Comprehensive genomic landscape of antibiotic resistance in Staphylococcus epidermidis.

Staphylococcus epidermidis, a common commensal bacterium found on human skin, can cause infections in clinical settings, and the presence of antibiotic resistance genes (ARGs) impedes the treatment of S. epidermidis infections. However, studies characterizing the ARGs in S. epidermidis with regard to genomic and ecological diversities are limited. Thus, we performed a comprehensive and comparative analysis of 405 high-quality S. epidermidis genomes, including those of 35 environmental isolates from the Han River, to investigate the genomic diversity of antibiotic resistance in this pathogen. Comparative genomic analysis revealed the prevalence of ARGs in S. epidermidis genomes associated with multi-locus sequence types. The genes encoding dihydrofolate reductase (dfrC) and multidrug efflux pump (norA) were genome-wide core ARGs. ß-Lactam class ARGs were also highly prevalent in the S. epidermidis genomes, which was consistent with the resistance phenotype observed in river isolates. Furthermore, we identified chloramphenicol acetyltransferase genes (cat) in the plasmid-like sequences of the six river isolates, which have not been reported previously in S. epidermidis genomes. These genes were identical to those harbored by the Enterococcus faecium plasmids and associated with the insertion sequence 6 family transposases, homologous to those found in Staphylococcus aureus plasmids, suggesting the possibility of horizontal gene transfer between these Gram-positive pathogens. Comparison of the ARG and virulence factor profiles between S. epidermidis and S. aureus genomes revealed that these two species were clearly distinguished, suggesting genomic demarcation despite ecological overlap. Our findings provide a comprehensive understanding of the genomic diversity of antibiotic resistance in S. epidermidis. IMPORTANCE: A comprehensive understanding of the antibiotic resistance gene (ARG) profiles of the skin commensal bacterium and opportunistic pathogen Staphylococcus epidermidis needs to be documented from a genomic point of view. Our study encompasses a comparative analysis of entire S. epidermidis genomes from various habitats, including those of 35 environmental isolates from the Han River sequenced in this study. Our results shed light on the distribution and diversity of ARGs within different S. epidermidis multi-locus sequence types, providing valuable insights into the ecological and genetic factors associated with antibiotic resistance. A comparison between S. epidermidis and Staphylococcus aureus revealed marked differences in ARG and virulence factor profiles, despite their overlapping ecological niches.

Time resolved multi-omics reveals diverse metabolic strategies of Salmonella during diet-induced inflammation.

With a rise in antibiotic resistance and chronic infection, the metabolic response of Salmonella enterica serovar Typhimurium to various dietary conditions over time remains an understudied avenue for novel, targeted therapeutics. Elucidating how enteric pathogens respond to dietary variation not only helps us decipher the metabolic strategies leveraged for expansion but also assists in proposing targets for therapeutic interventions. Here, we use a multi-omics approach to identify the metabolic response of Salmonella enterica serovar Typhimurium in mice on both a fibrous diet and high-fat diet over time. When comparing Salmonella gene expression between diets, we found a preferential use of respiratory electron acceptors consistent with increased inflammation of the high-fat diet mice. Looking at the high-fat diet over the course of infection, we noticed heterogeneity of samples based on Salmonella ribosomal activity, which separated into three infection phases: early, peak, and late. We identified key respiratory, carbon, and pathogenesis gene expression descriptive of each phase. Surprisingly, we identified genes associated with host-cell entry expressed throughout infection, suggesting sub-populations of Salmonella or stress-induced dysregulation. Collectively, these results highlight not only the sensitivity of Salmonella to its environment but also identify phase-specific genes that may be used as therapeutic targets to reduce infection. Importance: Identifying novel therapeutic strategies for Salmonella infection that occur in relevant diets and over time is needed with the rise of antibiotic resistance and global shifts towards Western diets that are high in fat and low in fiber. Mice on a high-fat diet are more inflamed compared to those on a fibrous diet, creating an environment that results in more favorable energy generation for Salmonella . Over time on a high-fat diet, we observed differential gene expression across infection phases. Together, these findings reveal the metabolic tuning of Salmonella to dietary and temporal perturbations. Research like this, exploring the dimensions of pathogen metabolic plasticity, can pave the way for rationally designed strategies to control disease.

Gut microbiome carbon and sulfur metabolisms support Salmonella during pathogen infection.

Salmonella enterica serovar Typhimurium is a pervasive enteric pathogen and an ongoing global threat to public health. Ecological studies in the Salmonella impacted gut remain underrepresented in the literature, discounting the microbiome mediated interactions that may inform Salmonella physiology during colonization and infection. To understand the microbial ecology of Salmonella remodeling of the gut microbiome, here we performed multi-omics approaches on fecal microbial communities from untreated and Salmonella -infected mice. Reconstructed genomes recruited metatranscriptomic and metabolomic data providing a strain-resolved view of the expressed metabolisms of the microbiome during Salmonella infection. This data informed possible Salmonella interactions with members of the gut microbiome that were previously uncharacterized. Salmonella- induced inflammation significantly reduced the diversity of transcriptionally active members in the gut microbiome, yet increased gene expression was detected for 7 members, with Luxibacter and Ligilactobacillus being the most active. Metatranscriptomic insights from Salmonella and other persistent taxa in the inflamed microbiome further expounded the necessity for oxidative tolerance mechanisms to endure the host inflammatory responses to infection. In the inflamed gut lactate was a key metabolite, with microbiota production and consumption reported amongst transcriptionally active members. We also showed that organic sulfur sources could be converted by gut microbiota to yield inorganic sulfur pools that become oxidized in the inflamed gut, resulting in thiosulfate and tetrathionate that supports Salmonella respiration. Advancement of pathobiome understanding beyond inferences from prior amplicon-based approaches can hold promise for infection mitigation, with the active community outlined here offering intriguing organismal and metabolic therapeutic targets.

ApoE4-dependent lysosomal cholesterol accumulation impairs mitochondrial homeostasis and oxidative phosphorylation in human astrocytes.

Recent developments in genome sequencing have expanded the knowledge of genetic factors associated with late-onset Alzheimer's disease (AD). Among them, genetic variant ε4 of the APOE gene (APOE4) confers the greatest disease risk. Dysregulated glucose metabolism is an early pathological feature of AD. Using isogenic ApoE3 and ApoE4 astrocytes derived from human induced pluripotent stem cells, we find that ApoE4 increases glycolytic activity but impairs mitochondrial respiration in astrocytes. Ultrastructural and autophagy flux analyses show that ApoE4-induced cholesterol accumulation impairs lysosome-dependent removal of damaged mitochondria. Acute treatment with cholesterol-depleting agents restores autophagic activity, mitochondrial dynamics, and associated proteomes, and extended treatment rescues mitochondrial respiration in ApoE4 astrocytes. Taken together, our study provides a direct link between ApoE4-induced lysosomal cholesterol accumulation and abnormal oxidative phosphorylation.

Subcutaneous implantation of thyroid carcinoma and benign tissue after thyroidectomy: report on two cases and review of the current literature.

Background: Subcutaneous implantation of thyroid tissue after thyroidectomy is a rare occurrence involving both benign and malignant thyroid tissue. Clinically, subcutaneous implantation of thyroid tissue can be challenging to diagnose. We present two cases of subcutaneous implantation of thyroid tissue following thyroidectomy and discuss the differential diagnosis, clinicopathological characteristics, and the possible mechanism of implantation. Case Description: A 35-year-old woman (age in 2009) who underwent total thyroidectomy in 2009 whose histopathological examination revealed a nodular hyperplasia and lymphocytic thyroiditis complained of palpable mass in her neck 10 years after operation and underwent excision. Follicular adenoma was confirmed in histopathological results. A 58-year-old woman (age in 2010) who underwent lobectomy in 2010 for nodular hyperplasia had a 6 cm sized huge mass in her anterior neck 9 years after operation. Anterior neck mass excision was done and poorly differentiated carcinoma was confirmed in histopathological results. The patient showed no sign of recurrence after 3 years follow-up. Conclusions: Subcutaneous implantation of benign thyroid tissue or thyroid cancer can occur after thyroidectomy. Minimizing the likelihood of subcutaneous implantation requires careful consideration of various factors at every stage of the surgical procedure. Surgeons should be aware of this potential long-term complication that can occur in both conventional thyroidectomy and remote access surgery, effectively communicate and provide appropriate guidance to their patients, and try to avoid seeding of both malignant and benign thyroid tissue.

Flavobacterium psychrotrophum sp. nov. and Flavobacterium panacagri sp. nov., Isolated from Freshwater and Soil.

Two novel bacterial strains CJ74T and CJ75T belonging to the genus Flavobacterium were isolated from freshwater of Han River and ginseng soil, South Korea, respectively. Strain CJ74T was Gram-stain-negative, aerobic, rod-shaped, non-motile, and non-flagellated, and did not produce flexirubin-type pigments. Strain CJ75T was Gram-stain-negative, aerobic, rod-shaped, motile by gliding, and non-flagellated, and produced flexirubin-type pigments. Both strains were shown to grow optimally at 30 °C in the absence of NaCl on R2A medium. Phylogenetic analysis based on 16S rRNA gene sequences showed that strains CJ74T and CJ75T belonged to the genus Flavobacterium and were most closely related to Flavobacterium niveum TAPW14T and Flavobacterium foetidum CJ42T with 96.17% and 97.29% 16S rRNA sequence similarities, respectively. Genomic analyses including the reconstruction of phylogenomic tree, average nucleotide identity, and digital DNA-DNA hybridization suggested that they were novel species of the genus Flavobacterium. Both strains contained menaquinone 6 (MK-6) as the primary respiratory quinone and phosphatidylethanolamine as a major polar lipid. The predominant fatty acids of both strains were iso-C15:0 and summed feature 3 (C16:1 ω7c and/or C16:1 ω6c). Based on the polyphasic taxonomic study, strains CJ74T and CJ75T represent novel species of the genus Flavobacterium, for which names Flavobacterium psychrotrophum sp. nov. and Flavobacterium panacagri sp. nov. are proposed, respectively. The type strains are CJ74T (=KACC 19819T =JCM 32889T) and CJ75T (=KACC 23149T =JCM 36132T).

Impacts of meteorological variables and machine learning algorithms on rice yield prediction in Korea.

As crop productivity is greatly influenced by weather conditions, many attempts have been made to estimate crop yields using meteorological data and have achieved great progress with the development of machine learning. However, most yield prediction models are developed based on observational data, and the utilization of climate model output in yield prediction has been addressed in very few studies. In this study, we estimate rice yields in South Korea using the meteorological variables provided by ERA5 reanalysis data (ERA-O) and its dynamically downscaled data (ERA-DS). After ERA-O and ERA-DS are validated against observations (OBS), two different machine learning models, Support Vector Machine (SVM) and Long Short-Term Memory (LSTM), are trained with different combinations of eight meteorological variables (mean temperature, maximum temperature, minimum temperature, precipitation, diurnal temperature range, solar irradiance, mean wind speed, and relative humidity) obtained from OBS, ERA-O, and ERA-DS at weekly and monthly timescales from May to September. Regardless of the model type and the source of the input data, training a model with weekly datasets leads to better yield estimates compared to monthly datasets. LSTM generally outperforms SVM, especially when the model is trained with ERA-DS data at a weekly timescale. The best yield estimates are produced by the LSTM model trained with all eight variables at a weekly timescale. Altogether this study shows the significance of high spatial and temporal resolution of input meteorological data in yield prediction, which can also serve to substantiate the added value of dynamical downscaling.

Predictive biological factors for late survival in patients with HER2-positive breast cancer.

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 < 0.001), and pN3 (p < 0.001), respectively. Only pT4 level was statistically significant in the pT group (HRa, 4.528; p = 0.007). Age (HRa, 1.045, p < 0.001) and hormone receptor-positive status (HRa, 1.705, p = 0.022) were also associated to worse BCSS. Although lymphatic invasion was not significantly associated with BCSS, there was a tendency toward a relationship (p = 0.079) with worse BCSS. In HER2-positive breast cancer patients, node status had a more significant relationship with long-term prognosis than T stage. Patients with HER2-positive breast cancer who have T4 or node-positive should be considered for clinical observation and education beyond 5 years.

The Relationship Between Gambling Accessibility and Behavior Among Korean Adults.

This is the first population-based study in South Korea to examine the comprehensive nature of gambling accessibility. While most previous studies have examined only the physical aspects of gambling accessibility, this study accepts that gambling accessibility is multi-dimensional comprising physical, social, and cognitive accessibility, and tests the predictive power of each dimension of gambling behavior. We measured gambling behaviors in three ways: problem gambling, time spent on gambling, and gambling expenditure. Using a proportional quota sampling method (based on gender, age, and region) to represent the general Korean population, we identified 8245 adults (aged 19-69 years), and 2044 participated in online survey from July 1 to July 9, 2021. Study findings revealed that, among the three accessibility dimensions, social accessibility was the strongest predictor of all three gambling behavior measures. Study findings provide insights for developing culturally sensitive gambling prevention programs and highlight the importance of a comprehensive examination of the relationship between gambling accessibility and gambling behavior.

A randomized controlled trial using surgical gloves to prevent chemotherapy-induced peripheral neuropathy by paclitaxel in breast cancer patients (AIUR trial).

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane treatment and can significantly affect patient quality of life. Currently, there are no effective treatments to alleviate symptoms of CIPN; thus, starting with prevention steps in high-risk patients is considered advantageous. However, for these prevention steps to be applicable to all patients, their side effects or accompanying discomforts should be minimal, and the intervention cost-effective. Compression therapy can be considered a prevention intervention, and using surgical gloves is feasible and cost-effective (approximately $0.6 per pair). Although previous studies on compression therapy using surgical gloves have reported decreased incidence of PN, these studies were non-randomized, limited to nab-paclitaxel treatment, and involved the use of small gloves, which may have caused discomfort. Therefore, this study aimed to assess the preventive effects of compression therapy using normal-sized surgical gloves on CIPN in patients treated with paclitaxel. METHODS: This clinical trial is designed to evaluate the preventive effects of compression therapy using surgical gloves on CIPN in women with stage II-III breast cancer who received paclitaxel chemotherapy for at least 12 weeks. This multicenter, randomized-controlled, open-label study will be conducted in six academic hospitals. Patients with medication or a medical history related to neuropathy or hand disease will be excluded. The primary outcome will be the preventive effect of compression therapy using surgical gloves, measured based on changes in the neurotoxicity component of the Functional Assessment of Cancer Therapy-Taxane questionnaire. Furthermore, we will assess the National Cancer Institute's Common Terminology Criteria for Adverse Events grade of CIPN after 6 months. Notably, the estimated sample size, based on a p-value < 0.025 and statistical power of 0.9, will consist of 104 patients (52 per group), accounting for a 10% sample loss. DISCUSSION: This intervention can be easily implemented in clinical practice and may serve as a preventive strategy for CIPNs with strong patient adherence. If successful, this intervention could improve the quality of life and treatment adherence in patients receiving chemotherapy that can induce PN, extending beyond paclitaxel treatment alone. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05771974; Registered on March 16, 2023.

Two-step structural changes in M3 muscarinic receptor activation rely on the coupled Gq protein cycle.

G protein-coupled receptors (GPCRs) regulate diverse intracellular signaling pathways through the activation of heterotrimeric G proteins. However, the effects of the sequential activation-deactivation cycle of G protein on the conformational changes of GPCRs remains unknown. By developing a Förster resonance energy transfer (FRET) tool for human M3 muscarinic receptor (hM3R), we find that a single-receptor FRET probe can display the consecutive structural conversion of a receptor by G protein cycle. Our results reveal that the G protein activation evokes a two-step change in the hM3R structure, including the fast step mediated by Gq protein binding and the subsequent slower step mediated by the physical separation of the Gαq and Gßγ subunits. We also find that the separated Gαq-GTP forms a stable complex with the ligand-activated hM3R and phospholipase Cß. In sum, the present study uncovers the real-time conformational dynamics of innate hM3R during the downstream Gq protein cycle.

Chryseobacterium paludis sp. nov. and Chryseobacterium foetidum sp. nov. Isolated from the Aquatic Environment, South Korea.

Two novel bacterial species CJ51T and CJ63T belonging to the genus Chryseobacterium were isolated from the Upo wetland and the Han River, South Korea, respectively. Cells of these strains were Gram-stain-negative, aerobic, non-motile, rod-shaped, and catalase- and oxidase-positive. Both strains were shown to grow optimally at 30 °C and pH 7 in the absence of NaCl on tryptic soy agar. Phylogenetic analysis based on 16S rRNA gene sequences showed that strains CJ51T and CJ63T belonged to the genus Chryseobacterium and were most closely related to Chryseobacterium piperi CTMT and Chryseobacterium piscicola VQ-6316sT with 98.47% and 98.46% 16S rRNA sequence similarities, respectively. The average nucleotide identity values of strains CJ51T and CJ63T with its closely related type strains Chryseobacterium piperi CTMT and Chryseobacterium piscicola VQ-6316sT were 81.9% and 82.1%, respectively. The major fatty acids of strains CJ51T and CJ63T were iso-C15:0, iso-C17:0 3-OH and summed feature 9 (C16:0 10-methyl and/or iso-C17:1ω9c). Menaquinone 6 (MK-6) was identified as the primary respiratory quinone in both strains. The major polar lipids of strains CJ51T and CJ63T were phosphatidylethanolamine and several unidentified amino lipids and lipids. Based on polyphasic taxonomy data, strains CJ51T and CJ63T represent novel species of the genus Chryseobacterium, for which names Chryseobacterium paludis sp. nov. and Chryseobacterium foetidum sp. nov. are proposed respectively. The type strains are CJ51T (= KACC 22749T = JCM 35632T) and CJ63T (= KACC 22750T = JCM 35633T).

Reversibility and developmental neuropathology of linear nevus sebaceous syndrome caused by dysregulation of the RAS pathway.

Linear nevus sebaceous syndrome (LNSS) is a neurocutaneous disorder caused by somatic gain-of-function mutations in KRAS or HRAS. LNSS brains have neurodevelopmental defects, including cerebral defects and epilepsy; however, its pathological mechanism and potentials for treatment are largely unclear. We show that introduction of KRASG12V in the developing mouse cortex results in subcortical nodular heterotopia and enhanced excitability, recapitulating major pathological manifestations of LNSS. Moreover, we show that decreased firing frequency of inhibitory neurons without KRASG12V expression leads to disrupted excitation and inhibition balance. Transcriptional profiling after destabilization domain-mediated clearance of KRASG12V in human neural progenitors and differentiating neurons identifies reversible functional networks underlying LNSS. Neurons expressing KRASG12V show molecular changes associated with delayed neuronal maturation, most of which are restored by KRASG12V clearance. These findings provide insights into the molecular networks underlying the reversibility of some of the neuropathologies observed in LNSS caused by dysregulation of the RAS pathway.

Investigating the effect of road lighting color temperature on road visibility in night foggy conditions.

Night foggy road conditions limit visibility distance of drivers and are associated with higher accident and fatality rates than other weather conditions. Therefore, ensuring road visibility in night foggy road is critical. However, it is difficult to reproduce fog on a real road and only a few studies have researched foggy road conditions and visibility in a laboratory as a small scale. Previous studies have suggested that a color temperature of road lighting is related to visibility. However, many have only investigated the effects of relative transmittance in limited indoor experiments, and the impacts of differences in transmittance on visibility have thus far not been studied in real-scale conditions. In this study, a real-scale test involving 91 subjects was conducted to investigate how the visibility distance under night foggy conditions is affected by different lighting color temperatures. Based on the real scale experiments, the correlation between the visibility distance and lighting color temperature was derived. Road lighting with a low color temperature (i.e., yellow) was found to provide longer visibility distances than that with high color temperatures under night foggy conditions having measured visibility of approximately 102m. The impact of the differences in lighting color increased as the visibility distance decreased. In contrast, road lighting with a high color temperature (i.e., white) improved driver visibility in higher-visibility conditions. Therefore, this study confirmed the correlation between lighting color temperature and visibility distance for different visibility conditions and could serve as a foundation for the development of roadway design standards as well as future studies.

Protein quaternary structures in solution are a mixture of multiple forms.

Over half the proteins in the E. coli cytoplasm form homo or hetero-oligomeric structures. Experimentally determined structures are often considered in determining a protein's oligomeric state, but static structures miss the dynamic equilibrium between different quaternary forms. The problem is exacerbated in homo-oligomers, where the oligomeric states are challenging to characterize. Here, we re-evaluated the oligomeric state of 17 different bacterial proteins across a broad range of protein concentrations and solutions by native mass spectrometry (MS), mass photometry (MP), size exclusion chromatography (SEC), and small-angle X-ray scattering (SAXS), finding that most exhibit several oligomeric states. Surprisingly, some proteins did not show mass-action driven equilibrium between the oligomeric states. For approximately half the proteins, the predicted oligomeric forms described in publicly available databases underestimated the complexity of protein quaternary structures in solution. Conversely, AlphaFold multimer provided an accurate description of the potential multimeric states for most proteins, suggesting that it could help resolve uncertainties on the solution state of many proteins.

Colistin-degrading proteases confer collective resistance to microbial communities during polymicrobial infections.

BACKGROUND: The increasing prevalence of resistance against the last-resort antibiotic colistin is a significant threat to global public health. Here, we discovered a novel colistin resistance mechanism via enzymatic inactivation of the drug and proposed its clinical importance in microbial communities during polymicrobial infections. RESULTS: A bacterial strain of the Gram-negative opportunistic pathogen Stenotrophomonas maltophilia capable of degrading colistin and exhibiting a high-level colistin resistance was isolated from the soil environment. A colistin-degrading protease (Cdp) was identified in this strain, and its contribution to colistin resistance was demonstrated by growth inhibition experiments using knock-out (Δcdp) and complemented (Δcdp::cdp) mutants. Coculture and coinfection experiments revealed that S. maltophilia carrying the cdp gene could inactivate colistin and protect otherwise susceptible Pseudomonas aeruginosa, which may seriously affect the clinical efficacy of the drug for the treatment of cystic fibrosis patients with polymicrobial infection. CONCLUSIONS: Our results suggest that Cdp should be recognized as a colistin resistance determinant that confers collective resistance at the microbial community level. Our study will provide vital information for successful clinical outcomes during the treatment of complex polymicrobial infections, particularly including S. maltophilia and other colistin-susceptible Gram-negative pathogens such as P. aeruginosa. Video abstract.

Changes in Emergency Department Case Severity and Length of Stay before and after COVID-19 Outbreak in Korea.

Severe patients visited regional emergency centers more frequently during the COVID-19 period, and disposition status warranting admission to the intensive care unit or resulting in death was more common during the COVID-19 period. This study was conducted to compare the characteristics and severity of patients, and emergency department length of stay before and after the COVID-19 outbreak. Subjects were 75,409 patients who visited the regional emergency medical center from 1 February 2019 to 19 January 2020 and from 1 February 2020 to 19 January 2021. Data was analyzed using the SPSS/WIN 22.0 program. The significance level was p < 0.05. The chi-square test and t-test were used for variables, and Cramer V was used for correlation. We found that the total number of patients visiting the emergency room decreased by 37.6% after COVID-19, but emergency department length of stay among severely ill patients increased by 203.7%. Additionally, the utilization rate of 119 ambulances and relatively more severe patients increased by 9.0% and by 2.1%. More studies about emergency department designs and operational programs should be conducted for better action not only during regular periods but also during periods of pandemic.

Analysis of Genomic Alterations Associated with Recurrence in Early Stage HER2-Positive Breast Cancer.

We aimed to compare gene expression in primary tumors of patients with recurrence and nonrecurrence to gain insight into the biology of high-risk HER2-positive early breast cancer. Patients who underwent curative resection and received adjuvant trastuzumab for HER2-positive early breast cancer were evaluated. Gene expression analyses were performed using NanoString Technologies' nCounter Breast Cancer 360 Panel. PAM50 intrinsic subtypes and Breast Cancer Signatures including tumor inflammation signature (TIS) were evaluated. Of 247 patients, 28 (11.3%) had recurrence at a median follow-up of 54.2 months. Patients with pathological stage III, tumor size > 5 cm, axillary lymph node metastases, and hormone receptor-negativity were more frequently observed in the recurrent group compared with the nonrecurrent group. In patients with recurrence, seven genes were upregulated significantly, including WNT11, HAPLN1, FGF10, BBOX1, CXADR, NDP, and EREG, and two genes were downregulated, including CXCL9 and GNLY. TIS score was significantly lower in patients with recurrence compared with controls without recurrence. These findings suggest that activation of oncogenic signaling pathways related to cell proliferation, adhesion, cancer stemness, and noninflamed tumor microenvironment are associated with the risk of recurrence in early stage, HER2-positive breast cancer.

Simulation of Energy-Resolved Mass Spectrometry Distributions from Surface-Induced Dissociation.

Understanding the relationship between protein structure and experimental data is crucial for utilizing experiments to solve biochemical problems and optimizing the use of sparse experimental data for structural interpretation. Tandem mass spectrometry (MS/MS) can be used with a variety of methods to collect structural data for proteins. One example is surface-induced dissociation (SID), which is used to break apart protein complexes (via a surface collision) into intact subcomplexes and can be performed at multiple laboratory frame SID collision energies. These energy-resolved MS/MS experiments have shown that the profile of the breakages depends on the acceleration energy of the collision. It is possible to extract an appearance energy (AE) from energy-resolved mass spectrometry (ERMS) data, which shows the relative intensity of each type of subcomplex as a function of SID acceleration energy. We previously determined that these AE values for specific interfaces correlated with structural features related to interface strength. In this study, we further examined the structural relationships by developing a method to predict the full ERMS plot from the structure, rather than extracting a single value. First, we noted that for proteins with multiple interface types, we could reproduce the correct shapes of breakdown curves, further confirming previous structural hypotheses. Next, we demonstrated that interface size and energy density (measured using Rosetta) correlated with data derived from the ERMS plot (R2 = 0.71). Furthermore, based on this trend, we used native crystal structures to predict ERMS. The majority of predictions resulted in good agreement, and the average root-mean-square error was 0.20 for the 20 complexes in our data set. We also show that if additional information on cleavage as a function of collision energy could be obtained, the accuracy of predictions improved further. Finally, we demonstrated that ERMS prediction results were better for the native than for inaccurate models in 17/20 cases. An application to run this simulation has been developed in Rosetta, which is freely available for use.

Is Gross Extrathyroidal Extension to Strap Muscles (T3b) Only a Risk Factor for Recurrence in Papillary Thyroid Carcinoma? A Propensity Score Matching Study.

The presence of extrathyroidal extension (ETE) is associated with locoregional recurrence and distant metastases in papillary thyroid carcinoma (PTC). This study was designed to compare the recurrence risk between minimal ETE (mETE) and gross ETE (gETE) in patients with PTC using propensity score matching. In this study, 4452 patients with PTC who underwent thyroid surgery in a single center were retrospectively analyzed, and clinicopathological characteristics were compared according to the ETE status. Disease-free survival (DFS) and recurrence risk were compared between mETE and gETE after propensity score matching. The mean follow-up duration was 122.7 ± 22.5 months. In multivariate analysis, both mETE and gETE were not associated with recurrence risk before propensity score matching (p = 0.154 and p = 0.072, respectively). After propensity score matching, no significant difference in recurrence rates was observed between the two groups (p = 0.668). DFS of the gETE group did not significantly differ from that of the mETE group (log-rank p = 0.531). This study revealed that both mETE and gETE are not independent risk factors for the risk of recurrence in PTC. Our findings suggest that gETE invading strap muscles only might not be associated with worse oncological outcomes in PTC.