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Despite widespread concern about energy imbalance due to tumor and chemotherapy-related side effects, little is known about detailed variations in energy input, metabolic rate, and physical activity. This study explored changes in energy balance components and serum biomarkers of patients with hematologic malignancies undergoing chemotherapy. Our prospective study included 40 patients with hematologic malignancies hospitalized for chemotherapy. We measured energy balance components, physical function, and serum biomarkers at baseline and weekly after chemotherapy for 3 weeks. Significant weight loss, representing negative energy balance, occurred at 2 (p = 0.002) and 3 weeks (p 0.001) post-chemotherapy. Statistically reduced oral intake was observed at 3 weeks post-chemotherapy (p = 0.040), and resting energy expenditure statistically decreased according to Harris-Benedict equation, but not to Penn State University equation. Physical function according to DEMMI score decreased significantly at 3 weeks post-chemotherapy (p = 0.002). Serum biomarker analysis demonstrated significant changes in albumin, total protein, CXCL13, and GDF15, with exception of leptin. Although conventional serum biomarkers (total protein and albumin) did not reach pathological states despite their statistical differences, subgroup analysis showed CXCL13 in weight loss group and GDF15 in reduced oral intake group were significantly changed. Over half of patients (65.0%, n = 26) suffered from energy imbalance associated with weight loss and reduced oral intake during chemotherapy. Serial laboratory results suggested that novel biomarkers (CXCL13, GDF15) could be correlated with cachexic state and reduced food intake. Monitoring clinical and serum biomarkers associated with energy balance together can help identify needs for nutritional support in patients with hematologic malignancies undergoing chemotherapy.

Although the loss of skeletal limb muscle mass and muscle strength in the elderly have been demonstrated, the aging process of the back muscles to maintain core stability is not well known. This 1-year prospective observational study aimed to investigate the natural aging course of the lumbar extensor muscles (LEMs) compared with the extremity muscles and determine whether muscle strength or mass decreases more in community-dwelling older women.Twenty-four older urban-dwelling women aged 70 years or older were initially enrolled. Their demographic variables, conventional and spinal sarcopenia indices, and functional outcome parameters were evaluated. We also measured back extensor strength, radiological parameters for spinal sagittal balance on whole-spine radiography, and volumetric parameters of the LEM on computed tomography.After the exclusion of 6 subjects, 18 older women were finally analyzed. All variables related to extremity muscle mass, muscle strength, physical performance, and LEM volume declined over the study period, but the changes were insignificant. However, back extensor strength decreased significantly (median, first, and third quartile: 35.20 [30.80, 44.00] N to 31.40 [29.25, 37.90] N, P = 0.026). Among spinal sagittal balance-related parameters, lumbar lordosis (44.25 [39.30, 47.35]° to 43.15 [31.43, 45.75]°, P = 0.043) and sagittal vertical axis (33.85 [3.57, 58.75] mm to 45.15 [25.35, 58.68] mm, P = 0.004) showed significant changes during the study.When the natural aging course of LEM in women aged 70 years or older was observed for 1 year, muscle mass decreased less than back extensor strength and spinal sagittal balance. Measurements of back extensor strength and spinal sagittal balance are necessary for the clinical evaluation of spinal aging.

Background Korea is expected to become a super-aged society in 2026, and improving nutritional status, which is directly related to health problems, is therefore important for increasing healthy life expectancy. Frailty is the most complex phenotype of aging, and leads to adverse health outcomes, disability, poor quality of life, hospitalization, and mortality. Malnutrition is a major risk factor for frailty syndrome. This study aimed to investigate the incidence of pre-frailty or frailty in the second wave (T2, 2018–2019) according to general characteristics and nutritional status in the first wave (T1, 2016–2017); and examine the longitudinal association of nutritional status in T1 and the incidence of pre-frailty or frailty in T2 among older adults living in a community. Methods A secondary data analysis was performed using the Korean Frailty and Aging Cohort Study (KFACS). Participants comprised 1125 community-dwelling older Korean adults aged 70–84 years (mean age: 75.03 ± 3.56 years; 53.8% males). Frailty was assessed using the Fried frailty index, and nutritional status was assessed using the Korean version of the Mini Nutritional Assessment Short-Form and blood nutritional biomarkers. Binary logistic regression was used to identify longitudinal associations between the nutritional status at T1 and pre-frailty or frailty at T2. Results Over the two-year follow-up period, 32.9% and 1.7% of the participants became pre-frail and frail, respectively. After the potential confounders were adjusted (sociodemographic, health behaviors, and health status characteristics), pre-frailty or frailty had a significant longitudinal association with severe anorexia (adjusted odds ratio [AOR], 4.17; 95% confidence interval [CI], 1.05–16.54), moderate anorexia (AOR, 2.31; 95% CI, 1.46–3.64), psychological stress or acute disease (AOR, 2.61; 95% CI, 1.26–5.39), and body mass index (BMI) less than 19 (AOR, 4.11; 95% CI, 1.20–14.04). Conclusions Anorexia, psychological stress, acute disease, and low BMI are the most significant longitudinal risk factors for pre-frailty or frailty in older adults. As nutritional risk factors may be preventable or modifiable, it is important to develop interventions targeting the same. Community-based health professionals in health-related fields should recognize and manage these indicators appropriately to prevent frailty among older adults living in the community.

Acid sphingomyelinase (ASM) has been implicated in neurodegenerative disease pathology, including Alzheimer’s disease (AD). However, the specific role of plasma ASM in promoting these pathologies is poorly understood. Herein, we explore plasma ASM as a circulating factor that accelerates neuropathological features in AD by exposing young APP/PS1 mice to the blood of mice overexpressing ASM, through parabiotic surgery. Elevated plasma ASM was found to enhance several neuropathological features in the young APP/PS1 mice by mediating the differentiation of blood-derived, pathogenic Th17 cells. Antibody-based immunotherapy targeting plasma ASM showed efficient inhibition of ASM activity in the blood of APP/PS1 mice and, interestingly, led to prophylactic effects on neuropathological features by suppressing pathogenic Th17 cells. Our data reveals insights into the potential pathogenic mechanisms underlying AD and highlights ASM-targeting immunotherapy as a potential strategy for further investigation.

In this study, we aimed to comprehensively characterize the microbiomes of various samples from pregnant women and their neonates, and to explore the similarities and associations between mother-neonate pairs, sample collection sites, and obstetrical factors. We collected samples from vaginal discharge and amniotic fluid in pregnant women and umbilical cord blood, gastric liquid, and meconium from neonates. We identified 19,597,239 bacterial sequences from 641 samples of 141 pregnant women and 178 neonates. By applying rigorous filtering criteria to remove contaminants, we found evidence of microbial colonization in traditionally considered sterile intrauterine environments and the fetal gastrointestinal track. The microbiome distribution was strongly grouped by sample collection site, rather than the mother-neonate pairs. The distinct bacterial composition in meconium, the first stool passed by newborns, supports that microbial colonization occurs during normal pregnancy. The microbiome in neonatal gastric liquid was similar, but not identical, to that in maternal amnionic fluid, as expected since fetuses swallow amnionic fluid in utero and their urine returns to the fluid under normal physiological conditions. Establishing a microbiome library from various samples formed only during pregnancy is crucial for understanding human development and identifying microbiome modifications in obstetrical complications.

Artificial intelligence as a screening tool for eyelid lesions will be helpful for early diagnosis of eyelid malignancies and proper decision-making. This study aimed to evaluate the performance of a deep learning model in differentiating eyelid lesions using clinical eyelid photographs in comparison with human ophthalmologists. We included 4954 photographs from 928 patients in this retrospective cross-sectional study. Images were classified into three categories: malignant lesion, benign lesion, and no lesion. Two pre-trained convolutional neural network (CNN) models, DenseNet-161 and EfficientNetV2-M architectures, were fine-tuned to classify images into three or two (malignant versus benign) categories. For a ternary classification, the mean diagnostic accuracies of the CNNs were 82.1% and 83.0% using DenseNet-161 and EfficientNetV2-M, respectively, which were inferior to those of the nine clinicians (87.0–89.5%). For the binary classification, the mean accuracies were 87.5% and 92.5% using DenseNet-161 and EfficientNetV2-M models, which was similar to that of the clinicians (85.8–90.0%). The mean AUC of the two CNN models was 0.908 and 0.950, respectively. Gradient-weighted class activation map successfully highlighted the eyelid tumors on clinical photographs. Deep learning models showed a promising performance in discriminating malignant versus benign eyelid lesions on clinical photographs, reaching the level of human observers.

Summary Background. Uterine leiomyosarcoma is a rare aggressive smooth muscle cancer with poor survival rates. RNA Polymerase I (Pol I) activity is elevated in many cancers supporting tumour growth and prior studies in uterine leiomyosarcoma revealed enlarged nucleoli and upregulated Pol I activity-related genes. This study aimed to investigate the anti-tumour potential of CX-5461, a Pol I transcription inhibitor currently being evaluated in clinical trials for several cancers, against the human uterine leiomyosarcoma cell line, SK-UT-1. Methods. SK-UT-1 was characterised using genome profiling and western blotting. The anti-tumour effects of CX-5461 were investigated using cell proliferation assays, expression analysis using qRT-PCR, and BrdU/PI based cell cycle analysis. Results. Genetic analysis of SK-UT-1 revealed mutations in TP53, RB1, PTEN, APC and TSC1 & 2, all potentially associated with increased Pol I activity. Protein expression analysis showed dysregulated p53, RB1 and c-Myc. CX-5461 treatment resulted in an anti-proliferation response, G2 phase cell-cycle arrest and on-target activity demonstrated by reduced ribosomal DNA transcription. Conclusions. SK-UT-1 was confirmed as a representative model of uterine leiomyosarcoma and CX-5461 has significant potential as a novel adjuvant for this rare cancer.

Sarcopenia is becoming prevalent in an increasing number of older adults undergoing total knee replacement (TKR) surgery. Metal implants may overestimate lean mass (LM) measured using dual-energy X-ray absorptiometry (DXA). This study aimed to examine the effects of TKR on LM measurements according to automatic metal detection (AMD) processing. The participants from Korean Frailty and Aging Cohort Study, who had underwent TKR were enrolled. A total of 24 older adults (mean age 76.4 ± 4.0 years, 92% female) were included in the analysis. The SMI with AMD processing was 6.1 ± 0.6 kg/m2, which was lower than that without AMD processing of 6.5 ± 0.6 kg/m2 (p p p

Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). We report the cryo-electron microscopy structures of Cx43 GJICh, revealing the dynamic equilibrium state of various channel conformations in detergents and lipid nanodiscs. We identify three different N-terminal helix conformations of Cx43—gate-covering (GCN), pore-lining (PLN), and flexible intermediate (FIN)—that are randomly distributed in purified GJICh particles. The conformational equilibrium shifts to GCN by cholesteryl hemisuccinates and to PLN by C-terminal truncations and at varying pH. While GJIChs that mainly comprise GCN protomers are occluded by lipids, those containing conformationally heterogeneous protomers show markedly different pore sizes. We observe an α-to-π-helix transition in the first transmembrane helix, which creates a side opening to the membrane in the FIN and PLN conformations. This study provides basic structural information to understand the mechanisms of action and regulation of Cx43 GJICh.

Background Age-related obesity and body composition changes include loss of muscle mass and increased body fat. This study aimed to investigate sex differences in the impact of sarcopenia, defined by the Asian Working Group for Sarcopenia (AWGS), on obesity in Korean older adults. Methods In this 2-year longitudinal study, 3014 participants were excluded based on AWGS sarcopenia parameters (if any one of the sarcopenic parameter criteria was satisfied), including low handgrip strength (HGS), low appendicular skeletal muscle mass index (ASMI), and low short physical performance battery (SPPB). A total of 926 non-sarcopenic participants were recruited for the study. The obese and non-obese groups were compared according to the sarcopenia parameters. The following variables were selected for obesity analysis: body mass index (BMI), waist circumference (WC), and body fat percentage. Unadjusted and fully adjusted logistic regression analyses were performed for each variable to predict sarcopenia and sarcopenic obesity according to sex. Results Among the sarcopenia parameters, reduction in ASMI was significantly lower in the obese group with high WC and percentage of body fat (PBF) in both men and women (P Conclusions Our study identified that high BMI had a protective effect on the reduction of muscle mass in men and women. However, obesity parameters including BMI, WC, and PBF were positively correlated with a lower incidence of sarcopenia only in women. Obesity in older women may have a protective effect in reducing ASMI and the incidence of sarcopenia.

The epitaxial growth of high-quality thin films provides a powerful method for the rapid preparation of new materials and discovery of materials with promising properties. Here, we report the effect of substrate temperature on the epitaxial growth of high-quality and large-area epitaxial CdTe films on GaAs(100) by molecular beam epitaxy. RHEED patterns as a function of the substrate temperature showed sharp streaky lines. A CdTe epilayer grown at 320 °C showed the narrowest full-width at half-maximum (FWHM) of 180 arcsec from (004) reflection in X-ray rocking curve measurements. The smooth and flat surface observed in the AFM image showed the excellent uniformity of the thin film, and the surface roughness decreased monotonically with the substrate temperature. From the substrate temperature dependence of the (A0, X) emission line, the luminescence intensity was found to increase with increasing substrate temperature, while the FWHM decreased with substrate temperature. Our experimental data suggest that the substrate temperature plays an important role in establishing hetero-epitaxial film growth for semiconductor devices.

Brain-derived neurotrophic factor (BDNF), an exercise-induced neurotrophin, is an important factor in memory consolidation and cognitive function. This study evaluates the association between plasma BDNF levels and frailty in community-dwelling older adults. Plasma BDNF levels were analyzed in a total of 302 individuals aged 70–84 years from the Korean Frailty and Aging Cohort Study. There were 30 (9.9%) participants with frailty. They were older and had a higher prevalence of dementia and depression than those without frailty. There were no differences in the proportion of male sex between the frail and non-frail groups. Plasma BDNF levels were significantly lower in participants with frailty than in those without frailty. The presence of frailty was significantly associated with plasma BDNF levels (odds ratio 0.508, 95% confidence interval 0.304–0.849) as well as age, hemoglobin, and the presence of dementia, and depression. After adjustment for confounding factors, the significant association between plasma BDNF and frailty was maintained (0.495, 0.281–0.874). This association remained consistent after exclusion of individuals with dementia, depression, stroke, diabetes, and osteoporosis. Plasma BDNF levels were significantly associated with frailty in community-dwelling older adults. Our study may suggest the possible role of BDNF as a novel biomarker of frailty.