Single-cell atlas of ABCA7 loss-of-function reveals impaired neuronal respiration via choline-dependent lipid imbalances.

Loss-of-function (LoF) variants in the lipid transporter ABCA7 significantly increase the risk of Alzheimer's disease (odds ratio ∼2), yet the pathogenic mechanisms and the neural cell types affected by these variants remain largely unknown. Here, we performed single-nuclear RNA sequencing of 36 human post-mortem samples from the prefrontal cortex of 12 ABCA7 LoF carriers and 24 matched non-carrier control individuals. ABCA7 LoF was associated with gene expression changes in all major cell types. Excitatory neurons, which expressed the highest levels of ABCA7, showed transcriptional changes related to lipid metabolism, mitochondrial function, cell cycle-related pathways, and synaptic signaling. ABCA7 LoF-associated transcriptional changes in neurons were similarly perturbed in carriers of the common AD missense variant ABCA7 p.Ala1527Gly (n = 240 controls, 135 carriers), indicating that findings from our study may extend to large portions of the at-risk population. Consistent with ABCA7's function as a lipid exporter, lipidomic analysis of isogenic iPSC-derived neurons (iNs) revealed profound intracellular triglyceride accumulation in ABCA7 LoF, which was accompanied by a relative decrease in phosphatidylcholine abundance. Metabolomic and biochemical analyses of iNs further indicated that ABCA7 LoF was associated with disrupted mitochondrial bioenergetics that suggested impaired lipid breakdown by uncoupled respiration. Treatment of ABCA7 LoF iNs with CDP-choline (a rate-limiting precursor of phosphatidylcholine synthesis) reduced triglyceride accumulation and restored mitochondrial function, indicating that ABCA7 LoF-induced phosphatidylcholine dyshomeostasis may directly disrupt mitochondrial metabolism of lipids. Treatment with CDP-choline also rescued intracellular amyloid ß -42 levels in ABCA7 LoF iNs, further suggesting a link between ABCA7 LoF metabolic disruptions in neurons and AD pathology. This study provides a detailed transcriptomic atlas of ABCA7 LoF in the human brain and mechanistically links ABCA7 LoF-induced lipid perturbations to neuronal energy dyshomeostasis. In line with a growing body of evidence, our study highlights the central role of lipid metabolism in the etiology of Alzheimer's disease.

Clinical Outcomes of Endoscopic Butterfly Inlay Cartilage Myringoplasty.

OBJECTIVE: To review a 3-year case series of endoscopic butterfly inlay cartilage myringoplasty performed by a single surgeon (W.S.K.) and analyze the clinical surgical outcomes. STUDY DESIGN: Retrospective study. SETTING: Tertiary care academic center. PATIENTS: We enrolled 60 ears with tympanic membrane (TM) perforation, receiving endoscopic inlay butterfly myringoplasty between 2019 and 2022. MAIN OUTCOMES AND MEASURES: We reviewed patients' demographics, size and location of TM perforation, operation time, complications, and postoperative pain evaluated by the numerical rating scale (NRS). We analyzed the graft uptake success rate in 5 weeks and the perforation closure rate in 4 months after surgery. We also compared the air-bone gap (ABG) before and after the surgery. RESULTS: Among the 60 ears included, the mean age was 57.0 years, and 78.3% (47 of 60) had small perforations. The average operation time was 48.9 ± 11.5 minutes, and the postoperative NRS was 2.0 ± 1.6. The immediate graft uptake success rate evaluated at postoperative 5 weeks was 96.7% (58 of 60), with myringitis occurring in three ears. Except for 11 patients lost to follow-up, the perforation closure rate evaluated at postoperative 4 months was 100% (49 of 49). The mean ABG significantly improved from preoperative status (8.87 ± 5.51 dB HL) to postoperative 4 months (6.22 ± 6.03 dB HL) ( p = 0.019). CONCLUSIONS: A single surgeon's success rate for endoscopic butterfly inlay cartilage myringoplasty was almost 100%. This surgical procedure is safe and effective, with a high graft success rate.

Predicting cerebrovascular age and its clinical relevance: Modeling using 3D morphological features of brain vessels.

Aging manifests as many phenotypes, among which age-related changes in brain vessels are important, but underexplored. Thus, in the present study, we constructed a model to predict age using cerebrovascular morphological features, further assessing their clinical relevance using a novel pipeline. Age prediction models were first developed using data from a normal cohort (n = 1181), after which their relevance was tested in two stroke cohorts (n = 564 and n = 455). Our novel pipeline adapted an existing framework to compute generic vessel features for brain vessels, resulting in 126 morphological features. We further built various machine learning models to predict age using only clinical factors, only brain vessel features, and a combination of both. We further assessed deviation from healthy aging using the age gap and explored its clinical relevance by correlating the predicted age and age gap with various risk factors. The models constructed using only brain vessel features and those combining clinical factors with vessel features were better predictors of age than the clinical factor-only model (r = 0.37, 0.48, and 0.26, respectively). Predicted age was associated with many known clinical factors, and the associations were stronger for the age gap in the normal cohort. The age gap was also associated with important factors in the pooled cohort atherosclerotic cardiovascular disease risk score and white matter hyperintensity measurements. Cerebrovascular age, computed using the morphological features of brain vessels, could serve as a potential individualized marker for the early detection of various cerebrovascular diseases.

The Relationship Between Lower Vitamin D Levels and Hearing Loss in Older Adults.

Background and Objectives: : Age-related hearing loss (ARHL) is a sensorineural disease that is associated with a number of factors. In addition to age, sex, environment, lifestyle, and comorbidities are all known to be related to ARHL as well. The prevalence of ARHL can be reduced by controlling the adjustable factors that cause it. Vitamin D levels are strongly related to calcium metabolism, which can affect ARHL. This study aimed to investigate the association between vitamin D and ARHL. Subjects and Methods: : A total of 1,104 subjects aged >65 years were enrolled from the fifth Korean National Health and Nutrition Examination Survey, which was conducted from 2010-2012. Every participant received both an audiological assessment and a nutritional survey. The association between ARHL and serum vitamin D concentration was analyzed using logistic regression analyses with complex sampling adjusted for confounding factors such as alcohol consumption, smoking status, mobility, and bone mineral density. Results: : Our multivariable analysis revealed that males in the group with lower serum levels of vitamin D (< 20 ng/mL) had a higher prevalence of ARHL (odds ratio, 1.638, 95% confidence interval, 1.058-2.538, p=0.027). Conclusions: : This finding suggests that lower serum levels of vitamin D are associated with ARHL in the older male population.

Efficacy and safety of a self-expandable retainer in endoscopic ear surgery.

PURPOSE: During endoscopic ear surgery (EES), it is important to maintain a clear view of the endoscopic camera to achieve a clean field. In this study, a self-expandable external auditory canal (EAC) retainer was developed to enable a more efficient and safer EES. This study aimed to evaluate the retainer's efficacy and safety in EES. METHODS: Among adult patients scheduled for endoscopic tympanoplasty, 50 participants were recruited. They were assigned to either the retainer or control group in a 1:1 ratio. The anatomical characteristics, number of endoscopic cleanings during surgery, surgeon's satisfaction, and other factors were evaluated. RESULTS: No differences were observed in the surgical direction, EAC size measured on preoperative temporal bone computed tomography scans, location and size of tympanic membrane perforation, or bleeding degree between the two groups. When comparing the surgical time, including retainer insertion and removal, the time was similar between groups (retainer group, 35 min; control group, 33.2 min). The frequency of endoscopic cleaning per minute was statistically significantly lower in the retainer group than in the control group (0.18 times per minute, p = 0.048). No side effects, including sensory abnormalities or allergic reactions, were reported in any patient who used the retainer. CONCLUSION: A reduction in unnecessary endoscopic cleaning during EES was observed while using the self-expandable retainer, leading to increased surgeon satisfaction and efficiency. Furthermore, as a safe method without side effects, the retainer could be widely used to various indications for EES beyond tympanoplasty.

Machine Learning-Based Etiologic Subtyping of Ischemic Stroke Using Circulating Exosomal microRNAs.

Ischemic stroke is a major cause of mortality worldwide. Proper etiological subtyping of ischemic stroke is crucial for tailoring treatment strategies. This study explored the utility of circulating microRNAs encapsulated in extracellular vesicles (EV-miRNAs) to distinguish the following ischemic stroke subtypes: large artery atherosclerosis (LAA), cardioembolic stroke (CES), and small artery occlusion (SAO). Using next-generation sequencing (NGS) and machine-learning techniques, we identified differentially expressed miRNAs (DEMs) associated with each subtype. Through patient selection and diagnostic evaluation, a cohort of 70 patients with acute ischemic stroke was classified: 24 in the LAA group, 24 in the SAO group, and 22 in the CES group. Our findings revealed distinct EV-miRNA profiles among the groups, suggesting their potential as diagnostic markers. Machine-learning models, particularly logistic regression models, exhibited a high diagnostic accuracy of 92% for subtype discrimination. The collective influence of multiple miRNAs was more crucial than that of individual miRNAs. Additionally, bioinformatics analyses have elucidated the functional implications of DEMs in stroke pathophysiology, offering insights into the underlying mechanisms. Despite limitations like sample size constraints and retrospective design, our study underscores the promise of EV-miRNAs coupled with machine learning for ischemic stroke subtype classification. Further investigations are warranted to validate the clinical utility of the identified EV-miRNA biomarkers in stroke patients.

Virtual Reality Simulation-Based Clinical Procedure Skills Training for Nursing College Students: A Quasi-Experimental Study.

Core nursing skills are emphasized in nursing education, given their vital role in nurses' competence; however, invasive nursing procedures like catheterization and enemas are infrequently performed in actual clinical practice, primarily being observed rather than executed. Virtual reality simulation training involves performing core nursing skills on virtual patients in a three-dimensional virtual reality environment, following the correct procedures. The purpose of this study is to examine the effects of VR simulation on nursing students' confidence, proficiency, task engagement, and satisfaction. The study participants included 76 second-year nursing students, with 37 in the VR group and 39 in the control group. The VR group engaged in immersive VR (IVR) training sessions including enemas, nasogastric feeding, and nelaton catheterization. Conversely, the control group practiced these skills using mannequins. Assessments evaluated confidence, proficiency, learning satisfaction, and task engagement before and after the intervention. The average age of the study participants was 21.07 years, with 78.95% being female and 21.05% being male. The study findings revealed no significant differences between the VR and control groups regarding confidence (F = 3.878, p = 0.053), task engagement (F = 0.164, p = 0.687), and learning satisfaction (F = 0.668, p = 0.416). However, the VR group demonstrated significantly higher proficiency in the overall assessment of nasogastric feeding (F = 5.389, p = 0.023) and core components of nelaton catheterization (F = 4.046, p = 0.048). The IVR program emerged as an effective and valuable teaching tool, particularly well-suited for second-year nursing students, significantly enhancing proficiency.

Audiological Outcome of the Simultaneous Tumor Resection and Cochlear Implantation in Two Cases of Sporadic and Two Cases of Neurofibromatosis Type 2-Associated Intracochlear Schwannoma.

Objectives: Simultaneous removal and cochlear implantation (CI) have been reported in intralabyrinthine and intracochlear schwannoma. A wide range of postoperative hearing outcomes have been reported after CI in these cases. This study evaluated the outcomes of performing a simultaneous resection of Schwannoma in cochlea and cochlear implantation (CI), aiming to assess the effectiveness of this combined surgical approach for hearing rehabilitation with CI. Methods: This retrospective case series was conducted at a tertiary care center. The study included four consecutive patients with profound sensorineural hearing loss due to a mass inside the cochlea. These patients underwent simultaneous single-sided CI and tumor resection performed by the same surgeon. Preoperative and postoperative audiological assessments were conducted to evaluate the patients' hearing outcomes before and after the surgical intervention. Results: Simultaneous CI with tumor resection was successful in all cases. Two of the four patients had a unilateral tumor, while the other two had a bilateral tumor with the involvement of the internal auditory canal and cerebellopontine angle (neurofibromatosis type 2 (NF2)). In two cases of unilateral tumor, aided free-field pure tone average (PTA) was 26 dB, and 46 dB hearing level (HL), and word recognition score (WRS) at 65 dB was 40% and 68%, respectively, 3 months after surgery. In two cases of tumor with NF2, aided free-field PTA was 36 dB and 60 dB HL, and both cases showed 0% WRS at 65 dB 3 months after surgery. Conclusions: Simultaneous schwannoma excision and CI in patients with Schwannoma inside cochlea are surgically practical and safe. Postoperatively, there was a notable improvement in hearing in cases of sporadic schwannoma, regardless of the type of CI used. However, there was 0% WRS in the two NF2 patients with a mass in the internal auditory canal.

Deep Learning-Based Automatic Classification of Ischemic Stroke Subtype Using Diffusion-Weighted Images.

BACKGROUND AND PURPOSE: Accurate classification of ischemic stroke subtype is important for effective secondary prevention of stroke. We used diffusion-weighted image (DWI) and atrial fibrillation (AF) data to train a deep learning algorithm to classify stroke subtype. METHODS: Model development was done in 2,988 patients with ischemic stroke from three centers by using U-net for infarct segmentation and EfficientNetV2 for subtype classification. Experienced neurologists (n=5) determined subtypes for external test datasets, while establishing a consensus for clinical trial datasets. Automatically segmented infarcts were fed into the model (DWI-only algorithm). Subsequently, another model was trained, with AF included as a categorical variable (DWI+AF algorithm). These models were tested: (1) internally against the opinion of the labeling experts, (2) against fresh external DWI data, and (3) against clinical trial dataset. RESULTS: In the training-and-validation datasets, the mean (±standard deviation) age was 68.0±12.5 (61.1% male). In internal testing, compared with the experts, the DWI-only and the DWI+AF algorithms respectively achieved moderate (65.3%) and near-strong (79.1%) agreement. In external testing, both algorithms again showed good agreements (59.3%-60.7% and 73.7%-74.0%, respectively). In the clinical trial dataset, compared with the expert consensus, percentage agreements and Cohen's kappa were respectively 58.1% and 0.34 for the DWI-only vs. 72.9% and 0.57 for the DWI+AF algorithms. The corresponding values between experts were comparable (76.0% and 0.61) to the DWI+AF algorithm. CONCLUSION: Our model trained on a large dataset of DWI (both with or without AF information) was able to classify ischemic stroke subtypes comparable to a consensus of stroke experts.

Temporal trends of sex differences in acute reperfusion therapy and early outcomes of acute ischemic stroke in South Korea: 10-year analysis of the nationwide stroke registry.

BACKGROUND: Sex differences in stroke outcomes are notable, with women experiencing higher incidence rates, greater disability-adjusted life years, and poorer recovery compared to men, even after adjusting for age and comorbidities. Despite the disproportionate burden in women, studies have reported that women are less likely to receive appropriate stroke treatment than men. AIM: This study investigated temporal trends of sex differences in acute reperfusion therapy and early outcomes in patients with acute ischemic stroke over 10 years in South Korea. METHODS: A retrospective analysis of Korean Stroke Registry included patients with acute ischemic stroke from 2012 to 2021. The study outcomes were the temporal trends of acute reperfusion therapy and early outcomes over 10 years in men and women, respectively. In addition, this study analyzed the temporal trends of sex differences in these parameters during the same period. Early outcomes include the proportions of favorable functional outcomes at discharge, discharge patterns, and in-hospital mortality. RESULTS: A total of 93,692 patients (68.4 years, 40.1% women) with acute ischemic stroke were finally enrolled. Women had a higher age at stroke onset, a higher prevalence of atrial fibrillation, and more severe strokes than men. Women had lower proportion of favorable functional outcomes at discharge and higher proportion of in-hospital mortality compared to men each year. The proportion of patients who received intravenous thrombolysis was lower or similar in women compared to men in most years, and the proportion of patients who received endovascular thrombectomy did not significantly differ between sexes annually. Sex differences in acute reperfusion therapy remained unchanged over 10 years. CONCLUSION: Women have received acute reperfusion therapy at similar or lower rates than men and experienced poorer outcomes, despite having more stroke risk factors and often more severe strokes.

Sternoclavicular xanthogranulomatous osteomyelitis in a patient after kidney transplantation: a case report.

Xanthogranulomatous osteomyelitis (XO) is a rare chronic inflammatory bone disease characterized by the presence of cholesterol-laden foam macrophages, histiocytes, and plasma cells. We report the case of a 41-year-old man with end-stage renal disease who had undergone deceased donor kidney transplantation 4 years earlier. He presented with a chest wall mass that he had first identified 2 weeks prior to admission. Computed tomography revealed a periosseous heterogeneously enhancing soft tissue mass adjacent to the sternal end of the left clavicle, accompanied by irregular and destructive osteolytic lesions on the left side of the sternal manubrium. A total mass resection, which included partial clavicle and sternum removal, was performed. Pathological examination revealed foamy histiocytes along with numerous lymphoplasmacytic cells, confirming the diagnosis of XO. This case underscores the potential for XO to develop following kidney transplantation.

Global intracranial arterial tortuosity is associated with intracranial atherosclerotic burden.

The effect of arterial tortuosity on intracranial atherosclerosis (ICAS) is not well understood. This study aimed to evaluate the effect of global intracranial arterial tortuosity on intracranial atherosclerotic burden in patients with ischemic stroke. We included patients with acute ischemic stroke who underwent magnetic resonance angiography (MRA) and classified them into three groups according to the ICAS burden. Global tortuosity index (GTI) was defined as the standardized mean curvature of the entire intracranial arteries, measured by in-house vessel analysis software. Of the 516 patients included, 274 patients had no ICAS, 140 patients had a low ICAS burden, and 102 patients had a high ICAS burden. GTI increased with higher ICAS burden. After adjustment for age, sex, vascular risk factors, and standardized mean arterial area, GTI was independently associated with ICAS burden (adjusted odds ratio [adjusted OR] 1.33; 95% confidence interval [CI] 1.09-1.62). The degree of association increased when the arterial tortuosity was analyzed limited to the basal arteries (adjusted OR 1.48; 95% CI 1.22-1.81). We demonstrated that GTI is associated with ICAS burden in patients with ischemic stroke, suggesting a role for global arterial tortuosity in ICAS.

Soft-tissue volume augmentation using a connective tissue graft and a volume-stable collagen matrix with polydeoxyribonucleotide for immediate implant placement: a pilot study in a dog model.

PURPOSE: The aims of this study were 1) to investigate the effects of a subepithelial connective tissue graft (SCTG) and a volume-stable collagen matrix (VCMX) on soft-tissue volume gain in the immediate implant placement protocol, and 2) to determine whether polydeoxyribonucleotide (PDRN) can enhance the effects of a VCMX. METHODS: Dental implants were placed in 4 mongrel dogs immediately after extracting the distal roots of their third and fourth mandibular premolars. The gap between the implant and the buccal bone plate was filled with synthetic bone substitute particles. The following soft-tissue augmentation modalities were applied buccally: 1) control (no augmentation), 2) SCTG, 3) VCMX, and 4) VCMX/PDRN. After 4 months, histomorphometric analysis was performed. Tissue changes were evaluated using superimposed standard tessellation language (STL) files. RESULTS: Wound dehiscence was found in more than half of the test groups, but secondary wound healing was successfully achieved in all groups. Histomorphometrically, tissue thickness was favored in group SCTG at or above the implant platform level (IP), and group SCTG and the groups with VCMX presented similar tissue thickness below the IP. However, the differences in such thickness among the groups were minor. The keratinized tissue height was greater in group VCMX/PDRN than in groups SCTG and VCMX. Superimposing the STL files revealed a decrease in soft-tissue volume in all groups. CONCLUSIONS: Wound dehiscence after soft-tissue volume augmentation might be detrimental to obtaining the expected outcomes. PDRN appears not to have a positive effect on the soft-tissue volume gain.

The Role of Measuring Preoperative Social Maturation Score in Children With Additional Needs Who Underwent Cochlear Implantation.

BACKGROUND AND OBJECTIVES: Additional needs refer to specific requirements or support for individuals with disabilities or syndromes. Intellectual ability is a crucial outcome determinant of a cochlear implant. The social quotient (SQ) is an indirect predictor of intellectual capacity and social skills. This study aimed to investigate the clinical significance of the SQ on children with additional needs who received cochlear implants. Subjects and. METHODS: This study included 24 patients with diagnosed developmental delays and syndromes, who demonstrated SQ scores of <70. Preoperative social skills were evaluated using the SQ. All patients underwent cochlear implantation (CI) surgery before 7 years of age. Outcomes were evaluated using the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and Categories of Auditory Performance (CAP) scores. Data were collected through a retrospective chart review. RESULTS: Children were categorized into three groups based on their SQ. There were no correlations between the preoperative SQ and IT-MAIS or CAP scores at 2 and 5 years of follow-up postoperatively. The CI outcomes of children with low SQ (<70) differed from those with normal development (SQ>70). In the low-SQ group, inner ear anomalies were observed in 10 (41.7%) patients. Although not statistically significant, these children exhibited a trend of lower average outcomes than children without inner ear anomalies. CONCLUSIONS: CI outcomes in children with additional needs positively affected auditory performance. Postoperative auditory and language skills tended to improve slowly in children with additional needs and a lower SQ. Over time, development gradually became more comparable to the other groups of children. However, this improvement was less than that observed in children without additional needs. Our findings support CI for children with additional needs as part of long-term auditory rehabilitation following surgery.

Long-term follow-up results of facial nerve schwannoma with good facial nerve function: a multicenter study.

PURPOSE: Facial nerve schwannomas (FNSs) are rare intracranial tumors, and the optimal management of these tumors remains unclear. We investigated the long-term follow-up results of FNS with good facial nerve function. METHODS: At nine medical centers in the Korean Facial Nerve Study Group, 43 patients undergoing observation periods longer than 12 months for FNS with good facial nerve function (House-Brackmann grade ≤ II) were enrolled, and clinical and radiographic data were obtained for these cases. RESULTS: The mean follow-up period was 63 months. In the majority of cases, tumors involved multiple segments (81.4%) and only eight cases were confined to a single site. There were no cases where the tumor was confined to the extratemporal region. Tumor size increased slightly, with an average estimated change of 0.48 mm/year. Twenty (46.5%) of 43 patients showed no change in tumor size. Seven patients (16.3%) showed worsening House-Brackmann (H-B) grade, of which two patients deteriorated from H-B grade I to II, four worsened to grade III, and one deteriorated to grade IV. The remaining 36 patients (83.7%) showed no change in facial nerve function. There was no difference in H-B grade according to tumor size at the time of diagnosis or change in tumor size. CONCLUSION: We conducted a large-scale observational study of FNS with good facial nerve function. Our study showed that many patients maintained facial nerve function during long-term follow-up. Conservative management with regular examination and imaging can be an appropriate option for managing FNS with good facial nerve function.

Educational simulator for mastoidectomy considering mechanical properties using 3D printing and its usability evaluation.

Complex temporal bone anatomy complicates operations; thus, surgeons must engage in practice to mitigate risks, improving patient safety and outcomes. However, existing training methods often involve prohibitive costs and ethical problems. Therefore, we developed an educational mastoidectomy simulator, considering mechanical properties using 3D printing. The mastoidectomy simulator was modeled on computed tomography images of a patient undergoing a mastoidectomy. Infill was modeled for each anatomical part to provide a realistic drilling sensation. Bone and other anatomies appear in assorted colors to enhance the simulator's educational utility. The mechanical properties of the simulator were evaluated by measuring the screw insertion torque for infill specimens and cadaveric temporal bones and investigating its usability with a five-point Likert-scale questionnaire completed by five otolaryngologists. The maximum insertion torque values of the sigmoid sinus, tegmen, and semicircular canal were 1.08 ± 0.62, 0.44 ± 0.42, and 1.54 ± 0.43 N mm, displaying similar-strength infill specimens of 40%, 30%, and 50%. Otolaryngologists evaluated the quality and usability at 4.25 ± 0.81 and 4.53 ± 0.62. The mastoidectomy simulator could provide realistic bone drilling feedback for educational mastoidectomy training while reinforcing skills and comprehension of anatomical structures.

Comparative Analysis of Polyphenolic Compounds in Different Amaranthus Species: Influence of Genotypes and Harvesting Year.

Amaranth is a nutritionally valuable crop, as it contains phenolic acids and flavonoids, yielding diverse plant secondary metabolites (PSMs) like phytosterol, tocopherols, and carotenoids. This study explored the variations in the contents of seventeen polyphenolic compounds within the leaves of one hundred twenty Amaranthus accessions representing nine Amaranthus species. The investigation entailed the analysis of phenolic content across nine Amaranthus species, specifically A. hypochondriacus, A. cruentus, A. caudatus, A. tricolor, A. dubius, A. blitum, A. crispus, A. hybridus, and A. viridis, utilizing ultra performance liquid chromatography with photodiode array detection (UPLC-PDA). The results revealed significant differences in polyphenolic compounds among accessions in which rutin content was predominant in all Amaranthus species in both 2018 and 2019. Among the nine Amaranthus species, the rutin content ranged from 95.72 ± 199.17 µg g-1 (A. dubius) to 1485.09 ± 679.51 µg g-1 (A. viridis) in 2018 and from 821.59 ± 709.95 µg g-1 (A. tricolor) to 3166.52 ± 1317.38 µg g-1 (A. hypochondriacus) in 2019. Correlation analysis revealed, significant positive correlations between rutin and kaempferol-3-O-ß-rutinoside (r = 0.93), benzoic acid and ferulic acid (r = 0.76), and benzoic acid and kaempferol-3-O-ß-rutinoside (r = 0.76), whereas gallic acid showed consistently negative correlations with each of the 16 phenolic compounds. Wide variations were identified among accessions and between plants grown in the two years. The nine species and one hundred twenty Amaranthus accessions were clustered into six groups based on their seventeen phenolic compounds in each year. These findings contribute to expanding our understanding of the phytochemical traits of accessions within nine Amaranthus species, which serve as valuable resources for Amaranthus component breeding and functional material development.

Synergistic Renoprotective Effects of Green Tea Extract and Gemigliptin against Tacrolimus-Induced Nephrotoxicity in Mice

SUMMARY: Although tacrolimus (TAC) significantly reduces allograft rejection incidence in solid-organ transplantation, its long-term use is associated with an increased risk of TAC-induced nephrotoxicity. In this study, we investigated the renoprotective effects of green tea extract (GTE) with or without the dipeptidyl peptidase 4 inhibitor, gemigliptin, by assessing serum creatinine levels, the amount of proteinuria, and histopathology in TAC-induced nephrotoxicity. TAC-induced nephrotoxicity was induced by intraperitoneal TAC injection, GTE was administered via subcutaneous injection, and gemigliptin was administered orally. Mice with TAC-induced nephrotoxicity exhibited a significant increase in both serum creatinine levels and 24-hour urine protein. However, when treated with GTE via subcutaneous injection, mice showed a decrease in serum creatinine levels and the amount of proteinuria. When GTE was combined with gemigliptin, further renoprotective effects were observed in biochemical assessments, consistent with the attenuation of TAC-induced nephrotoxicity in histopathology. The expression of p53 protein was lower in the mice treated with the combination of GTE and gemigliptin compared to mice with TAC-induced nephrotoxicity. Our results demonstrate that the combination of GTE and gemigliptin treatment reveals synergistic renoprotective effects by decreasing the expression of p53 protein. These findings suggest that the combination of GTE and gemigliptin could potentially be used as a prophylactic or therapeutic strategy for TAC-induced nephrotoxicity.

Aunque tacrolimus (TAC) reduce significativamente la incidencia de rechazo de aloinjertos en trasplantes de órganos sólidos, su uso a largo plazo se asocia con un mayor riesgo de nefrotoxicidad inducida por TAC. En este estudio, investigamos los efectos renoprotectores del extracto de té verde (GTE) con o sin el inhibidor de la dipeptidil peptidasa 4, gemigliptina, mediante la evaluación de los niveles de creatinina sérica, la cantidad de proteinuria y la histopatología en la nefrotoxicidad inducida por TAC. La nefrotoxicidad inducida por TAC se indujo mediante inyección intraperitoneal de TAC, el GTE se administró mediante inyección subcutánea y la gemigliptina se administró por vía oral. Los ratones con nefrotoxicidad inducida por TAC mostraron un aumento significativo tanto en los niveles de creatinina sérica como en la proteína en orina de 24 horas. Sin embargo, cuando se trataron con GTE mediante inyección subcutánea, los ratones mostraron una disminución en los niveles de creatinina sérica y en la cantidad de proteinuria. Cuando se combinó GTE con gemigliptina, se observaron efectos renoprotectores adicionales en las evaluaciones bioquímicas, lo que concuerda con la atenuación de la nefrotoxicidad inducida por TAC en histopatología. La expresión de la proteína p53 fue menor en los ratones tratados con la combinación de GTE y gemigliptina en comparación con los ratones con nefrotoxicidad inducida por TAC. Nuestros resultados demuestran que la combinación de tratamiento con GTE y gemigliptina revela efectos renoprotectores sinérgicos al disminuir la expresión de la proteína p53. Estos hallazgos sugieren que la combinación de GTE y gemigliptina podría usarse potencialmente como estrategia profiláctica o terapéutica para la nefrotoxicidad inducida por TAC.

A comprehensive analysis integrating phenotypic assessment uncovering thornless cultivar lineages in Aralia elata.

Aralia elata is an Araliaceae woody plant species found in Northeastern Asia. To understand how genetic pools are distributed for A.elata clones, we were to analyze the population structure of A.elata cultivars and identify how these are correlated with thorn-related phenotype which determines the utility of A.elata. We found that the de novo assembled genome of 'Yeongchun' shared major genomic compartments with the public A.elata genome assembled from the wild-type from China. To identify the population structure of the 32 Korean and Japanese cultivars, we identified 44 SSR markers and revealed three main sub-clusters using ΔK analysis with one isolated cultivar. Machine-learning based clustering with thorn-related phenotype correlated moderately with population structure based on SSR analysis suggested multi-layered genetic regulation of thorn-related phenotypes. Thus, we revealed genetic lineage of A.elata and uncovered isolated cultivar which can provide new genetic material for further breeding.

Effectiveness of COVID-19 vaccines against severe outcomes in cancer patients: Real-world evidence from self-controlled risk interval and retrospective cohort studies.

BACKGROUND: The effectiveness of COVID-19 vaccines is generally reduced in cancer patients compared to the general population. However, there are only a few studies that compare the relative risk of breakthrough infections and severe COVID-19 outcomes in fully vaccinated cancer patients versus their unvaccinated counterparts. METHODS: To assess the effectiveness of COVID-19 vaccines in cancer patients, we employed (1) a self-controlled risk interval (SCRI) design, and (2) a retrospective matched cohort design. A SCRI design was used to compare the risk of breakthrough infection in vaccinated cancer patients during the period immediately following vaccination ("control window") and the period in which immunity is achieved ("exposure windows"). The retrospective matched cohort design was used to compare the risk of severe COVID-19 outcomes between vaccinated and unvaccinated cancer patients. For both studies, data were extracted from the Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service cohort, including demographics, medical history, and vaccination records of all individuals confirmed with COVID-19. We used conditional Poisson regression to calculate the incidence rate ratio (IRR) for breakthrough infection and Cox regression to estimate the hazard ratio (HR) for severe outcomes. RESULTS: Of 14,448 cancer patients diagnosed with COVID-19 between October 2020 and December 2021, a total of 217 and 3996 cancer patients were included in the SCRI and cohort study respectively. While the risk of breakthrough infections, measured by the incidence rate in the control and exposure windows, did not show statistically significant difference in vaccinated cancer patients (IRR=0.88, 95% CI: 0.64-1.22), the risk of severe COVID-19 outcomes was significantly lower in vaccinated cancer patients compared to those unvaccinated (HR=0.27, 95% CI: 0.22-0.34). CONCLUSION: COVID-19 vaccines significantly reduce the risk of severe outcomes in cancer patients, though their efficacy against breakthrough infections is less evident.