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Vigilin, a nucleocytoplasmic shuttling protein, post-transcriptionally suppresses proto-oncogene c-fms expression (encoding CSF-1R) in breast cancer by binding to a 69 nt cis-acting 3-UTR element in CSF-1R mRNA. CSF-1R is an important mediator of breast cancer development, metastasis, and survival. We confirm that vigilin decreases in vitro reporter luciferase activity as well as the translation rate of target mRNAs. We further explore the mechanism of suppression of CSF-1R. We show that the 69 nt binding element has profound effects on translation efficiency of CSF-1R mRNA, not seen in the presence of mutation of the element. Also, mutation of the 69 nt element in the CSF-1R mRNA 3′UTR both interferes with direct vigilin binding and obviates effect of vigilin overexpression on translational repression of CSF-1R. We show that stable vigilin binding requires the full length 69 nt CSF-1R element, including the 26 nt pyrimidine-rich core. Furthermore, titration of endogenous vigilin and other proteins which bind the 69 nt element, by exogenously introduced CSF-1R mRNA 3′UTR containing the pyrimidine-rich sequence, increases the adhesion, motility, and invasion of breast cancer cells. This phenotypic effect is not seen when the 69 nt element is deleted. Lastly, we are the first to show that human breast tissues exhibit strong vigilin expression in normal breast epithelium. Our pilot data suggest decreased vigilin protein expression, along with shift from the nucleus to the cytoplasmic location, in the transition to ductal carcinoma in situ.

Isotopes are an important aspect of modern medical and scientific research and cyclotron-based isotope production is of particular interest. Cooling devices are required to manage the heat generated by high-energy particle beams to ensure that they can be delivered securely. However, there is considerable scope for further advancements in the design of cooling systems. Therefore, this study uses simulations to investigate the design of innovative cooling systems. Various designs and materials are considered using a variable four-sector collimator and various particle-beam conditions. Thus, new design principles and material and structural optimization strategies are proposed, which can be used to improve the stability and efficiency of isotope production. The results provide insight into technical challenges and may contribute toward advances in medical diagnostics, radiotherapy, and fundamental scientific research. In particular, they can guide the development of isotope-based technologies in nuclear medicine.

Panax species include Panax ginseng Meyer, Panax quinquefolium L., Panax notoginseng, Panax japonicum, Panax trifolium, and Panax pseudoginseng, which contain bioactive components (BCs) such as ginsenosides and polysaccharides. Recently, growing evidence has revealed the pharmacological effects of Panax species and their BCs on allergic airway diseases (AADs), including allergic asthma (AA) and allergic rhinitis (AR). AADs are characterized by damaged epithelium, sustained acquired immune responses with enforced Th2 responses, allergen-specific IgE production, and enhanced production of histamine and leukotrienes by activated mast cells and basophils. In this review, we summarize how Panax species and their BCs modulate acquired immune responses involving interactions between dendritic cells and T cells, reduce the pro-inflammatory responses of epithelial cells, and reduce allergenic responses from basophils and mast cells in vitro. In addition, we highlight the current understanding of the alleviative effects of Panax species and their BCs against AA and AR in vivo. Moreover, we discuss the unmet needs of research and considerations for the treatment of patients to provide basic scientific knowledge for the treatment of AADs using Panax species and their BCs.

Background: Herbal medicine Ja-Geum-Jeong (JGJ) has been used for the treatment of detoxification in Eastern Asia. However, the mechanisms involved are not clearly defined. The purpose of the present study was to investigate if herb medication inhibits Methamphetamine (METH)’s reinforcing effect and also examined if a combination of herb medication and acupuncture produces a synergistic effect on METH. Methods: Male Sprague-Dawley rats were given acute METH intraperitoneally and the locomotor activity and ultrasonic vocalization (USV) calls were measured. Rats were administered JGJ orally and acupuncture was given at HT7 or SI5. Monosodium glutamate (MSG) and gamma-aminobutyric acid (GABA) agonists were injected into the Central amygdala (CeA) to investigate a possible neuroscientific mechanism. Tyrosine hydroxylase (TH) and fast scan cyclic voltammetry (FSCV) were measured to immunohistochemically and electrically confirm the behavioral data. Results: Locomotor activity and USV calls were increased by METH (P < 0.05) and these increases were inhibited by JGJ (P < 0.05). Also, JGJ had no effect on the normal group given saline, and acupuncture at SI5 acupoint, but not at HT7 acupoint, produced a synergistic effect when combined with JGJ (P < 0.05). The JGJ's inhibition was blocked by the inactivation of CeA (P < 0.05), and MSG mimicked JGJ (P < 0.05). TH and FSCV measures showed the same pattern with the behavioral data (P < 0.05). Conclusion: Results of the present study suggest that JGJ had inhibitory effects on the METH which was mediated through the activation of CeA and that combination of acupuncture and herb produced synergistic effect.

Introduction: Dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) improves bystander CPR rates and survival outcomes. This study aimed to identify barriers to successful DA-CPR in patients with out-of-hospital cardiac arrest (OHCA). Methods: This retrospective observational study used data from a nationwide OHCA database from 2017 to 2021. Adult emergency medical services (EMS)-treated patients with OHCA with a presumed cardiac etiology were enrolled. The main exposure variable was compliance with DA-CPR. The primary outcome was good neurological recovery at hospital discharge. Multivariable logistic regression analysis was conducted to identify the major factors associated with unsuccessful DA-CPR with and without multiple imputations. Causal mediation analysis was conducted using witnessed status as a mediator. Results: In the final analysis, 49,165 patients with OHCA were included. A total of 36,865 (75.0%) patients successfully underwent DA-CPR. A higher proportion of good neurological recovery was observed in the successful DA-CPR group than in the non-successful DA-CPR group (P 65 years, male sex, OHCA occurring in a non-metropolitan area or private place, unwitnessed status, whether the bystander was a non-family member or non-cohabitant, female sex or had not received CPR training, and primary call dispatchers not receiving any first-aid training. Additional analyses after multiple imputations showed similar results. Mediation effect was significant for most risk factors for unsuccessful DA-CPR. Conclusions: Bystander characteristics (non-family member or non-cohabitant, female, and uneducated status for CPR) and primary call dispatchers not receiving first-aid training were identified as risk factors for unsuccessful DA-CPR.

Background/Purpose: To develop a prediction model for emergency medical technicians (EMTs) to identify trauma patients at high risk of deterioration to emergency medical service (EMS)-witnessed traumatic cardiac arrest (TCA) on the scene or en route. Methods: We developed a prediction model using the classical cross-validation method from the Pan-Asia Trauma Outcomes Study (PATOS) database from 1 January 2015 to 31 December 2020. Eligible patients aged ≥18 years were transported to the hospital by the EMS. The primary outcome (EMS-witnessed TCA) was defined based on changes in vital signs measured on the scene or en route. We included variables that were immediately measurable as potential predictors when EMTs arrived. An integer point value system was built using multivariable logistic regression. The area under the receiver operating characteristic (AUROC) curve and Hosmer-Lemeshow (HL) test were used to examine discrimination and calibration in the derivation and validation cohorts. Results: In total, 74,844 patients were eligible for database review. The model comprised five prehospital predictors: age 20/minute, pulse oximetry

Background: Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology. Materials and Methods: Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins. Results: We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy. Conclusion: RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.

Background: Several studies have shown that there are no significant differences in anastomotic leakage associated with Transanal total mesorectal excision (taTME) versus laparoscopic TME (lapTME) for rectal cancer; however, little is known about late anastomotic leakage, such as that primarily found in the chronic presacral sinus. We aimed to compare the occurrence of anastomotic leakage and chronic presacral sinus in rectal cancer for taTME and lapTME. Methods: In this retrospective cohort study, data were collected for patients with rectal cancer who underwent surgery between January 2009 and September 2019. Of the 220 patients included in this study, 182 were in the lapTME group and 38 in the taTME group. We compared factors associated with anastomotic leakage and chronic presacral sinus formation between the two groups. A binary-logistic model was used to determine the risk factors for chronic presacral sinus. Results: Anastomotic leakage occurred in six patients (15.8%) in the taTME group and 36 patients (19.7%) in the lapTME group. Chronic presacral sinus occurred in three patients (7.9%) in the taTME group and 15 patients (8.2%) in the lapTME group. There was no significant difference in anastomotic leakage or chronic presacral sinus between groups (P = 0.569 and P = 1.000, respectively). Pathologic stage III or higher was significantly associated with chronic presacral sinus formation (P = 0.006). Conclusion: There were no significant differences between taTME and lapTME regarding the incidence of anastomotic leakage or chronic presacral sinus. Almost one-third of anastomotic leakages developed into chronic presacral sinus.

Summary: Background: Compared with normal cells, tumour cells contain elevated levels of reactive oxygen species (ROS). Increased levels of the antioxidant protein NAD(P)H:quinone oxidoreductase 1 (NQO1) and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) correlate negatively with the survival of patients with pancreatic cancer. Napabucasin is an investigational, orally administered ROS generator bioactivated by NQO1. Methods: In the open-label, phase 3 CanStem111P study (NCT02993731), adults with previously untreated metastatic pancreatic adenocarcinoma (mPDAC) were randomised (1:1) to napabucasin plus nab-paclitaxel with gemcitabine or nab-paclitaxel with gemcitabine alone. The primary endpoint was overall survival (OS). In exploratory analyses, OS was evaluated in the subgroup of patients with tumours positive for pSTAT3 (biomarker-positive). Findings: Between 30 January 2017 and 20 February 2019, a total of 1779 patients were screened across 165 study sites in Austria, Australia, Belgium, Canada, China, Czech Republic, France, Germany, Italy, Japan, Korea, Netherlands, Poland, Portugal, Russia, Singapore, Spain, Taiwan, Ukraine, and the US. Of the 565 and 569 patients randomised to the napabucasin and control treatment arms, respectively, 206 and 176 were biomarker-positive. Median (95% confidence interval [CI]) OS in the napabucasin and control treatment arms was 11.4 (10.5–12.2) and 11.7 (10.7–12.7) months, respectively (hazard ratio, 1.07; 95% CI, 0.93–1.23). Due to the lack of OS improvement in the napabucasin arm, CanStem111P was terminated due to futility. In the biomarker-positive subgroup, no difference between treatment arms was found for OS. Grade ≥3 adverse events were reported in 85.4% and 83.9% of napabucasin-treated and control-treated patients, respectively. The incidence of gastrointestinal-related grade ≥3 events was higher with napabucasin (diarrhoea: 11.6% vs 4.9%; abdominal pain: 10.0% vs 4.8%). Interpretation: Our findings suggested that although the addition of napabucasin to nab-paclitaxel with gemcitabine did not improve efficacy in patients with previously untreated mPDAC, the safety profile of napabucasin was consistent with previous reports. CanStem111P represents the largest cohort of patients with mPDAC administered nab-paclitaxel with gemcitabine in the clinical trial setting. Our data reinforce the value of nab-paclitaxel plus gemcitabine as a platform for novel therapeutics approaches in mPDAC. Funding: The Sumitomo Pharma Oncology, Inc.

Senescence is a phenomenon defined by alterations in cellular organelles and is the primary cause of aging and aging-related diseases. Recent studies have shown that oncogene-induced senescence is driven by activation of serine/threonine protein kinases (AKT1, AKT2 and AKT3). In this study, we evaluated twelve AKT inhibitors and revealed GDC0068 as a potential agent to ameliorate senescence. Senescence-ameliorating effect was evident from the finding that GDC0068 yielded lysosomal functional recovery as observed by reduction in lysosomal mass and induction in autophagic flux. Furthermore, GDC0068-mediated restoration of lysosomal function activated the removal of dysfunctional mitochondria, resulting in restoration of mitochondrial function. Together, our findings revealed a unique mechanism by which senescence is recovered by functional restoration of lysosomes and mitochondria through modulation of AKT activity.

Most countries in Sub-Saharan Africa have struggled to utilize health information technology and thus lack in accurate patient data. This paper describes the method of collecting patient data and patient characteristics in an emergency centre in Yaoundé, Cameroon.We developed an Epi InfoTM-based data entry form to collect data of the patients who visited the Centre des Urgences de Yaoundé (CURY) from January 2016 to June2018. Demographic, clinical symptoms, treatments and outcome data were collected.Additional data on the patients with multiple trauma, chest pain, sepsis/septic shock, and stroke were also collected.During the study period, a total of 18,875 patients’ data were collected (44.5% women, median age of 36). Of the total patients, 2.4% had chest pain, 2.7% had stroke, 1.9% had sepsis/septic shock, and 1.6% had multiple trauma. About 6.0% patients received operation and majority of patients were discharged either normally (48.2%) or with continuity of care (26.3%). About 5.0% of patients were transferred to other hospital and 5.2% of patients were dead.This study serves to broaden understanding of the emergency patients in Yaoundé, Cameroon.

Traumatic coronary artery dissection resulting from blunt trauma, is a relatively rare and life-threatening event. We present a case report of a 42-year-old male who presented with electrocardiogram abnormality and cardiac enzyme elevation following a fall from a height of 3 m. The patient was misdiagnosed with stress-induced cardiomyopathy because of the absence of clinical signs of acute coronary syndrome. The patient was subsequently diagnosed with traumatic coronary artery dissection using coronary angiography, and the relevance of the trauma was confirmed using intravascular ultrasonography (IVUS). Herein, we highlight that trauma team should maintain a high suspicion of traumatic coronary artery dissection, although the early recognition of traumatic coronary artery dissection can be difficult. Additionally, the importance of coronary angiography with IVUS modalities for the evaluation of traumatic coronary artery dissection is highlighted.

Introduction: Actinomycosis of the nasal cavity is very rare. Objective: The purpose of this study was to investigate the clinical features, treatment methods, and treatment results of actinomycosis of the nasal cavity in our hospital. Methods: We retrospectively enrolled 11 patients with histopathologically identified actinomycosis of the nasal cavity from January 2010 to May 2020. Results: This study included five males and six females. The most common symptom was purulent nasal discharge (36.4%). Nasal actinomycosis occurred in the maxillary sinus in 5 (45.5%) patients, the ethmoid sinus in two, the hard palate in two, the frontal sinus in one, and the nasal septum in one. After surgery, intravenous administration of antibiotics was performed on average for 7.4 days and oral antibiotics were prescribed for about 120.5 days. The clinical characteristics of the patients with nasal actinomycosis and the duration of antibiotic usage were not significantly different. Trauma was significantly associated with repeated nasal actinomycosis infections (p

A low-cost hydrogenation–dehydrogenation (HDH) Ti powder was employed to reduce the cost of the material used in powder bed fusion (PBF) additive manufacturing. HDH Ti powder was hydrophobic surface-treated with methyltrichlorosilane and mixed with spherical powder at a 1:1 ratio to ensure flowability for PBF process. Subsequently, PBF process with practical recoating speed (50 mm/s) and heat treatment process were optimized. It was confirmed that a high specific strength structural material with interesting mechanical properties at a low cost was formed, with a tensile strength of 924 MPa and an elongation of 9.5 %. This paper also discusses an intuitive and accurate apparatus for measuring the spreadability of metal powders for PBF applications. A recoating tester was developed for direct quantification of the spreadability in PBF, and this confirmed the possibility of using the mixed Ti powder containing low price HDH Ti in PBF with practical recoating speed.

Parkinson's disease (PD) is the second most common neurodegenerative disease, after Alzheimer's disease, and becomes increasingly prevalent with age. α-Synuclein (α-syn) forms the major filamentous component of Lewy bodies, which are pathological hallmarks of α-synucleinopathies such as PD. We evaluated the neuroprotective effects of MT101-5, a standardized herbal formula that consists of an ethanolic extract of Genkwae Flos, Clematidis Radix, and Gastrodiae Rhizoma, against α-synuclein-induced cytotoxicity in vivo. MT101-5 protected against behavioral deficits and loss of dopaminergic neurons in human α-syn-overexpressing transgenic mice after treatment with 30 mg/kg/day for 5 months. We investigated transcriptomic changes within MT101-5 mechanisms of action (MOA) suppressing α-syn aggregation in an α-synuclein preformed fibril (α-syn PFF) mouse model of sporadic PD. We found that inhibition of α-syn fibril formation was associated with changes in transcripts in mitochondrial biogenesis, electron transport, chaperones, and proteasomes following treatment with MT101-5. These results suggest that the mixed herbal formula MT101-5 may be used as a pharmaceutical agent for preventing or improving PD.

LINC00461 is located in the intergenic region between the protein-coding genes MEF2C and TMEM161B. LINC00461 upregulation was associated with the risk of 13 tumors and was strongly associated with clinicopathologic features and poor prognosis in 11 tumors. LINC00461 is involved in resistance to four anticancer drugs, including sunitinib for renal cell carcinoma, cisplatin for head and neck squamous cell carcinoma and rectal cancer, temozolomide for glioma, and docetaxel for breast cancer. LINC00461 can sponge 18 miRNAs to form a complex ceRNA network that regulates the expression of a large number of downstream genes. LINC00461 is involved in the MAPK/ERK signaling pathway and PI3K/AKT signaling pathway, thereby promoting tumorigenesis. Notably, knockdown of LINC00461 in exosomes antagonizes tumor cell proliferation in multiple myeloma. This article summarizes the diagnostic, prognostic, and therapeutic value of LINC00461 in various tumors, and systematically describes the ceRNA network and signaling pathways associated with LINC00461, providing potential directions for future LINC00461 research.

Background: The present study investigated the association of serum parathyroid hormone (PTH), vitamin D, and calcium levels with prostate cancer (CaP). Methods: The study population consisted of an experimental group [459 patients including 216 patients with CaP and 243 patients with benign prostate hyperplasia (BPH)] and a prostatectomy group (47 patients who underwent radical prostatectomy). Patients with serum creatinine levels >1.4 mg/dl, parathyroid disease, and/or PTH levels 20 ng/ml), Gleason score (≤7 or ≥8), and stage (≤T3 or ≥ T4), there was no significant difference in PTH levels between the two groups. Mean postoperative PTH levels (26.93 ± 13.58 pg/ml) were significantly lower than preoperative PTH levels (36.71 ± 21.04 pg/ml) in the same patients who underwent radical prostatectomy. Conclusion: Serum PTH levels were higher in patients with CaP than in patients with BPH and decreased significantly after radical prostatectomy. The present results suggest an association between serum PTH and CaP. Further large cohort studies are necessary to validate the present data.

Novel (Ti33Zr33Hf33)x(Ni50Cu50)100−x with x = 40–80 at.%, high entropy alloys (HEAs) developed by equiatomic substitution, each element is varied with five levels so that their microstructure and mechanical properties could be compared to define the effect of different contents. Above all, the (Ti33Zr33Hf33)60(Ni50Cu50)40 HEA exhibits enhanced the plasticity with maintaining high strength due to the occurrence of the C14-type phase of homogeneity morphology.Consequently, in this series of HEAs with equiatomic substitution selected composition with a relatively simple phase, and proceeded with the addition of other elements with good chemical compatibility factors such as atomic size different, valence electron concentration, and mixing enthalpy to induce phase transformation.

Defect inspection system for industrial applications takes the important portion. Non-destructive inspection method has been significantly improved. Infrared thermography, as one of method for non-destructive inspection, can provide relatively precise data and quick inspection time. This study, it was performed to measure defect according to the measurement limit of the non-visible areas such as the back surface of the pipe using reflection plate using reflection plate based on Infrared thermography. The materials of the reflection plate were determined in consideration of the space limitation and the thermal characteristics, and defects were detected by the manufactured reflection plate. Detection of defect in non-visible area using the candidate materials for reflection plate was conducted. Keywords: Reflection plate, Defect detection, Infrared thermography, Invisible area

Experimental binary equilibrium data for the adsorption of hydrocarbon mixtures on activated carbon at given temperature are presented and discussed. Pure-component adsorption isotherms were fitted by using Langmuir model. Then adsorption isotherms were determined for different binary mixtures. Adsorption isotherms of binary mixtures were calculated using the real adsorbed solution theories, which requires the calculation of the activity coefficients for the components in the adsorbed phase. Activity coefficients are evaluated using Margules activity model and UNIQUAC model. We described the adsorption equilibria using proposed model parameters with taken to be equal to those of VLE. The results show that, except for a few systems, the calculated results were in good agreement with experimental adsorption equilibrium data. Keywords: Adsorption equilibria, Real adsorption solution theory, Gas-adsorbed equilibrium

Plasmacytoma in the sellar region is an extremely rare occurrence. Sellar plasmacytoma is often difficult to differentiate from pituitary tumors both clinically and radiologically. The occurrence of cranial nerve palsy, the preservation of pituitary hormone function, the presence of sellar floor destruction, and better contrast enhancement are regarded as the differentiating factors between sellar plasmacytoma and pituitary tumors. We recommend adding the massive bleeding properties of sellar plasmacytoma as another characteristic which differentiates it from a pituitary tumor.

The human visual system is able to extract summary statistics from sets of similar items, but the underlying neural mechanism remains poorly understood. Using functional magnetic resonance imaging (fMRI) and an encoding model, we examined how the neural representation of ensemble coding is constructed by manipulating the task-relevance of ensemble features. We found a gradual increase in orientation-selective responses to the mean orientation of multiple stimuli along the visual hierarchy only when these orientations were task-relevant. Such responses to the ensemble orientation were present in the extrastriate area, V3, even when the mean orientation was not task-relevant, indicating that the ensemble representation can co-exist with the task-relevant individual feature representation. Ensemble orientations were also represented in frontal regions, but those representations were robust only when each mean orientation was linked to a motor response dimension. Together, our findings suggest that the neural representation of the ensemble percept is formed by pooling signals at multiple levels of the visual processing stream.

Introduction: Warthin tumors are the second most common benign tumors of the parotid gland. We examined the clinical features of Warthin tumors in our hospital, and analyzed the consistency within the literatures. Objective: The aim of this study is to analyze the clinical features of Warthin tumors in our 10-year experience of 118 Warthin tumors undergoing surgery at a single institute. Methods: From December 2006 to December 2016, 110 patients who underwent surgical treatment for Warthin tumors were identified based on their medical records. Results: A total of 118 parotid gland operations were performed in 110 patients. Almost 90% of Warthin tumors were found in males, and average patient age was 66.1 ± 6.1 years. The prevalence of smoking history was 89.1% (98/110). Eight patients (7.3%) had bilateral Warthin tumors. Seventy-seven lesions (65.3%) were located in the parotid tail portion, followed by 34 lesions in the superficial lobe (28.8%) and 7 lesions in the deep lobe (5.9%). Conclusion: We determined the appropriate extent of surgery depending on the fine needle aspiration cytology and tumor location by computed tomography scans. Partial facial dysfunction after the operation was detected in 12 cases, and facial nerve function recovered within 3 months. Only one patient experienced a recurrence, and was disease free after the re-operation. We suggest that our treatment algorithm, depending on the location of tumors and the result of fine needle aspiration cytology, can be useful to determine the appropriate extent of surgery for Warthin tumors. Resumo: Introdução: Os tumores de Warthin são os segundos tumores benignos mais comuns da glândula parótida. Avaliamos as características clínicas dos tumores de Warthin em nosso hospital e analisamos a consistência com a literatura. Objetivo: Analisar as características clínicas dos tumores de Warthin em nossa experiência de 10 anos de 118 tumores de Warthin submetidos a tratamento cirúrgico em um único instituto. Método: De dezembro de 2006 a dezembro de 2016, 110 pacientes que receberam tratamento cirúrgico para tumores de Warthin foram identificados com base em seus prontuários médicos. Resultados: Foram feitas 118 cirurgias na glândula parótida em 110 pacientes. Quase 90% dos tumores de Warthin foram encontrados em homens e a média da idade dos pacientes foi de 66,1 ± 6,1 anos. A prevalência de tabagismo foi de 89,1% (98/110). Oito pacientes (7,3%) tinham tumores de Warthin bilaterais na glândula parótida. Das lesões, 77 (65,3%) localizavam-se na porção da cauda da parótida, seguidas por 34 no lobo superficial (28,8%) e 7 no lobo profundo (5,9%). Conclusão: Determinamos a extensão apropriada da cirurgia de acordo com a punção aspirativa com agulha fina e localização do tumor por tomografia computadorizada. Disfunção facial parcial após a cirurgia foi detectada em 12 casos e a função do nervo facial foi recuperada em 3 meses. Apenas um paciente apresentou recidiva e ficou livre da doença após reoperação. Sugerimos que nosso algoritmo de tratamento, a depender da localização dos tumores e do resultado da PAAF, pode ser útil para determinar a extensão apropriada da cirurgia para os tumores de Warthin. Keywords: Warthin tumor, Parotid gland, Computed tomography, Fine-needle biopsy, Surgical procedures, Palavras-chave: Tumor de Warthin, Glândula parótida, Tomografia computadorizada, Biópsia por agulha fina, Procedimentos cirúrgicos

Summary: Aim: To report our institution's experiences with pure transanal total mesorectal excision (TME) of rectal cancer using single-port equipment and to discuss the feasibility and safety of the technique. Methods: Between February and December 2017, 12 patients who were selected underwent NOTES TME in our institution. The preoperative assessment included blood analyses with carcinoembryonic antigen serum concentration, full colonoscopy, pelvic magnetic resonance imaging (MRI), and computed tomography (CT) of the abdomen and chest. Results: Ten patients (male:female, 6:4) treated with transanal TME with colorectal anastomosis in our institution were reviewed. Pure TME was performed without laparoscopic assistance in 6 of 10 patients. The mean operative time was 303.5 min. The median distal margin was 2.1 (0.2–4.2) cm. The median number of harvested lymph nodes is 17.5. Except one patient with anastomotic leak, most patients started dietary intake on postoperative day (POD) 3 and were discharged on POD 7. Anastomotic leak was the only postoperative complication. Conclusion: This study showed that pure natural orifice transluminal endoscopic surgery (NOTES) TME with coloanal anastomosis for rectal cancer is safe and feasible in selected cases. Keywords: NOTES, Transanal TME, Rectal cancer

Background: To diagnose and treat respiratory allergic diseases, it is important to identify the specific allergens involved. Many differences exist between common inhalant allergens depending on the residential environment and demographic factors. This study aimed to compare common inhalant allergens between Koreans and non-Koreans according to their residential region, age, and sex. Methods: This study evaluated 15,334 individuals who underwent serum tests for multiple allergen-specific immunoglobulin E at a tertiary academic medical center between January 2010 and December 2016. The individuals included 14,786 Koreans and 548 non-Koreans. The AdvanSure™ Allostation assay (LG Life Science, Korea) was used to test for 33 inhalant allergens. Results: The house dust mite (HDM) was the most common allergen in both Koreans and non-Koreans, although the proportion of individuals with HDM sensitization was greater among Koreans. High sensitization rates for various pollen types were detected among Koreans in Gangwon region, whereas Japanese cedar pollen was unique among Koreans in Jeju region. Grass pollen and animal dander were relatively common among individuals from the Americas, whereas weed and grass pollen accounted for the 10 most common allergens for individuals from Central Asia. The total sensitization rate, sensitization to HDM, and sensitization to animal dander peaked among adolescents and young adults, then subsequently decreased with age. Conclusions: This large-scale study demonstrates that various regional and age-related differences exist in the allergen sensitization rates of Koreans and non-Koreans. These data could be useful for development of avoidance measures, immunotherapy for causative allergens, and policymaking regarding allergic diseases. Key words: Allergen, Epidemiology, House dust mite, Pollen, Sensitization

Introduction: Parotid carcinomas have varying histological types and diverse biologic behaviors. Establishing an adequate treatment plan and predicting recurrence is important. Objective: To analyze the risk factors associated with recurrence in our 5 year experience with 30 cases of primary parotid carcinoma undergoing surgery at a single institute. Methods: From January 2009 to December 2013, 30 patients with surgical treatment of parotid carcinoma were identified based on their medical records. Results: The 30 patients were comprised of 17 males and 13 females. Among 11 patients with T4 tumors, seven patients had recurrence. Among seven patients with cervical nodal metastasis, all patient except one had recurrence. Clinically late stages (stage III and IV) showed more common recurrence than early stage (stage I and II) lesions. Lymphovascular invasion was seen in 5 patients, and all patients had recurrence. Among 11 patients with extracapsular spread, 7 patients had recurrence. In 17 patients with high grade carcinomas, ten patients had recurrence. In 13 patients with low grade carcinomas, no patients experienced recurrence. Conclusion: T- and N-stage, clinical stage, lymphovascular invasion, extracapsular spread, and histopathologic grade correlate significantly with recurrence in parotid carcinoma. Resumo: Introdução: Os carcinomas da parótida têm diferentes tipos histológicos e comportamentos biológicos diversos. O estabelecimento de um plano de tratamento adequado e a previsão de recorrência são muito importantes. Objetivo: Analisar os fatores de risco associados à recorrência em nossa experiência de cinco anos com 30 casos de carcinoma parotídeo primário submetidos a cirurgia em uma única instituição. Método: De janeiro de 2009 a dezembro de 2013, 30 pacientes com tratamento cirúrgico de carcinoma parotídeo foram identificados com base nos prontuários. Resultados: Entre os 30 pacientes, 17 eram homens e 13, mulheres. Dos 11 pacientes com tumores T4, sete apresentaram recorrência. Entre sete pacientes com metástase em linfonodo cervical, todos, exceto um, apresentaram recorrência. Lesões em estágios clínicos tardios (III e IV) apresentaram recorrência mais comumente do que as dos estágios iniciais (I e II). A invasão linfovascular foi observada em cinco pacientes e todos os cinco apresentaram recorrência. Entre 11 pacientes com disseminação extracapsular, sete apresentaram recorrência. Dos 17 pacientes com carcinomas de alto grau, dez apresentaram recorrência. Em 13 pacientes com carcinomas de baixo grau, nenhum apresentou recorrência. Conclusão: Estágios T e N, estágio clínico, invasão linfovascular, disseminação extracapsular e grau histopatológico correlacionam-se de maneira significante com recorrência do carcinoma de parótida. Keywords: Parotid gland, Parotid cancer, Recurrence, Surgical procedures, Radiotherapy, Palavras-chave: Glândula parótida, Câncer de parótida, Recorrência, Procedimentos cirúrgicos, Radioterapia

Traumatic pulmonary giant hematoma, resulting from blunt trauma, is a relatively rare event. Here, we report the rare case of a patient with a giant traumatic pulmonary hematoma that was associated with blunt trauma. A 50-year-old man was admitted to our medical center after a fall from a height of 5 m. He was diagnosed with pulmonary contusion, and tests showed a huge pulmonary hematoma of approximately 8.2 × 5.3 × 13.2 cm in the left lung field along with other significant injuries. Treatment comprised of aggressive coagulation management, broad-spectrum antibiotics, and pulmonary hygiene. The patient's symptoms gradually improved and magnetic resonance scan revealed that he did not develop an abscess formation. No complications were seen at the 6 months follow-up visit. If the above mentioned measures would have failed to control the bleeding or secondary infection, then emergency surgery would have been warranted. Awareness of this kind of injury and efforts to reduce infection are important to guide the giant traumatic pulmonary hematoma to the benign course.

Human prostaglandin E2 receptor 4 (EP4) is one of the four subtypes of prostaglandin E2 (PGE2) receptors and belongs to the rhodopsin-type G protein-coupled receptor (GPCR) family. Particularly, EP4 is expressed in various cancer cells and is involved in cancer-cell proliferation by a G protein signaling cascade. To prepare an active form of EP4 for biochemical characterization and pharmaceutical application, this study designed a recombinant protein comprising human EP4 fused to the P9 protein (a major envelope protein of phi6 phage) and overexpressed the P9-EP4 fusion protein in the membrane fraction of E. coli. The solubilized P9-EP4 with sarkosyl (a strong anionic detergent) was purified by affinity chromatography. The purified protein was stabilized with amphiphilic polymers derived from poly-γ-glutamate. The polymer-stabilized P9-EP4 showed specific interaction with the alpha subunits of Gs or Gi proteins, and a high content of α-helical structure by a circular dichroism spectroscopy. Furthermore, the polymer-stabilized P9-EP4 showed strong heat resistance compared with P9-EP4 in detergents. The functional preparation of EP4 and its stabilization with amphiphilic polymers could facilitate both the biochemical characterization and pharmacological applications targeting EP4.

Here, novel lightweight Al alloys were designed with an objective to achieve diverse color range and improved mechanical properties. The alloy design strategy was based on a scientific color expression method controlling the microstructural attributes, such as constitutive phases, and their morphology (length-scale). The intrinsic difference in colors between the constitutive phases, their spatial arrangement/dimension, and fraction play a critical role in determining chromatic characteristic of the alloys. Our current research demonstrates the feasibility of the present color alloy design concept with three groups which allows blue color diversification and mechanical properties for ultra-light aluminum-magnesium-silicon alloys.

Summary: Pluripotent stem cells (PSCs) represent the most promising clinical source for regenerative medicine. However, given the cellular heterogeneity within cultivation and safety concerns, the development of specific and efficient tools to isolate a pure population and eliminate all residual undifferentiated PSCs from differentiated derivatives is a prerequisite for clinical applications. In this study, we raised a monoclonal antibody and identified its target antigen as desmoglein-2 (DSG2). DSG2 co-localized with human PSC (hPSC)-specific cell surface markers, and its expression was rapidly downregulated upon differentiation. The depletion of DSG2 markedly decreased hPSC proliferation and pluripotency marker expression. In addition, DSG2-negative population in hPSCs exhibited a notable suppression in embryonic body and teratoma formation. The actions of DSG2 in regulating the self-renewal and pluripotency of hPSCs were predominantly exerted through the regulation of β-catenin/Slug-mediated epithelial-to-mesenchymal transition. Our results demonstrate that DSG2 is a valuable PSC surface marker that is essential for the maintenance of PSC self-renewal. : DSG2 is a desmosomal cadherin molecule. In this article, Min and colleagues show that DSG2 is a valuable PSC surface marker that is essential for the maintenance of PSC self-renewal and pluripotency and the acquisition of pluripotency during somatic cell reprogramming through the regulation of β-catenin-mediated EMT signaling. keywords: desmoglein-2, cell surface marker, pluripotent stem cells, monoclonal antibody, EMT

Background/Objective: Although consensus has been reached on the superiority of laparoscopy for a majority of conditions underlying acute abdominal pain, the safety and feasibility of single-port laparoscopic colectomy (SPLC) in emergency situations have not been determined. Methods: A prospective electronic database of all emergency patients who underwent either multiport laparoscopic colectomy (MPLC) or SPLC between April 2006 and December 2014 was used to compare the surgical outcomes of these operative methods. Results: During the study period, 31 MPLCs and 76 SPLCs were performed. These two operative methods resulted in similar operating times, transfusion amounts, lengths of stay, postoperative complications, attainment of lymph nodes, and proximal and distal cut margins. However, the SPLC group had a shorter time to first flatus (2.8±1.9 days vs. 3.8±1.5 days, p=0.005), earlier reinitiation of free oral fluids (3.2±2.1 days vs. 4.4±1.8 days, p=0.002), and lesser requirement of narcotic analgesics (2.5±3.9 times vs. 4.7±4.8 times, p=0.017). Conclusion: SPLC could be a safe and effective alternative to MPLC, even in emergency situations when performed by surgeons who have overcome the learning curve associated with single-port laparoscopic techniques. The tendency toward earlier returns to bowel function and decreased incidence of postoperative analgesic use would be potential benefits of SPLC in emergency situations.

Background: Because acute cholecystitis has a different prognosis according to the degree of inflammation, early detection and prompt operation of severe cholecystitis are critical to the success of treatment. However, computed tomography (CT) has a low discriminative value for differentiating between simple and severe cholecystitis. Therefore, to enhance the diagnostic accuracy of CT scan, the imaging studies should be supplemented by preoperative clinical variables. Methods: Patients undergoing laparoscopic cholecystectomy for simple and severe cholecystitis between 2007 and 2014 were compared. Severe cholecystitis included hemorrhagic, gangrenous, emphysematous, xanthogranulomatous, and perforated cholecystitis. Prediction models for severe cholecystitis were developed based on multivariate analyses of preoperative clinical and radiologic variables. Results: Independent factors related with severe cholecystitis were age ≥65 years, male gender, body mass index (BMI) ≥25, serum leukocyte count ≥10,000/mm3, serum neutrophil fraction ≥80%, serum platelet count ≥20,000/mm3, serum alanine transaminase (ALT) level ≥40 IU/L, admission via the emergency department, and radiologic features of gallbladder wall thickening ≥4 mm, and presence of pericholecystic fluid collection (p

Spliceosomes are the core host of pre-mRNA splicing, allowing multiple protein isoforms to be produced from a single gene. Herein, we reveal that spliceosomes are more abundant in human pluripotent stem cells (hPSs), including human embryonic stem cells (hESs) and human induced pluripotent stem cells (hiPSs), than non-hPSs, and their presence is associated with high transcriptional activity. Supportively, spliceosomal components involved in the catalytically active pre-mRNA splicing step were mainly co-localized with hPS spliceosomes. By profiling the gene expression of 342 selected splicing factors, we found that 71 genes were significantly altered during the reprogramming of human somatic cells into hiPSs. Among them, SNRPA1, SNRPD1, and PNN were significantly up-regulated during the early stage of reprogramming, identified as hub genes by interaction network and cluster analysis. SNRPA1, SNRPD1, or PNN depletion led to a pronounced loss of pluripotency and significantly blocked hiPS generation. SNRPA1, SNRPD1, and PNN co-localized with the hPS spliceosomes, physically interacted with each other, and positively influenced the appearance of hPS spliceosomes. Our data suggest that SNRPA1, SNRPD1, and PNN are key players in the regulation of pluripotency-specific spliceosome assembly and the acquisition and maintenance of pluripotency.

Background: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. Methods: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides. H2O2 productions, glutathione contents, lactate dehydrogenase activities, mitochondrial membrane permeabilities, apoptotic cell subpopulations, caspase-3/-7 activities, transferase dUTP nick end labeling (TUNEL) staining, and immunoblot analysis were performed to elucidate the molecular mechanism responsible for ginsenoside-mediated cytotoxicity. Involvement of the AMP-activated protein kinase (AMPK)-related signaling pathway was examined using a chemical inhibitor and small interfering RNA (siRNA) transfection. Results and conclusion: Of the 11 ginsenosides tested, 20S-protopanaxadiol (PPD) showed the most potent cytotoxic activity in both LX-2 cells and primary activated HSCs. Oxidative stress-mediated apoptosis induced by 20S-PPD was blocked by N-acetyl-l-cysteine pretreatment. In addition, 20S-PPD concentration-dependently increased the phosphorylation of AMPK, and compound C prevented 20S-PPD-induced cytotoxicity and mitochondrial dysfunction. Moreover, 20S-PPD increased the phosphorylation of liver kinase B1 (LKB1), an upstream kinase of AMPK. Likewise, transfection of LX-2 cells with LKB1 siRNA reduced the cytotoxic effect of 20S-PPD. Thus, 20S-PPD appears to induce HSC apoptosis by activating LKB1–AMPK and to be a therapeutic candidate for the prevention or treatment of liver fibrosis.

Post-stroke depression (PSD) is the most common neuropsychological sequela of stroke and occurs in approximately one-third of all stroke survivors. However, there are no well-established predictors of PSD. Depression in stroke patients is correlated with unfavorable outcomes. Meta-analyses of the relationship between PSD and lesion location have yielded contradictory results and have not adequately addressed the impact of cerebellar lesions. Furthermore, other brain regions associated with depression in patients with cerebellar stroke remain a matter of debate. For these reasons, this cross-sectional study investigated the relationship between PSD and lesion location in patients with isolated cerebellar stroke. Twenty-four patients in the subacute rehabilitative period following a first-ever isolated cerebellar stroke were enrolled in the study. Depressive mood were evaluated using the Geriatric Depression Scale. Regions of interest were drawn manually on T1-weighted magnetic resonance images using MRIcron software, and data were normalized to a standard brain template in order to examine the neural correlates of depression using voxel-based lesion-symptom mapping analysis. Voxel-wise subtraction and χ (Ayerbe et al., 2014) analyses indicated that damage to the left posterior cerebellar hemisphere was associated with depression. Significant correlations were also found between the severity of depressive symptoms and lesions in lobules VI, VIIb, VIII, Crus I, and Crus II of the left cerebellar hemisphere (Pcorrected = 0.045). Our results suggest that damage to the left posterior cerebellum is associated with increased depressive mood severity in patients with isolated cerebellar stroke.

The gradient Al2O3 layer coated bimodal structured composite substrate was fabricated using combined chemical and hydrothermal processes. Selective etching was performed to remove micrometer-sized α-Al dendrites from the ultrafine structured matrix. Simultaneously, a hydrothermal oxidation process was used to grow Al2O3 on the surface of the porous structured substrate. In particular, the architecture of coated metal oxide (Al2O3) can be altered from a rectangular to a pyramidal shape depending on the hydrothermal process time. Keywords: Ultrafine eutectic composite, Porous materials, Dealloying, Hydrothermal process

Summary: Katanin was the first microtubule (MT)-severing enzyme discovered, but how katanin executes MT severing remains poorly understood. Here, we report X-ray crystal structures of the apo and ATPγS-bound states of the catalytic AAA domain of human katanin p60 at 3.0 and 2.9 Å resolution, respectively. Comparison of the two structures reveals conformational changes induced by ATP binding and how such changes ensure hexamer stability. Moreover, we uncover structural details of pore loops (PLs) and show that Arg283, a residue unique to katanin among MT-severing enzymes, protrudes from PL1 and lines the entry of the catalytic pore. Functional studies suggest that PL1 and Arg283 play essential roles in the recognition and remodeling of the glutamylated, C-terminal tubulin tail and regulation of axon growth. In addition, domain-swapping experiments in katanin and spastin suggest that the non-homologous N-terminal region, which contains the MT-interacting and trafficking domain and a linker, confers specificity to the severing process. : Shin et al. report structures of the apo and ATPγS-bound AAA domain of katanin p60. Structural modeling and functional studies suggest that Arg283 in the YRG motif, unique to katanin, crowns the entry of the catalytic core and is essential for remodeling of glutamylated microtubules and regulation of axon growth. Keywords: katanin, microtubule severing, AAA ATPase, crystal structure, axon growth, glutamylation

Paeonia japonica root has been widely used for its antioxidative, anti-inflammatory, and analgesic effects. This research investigated the effects of P. japonica root extract (PJE) on hepatotoxicity and the underlying molecular mechanisms. PJE blocked the arachidonic acid (AA) + iron-induced hepatotoxicity of HepG2 cells in a dose-dependent manner. In addition, PJE inhibited H2O2 production, and decreased GSH levels and mitochondrial dysfunction induced by AA + iron in HepG2 cells. The cytoprotective effects of PJE were found to be associated with AMPK-mediated inhibitory phosphorylation of GSK3β. More importantly, based on the histopathological observations, 300 mg/kg PJE showed marked hepatoprotective effects against phenylhydrazine-induced peripheral hepatic damage and inhibited nitrotyrosine and 4-HNE immunoreactivity in hepatocytes. This finding provides evidence that PJE exerts beneficial hepatoprotective effects through activation of an anti-oxidative pathway. Thus, PJE would be a promising nutraceutical for the prevention and treatment of liver disorders.

Background: Korean Red Ginseng (KRG) is known to have antianxiety properties. This study was conducted to investigate the anxiolytic effects of KRG extract (KRGE) during ethanol withdrawal (EW) and the involvement of the mesoamygdaloid dopamine (DA) system in it. Methods: Rats were treated with 3 g/kg/d of ethanol for 28 d, and subjected to 3 d of withdrawal. During EW, KRGE (20 mg/kg/d or 60 mg/kg/d, p.o.) was given to rats once/d for 3 d. Thirty min after the final dose of KRGE, anxiety-like behavior was evaluated in an elevated plus maze (EPM), and plasma corticosterone (CORT) levels were determined by a radioimmunoassay (RIA). In addition, concentrations of DA and 3,4-dihydroxyphenylacetic acid (DOPAC) in the central nucleus of the amygdala (CeA) were also measured by high performance liquid chromatography (HPLC). Results: The EPM test and RIA revealed KRGE inhibited anxiety-like behavior and the over secretion of plasma CORT during EW. Furthermore, the behavioral effect was blocked by a selective DA D2 receptor (D2R) antagonist (eticlopride) but not by a selective DA D1 receptor (D1R) antagonist (SCH23390). HPLC analyses showed KRGE reversed EW-induced decreases of DA and DOPAC in a dose-dependent way. Additionally, Western blotting and real-time polymerase chain reaction (PCR) assays showed that KRGE prevented the EW-induced reductions in tyrosine hydroxylase (TH) protein expression in the CeA and TH mRNA expression in the ventral tegmental area (VTA). Conclusion: These results suggest that KRGE has anxiolytic effects during EW by improving the mesoamygdaloid DA system.

Surface-enhanced Raman scattering (SERS) is a promising technology owing to its single-molecular sensitivity and molecular specificity. However, producing strong and stable SERS signal from plasmonic nanostructures remains a challenge. Herein, we present a facile generation of SERS-active nanomaterials by organizing metallic nanoparticles onto dye-labeled three-dimensional DNA nanostructures. Stable formations of metal clusters with the dye located in hot spots enabled detection of SERS signals. SERS signals were further regulated via interaction of pyramidal DNA scaffold with target biomolecules. We believe our SERS-active nanomaterials with controllable geometry and reversible SERS effects meet significant requirements for practical SERS-based sensors. By integrating versatile properties of DNA and introducing various Raman dyes into plasmonic nanostructures, the emergence of powerful and multiplexed biosensors should be possible. Keywords: DNA nanostructures, Surface-enhanced Raman scattering, Plasmonic nanostructures, DNA pyramid

Acetylation is one of the most crucial post-translational modifications that affect protein function. Protein lysine acetylation is catalyzed by acetyltransferases, and acetyl-CoA functions as the source of the acetyl group. Additionally, acetyl-CoA plays critical roles in maintaining the balance between carbohydrate metabolism and fatty acid synthesis. Here, we sought to determine whether lysine acetylation is an important process for adipocyte differentiation. Based on an analysis of the acetylome during adipogenesis, various proteins displaying significant quantitative changes were identified by LC-MS/MS. Of these identified proteins, we focused on malate dehydrogenase 1 (MDH1). The acetylation level of MDH1 was increased up to 6-fold at the late stage of adipogenesis. Moreover, overexpression of MDH1 in 3T3-L1 preadipocytes induced a significant increase in the number of cells undergoing adipogenesis. The introduction of mutations to putative lysine acetylation sites showed a significant loss of the ability of cells to undergo adipogenic differentiation. Furthermore, the acetylation of MDH1 dramatically enhanced its enzymatic activity and subsequently increased the intracellular levels of NADPH. These results clearly suggest that adipogenic differentiation may be regulated by the acetylation of MDH1 and that the acetylation of MDH1 is one of the cross-talk mechanisms between adipogenesis and the intracellular energy level.

Background: The impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on atrial fibrillation (AF) recurrence outcomes and adverse cardiovascular outcomes in heart failure (HF) patients after AF ablation is unknown., Objective: We investigated whether SGLT2i reduces the risk of AF recurrence and adverse cardiovascular outcomes in HF patients after AF ablation., Methods: HF patients with AF undergoing catheter ablation between January 2017 and December 2022 from the China-AF Registry were included. Patients were stratified into 2 groups on the basis of the use of SGLT2i at discharge and were 1:1 matched by propensity score, with SGLT2i using (n = 368) and non-SGLT2i using (n = 368) in each group. The primary outcome was AF recurrence after a 3-month blanking period., Results: During a total of 1315 person-years of follow-up, AF recurred in 83 patients (22.6%) in the SGLT2i group and 132 patients (35.8%) in the non-SGLT2i group. SGLT2i was associated with a lower risk of AF recurrence (adjusted hazard ratio, 0.56; 95% CI, 0.43-0.74; P < .001). The composite risk of cardiovascular death, thrombotic events, or cardiovascular hospitalization was significantly lower in the SGLT2i group compared with those without SGLT2i (adjusted hazard ratio, 0.58; 95% CI, 0.41-0.80; P = .001). Although there was a trend toward benefit, the differences in all-cause mortality, cardiovascular death, or thrombotic events were insignificant between the 2 groups., Conclusion: The use of SGLT2i was associated with a lower risk of AF recurrence and the composite outcome of cardiovascular death, thrombotic events, or cardiovascular hospitalization after catheter ablation for AF in patients with HF., Competing Interests: Disclosures Changsheng Ma has received honoraria for presentations from AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, and Pfizer. Jianzeng Dong has received honoraria for presentations from Johnson & Johnson., (Copyright © 2024. Published by Elsevier Inc.)

Land use types have a significant impact on river ecosystems. The Yiluo River is the largest tributary below Xiaolangdi Reservoir in the middle reaches of the Yellow River, and is one of the important water conservation areas in the Yellow River Basin. Studying the ecological status of the Yiluo River under varied land use types in this basin is crucial for both ecological protection and the high-quality development of the Yellow River Basin. This study investigated the impacts of land use types on the macroinvertebrate community and functional structure in the Yiluo River Basin and introduced the concept of the land use health index (LUI). During the survey period, a total of 11,894 macroinvertebrates were collected, and 143 species were identified, belonging to 4 phyla, 7 orders, 22 families, and 75 families. The results showed that LUI had the most significant impact on macroinvertebrate community structure, with substrate type, dry plant weight, total phosphorus, turbidity, and attached algae biomass also playing significant roles in affecting macroinvertebrate communities. The species richness, the Shannon-Wiener index, and the Margalef richness index exhibited a nonlinear positive correlation with LUI of the sampling site, increasing as LUI enhancing and eventually reaching a plateau. Functional richness showed a linear and positive correlation with LUI, increasing with its enhancement, while functional evenness and functional divergence exhibited a nonlinear correlation with LUI. Functional evenness initially increased and then decreased with the enhancement of LUI, while functional divergence decreased with LUI enhancement. This study can provide a scientific reference for river ecological management under various land use scenarios.The Yiluo River is the largest tributary below Xiaolangdi Reservoir in the middle reaches of the Yellow River, and is one of the important water conservation areas in the Yellow River Basin. Studying the ecological status of the Yiluo River under varied land use types in this basin is crucial for both ecological protection and the high-quality development of the Yellow River Basin. This study investigated the impacts of land use types on the macroinvertebrate community and functional structure in the Yiluo River Basin and introduced the concept of the land use health index (LUI). During the survey period, a total of 11,894 macroinvertebrates were collected, and 143 species were identified, belonging to 4 phyla, 7 orders, 22 families, and 75 families. The results showed that LUI had the most significant impact on macroinvertebrate community structure, with substrate type, dry plant weight, total phosphorus, turbidity, and attached algae biomass also playing significant roles in affecting macroinvertebrate communities. The species richness, the Shannon-Wiener index, and the Margalef richness index exhibited a nonlinear positive correlation with LUI of the sampling site, increasing as LUI enhancing and eventually reaching a plateau. Functional richness showed a linear and positive correlation with LUI, increasing with its enhancement, while functional evenness and functional divergence exhibited a nonlinear correlation with LUI. Functional evenness initially increased and then decreased with the enhancement of LUI, while functional divergence decreased with LUI enhancement. This study can provide a scientific reference for river ecological management under various land use scenarios., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Na Zhao reports financial support, administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, travel, and writing assistance were provided by National Natural Science Foundation of China (51809086). Na Zhao reports financial support, administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, travel, and writing assistance were provided by Henan Provincial Science and Technology Research Project (222102320144). Na Zhao reports financial support, administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, travel, and writing assistance were provided by Young Backbone Teacher Project of Henan University of Science and Technology (13450005). Weijun Chen reports financial support, administrative support, article publishing charges, equipment, drugs, or supplies, statistical analysis, travel, and writing assistance were provided by National Natural Science Foundation of China32202952). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Although the electrocardiographic and electrophysiological properties of ventricular arrhythmias (VAs) from the vicinity of the lateral tricuspid annulus (TA) have been reported in previous studies, their precise site of origin have not been addressed., Objective: The purpose of this study was to describe the precise origin of lateral TA-VA and the relevant anatomy., Methods: Consecutive patients with idiopathic lateral TA-VAs were reviewed and analyzed. Three-dimensional mapping system combined with intracardiac echocardiography (ICE) was used for anatomic reconstruction, mapping, and ablation., Results: During the study period, 63 patients with lateral TA-VAs were included. Under ICE view, a prominent enfoldment structure was observed under the valve along the lateral TA. The muscular bundle was documented in all patients (100%) within the subvalvular enfoldment with an average number and diameter of 4 ± 2 and 4.10 ± 0.73 mm, respectively. Initial ablation was attempted via the anterograde approach in 15 patients but succeeded in none. To reach the ventricular side of the TA, the catheter needed to enter the ventricular chamber and retroflexed toward the atrial side with a reverse curve. The earliest activation site was found at the valvular end of muscular bundles in 51 of the 63 patients (80.9%) with a local activation time of -26.78 ± 4.63 ms. The VAs were eliminated after an average of 4 ± 2 seconds of ablation., Conclusion: The ventricular side adjacent to the lateral TA exhibits a subvalvular enfoldment-like structure, which is rich in muscular bundles and serves as the origin of TA-VAs in most patients. To reach the origins, a reverse technique is required., Competing Interests: Disclosures Dr Ma has received honoraria for presentations from AstraZeneca, Bayer Healthcare, Boehringer Ingelheim, Bristol Myers Squibb, Johnson & Johnson, and Pfizer. Dr Long and Dr Dong have received honoraria for presentations from Johnson & Johnson and Abbott. All other authors have no conflicts of interest to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The association between serum potassium and atrial fibrillation (AF) recurrence after catheter ablation remains unclear., Objective: The purpose of this study was to investigate whether preprocedural serum potassium influences AF recurrence in patients who underwent catheter ablation., Methods: We used data of patients with AF who underwent de novo catheter ablation from the prospective Chinese Atrial Fibrillation Registry Study. Patients with prior ablation and without baseline serum potassium were excluded. The primary outcome was 1-year AF recurrence after a 3-month blanking period from the ablation procedure. Restricted cubic spline and Cox proportional models were used to compare outcomes across serum potassium categories., Results: A total of 4838 patients with AF who underwent de novo catheter ablation was enrolled. At 1 year, AF recurrence occurred in 1347 patients (27.8%). The relationship between preprocedural serum potassium and 1-year AF recurrence after ablation presented as U shape (P for nonlinear = .048). Compared with the group of serum potassium within 4.41-4.60 mmol/L, the risk of AF recurrence increased significantly in the lowest serum potassium group (≤4.00 mmol/L) after multivariate analysis (hazard ratio [HR] 1.26; 95% confidence interval 1.06-1.51; P = .010). Other categories with lower or higher serum potassium levels including 4.01-4.20 mmol/L (HR 1.18), 4.21-4.40 mmol/L (HR 1.16), 4.61-4.80 mmol/L (HR 1.07), and ≥4.81 mmol/L (HR 1.11) showed nonsignificant higher recurrence risk., Conclusion: The relationship between preprocedural potassium and AF recurrence was U shaped, with an optimal potassium range (4.41-4.60 mmol/L). Lower potassium level is associated with increased AF recurrence risk after catheter ablation., (Copyright © 2024. Published by Elsevier Inc.)

The degradation of water quality induced by the construction of large-scale hydraulic projects is one of the primary public concerns; however, it is rarely addressed with long-term field observation data. Here, we reported the long-term (2003-2021) trends, seasonal patterns, and overall condition of water quality of the Three Gorges Reservoir (TGR) with an enhanced water quality index (WQI). Specifically, to emphasize the importance of the biological role in water quality assessment, chlorophyll-a (Chla) was incorporated into WQI, and then a novel workflow using machine learning approach based on Random Forest (RF) model was constructed to develop a minimal water quality index (WQI min ). The enhanced WQI indicated an overall "good" water quality condition, exhibiting a gradually improving trend subsequent to the reservoir impoundment in 2003. Meanwhile, the assessment revealed that the water quality has discernible seasonal patterns, characterized by poorer conditions in the spring and summer seasons. Furthermore, the RF model identified Chla, dissolved oxygen (DO), ammonium nitrogen (NH 4 -N), water temperature (WT), pH, and total nitrogen (TN) as key parameters for the WQI min , with Chla emerging as the most important factor in determining WQI min in our study. Moreover, weighted WQI min models exhibited improved performance in estimating WQI. Our study emphasizes the importance of biological parameters in water quality assessment, and introduces a systematic workflow to facilitate the development of WQI min for accurate and cost-efficient water quality assessment. Furthermore, our study makes a substantial contribution to the advancement of knowledge regarding long-term trends and seasonal patterns in water quality of large reservoirs, which provides a foundational basis for guiding water quality management practices for reservoirs worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Magnesium ions (Mg 2+ ) are essential for the folding, functional expression, and structural stability of RNA molecules. However, predicting Mg 2+ -binding sites in RNA molecules based solely on RNA structures is still challenging. The molecular surface, characterized by a continuous shape with geometric and chemical properties, is important for RNA modelling and carries essential information for understanding the interactions between RNAs and Mg 2+ ions. Here, we propose an approach named RNA-magnesium ion surface interaction fingerprinting (RMSIF), a geometric deep learning-based conceptual framework to predict magnesium ion binding sites in RNA structures. To evaluate the performance of RMSIF, we systematically enumerated decoy Mg 2+ ions across a full-space grid within the range of 2 to 10 Å from the RNA molecule and made predictions accordingly. Visualization techniques were used to validate the prediction results and calculate success rates. Comparative assessments against state-of-the-art methods like MetalionRNA, MgNet, and Metal3DRNA revealed that RMSIF achieved superior success rates and accuracy in predicting Mg 2+ -binding sites. Additionally, in terms of the spatial distribution of Mg 2+ ions within the RNA structures, a majority were situated in the deep grooves, while a minority occupied the shallow grooves. Collectively, the conceptual framework developed in this study holds promise for advancing insights into drug design, RNA co-transcriptional folding, and structure prediction., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Coronary angiography-derived index of microcirculatory resistance (caIMR) can effectively assess coronary microvascular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to explore the role of caIMR in the occurrence of new-onset atrial fibrillation (NOAF) in patients with STEMI., Methods: This was a single-centre retrospective clinical observational study. Patients diagnosed with STEMI from September 2019 to December 2022 were included. caIMR was calculated using computational flow and pressure simulations. During admission, suspicious heart rhythm was recorded by electrocardiographic (ECG) monitoring, and NOAF was confirmed by an immediate 12-lead ECG., Results: A total of 739 patients were enrolled, including 57 (7.7) with NOAF. caIMR was significantly correlated with microvascular obstruction (R = 0.604; P < 0.001) and infarct size (R = 0.514; P < 0.001). After adjusting for potential confounding factors, the results showed that caIMR (odds ratio 1.058, 95% confidence interval 1.035-1.083; P < 0.001) was an independent risk factor for NOAF in patients with STEMI. Receiver operating characteristic analysis showed that the area under the curve of caIMR for predicting NOAF was 0.716. Compared with the caIMR < 27.35 U group, the caIMR ≥ 27.35 U group had higher high-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide levels. When caIMR was added to the model, the reclassification and discriminant abilities improved significantly., Conclusions: Higher caIMR was an independent risk factor for NOAF in patients with STEMI. The caIMR had high specificity and sensitivity for predicting NOAF in patients with STEMI. The integration of caIMR into clinical risk factors showed significantly increased predictability for NOAF in patients with STEMI., (Copyright © 2023 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Due to the variety and activity of secondary metabolites of endophytic fungi (SMEF) from medicinal plants, and the operation cumbersome of existing methods for evaluating the activity, there is urgent to establish a simple, efficient and sensitive evaluation and screening technology. In this study, the prepared chitosan functionalized activated carbon (AC@CS) composite as the electrode substrate material was used to modify glassy carbon electrode (GCE), and the gold nanoparticles (AuNPs) was deposited on AC@CS/GCE by cyclic voltammetry (CV). A ds-DNA/AuNPs/AC@CS/GCE electrochemical biosensor for evaluating the antioxidant activity of SMEF from Hypericum perforatum L. (HP L.) was fabricated using the method of layer by layer assembly. The experimental conditions affecting the evaluation results of the biosensor were optimized by square wave voltammetry (SWV) using Ru(NH 3 ) 6 3+ as the probe, and the antioxidant activity of various SMEF from HP L. was evaluated by the proposed biosensor. Meanwhile, the results of the biosensor were also verified by UV-vis. According to the optimized experimental results, the biosensors had a high levels of oxidative DNA damage at pH 6.0 and Fenton solution system with Fe 2+ to OH - ratio of 1:3 for 30 min. Among the crude extracts of SMEF from roots, stems and leaves of HP L., the crude extracts from stems presents a high antioxidant activity, but it was weaker than l-ascorbic acid. This result was consistent with the evaluation results of UV-vis spectrophotometric method, also the fabricated biosensor presents high stability and sensitivity. This study not only provides a novel, convenient and efficient way for rapid evaluating the antioxidant activity of a wide variety of SMEF from HP L., but also provides a novel evaluation strategy for the SMEF from medicinal plants., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)