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Masoumeh Azimirad,1,* YoungJae Jo,2,* Min-Sueng Kim,2 Minsoo Jeong,2 Shabnam Shahrokh,3 Hamid Asadzadeh Aghdaei,4 Mohammad Reza Zali,3 Seungjun Lee,5 Abbas Yadegar,1 Jae-Ho Shin2 1Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 2Department of Applied Biosciences, Kyungpook National University, Daegu, 41566, Republic of Korea; 3Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 4Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran; 5Department of Food Science and Nutrition, College of Fisheries Science, Pukyong National University, Busan, Republic of Korea*These authors contributed equally to this workCorrespondence: Abbas Yadegar; Jae-Ho Shin Tel +98-21-22432518; +82 53-950-5716Fax +98-21-22432527; +82 53-953-7233Email babak_y1983@yahoo.com; jhshin@knu.ac.krBackground and Purpose: Fecal microbiota transplantation (FMT) has emerged for the therapeutic treatment of recurrent Clostridioides difficile infection (rCDI) with concurrent inflammatory bowel disease (IBD). As the first Iranian population cohort, we examined how gut microbiota and their functional profiles change in Iranian rCDI patients with underlying IBD before and after FMT.Patients and Methods: FMT was performed to eight IBD patients via colonoscopy. Profiles of gut microbiota from donors and recipients were investigated using 16S rRNA gene sequence analysis.Results: Patients experienced no IBD flare-ups or other adverse effects, and all recovered to full health. Moreover, all rCDI patients lacked the Bacteroidetes present in donor samples. After FMT, the proportion of Bacteroidetes increased until a normal range was achieved. More specifically, the relative abundance of Prevotella was found to increase significantly following FMT. Prevotella was also found to correlate negatively with inflammation metrics, suggesting that Prevotella may be a key factor for resolving CDI and IBD. Gut microbiota diversity was found to increase following FMT, while dysbiosis decreased. However, the similarity of microbial communities of host and recipients did not increase, and wide variation in the extent of donor stool engraftment indicated that the gut bacterial communities of recipients do not shift towards those of donors.Conclusion: FMT leads to significant alterations of the community structure of gut bacteria in rCDI patients with IBD. The change in relative abundance of Proteobacteria and bacterial diversity indicated that FMT promotes recovery from intestinal permeability and inflammation in rCDI patients. Moreover, strong negative correlation between Prevotella and inflammation index, and decreased dysbiosis index advocate that the improvement of CDI is possibly due to gut microbiome alteration. Collectively, our findings show that FMT would be a promising therapy to help reprogram the gut microbiome of Iranian rCDI patients with IBD.Keywords: fecal microbiota transplantation, Clostridioides difficile infection, inflammatory bowel disease, gut microbiome, functional profiles, gut dysbiosis

Moo-Yong Rhee,1 Cheol Ho Kim,2 Youngkeun Ahn,3 Joon-Han Shin,4 Seung Hwan Han,5 Hyun-Jae Kang,6 Soon Jun Hong,7 Hae-Young Kim8 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, Republic of Korea; 2Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea; 3Division of Cardiology, Department of Internal Medicine, Chonnam National University Hospital, Gwangju, Republic of Korea; 4Department of Cardiology, Ajou University Medical Center, Suwon, Republic of Korea; 5Division of Cardiology, Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea; 6Department of Internal Medicine, Seoul National University Cardiovascular Center, Seoul National University Hospital, Seoul, Republic of Korea; 7Department of Cardiology, Cardiovascular Center, Korea University Anam Hospital, Seoul, Republic of Korea; 8Department of Health Policy and Management, College of Health Science & Department of Public Health Science, Graduate School, Korea University, Seoul, Republic of KoreaCorrespondence: Cheol Ho Kim Department of Internal MedicineSeoul National University Bundang Hospital, Seongnam, Republic of KoreaTel +82 31 787 7001Fax +82 31 787 4051Email cheolkim55@gmail.comPurpose: We evaluated the efficacy and safety of nebivolol and rosuvastatin combination treatment in patients with hypertension and hyperlipidemia.Patients and Methods: Eligible patients, after more than 4 weeks of therapeutic lifestyle change, were randomly assigned to three groups: 5 mg nebivolol plus 20 mg rosuvastatin (NEBI/RSV), 20 mg rosuvastatin (RSV), or 5 mg nebivolol (NEBI). Treatments lasted 8 weeks.Results: Efficacy was analyzed using data from 276 patients. Sitting systolic and diastolic blood pressures differed between the NEBI/RSV and RSV groups (LSmean difference = − 5.89 and − 5.99 mmHg; 95% confidence interval [CI] = − 9.88 to − 1.90 mmHg and − 8.13 to − 3.84 mmHg, respectively). Reductions in the two pressures did not differ between the NEB/RSV and NEB groups. The percent reduction in low-density lipoprotein (LDL) cholesterol differed between the NEBI/RSV and NEBI groups (LSmean difference = − 47.76%, 95% CI = − 52.69 to − 42.84%) but not between the NEBI/RSV and RSV groups. The blood pressure (BP) control rate was higher in the NEBI/RSV group than in the RVS group (51.09% vs 29.67%, p = 0.003). The LDL cholesterol goal achievement rate was higher in the NEBI/RSV group than in the NEBI group (85.87% vs 11.83%, p < 0.001). The incidence of adverse drug reactions in the NEBI/RSV, RSV, and NEBI groups was 8.51%, 7.45%, and 8.60%, respectively (p = 0.950).Conclusion: Nebivolol plus rosuvastatin treatment is effective in reducing BP and LDL cholesterol levels and is safe in patients with hypertension and hypercholesterolemia without the loss of BP or the LDL cholesterol-lowering effect of each drug.Trial Registration: CRIS registration number KCT0002148.Keywords: hypertension, hypercholesterolemia, nebivolol, rosuvastatin

Jin-Sun Park,1,* Joon-Han Shin,1,* Taek-Jong Hong,2 Hong-Seog Seo,3 Wan-Joo Shim,4 Sang-Hong Baek,5 Jin-Ok Jeong,6 Youngkeun Ahn,7 Woong-Chol Kang,8 Young-Hak Kim,9 Sang-Hyun Kim,10 Min-Su Hyon,11 Dong-Hoon Choi,12 Chang-Wook Nam,13 Tae-Ho Park,14 Sang-Chol Lee,15 Hyo-Soo Kim16 1Department of Cardiology, Ajou University School of Medicine, Suwon, 2Division of Cardiology, Pusan National University Hospital, Busan, 3Division of Cardiology, Korea University Guro Hospital, Korea University College of Medicine, 4Division of Cardiology, Korea University Anam Hospital, 5Cardiovascular Division, Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 6Division of Cardiology, Chungnam National University Hospital, Daejeon, 7Division of Cardiology, Chonnam National University Hospital, Gwangju, 8Division of Cardiology, Gachon University Gil Hospital, Incheon, 9Division of Cardiology, Asan Medical Center, College of Medicine, University of Ulsan, 10Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, 11Division of Cardiology, Soonchunhyang University Hospital, 12Division of Cardiology, Yonsei University Severance Hospital, Seoul, 13Department of Internal Medicine, Keimyung University Dongsan Medical Center, Daegu, 14Division of Cardiology, Dong-A University Hospital, Busan, 15Cardiovascular Imaging Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 16Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul, Korea *These authors contributed equally to this work Abstract: The pill burden of patients with hypertension and dyslipidemia can result in poor medication compliance. This study aimed to evaluate the efficacy and safety of fixed-dose combination (FDC) therapy with olmesartan medoxomil (40 mg) and rosuvastatin (20 mg) in Korean patients with mild to moderate hypertension and dyslipidemia. This multicenter, randomized, double-blind, factorial-design study included patients aged ≥20 years with mild to moderate essential hypertension and dyslipidemia. Patients were randomly assigned to receive FDC therapy (40 mg olmesartan medoxomil, 20 mg rosuvastatin), 40 mg olmesartan medoxomil, 20 mg rosuvastatin, or a placebo. The percentage change from baseline in low-density lipoprotein cholesterol levels was compared between FDC therapy and olmesartan medoxomil, and the change from baseline in diastolic blood pressure was compared between FDC therapy and rosuvastatin 8 weeks after treatment. A total of 162 patients were included. The least square mean percentage change (standard error) from baseline in low-density lipoprotein cholesterol levels 8 weeks after treatment was significantly greater in the FDC than in the olmesartan medoxomil group (–52.3% [2.8%] vs –0.6% [3.5%], P

Cy Hyun Kim,1,2,* Jin-Hong Shin,1,3,* Sung Jun Hwang,1,2 Yung Hyun Choi,4 Dae-Seong Kim,1,3 Cheol Min Kim2,51Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 2Center for Anti-Aging Industry, Pusan National University, Busan, 3Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 4Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 5Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Republic of Korea*These authors contributed equally to this work Abstract: Schisandrae fructus (SF) has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1–10 µg/mL) of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 µg/mL of SF extract, enhancing differentiation up to 1.4-fold in fusion index and 1.6-fold in myotube area at 8 days after induction of differentiation compared to control. Phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 and 70 kDa ribosomal protein S6 kinase, which initiate translation as downstream of mammalian target of rapamycin pathway, was upregulated in early phases of differentiation after SF treatment. SF also attenuated dexamethasone-induced atrophy. In conclusion, we show that SF augments myogenic differentiation and attenuates atrophy by increasing protein synthesis through mammalian target of rapamycin/70 kDa ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway in human myotubes. SF can be a useful natural dietary supplement in increasing skeletal muscle mass, especially in the aged with sarcopenia and the patients with disuse atrophy.Keywords: Schisandrae fructus, mTOR signaling, human skeletal muscle cells, myotubes

Youngmok Park,1 Young Sam Kim,1 Young Ae Kang,1 Ju Hye Shin,1 Yeon Mok Oh,2 Joon Beom Seo,3 Ji Ye Jung,1 Sang Do Lee2 On behalf of the KOLD study 1Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Institute of Chest Diseases, Yonsei University College of Medicine, 2Department of Pulmonary and Critical Care Medicine, Clinical Research Center for Chronic Obstructive Airway Diseases, 3Department of Radiology and Research Institute of Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Background: In chronic obstructive pulmonary disease (COPD), the blood vitamin D3 level is generally low, and genetic polymorphisms of vitamin D-binding protein encoded by the GC gene are associated with COPD development. In this study, we examined the relationship between GC polymorphisms and plasma vitamin D3 level in Korean patients with COPD. Methods: The study included 175 COPD patients from the Korean Obstructive Lung Disease Cohort. Multivariate analysis was conducted with adjustment for age, body mass index (BMI), lung function, smoking status, smoking amount, and seasonal variation in blood vitamin D level. Vitamin D deficiency was defined as a plasma 25-hydroxyvitamin D3 level lower than 20 ng/mL. Results: The mean plasma vitamin D3 level was 17.5 ng/mL. The GC1F variant (44.3%) and genotype 1F-2 (27.4%) were the most common. The plasma vitamin D3 level was lower in patients with the GC2 variant (estimated =-3.73 ng/mL) and higher in those with genotype 1F-1S (estimated =4.08 ng/mL). The GC2 variant was a significant risk factor for vitamin D deficiency (odds ratio =2.41). Among COPD clinical parameters, vitamin D deficiency was associated with a lower ratio of forced expiratory volume in 1 second to forced vital capacity (FEV1/FVC) regardless of GC polymorphisms. FEV1/FVC was higher in patients with genotype 1F-1F (estimated =3.61%) and lower in those with genotype 1F-2 (estimated =-3.31%). The 6-minute walking distance was shorter for patients with the GC1F variant (estimated =-38.91 m) and longer for those with the GC2 variant (estimated =26.98 m). The emphysema index was higher for patients with the GC1S variant (estimated =6.56%) and genotype 1F-1S (estimated =9.86%), regardless of the vitamin D level. Conclusion: The GC2 variant is a risk factor for vitamin D deficiency, and genotype 1F-1S is a protective factor against vitamin D deficiency. GC polymorphisms and vitamin D deficiency correlate with clinical outcomes for Korean patients with COPD. Keywords: vitamin D-binding protein, polymorphism, vitamin D, chronic obstructive pulmonary disease

Moo-Yong Rhee,1 Sang Hong Baek,2 Weon Kim,3 Chang Gyu Park,4 Seung Woo Park,5 Byung-Hee Oh,6 Sang-Hyun Kim,7 Jae-Joong Kim,8 Joon-Han Shin,9 Byung-Su Yoo,10 Se-Joong Rim,11 Jong-Won Ha,12 Joon Hyung Doh,13 Youngkeun Ahn,14 Jei Keon Chae,15 Jeong Bae Park,16 Soon-Kil Kim,17 Cheol Ho Kim18 1Cardiovascular Center, Dongguk University Ilsan Hospital, Goyang, 2Catholic University of Korea, Seoul St Mary’s Hospital, Seoul, 3Cardiovascular Department of Internal Medicine, Kyung Hee University Medical Center, Seoul, 4Division of Cardiology, Guro Hospital, Korea University College of Medicine, Seoul, 5Division of Cardiology, Samsung Medical Center, Seoul, 6Department of Internal Medicine, Seoul National University Hospital, Seoul, 7Division of Cardiology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, 8Division of Cardiology, Asan Medical Center, Seoul, 9Division of Cardiology, Ajou University Hospital, Suwon, 10Division of Cardiology, Wonju Severance Christian Hospital, Wonju, 11Division of Cardiology, GangNam Severance Hospital, Seoul, 12Division of Cardiology, Severance Hospital, Seoul, 13Division of Cardiology, Inje University Ilsan Hospital, Goyang, 14Department of Cardiology, Chonnam National University Hospital, Gwangju, 15Chonbuk National University Hospital, Jeonju, 16Department of Cardiology, Cheil General Hospital, Dankook University College of Medicine, Seoul, 17Department of Cardiology, Hanyang University Guri Hospital, Guri, 18Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea Background: The study reported here compared the blood pressure (BP)-lowering efficacy of fimasartan alone with that of fimasartan/hydrochlorothiazide (HCTZ) combination in patients whose BP goal was not achieved after 4 weeks of treatment with once-daily fimasartan 60 mg.Methods: Patients with sitting diastolic blood pressure (siDBP) ≥90 mmHg with 4 weeks of once-daily fimasartan 60 mg were randomly assigned to receive either once-daily fimasartan 60 mg/HCTZ 12.5 mg or fimasartan 60 mg for 4 weeks. After 4 weeks, the dose was increased from fimasartan 60 mg/HCTZ 12.5 mg to fimasartan 120 mg/HCTZ 12.5 mg or from fimasartan 60 mg to fimasartan 120 mg if siDBP was ≥90 mmHg.Results: Of the 263 randomized patients, 256 patients who had available efficacy data were analyzed. The fimasartan/HCTZ treatment group showed a greater reduction of siDBP compared to the fimasartan treatment group at Week 4 (6.88±8.10 mmHg vs 3.38±7.33, P=0.0008), and the effect persisted at Week 8 (8.67±9.39 mmHg vs 5.02±8.27 mmHg, P=0.0023). Reduction of sitting systolic BP in the fimasartan/HCTZ treatment group was also greater than that in the fimasartan treatment group (at Week 4, 10.50±13.76 mmHg vs 5.75±12.18 mmHg, P=0.0069 and, at Week 8, 13.45±15.15 mmHg vs 6.84±13.57 mmHg, P=0.0007). The proportion of patients who achieved a reduction of siDBP ≥10 mmHg from baseline and/or a mean siDBP

Jeong-Sup Hong,1,2 Myeong-Kyu Park,1 Min-Seok Kim,1 Jeong-Hyeon Lim,1 Gil-Jong Park,1 Eun-Ho Maeng,1 Jae-Ho Shin,3 Meyoung-Kon Kim,4 Jayoung Jeong,5 Jin-A Park,2 Jong-Choon Kim,6 Ho-Chul Shin2 1Health Care Research Laboratory, Korea Testing and Research Institute, Gimpo, South Korea; 2College of Veterinary Medicine, Konkuk University, Seoul, South Korea; 3Department of Biomedical Laboratory Science, Eulji University, Seongnam-si, South Korea; 4Department of Biochemistry and Molecular Biology, Korea University Medical School and College, Seoul, South Korea; 5Toxicological Research Division, National Institute of Food and Drug Safety Evaluation, Chungcheongbuk-do, South Korea; 6College of Veterinary Medicine, Chonnam National University, Gwangju, South Korea Abstract: This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnOSM20(+) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo–fetal development after maternal exposure over the period of gestational days 5–19 with Sprague-Dawley rats. ZnOSM20(+) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations. Toxicity in the dams manifested as significantly decreased body weight after administration of 400 mg/kg/day NPs; reduced food consumption after administration of 200 and 400 mg/kg/day NPs; and decreased liver weight and increased adrenal glands weight after administration of 400 mg/kg/day NPs. However, no treatment-related difference in: number of corpora lutea; number of implantation sites; implantation rate (%); resorption; dead fetuses; litter size; fetal deaths and placental weights; and sex ratio were observed between the groups. On the other hand, significant decreases between treatment groups and controls were seen for fetal weights after administration of 400 mg/kg/day NPs. Morphological examinations of the fetuses demonstrated significant differences in incidences of abnormalities in the group administered 400mg/kg/day. Meanwhile, no significant difference was found in the Zn content of fetal tissue between the control and high-dose groups. These results showed that oral doses for the study with 15-days repeated of ZnOSM20(+) NPs were maternotoxic in the 200 mg/kg/day group, and embryotoxic in the 400 mg/kg/day group. Keywords: developmental toxicity, maternal toxicity, nanotoxicology, teratogenicity

The phenoconversion trajectory from idiopathic/isolated Rapid eye movement (REM) sleep behavior disorder (iRBD) towards either Parkinson's Disease (PD) or Dementia with Lewy Bodies (DLB) is currently uncertain. We investigated the capability of baseline brain [ 18 F]FDG-PET in differentiating between iRBD patients eventually phenoconverting to PD or DLB, by deriving the denovoPDRBD-related pattern (denovoPDRBD-RP) from 32 de novo PD patients; and the denovoDLBRBD-RP from 30 de novo DLB patients, both with evidence of RBD at diagnosis. To explore [ 18 F]FDG-PET phenoconversion trajectories prediction power, we applied these two patterns on a group of 115 iRBD patients followed longitudinally. At follow-up (25.6 ± 17.2 months), 42 iRBD patients progressed through overt alpha-synucleinopathy (21 iRBD-PD and 21 iRBD-DLB converters), while 73 patients remained stable at the last follow-up visit (43.2 ± 27.6 months). At survival analysis, both patterns were significantly associated with the phenoconversion trajectories. Brain [ 18 F]FDG-PET is a promising biomarker to study progression trajectories in the alpha-synucleinopathy continuum., (© 2024. The Author(s).)

Background: Previous studies have demonstrated geographical disparities regarding the quality of care for acute myocardial infarction (AMI). The aim of this study was two-fold: first, to calculate the proportion of patients with AMI who received primary percutaneous coronary interventions (pPCIs) by secondary medical areas (SMAs), which provide general inpatient care, as a quality indicator (QI) of the process of AMI practice. Second, to identify patterns in their trajectories and to investigate the factors related to regional differences in their trajectories., Methods: We included patients hospitalized with AMI between April 2014 and March 2020 from the national health insurance claims database in Japan and calculated the proportion of pPCIs across 335 SMAs and fiscal years. Using these proportions, we conducted group-based trajectory modeling to identify groups that shared similar trajectories of the proportions. In addition, we investigated area-level factors that were associated with the different trajectories., Results: The median (interquartile range) proportions of pPCIs by SMAs were 63.5% (52.9% to 70.5%) in FY 2014 and 69.6% (63.3% to 74.2%) in FY 2020. Four groups, named low to low (LL; n = 48), low to middle (LM; n = 16), middle to middle (MM; n = 68), and high to high (HH; n = 208), were identified from our trajectory analysis. The HH and MM groups had higher population densities and higher numbers of physicians and cardiologists per capita than the LL and LM groups. The LL and LM groups had similar numbers of physicians per capita, but the number of cardiologists per capita in the LM group increased over the years of the study compared with the LL group., Conclusion: The trajectory of the proportion of pPCIs for AMI patients identified groups of SMAs. Among the four groups, the LM group showed an increasing trend in the proportions of pPCIs, whereas the three other groups showed relatively stable trends., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Itoshima et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Although depression is linked to an increased risk of dementia, the association between late-onset depression (LOD) and amyloid burden remains unclear. This study aimed to determine amyloid deposition in patients with LOD compared to healthy controls (HC) using amyloid-beta (Aβ) positron emission tomography (PET) images and neuropsychological assessments., Methods: Forty patients first diagnosed with major depressive disorder after the age of 60 (LOD) and twenty-one healthy volunteers (HC) were enrolled. Depression and anxiety were evaluated using the 17-item Hamilton Depression Scale, Hamilton Anxiety Rating Scale, and Clinical Global Impression Scale. Cognitive function was assessed using the Korean versions of the Mini-Mental Status Examination, Montreal Cognitive Assessment, and Seoul Neuropsychological Screening Battery at baseline and 3-month follow-up. 18 F-florbetapir PET images were co-registered with T1-weighted magnetic resonance images., Results: There was no significant difference in Aβ deposition between LOD and HC groups. No significant correlation between Aβ burden and depressive symptom severity was found in LOD patients. Higher somatic anxiety was correlated with lower Aβ burden in multiple brain regions, including the left inferior frontal lobe (p = 0.009), right anterior cingulate (p = 0.003), and right superior frontal lobe (p = 0.009). Despite cognitive recovery in areas such as attention (Digit Span Forward, p = 0.026), memory (Auditory Verbal Learning Test Recall Total, p = 0.010; Rey Complex Figure Test Delayed Recall, p = 0.039), and frontal executive function (Contrasting Program, p = 0.033) after three months of antidepressant treatment, cognitive improvement showed no association with amyloid deposition., Conclusions: These findings suggest distinct mechanisms may underlie amyloid deposition in neurodegenerative changes associated with depression. While amyloid burden in specific brain regions negatively correlated with somatic anxiety, it showed no significant correlation with the severity of depression or overall cognitive function., (© 2024. The Author(s).)

Endometriosis affects a significant portion of women during their reproductive years, causing substantial pain and impacting their quality of life. Telehealth services have emerged as a promising avenue for enhancing endometriosis care, especially in the post-COVID-19 era. For endometriosis patients, who often require frequent appointments and specialized care, telehealth offers a convenient and accessible solution, particularly for addressing pain management and interdisciplinary concerns. Despite the challenges posed by the lack of physical examinations in telehealth, studies show that it can be a viable option for endometriosis care. Integrating telehealth with in-person visits for initial assessments can build trust and ensure comprehensive care delivery. Moreover, telehealth facilitates collaboration among multidisciplinary teams, including gynecologists, psychologists, and physiotherapists, to provide holistic treatment plans addressing physical, psychological, and interpersonal aspects of endometriosis. Here, we explore the potential benefits of telehealth in managing endometriosis, highlighting its role in providing comprehensive, multidisciplinary care while overcoming barriers like diagnostic delays and limited access to specialists. Further research and integration of telehealth into routine practice are warranted to maximize its benefits and address the complex challenges associated with endometriosis management.

Study Design: Retrospective propensity-score matched, case control study at 2 academic tertiary care centers., Objective: To assess the effect of PE on (1) intraoperative blood loss, defined as conventional estimates of blood loss (EBL) and hemoglobin mass loss, and (2) secondary outcomes in patients with spinal metastases from hypervascular histologies., Background Context: Preoperative embolization (PE) intends to reduce blood loss during surgery for spinal metastases of hypervascular tumors such as renal cell carcinoma. However, studies investigating the effect of PE in hypervascular tumors often consist of small cohorts, do not correct for confounding factors, and have conflicting results., Methods: After propensity score matching (PSM), 46 PE patients were matched to 46 non-PE patients without baseline differences. The constraints of PSM did not allow analysis of patients with tumor volumes>9 cm3. Multiple linear regression models were fitted for EBL and hemoglobin mass loss. Poisson regression models were fitted for both intraoperative and postoperative transfusions., Results: There was no difference in EBL (948 mL [IQR 500-1750] vs. 1100 mL [IQR 388-1925], P=0.68) and hemoglobin mass loss (201g [IQR 119-307] vs. 232g [IQR 173-373], P=0.18) between PE and non-PE patients. Other than higher 1-year survival rates (65% vs. 43%, P=0.05) in PE-patients, there were no differences in secondary outcomes. In multiple regression analyses, PE was not associated with decreased intraoperative blood loss, hemoglobin mass loss or perioperative blood transfusions., Conclusions: Our study demonstrated that, for tumors <9 cm3, PE did not reduce EBL, hemoglobin mass loss or perioperative blood transfusions in patients undergoing spine surgery for metastases from hypervascular histologies. These findings suggest that urgent spine surgeries indicated for hypervascular histologies should not be delayed based on the availability of PE and accurate detection of pre-operative hypervascularity, beyond histology, will likely be an important determination of future PE utilization for spinal metastases., Level of Evidence: Treatment Benefits, Level III., Competing Interests: Conflicts of Interest and Source of Funding: each author certifies that he or she has no commercial associations (e.g., consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article. None of the authors had any conflicts of interests., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The pragmatic role of dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) needs to be evaluated and compared across distinct lymphatic disorders. We aimed to evaluate the performance of DCMRL for identifying the underlying causes of lymphatic disorders and to define the potential benefit of DCMRL for planning lymphatic interventions., Methods: Patients who underwent DCMRL between August 2017 and July 2022 were included in this retrospective analysis. DCMRL was performed with intranodal injection of a gadolinium-based contrast medium through inguinal lymph nodes under local anesthesia. Technical success of DCMRL and feasibility of percutaneous embolization were assessed based on the lymphatic anatomy visualized by DCMRL. Based on the underlying causes, clinical outcomes were evaluated and compared., Results: Seventy consecutive patients were included. The indications were traumatic chylothorax (n = 42), traumatic chylous ascites (n = 11), and nontraumatic lymphatic leak (n = 17). The technical success rate of DCMRL was the highest in association with nontraumatic lymphatic disorders (94.1% [16/17]), followed by traumatic chylothorax (92.9% [39/42]) and traumatic chylous ascites (81.8% [9/11]). Thirty-one (47.7%) patients among 65 patients who underwent technically successful DCMRL had feasible anatomy for intervention. Clinical success was achieved in 90.3% (28/31) of patients with feasible anatomy for radiologic intervention, while 62.5% (10/16) of patients with anatomical challenges showed improvement. Most patients with traumatic chylothorax showed improvement (92.9% [39/42]), whereas only 23.5% (4/17) of patients with nontraumatic lymphatic disorders showed clinical improvement., Conclusion: DCMRL can help identify the underlying causes of lymphatic disorders. The performance of DCMRL and clinical outcomes vary based on the underlying cause. The feasibility of lymphatic intervention can be determined using DCMRL, which can help in predicting clinical outcomes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Excessive alcohol consumption is a leading cause of preventable death worldwide. To improve understanding of neurobiological mechanisms associated with alcohol use disorder (AUD) in humans, we compared gene expression data from deceased individuals with and without AUD across two addiction-relevant brain regions: the nucleus accumbens (NAc) and dorsolateral prefrontal cortex (DLPFC). Bulk RNA-seq data from NAc and DLPFC (N ≥50 with AUD, ≥46 non-AUD) were analyzed for differential gene expression using modified negative binomial regression adjusting for technical and biological covariates. The region-level results were meta-analyzed with those from an independent dataset (N NAc  = 28 AUD, 29 non-AUD; N PFC  = 66 AUD, 77 non-AUD). We further tested for heritability enrichment of AUD-related phenotypes, gene co-expression networks, gene ontology enrichment, and drug repurposing. We identified 176 differentially expressed genes (DEGs; 12 in both regions, 78 in NAc only, 86 in DLPFC only) for AUD in our new dataset. After meta-analyzing with published data, we identified 476 AUD DEGs (25 in both regions, 29 in NAc only, 422 in PFC only). Of these DEGs, 17 were significant when looked up in GWAS of problematic alcohol use or drinks per week. Gene co-expression analysis showed both concordant and unique gene networks across brain regions. We also identified 29 and 436 drug compounds that target DEGs from our meta-analysis in NAc and PFC, respectively. This study identified robust AUD-associated DEGs, contributing novel neurobiological insights into AUD and highlighting genes targeted by known drug compounds, generating opportunity for drug repurposing to treat AUD., (© 2024. The Author(s).)

The current COVID-19 mRNA vaccines were developed and applied for pandemic-emergent conditions. These vaccines use a small piece of the virus's genetic material (mRNA) to stimulate an immune response against COVID-19. However, their potential effects on individuals with chronic inflammatory conditions and vaccination routes remain questionable. Therefore, we investigated the effects of mRNA vaccines in a mouse model of chronic inflammation, focusing on their cardiac toxicity and immunogenicity dependent on the injection route. mRNA vaccine intravenous administration with or without chronic inflammation exacerbated cardiac pericarditis and myocarditis; immunization induced mild inflammation and inflammatory cytokine IL-1beta and IL-6 production in the heart. Further, IV mRNA vaccination induced cardiac damage in LPS chronic inflammation, particularly serum troponin I (TnI), which dramatically increased. IV vaccine administration may induce more cardiotoxicity in chronic inflammation. These findings highlight the need for further research to understand the underlying mechanisms of mRNA vaccines with chronic inflammatory conditions dependent on injection routes., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Jeon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The genus Anomalohalacarus Newell, 1949, which is known to occur exclusively inhabiting sand, has not been previously reported from Korea. During a recent survey of the meiofauna from several intertidal sandy beaches in South Korea, we found both sexes of two psammobiont halacarids, Anomalohalacarusangustus sp. nov. and A.biformis Abé, 1996., New Information: Both species are similar to each other in sharing an undivided posterior dorsal plate, three and two setae on the anterior and posterior epimeral plates, respectively, three bipectinate setae on tibia IV, and four ventral setae on tarsus I. However, A.angustus sp. nov. is distinguished from A.biformis by the absence of areolae posteriorly on the anterior dorsal plate, a much more slender posterior dorsal plate, a pair of subgenital setae on the genital foramen in females, and seven branched perigenital setae on the genitoanal plate in males. The feature of branched perigenital setae in males is reported for the first time in the genus Anomalohalacarus . The Korean specimens of A.biformis agree well with the original description from Japan, except for the number of ventral bipectinate setae on tibia II. This study presents (re)descriptions of both species with detailed illustrations and provides a dichotomous key to Anomalohalacarus species, including the new species, based on morphological characters. The genus Anomalohalacarus is reported for the first time in South Korea., (Jong Hak Shin, Cheon Young Chang, Jimin lee.)

Objective: Semaglutide, a novel glucagon-like peptide-1 receptor agonist, has transformed the therapeutic landscape for type 2 diabetes mellitus. However, its effect on osteoclast activity and its potential to induce weight-related muscle loss raises concerns about its impact on spine surgery outcomes. As such, evaluating semaglutide's influence on transforaminal lumbar interbody fusion (TLIF) is imperative, given the procedure's reliance on successful bony fusion to prevent postoperative instability and further interventions., Methods: Using an all-payer database (MARINER), the authors analyzed data from patients with type 2 diabetes mellitus who were 18-74 years of age and who underwent short-segment fusion (≤ 3-level) TLIFs between January 2018 and October 2022. Patients were either exposed to semaglutide or not. A comprehensive 1:3 (exposure vs no exposure) matching was performed based on age, sex, obesity, hypertension, coronary artery disease, chronic kidney disease, smoking status, osteoporosis, levels of surgery, and basal-bolus insulin dependence. Kaplan-Meier survival curves and log-rank testing were performed to study the probability of additional lumbar fusion surgery within 1 year., Results: After the 1:3 matching, 1781 patients were identified, with 447 in the semaglutide-exposed cohort and 1334 in the nonexposed cohort. Most patients in both groups were 55-69 years old, and 59.3% were female. Analysis showed that the likelihood of undergoing additional lumbar fusion surgery within 1 year post-TLIF was significantly higher in the semaglutide-exposed group than in the nonexposed group (OR 11.79, 95% CI 8.17-17.33). Kaplan-Meier plots and log-rank testing further confirmed a statistically significant divergent probability in the need for additional surgery within 1 year between the cohorts (log-rank, p < 0.001)., Conclusions: Semaglutide exposure appears to be associated with a higher likelihood of additional lumbar fusion surgeries within 1 year post-TLIF, especially in patients receiving the medication for longer durations. Although the mechanisms remain speculative, potential impacts on bone turnover and the onset of muscle loss may be contributory factors. Further research is needed to elucidate the exact mechanisms and to develop strategies for optimizing surgical outcomes in these patients.

Cervical adenocarcinoma (AC), a subtype of uterine cervical cancer (CC), poses a challenge due to its resistance to therapy and poor prognosis compared with squamous cervical carcinoma. Streptococcus agalactiae [group B Streptococcus (GBS)], a Gram-positive coccus, has been associated with cervical intraepithelial neoplasia in CC. However, the underlying mechanism interaction between GBS and CC, particularly AC, remains elusive. Leveraging The Cancer Genome Atlas public data and time-series transcriptomic data, the present study investigated the interaction between GBS and AC, revealing activation of two pivotal pathways: 'MAPK signaling pathway' and 'mTORC1 signaling'. Western blotting, reverse transcription-quantitative PCR and cell viability assays were performed to validate the activation of these pathways and their role in promoting cancer cell proliferation. Subsequently, the present study evaluated the efficacy of two anticancer drugs targeting these pathways (binimetinib and ridaforolimus) in AC cell treatment. Binimetinib demonstrated a cytostatic effect, while ridaforolimus had a modest impact on HeLa cells after 48 h of treatment, as observed in both cell viability and cytotoxicity assays. The combination of binimetinib and ridaforolimus resulted in a significantly greater cytotoxic effect compared to binimetinib or ridaforolimus monotherapy, although the synergy score indicated an additive effect. In general, the MAPK and mTORC1 signaling pathways were identified as the main pathways associated with GBS and AC cells. The combination of binimetinib and ridaforolimus could be a potential AC treatment., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Nguyen et al.)

Folded RNAs contain tertiary contact motifs whose structures and energetics are conserved across different RNAs. The transferable properties of RNA motifs simplify the RNA folding problem, but measuring energetic and conformational properties of many motifs remains a challenge. Here, we use a high-throughput thermodynamic approach to investigate how sequence changes alter the binding properties of naturally-occurring motifs, the GAAA tetraloop•tetraloop receptor (TLR) interactions. We measured the binding energies and conformational preferences of TLR sequences that span mutational pathways from the canonical 11ntR to two other natural TLRs, the IC3R and Vc2R. While the IC3R and Vc2R share highly similar energetic and conformational properties, the landscapes that map the sequence changes for their conversion from the 11ntR to changes in these properties differ dramatically. Differences in the energetic landscapes stem from the mutations needed to convert the 11ntR to the IC3R and Vc2R rather than a difference in the intrinsic energetic architectures of these TLRs. The conformational landscapes feature several non-native TLR variants with conformational preferences that differ from both the initial and final TLRs; these species represent potential branching points along the multidimensional sequence space to sequences with greater fitness in other RNA contexts with alternative conformational preferences. Our high-throughput, quantitative approach reveals the complex nature of sequence-fitness landscapes and leads to models for their molecular origins. Systematic and quantitative molecular approaches provide critical insights into understanding the evolution of natural RNAs as they traverse complex landscapes in response to selective pressures., (Published by Cold Spring Harbor Laboratory Press for the RNA Society.)

The clonal transmission of fluconazole-resistant Candida glabrata isolates within hospitals has seldom been analyzed by whole-genome sequencing (WGS). We performed WGS on 79 C . glabrata isolates, comprising 31 isolates from three premature infants with persistent C. glabrata bloodstream infection despite antifungal treatment in the same neonatal intensive care unit (NICU) in 2022 and 48 (27 fluconazole-resistant and 21 fluconazole-susceptible dose-dependent) bloodstream isolates from 48 patients in 15 South Korean hospitals from 2010 to 2022. Phylogenetic analysis based on WGS single-nucleotide polymorphisms (SNPs) distinguished the 79 isolates according to multilocus sequence typing (MLST) (17 sequence type [ST]3, 13 ST7, two ST22, 41 ST26, four ST55, and two ST59 isolates) and unveiled two possible clusters of nosocomial transmission among ST26 isolates. One cluster from two premature infants with overlapping NICU hospitalizations in 2022 encompassed 15 fluconazole-resistant isolates harboring pleiotropic drug-resistance transcription factor (Pdr1p) P258L (13 isolates) or N1086I (two isolates), together with 10 fluconazole-susceptible dose-dependent isolates lacking Pdr1p SNPs. The other cluster indicated unforeseen clonal transmission of fluconazole-resistant bloodstream isolates among five patients (four post-lung transplantation and one with diffuse interstitial lung disease) in the same hospital over 8 months. Among these five isolates, four obtained after exposure to azole antifungals harbored distinct Pdr1p SNPs (N1091D, E388Q, K365E, and R376Q). The findings reveal the transmission patterns of clonal bloodstream isolates of C. glabrata among patients undergoing antifungal treatment, exhibiting different levels of fluconazole susceptibility or distinct Pdr1p SNP profiles., Importance: The prevalence of fluconazole-resistant bloodstream infections caused by Candida glabrata is increasing globally, but the transmission of these resistant strains within hospitals has rarely been documented. Through whole-genome sequencing and epidemiological analyses, this study identified two potential clusters of C. glabrata bloodstream infections within the same hospital, revealing the transmission of clonal C. glabrata strains with different levels of fluconazole susceptibility or distinct transcription factor pleiotropic drug resistance protein 1 (Pdr1p) single-nucleotide polymorphism profiles among patients receiving antifungal therapy., Competing Interests: The authors declare no conflict of interest.

Objective: To evaluate the efficacy and safety of the through-and-through wire (TTW) technique for antegrade ureteral Double-J stent placement after failure of either antegrade or retrograde ureteral stent placement., Method: This retrospective study analyzed the medical records of consecutive patients who underwent Double-J stent placement with the TTW technique at Asan Medical Center and Gil Medical Center between January 2016 and February 2023. Patient histories, reasons for employing the TTW technique, TTW pathways, and complications were reviewed. Eight patients were included in the study. The reasons for using the TTW technique were failure to advance a larger-diameter catheter, balloon catheter, or Double-J stent passing over the guidewire beyond the stricture (6/8, 75.0%); failure to negotiate the stricture with a guidewire (1/8, 12.5%); and guidewire passing through a ureteropelvic junction defect (1/8, 12.5%)., Results: TTW was applied either between a percutaneous nephrostomy (PCN) and the urethral orifice (n=4), between a PCN and an ileostomy pouch (n=3), or between a left and right PCN (n = 1). Urologic assistance was required for retrograde ureteral cannulation in one male patient (12.5%). Subsequently, balloon dilation and/or Double-J stent placement were performed in all eight patients, resulting in 100% technical success. No major or minor complications occurred., Conclusions: The TTW technique was safe and effective in the undertaking of PCN and antegrade Double-J stent placement in patients for whom either antegrade or retrograde access had failed., Competing Interests: Conflict of interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Tumour necrosis factor receptor 1 (TNFR1) induces the nuclear factor kappa-B (NF-κB) signalling pathway and regulated cell death processes when TNF-α ligates with it. Although mechanisms regulating the downstream pathways of TNFR1 have been elucidated, the direct regulation of TNFR1 itself is not well known. In this study, we showed that the kinase domain of the epidermal growth factor receptor (EGFR) regulates NF-κB signalling and TNF-α-induced cell death by directly phosphorylating TNFR1 at Tyr 360 and 401 in its death domain. In contrast, EGFR inhibition by EGFR inhibitors, such as erlotinib and gefitinib, prevented their interaction. Once TNFR1 is phosphorylated, its death domain induces the suppression of the NF-κB pathways, complex II-mediated apoptosis, or necrosome-dependent necroptosis. Physiologically, in mouse models, EGF treatment mitigates TNF-α-dependent necroptotic skin inflammation induced by treatment with IAP and caspase inhibitors. Our study revealed a novel role for EGFR in directly regulating TNF-α-related pathways., (© 2024. The Author(s).)

Introduction: Parkinson's disease (PD) encompasses a range of non-motor symptoms attributed to deficits in various neurotransmitter systems. This study aimed to investigate the associations between cognitive and autonomic symptoms and the degeneration of brainstem monoaminergic nuclei, particularly the serotonergic and noradrenergic nuclei, in a prospective cohort of early PD patients., Methods: Twenty-eight early PD patients (with an average disease duration of approximately three years) underwent baseline [ 18 F]FP-CIT positron emission tomography (PET) scans, Montreal Cognitive Assessment (MoCA), and Composite Autonomic Symptom Scale-31 (COMPASS-31) evaluations, followed by repeat MoCA and COMPASS-31 assessments three years later. Regression models were utilized to analyze both cross-sectional and longitudinal changes in non-motor symptoms relative to baseline degeneration of the noradrenergic locus coeruleus (LC) and serotonergic raphe, normalized by striatal dopaminergic terminal loss., Results: Baseline LC and raphe degeneration in early PD was cross-sectionally associated with poorer MoCA performances. Over the three-year follow-up, gastrointestinal symptoms exhibited progression, while cognitive scores remained stable. Profound baseline degeneration of the LC and raphe, relative to nigrostriatal terminal loss, were predictive of subsequent accelerated deterioration in gastrointestinal symptoms., Conclusion: Brainstem non-dopaminergic dysfunction in early PD is linked to cognitive dysfunction and predicts progression in gastrointestinal symptoms, offering potential indicators for worsening non-motor trajectories., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jung Hwan Shin reports financial support provided by the Ministry of Science and ICT (MSIT), South Korea. Other authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Defect engineering of metal-organic frameworks (MOFs) is a promising strategy for tailoring the interfacial characteristics between MOFs and polymers, aiming to create high-performance mixed matrix membranes (MMMs). This study introduces a new approach using dual defective alkylamine (AA)-modulated zeolitic imidazolate framework-8 (DAZIF-8), to develop high-flux MMMs. Tributylamine (TBA) and triethylamine (TEA) monodentate ligands coordinate with zinc ions in varying compositions. A mixture of Zn(CH 3 COO) 2 ·2H 2 O:2-methylimidazole (Mim):AA in a 1:1.75:5 molar ratio facilitates high-yield coordination between Zn and multiple organic ligands, including Zn-Mim, Zn-TEA, and Zn-TBA (>80%). Remarkably, DAZIF-8 containing 3 mol% TBA and 2 mol% TEA exhibits exceptional characteristics, such as a Brunauer-Emmett-Teller surface area of 1745 m 2 g -1 and enhanced framework rigidity. Furthermore, dual Zn-AA coordination sites on the framework's outer surface enhance compatibility with the polyimide (PI) matrix through electron donor-acceptor interactions, enabling the fabrication of high-loading MMMs with excellent mechanical durability. Importantly, the PI/DAZIF-8 (60/40 w/w) MMM demonstrates an unprecedented 759% enhancement in ethylene (C 2 H 4 ) permeability (281 Barrer) with a moderate ethylene/ethane (C 2 H 4 /C 2 H 6 ) selectivity of 2.95 compared to the PI, surpassing the polymeric upper limit for C 2 H 4 /C 2 H 6 separation., (© 2024 Wiley‐VCH GmbH.)

Polycystic ovary syndrome (PCOS) is one of the most common endocrine anomalies among females of reproductive age, highlighted by hyperandrogenism. PCOS is multifactorial as it can be associated with obesity, insulin resistance, low-grade chronic inflammation, and dyslipidemia. PCOS also leads to dysbiosis by lowering microbial diversity and beneficial microbes, such as Faecalibacterium, Roseburia, Akkermenisa, and Bifidobacterium, and by causing a higher load of opportunistic pathogens, such as Escherichia/Shigella, Fusobacterium, Bilophila, and Sutterella. Wherein, butyrate producers and Akkermansia participate in the glucose uptake by inducing glucagon-like peptide-1 (GLP-1) and glucose metabolism, respectively. The abovementioned gut microbes also maintain the gut barrier function and glucose homeostasis by releasing metabolites such as short-chain fatty acids (SCFAs) and Amuc&#95;1100 protein. In addition, PCOS-associated gut is found to be higher in gut-microbial enzyme β-glucuronidase, causing the de-glucuronidation of conjugated androgen, making it susceptible to reabsorption by entero-hepatic circulation, leading to a higher level of androgen in the circulatory system. Overall, in PCOS, such dysbiosis increases the gut permeability and LPS in the systemic circulation, trimethylamine N-oxide (TMAO) in the circulatory system, chronic inflammation in the adipose tissue and liver, and oxidative stress and lipid accumulation in the liver. Thus, in women with PCOS, dysbiosis can promote the progression and severity of type 2 diabetes, non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD). To alleviate such PCOS-associated complications, microbial therapeutics (probiotics and fecal microbiome transplantation) can be used without any side effects, unlike in the case of hormonal therapy. Therefore, this study sought to understand the mechanistic significance of gut microbes in PCOS and associated comorbidities, along with the role of microbial therapeutics that can ease the life of PCOS-affected women., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that leads to respiratory failure and death due to irreversible scarring of the distal lung. While historically considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now recognized to play a central role in IPF pathophysiology., Purpose: This study aimed to investigate the regenerative capacity of AT2 cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity., Method: Lung tissues from 3 pneumothorax patients and 6 IPF patients (early and advanced stages) were obtained by VATS and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-EpCAM+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immuno-staining was used to confirm the presence of AT2 cells., Results: FACS sorting yielded approximately 1% AT2 cells of the total cells in early IPF tissue, and the number decreased as the disease progressed, compared with 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller in size and fewer in number compared to those from pneumothorax patients. The colony-forming efficiency decreased as the disease progressed. In immuno-staining results, the IPF organoids showed lower expression of SFTPC compared to the pneumothorax group and contained KRT5+ cells., Conclusion: This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, and IPF AT2 cells inherently exhibit functional abnormalities and altered differentiation plasticity.

Additive Manufacturing (AM) is a pivotal technology for transforming complex geometries with minimal tooling requirements. Among the several AM techniques, Wire Arc Additive Manufacturing (WAAM) is notable for its ability to produce large metal components, which makes it particularly appealing in the aerospace sector. However, precise control of the bead geometry, specifically bead width and height, is essential for maintaining the structural integrity of WAAM-manufactured parts. This paper introduces a methodology using a Deep Neural Network (DNN) model for forecasting the bead geometry in the WAAM process, focusing on gas metal arc welding cold metal transfer (GMAW-CMT) WAAM. This study addresses the challenges of bead geometry prediction by developing a robust predictive framework. Key process parameters, such as the wire travel speed, wire feed rate, and bead dimensions of the previous layer, were monitored using a Coordinate Measuring Machine (CMM) to ensure precision. The collected data were used to train and validate various regression models, including linear regression, ridge regression, regression, polynomial regression (Quadratic and Cubic), Random Forest, and a custom-designed DNN. Among these, the Random Forest and DNN models were particularly effective, with the DNN showing significant accuracy owing to its ability to learn complex nonlinear relationships inherent in the WAAM process. The DNN model architecture consists of multiple hidden layers with varying neuron counts, trained using backpropagation, and optimized using the Adam optimizer. The model achieved mean absolute percentage error (MAPE) values of 0.014% for the width and 0.012% for the height, and root mean squared error (RMSE) values of 0.122 for the width and 0.153 for the height. These results highlight the superior capability of the DNN model in predicting bead geometry compared to other regression models, including the Random Forest and traditional regression techniques. These findings emphasize the potential of deep learning techniques to enhance the accuracy and efficiency of WAAM processes.

Background: Risk Analysis Index (RAI) has been increasingly used to assess surgical frailty in various procedures, but its effectiveness in predicting mortality or in-patient hospital outcomes for spine surgery in metastatic disease remains unclear. The aim of this study was to compare the predictive values of the revised RAI (RAI-rev), the modified frailty index-5 (mFI-5), and advanced age for extended length of stay, 30-day readmission, complications, and mortality among patients undergoing spine surgery for metastatic spinal tumors., Methods: A retrospective cohort study was performed using the 2012-2022 ACS NSQIP database to identify adult patients who underwent spinal surgery for metastatic spinal pathologies. Using receiver operating characteristic (ROC) and multivariable analyses, we compared the discriminative thresholds and independent associations of RAI-rev, mFI-5, and greater patient age with extended length of stay (LOS), 30-day complications, hospital readmission, and mortality., Results: A total of 1,796 patients were identified, of which 1,116 (62.1%) were male and 1,008 (70.7%) were non-Hispanic White. RAI-rev identified 1,291 (71.9%) frail and 208 (11.6%) very frail patients, while mFI-5 identified 272 (15.1%) frail and 49 (2.7%) very frail patients. In the ROC analysis for extended LOS, both RAI-rev and mFI-5 showed modest predictive capabilities with area under the curve (AUC) values of 0.5477 and 0.5329, respectively, and no significant difference in their predictive abilities (p = 0.446). When compared to age, RAI-rev demonstrated superior prediction (p = 0.015). With respect to predicting 30-day readmission, no significant difference was observed between RAI-rev and mFI-5 (AUC 0.5394 l respectively, p = 0.354). However, RAI-rev outperformed age (p = 0.001). When assessing the risk of 30-day complications, RAI-rev significantly outperformed mFI-5 (AUC: 0.6016 and 0.5542 respectively, p = 0.022) but not age. Notably, RAI-rev demonstrated superior ability for predicting 30-day mortality compared to mFI-5 and age (AUC: 0.6541, 0.5652, and 0.5515 respectively, p < 0.001). Multivariate analysis revealed RAI-rev as a significant predictor of extended LOS [aOR: 1.96, 95% CI: 1.13-3.38, p = 0.016] and 30-day mortality [aOR: 5.27, 95% CI: 1.73-16.06, p = 0.003] for very frail patients. Similarly, the RAI-rev significantly predicted 30-day complications for frail [aOR: 2.63, 95% CI: 1.21-5.72, p = 0.015] and very frail [aOR: 3.69, 95% CI: 1.60-8.51, p = 0.002] patients. However, the RAI did not significantly predict 30-day readmission [Very Frail aOR: 1.52, 95% CI: 0.75-3.07, p = 0.245; Frail aOR: 1.46, 95% CI: 0.79-2.68, p = 0.225]., Conclusion: Our study demonstrates the utility of RAI-rev in predicting morbidity and mortality in patients undergoing spine surgery for metastatic spinal pathologies. Particularly, the superiority that RAI-rev has in predicting 30-day mortality may have significant implications in multidisciplinary decision making., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)