Exploring phytochemicals and pharmacological properties of Populus × tomentiglandulosa.

Populus × tomentiglandulosa (PT), a tree endemic to Korea, shows promising potential as a natural therapeutic agent owing to its potent anti-inflammatory properties. However, the isolation and analysis of phytochemical compounds in PT and related species remains underexplored. Therefore, this study aims to investigate the biochemical profile of PT and evaluate its extracts and fractions for anti-inflammatory activities. Nine compounds were isolated, including two novel flavonoids (luteolin 7-O-ß-d-glucuronide butyl ester and chrysoeriol 7-O-ß-d-glucuronide butyl ester) from the Salicaceae family for the first time. The ethyl acetate fraction exhibited significant radical scavenging activity against various radicals, including DPPH, ABTS+, •OH, and O2 - radicals. PT extracts and the ethyl acetate fraction showed minimal cytotoxicity in Raw 264.7 macrophages at concentrations below 500 and 100 µg/mL, respectively. Furthermore, PT extracts and fractions significantly suppressed the protein expression of proinflammatory mediators (iNOS and IL-6) in LPS-stimulated Raw 264.7 macrophages, highlighting their potent anti-inflammatory effects. These findings suggest that PT holds promise as a valuable natural therapeutic intervention for various oxidative stress and inflammation-related disorders, underscoring the need for further exploration of its clinical applications.

Edoxaban Antithrombotic Therapy for Atrial Fibrillation and Stable Coronary Artery Disease.

BACKGROUND: Despite consistent recommendations from clinical guidelines, data from randomized trials on a long-term antithrombotic treatment strategy for patients with atrial fibrillation and stable coronary artery disease are still lacking. METHODS: We conducted a multicenter, open-label, adjudicator-masked, randomized trial comparing edoxaban monotherapy with dual antithrombotic therapy (edoxaban plus a single antiplatelet agent) in patients with atrial fibrillation and stable coronary artery disease (defined as coronary artery disease previously treated with revascularization or managed medically). The risk of stroke was assessed on the basis of the CHA2DS2-VASc score (scores range from 0 to 9, with higher scores indicating a greater risk of stroke). The primary outcome was a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, and major bleeding or clinically relevant nonmajor bleeding at 12 months. Secondary outcomes included a composite of major ischemic events and the safety outcome of major bleeding or clinically relevant nonmajor bleeding. RESULTS: We assigned 524 patients to the edoxaban monotherapy group and 516 patients to the dual antithrombotic therapy group at 18 sites in South Korea. The mean age of the patients was 72.1 years, 22.9% were women, and the mean CHA2DS2-VASc score was 4.3. At 12 months, a primary-outcome event had occurred in 34 patients (Kaplan-Meier estimate, 6.8%) assigned to edoxaban monotherapy and in 79 patients (16.2%) assigned to dual antithrombotic therapy (hazard ratio, 0.44; 95% confidence interval [CI], 0.30 to 0.65; P<0.001). The cumulative incidence of major ischemic events at 12 months appeared to be similar in the trial groups. Major bleeding or clinically relevant nonmajor bleeding occurred in 23 patients (Kaplan-Meier estimate, 4.7%) in the edoxaban monotherapy group and in 70 patients (14.2%) in the dual antithrombotic therapy group (hazard ratio, 0.34; 95% CI, 0.22 to 0.53). CONCLUSIONS: In patients with atrial fibrillation and stable coronary artery disease, edoxaban monotherapy led to a lower risk of a composite of death from any cause, myocardial infarction, stroke, systemic embolism, unplanned urgent revascularization, or major bleeding or clinically relevant nonmajor bleeding at 12 months than dual antithrombotic therapy. (Funded by the CardioVascular Research Foundation and others; EPIC-CAD ClinicalTrials.gov number, NCT03718559.).

Efficacy and safety of dapagliflozin in children with kidney disease: real-world data.

BACKGROUND: Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, has shown results in slowing estimated glomerular filtration rate (eGFR) decline and reducing proteinuria in adult patients with chronic kidney disease. This retrospective study examines dapagliflozin's effects in 22 children with kidney disease and proteinuria. METHODS: Children with a median age of 15.6 years were treated with dapagliflozin for > 3 months between July 2022 and December 2023. All children had been treated with either an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker for at least 1 month before starting dapagliflozin. RESULTS: The most common kidney disease diagnoses in this study included Alport syndrome (n = 7) and medication-resistant nephrotic syndrome or focal segmental glomerulosclerosis (n = 7). After 6.1 months of treatment, dapagliflozin treatment did not result in significant changes in eGFR or proteinuria. However, at the latest follow-up, a statistically significant decrease in eGFR was noted (65.5 compared to the baseline 71.1 mL/min/1.73 m2, P = 0.003). Proteinuria remained stable between baseline and the last follow-up (final spot urine protein/creatinine ratio (uPCR) 0.7 vs. baseline uPCR 0.6 mg/mg, P = 0.489). In the subgroup analysis of children treated for > 8 months, the eGFR decline post-treatment changed from - 0.5 to - 0.2 ml/min/1.73 m2 per month (P = 0.634). Only two children discontinued dapagliflozin due to suspected adverse events. CONCLUSIONS: Dapagliflozin has not been associated with serious side effects. Further prospective clinical trials are needed to confirm the efficacy and safety of dapagliflozin in children with kidney disease.

Protective effect of Phyllostachys edulis (Carrière) J. Houz against chronic ethanol-induced cognitive impairment in vivo.

BACKGROUND/OBJECTIVES: Chronic alcohol consumption causes oxidative stress in the body, which may accumulate excessively and cause a decline in memory; problem-solving, learning, and exercise abilities; and permanent damage to brain structure and function. Consequently, chronic alcohol consumption can cause alcohol-related diseases. MATERIALS/METHODS: In this study, the protective effects of Phyllostachys edulis (Carrière) J. Houz (PE) against alcohol-induced neuroinflammation and cognitive impairment were evaluated using a mouse model. Alcohol (16%, 5 g/kg/day for 6 weeks) and PE (100, 250, and 500 mg/kg/day for 21 days) were administered intragastrically to mice. RESULTS: PE showed a protective effect against memory deficits and cognitive dysfunction caused by alcohol consumption, confirmed through behavioral tests such as the T-maze, object recognition, and Morris water maze tests. Additionally, PE attenuated oxidative stress by reducing lipid oxidation, nitric oxide, and reactive oxygen species levels in the mice's brains, livers, and kidneys. Improvement of neurotrophic factors and downregulation of apoptosis-related proteins were confirmed in the brains of mice fed low and medium concentrations of PE. Additionally, expression of antioxidant enzyme-related proteins GPx-1 and SOD-1 was enhanced in the liver of PE-treated mice, related to their inhibitory effect on oxidative stress. CONCLUSION: This suggests that PE has both neuroregenerative and antioxidant effects. Collectively, these behavioral and histological results confirmed that PE could improve alcohol-induced cognitive deficits through brain neurotrophic and apoptosis protection and modulation of oxidative stress.

Fully autonomous water monitoring by plant-inspired robots.

Developing countries struggle with water quality management owing to poor infrastructure, limited expertise, and financial constraints. Traditional water testing, relying on periodic site visits and manual sampling, is impractical for continuous wide-area monitoring and fails to detect sudden heavy metal contamination. To address this, plant-inspired robots capable of fully autonomous water quality monitoring are proposed. Constructed from paper, the robot absorbs surrounding water through its roots. This paper robot is controlled by paper-based microfluidic logic that sends absorbed water to petal-shaped actuators only when the water is polluted by heavy metals. This triggers the actuators to swell and bend like a blooming flower, visually signaling contamination to local residents. In tests with copper-contaminated water, the robotic flower's diameter increased from 4.69 cm to 14.89 cm, a more than threefold expansion (217.25 %). This significant blooming movement serves as a highly visible and easily recognizable indicator of water pollution, even for the public. Furthermore, the paper robot can be mass-produced at a low cost (∼$0.2 per unit) and deployed over large areas. Once installed, the paper robot operates autonomously using surrounding water as a power source, eliminating the need for external electrical infrastructure and expert intervention. Therefore, this autonomous robot offers a new approach to water quality monitoring suitable for resource-limited environments, such as Sub-Saharan Africa.

Protocol for Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR): A randomized, double-blind, sham-controlled trial.

In this randomized, double-blind, sham-controlled trial of Cerebellar Stimulation for Aphasia Rehabilitation (CeSAR), we will determine the effectiveness of cathodal tDCS (transcranial direct current stimulation) to the right cerebellum for the treatment of chronic aphasia (>6 months post stroke). We will test the hypothesis that cerebellar tDCS in combination with an evidenced-based anomia treatment (semantic feature analysis, SFA) will be associated with greater improvement in naming untrained pictures (as measured by the change in Philadelphia Picture Naming Test), 1-week post-treatment, compared to sham plus SFA. We will also evaluate the effects of cerebellar tDCS on naming trained items as well as the effects on functional communication, content, efficiency, and word-retrieval of picture description, and quality of life. Finally, we will identify imaging and linguistic biomarkers to determine the characteristics of stroke patients that benefit from cerebellar tDCS and SFA treatment. We expect to enroll 60 participants over five years. Participants will receive 15, 25-minute sessions of cerebellar tDCS (3-5 sessions per week) or sham tDCS combined with 1 hour of SFA treatment. Participants will be evaluated prior to the start of treatment, one-week post-treatment, 1-, 3-, and 6-months post-treatment on primary and secondary outcome variables. The long-term aim of this study is to provide the basis for a Phase III randomized controlled trial of cerebellar tDCS vs sham with concurrent language therapy for treatment of chronic aphasia. Trial registration: The trial is registered with ClinicalTrials.gov NCT05093673.

Diagnostic value of a deep learning-based hyoid bone tracking model for aspiration in patients with post-stroke dysphagia.

Objective: Hyoid bone movement is potentially related to aspiration risk in post-stroke dysphagia (PSD) patients but is difficult to assess quantitatively. This study aimed to measure the distance of hyoid bone movement more efficiently and accurately using a deep learning model and determine the clinical usefulness of the model in PSD patients. Methods: This study included 85 patients with PSD within 6 months from onset. Patients were grouped into an aspiration group (n = 35) and a non-aspiration group (n = 50) according to the results of a videofluoroscopic swallowing study. Hyoid bone movement was tracked using a deep learning model constructed with the BiFPN-U-Net(T) architecture. The maximum distance of hyoid bone movement was measured horizontally (H max), vertically (V max), and diagonally (D max). Results: Compared with the non-aspiration group, the aspiration group showed significant decreases in hyoid bone movement in all directions. The area under the curve of V max was highest at 0.715 with a sensitivity of 0.680 and specificity of 0.743. The V max cutoff value for predicting aspiration risk was 1.61 cm. The success of oral feeding at the time of discharge was significantly more frequent when hyoid movement was equal to or larger than the cutoff value although no significant relationship was found between hyoid movement and other clinical characteristics. Conclusion: Hyoid bone movement of PSD patients can be measured quantitatively and efficiently using a deep learning model. Deep learning model-based analysis of hyoid bone movement seems to be useful for predicting aspiration risk and the possibility of resuming oral feeding.

Ontogenic transformation of the ankle from the initial mediolateral arrangement of the calcaneus and talus: A histological study of human embryos and early fetuses.

The human calcaneus is robust and provides a prominent heel for effective bipedal locomotion, although the adjacent talus has no muscle attachments. However, there is incomplete information about the morphological changes in these prominent bones during embryo development. We examined serial histological sections of 23 human embryos and early-term fetuses (approximately 5-10 weeks' gestational age [GA]). At a GA of 5 weeks, the precartilage talus was parallel to and on the medial side of the calcaneus, which had a prolate spheroid shape and consisted of three masses. At a GA of 6 weeks, the cartilaginous talus extended along the proximodistal axis, and the tuber calcanei became long and bulky, with a small sustentaculum talus at the "distal" side. At a GA of 6 to 8 weeks, the sustentaculum had a medial extension below the talus so that the talus "rode over" the calcaneus. In contrast, the talus had a more complex shape, depending on the growth of adjacent bones. At a GA of 9 to 10 weeks, the talus was above the calcaneus, but the medial part still faced the plantar subcutaneous tissue because of the relatively small sustentaculum. Therefore, the final morphology appeared after an additional several weeks. Muscle activity seemed to facilitate growth of the tuber calcanei, but growth of the other parts of calcaneus, including the sustentaculum, seemed to depend on active proliferation at the different sites of cartilage. Multiple tendons and ligaments seemed to fix the talus so that it remained close to the calcaneus.

Unveiling the critical role of K+ for xanthorhodopsin expression in E. coli.

Xanthorhodopsin (XR), a retinal-binding 7-transmembrane protein isolated from the eubacterium Salinibacter ruber, utilizes two chromophores (retinal and salinixanthin (SAL)) as an outward proton pump and energy-donating carotenoid. However, research on XR has been impeded owing to limitations in achieving heterogeneous expression of stable forms and high production levels of both wild-type and mutants. We successfully expressed wild-type and mutant XRs in Escherichia coli in the presence of K+. Achieving XR expression requires significant K+ and a low inducer concentration. In particular, we highlight the significance of Ser-159 in helix E located near Gly-156 (a carotenoid-binding position) as a critical site for XR expression. Our findings indicate that replacing Ser-159 with a smaller amino acid, alanine, can enhance XR expression in a manner comparable to K+, implying that Ser-159 poses a steric hindrance for pigment formation in XR. In the presence of K+, the proton pumping and photocycle of the wild-type and mutants were characterized and compared; the wild-type result suggests similar properties to the first reported XR isolation from the S. ruber membrane fraction. We propose that the K+ gradient across the cell membrane of S. ruber serves to uphold the membrane potential of the organism and plays a role in the expression of proteins, such as XR, as demonstrated in our study. Our findings deepen the understanding of adaptive protein expression, particularly in halophilic organisms. We highlight salt selection as a promising strategy for improving protein yield and functionality.

Gastric and colorectal cancer incidence attributable to dietary factors in Korea.

Background: Dietary factors play a role in the etiology of gastrointestinal cancer. We aimed to estimate the burden of gastric and colorectal cancer that can be attributable to dietary factors in adults aged 20 years and older in Korea in 2018. Methods: Dietary intakes in 2000 were estimated using data from the 2001, 2005, and 2007-2018 Korea National Health and Nutrition Examination Survey (KNHANES). For counterfactual scenarios, the optimal level of intake suggested by the Global Burden of Disease (GBD) study was used if it was available. Otherwise, the average intake values of reference groups among published studies globally were used. Relative risks (RRs) were pooled through dose-response meta-analyses of Korean studies. Results: In Korea in 2018, an estimated 18.6% of gastric cancer cases and 34.9% of colorectal cancer cases were attributed to the combined effect of evaluated dietary factors. High intake of salted vegetables accounted for 16.0% of gastric cancer cases, followed by salted fish at 2.4%. Low intakes of whole grains (16.6%) and milk (13.7%) were leading contributors to colorectal cancer cases, followed by high intakes of processed meat (3.1%) and red meat (5.9%), and a low intake of dietary fiber (0.5%). Conclusions: These results suggest that a considerable proportion of gastric and colorectal cancer incidence might be preventable by healthy dietary habits in Korea. However, further research is needed to confirm the associations between dietary factors and gastric and colorectal cancers in Korea and to formulate and apply effective cancer prevention strategies to Koreans.

Prognostic Role of CA-125 Elimination Rate Constant (KELIM) in Patients with Advanced Epithelial Ovarian Cancer Who Received PARP Inhibitors.

BACKGROUND: This multicenter retrospective study aimed to investigate the prognostic value of the CA-125 elimination rate constant K (KELIM) in EOC patients who received platinum-based chemotherapy followed by PARP inhibitors, in either upfront or interval treatment settings. METHODS: Between July 2019 and November 2022, we identified stage III-IV EOC patients who underwent primary or interval cytoreductive surgery and received olaparib or niraparib. Individual KELIM values were assessed based on validated kinetics and classified into favorable and unfavorable cohorts. RESULTS: In a study of 252 patients undergoing frontline maintenance therapy with olaparib or niraparib, favorable KELIM (≥1) scores were associated with a higher PFS benefit in the primary cytoreductive surgery (PCS) cohort (hazard ratio (HR) for disease progression or death 3.51, 95% confidence interval (CI); 1.37-8.97, p = 0.009). Additionally, within the interval cytoreductive surgery (ICS) cohort, a favorable KELIM score (≥1) significantly increased the likelihood of achieving complete resection following cytoreductive surgery, with 59.4% in the favorable KELIM group compared to 37.8% in those with unfavorable KELIM. CONCLUSIONS: A favorable KELIM score was associated with improved PFS in patients with advanced EOC undergoing PCS. Furthermore, in the ICS cohort, a favorable KELIM score increased the probability of complete cytoreduction.

Deep Learning-Based Dynamic Risk Prediction of Venous Thromboembolism for Patients With Ovarian Cancer in Real-World Settings From Electronic Health Records.

PURPOSE: Patients with epithelial ovarian cancer (EOC) have an elevated risk for venous thromboembolism (VTE). To assess the risk of VTE, models were developed by statistical or machine learning algorithms. However, few models have accommodated deep learning (DL) algorithms in realistic clinical settings. We aimed to develop a predictive DL model, exploiting rich information from electronic health records (EHRs), including dynamic clinical features and the presence of competing risks. METHODS: We extracted EHRs of 1,268 patients diagnosed with EOC from January 2007 through December 2017 at the National Cancer Center, Korea. DL survival networks using fully connected layers, temporal attention, and recurrent neural networks were adopted and compared with multi-perceptron-based classification models. Prediction accuracy was independently validated in the data set of 423 patients newly diagnosed with EOC from January 2018 to December 2019. Personalized risk plots displaying the individual interval risk were developed. RESULTS: DL-based survival networks achieved a superior area under the receiver operating characteristic curve (AUROC) between 0.95 and 0.98 while the AUROC of classification models was between 0.85 and 0.90. As clinical information benefits the prediction accuracy, the proposed dynamic survival network outperformed other survival networks for the test and validation data set with the highest time-dependent concordance index (0.974, 0.975) and lowest Brier score (0.051, 0.049) at 6 months after a cancer diagnosis. Our visualization showed that the interval risk fluctuating along with the changes in longitudinal clinical features. CONCLUSION: Adaption of dynamic patient clinical features and accounting for competing risks from EHRs into the DL algorithms demonstrated VTE risk prediction with high accuracy. Our results show that this novel dynamic survival network can provide personalized risk prediction with the potential to assist risk-based clinical intervention to prevent VTE among patients with EOC.

Proton-pumping photoreceptor controls expression of ABC transporter by regulating transcription factor through light.

Light is a significant factor for living organisms with photosystems, like microbial rhodopsin-a retinal protein that functions as an ion pump, channel, and sensory transduction. Gloeobacter violaceus PCC7421, has a proton-pumping rhodopsin gene, the Gloeobacter rhodopsin (GR). The helix-turn-helix family of transcriptional regulators has various motifs, and they regulate gene expression in the presence of various metal ions. Here, we report that active proton outward pumping rhodopsin interacted with the helix-turn-helix transcription regulator and regulated gene expression. This interaction is confirmed using ITC analysis (KD of 8 µM) and determined the charged residues required. During in vitro experiments using fluorescent and luciferase reporter systems, ATP-binding cassette (ABC) transporters and the self-regulation of G. violaceus transcriptional regulator (GvTcR) are regulated by light, and gene regulation is observed in G. violaceus using the real-time polymerase chain reaction. These results expand our understanding of the natural potential and limitations of microbial rhodopsin function.

The pathologic and clinical outcomes of risk-reducing salpingo-oophorectomy in asymptomatic carriers of homologous recombination repair gene mutation.

OBJECTIVE: To investigate the prevalence of pathological findings and clinical outcomes of risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic carriers with germline homologous recombination repair (HRR) gene pathogenic/likely pathogenic variants (PV/LPV). METHODS: This retrospective study enrolled asymptomatic carriers with germline HR gene PV/LPV who underwent RRSO between 2006 and 2022 at the National Cancer Center in Korea. Clinical characteristics, including history of breast cancer, family history of ovarian/breast cancer, parity, and oral contraceptive use, were analyzed. RESULTS: Of the 255 women who underwent RRSO, 129 (50.6%) had PV/LPV in BRCA1, 121 (47.5%) in BRCA2, and 2 (0.7%) had both BRCA1 and BRCA2 PV/LPV. In addition, 1 carried PV/LPV in RAD51D, and 2 in BRIP1. Among the BRCA1/2 PV/LPV carriers, occult neoplasms were identified in 3.5% of patients: serous tubal intraepithelial carcinoma (1.1%, n=3), fallopian tubal cancers (0.8%, n=2), ovarian cancer (1.2%, n=3), and breast cancer (0.4%, n=1). Of the 9 patients with occult neoplasms, 5 (2.0%) were identified from the 178 breast cancer patients, and 4 (1.6%) were detected in 65 healthy mutation carriers. During the median follow-up period of 36.7 months (interquartile range, 25.9-71.4), 1 (0.4%) BRCA1 PV carrier with no precursor lesions at RRSO developed primary peritoneal carcinomatosis after 30.1 months. CONCLUSION: Women with HRR gene mutations PV/LPV who undergo RRSO are at a risk of detecting occult neoplasms, with a of 3.5%. Even in the absence of precursor lesions during RRSO, there was a cumulative risk of peritoneal carcinomatosis development, emphasizing the need for continued surveillance.

Mortality in patients receiving renal replacement therapy in South Korea.

Background: This study analyzed data from the end-stage renal disease patient registry collected by the Korean Society of Nephrology to explore trends in mortality among dialysis patients from 2001 to 2022. Methods: Mortality was analyzed in two ways: firstly, using the annual mortality rate; and secondly, by assessing survivability after a certain period of time since the initiation of dialysis. Additionally, we categorized the causes of death by disease group annually to observe how the proportions changed. Results: Since 2001, annual mortality for dialysis patients generally declined, except for a rise in 2020 and 2021 among hemodialysis patients. Overall mortality rates for all dialysis patients dropped from 74.2/1,000 person-years in 2001 to 42.3/1,000 person-years in 2022, with a more pronounced decrease in peritoneal dialysis. While survival probability over the 5 years following initiation of dialysis has shown a steady increase, short-term mortality from 2018 to 2020 affected by coronavirus disease 2019 (COVID-19) has shown a yearly increase by age group, with a greater effect in those aged 75 years and older. The leading causes of death for all dialysis patients have changed little, in the order of heart disease, infection, and vascular problems. Conclusion: While annual mortality and survival probability after dialysis initiation have generally improved in dialysis patients, there has been a temporary deterioration during the COVID-19 pandemic, most pronounced in the elderly.

Striated muscle fiber crossings of the head and neck: a histological study using near-term human fetuses and elderly cadavers.

Striated muscle fiber crossings at almost right angle are known to exist in the face, soft palate, pharyngeal wall and tongue. We aimed to identify a specific interface tissue at the crossing. We observed histological sections from 22 half-heads of 12 near-term fetuses at 26-40 weeks (crown-rump length, 215-334 mm). For comparison, we also observed tongue frontal sections from 5 elderly cadavers (75-85 years old). At the angle of mouth as well as in the soft palate and pharyngeal wall, a solitary striated muscle fiber (e.g., levator) consistently crossed a fiber bundle of the antagonist muscle (e.g., depressor), but a solitary-to-solitary fiber interdigitation was unlikely with the antagonist muscle. Near the external nasal orifice as well as in the tongue intrinsic muscle layer, at every section, there was a crossing with an endomysium-to-endomysium contact: the nasalis and platysma muscles and; the vertical and transverse (or inferior longitudinal) tongue muscles. Therein, the functional vectors crossed at almost right angle. Also in adult tongue, the vertical and transverse muscle fibers sometimes (0-2 sites per section) crossed with an endomysium-to-endomysium contact. At the muscle crossing with an endomysium contact, the endomysium and basement membrane seemed to receive a friction stress between two muscles. Although some crossings might disappear due to high muscle activity after birth, not a few of them were likely to maintain. To minimize the mechanical stress, a minute nervous control of the timing, duration and strength of muscle contraction seemed to be necessary.

Trends in clinical outcomes of older hemodialysis patients: data from the 2023 Korean Renal Data System (KORDS).

With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65-74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.

Risk of Ischemic Stroke in Relation to Helicobacter pylori Infection and Eradication Status: A Large-Scale Prospective Observational Cohort Study.

Background/Aims: : A few studies have suggested the association between Helicobacter pylori (HP) infection and ischemic stroke. However, the impact of HP eradication on stroke risk has not been well evaluated. This study aimed to assess the influence of HP eradication on the incidence of ischemic stroke, considering the potential effect of sex. Methods: : This prospective observational cohort study was conducted at Seoul National University Bundang Hospital, from May 2003 to February 2023, and involved gastroscopy-based HP testing. Propensity score (PS) matching was employed to ensure balanced groups by matching patients in the HP eradicated group (n=2,803) in a 3:1 ratio with patients in the HP non-eradicated group (n=960). Cox proportional hazard regression analysis was used to evaluate the risk of ischemic stroke. Results: : Among 6,664 patients, multivariate analysis after PS matching indicated that HP eradication did not significantly alter the risk of ischemic stroke (hazard ratio, 0.531; 95% confidence interval, 0.221 to 1.270; p=0.157). Sex-specific subgroup analyses, both univariate and multivariate, did not yield statistically significant differences. However, Kaplan-Meier analysis revealed a potential trend: the females in the HP eradicated group exhibited a lower incidence of ischemic stroke than those in the HP non-eradicated group, although this did not reach statistical significance (p=0.057). Conclusions: : This finding suggests that HP eradication might not impact the risk of ischemic stroke. However, there was a trend showing that females potentially had a lower risk of ischemic stroke following HP eradication, though further investigation is required to establish definitive evidence.

Efficacy of immune-checkpoint inhibitors combined with cytotoxic chemotherapy in advanced or recurrent endometrial cancer: A systematic review and meta-analysis.

BACKGROUND: The combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. METHODS: We conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). FINDINGS: Four trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62-0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63-0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26-0.43; OS; HR, 0.37; 95% CI, 0.22-0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54-0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56-0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19-0.81) over PD-L1 negative population. INTERPRETATION: ICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.

Insertions of the striated muscles in the skin and mucosa: a histological study of fetuses and cadavers.

Striated muscle insertions into the skin and mucosa are present in the head, neck, and pelvic floor. We reexamined the histology of these tissues to elucidate their role in transmission of the force. We examined histological sections of 25 human fetuses (gestational ages of ~11-19 weeks and ~26-40 weeks) and 6 cadavers of elderly individuals. Facial muscle insertion or terminal almost always formed as an interdigitation with another muscle or as a circular arrangement in which muscle fiber insertions were sandwiched and mechanically supported by other muscle fibers (like an in-series muscle). Our examination of the face revealed some limited exceptions in which muscle fibers that approached the dermis were always in the nasalis and mentalis muscles, and often in the levator labii superioris alaeque nasi muscle. The buccinator muscle was consistently inserted into the basement membrane of the oral mucosa. Parts of the uvulae muscle in the soft palate and of the intrinsic vertical muscle of the tongue were likely to direct toward the mucosa. In contrast, the pelvic floor did not contain striated muscle fibers that were directed toward the skin or mucosa. Although 'cutaneous muscle' is a common term, the actual insertion of a muscle into the skin or mucosa seemed to be very rare. Instead, superficial muscle insertion often consisted of interdigitated muscle bundles that had different functional vectors. In this case, the terminal of one muscle bundle was sandwiched and fixed mechanically by other bundles.