Search

Abstract Background HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay. Methods A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX® test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed. Results Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value

Piezoelectricity offers an electromechanical coupling that is widely utilized in transducer applications. There has been a consistent demand for transparent piezoelectric materials for optoelectrical applications. Therefore, despite the inherent tradeoff between the transparency and the piezoelectricity, numerous strategies have been explored to develop the transparent piezoelectric materials. Nonetheless, the most transparent piezoelectric materials developed to date is either a single crystal or materials that achieve transparency via hot-press sintering, limiting its industrial applicability. Therefore, we introduce a novel piezoelectric material that ensures transparency through co-doping and pressureless sintering of polycrystalline ceramics. In this study, we employed a compositional optimization approach to enhance the synergistic effect between the transparency and the piezoelectric properties of 0.71Pb(Mg1/3Nb2/3)O3–0.29PbTiO3 (PMN–0.29PT) ceramics. By utilizing the tape casting process for mass production and large-area manufacturing, our Pb0.913La0.0145Sm0.0145(Mg1/3Nb2/3)0.71Ti0.29O3 (TP2.9) ceramics exhibited over 60% transparency and large piezoelectric coefficient (d33) of 1104 pC/N. This material holds considerable promise for a wide range of industrial applications in both the optical and electronic domains.

Background: Second-hand smoke (SHS) exposure appears to be more common among individuals with depression. However, self-report of SHS exposure is an inaccurate classification compared to confirming SHS exposure using urinary cotinine (UC). Additionally, the dose-response relationship between depression and UC is controversial. Methods: The severe stress rate and depression prevalence was estimated among 14530 Korean participants aged ≥19 years using data patient health questionnaire-9 (PHQ-9) and on UC from the Korean National Health and Nutrition Examination Survey. Measured UCs were divided into four categories: UC– (≤0.3 μg/L), UC± (0.4 μg/L–0.9 μg/L), UC+ (1.0 μg/L–11.9 μg/L), and UC++ (≥12.0 μg/L). Results: About 55.0 % participants were female and participants’ mean age was 51.1 years. Non-smokers were 80.3 %. Among non-smokers, non-SHS exposure participants (SR–) and SHS exposure participants (SR+) were 83.0 % and 17.0 %, respectively. When UC– was used as the reference subgroup, the UC++ subgroup showed a higher depression prevalence, whereas the UC ± subgroup showed a lower prevalence. In the same UC categories, the depression prevalence and severe stress rate were higher among females than among males. Furthermore, the SR + subgroup had a higher severe stress rate than the SR– subgroup. Conclusions: Our study showed a paradoxical reduction in the depression prevalence and severe stress rate in the UC ± subgroup compared to the UC– subgroup. Additionally, the dose-response relationship between the SHS exposure biomarker and the depression prevalence was not linear. Our study indicates that an emotional stress-based model may be more appropriate for explaining the relationship between depression and SHS exposure.

Abstract The human epidermal growth factor receptor-2 (HER2) enriched subtype of breast cancer is associated with early recurrence, mostly within 5 years. However, anti-HER2 therapies have improved outcomes and their benefits persist in the long term. This study aimed to determine predictive factors for late survival in patients with HER2-positive breast cancer. We analyzed 20,672 patients with HER2-positive stage I–III breast cancer. The patients were divided into two groups based on a follow-up period of 60 months. The multivariate analysis of factors associated with poor overall survival included old age, advanced pathologic tumor size stage (pT), advanced pathologic regional lymph node stage (pN), high histological grade, presence of lymphatic and vascular invasion, and HR-negative status within 60 months. In the breast cancer-specific survival (BCSS) of the > 60 months follow-up group, the hazard ratios (HRa) based on pN-negative were 3.038, 3.722, and 4.877 in pN1 (p = 0.001), pN2 (p

Background: The incidence and clinical importance of nonalcoholic fatty liver disease (NAFLD) has emerged. However, effective therapeutic strategies for NAFLD have yet to be found. Panax ginseng (P. ginseng) is a traditional herb in Eastern Asia with therapeutic effects in many chronic disorders. However, the precise effects of ginseng extract on NAFLD are currently unknown. In present study, the therapeutic effects of Rg3-enriched red ginseng extract (Rg3-RGE) on the progression of NAFLD were explored. Methods: Twelve-week-old C57BL/6 male mice were fed a chow or western diet supplemented with high sugar water solution with or without Rg3-RGE. Histopathology, immunohistochemistry, immunofluorescence, serum biochemistry, western blot analysis, and quantitative RT-PCR were used for in vivo experiment. Conditionally immortalized human glomerular endothelial cell (CiGEnC) and primary liver sinusoidal endothelial cells (LSECs) were used for in vitro experiments. Results: Eight weeks of Rg3-RGE treatment significantly attenuated the inflammatory lesions of NAFLD. Furthermore, Rg3-RGE inhibited the inflammatory infiltrate in liver parenchyma and the expression of adhesive molecules to LSECs. Moreover, the Rg3-RGE exhibited similar patterns on the in vitro assays. Conclusion: The results demonstrate that Rg3-RGE treatment ameliorates NAFLD progression by inhibiting chemotaxis activities in LSECs.

Abstract Background Most extramedullary plasmacytomas (EMPs) aresolitary and located in the head and neck region. They may also occur in the visceral parts of the body. Objectives Here, we report a case of oral EMP followed by neoplastic plasma cell metastasis to both kidneys in a neutered male Pomeranian. Methods Oral plasmacytoma recurred 11 months aftersurgical removal of an oral mass and partial maxillectomy was performed. Eighteen months after partial maxillectomy, neoplastic masses were detected in both kidneys on computed tomography. The dog died 12 months after detection of bilateral kidney neoplasms. The resected neoplastic masses were routinely processed for histopathological observation and immunohistochemistry against pan‐cytokeratin, desmin, CD3, and MUM‐1. Results The recurred mass mainly consisted of well‐differentiated plasma cells and contained a small portion of aggressive cells with malignant features. Monoclonal gammopathy was not observed on serumelectrophoresis performed to exclude multiple myeloma. The mass was composed of plasma cells with high nuclear pleomorphism and abundant mitotic figures. The neoplasm stained positive for MUM‐1 with a more aggressive morphology than in oral EMP. Conclusion Based on serum biomarker and pathological observations, a diagnosis of recurrence and metastasis of oral‐to‐renal EMP was established. To the best of our knowledge, metastasis of oral EMP into the bilateral kidneys, as described in the current case, has not been previously reported in dogs.

A 25-day-old male common bottlenose dolphin (Tursiops truncatus) died suddenly while swimming at a dolphinarium. The gross examination revealed ulceration on the dorsal and pectoral fins and rostrum. Severe congestion, hemorrhage, and edema were observed in the gastrointestinal tract, liver, mesenteric lymph nodes, lungs, and kidneys. Fibrinosuppurative arthritis of the atlantooccipital joint and extension of fibrin into the spinal canal caused compression of the spinal cord. Histopathological examination revealed tracheitis, fibrinosuppurative bronchopneumonia and enteritis. In the central nervous system, meningeal vessel congestion in the brain, and intraparenchymal hemorrhages with neurodegeneration were observed in the spinal cord. Based on the histopathological findings, representative samples, including lung, liver, mesenteric lymph node, blood obtained from the jugular vein, and fluid sample of the ascites, were inoculated on tryptic soy agar and blood agar for routine bacterial isolation. Each isolated bacterial colony was streaked aseptically onto tryptic soy agar and blood agar for pure culture. After then, polymerase chain reaction (PCR) was performed for further identification of pathogenic microorganisms. PCR identified Escherichia fergusonii, Shewanella haliotis, Enterococcus faecalis, and Staphylococcus schleiferi. E. fergusonii was considered the primary etiologic agent in this case since it was the only species identified in all representative samples. The cause of death in this animal was E. fergusonii sepsis. To the best of our knowledge, this is the first case of neonatal sepsis associated with E. fergusonii infection in a dolphin, and suggests E. fergusonii as an opportunistic pathogen associated with sepsis in dolphins.

Waste plastics are degraded into microplastics (MPs), which are easily accumulated in the human body through digestive tracts, via the food chain. Alcohol is a widely consumed chemical throughout the world with the ability to alter the intestinal barrier. For this reason, this study was aimed to investigate exact relevance between alcohol consumption and organ distributions of MPs in an ethanol feeding animal model characterized by disrupted intestinal mucosal barriers.In this study, C57BL/6 mice were separated into control, control + MP, ethanol (EtOH), and EtOH + MP groups. Mice in the EtOH group ingested a Lieber–DeCarli diet containing EtOH. Mice in the MP groups ingested 0.1 mg/kg fluorophore polymerized polystyrene microplastics via oral gavage polystyrene MPs via oral gavage. The EtOH + MP group showed higher MP accumulation in the liver than the control + MP group. The same pattern was observed in the intestines, spleen, and brain. This pattern was more prominent in the intestines, with the EtOH + MP group showing the most severe damage due to EtOH ingestion. This result suggests that the intestinal mucosa disruption caused by EtOH ingestion exacerbates MP accumulation in the organs. Moreover, hepatic steatosis was more severe in the EtOH + MP group than in the EtOH group, suggesting the secondary manifestation mediated by MP accumulation. This study reports a novel MP accumulation pattern in the body by providing novel insights into alcohol-induced gut permeability and microplastics toxicity from the perspective of gut-liver axis.

Abstract Background Programmed death‐ligand 1 (PD‐L1) has functional roles in cancer stem‐like cell (CSC) phenotypes and chemoresistance besides immune evasion. Chemotherapy is a common treatment choice for colorectal cancer (CRC) patients; however, chemoresistance limits its effectiveness of treatment. Methods We examined the role of S100A14 (SA14) in CRC by adopting PD‐L1high subpopulations within CRC cell lines and patient tumours, by establishing PD‐L1high chemoresistant CRC sublines through prolonged exposure to 5‐fluorouracil/oxaliplatin‐based chemotherapy in vitro and in vivo, and by analysing a public database. Results We identified a novel function of SA14 as a regulator of immune surveillance, major CSC phenotypes, and survival capacity under hostile microenvironments, including those harbouring chemotherapeutics, and as a prognostic biomarker in CRC. Mechanistically, SA14 inhibits PD‐L1 expression by directly interacting with signal transducer and activator of transcription 3 (STAT3) and inducing its proteasome‐mediated degradation. While gain‐of‐SA14 causes loss of PD‐L1 expression and tumourigenic potential and sensitisation to chemotherapy‐induced apoptosis in chemoresistant CRC cells, loss‐of‐SA14 causes increases in PD‐L1 expression, tumourigenic potential, and chemoresistance in vitro and in vivo. We further show that a combinatorial treatment with chemotherapy and recombinant SA14 protein effectively induces apoptosis in PD‐L1high chemoresistant CRC cells. Conclusions Our results suggest that SA14‐based therapy is an effective strategy to prevent tumour progression and that SA14 is a predictive biomarker for anti‐PD‐L1 immunotherapy and chemotherapy in combination.

Background and objective: This study examined the relationships between the perceived severity of unwanted pregnancy and attitudes toward four contraceptive methods (condoms, oral contraceptive pills, the withdrawal method, and the rhythm method) according to gender and sexual experience among unmarried university students in Korea. Material and methods: A descriptive cross-sectional comparative study was conducted among 1,372 unmarried university students (men, n = 755; women, n = 617). This was a secondary analysis based on a prior online survey. Descriptive statistics, the Kruskal-Wallis test, pairwise comparisons using the Mann-Whitney U test with the Bonferroni correction, and logistic regression were used to analyze the data in this study. Results: Female students with sexual experience had the highest scores for the perceived severity of unwanted pregnancy. In each group defined according to gender and sexual experience, differences in attitudes toward contraceptive methods significantly influenced the perceived severity of unwanted pregnancy. Conclusion: Efforts should be made to increase the perceived severity of unwanted pregnancy among female students who have favorable attitudes toward the rhythm and withdrawal methods. Students with sexual experience who use the rhythm and withdrawal methods should be targeted for educational interventions aiming to strengthen the perceived severity of unwanted pregnancy.

Abstract Background The successful deliveries of siRNA depend on their stabilities under physiological conditions because greater in vivo stability enhances cellular uptake and enables endosomal escape. Viral-based systems appears as most efficient approaches for gene delivery but often compromised in terms of biocompatibility, patient safety and high cost scale up process. Here we describe a novel platform of gene delivery by elastin-like polypeptide (ELP) based targeting biopolymers. Results For better tumor targeting and membrane penetrating characteristics, we designed various chimeric ELP-based carriers containing a cell penetrating peptide (Tat), single or multiple copies of AP1 an IL-4 receptor targeting peptide along with coding sequence of ELP and referred as Tat-A1E28 or Tat-A4V48. These targeted polypeptides were further analyzed for its ability to deliver siRNA (Luciferase gene) in tumor cells in comparison with non-targeted controls (Tat-E28 or E28). The positively charged amino acids of these polypeptides enabled them to readily complex with negatively charged nucleic acids. The complexation of nucleic acid with respective polypeptides facilitated its transfection efficiency as well as stability. The targeted polypeptides (Tat-A1E28 or Tat-A4V48) selectively delivered siRNA into tumor cells in a receptor-specific fashion, achieved endosomal and lysosomal escape, and released gene into cytosol. The target specific delivery of siRNA by Tat-A1E28 or Tat-A4V48 was further validated in murine breast carcinoma 4T1 allograft mice model. Conclusion The designed delivery systems efficiently delivered siRNA to the target site of action thereby inducing significant gene silencing activity. The study shows Tat and AP1 functionalized ELPs constitute a novel gene delivery system with potential therapeutic applications.

In the original article [...]

When a railway vehicle moves on a curved rail, sliding contact between the rail head side and wheel flange causes wear on the wheel flange. Traditionally, a wheel with thinned flange is machined to get a minimum flange thickness specified for structural safety. This operation reduces the rim thickness and shortens the life of the wheel. In the present study, the thinned flanges were hard-faced by submerged arc welding. A welding wire, which has good weldability to the base material of the wheel and does not generate thermal cracking, was developed. The effects of welding polarity on the microstructure, hardness, friction coefficient, and wear characteristics of the welded wheel were studied. The hardness of the wheel welded with reverse polarity was similar to that of welded with straight polarity. The wear rates of the wheel disc welded with reverse polarity and its counterpart rail disc were 11% and 27% lower than those welded with straight polarity. Delamination wear due to subsurface crack propagation and oxidation wear were mixed. The hardness of the rail before the wear test was in the range of 250–300 HV. After the wear test, it soared to 500 HV.

Chaga mushroom (Inonotus obliquus) comprises polyphenolic compounds, triterpenoids, polysaccharides, and sterols. Among the triterpenoid components, inotodiol has been broadly examined because of its various biological activities. The purpose of this study is to examine inotodiol from a safety point of view and to present the potential possibilities of inotodiol for medical usage. From chaga mushroom extract, crude inotodiol (INO20) and pure inotodiol (INO95) were produced. Mice were treated with either INO20 or INO95 once daily using oral administration for repeated dose toxicity evaluation. Serum biochemistry parameters were analyzed, and the level of pro-inflammatory cytokines in the serum was quantified. In parallel, the effect of inotodiol on food allergic symptoms was investigated. Repeated administration of inotodiol did not show any mortality or abnormalities in organs. In food allergy studies, the symptoms of diarrhea were ameliorated by administration with INO95 and INO20. Furthermore, the level of MCPT-1 decreased by treatment with inotodiol. In this study, we demonstrated for the first time that inotodiol does not cause any detrimental effect by showing anti-allergic activities in vivo by inhibiting mast cell function. Our data highlight the potential to use inotodiol as an immune modulator for diseases related to inflammation.

BackgroundIn patients with hormone receptor-positive (HR+)/premenopausal breast cancer, luteinizing hormone-releasing hormone analogs (LHRHas) are used as standard endocrine treatment. Based on previous clinical studies, 1-month formulations are recommended in most breast cancer treatment guidelines, but long-acting formulations facilitate reductions in side effects and patient discomfort caused by frequent administration. However, few efficacy studies have been conducted on 6-month formulations. Therefore, this study aimed to evaluate the efficacy of 6-month formulations of LHRHas.MethodsThis retrospective study was conducted from January 2018 to December 2019 and involved premenopausal patients with HR+ breast cancer administered 6-month LHRHas as adjuvant treatment after surgery, and those previously administered chemotherapy or other LHRHa types were excluded. Patients’ estradiol (E2) and follicle-stimulating hormone (FSH) levels were measured before surgery, and their E2 levels were also measured at 3, 6, 12, 18, and 24 months at periodic postsurgical examinations.ResultsA total of 228 patients were included, and the median patient age was 44 (range, 25–54) years. The mean serum E2 and FSH levels before surgery were 69.7 (range, 4–683) pg/mL and 7.3 (range, 0.4–88.9) mIU/mL, respectively, whereas the mean serum E2 level monitored at intervals during the 6-month LHRHa administration was 5.5 (range, 4.0–52) pg/mL. No women menstruated during the follow-up period after the LHRHas administration, and the E2 levels were less than 30 pg/mL in all patients except one.ConclusionsThe 6-month LHRHa formulation adequately suppressed ovarian function in premenopausal patients with HR+ breast cancer. This indicates that long-acting LHRHas can be effectively used for patient convenience and that there is high compliance with long-term use.

Autophagy is a conserved mechanism among eukaryotes that degrades and recycles cytoplasmic components. Autophagy is known to influence the plant metabolome, including lipid content; however, its impact on the plant lipidome is not fully understood, and most studies have analyzed a single or few mutants defective in autophagy. To gain more insight into the effect of autophagy on lipid concentrations and composition, we quantitatively profiled glycerolipids from multiple Arabidopsis thaliana mutants altered in autophagy and compared them with wild-type seedlings under nitrogen replete (+N; normal growth) and nitrogen starvation (−N; autophagy inducing) conditions. Mutants include those in genes of the core autophagy pathway, together with other genes that have been reported to affect autophagy. Using Matrix-Assisted Laser Desorption/Ionization—Mass Spectrometry (MALDI-MS), we imaged the cellular distribution of specific lipids in situ and demonstrated that autophagy and nitrogen treatment did not affect their spatial distribution within Arabidopsis seedling leaves. We observed changes, both increases and decreases, in the relative amounts of different lipid species in the mutants compared to WT both in +N and −N conditions, although more changes were seen in −N conditions. The relative amounts of polyunsaturated and very long chain lipids were significantly reduced in autophagy-disrupted mutants compared to WT plants. Collectively, our results provide additional evidence that autophagy affects plant lipid content and that autophagy likely affects lipid properties such as chain length and unsaturation.

Abstract Background Reverse genetic strategies, such as virus-induced gene silencing, are powerful techniques to study gene function. Currently, there are few tools to study the spatial dependence of the consequences of gene silencing at the cellular level. Results We report the use of multimodal Raman and mass spectrometry imaging to study the cellular-level biochemical changes that occur from silencing the phytoene desaturase (pds) gene using a Foxtail mosaic virus (FoMV) vector in maize leaves. The multimodal imaging method allows the localized carotenoid distribution to be measured and reveals differences lost in the spatial average when analyzing a carotenoid extraction of the whole leaf. The nature of the Raman and mass spectrometry signals are complementary: silencing pds reduces the downstream carotenoid Raman signal and increases the phytoene mass spectrometry signal. Conclusions Both Raman and mass spectrometry imaging show that the biochemical changes from FoMV-pds silencing occur with a mosaic spatial pattern at the cellular level, and the Raman images show carotenoid expression was reduced at discrete locations but not eliminated. The data indicate the multimodal imaging method has great utility to study the biochemical changes that result from gene silencing at the cellular spatial level of expression in many plant tissues including the stem and leaf. Our demonstrated method is the first to spatially characterize the biochemical changes as a result of VIGS at the cellular level using commonly available instrumentation.

Splicing factors (SFs) are involved in oncogenesis or immune modulation, the common underlying processes giving rise to pleural effusion (PE). The expression profiles of three SFs (HNRNPA1, SRSF1, and SRSF3) and their clinical values have never been assessed in PE. The three SFs (in pellets of PE) and conventional tumor markers were analyzed using PE samples in patients with PE (N = 336). The sum of higher–molecular weight (Mw) forms of HNRNPA1 (Sum-HMws-HNRNPA1) and SRSF1 (Sum-HMws-SRSF1) and SRSF3 levels were upregulated in malignant PE (MPE) compared to benign PE (BPE); they were highest in cytology-positive MPE, followed by tuberculous PE and parapneumonic PE. Meanwhile, the lowest-Mw HNRNPA1 (LMw-HNRNPA1) and SRSF1 (LMw-SRSF1) levels were not upregulated in MPE. Sum-HMws-HNRNPA1, Sum-HMws-SRSF1, and SRSF3, but neither LMw-HNRNPA1 nor LMw-SRSF1, showed positive correlations with cancer cell percentages in MPE. The detection accuracy for MPE was high in the order of carcinoembryonic antigen (CEA, 85%), Sum-HMws-HNRNPA1 (76%), Sum-HMws-SRSF1 (68%), SRSF3, cytokeratin-19 fragments (CYFRA 21-1), LMw-HNRNPA1, and LMw-SRSF1. Sum-HMws-HNRNPA1 detected more than half of the MPE cases that were undetected by cytology and CEA. Sum-HMws-HNRNPA1, but not other SFs or conventional tumor markers, showed an association with longer overall survival among patients with MPE receiving chemotherapy. Our results demonstrated different levels of the three SFs with their Mw-specific profiles depending on the etiology of PE. We suggest that Sum-HMws-HNRNPA1 is a supplementary diagnostic marker for MPE and a favorable prognostic indicator for patients with MPE receiving chemotherapy.

Soybean aphids (Aphis glycines Matsumura) are specialized insects that feed on soybean (Glycine max) phloem sap. Transcriptome analyses have shown that resistant soybean plants mount a fast response that limits aphid feeding and population growth. Conversely, defense responses in susceptible plants are slower and it is hypothesized that aphids block effective defenses in the compatible interaction. Unlike other pests, aphids can colonize plants for long periods of time; yet the effect on the plant transcriptome after long-term aphid feeding has not been analyzed for any plant–aphid interaction. We analyzed the susceptible and resistant (Rag1) transcriptome response to aphid feeding in soybean plants colonized by aphids (biotype 1) for 21 days. We found a reduced resistant response and a low level of aphid growth on Rag1 plants, while susceptible plants showed a strong response consistent with pattern-triggered immunity. GO-term analyses identified chitin regulation as one of the most overrepresented classes of genes, suggesting that chitin could be one of the hemipteran-associated molecular pattern that triggers this defense response. Transcriptome analyses also indicated the phenylpropanoid pathway, specifically isoflavonoid biosynthesis, was induced in susceptible plants in response to long-term aphid feeding. Metabolite analyses corroborated this finding. Aphid-treated susceptible plants accumulated daidzein, formononetin, and genistein, although glyceollins were present at low levels in these plants. Choice experiments indicated that daidzein may have a deterrent effect on aphid feeding. Mass spectrometry imaging showed these isoflavones accumulate likely in the mesophyll cells or epidermis and are absent from the vasculature, suggesting that isoflavones are part of a non-phloem defense response that can reduce aphid feeding. While it is likely that aphid can initially block defense responses in compatible interactions, it appears that susceptible soybean plants can eventually mount an effective defense in response to long-term soybean aphid colonization.

Recently, the total variation (TV) algorithm has been used for noise reduction distribution in degraded nuclear medicine images. To acquire positron emission tomography (PET) to correct the attenuation region in the PET/magnetic resonance (MR) system, the MR Dixon pulse sequence, which is based on controlled aliasing in parallel imaging, results from higher acceleration (CAIPI; MR-ACDixon-CAIPI) and generalized autocalibrating partially parallel acquisition (GRAPPA; MR-ACDixon-GRAPPA) algorithms are used. Therefore, this study aimed to evaluate the image performance of the TV noise reduction algorithm for PET/MR images using the Jaszczak phantom by injecting 18F radioisotopes with PET/MR, which is called mMR (Siemens, Germany), compared with conventional noise-reduction techniques such as Wiener and median filters. The contrast-to-noise (CNR) and coefficient of variation (COV) were used for quantitative analysis. Based on the results, PET images with the TV algorithm were improved by approximately 7.6% for CNR and decreased by approximately 20.0% for COV compared with conventional noise-reduction techniques. In particular, the image quality for the MR-ACDixon-CAIPI PET image was better than that of the MR-ACDixon-GRAPPA PET image. In conclusion, the TV noise-reduction algorithm is efficient for improving the PET image quality in PET/MR systems.

Nephron progenitor number determines nephron endowment; a reduced nephron count is linked to the onset of kidney disease. Several transcriptional regulators including Six2, Wt1, Osr1, Sall1, Eya1, Pax2, and Hox11 paralogues are required for specification and/or maintenance of nephron progenitors. However, little is known about the regulatory intersection of these players. Here, we have mapped nephron progenitor-specific transcriptional networks of Six2, Hoxd11, Osr1, and Wt1. We identified 373 multi-factor associated 'regulatory hotspots' around genes closely associated with progenitor programs. To examine their functional significance, we deleted 'hotspot' enhancer elements for Six2 and Wnt4. Removal of the distal enhancer for Six2 leads to a ~40% reduction in Six2 expression. When combined with a Six2 null allele, progeny display a premature depletion of nephron progenitors. Loss of the Wnt4 enhancer led to a significant reduction of Wnt4 expression in renal vesicles and a mildly hypoplastic kidney, a phenotype also enhanced in combination with a Wnt4 null mutation. To explore the regulatory landscape that supports proper target gene expression, we performed CTCF ChIP-seq to identify insulator-boundary regions. One such putative boundary lies between the Six2 and Six3 loci. Evidence for the functional significance of this boundary was obtained by deep sequencing of the radiation-induced Brachyrrhine (Br) mutant allele. We identified an inversion of the Six2/Six3 locus around the CTCF-bound boundary, removing Six2 from its distal enhancer regulation, but placed next to Six3 enhancer elements which support ectopic Six2 expression in the lens where Six3 is normally expressed. Six3 is now predicted to fall under control of the Six2 distal enhancer. Consistent with this view, we observed ectopic Six3 in nephron progenitors. 4C-seq supports the model for Six2 distal enhancer interactions in wild-type and Br/+ mouse kidneys. Together, these data expand our view of the regulatory genome and regulatory landscape underpinning mammalian nephrogenesis.

YKL-40 is associated with various neurological disorders. However, circulatory YKL-40 levels early after onset of acute ischemic stroke (AIS) have not been systematically assessed. We aimed to identify the temporal changes and clinical usefulness of measuring serum YKL-40 immediately following AIS.Serum YKL-40 and C-reactive protein (CRP) levels were monitored over time in AIS patients (n = 105) and compared with those of stroke-free controls (n = 34). Infarct volume and stroke severity (National Institutes of Health Stroke Scale; NIHSS) were measured within 48 hours of symptom onset, and functional outcome (modified Rankin Scale; mRS) was measured 3 months after AIS.Within 12 hours of symptom onset, levels of YKL-40 (251 vs. 41 ng/mL) and CRP (1.50 vs. 0.96 µg/mL) were elevated in AIS patients compared to controls. The power of YKL-40 for discriminating AIS patients from controls was superior to that of CRP (area under the curve 0.84 vs. 0.64) and YKL-40 (r = 0.26, P

Submissions to an online homework tutor were analyzed to determine whether they were copied. The fraction of copied submissions increased rapidly over the semester, as each weekly deadline approached and for problems later in each assignment. The majority of students, who copied less than 10% of their problems, worked steadily over the three days prior to the deadline, whereas repetitive copiers (those who copied >30% of their submitted problems) exerted little effort early. Importantly, copying homework problems that require an analytic answer correlates with a 2(σ) decline over the semester in relative score for similar problems on exams but does not significantly correlate with the amount of conceptual learning as measured by pretesting and post-testing. An anonymous survey containing questions used in many previous studies of self-reported academic dishonesty showed ∼1/3 less copying than actually was detected. The observed patterns of copying, free response questions on the survey, and interview data suggest that time pressure on students who do not start their homework in a timely fashion is the proximate cause of copying. Several measures of initial ability in math or physics correlated with copying weakly or not at all. Changes in course format and instructional practices that previous self-reported academic dishonesty surveys and/or the observed copying patterns suggested would reduce copying have been accompanied by more than a factor of 4 reduction of copying from ∼11% of all electronic problems to less than 3%. As expected (since repetitive copiers have approximately three times the chance of failing), this was accompanied by a reduction in the overall course failure rate. Survey results indicate that students copy almost twice as much written homework as online homework and show that students nationally admit to more academic dishonesty than MIT students.

We present mathematical learning models—predictions of student’s knowledge vs amount of instruction—that are based on assumptions motivated by various theories of learning: tabula rasa, constructivist, and tutoring. These models predict the improvement (on the post-test) as a function of the pretest score due to intervening instruction and also depend on the type of instruction. We introduce a connectedness model whose connectedness parameter measures the degree to which the rate of learning is proportional to prior knowledge. Over a wide range of pretest scores on standard tests of introductory physics concepts, it fits high-quality data nearly within error. We suggest that data from MIT have low connectedness (indicating memory-based learning) because the test used the same context and representation as the instruction and that more connected data from the University of Minnesota resulted from instruction in a different representation from the test.

We investigate short-term learning from hints and feedback in a Web-based physics tutoring system. Both the skill of students and the difficulty and discrimination of items were determined by applying item response theory (IRT) to the first answers of students who are working on for-credit homework items in an introductory Newtonian physics course. We show that after tutoring a shifted logistic item response function with lower discrimination fits the students’ second responses to an item previously answered incorrectly. Student skill decreased by 1.0 standard deviation when students used no tutoring between their (incorrect) first and second attempts, which we attribute to “item-wrong bias.” On average, using hints or feedback increased students’ skill by 0.8 standard deviation. A skill increase of 1.9 standard deviation was observed when hints were requested after viewing, but prior to attempting to answer, a particular item. The skill changes measured in this way will enable the use of IRT to assess students based on their second attempt in a tutoring environment.

Purpose: The aim of this study was to identify novel vaginal probiotics with the potential to prevent vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV). Materials and Methods: Eighteen strains of Lactiplantibacillus plantarum were isolated from healthy Korean women, and their antimicrobial effects against Candida albicans and Gardnerella vaginalis were assessed. Three strains (L. plantarum LM1203, LM1209, and LM1215) were selected for further investigation, focusing on their growth inhibition, biofilm regulation, and cellular mechanisms against these vaginal pathogens. Additionally, electron microscopy revealed damage to G. vaginalis induced by L. plantarum LM1215, and genomic analysis was conducted on this strain. Results: L. plantarum LM1203, LM1209, and LM1215 showed approximately 1 and 2 Log CFU/mL growth reduction in C. albicans and G. vaginalis, respectively. These L. plantarum strains effectively inhibited biofilm formation and eliminated the mature biofilms formed by C. albicans. Furthermore, L. plantarum LM1215 decreased tricarboxylic acid cycle activity by 51.75 (p<0.001) and respiratory metabolic activity by 52.88% (p<0.001) in G. vaginalis. L. plantarum induced cellular membrane damage, inhibition of protein synthesis, and cell wall collapse in G. vaginalis. Genomic analysis confirmed L. plantarum LM1215 as a safe strain for vaginal probiotics. Conclusion: The L. plantarum LM1215 is considered a safe probiotic agent suitable for the prevention of VVC and BV. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to conduct a pre-conception care program for women of childbearing age with inflammatory bowel disease (IBD) in Korea and verify its effects on self-efficacy for IBD management, IBD-related pregnancy knowledge, and IBD-related pregnancy anxiety. It also aimed to explore the changes in participants through the program. Methods: A convergent mixed-methods study design was adopted. In the quantitative phase, 35 women (17 and 18 in the intervention and control group, respectively) participated. The intervention group attended a program that included small-group sessions and individual tele-coaching. To confirm the effects, data were collected before and one and four weeks after the intervention. In the qualitative stage, focus group interviews and tele-coaching were conducted with the intervention group. Results: After the program ended, significant differences were observed over time between the intervention and control groups for self-efficacy for IBD management (Wald χ² = 4.41, p = .036), IBD-related pregnancy knowledge (Wald χ² = 13.80, p < .001) and IBD-related pregnancy anxiety (Wald χ² = 8.61, p = .003). Qualitative data analysis revealed the following themes: (1) improving confidence in IBD management and awareness for planned pregnancy; (2) improving IBD awareness related to pregnancy and childbirth; and (3) relieving anxiety about and actively facing pregnancy. Conclusion: This study is meaningful in that, to the best of our knowledge, it is the first to develop a pre-conception care program for women diagnosed with IBD and confirm its effectiveness. Furthermore, this program is expected to be suitable for patient counseling and education in clinical practice. [ABSTRACT FROM AUTHOR]

The commonly used analytical tools for metabolomics cannot directly probe metabolic activities or distinguish metabolite differences between cells and suborgans in multicellular organisms. These issues can be addressed by invivo isotope labeling and mass spectrometry imaging (MSI), respectively, but the combination of the two, a newly emerging technology we call MSIi, has been rarely applied to plant systems. In this study, we explored MSIi of Arabidopsis thaliana with D2O labeling to study and visualize D-labeling in three classes of lipids: arabidopsides, chloroplast lipids, and epicuticular wax. Similar to other stress responses, D2O-induced stress increased arabidopsides in an hour, but it was relatively minor for matured plants and reverted to the normal level in a few hours. The D-labeling isotopologue patterns of arabidopsides matched with those of galactolipid precursors, supporting the currently accepted biosynthesis mechanism. Matrix-assisted laser desorption/ionization (MALDI)-MSI was used to visualize the spatiotemporal distribution of deuterated chloroplast lipids, pheophytin a, MGDGs, and DGDGs, after growing day-after-sowing (DAS) 28 plants in D2O condition for 3-12 days. There was a gradual change of deuteration amount along the leaf tissues and with a longer labeling time, which was attributed to slow respiration leading to low D2O concentration in the tissues. Finally, deuterium incorporation in epicuticular wax was visualized on the surfaces of the stem and flower. The conversion efficiency of newly synthesized C30 aldehyde to C29 ketone was very low in the lower stem but very high at the top of the stem near the flower or on the flower carpel. This study successfully demonstrated that MSIi can unveil spatiotemporal metabolic activities in various tissues of A. thaliana. [ABSTRACT FROM AUTHOR]

Background/Aim: Chronic kidney disease (CKD) is one of the most common causes of mortality in wild nondomestic felidae. The molecular mechanism regulating renal fibrosis in nephropathy is not fully understood especially in the felidae. This study aimed to elucidate senescence marker protein 30 (SMP30) expression patterns and its relationship with epithelial-mesenchymal transition (EMT) by immunostaining in two necropsied Siberian tigers (Panthera tigris altaica) with CKD. Materials and Methods: Two kidney samples from male Siberian tigers were fixed and tissue sections were stained for histopathological assay. Results: In CKD, renal tubular epithelial cells lost their tubular structures surrounded by severe interstitial fibrosis and were detached from the basement membrane. These damaged cells resembled the morphology of mesenchymal cells and showed much lower SMP30 expression compared with intact tubular epithelial cells. These cells also expressed vimentin, which is specifically expressed by mesenchymal cells, and through double staining, it was observed that vimentin was expressed in the tubular epithelial cells where SMP30 was not expressed. In addition, double-positive expression of pan-cytokeratin (pan-CK) and vimentin was found in damaged epithelial cells with mesenchymal features. Conclusion: We demonstrated possible evidence to understand the role of SMP30 as a new pivotal factor and the possibility of decreased SMP30 as a potential indicator of EMT at the end stage of CKD. [ABSTRACT FROM AUTHOR]