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In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Abstract Hormone receptor (HR)-positive breast cancer can become aggressive after developing hormone-treatment resistance. This study elucidated the role of long non-coding RNA (lncRNA) SOX2OT in tamoxifen-resistant (TAMR) breast cancer and its potential interplay with the tumor microenvironment (TME). TAMR breast cancer cell lines TAMR-V and TAMR-H were compared with the luminal type A cell line (MCF-7). LncRNA expression was assessed via next-generation sequencing, RNA extraction, lncRNA profiling, and quantitative RT-qPCR. SOX2OT overexpression effects on cell proliferation, migration, and invasion were evaluated using various assays. SOX2OT was consistently downregulated in TAMR cell lines and TAMR breast cancer tissue. Overexpression of SOX2OT in TAMR cells increased cell proliferation and cell invasion. However, SOX2OT overexpression did not significantly alter SOX2 levels, suggesting an independent interaction within TAMR cells. Kaplan–Meier plot analysis revealed an inverse relationship between SOX2OT expression and prognosis in luminal A and B breast cancers. Our findings highlight the potential role of SOX2OT in TAMR breast cancer progression. The downregulation of SOX2OT in TAMR breast cancer indicates its involvement in resistance mechanisms. Further studies should explore the intricate interactions between SOX2OT, SOX2, and TME in breast cancer subtypes.

Abstract Background Extramammary Paget's disease (EMPD) is rare. There are no standard treatments due to its rarity and few clinical trials. Methods The objective of this multicenter study was to investigate treatment outcomes of Korean patients with advanced/metastatic EMPD. Data were collected retrospectively from 14 institutions participating in Korean Cancer Study Group (KCSG) Rare Cancer Committee. Results A total of 37 patients were identified. Of these 37 patients, 6 received locoregional therapy as a first‐line treatment. In 31 patients who received systemic chemotherapy as a first‐line treatment, platinum‐based chemotherapy (n = 22) achieved an objective response rate (ORR) of 45.5% and a median progression‐free survival (PFS) of 7.89 months. Taxane‐based chemotherapy (n = 8) achieved an objective response rate of 62.5% and median PFS of 9.73 months. In second‐line chemotherapy, platinum‐based chemotherapy (n = 4) had a disease control rate (DCR) of 75.0% and median PFS of 3.45 months. Taxane‐based chemotherapy (n = 8) had a DCR of 75.0% and a median PFS of 8.67 months. Six patients received anti‐human epidermal growth factor receptor 2 (HER2) antibody during first‐ and second‐line chemotherapy. Overall, systemic chemotherapy combined with anti‐HER2 antibody had an ORR of 100% and a median PFS of 13.31 months. The ORR and PFS with systemic chemotherapy combined with trastuzumab was better than platinum‐ and taxane‐based chemotherapy only. Conclusions Due to its rarity, advanced or metastatic EMPD still has no established standard treatment. Results of our study indicate that the combination of trastuzumab with taxane has longer survival than trastuzumab monotherapy or conventional platinum‐ or taxane‐based chemotherapy.

Background Several previous studies have reported that quality of life (QoL) in hemodialysis patients affects mortality. However, the 36-item Short Form Health Survey, which has been used mainly in previous studies, is complicated in terms of questionnaire composition and interpretation. This study aimed to identify the impact of QoL on mortality in hemodialysis patients using an easier and simpler diagnostic tool. Methods This retrospective study included 160 hemodialysis patients. QoL was evaluated using the World Health Organization Quality of Life Questionnaire-Brief version (WHOQOL-BREF). Psychosocial factors were evaluated using the Hospital Anxiety and Depression Scale, Multidimensional Scale of Perceived Social Support, Montreal Cognitive Assessment, and Pittsburgh Sleep Quality Index. We also evaluated medical factors, such as dialysis adequacy and laboratory results. Results The mean hemodialysis vintage was 70.7±38.0 months. The proportion of patients who were elderly was higher in the mortality group than in the surviving group, and the Charlson Comorbidity Index score was also higher in the former group. Of the four domains of the WHOQOL-BREF, the physical health and psychological scores of the mortality group were significantly lower than those of the survival group. When the score in the physical health domain or psychological domain was ≤10, the 10-year mortality rate after hemodialysis initiation increased by approximately 2.3- and 2-fold, respectively. Conclusion QoL may have a significant effect on mortality in patients undergoing hemodialysis. The WHOQOL-BREF is an instrument that can measure QoL relatively easily and can be used to improve the long-term prognosis of patients undergoing hemodialysis.

Abstract The surgical range of breast cancer that shows pathologic complete response (pCR) without change in microcalcifications after neoadjuvant chemotherapy (NAC) is controversial. This study examined whole breast specimens to evaluate the necessity of mastectomy in those cases. The viability of cancer cells around the residual microcalcification was assessed using prospectively collected breast samples to confirm the presence or absence of cancer cells. A total of 144 patients with breast cancer and diffuse microcalcifications were classified into the reduced mass with no change in residual microcalcification (RESMIN, n = 49) and non-RESMIN (n = 95) groups. Five specimens were prospectively evaluated to assess the presence of viable cancer cells around the microcalcification. Tumor responses to NAC were significantly better with high pCR rates in the RESMIN group (p = 0.005 and p = 0.002). The incidence of human epidermal growth factor receptor 2-positive and triple-negative breast cancers was significantly high in the RESMIN group (p = 0.007). Although five (10.2%) patients had locoregional recurrence in the RESMIN group, no local recurrence in the breast was reported. Although pCR was highly estimated, residual cancers, including ductal carcinoma in situ, remained in 80% cases. Therefore, given the weak scientific evidence available currently, complete removal of residual microcalcifications should be considered for oncologic safety.

Abstract The pathogenic variant (PV) or likely pathogenic variant (LPV) BRCA1/2 gene is strongly associated with hereditary breast or ovarian cancer. Therefore, it is important to screen blood relatives to establish preventive modalities and surveillance. This study evaluated the feasibility of targeted cascade genetic testing for family members of BRCA1/2 gene PV or LPV carriers. We screened 18 families for BRCA1/2 gene status via the conventional cascade genetic test (n = 9) and targeted cascade genetic test (n = 9), which targeted the exon region wherein the index patient showed PV or LPV. The pedigree and clinicopathologic characteristics were reviewed and analyzed. All index patients were diagnosed with breast cancer, while the third family members were all healthy. In the conventional cascade test group, 3 index patients and 3 family members had the BRCA1/2 gene PV or LPV. In the targeted cascade test group, 5 family members had same type of BRCA1/2 gene PV or LPV as their index patients. Two families had an identical string of BRCA1/2 gene PV or LPV. Although the targeted cascade genetic test cannot completely characterize the BRCA1/2 gene, it is sufficient for determining its PV or LPV status. This limited genetic test can be used for family members of PV or LPV carriers.

Background Cancer patients have been disproportionally affected by the coronavirus disease 2019 (COVID-19) pandemic, with high rates of severe outcomes and mortality. Fever is the most common symptom in COVID-19 patients. During the COVID-19 pandemic, physicians may have difficulty in determining the cause of fever (COVID-19, another infection, or cancer fever) in cancer patients. Furthermore, there are no specific guidelines for managing cancer patients with fever during the COVID-19 pandemic. Thus, this study evaluated the clinical characteristics and outcomes of cancer patients with fever during the COVID-19 pandemic. Methods This study retrospectively reviewed the medical records of 328 cancer patients with COVID-19 symptoms (fever) admitted to five hospitals in Daegu, Korea from January to October 2020. We obtained data on demographics, clinical manifestations, laboratory test results, chest computed tomography images, cancer history, cancer treatment, and outcomes of all enrolled patients from electronic medical records. Results The most common COVID-19-like symptoms were fever (n=256, 78%). Among 256 patients with fever, only three (1.2%) were diagnosed with COVID-19. Most patients (253, 98.8%) with fever were not diagnosed with COVID-19. The most common solid malignancies were lung cancer (65, 19.8%) and hepatobiliary cancer (61, 18.6%). Twenty patients with fever experienced a delay in receiving cancer treatment. Eighteen patients discontinued active cancer treatment because of fever. Major events during the treatment delay period included death (2.7%), cancer progression (1.5%), and major organ dysfunction (2.7%). Conclusion Considering that only 0.9% of patients tested for COVID-19 were positive, screening for COVID-19 in cancer patients with fever should be based on the physician’s clinical decision, and patients might not be routinely tested.

Abstract. Rationale:. Double-J stents (DJSs) are urologic devices widely used for urinary tract obstruction treatment. Perinephric abscess is a condition with purulent accumulation resulting from urinary tract infection retained between the renal capsule and Gerota's fascia. Emphysematous urinary tract infection in patients with a forgotten DJS is extremely rare. Herein, we report a case of emphysematous perinephric abscess as a complication in a 56-year-old non-diabetic woman who neglected a 10-year-old DJS placed for obstructive uropathy treatment. Patient concerns:. The patient presented with fever and abdominal pain that persisted for 4 days. Laboratory examinations showed leukocytosis, hypoalbuminemia (2.3 g/dL), and elevated C-reactive protein level (305.5 mg/L) with no azotemia. Diagnosis:. Abdominal computed tomography scan revealed a DJS with encrustation and multiple stones in the right kidney as well as a perinephric abscess with gas formation. Interventions:. Intravenous administration of piperacillin/tazobactam was initiated immediately and percutaneous catheter drainage was performed. Extended-spectrum beta-lactamase-producing Escherichia coli was identified on abscess culture and antibiotics were switched to meropenem, resulting in gradual improvement of the inflammatory lesion. The patient was referred to the urology department for retained DJS removal and vesicolitholapaxy. A piece of fractured stent was removed via open ureterolithotomy. Outcomes:. Since discharge on hospital day 42, she has been under regular follow-up, and the surgical wound has been healing with no significant sequelae. Lessons:. Prompt medical therapy for inflammation and thorough urologic correction of the stent-induced structural deformities are crucial in long-term neglected DJS and resulting emphysematous perinephric abscess. Patients who undergo DJS placement should be systematically followed up to prevent potential neglect of device management.

Background/Aims For metastatic renal cell carcinoma (RCC), various prognostic scoring systems have been developed. However, owing to the low prevalence of nonclear cell RCC, the three most commonly used tools were mainly developed based on patients with clear cell histology. Accordingly, this study applied three prognostic models to Korean non-clear cell RCC patients treated with first-line temsirolimus. Methods (59.5%) were assigned to the poor prognosis groups of the Memorial Sloan-Kettering Cancer Center (MSKCC This study analyzed data for 74 patients with non-clear cell RCC who were treated with temsirolimus as the first-line therapy at eight medical centers between 2011 and 2016. The receiver-operating characteristic (ROC) curves for the different prognostic models were analyzed. Results Twenty-seven (36.5%), 24 (32.4%), and 44 patients), International Metastatic RCC Database Consortium (IMDC), and Advanced Renal Cell Carcinoma (ARCC) risk stratification models, respectively. All three prognostic models reliably discriminated the risk groups to predict progression-free survival and overall survival (p < 0.001). The area under the ROC curve (AUC) for progression and survival was highest for the ARCC model (0.777; 0.734), followed by the IMDC (0.756; 0.724) and the MSKCC (0.742; 0.712) models. Furthermore, the sensitivity and specificity for predicting progression were highest with the ARCC model (sensitivity 63.6%, specificity 85.7%), followed by the MSKCC (sensitivity 58.2%, specificity 86.5%) and the IMDC models (sensitivity 56.4%, specificity 85.7%). Conclusions All three prognostic models accurately predicted the survival of the non-clear cell RCC patients treated with temsirolimus as the first-line therapy. Furthermore, the ARCC risk model performed better than the other risk models in predicting survival.

Abstract Background Pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) is a predictor of improved outcomes in breast cancer. In patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2) -negative breast cancer, the response to NAC is variable and mostly limited. This study was an investigation of the predictive relevance of parameters of 18F-FDG PET/CT for the pCR to NAC in patients with HR-positive, HER2–negative breast cancer. Methods: AH total of 109 consecutive HR-positive and HER2-negative breast cancer patients who were treated with NAC were enrolled in this prospective cohort study. The relationships between pretreatment 18F-FDG PET/CT and clinical outcomes including pathologic response to NAC were evaluated. Results: All patients finished their planned NAC cycles and eight patients (7.3%) achieved pCR. In the receiver operating characteristic (ROC) curve analysis, pSUVmax exhibited high sensitivity and specificity for predicting pCR. Furthermore, multivariate logistic regression analysis revealed pSUVmax as a predictive factor for pCR (hazard ratio = 17.452; 95% CI = 1.847–164.892; p = 0.013). Conclusion The results of this study suggest that 18F-FDG PET/CT pSUVmax is a predictive factor for pCR of HR-positive, HER2-negative breast cancer to NAC.

Students with reading disabilities generally know fewer words (breadth) with less in-depth knowledge of those words (depth) than typical students. The present study examined the effects of a "moderately rich vocabulary instruction" in which both breadth and depth of vocabulary are addressed. Nineteen U.S. 4th- and 5th-grade students with reading disabilities learned 12 words in the moderate-encounter condition, where students practiced the target words six times in the context of rich vocabulary instructional activities. The results showed that students with reading disabilities remembered more taught word definitions and understood more sentences that contained taught words than those from the control condition. The findings suggest that providing moderately rich vocabulary instruction with a moderate number of rich vocabulary practices can yield good word learning and sentence comprehension containing target words for students with reading difficulties.

The purpose of the study was to describe and analyze the self-efficacy of South Korean adapted physical education (APE) majors in teaching persons with disabilities. The research design was a qualitative descriptive case study. The participants were five APE majors (four men and one woman, age ranged from 20 to 25) attending a university in South Korea. The data sources were interviews, program curriculum reviews, and a researcher's journal entries; and analyzed using thematic analysis. Four themes emerged, which were: (a) determinants of self-efficacy, (b) relationships with APE faculty, (c) increased awareness, and (d) I am not confident. Findings exposed APE majors as more likely to gain confidence after volunteering to work with persons with disabilities and developing relationships with them. The results showed the importance of integrating hands-on practicum teaching experiences in APE courses for the majors to develop their positive self-efficacy in teaching persons with disabilities.

ObjectivesThe purpose of this study was to analyze the records of patients diagnosed with essential hypertension using association rule mining (ARM).MethodsPatients with essential hypertension (ICD code, I10) were extracted from a hospital's data warehouse and a data mart constructed for analysis. Apriori modeling of the ARM method and web node in the Clementine 12.0 program were used to analyze patient data.ResultsPatients diagnosed with essential hypertension totaled 5,022 and the diagnostic data extracted from those patients numbered 53,994. As a result of the web node, essential hypertension, non-insulin dependent diabetes mellitus (NIDDM), and cerebral infarction were shown to be associated. Based on the results of ARM, NIDDM (support, 35.15%; confidence, 100%) and cerebral infarction (support, 21.21%; confidence, 100%) were determined to be important diseases associated with essential hypertension.ConclusionsEssential hypertension was strongly associated with NIDDM and cerebral infarction. This study demonstrated the practicality of ARM in co-morbidity studies using a large clinic database.

This paper describes two platforms for autonomous sensing microsystems that are intended for deployment in chemically corrosive environments at elevated temperatures and pressures. Following the deployment period, the microsystems are retrieved, recharged, and interrogated wirelessly at close proximity. The first platform is the Michigan Micro Mote for High Temperature (M3HT), a chip stack 2.9 × 1.1 × 1.5 mm3 in size. It uses RF communications to support pre-deployment and post-retrieval functions, and it uses customized electronics to achieve ultralow power consumption, permitting the use of a chip-scale battery. The second platform is the Environmental Logging Microsystem (ELM). This system, which is 6.5 × 6.3 × 4.5 mm3 in size, uses the smallest suitable off-the-shelf electronic and battery components that are compatible with assembly on a flexible printed circuit board. Data are stored in non-volatile memory, permitting retrieval even after total power loss. Pre-deployment and post-retrieval functions are supported by optical communication. Two types of encapsulation methods are used to withstand high pressure and corrosive environments: an epoxy filled volume is used for the M3HT, and a hollow stainless-steel shell with a sapphire lid is used for both the M3HT and ELM. The encapsulated systems were successfully tested at temperature and pressure reaching 150 °C and 10,000 psi, in environments of concentrated brine, oil, and cement slurry. At elevated temperatures, the limited lifetimes of available batteries constrain the active deployment period to several hours.

Background and aims: eBooks have become a ubiquitous presence in many classrooms today. Yet, empirical evidence on literacy development has not been well produced, especially for children with autism spectrum disorder (ASD). This mixed-method case study aimed to explore how four children with ASD interact with ebooks and printed books with parents at home. Methods: Four children (age 5-7 years) with ASD and their parents read one animated ebook and another printed book over four separate sessions. Parents also explained preselected word meanings to their children. In this mixed-method case study, we examined multiple quantitative and qualitative sources of evidence related to reading with parents at home. Results: Quantitatively, all four children with ASD learned more word meanings from ebook than from the printed book, and three demonstrated a higher engagement with ebook than the printed book reading. Qualitatively, the majority of parents felt their children's engagement was higher with ebook than with printed book. Children with ASD tend to have tactile-related experiences while reading the printed book and auditory-related experiences during the ebook reading. Qualitative data also demonstrated a particular feature reported to be beneficial in previous research could be distracting for some children with ASD. Implications: When parents are trained to explain critical word meanings to their children, animated ebooks can effectively improve the meaning-making skills of children with ASD. Findings also highlight the importance of individualized attention when choosing and using ebooks for children with ASD.

Cavitation is a common issue in pumps, causing a decrease in pump head, a fall in volumetric efficiency, and an intensification of outlet flow pulsation. It is one of the main hazards that affect the regular operation of the pump. Research on pump cavitation mainly focuses on mixed flow pumps, jet pumps, external spur gear pumps, etc. However, there are few cavitation studies on external herringbone gear pumps. In addition, pumps with different working principles significantly differ in the flow and complexity of the internal flow field. Therefore, it is urgent to study the cavitation characteristics of external herringbone gear pumps. Compared with experimentalmethods, visual research and cavitation area identification are achieved through computation fluid dynamic (CFD), and changing the boundary conditions and shape of the gear rotor is easier. The simulation yields a head error of only 0.003% under different grid numbers, and the deviation between experimental and simulation results is less than 5%. The study revealed that cavitation causes flow pulsation at the outlet, and the cavitation serious area is mainly distributed in the meshing gap and meshing area. Cavitation can be inhibited by reducing the speed, increasing the inlet pressure, and changing the helix angle can be achieved. For example, when the inlet pressure is 5 bar, the maximumgas volume fraction in themeshing area is less than 50%. These results provide a reference for optimizing the design and finding the optimal design parameters to reduce or eliminate cavitation. [ABSTRACT FROM AUTHOR]

Physiological needs evoke motivational drives that produce natural behaviors for survival. In previous studies, the temporally intertwined dynamics of need and motivation have made it challenging to differentiate these two components. On the basis of classic homeostatic theories, we established a normative framework to derive computational models for need-encoding and motivation-encoding neurons. By combining the model-based predictions and naturalistic experimental paradigms, we demonstrated that agouti-related peptide (AgRP) and lateral hypothalamic leptin receptor (LHLepR) neuronal activities encode need and motivation, respectively. Our model further explains the difference in the dynamics of appetitive behaviors induced by optogenetic stimulation of AgRP or LHLepR neurons. Our study provides a normative modeling framework that explains how hypothalamic neurons separately encode need and motivation in the mammalian brain. [ABSTRACT FROM AUTHOR]

Objective: Bipolar disorder (BD) is marked by significant change in mood and energy levels with sleep disturbance a common feature, resulting in diminished quality of life and impaired daily functioning. This study assessed the association between BD-polygenic risk scores (PRS) and hypnotics in bipolar I disorder (BD-I) patients. Methods: Large-sample data were collected from the genome-wide association study of a multicenter Bipolar Genomic Study, and 1,394 BD-I patients with available medication information were divided into two groups depending on whether they used hypnotics or not. The Diagnostic Interview for Genetic Studies (DIGS) score was used to assess the clinical manifestations and function of the participants and the association between the use of hypnotics and genetic risk was analyzed. Results: Of the 1,394 total participants, 556 (40%) patients received hypnotics, mostly benzodiazepines, administered singly or in combination with other sleeping agents such as, Z-drugs, melatonin-related drugs, and trazodone. The DIGS score was significantly higher for negative categories in the group prescribed hypnotics as was the BD-PRS score, according to the four p value thresholds (p = 0.3, 0.2, 0.1, and 0.05). Logistic regression analysis confirmed a statistically significant association between the BD-PRS and hypnotic use. Conclusion: Our results suggest an association between hypnotic use and genetic susceptibility to BD. Sleep disturbances in participants were based on the prescription status of hypnotics supporting the hypothesis that sleep disturbances may be associated with genetic aspects of BD-I. Further genetic studies on genetic overlaps between BD and specific phenotypes or medication responses are required. [ABSTRACT FROM AUTHOR]

Background: The incidence of monoclonal gammopathy of undetermined significance (MGUS) in the population of over 50-year-olds is approximately 3% and increases with age. The association between MG and neuropathy has been of interest for several years, but the causal relationship has not yet been clarified. Methods: For 682 patients who visited the Department of Neurology and requested tests for MG work-up, we retrospectively collected demographic and clinical information, such as age, gender, diagnosis, and neurologic and laboratory test results, from their medical records. Results: Out of a total of 682 patients who were suspected of neuropathy and tested for monoclonal gammopathy (MG), twelve (1.76%) showed MG on their serum protein electrophoresis. The most common form was IgM-κ with five patients, followed by IgG-κ, IgG-λ, and biclonal IgG-λ and IgA-κ. The results of the immunoglobulin quantitation test and free light chain assay showed that involved M-protein values in these patients were increased. Some patients were positive for anti-myelin-associated glycoprotein (MAG) antibody, anti-GD1b IgM antibody, anti-GM1 IgG & IgM antibody, and anti-cardiolipin IgM antibody. Also, some had antinuclear antibody (ANA) or antineutrophil cytoplasmic antibody (ANCA). Conclusions: In the future, it is necessary to investigate the pathogenic relationship between M-protein and autoantibodies in patients with neuropathies. [ABSTRACT FROM AUTHOR]

Background: Detecting monoclonal protein (M-protein), a hallmark of plasma cell disorders, traditionally relies on methods such as protein electrophoresis, immune-electrophoresis, and immunofixation electrophoresis (IFE). Mass spectrometry (MS)-based methods, such as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization-quadrupole time-of-flight (ESI-qTOF) MS, have emerged as sensitive methods. We explored the M-protein-detection efficacies of different MS techniques. Methods: To isolate immunoglobulin and light chain proteins, six types of beads (IgG, IgA, IgM, kappa, lambda, and mixed kappa and lambda) were used to prepare samples along with CaptureSelect nanobody affinity beads (NBs). After purification, both MALDI-TOF MS and liquid chromatography coupled with Synapt G2 ESI-qTOF high-resolution MS analysis were performed. We purified 25 normal and 25 abnormal IFE samples using NBs and MALDI-TOF MS (NB-MALDI-TOF). Results: Abnormal samples showed monoclonal peaks, whereas normal samples showed polyclonal peaks. The IgG and mixed kappa and lambda beads showed monoclonal peaks following the use of daratumumab (an IgG/kappa type of monoclonal antibody) with both MALDI-TOF and ESI-qTOF MS analysis. The limits of detection for MALDI-TOF MS and ESI-qTOF MS were established as 0.1 g/dL and 0.025 g/dL, respectively. NB-MALDI-TOF and IFE exhibited comparable sensitivity and specificity (92% and 92%, respectively). Conclusions: NBs for M-protein detection, particularly with mixed kappa-lambda beads, identified monoclonal peaks with both MALDI-TOF and ESI-qTOF analyses. Qualitative analysis using MALDI-TOF yielded results comparable with that of IFE. NB-MALDI-TOF might be used as an alternative method to replace conventional tests (such as IFE) to detect M-protein with high sensitivity. [ABSTRACT FROM AUTHOR]

Background: Uteroglobin is a multifunctional protein with anti-inflammatory properties. Studies have revealed the importance of inflammation in type 2 diabetes mellitus (T2D) pathogenesis. Here, we investigated the relationship between uteroglobin and T2D. Methods: We performed diagnostic tests for diabetes in subjects who had not been diagnosed with or treated for T2D. We established three groups, containing those with normal glucose tolerance (NGT), prediabetes and T2D, consisting of 80 people each, and compared their uteroglobin levels. In addition, 28 patients newly diagnosed with T2D were treated with metformin for 12 weeks, and 63 patients newly diagnosed with dyslipidaemia during the treatment for T2D were treated with statin for 12 weeks. Results: This study showed that uteroglobin levels were significantly lower in prediabetes and T2D groups than in the NGT group. Uteroglobin levels were not significantly correlated with other metabolic parameters, except BMI, HOMA-b and eGFR. In the group treated with metformin or statin, uteroglobin levels increased after treatment compared to before treatment. Conclusions: Uteroglobin is a sensitive factor that was decreased even in prediabetes and increased upon treatment with drugs with anti-inflammatory effects. Uteroglobin is a potential early biomarker that reflects a chronic inflammatory condition in T2D. [ABSTRACT FROM AUTHOR]

Introduction: Abnormalities in the hippocampus have been extensively reported in schizophrenia research. However, inconsistent findings exist, and how structural and functional abnormalities of the hippocampus are associated with clinical symptoms in schizophrenia, especially concerning clozapine treatment, remains uncertain. Methods: We recruited 52 patientswith schizophrenia, eachwith an illness duration of at least 5 years, and categorized them based on clozapine treatment. T1- weighted images and resting-state functional magnetic resonance imaging scans were obtained and analyzed to perform group comparisons of the structural and functional changes in the hippocampus. Volumes of the hippocampal subregions, as well as resting-state functional connectivity maps from these areas were compared between the groups. Associations with clinical symptoms, including the severity of psychiatric symptoms and cognitive functions, were investigated. Results: The clozapine group (n=23) exhibited smaller volumes in several hippocampal subregions, including the CA1, CA4, granule cell and molecular layers of the dentate gyrus, compared to the non-clozapine group (n=29). Seven clusters with significant group differences in functional connectivity with these hippocampal subregions were identified, with six of these clusters showing increased functional connectivity in the clozapine group. The reduced volumes of the hippocampal subregions were moderately associated with the severity of negative symptoms, general intelligence, and executive function. Discussion: Patients with schizophrenia undergoing clozapine treatment exhibited smaller volumes in the hippocampal subregions, which were moderately associated with negative symptoms and cognitive functions, compared to those without clozapine treatment. [ABSTRACT FROM AUTHOR]

Background: Epinephrine (EPI) or norepinephrine (NOR) is widely used to treat cardiovascular collapse during lipid emulsion (LE) resuscitation for drug toxicity. However, the effect of LE on the vasoconstriction caused by EPI or NOR remains unknown. The purpose of this study was to examine the effect of an LE (Intralipid) on the vasoconstriction caused by EPI and NOR in isolated rat aorta. Methods: The effect of LE on the vasoconstriction caused by EPI or NOR in isolated rat aorta was examined. Additionally, the effect of LE on the calcium increase caused by EPI or NOR was investigated. The distribution constant (KD: lipid to aqueous phase) of EPI or NOR between a LE (1%) and an aqueous phase was determined. Results: LE (1 and 2%) did not significantly alter vasoconstriction caused by EPI or NOR in isolated endothelium-intact aorta. Moreover, the LE did not significantly alter the increased calcium level caused by EPI or NOR. The log KD of EPI in the LE (1%) was -0.71, -0.99, and -1.00 at 20, 50, and 100 mM ionic strength, respectively. The log KD of NOR in the LE (1%) was -1.22, -1.25, and -0.96 at 20, 50, and 100 mM ionic strength, respectively. Conclusions: Taken together, the Intralipid emulsion did not alter vasoconstriction induced by EPI or NOR that seems to be due to the hydrophilicity of EPI or NOR, leading to sustained hemodynamic support produced by EPI or NOR used during LE resuscitation. [ABSTRACT FROM AUTHOR]

Among the family of GPCR kinases (GRKs) that regulate receptor phosphorylation and signaling termination, G-protein-coupled receptor kinase 2 (GRK2) binds to HSP90 in response to hypoxia or other stresses. In this study, we investigated the effects of GRK2 knockdown and inhibition on porcine embryonic development from the zygote stage. Immunofluorescence and western blotting were used to determine the localization and expression, respectively, of GRK2 and related proteins. First, GRK2 and p-GRK2 were expressed in both the cytoplasm and membrane and co-localized with HSP90 on the membrane. The mRNA level of GRK2 increased until the 8C-morula stage, suggesting that GRK2 may play an essential role during the early development of the porcine embryos. GRK2 knockdown reduced porcine embryo development capacity and led to significantly decreased blastocyst quality. In addition, inhibition of GRK2 also induced poor ability of embryo development at an early stage, indicating that GRK2 is critical for embryonic cleavage in pigs. Knockdown and inhibition of GRK2 reduced HSP90 expression, AKT activation, and cAMP levels. Additionally, GRK2 deficiency increased LC3 expression, suggesting enhanced autophagy during embryo development. In summary, we showed that GRK2 binds to HSP90 on the membrane to regulate embryonic cleavage and AKT activation during embryonic development in pigs. [ABSTRACT FROM AUTHOR]

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D. [ABSTRACT FROM AUTHOR]

Background We aimed to investigate the radiation dose to the eye lens (lens dose) during cerebral angiography and to evaluate the effectiveness of the lens dose reduction protocol for 3-dimensional rotational angiography (3D-RA) in reducing overall lens dose exposure. Methods We conducted a randomized, controlled clinical trial at a tertiary hospital with patients undergoing cerebral angiography. The lens dose reduction protocol in 3D-RA involved raising the table to position the patient's eye lens away from the rotation axis. The lens dose was estimated by measuring the entrance surface air kerma using a photoluminescent glass dosimeter. The lens doses of 3D-RA, overall examination, and image quality were analyzed and compared between the two groups. Results A total of 20 participants (mean age, 58±9.4 years; including 12 men [60%]) were enrolled and randomly assigned to either the conventional group or the dose reduction group. The median lens dose in 3D-RA was significantly lower in the dose reduction group compared with the conventional group (1.1 mGy vs 4.5 mGy, p<0.001). The total dose was significantly lower in the dose reduction group (median of 7.5 mGy vs 10.2 mGy, p=0.003). In the conventional group, 3D-RA accounted for 46% of the total lens dose, while in the dose reduction group, its proportion decreased to 16%. No significant differences were observed in the image quality between the groups. Conclusion The lens dose reduction protocol resulted in a significant reduction in the lens dose of the 3D-RA as well as entire cerebral angiography, while maintaining the image quality. [ABSTRACT FROM AUTHOR]

Probiotics and their derivatives offer significant health benefits by supporting digestive health, boosting the immune system, and regulating the microbiomes not only of the internal gastrointestinal track but also of the skin. To be effective, probiotics and their derivatives must exhibit robust antimicrobial activity, resilience to adverse conditions, and colonization capabilities in host tissues. As an alternative to animal-derived probiotics, plant-derived lactic acid bacteria (LAB) present promising advantages, including enhanced diversity and tolerance to challenging environments. Our study focuses on exploring the potential of plant-derived LAB, particularly from the medicinal plant Centella asiatica, in improving skin conditions. Through a bacterial isolation procedure from C. asiatica leaves, Enterococcus rotai CMTB-CA6 was identified via 16S rRNA sequencing, whole genome sequencing, and bioinformatic analyses. Based on genomic analysis, antimicrobial-resistance and virulence genes were not detected. Additionally, the potential functions of E. rotai CMTB-CA6 were characterized by its lysates' ability to regulate skin microbes, such as stimulating the growth of Staphylococcus epidermidis while inhibiting that of Cutibacterium acnes, to restore the viability of human dermal fibroblasts under inflammatory conditions, and to demonstrate effective antioxidant activities both in a cellfree system and in human dermal fibroblasts. Our investigation revealed the efficacy of E. rotai CMTB-CA6 lysates in improving skin conditions, suggesting its potential use as a probiotic-derived agent for skin care products. Considering the ecological relationship between plant-inhabited bacteria and their host plants, we suggest that the utilization of E. rotai CMTB-CA6 strain for fermenting its host plant, C. asiatica, could be a novel approach to efficiently enriching bioactive molecules for human health benefits. [ABSTRACT FROM AUTHOR]

Study Design. A retrospective study. Objectives. To analyze factors associated with rod fracture (RF) in adult spinal deformity (ASD), and to assess whether the accessory rod (AR) technique can reduce RF occurrence in deformity correction in the setting of minimally invasive lateral lumbar interbody fusion (LLIF). Summary of Background Data. Instrumentation failure is the most common reason for revision surgery in ASD. Several RF reduction methods have been introduced. However, there are insufficient studies on postoperative RF after deformity correction using minimally invasive LLIF. Materials and Methods. This study included 239 patients (average age 71.4 y and a minimum 2-year follow-up) with ASD who underwent long-segment fusion from T10 to sacrum with sacropelvic fixation. Patients were classified into the non-RF group and the RF group. After logistic regression analysis of the risk factors for RF, subgroup analyses were performed: pedicle subtraction osteotomy (PSO) with two-rod (P2 group) versus PSO with two-rod and AR (P4 group), and LLIF with two-rod (L2 group) versus LLIF with two-rod and AR (L4 group). Results. RF occurred in 50 patients (21%) at an average of 25 months. RF occurred more frequently in patients who underwent PSO than in those who underwent LLIF (P = 0.002), and the use of the AR technique was significantly higher in the non-RF group (P< 0.05). Following logistic regression analysis, pre-operative PI-LL mismatch, PSO, and the AR technique were associated with RF. In subgroup analyses, RF incidence was 65% (24/37 cases) of the P2 group, 8% (4/51 cases) of the P4 group, and 21% (22/105 cases) of the L2 group. In the L4 group, there was no RF. Conclusion. Minimally invasive multilevel LLIF with the AR technique is capable of as much LL correction as conventional PSO and appears to be an effective method for reducing RF. [ABSTRACT FROM AUTHOR]