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In this paper, a switching method is proposed for power device temperature-balancing in a phase-shift full-bridge (PSFB) converter. PSFB is commonly used for applications that require high efficiency, because a zero-voltage switching (ZVS) operation is possible on the primary-side. In PSFB, the circulation current complicates ZVS under a light-load condition, which generates heat. Meanwhile, the heat generated in PSFB creates a temperature deviation between the lagging leg and the leading leg, which shortens the lifetime of the power device, thereby reducing system reliability and efficiency. To solve this problem, previous studies applied a pulse-width modulation (PWM) switching method for light and medium loads, and a phase-shift switching method for the region where ZVS is possible. Although this method has the advantage of easy control, the maximum temperature of the legs of the PSFB increases with medium loads. In this paper, a temperature-balancing algorithm—a temperature-balance control—is proposed to decrease the leg temperature using switching based on position exchanges of the leading leg and lagging leg along with PWM switching. Temperature-balance control minimizes leg temperature deviation under light load conditions. The proposed control method provides a minimum temperature difference between the two legs and high efficiency.

Abstract DNA-loop extrusion is considered to be a universal principle of structural maintenance of chromosome (SMC) proteins with regard to chromosome organization. Despite recent advancements in structural dynamics studies that involve the use of cryogenic-electron microscopy (Cryo-EM), atomic force microscopy (AFM), etc., the precise molecular mechanism underlying DNA-loop extrusion by SMC proteins remains the subject of ongoing discussions. In this context, we propose a scrunching model that incorporates the anisotropic motion of SMC folding with a baton-pass mechanism, offering a potential explanation of how a “DNA baton” is transferred from the hinge domain to a DNA pocket via an anisotropic hinge motion. This proposed model provides insights into how SMC proteins unidirectionally extrude DNA loops in the direction of loop elongation while also maintaining the stability of a DNA loop throughout the dynamic process of DNA-loop extrusion.

Abstract Chromosomal phase separation is involved in a broad spectrum of chromosome organization and functional processes. Nonetheless, the intricacy of this process has left its molecular mechanism unclear. Here, we introduce the principles governing phase separation and its connections to physiological roles in this context. Our primary focus is contrasting two phase separation mechanisms: self-association-induced phase separation (SIPS) and bridging-induced phase separation (BIPS). We provide a comprehensive discussion of the distinct features characterizing these mechanisms and offer illustrative examples that suggest their broad applicability. With a detailed understanding of these mechanisms, we explore their associations with nucleosomes and chromosomal biological functions. This comprehensive review contributes to the exploration of uncharted territory in the intricate interplay between chromosome architecture and function.

Background: Early-stage lung cancers detected by low-dose computed tomography (CT) often require confirmation through invasive procedures due to the absence of endobronchial lesions. This study assesses the diagnostic utility of bronchial washing fluid (BW) sequencing, a less invasive alternative, aiming to identify patient characteristics most suited for this approach. Methods: From June 2017 to March 2018, we conducted a prospective cohort study by enrolling patients with incidental lung lesions suspected of early-stage lung cancer at two independent hospitals, and 114 were diagnosed with lung cancer while 50 were diagnosed with benign lesions. BW sequencing was performed using a targeted gene panel, and the clinical characteristics of patients detected with cancer through sequencing were identified. Results: Malignant cells were detected in 33 patients (28.9 %) through BW cytology. By applying specificity-focused mutation criteria, BW sequencing classified 42 patients (36.8 %) as having cancer. Among the cancer patients who were BW sequencing positive and BW cytology negative, 15 patients (75.0 %) showed necrosis on CT. The sensitivity of BW sequencing was particularly enhanced in patients with necrotic tumors, reaching 75 %. Conclusions: BW sequencing presents a viable, non-invasive diagnostic option for early-stage lung cancer, especially valuable in patients with necrotic lesions. By potentially reducing the reliance on more invasive diagnostic procedures, this method could streamline clinical workflows, decrease patient burden, and improve overall diagnostic efficiency.

Objectives: The objective of this study was to identify factors associated with adolescent obesity, as well as any new factors that correlated with a change in the rate of obesity over time. Methods: The study used 5-yearly data collected by the Korea Youth Risk Behavior Survey starting from the year 2006 up until 2021 (data from 2nd, 7th, 11th, and 17th surveys were analyzed). Factors such as demographics, dietary factors, health behavioral factors, and mental health factors were studied. All data were analyzed using IBM SPSS 27.0, employing chi-square tests and multiple logistic regression analysis. Results: This study included data from a total of 255,200 participants. Factors contributing to obesity varied with time. Over the survey duration of 15 years, low academic achievement, parents with low levels of education, low frequency of fruit consumption, low frequency of fast food intake, long periods of being seated, and high levels of stress were significantly associated with a high rate of obesity. Factors that showed a new correlation with an increase in obesity rates included living with single parents, low frequency of muscle strengthening exercises, and experiencing intense sadness and despair in the past year. Factors that were correlated with a change in obesity rates over time included household economic status, frequency of carbonated beverage consumption, frequency of intense physical activity, and frequency of alcohol consumption. Breakfast intake and smoking were not significantly associated with obesity rates in the 15-year period. Conclusions: While several factors associated with obesity remained consistent over time, several new factors have emerged in response to social, economic, and environmental changes contributed to a change in obesity rate over time. Therefore, to prevent and manage adolescent obesity, continuous research into the new emergent factors contributing to obesity is needed.

Abstract Current guidelines recommend that cytotoxic chemotherapy be considered first in non-small cell lung cancer (NSCLC) patients with multiple metastases, and whole-brain radiotherapy (WBRT) is not initially recommended even if brain metastases are present. However, cytotoxic chemotherapeutic agents are less effective in brain metastases due to poor blood–brain barrier permeability. We investigated the effect of WBRT in combination with cytotoxic chemotherapy on survival in NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases. From January 2005 to December 2018, histologically confirmed NSCLC patients who were EGFR, ALK, and PD-L1 negative, had an ECOG PS of 2, and had multiple metastases including brain metastases were included in this study. Patients were classified into two groups based on receiving WBRT prior to or concurrently with administration of first-line chemotherapeutic agents or receiving chemotherapy only. We compared intracranial progression-free survival (iPFS) and overall survival (OS). Of the 240 NSCLC patients with brain metastases at diagnosis and an ECOG PS of 2, 67 patients were EGFR, ALK, and PD-L1 negative with multiple metastases including brain metastases. Among those patients, 43 (64.2%) received WBRT prior to or concurrently with platinum-based chemotherapy. Patients who received WBRT prior to or concurrently with chemotherapy had better iPFS (7.7 months [4.8–10.6] vs. 3.5 months [2.1–4.9], p = 0.009) and OS (10.8 months [5.9–15.7] vs. 6.1 months [1.9–10.3], p = 0.038) than those who did not receive WBRT. In multivariate analyses, WBRT was significantly associated with iPFS (HR: 1.94 and 95% CI 1.11–3.40, p = 0.020) and OS (HR: 1.92 and 95% CI 1.08–3.42, p = 0.027). In NSCLC patients who are EGFR, ALK, and PD-L1 negative, have an ECOG PS of 2, and have multiple metastases including brain metastases, WBRT prior to or concurrently with chemotherapy could improve iPFS and OS. Therefore, the combination of WBRT with cytotoxic chemotherapy should be considered in these patients.

Background: Thickening of the inner nuclear layer (INL) or microcystic macular changes has been reported to be implicated in glaucoma patients, but their potential impact on disease progression remains unclear. We investigated the relationship between baseline microcystic macular edema in the INL or INL thickness and subsequent visual field (VF) progression in glaucoma patients. Methods: This retrospective observational study included primary open-angle glaucoma with follow-up exceeding 3 years. We identified macular cystic changes through Spectralis optical coherence tomography and measured the INL thickness using automated segmentation. Glaucoma progression was determined using the Guided Progression Analysis program of the Humphrey filed analyzer, calculating the mean deviation (MD) changes (dB/year). Results: Microcystic macular changes were observed in 12 (7.5%) of 162 patients. Patients with microcystic macular change had thicker INL thickness than those without it (p = 0.010). Progressors had a higher probability of having microcystic macular changes and a thicker average INL thickness than nonprogressors (p = 0.003, p = 0.019). Thicker INL thickness was associated with faster VF progression based on MD slope (dB/year) in the multivariate regression analysis (p = 0.045). Additionally, greater intraocular pressure (IOP) fluctuation was found to be associated with both a thicker INL and the presence of microcystic changes in the multivariate regression analysis (p = 0.003, 0.028). Conclusions: Increased macular INL thickness indicative of INL changes was linked to subsequent VF progression in glaucoma patients. These findings suggest that retinal inner nuclear change could serve as an indicator of progressive glaucoma.

Objectives: This study examines the status of iodine intake and compares the characteristics (region and thyroid disease prevalence) according to the iodine-sourced food intake pattern in Chinese adults. Methods: An online survey was conducted by enrolling 437 Chinese adults aged 18-65 years, living in three regions with different iodine nutritional statuses: Sichuan, Chongqing, and Guangdong. Results: The prevalence of thyroid diseases in Sichuan, Chongqing, and Guangdong were 12.5%, 8.5%, and 2.8%, respectively. Conversely, the proportion of people who received thyroid disease-related examinations was a mere 37.5%. Among the subjects who underwent thyroid examination, the prevalence of thyroid disease in the three regions was 32.2%, 21.8%, and 8.0%, respectively. No differences were obtained in the total iodine intake by region, but the type of iodine source foods differed. Regardless of the region, the highest iodine content was obtained from seaweed. However, the iodine content from iodized salt and other foods differed significantly by region. Factor analysis revealed three food intake patterns according to the iodine food source. The study further determined regional differences and differences in the prevalence of thyroid disease according to food intake patterns. Conclusions: High salt intake can also increase iodine intake, which is thought to have an effect on the occurrence of iodine-excess thyroid disease. Hence, efforts focused on improving salty eating habits need to be implemented.

Abstract Cholesterol is essential for neuronal activity and function. Cholesterol depletion in the plasma membrane impairs synaptic transmission. However, the molecular mechanisms by which cholesterol deficiency leads to defects in vesicle fusion remain poorly understood. Here, it is shown that cholesterol is required for Ca2+‐dependent native vesicle fusion using the in vitro reconstitution of fusion and amperometry to monitor exocytosis in chromaffin cells. Purified native vesicles are crucial for the reconstitution of physiological Ca2+‐dependent fusion, because vesicle‐mimicking liposomes fail to reproduce the cholesterol effect. Intriguingly, cholesterol has no effect on the membrane binding of synaptotagmin‐1, a Ca2+ sensor for ultrafast fusion. Cholesterol strengthens local membrane deformation and bending induced by synaptotagmin‐1, thereby lowering the energy barrier for Ca2+‐dependent fusion to occur. The data provide evidence that cholesterol depletion abolishes Ca2+‐dependent vesicle fusion by disrupting synaptotagmin‐1‐induced membrane bending, and suggests that cholesterol is an essential lipid regulator for Ca2+‐dependent fusion.

Background and Objectives: The mechanisms involved in the development of brain metastasis (BM) remain elusive. Here, we investigated whether BM is associated with spine involvement in patients with non-small-cell lung cancer (NSCLC). Materials and Methods: A consecutive 902 patients with metastatic NSCLC were included from the Inha Lung Cancer Cohort. Patients with BM at diagnosis or subsequent BM development were evaluated for both spine involvement in NSCLC and anatomic proximity of BM to the cerebrospinal fluid (CSF) space. Results: At diagnosis, BM was found in 238 patients (26.4%) and bone metastasis was found in 393 patients (43.6%). In patients with bone metastasis, spine involvement was present in 280 patients. BM subsequently developed in 82 (28.9%) of 284 patients without BM at diagnosis. The presence of spine metastasis was associated with BM at diagnosis and subsequent BM development (adjusted odd ratios and 95% confidence intervals = 2.42 and 1.74–3.37, p < 0.001; 1.94 and 1.19–3.18, p = 0.008, respectively). Most patients with spine metastasis, either with BM at diagnosis or subsequent BM, showed BM lesions located adjacent (within 5mm) to the CSF space (93.8% of BM at the diagnosis, 100% of subsequent BM). Conclusions: These findings suggest that the presence of spine involvement is a risk factor for BM development in NSCLC patients with bone metastasis.

The surface area of encapsulation around the Ahmed glaucoma valve (AGV) endplate is a critical factor in the surgical outcome as it is associated with the degree of IOP reduction. We investigated the surgical outcome of AGV implantation with an additional pericardium graft inserted adjacent to the endplate, with the intent of expanding the surface area of encapsulation. We enrolled 92 patients (92 eyes) who underwent AGV implantation. Of them, 50 patients underwent conventional surgery (termed the without-expansion group), and 42 received an additional an 8 × 6 mm pericardium graft inserted adjacent to the AGV endplate at the sub-Tenon’s space (with-expansion). The hypertensive phase was classified as mild (>21 mmHg), moderate (>25 mmHg), and severe (>30 mmHg). Six months post-surgery, the with-expansion group exhibited a lower IOP (14.90 ± 4.27 mmHg) and lower peak IOP (22.29 ± 4.95 mmHg) than the without-expansion group (17.56 ± 4.88 mmHg and 25.06 ± 6.18 mmHg, p = 0.008 and p = 0.021, respectively). The with-expansion group exhibited a relatively low rate of moderate (16.7%) and severe (4.8%) hypertensive phases compared to the without-expansion group (40.0% and 20.0%, with p = 0.014 and p = 0.031, respectively). The additional pericardium graft was associated with a reduced occurrence of moderate hypertensive phase in both univariate and multivariate analysis logistic regression analyses (p = 0.017 and p = 0.038, respectively). Endplate surface area expansion using an additional pericardium graft reduced the occurrence of moderate and severe hypertensive phases, and lower postoperative 6-month IOP could be achieved.

The major sites of metastasis in non-small cell lung cancer (NSCLC) are bones, the brain, adrenal glands, the liver, the contralateral lung, and distant lymph nodes. Solitary metastasis in an uncommon site is very rare; therefore, it has not often been reported. Identifying whether a solitary lesion is a metastatic lesion is important because it decisively influences the stage and treatment decisions. We report a series of cases of NSCLC diagnosis with uncommon solitary metastasis. (1) A 71-year-old man was diagnosed with poorly differentiated NSCLC after a bronchoscopic biopsy of a tumor in the bronchus of the right middle lobe. A hypermetabolic lesion was observed in the tail of the pancreas using positron emission tomography/computed tomography (PET/CT), and metastasis of NSCLC was confirmed using endoscopic ultrasound fine-needle aspiration (EUS-FNA). (2) A 77-year-old man was diagnosed with squamous cell carcinoma after a bronchoscopic biopsy of a tumor in the bronchus of the left upper lobe. A hypermetabolic lesion was observed in the bilateral lobes of the thyroid gland using PET/CT, and metastasis of the squamous cell carcinoma was confirmed by FNA and cytology. (3) A 79-year-old woman was diagnosed with adenocarcinoma by brushing cytology performed on the apicoposterior segmental bronchus of the left upper lobe. Hypermetabolic lesions were observed using PET/CT in the subcutaneous layer of the right back and the left breast, and metastases of adenocarcinoma were confirmed by biopsies in each lesion. These three patients were treated with platinum-based chemotherapy for stage IV lung cancer. With this case series, we recommend that, when a solitary lesion is observed in NSCLC patients, a tissue biopsy should be performed, even if the lesion is located in an organ where lung cancer metastasis is uncommon.

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.

Structural maintenance of chromosome (SMC) proteins play a key roles in the chromosome organization by condensing two meters of DNA into cell-sized structures considered as the SMC protein extrudes DNA loop. Recent sequencing-based high-throughput chromosome conformation capture technique (Hi-C) and single-molecule experiments have provided direct evidence of DNA-loop extrusion. However, the molecular mechanism by which SMCs extrude a DNA loop is still under debate. Here, we review DNA-loop extrusion studies with single-molecule assays and introduce recent structural studies of how the ATP-hydrolysis cycle is coupled to the conformational changes of SMCs for DNA-loop extrusion. In addition, we explain the conservation of the DNA-binding sites that are vital for dynamic DNA-loop extrusion by comparing Cryo-EM structures of SMC complexes. Based on this information, we compare and discuss four compelling working models that explain how the SMC complex extrudes a DNA loop. [ABSTRACT FROM AUTHOR]