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Background To investigate the association of glycemic control and retinal microvascular changes in patients with type 2 diabetes mellitus (T2DM) without diabetic retinopathy (DR). Methods This retrospective, observational, cohort study included patients with T2DM without DR. The patients were categorized into intensive control (IC; mean glycosylated hemoglobin [HbA1c] ≤7.0%) and moderate control (MC; mean HbA1c >7.0%) groups. Optical coherence tomography (OCT) and swept-source OCT angiography (OCTA) image parameters were compared between three groups, including healthy controls. Results In total, 259 eyes of 259 participants (88 IC, 81 MC, and 90 controls) were included. The foveal avascular zone area was significantly larger in the MC group than IC and control groups (all P

Background: Major pulmonary resection after neoadjuvant concurrent chemoradiation therapy (nCCRT) is associated with a substantial risk of postoperative complications. This study investigated postoperative complications and associated risk factors to facilitate the selection of suitable surgical candidates following nCCRT in stage IIIA–N2 non-small cell lung cancer (NSCLC). Methods: We conducted a retrospective analysis of patients diagnosed with clinical stage IIIA–N2 NSCLC who underwent surgical resection following nCCRT between 1997 and 2013. Perioperative characteristics and clinical factors associated with morbidity and mortality were analyzed using univariable and multivariable logistic regression. Results: A total of 574 patients underwent major lung resection after induction CCRT. Thirty-day and 90-day postoperative mortality occurred in 8 patients (1.4%) and 41 patients (7.1%), respectively. Acute respiratory distress syndrome (n=6, 4.5%) was the primary cause of in-hospital mortality. Morbidity occurred in 199 patients (34.7%). Multivariable analysis identified significant predictors of morbidity, including patient age exceeding 70 years (odds ratio [OR], 1.8; p=0.04), low body mass index (OR, 2.6; p=0.02), and pneumonectomy (OR, 1.8; p=0.03). Patient age over 70 years (OR, 1.8; p=0.02) and pneumonectomy (OR, 3.26; p

A 70-year-old man with dilated cardiomyopathy underwent left ventricular assist device (LVAD) implantation, using a HeartWare ventricular assist device, as a bridge to candidacy. After 26 months, computed tomography (CT) angiography indicated stenosis in the LVAD outflow graft; however, the patient was asymptomatic, prompting a decision to manage his condition with close monitoring. Ten months later, the patient presented with dizziness and low-flow alerts. Subsequent CT angiography revealed a critical obstruction involving the entire LVAD outflow graft. The patient underwent emergency surgery, during which an organized seroma causing the graft obstruction was found between a wrapped expanded polytetrafluoroethylene (ePTFE) graft and a Dacron outflow graft. The covering of the outflow graft was removed, along with the organized seroma. Following removal of the ePTFE wrap and decompression of the outflow graft, normal LVAD flow was reestablished. The practice of wrapping the outflow graft with synthetic material, commonly done to facilitate later redo sternotomy, may pose a risk for outflow graft obstruction.

Abstract Excessive clotting or abnormal platelet accumulation can lead to serious cardiovascular disorders such as atherosclerosis, stroke, and thrombosis. Therefore, it is imperative to identify compounds capable of controlling or impeding platelet aggregation to prevent the onset of cardiovascular diseases. Arteanoflavone, a compound extracted from Artemisia iwayomogi, has not garnered scientific recognition for its potential health benefits, recent studies have substantiated its anti-inflammatory, antioxidant, and anti-allergic properties. However, the precise mechanisms by which arteanoflavone influences platelet aggregation and blood clot formation have not been conclusively established. This research investigates arteanoflavone’s role in these processes, particularly in platelets induced by collagen. The study reveals a significant increase in the production of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) correlating with the administered dosage of arteanoflavone. Concurrently, a noticeable escalation is observed in substrates of cAMP-dependent kinase and cGMP-dependent kinase, specifically VASP and inositol 1,4,5-trisphosphate receptor (IP3R). Arteanoflavone demonstrates its ability to limit Ca2+ movement in the dense tubular system through IP3R phosphorylation. Moreover, phosphorylated VASP inhibits the binding of fibrinogen to αIIb/β3, thus suppressing platelet activity. Arteanoflavone also stimulates the phosphorylation of PI3K/Akt, a protein linked to platelet granule release, and MAPK (ERK, JNK, and p38) protein, associated with both platelet granule release and TXA2 production. Lastly, arteanoflavone impedes collagen-induced platelet aggregation and blood clot formation by inhibiting fibrin production in thrombin-induced platelets. Hence, it is suggested that arteanoflavone could be valuable as an agent that effectively deters platelet inhibition and blood clot formation through antiplatelet mechanisms.

O inibidor de JAK1/2 aprovado pela FDA, Ruxolitinibe (Ruxo), é utilizado para tratar pacientes com neoplasias mieloproliferativas (NMP), oferecendo boa tolerabilidade e redução dos sintomas constitucionais. No entanto, o efeito do Ruxo na erradicação da célula iniciadora da leucemia é limitado. O estudo clínico TAMARIM mostrou que a monoterapia com tamoxifeno (Tam) reduziu a carga do alelo mutante em 13% dos pacientes. Aqui, exploramos se a combinação Ruxo+Tam poderia proporcionar um controle superior da doença em modelos pré-clínicos de NMP. In vitro, a terapia combinada de Ruxo (1-10 μM) e Tam (0,3-3 μM) por 72 horas exibiu forte efeito sinérgico (ZIP score = 24,4) na linhagem celular HEL. O tratamento com Ruxo ou Tam isoladamente reduziu o potencial da membrana mitocondrial (PMM) e as taxas de consumo de oxigênio em células HEL. Esses efeitos foram significativamente aprimorados com a combinação de Ruxo e Tam, sugerindo uma modulação do metabolismo mitocondrial como um mecanismo comum de ambos os fármacos. Para amostras primárias de NMP, realizamos triagem de fármacos ex vivo em 20 amostras de medula óssea (MO). A monoterapia com Ruxo (0,3-1 μM) não induziu apoptose de forma significativa, contudo a monoterapia com Tam ou em combinação com Ruxo induziu apoptose e reduziu o PMM em blastos (CD34+). A análise funcional da respiração confirmou diminuição do metabolismo mitocondrial tanto na monoterapia com Tam quanto na combinação Ruxo+Tam em amostras de NMP tratadas ex vivo. A análise por citometria de fluxo identificou uma população de blastos de NMP expressando CD36 associada à resistência à monoterapia com Tam. Essa resistência, contudo, pôde ser superada com a combinação com Ruxo. Para explorar os efeitos da terapia Ruxo+Tam in vivo, transplantamos 5 × 106 células da MO de um modelo murino de NMP JAK2 V617F (CD45.2) em camundongos B6 PepBoy irradiados letalmente (CD45.1). Quatro semanas após o transplante os camundongos foram randomizados em 4 grupos: veículo, Tam (75 mg/kg, intraperitoneal, 1 vez ao dia), Ruxo (120 mg/kg, oral, 2 vezes ao dia) e combinação Ruxo+Tam. Os camundongos foram tratados diariamente por 8 semanas e amostras de sangue periférico foram coletadas quinzenalmente para monitorar quimerismo, frequências de células imunes e contagens hematológicas. A análise de quimerismo mostrou uma redução significativa nas células CD45.2 a partir da semana 6 apenas no grupo Ruxo+Tam. A análise das células imunes no grupo Ruxo+Tam revelou uma redução na fração de células mieloides, o que foi associado à diminuição do PMM, sugerindo a modulação do metabolismo mitocondrial nestas células. Além disso, a terapia combinada resultou em uma diminuição significativa nas células CD36+ na semana 2. A análise hematológica indicou uma forte redução nos níveis de leucócitos, plaquetas e hematócrito a partir da semana 2 no grupo Ruxo+Tam, indicando um maior controle da doença. Em resumo, nossos dados apoiam a justificativa para usar a terapia combinada de Ruxo+Tam no tratamento de NMP. Demonstramos que ambos os fármacos atuam modulando o metabolismo mitocondrial, um efeito que é aprimorado quando usados em combinação, superando a resistência observada com as monoterapias. Além disso, Tam é um fármaco de baixo custo e sua incorporação na prática clínica poderia ser viável e benéfica em países de baixa e média renda. Esses achados apoiam a realização de novos estudos clínicos para explorar a eficácia dessa terapia combinada para pacientes com NMP.

Abstract Background High blood pressure variability (BPV) increases the risk of cardiovascular disease and may be better prognostic factor than blood pressure. Depressive mood is a common symptom among patients visiting primary care. This study aimed to investigate the association between depressive mood and high BPV among Korean primary care patients. Methods The Family Cohort Study in Primary Care (FACTS), conducted from April 2009 to November 2017, utilized a prospective cohort of Korean primary care patients, with a median follow-up period of 7.25 years. Depressive mood was assessed as a score of 21 points or more on the Korean-type Center for Epidemiologic Studies Depression scale. BP was measured at the initial visit and first and second follow-up visit. Visit-to visit SBP variability was analyzed using four metrics: intra-individual standard deviation, coefficient of variation, variation independent of mean, and average real variability. Logistic regression analysis was used to estimate the association of high BPV with depressive mood and other variables. Results Among 371 participants, 43 (11.6%) had depressive mood based on depression scores. Older age (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.01–1.07) were associated with high SBP variability regardless of taking antihypertensive medication. Among participants taking antihypertensive medication, those with depressive mood had twice the risk of high SBP variability compared with those who did not (OR: 2.95, 95% CI: 1.06–8.20). Conclusions Depressive mood was associated with high visit-to-visit SBP variability in primary care patients taking antihypertensive medication, potentially indicating increased cardiovascular risk. Primary care physicians should therefore closely monitor BPV in patients with depressive symptoms and provide appropriate interventions.

The HeartWare Ventricular Assist Device (HVAD) was widely used for mechanical circulatory support in patients with end-stage heart failure. However, there have been reports of a critical issue with HVAD pumps failing to restart, or experiencing delays in restarting, after being stopped. This case report describes 2 instances of HVAD failure-to-restart during heart transplantation surgery and routine outpatient care. Despite multiple attempts to restart the pump using various controllers and extensions, the HVAD failed to restart, triggering a hazard alarm for pump stoppage. In one case, the patient survived after receiving a heart transplantation, while in the other, the patient died immediately following the controller exchange. These cases highlight the rare but life-threatening complication of HVAD failure-to-restart, underscoring the importance of awareness among clinicians, patients, and caregivers, and adherence to the manufacturer’s guidelines and recommendations for HVAD management.

As feed-additive aquaculture expands to open ocean areas, there is concern that ecologically important habitats may be adversely impacted by sedimentation of farm wastes. In this study, we investigated assimilation of salmon faecal wastes by an ecosystem engineering bivalve that occurs in open ocean environments (Atrina zelandica), as well as effects on physiology and fatty acid metabolism. A. zelandica were subjected to one of 3 treatment diets (fish faeces, 1:1 mix of algae:faeces and algae) in a 51 d laboratory trial. We found a diet-related response in fatty acid composition, including increased prevalence of oleic acid (OA) in digestive tissues of A. zelandica fed on both the fish faeces diet and the mixed diet, indicating fish wastes were assimilated in both treatments. Fish waste consumption was related to a more marked reduction in fatty acid content of digestive gland, as well as lower proportions of long-chain polyunsaturated fatty acids (LC-PUFA) in digestive tissues. Fatty acid composition in gonad and muscle tissues was more strongly influenced by sex. Regardless of dietary treatment, females accumulated C18 fatty acids in gonad tissues, particularly OA, which may preclude the use of OA as a fish waste tracer in this organ. The accumulation of specific fatty acids according to sex may indicate a capacity for preferential selection and retention or biosynthesis of biologically important fatty acids. If present, these mechanisms may increase resilience of A. zelandica to stress from deficiencies in LC-PUFA when using fish wastes as a trophic subsidy.

Background: Contralateral pulmonary resection after pneumonectomy presents considerable challenges, and few reports in the literature have described this procedure. Methods: We retrospectively reviewed the medical records of all patients who underwent contralateral lung resection following pneumonectomy for any reason at our institution between November 1994 and December 2020. Results: Thirteen patients (9 men and 4 women) were included in this study. The median age was 57 years (range, 35–77 years), and the median preoperative forced expiratory volume in 1 second was 1.64 L (range, 1.17–2.12 L). Contralateral pulmonary resection was performed at a median interval of 44 months after pneumonectomy (range, 6–564 months). Surgical procedures varied among the patients: 10 underwent single wedge resection, 2 were treated with double wedge resection, and 1 underwent lobectomy. Diagnoses at the time of contralateral lung resection included lung cancer in 7 patients, lung metastasis from other cancers in 3 patients, and tuberculosis in 3 patients. Complications were observed in 4 patients (36%), including acute kidney injury, pneumothorax following chest tube removal, pneumonia, and prolonged air leak. No cases of operative mortality were noted. Conclusion: In carefully selected patients, contralateral pulmonary resection after pneumonectomy can be accomplished with acceptable operative morbidity and mortality.

ObjectiveThe objective of this study was to determine the implementation, clinical barriers, and unmet needs of repetitive transcranial magnetic stimulation (rTMS) and neuro-navigation systems for stroke rehabilitation.DesignWe employed a nationwide survey via Google Forms (web and mobile) consisting of 36 questions across rTMS and neuro-navigation systems, focusing on their implementation, perceptions, and unmet needs in stroke recovery. The survey targeted physiatrists registered in the Korean Society for Neuro-rehabilitation and in rehabilitation hospitals in South Korea.ResultsOf 1,129 surveys distributed, 122 responses were analyzed. Most respondents acknowledged the effectiveness of rTMS in treating post-stroke impairments; however, they highlighted significant unmet needs in standardized treatment protocols, guidelines, education, device usability, and insurance coverage. Unmet needs for neuro-navigation were also identified; only 7.4% of respondents currently used such systems, despite acknowledging their potential to enhance treatment accuracy. Seventy percent of respondents identified lack of prescription coverage, time and errors in preparation, and device cost as barriers to clinical adoption of neuro-navigation systems.ConclusionDespite recognition of the potential of rTMS in stroke rehabilitation, there is a considerable gap between research evidence and clinical practice. Addressing these challenges, establishing standardized protocols, and advancing accessible neuro-navigation systems could significantly enhance the clinical application of rTMS, offering a more personalized, effective treatment modality for stroke recovery.

Abstract Copper iodide (CuI) has garnered considerable attention as a promising alternative to p‐type transparent conducting oxides owing to its low cation vacancy formation energy, shallow acceptor level, and readily modifiable conductivity via doping. Although sulfur (S) doping through liquid iodination has exhibited high efficacy in enhancing the conductivity with record high figure of merit (FOM) of 630 00 MΩ−1, solution‐processed S‐doped CuI (CuI:S) for low‐cost large area fabrication has yet to be explored. Here, a highly conducting CuI:S thin‐film for p‐type transparent conducting electrode (TCE) is reported using low temperature solution‐processing with thiourea derivatives. The optimization of thiourea dopant is determined through a comprehensive acid‐base study, considering the effects of steric hindrance. The modification of active groups of thioureas facilitated a varying carrier concentration range of 9 × 1018–2.52 × 1020 cm−3 and conductivities of 4.4–390.7 S cm−1. Consequently, N‐ethylthiourea‐doped CuI:S exhibited a FOM value of 7 600 MΩ−1, which is the highest value among solution‐processed p‐type TCEs to date. Moreover, the formulation of CuI:S solution for highly conductive p‐type TCEs can be extended to CuI:S inks, facilitating high‐throughput solution‐processes such as inkjet printing and spray coating.

This study verified the mediating effects of creative home environment and self-directed learning ability on the relationship between creative personality and creative achievement intention of university students. Creative personality was set as independent variable, creative home environment and self-directed learning ability as mediating variables, and creative achievement intention as dependent variable. This study was conducted from June 10 to July 10, 2019 in Seoul, South Korea, and the participants were 587 university students. Data was collected through an online–offline test and analysed using SPSS Statistics 25.0. Creative personality affected creative achievement intention through the medium of creative home environment. However, self-directed learning ability had no mediating effect in the influence of creative personality on creative achievement intention. Therefore, creative home environment is important to improve the creative achievement intention of university students. Further, that the family’s environmental support affects the creative achievement intention to express creativity in course of development bears implications for parent education.

Background/Aims: Although an association between achalasia and esophageal cancer has been reported, whether achalasia confers a substantial increase in mortality is unknown. Moreover, the causes of death related to achalasia have not been investigated. We performed this nationwide, population-based cohort study on achalasia because no such study has been performed since the introduction of high-resolution manometry in 2008. Methods: This study was performed using data extracted from the Korean National Health Insurance Service database, covering a 9-year period from 2009 to 2017. Control participants without a diagnostic code for achalasia were randomly selected and matched by sex and birth year at a case-to-control ratio of 1:4. Data on the cause of death from Statistics Korea were also analyzed. Results: The overall incidence of achalasia was 0.68 per 100,000 person-years, and the prevalence was 6.46 per 100,000 population. Patients with achalasia (n=3,063) had significantly higher adjusted hazard ratio (aHR) for esophageal cancer (aHR, 3.40; 95% confidence interval [CI], 1.25 to 9.22; p=0.017), pneumonia (aHR, 2.30; 95% CI, 1.89 to 2.81; p

In patients with ulcerative colitis (UC), the development of an antidrug antibody (ADA) to anti-tumor necrosis factor (TNF)α agent is a crucial problem which aggravates the clinical course of the disease, being cited as one of the most common causes for discontinuing anti-TNFα treatment. This is due to ADA eventually causing secondary LOR, leading to discontinuation of anti-TNFα treatment. Recently, research on the microbiome and relationship between worsening UC and dysbiosis has been conducted. Further, investigations on the association between the microbiome and secondary LOR are increasing. Here, we present the therapeutic effect of fecal microbiota transplantation (FMT) on a 42-year-old man with secondary LOR and high ADA levels. FMT has recently been used for the treatment of, and for overcoming, drug resistance through microbiome modification. Stool samples were collected from the patient before and 4 weeks after FMT. Symptoms, including hematochezia and Mayo endoscopy sub-scores, improved after FMT, while ADA levels decreased by one-third to less than half the value (29 ng/mL) compared to before FMT (79 ng/mL). Additionally, the trough level of infliximab became measurable, which reflects the improvement in the area under the concentration (AUC). Butyricicoccus, Faecalibacterium, Bifidobacterium, Ligilactobacillus, Alistipes, and Odoribacter, which regulate immune responses and alleviate inflammation, also increased after FMT. We report a case in which microbiome modification by FMT increased the AUC of anti-TNFα in a patient who developed secondary LOR during anti-TNFα treatment, thereby improving symptoms and mucosal inflammation.

Serology testing of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is increasingly being used during the current pandemic of coronavirus disease 2019 (COVID‐19), although its clinical and epidemiologic utilities are still debatable. Characterizing these assays provides scientific basis to best use them. The current study assessed one chemiluminescent assay (Abbott COVID‐2 IgG) and two lateral flow assays (STANDARD Q [SQ] IgM/IgG Duo and Wondfo total antibody test) using 113 blood samples from 71 PCR‐confirmed COVID‐19 hospitalized patients, 119 samples with potential cross‐reactions, and 1068 negative controls including 942 pre‐pandemic samples. SARS‐CoV‐2 IgM antibodies became detectable 3‐4 days post‐symptom onset using SQ IgM test and IgG antibodies were first detected 5‐6 days post‐onset using SQ IgG. Abbott IgG and Wondfo Total were able to detect antibodies 7 to 8 days post‐onset. After 14 days post‐symptom onset, the SQ IgG, Abbott IgG and Wondfo Total tests were able to detect antibodies from 100% of the PCR‐confirmed patients in this series; 87.5% sensitivity for SQ IgM. Overall agreement was 88.5% between SQ IgM/IgG and Wondfo Total and 94.6% between SQ IgG and Abbott IgG. No cross‐reaction due to recent sera with three of the endemic coronaviruses was observed. Viral hepatitis and autoimmune samples were the main source of limited cross‐reactions. The specificities were 100% for SQ IgG and Wondfo Total, 99.62% for Abbott IgG, and 98.87% for SQ IgM. These findings demonstrated high sensitivity and specificity of appropriately validated SARS‐CoV‐2 serologic assays with implications for clinical use and epidemiological seroprevalence studies. Research Highlights: The validation included two lateral flow assays (Wondfo Total Antibody and SQ IgM/IgG combo) and one chemiluminescent assay (Abbott IgG)All tests except SQ IgM performed well with excellent sensitivities 2 weeks after symptom onset.The specificities were 100% for SQ IgG and Wondfo Total, 99.62% for Abbott IgG, and 98.87% for SQ IgM based on 1068 negative controls.Hepatitis and autoimmune samples were the main sources of limited cross‐reactions. [ABSTRACT FROM AUTHOR]

IntroductionGreen banana flour can be used as a prebiotic due to its ability to promote gut health and provide several health benefits. In this study, we investigated whether feeding mice green banana flour at different doses would alter intestinal microbiota composition.MethodsWe fed C57BL/6N mice either a Low-dose (500 mg/kg/day) or High-dose (2000 mg/kg/day) of green banana flour daily for 3 weeks, and fecal samples were collected on days 0, 14, and 21 for microbiota analysis.ResultsOur results showed that the composition of intestinal microbiota was significantly altered by day 21, regardless of the dose. Notably, the consumption of green banana flour increased the presence of beneficial bacteria, including Coriobacteriaceae_UCG-002, Turicibacter, Parasutterella, Gastranaerophilales_ge, and RF39_ge. These changes in the intestinal microorganisms were accompanied by increased biological processes such as amino acid biosynthesis and secondary metabolite biosynthesis. Conversely, the consumption of green banana flour resulted in a decrease in biological processes related to carbohydrate degradation, glycerol degradation, and similar functions.DiscussionThese results emphasize the potential of green banana flour as a prebiotic that can benefit the gut microbiome.

A combinação do inibidor de BCL2 venetoclax (VEN) com agentes hipometilantes (por exemplo, azacitidina, AZA) aumentou significativamente as taxas de remissão completa (RC) e prolongou a sobrevida global de adultos com leucemia mieloide aguda (LMA) que não eram elegíveis para quimioterapia intensiva. No entanto, VEN+AZA não são um tratamento curativo e a resistência a VEN e/ou recidivas são comuns. Portanto, é necessária a busca de novos agentes capazes de superar a resistência do VEN. O presente estudo objetivou analisar o efeito da cefalocromina (CPC), um composto natural obtido do Comospora vilior, em células de LMA. Inicialmente, CPC e VEN foram avaliados em monoterapia num painel de linhagens celulares de LMA (n = 12). Com 72h de incubação, os valores de concentração inibitória 50% (IC50) para CPC variaram de 0,45 a >20 μM entre as linhagens, enquanto os valores para VEN variaram de

Background/Aims: Epstein-Barr virus (EBV) and Helicobacter pylori (HP) coinfection may synergistically induce severe inflammatory responses in the stomach tissue, increasing the risk of developing gastric cancer. We aimed to analyze the effect of EBV and HP coinfection on the clinicopathologic features and prognosis of gastric cancer, as well as to evaluate the role of EBV infection in non-gastric carcinoma with lymphoid stroma (non-GCLS).Methods: Overall, 956 patients who underwent surgery for gastric cancer between September 2014 and August 2015 were eligible and divided into groups, according to GCLS morphology, EBV infection, and HP infection. Clinicopathologic characteristics and oncologic outcomes were analyzed retrospectively.Results: EBV and HP coinfection was significantly associated with male sex, proximal location, GCLS morphology, and equivocal p53 expression (p

The apprenticeship-based training method (ABTM) is highly effective for gastrointestinal (GI) endoscopic training. However, the conventional ABTM has significant issues. Although many supplementary training methods (TMs) have been developed and utilized, they cannot entirely replace the ABTM, which remains the major TM strategy. Currently, new TM construction is crucial and necessary due to financial constraints, difficulty of obtaining sufficient training time due to patient safety-related regulations, and catastrophic damage caused by disasters such as the coronavirus disease 2019 pandemic. The simulator-based TM (SBTM) is widely accepted as an alternative to the ABTM, owing to the SBTM’s advantages. Since the 1960s, many GI endoscopy training simulators have been developed and numerous studies have been published on their effectiveness. While previous studies have focused on the simulator’s validity, this review focused on the accessibility of simulators that were introduced by the end of 2021. Although the current SBTM is effective in GI endoscopic education, extensive improvements are needed to replace the ABTM. Incorporating simulator-incorporated TMs into an improved ABTM is an attempt to overcome the incompleteness of the current SBTM. Until a new simulator is developed to replace the ABTM, it is desirable to operate a simulator-integrated and well-coordinated TM that is suitable for each country and institution.

SUMMARY: In the red algal genus Gloiopeltis, five species (G. complanata, G. dura, G. frutex, G. furcata and G. tenax) are currently recognized, but genetic analyses have suggested considerably greater species diversity. Gloiopeltis specimens formed nine highly supported clades, six of which are morphologically referable to G. furcata. In order to identify the clade corresponding to true G. furcata, we examined the morphology and genetics of the type specimen of Dumontia furcata Postels & Ruprecht, the basionym of G. furcata, housed in the Herbarium of V.L. Komarov Botanical Institute (LE). A clade comprising the type and specimens from the northwestern to northeastern Pacific Ocean was determined to correspond G. furcata. We concluded that the type locality of G. furcata is Sitka, Alaska, based on the identity of haplotypes. We investigated the genetic divergence of populations within this species, using specimens covering most of its distributional range. We confirmed the merger of G. minuta and G. dura with G. furcata. [ABSTRACT FROM AUTHOR]

Benign convulsions with mild gastroenteritis (CwG) are characterized by afebrile convulsions associated with viral gastroenteritis in previously healthy infants and children. The main causative pathogens are rotavirus and norovirus. CwG occurs frequently in both East Asian and Western countries. The prevalence of CwG was reportedly not decreased by the introduction of rotavirus vaccines, and the prevalence of norovirus-associated CwG has been increasing annually. Convulsions in CwG are usually clustered, do not last longer than 5 minutes, and are mostly generalized. Laboratory diagnostics, electroencephalography (EEG), and imaging findings are usually normal. There is a probability of mild, transient abnormal findings on EEG or imaging limited to the acute disease phase. Although several reports have suggested that pathogens that affect the central nervous system through direct or indirect mechanisms could be related to the pathophysiology of CwG, its mechanism is not fully understood. Several antiepileptic drugs are effective during convulsions; however, long-term antiepileptic treatment is not required as CwG usually has a good prognosis.

The yes-associated protein (YAP) of the Hippo pathway regulates a variety of target genes involved in cell proliferation, survival, and inflammation. YAP and transcription activator with a PDZ-binding motif (TAZ) proteins act as mediators of the inflammatory response. Still, their role in atopic dermatitis (AD)—particularly, the association with the nuclear factor kappa-B and Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathways—is not fully understood. In this study, we found that YAP, is upregulated in AD patients and NC/Nga mouse model of AD. In addition, inhibition of YAP significantly reduced epidermal cell proliferation by 58% and mast cell numbers by 51% and attenuated the upregulation of both Th1- and Th2-associated cytokines. Among the JAK-STAT family proteins, the expressions of JAK1 and JAK2 and those of STAT1, STAT2, and STAT3 were also downregulated. These findings may explain the role of YAP in AD and suggest YAP inhibitors as promising therapeutic agents for AD.

Background/Aims: As pancreatic mucinous cystic neoplasms (MCNs) are considered premalignant lesions, the current guidelines recommend their surgical resection. We aimed to investigate the concordance between preoperative and postoperative diagnoses and evaluate preoperative clinical parameters that could predict the malignant potential of MCNs. Methods: Patients who underwent surgical resection at Samsung Medical Center for pancreatic cystic lesions and whose pathology was confirmed to be MCN, between July 2000 and December 2017, were retrospectively analyzed. Results: Among a total of 132 patients 99 (75%) were diagnosed with MCN preoperatively. The most discordant preoperative diagnosis was an indeterminate pancreatic cyst. The proportion of male patients was higher (24.2% vs 7.1%, p=0.05) in the diagnosis-discordance group and the presence of worrisome features in radiologic imaging studies, such as wall thickening/enhancement (12.1% vs 37.4%, p=0.02) or solid component/mural nodule (3.0% vs 27.3%, p=0.02), was lower in the diagnosis-discordance group. The presence of symptoms (57.7% vs 34.9%, p=0.02), tumor size greater than 4 cm (80.8% vs 55.7%, p=0.04), and radiologic presence of a solid component/mural nodule (42.3% vs 16.0%, p=0.01) or duct dilatation (19.2% vs 6.6%, p=0.01) were significantly associated with malignant MCNs. Conclusions: In our study, the overall diagnostic concordance rate was confirmed to be 75%, and our findings suggest that MCNs have a low malignancy potential when they are less than 4 cm in size, are asymptomatic and lack worrisome features on preoperative images.

Abstract Background Pre-(PRE) and post-ejection (POE) velocities by mitral annular tissue Doppler (TD) are biphasic and may be related to myocardial deformations. We investigated the predominance and concordance of TD-PRE and POE velocities and their effect on myocardial functions in controls and in heart failure (HF) patients. Methods Retrospectively, 84 HF patients [57.6 years, 28(33%) females, NYHA: 2.3 ± 0.6, EF: 55 ± 15%, 52(62%) preserved EF, and 32(38%) reduced EF], 42 normal young controls, and 26 asymptomatic age matched controls were included. Echocardiography was done and from mitral annular tissue Doppler recordings, the biphasic PRE and POE velocity signals were identified and compared between groups. Results While controls had almost always predominantly positive PRE and negative POE, HF had more negative PRE and positive POE. Moreover, almost all controls exhibited normal concordance (positive PRE and negative POE). HF exhibited more abnormal concordance which was significantly associated with worse NYHA, and parameters of diastolic and systolic functions. Opposite PRE and POE velocities correlated significantly in all groups (PREp vs POEn: young:r = 0.52, p

Pathogenic variants of DNMT3A have been implicated in Tatton-Brown-Rahman syndrome, an overgrowth disorder with macrocephaly and intellectual disability. However, there are recent reports of variants in the same gene giving rise to an opposing clinical phenotype presenting with microcephaly, growth failure, and impaired development—named Heyn-Sproul-Jackson syndrome (HESJAS). Here, we present a case of HESJAS caused by a novel pathogenic variant of DNMT3A. A five-year-old girl presented with severe developmental delay. Perinatal and family history were non-contributory. Physical exam showed microcephaly and facial dysmorphic features, and neurodevelopmental assessments revealed profound global developmental delay. Brain magnetic resonance imaging findings were normal; however, brain 3D computed tomography revealed craniosynostosis. Next generation sequencing revealed a novel heterozygous variant in DNMT3A (NM_175629.2: c.1012_1014 + 3del). The patient's parents did not carry the variant. In this report, a novel feature associated with HESJAS (craniosynostosis) is described, along with a more detailed account of clinical manifestations than those in the original report.

Abstract Background Papillary thyroid carcinoma (PTC), the most common endocrine cancer, accounts for 80–85% of all malignant thyroid tumors. This study focused on identifying targets that affect the multifocality of PTC. In a previous study, we determined 158 mRNAs related to multifocality in BRAF-mutated PTC using The Cancer Genome Atlas. Methods We used multi-omics data (miRNAs and mRNAs) to identify the regulatory mechanisms of the investigated mRNAs. miRNA inhibitors were used to determine the relationship between mRNAs and miRNAs. We analyzed the target protein levels in patient sera using ELISA and immunohistochemical staining of patients’ tissues. Results We identified 44 miRNAs that showed a negative correlation with mRNA expression. Using in vitro experiments, we identified four miRNAs that inhibit TEK and/or AXIN2 among the target mRNAs. We also showed that the downregulation of TEK and AXIN2 decreased the proliferation and migration of BRAF ( +) PTC cells. To evaluate the diagnostic ability of multifocal PTC, we examined serum TEK or AXIN2 in unifocal and multifocal PTC patients using ELISA, and showed that the serum TEK in multifocal PTC patients was higher than that in the unifocal PTC patients. The immunohistochemical study showed higher TEK and AXIN2 expression in multifocal PTC than unifocal PTC. Conclusions Both TEK and AXIN2 play a potential role in the multifocality of PTC, and serum TEK may be a diagnostic marker for multifocal PTC.

For investigating whether the MARSSIM nonparametric test has sufficient statistical power when a site has a specific contamination distribution before conducting a final status survey (FSS), a novel approach was proposed to predict the release probability of the site. Five distributions were assumed: lognormal distribution, normal distribution, maximum extreme value distribution, minimum extreme value distribution, and uniform distribution. Hypothetical radioactivity populations were generated for each distribution, and Sign tests were performed to predict the release probabilities after extracting samples using Monte Carlo simulations. The designed Type I error (0.01, 0.05, and 0.1) was always satisfied for all distributions, while the designed Type II error (0.01, 0.05, and 0.1) was not always met for the uniform, maximum extreme value, and lognormal distributions. Through detailed analyses for lognormal and normal distributions which are often found for contaminants in actual environmental or soil samples, it was found that a greater statistical power was obtained from survey units with normal distribution than with lognormal distribution. This study is expected to contribute to achieving the designed decision error when the contamination distribution of a survey unit is identified, by predicting whether the survey unit passes the statistical test before undertaking the FSS according to MARSSIM.

Various kinds of plastics have been developed over the past century, vastly improving the quality of life. However, the indiscriminate production and irresponsible management of plastics have led to the accumulation of plastic waste, emerging as a pressing environmental concern. To establish a clean and sustainable plastic economy, plastic recycling becomes imperative to mitigate resource depletion and replace non-eco-friendly processes, such as incineration. Although chemical and mechanical recycling technologies exist, the prevalence of composite plastics in product manufacturing complicates recycling efforts. In recent years, the biodegradation of plastics using enzymes and microorganisms has been reported, opening a new possibility for biotechnological plastic degradation and bio-upcycling. This review provides an overview of microbial strains capable of degrading various plastics, highlighting key enzymes and their role. In addition, recent advances in plastic waste valorization technology based on systems metabolic engineering are explored in detail. Finally, future perspectives on systems metabolic engineering strategies to develop a circular plastic bioeconomy are discussed.

In this Case Report, a patient with Buerger’s disease who had a leg amputation below his lower right knee and a vascular bypass of right leg, developed a wound caused by his prosthetic leg and subjective discomfort. The patient received skin flap surgery but the wound did not heal properly. He was admitted to the Korean Medicine Hospital where his wound, right leg coldness, and phantom pain were treated with combined Korean medicine. The patient was hospitalized again where he underwent micro-drilling surgery. The patient was re-admitted to the Korean Medicine Hospital where he received combined Korean medicine treatment (CKMT) and carbon arc light treatment (CALT) for his wound, leg coldness, stiffness, and hypoplasia. The temperature of his right leg increased, the numeric rating scale score for assessing pain fell from 5 to 1.5, and subjective discomfort was reduced (< 20%) suggesting this may be an effective treatment.

Background/Aims: Data regarding the prognosis of early esophageal cancer are lacking. This study investigated the long-term outcomes and factors affecting the survival of patients with mucosal esophageal squamous cell carcinoma (T1aESCC). Methods: We analyzed the clinical and tumor-specific parameters of 263 patients who received surgical resection (SR; n=63) or endoscopic resection (ER; n=200) for T1aESCC. Underlying comorbidities were scored using the Charlson comorbidity index (CCI). Overall survival (OS) was the primary outcome, and multivariate regression analysis was performed to predict factors for OS. Results: Of the study patients (age, 64.5±8.0 years), the CCI was 1.0±1.4 in the ER group and 0.6±0.9 in the SR group (p=0.107). The 5-year OS rate during follow-up (54.4±20.4 months) was 85.7% (ER group, 86.8%; SR group, 82.4%; p=0.631). The cumulative 5-year incidence of esophageal cancer recurrence was 10.5% in the ER group (vs 0% in the SR group). The overall mortality rate was 12.9% (ER group, 12.0%; SR group, 15.9%; p=0.399). The most common cause of mortality was second primary cancers in the ER group (75%) and organ dysfunction or postoperative complications in the SR group (70%). According to multivariate analysis, only CCI was significantly associated with OS (p2 and in those with a CCI ≤2 was 60.2% and 88.2%, respectively (p

The title compound, C18H12N2O2, was synthesized from a dinitrobiphenylbenzene derivative using a novel modification of the Cadogan reaction. The reaction has several possible ring-closed products and the title compound was separated as the major product. The X-ray crystallographic study revealed that the carbazole compound crystallizes in the monoclinic P\overline{1} space group and possesses a single closed Cadogan ring. There are two independent molecules in the asymmetric unit. In the crystal, the molecules are linked by N—H...O hydrogen bonding.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) is often associated with symptoms of cortisol excess, which may include neuropsychological symptoms. We report a patient with PBMAH who presented with manic symptoms that resolved following unilateral adrenalectomy.

Alterations in the intestinal microbial flora are known to cause various diseases, and many people routinely consume probiotics or prebiotics to balance intestinal microorganisms and the growth of beneficial bacteria. In this study, we selected a peptide from fish (tilapia) skin that induces significant changes in the intestinal microflora of mice and reduces the Firmicutes/Bacteroidetes ratio, which is linked to obesity. We attempted to verify the anti-obesity effect of selected fish collagen peptides in a high-fat-diet-based obese mouse model. As anticipated, the collagen peptide co-administered with a high-fat diet significantly inhibited the increase in the Firmicutes/Bacteroidetes ratio. It increased specific bacterial taxa, including Clostridium_sensu_stricto_1, Faecalibaculum, Bacteroides, and Streptococcus, known for their anti-obesity effects. Consequently, alterations in the gut microbiota resulted in the activation of metabolic pathways, such as polysaccharide degradation and essential amino acid synthesis, which are associated with obesity inhibition. In addition, collagen peptide also effectively reduced all obesity signs caused by a high-fat diet, such as abdominal fat accumulation, high blood glucose levels, and weight gain. Ingestion of collagen peptides derived from fish skin induced significant changes in the intestinal microflora and is a potential auxiliary therapeutic agent to suppress the onset of obesity.

We investigated the globally distributed red algal genus Pterocladiella, comprising 24 described species, many of which are economically important sources of agar and agarose. We used DNA-based species delimitation approaches, phylogenetic, and historical biogeographical analyses to uncover cryptic diversity and infer the drivers of biogeographic patterns. We delimited 43 species in Pterocladiella, of which 19 are undescribed. Our multigene time-calibrated phylogeny and ancestral area reconstruction indicated that Pterocladiella most likely originated during the Early Cretaceous in the Tethys Sea. Ancient Tethyan vicariance and long-distance dispersal have shaped current distribution patterns. The ancestor of Eastern Pacific species likely arose before the formation of the formidable Eastern Pacific Barrier—a first confirmation using molecular data in red algae. Divergences of Northeast and Southeast Pacific species have been driven by the Central American Seaway barrier, which, paradoxically, served as a dispersal pathway for Atlantic species. Both long- and short-distance dispersal scenarios are supported by genetic relationships within cosmopolitan species based on haplotype analysis. Asymmetrical distributions and the predominance of peripatry and sympatry between sister species suggest the importance of budding speciation in Pterocladiella. Our study highlights the underestimation of global diversity in these crucial components of coastal ecosystems and provides evidence for the complex evolution of current species distributions.