater decrease in the incidence of FS were found in the regions with high-risk of coronavirus. A result of segmented regression analysis proved the decrease was significant and made immediately after the pandemic started(p

ABSTRACTCircular RNA (circRNA) is a non-coding RNA with a covalently closed loop structure and usually more stable than messenger RNA (mRNA). However, coding sequences (CDSs) following an internal ribosome entry site (IRES) in circRNAs can be translated, and this property has been recently utilized to produce proteins as novel therapeutic tools. However, it is difficult to produce large proteins from circRNAs because of the low circularization efficiency of lengthy RNAs. In this study, we report that we successfully synthesized circRNAs with the splint DNA ligation method using RNA ligase 1 and the splint DNAs, which contain complementary sequences to both ends of precursor linear RNAs. This method results in more efficient circularization than the conventional enzymatic method that does not use the splint DNAs, easily generating circRNAs that express relatively large proteins, including IgG heavy and light chains. Longer splint DNA (42 nucleotide) is more effective in circularization. Also, the use of splint DNAs with an adenine analog, 2,6-diaminopurine (DAP), increase the circularization efficiency presumably by strengthening the interaction between the splint DNAs and the precursor RNAs. The splint DNA ligation method requires 5 times more splint DNA than the precursor RNA to efficiently produce circRNAs, but our modified splint DNA ligation method can produce circRNAs using the amount of splint DNA which is equal to that of the precursor RNA. Our modified splint DNA ligation method will help develop novel therapeutic tools using circRNAs, to treat various diseases and to develop human and veterinary vaccines.

Abstract An added value of SPECT/CT over planar lymphoscintigraphy for initial staging in patients with secondary extremity lymphedema was investigated. Furthermore, we developed a hybrid SPECT/CT classification combining dermal backflow (DBF) of SPECT and honeycomb pattern (HP) of CT, correlated it with lymphoscintigraphic staging and clinical severity. Forty-one patients with secondary extremity lymphedema who underwent lymphoscintigraphy with SPECT/CT were included retrospectively. The severity of extremity lymphedema was assessed using CT volumetry. Lymphoscintigraphic findings were evaluated using the Taiwan Lymphoscintigraphy Staging (TLS), and CT-based and SPECT-based quantitative analysis were performed. TLS was performed by planar scintigraphy only and with SPECT/CT, respectively. The SPECT/CT findings were classified into DBF−/HP−, DBF+/HP−, DBF+/HP+, and DBF−/HP+. Based on these findings, patients were categorized into five classes: Class 1 = DBF−HP− entire limb, Class 2 = DBF+/HP− proximal/distal limb without DBF+/HP+ or DBF−/HP+, Class 3 = DBF+/HP+ proximal/distal limb without DBF−/HP+, Class 4 = Mixed DBF+/HP+ and DBF−/HP+ in proximal/distal limb, Class 5 = DBF−/HP+ entire limb. Adding SPECT/CT to planar scintigraphy showed a 15.4% modification rate in lymphoscintigraphic staging. HP volume ratio significantly increased as clinical severity and lymphoscintigraphic staging increased, while DBF volume ratio increased with severity and followed expected patterns according to lymphoscintigraphic staging. Hybrid SPECT/CT lymphoscintigraphic classification showed strong positive correlation with clinical severity and TLS. Our results demonstrated substantial modification of lymphoscintigraphic staging by adding SPECT/CT to a conventional planar scintigraphy. In addition, a hybrid SPECT/CT is expected to provide new indicators reflecting lymphoscintigraphic staging and clinical severity by providing both of functional DBF and anatomical HP information.

Abstract Background Aptamers, which are biomaterials comprised of single-stranded DNA/RNA that form tertiary structures, have significant potential as next-generation materials, particularly for drug discovery. The systematic evolution of ligands by exponential enrichment (SELEX) method is a critical in vitro technique employed to identify aptamers that bind specifically to target proteins. While advanced SELEX-based methods such as Cell- and HT-SELEX are available, they often encounter issues such as extended time consumption and suboptimal accuracy. Several In silico aptamer discovery methods have been proposed to address these challenges. These methods are specifically designed to predict aptamer-protein interaction (API) using benchmark datasets. However, these methods often fail to consider the physicochemical interactions between aptamers and proteins within tertiary structures. Results In this study, we propose AptaTrans, a pipeline for predicting API using deep learning techniques. AptaTrans uses transformer-based encoders to handle aptamer and protein sequences at the monomer level. Furthermore, pretrained encoders are utilized for the structural representation. After validation with a benchmark dataset, AptaTrans has been integrated into a comprehensive toolset. This pipeline synergistically combines with Apta-MCTS, a generative algorithm for recommending aptamer candidates. Conclusion The results show that AptaTrans outperforms existing models for predicting API, and the efficacy of the AptaTrans pipeline has been confirmed through various experimental tools. We expect AptaTrans will enhance the cost-effectiveness and efficiency of SELEX in drug discovery. The source code and benchmark dataset for AptaTrans are available at https://github.com/pnumlb/AptaTrans .

Human microbiome refers to the genetic material of approximately 1013 microorganisms present in the human body. These microbiomes interact significantly with the physiological, metabolic, and immune systems, particularly during pregnancy. Microbiome dysbiosis in pregnant women and their fetuses is associated with obstetric complications and poor neonatal outcomes. Oral and gut microbiomes can influence the placenta, uterus, and fetus via hematogenous translocation. Through ascending translocation, vaginal microbiota can directly affect the uterine environment. Current research focuses on the presence of the placental microbiome, which is characterized by low biomass. However, more well-controlled studies are required to specifically address the contamination issues. Use of antibiotics during pregnancy and the mode of delivery, specifically cesarean section, have been linked to the establishment of the neonatal gut microbiome. Probiotic supplementation may be beneficial during pregnancy, particularly for women receiving antibiotic treatment.

Abstract The biological process of aging is thought to result in part from accumulation of senescent cells in organs. However, the present study identified a subset of fibroblasts and smooth muscle cells which are the major constituents of organ stroma neither proliferative nor senescent in tissues of the elderly, which we termed “mid-old status” cells. Upregulation of pro-inflammatory genes (IL1B and SAA1) and downregulation of anti-inflammatory genes (SLIT2 and CXCL12) were detected in mid-old cells. In the stroma, SAA1 promotes development of the inflammatory microenvironment via upregulation of MMP9, which decreases the stability of epithelial cells present on the basement membrane, decreasing epithelial cell function. Remarkably, the microenvironmental change and the functional decline of mid-old cells could be reversed by a young cell-originated protein, SLIT2. Our data identify functional reversion of mid-old cells as a potential method to prevent or ameliorate aspects of aging-related tissue dysfunction.

Background and Objectives: Fine particulate matter, PM2.5, is becoming a major threat to human health, particularly in terms of respiratory diseases. Pyroptosis is a recently discovered and distinct form of cell death, characterized by pore formation in the cell membrane and secretions of proinflammatory cytokines. There has been little research on the effect of PM2.5 on pyroptosis, especially in airway epithelium. We investigated whether PM2.5-related oxidative stress induces pyroptosis in bronchial epithelial cells and defined the underlying mechanisms. Materials and Methods: After exposure of a BEAS-2B cell line to PM2.5 concentration of 20 µg/mL, reactive oxygen species (ROS) levels, parameters related to pyroptosis, and NF-κB signaling were measured by Western blotting, immunofluorescence, and ELISA (Enzyme-linked immunosorbent assay). Results: PM2.5 induced pyroptotic cell death, accompanied by LDH (Lactate dehydrogenase) release and increased uptake of propidium iodide in a dose-dependent manner. PM2.5 activated the NLRP3-casp1-gasdermin D pathway, with resulting secretions of the proinflammatory cytokines IL-1β and IL-18. The pyroptosis activated by PM2.5 was alleviated significantly by NLRP3 inhibitor. In PM2.5-exposed BEAS-2B cells, levels of intracellular ROS and NF-κB p65 increased. ROS scavenger inhibited the expression of the NLRP3 inflammasome, and the NF-κB inhibitor attenuated pyroptotic cell death triggered by PM2.5 exposure, indicating that the ROS/NF-κB pathway is involved in PM2.5-induced pyroptosis. Conclusions: These findings show that PM2.5 exposure can cause cell injury by NLRP3-inflammasome-mediated pyroptosis by upregulating the ROS/NF-κB pathway in airway epithelium.

Background: Osteoarthritis (OA) is a complex disease marked by the degradation of articular cartilage. Objective: This study aimed to explore the relationship between cartilage volume/thickness and clinical outcomes in knee OA patients treated with intra-articular injections over one year. Methods: Twenty-four patients with mild-to-moderate OA were retrospectively analyzed using knee MRI. OA features were assessed semiquantitatively with the Whole-Organ Magnetic Resonance Imaging Score (WORMS), while cartilage thickness and volume in the medial femoral condyle (MFC) and medial tibial plateau (MTP) were measured. T1ρ and T2 values for MFC cartilage were also recorded. Clinical outcomes were evaluated using the Korean Western Ontario and McMaster Universities (K-WOMAC) and Knee Injury Osteoarthritis Outcomes (KOOS) scores. Spearman’s rank test assessed the associations between imaging changes and clinical outcomes. Results: The baseline MTP and MFC cartilage thickness and MTP cartilage volume showed significant correlations with clinical outcomes. Additionally, less progressive cartilage loss in the medial femorotibial joint (MFTJ) and overall joint was linked to a better clinical response over 12 months. Conclusions: In conclusion, thicker baseline MFTJ cartilage and minimal cartilage loss were associated with favorable clinical outcomes in knee OA patients receiving intra-articular injections.

Opportunistic osteoporosis screening using deep learning (DL) analysis of low-dose chest CT (LDCT) scans is a potentially promising approach for the early diagnosis of this condition. We explored bone mineral density (BMD) profiles across all adult ages and prevalence of osteoporosis using LDCT with DL in a Korean population. This retrospective study included 1915 participants from two hospitals who underwent LDCT during general health checkups between 2018 and 2021. Trabecular volumetric BMD of L1-2 was automatically calculated using DL and categorized according to the American College of Radiology quantitative computed tomography diagnostic criteria. BMD decreased with age in both men and women. Women had a higher peak BMD in their twenties, but lower BMD than men after 50. Among adults aged 50 and older, the prevalence of osteoporosis and osteopenia was 26.3% and 42.0%, respectively. Osteoporosis prevalence was 18.0% in men and 34.9% in women, increasing with age. Compared to previous data obtained using dual-energy X-ray absorptiometry, the prevalence of osteoporosis, particularly in men, was more than double. The automated opportunistic BMD measurements using LDCT can effectively predict osteoporosis for opportunistic screening and identify high-risk patients. Patients undergoing lung cancer screening may especially profit from this procedure requiring no additional imaging or radiation exposure.

Abstract As the importance of utilizing real‐world data (RWD)/real‐world evidence (RWE) for supporting regulatory scientific decision‐making continues to grow, experiences and inputs from experts become crucial for developing a systematic and practice‐oriented plan for the use of fit‐for‐purpose RWD/RWE. This study aimed to survey relevant experts from government agencies, industries, and academia to identify prerequisites for the drug life cycle in Korea. The questionnaire comprised the following: (A) the definition and categories of RWD/RWE, (B) the suitability and feasibility of using RWD/RWE at each authorization stage by the types of RWD, and (C) the challenges and solutions for the use of RWD/RWE. A total of 46 respondents completed the online survey, with 89.1% of them having prior experience with RWD/RWE usage. A majority of respondents agreed that RWD can be obtained from various sources. Among these sources, the registry was the most suitable source. It is suitable to compensate for the limitations of randomized control trials and ensure quality in data collection. Though there was consensus among the respondents for the use of RWD/RWE in post‐marketing surveillance, the use of such data in new drug application (NDA) was disagreeable. Respondents considered it necessary to write a protocol in advance for RWD collection and RWE generation, for all RWD types. In conclusion, this study examined the perceptions of experts for RWD/RWE use at each approval stage of drugs. The results suggest that guidelines for the fit‐for‐purpose use of RWD/RWE should be developed via careful deliberation among experts in the future.

Abstract Innate immune training involves myelopoiesis, dynamic gene modulation, and functional reprogramming of myeloid cells in response to secondary heterologous challenges. The present study evaluates whether systemic innate immune training can protect tissues from local injury. Systemic pretreatment of mice with β‐glucan, a trained immunity agonist, reduces the mortality rate of mice with bleomycin‐induced lung injury and fibrosis, as well as decreasing collagen deposition in the lungs. β‐Glucan pretreatment induces neutrophil accumulation in the lungs and enhances efferocytosis. Training of mice with β‐glucan results in histone modification in both alveolar macrophages (AMs) and neighboring lung epithelial cells. Training also increases the production of RvD1 and soluble mediators by AMs and efferocytes. Efferocytosis increases trained immunity in AMs by stimulating RvD1 release, thus inducing SIRT1 expression in neighboring lung epithelial cells. Elevated epithelial SIRT1 expression is associated with decreased epithelial cell apoptosis after lung injury, attenuating tissue damage. Further, neutrophil depletion dampens the effects of β‐glucan on macrophage accumulation, epigenetic modification in lung macrophages, epithelial SIRT1 expression, and injury‐mediated fibrosis in the lung. These findings provide mechanistic insights into innate immune training and clues to the potential ability of centrally trained immunity to protect peripheral organs against injury‐mediated disorders.

Background: The number of people with HIV/AIDS has consistently increased in Korea since the first case of HIV/AIDS infection was reported in 1985. The depressive symptoms of patients with HIV/AIDS may lead to medication non-adherence. This study sought to investigate the cross-sectional and longitudinal association between depression and antiretroviral treatment adherence in the Korean HIV/AIDS population. Methods: We included participants of the Korea HIV/AIDS cohort study between 2009 and 2017. All information was collected at the enrollment and every annual visit, including sociodemographic characteristics, health-related behaviors, HIV/AIDS infection-related factors, depression score, and frequency of skipped medication. We performed a cross-sectional analysis of 601 participants registered between 2009 and 2017. Longitudinal data were evaluated by panel regression analysis in 515 patients who registered from 2009 to 2013. Results: In cross-sectional analysis, the HIV/AIDS patients with depressive symptoms were more likely to be non-adherent (adjusted OR = 0.52, 95 % CI 0.34, 0.79, p = 0.002). Medication adherence was significantly associated with a health-related lifestyle; the adjusted odds ratio of the non-smoking and non-drinking group was 1.75 (95 % CI 1.05, 2.90, p = 0.031). The longitudinal panel regression model revealed a significant negative impact of depression on medication adherence (adjusted OR = 0.50, 95 % CI 0.30, 0.84, p = 0.009). Non-smoking and non-drinking participants were 2.31 times more likely to adhere to antiretroviral treatment (95 % CI 1.29, 4.15, p = 0.005). Conclusions: Our finding of depression and lifestyle modifications being significant contributors underscore the importance of proactive interventions to optimize the treatment outcomes of PLWH.

Objectives: Crohn’s disease is a chronic gastrointestinal disease that belongs to inflammatory bowel disease. This systematic review aims to assess the level of evidence in randomized controlled trials (RCTs) on the effects of acupuncture for Crohn’s disease.Methods : : We searched 12 databases from the date of the establishment of each database up to May, 2023 for relevant RCTs. The risk of bias of each study was assessed independently by three reviewers. The level of evidence of meta-analysis was assessed using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation).Results : : A total of 12 studies were included. The effective rate (odds ratio [OR] 3.23, 95% confidence interval [CI] 1.43, 7.30) for mild to moderate Crohn’s disease patients showed a significant difference between the acupuncture with moxibustion group and the shamacupuncture with sham-moxibustion group. CDAI change (mean difference [MD] –74.15, 95% CI –93.28, –55.01) for mild to moderate Crohn’s disease showed a significant difference between the acupuncture with moxibustion group and the sham-acupuncture with sham-moxibustion group.Conclusion : : Although acupuncture with moxibustion showed significant effects compared to sham-acupuncture with sham-moxibustion, the effect of acupuncture alone is inconclusive. Moreover, only the effect of acupuncture treatment on mild to moderate Crohn’s disease patients was derived as a remarkable result. To confirm the effectiveness of acupuncture treatment for Crohn’s disease, studies using only acupuncture for intervention or more RCTs targeting various Crohn’s disease patients according to the CDAI are required.

Abstract The widespread use of body weight control agents might be related to liver enzyme elevation, but this potential association has only been documented in a few case reports. This study aimed to investigate the associations between weight loss agents and elevated liver enzymes at the population-level. We conducted a cross-sectional study using Korea National Health and Nutrition Examination Survey (KNHANES) data from 2013 to 2019. This study included 36,259 participants over 20 years of age who completed the questionnaire and had no history of hepatitis, cancer, or renal failure. In these participants, we analyzed associations between weight loss agents and elevated liver enzymes by constructing multiple logistic regression models with adjustment for confounding factors and stratified by sex, age, and body mass index. The use of weight loss agents related to liver enzyme elevation in men (adjusted odds ratio (aOR): 1.36, 95% confidence interval (CI): 1.08–1.71) and participants aged less than 40 years (aOR: 1.44, 95% CI: 1.12–1.87). Using more types of weight loss agents was associated with liver enzyme elevation (aOR: 1.31, 95% CI: 1.03–1.67 for 1 weight loss agent, aOR: 1.93, 95% CI: 0.93–3.99 for ≥ 2 weight loss agents). Elevated liver enzymes were associated with the use of traditional medicines (aOR: 1.96, 95% CI: 1.14–3.34) and dietary supplements (aOR: 1.33, 95% CI: 1.02–1.72) in men. We observed an association between weight loss agents and liver enzyme elevation in men, particularly for traditional herbal medicines and dietary supplements. To confirm the observed associations, studies higher on the evidence hierarchy are needed.