The combination of physical activity with fruit and vegetable intake associated with life satisfaction among middle-aged and older adults: a 16-year population-based cohort study.

BACKGROUND: Life satisfaction (LS) is part of a positive psychological feeling that protects individuals from a physical decline in old age. A healthy lifestyle, including physical activity (PA) and a healthy diet, such as the intake of fruits and vegetables (F&V), can lead to a better experience of LS in older adults. However, the association between PA and F&V intake habits when occurring together in older adults is still unclear for LS. The study aimed to investigate the combined association of PA and F&V intake on LS among a cohort of older Taiwanese adults. METHODS: Five waves of population-based data gathered by the Taiwan Longitudinal Survey on Aging between 1999 and 2015 were analyzed. The year 1999 was set as the baseline, and the number of respondents was 4,440. The independent variables included the frequency, duration, and intensity of PA and the frequency of F&V intake. LS was assessed by using the Life Satisfaction Index. We performed generalized estimating equations (GEE) analysis with adjustment for covariates of health behaviors and health indicators. RESULTS: After adjusting for confounders, model 1 showed that moderate and high-PA levels significantly correlated with LS (odds ratio [OR] = 1.41, 95% CI = 1.12-1.79) and OR = 1.74, 95% CI = 1.50-2.02). Moreover, high-F&V intake significantly correlated with LS (OR = 2.07, 95% CI = 1.69-2.53). Regarding the combined association shown in model 2, compared with both the low PA and F&V intake group, there were significantly higher LS in the both-high-group (OR = 4.69, 95% CI = 3.49-6.31), only-high-F&V intake (OR = 2.87, 95% CI = 2.14-3.85), only-high-PA (OR = 2.48, 95% CI = 1.74-3.52). CONCLUSIONS: Our findings show the significant combined association of PA and F&V intake on LS among older adults. In addition, older adults who engaged in higher frequency, duration, and intensity of daily PA combined more than seven times a week of F&V intake had significantly higher LS than those who only engaged in low PA or only intake less F&V. Adopting multiple healthy behaviors in daily life is a safe and effective approach to promote LS among older adults.

Caregivers' Perceptions of Ride-On Cars and Behavioral Changes for Young Children With Motor Delays.

PURPOSE: To investigate caregivers' perceptions of using a ride-on car (ROC) and observe behavioral changes in their children following ROC training and conventional therapy. METHODS: The study included 37 toddlers with motor delays and their caregivers, divided into an ROC training group (27 participants) and a conventional therapy group (10 participants). A binary, multiple-choice, and open-ended questionnaire was administered before and after a 3-month intervention period. RESULTS: Over 70% of caregivers had no experience using mobility devices before the intervention. Before the intervention, children's ability and age were key barriers to using mobility devices. After the intervention, caregivers in the ROC group were more inclined than those in the control group to allocate a larger budget for these devices. CONCLUSIONS: The findings highlight the importance of pediatric physical and occupational therapists working collaboratively with caregivers during such interventions and raising awareness about government subsidies and resources available for mobility devices.

Human resource management research in healthcare: a big data bibliometric study.

Human resource management (HRM) in healthcare is an important component in relation to the quality and efficiency of healthcare delivery. However, a comprehensive overview is lacking to assess and track the current status and trends of HRM research in healthcare. This study aims to describe the current situation and global trends in HRM research in healthcare as well as to indicate the frontiers and future directions of research. The research methodology is based on bibliometric mapping using scientific visualization software (VOSviewer). The data were collected from the Web of Science(WoS) core citation database. After applying the search criteria, we retrieved 833 publications, which have steadily increased over the last 30 years. In addition, 93 countries and regions have published relevant research. The United States and Australia have made significant contributions in this area. Current research articles focus on topics clustered into performance, hospital/COVID-19, job satisfaction, human resource management, occupational/mental health, and quality of care. The most frequently co-occurring keywords are human resource management, job satisfaction, nurses, hospitals, health services, quality of care, COVID-19, and nursing. There is limited research on compensation management and employee relations management, so the current HRM research field still has not been able to present a complete and systematic roadmap. We propose that our colleagues should consider focusing on these research gaps in the future.

Presynaptic SNAP-25 regulates retinal waves and retinogeniculate projection via phosphorylation.

Patterned spontaneous activity periodically displays in developing retinas termed retinal waves, essential for visual circuit refinement. In neonatal rodents, retinal waves initiate in starburst amacrine cells (SACs), propagating across retinal ganglion cells (RGCs), further through visual centers. Although these waves are shown temporally synchronized with transiently high PKA activity, the downstream PKA target important for regulating the transmission from SACs remains unidentified. A t-SNARE, synaptosome-associated protein of 25 kDa (SNAP-25/SN25), serves as a PKA substrate, implying a potential role of SN25 in regulating retinal development. Here, we examined whether SN25 in SACs could regulate wave properties and retinogeniculate projection during development. In developing SACs, overexpression of wild-type SN25b, but not the PKA-phosphodeficient mutant (SN25b-T138A), decreased the frequency and spatial correlation of wave-associated calcium transients. Overexpressing SN25b, but not SN25b-T138A, in SACs dampened spontaneous, wave-associated, postsynaptic currents in RGCs and decreased the SAC release upon augmenting the cAMP-PKA signaling. These results suggest that SN25b overexpression may inhibit the strength of transmission from SACs via PKA-mediated phosphorylation at T138. Moreover, knockdown of endogenous SN25b increased the frequency of wave-associated calcium transients, supporting the role of SN25 in restraining wave periodicity. Finally, the eye-specific segregation of retinogeniculate projection was impaired by in vivo overexpression of SN25b, but not SN25b-T138A, in SACs. These results suggest that SN25 in developing SACs dampens the spatiotemporal properties of retinal waves and limits visual circuit refinement by phosphorylation at T138. Therefore, SN25 in SACs plays a profound role in regulating visual circuit refinement.

The First Evaluation of Proteinase K-Resistant Prion Protein (PrPSc) in Korean Appendix Specimens.

Background and Objectives: Prion diseases are fatal neurodegenerative disorders caused by the abnormal proteinase K-resistant prion protein (PrPSc). Since variant Creutzfeldt-Jakob disease (CJD) was first reported in the United Kingdom (UK) in 1996, the occurrence of variant CJD has been reported in over 10 countries. To date, variant CJD has not been reported in Korea. However, the E211K somatic mutation in the prion protein gene (PRNP), which is related to bovine spongiform encephalopathy (BSE), was reported in Korean Holstein cattle, and atypical BSE, which is supposed to be sporadic BSE, has been occurring in many countries, including Japan and the USA. These results suggest that BSE may occur naturally in Korea. Thus, we performed a preemptive PrPSc test in appendix specimens to diagnose variant CJD in a Korean population. Materials and Methods: In the present study, we investigated CJD-related mutations and polymorphisms of the PRNP gene and carried out an examination on PrPSc in appendix specimens of Korean patients after appendectomy. Results: In all Korean appendix specimens tested, PrPSc bands were not detected. Conclusion: To the best of our knowledge, this was the first evaluation of PrPSc in Korean appendix specimens.

Fine particulate matter constituents associated with emergency room visits for pediatric asthma: a time-stratified case-crossover study in an urban area.

BACKGROUND: Global asthma-related mortality tallies at around 2.5 million annually. Although asthma may be triggered or exacerbated by particulate matter (PM) exposure, studies investigating the relationship of PM and its components with emergency department (ED) visits for pediatric asthma are limited. This study aimed to estimate the impact of short-term exposure to PM constituents on ED visits for pediatric asthma. METHODS: We retrospectively evaluated non-trauma patients aged younger than 17 years who visited the ED with a primary diagnosis of asthma. Further, measurements of PM with aerodynamic diameter of < 10 µm (PM10), PM with aerodynamic diameter of < 10 µm (PM2.5), and four PM2.5 components (i.e., nitrate (NO3-), sulfate (SO42-), organic carbon (OC), and elemental carbon (EC)) were collected between 2007 and 2010 from southern particulate matter supersites. These included one core station and two satellite stations in Kaohsiung City, Taiwan. A time-stratified case-crossover study was conducted to analyze the hazard effect of PM. RESULTS: Overall, 1597 patients were enrolled in our study. In the single-pollutant model, the estimated risk increase for pediatric asthma incidence on lag 3 were 14.7% [95% confidence interval (CI), 3.2-27.4%], 13.5% (95% CI, 3.3-24.6%), 14.8% (95% CI, 2.5-28.6%), and 19.8% (95% CI, 7.6-33.3%) per interquartile range increments in PM2.5, PM10, nitrate, and OC, respectively. In the two-pollutant models, OC remained significant after adjusting for PM2.5, PM10, and nitrate. During subgroup analysis, children were more vulnerable to PM2.5 and OC during cold days (< 26 °C, interaction p = 0.008 and 0.012, respectively). CONCLUSIONS: Both PM2.5 concentrations and its chemical constituents OC and nitrate are associated with ED visits for pediatric asthma. Among PM2.5 constituents, OC was most closely related to ED visits for pediatric asthma, and children are more vulnerable to PM2.5 and OC during cold days.

Association between prehospital prognostic factors on out-of-hospital cardiac arrest in different age groups.

BACKGROUND: The prognosis of out-of-hospital cardiac arrest (OHCA) is very poor. While several prehospital factors are known to be associated with improved survival, the impact of prehospital factors on different age groups is unclear. The objective of the study was to access the impact of prehospital factors and pre-existing comorbidities on OHCA outcomes in different age groups. METHODS: A retrospective observational analysis was conducted using the emergency medical service (EMS) database from January 2015 to December 2019. We collected information on prehospital factors, underlying diseases, and outcome of OHCAs in different age groups. Kaplan-Meier type survival curves and multivariable logistic regression were used to analyze the association between modifiable pre-hospital factors and outcomes. RESULTS: A total of 4188 witnessed adult OHCAs were analyzed. For the age group 1 (age ≦75 years old), after adjustment for confounding factors, EMS response time (odds ratio [OR] = 0.860, 95% confidence interval [CI]: 0.811-0.909, p < 0.001), public location (OR = 1.843, 95% CI: 1.179-1.761, p < 0.001), bystander CPR (OR = 1.329, 95% CI: 1.007-1.750, p = 0.045), attendance by an EMT-Paramedic (OR = 1.666, 95% CI: 1.277-2.168, p < 0.001), and prehospital defibrillation by automated external defibrillator (AED)(OR = 1.666, 95% CI: 1.277-2.168, p < 0.001) were prognostic factors for survival to hospital discharge in OHCA patients. For the age group 2 (age > 75 years old), age (OR = 0.924, CI:0.880-0.966, p = 0.001), EMS response time (OR = 0.833, 95% CI: 0.742-0.928, p = 0.001), public location (OR = 4.290, 95% CI: 2.450-7.343, p < 0.001), and attendance by an EMT-Paramedic (OR = 2.702, 95% CI: 1.704-4.279, p < 0.001) were independent prognostic factors for survival to hospital discharge in OHCA patients. CONCLUSIONS: There were variations between younger and older OHCA patients. We found that bystander CPR and prehospital defibrillation by AED were independent prognostic factors for younger OHCA patients but not for the older group.

Human Case of Ehrlichia chaffeensis Infection, Taiwan.

In 2018, an immunosuppressed woman in southern Taiwan had onset of fever, chills, myalgia, malaise, thrombocytopenia, lymphocytopenia, and elevated hepatic transaminases. Investigation revealed infection with Ehrlichia chaffeensis. This autochthonous case of human monocytotropic ehrlichiosis was confirmed by PCR, DNA sequencing, and seroconversion.

Predictive factors of neurologic deterioration in patients with spontaneous cerebellar hemorrhage: a retrospective analysis.

BACKGROUND: Cerebellar hemorrhage is a potentially life-threatening condition and neurologic deterioration during hospitalization could lead to severe disability and poor outcome. Finds out the factors influencing neurologic deterioration during hospitalization is essential for clinical decision-making. METHODS: One hundred fifty-five consecutive patients who suffered a first spontaneous cerebellar hemorrhage (SCH) were evaluated in this 10-year retrospective study. This study aimed to identify potential clinical, radiological and clinical scales risk factors for neurologic deterioration during hospitalization and outcome at discharge. RESULTS: Neurologic deterioration during hospitalization developed in 17.4% (27/155) of the patient cohort. Obliteration of basal cistern (p≦0.001) and hydrocephalus (p≦0.001) on initial brain computed tomography (CT), median Glasgow Coma Scale (GCS) score at presentation (p≦0.001) and median intracerebral hemorrhage (ICH) score (P≦0.001) on admission were significant factors associated with neurologic deterioration. Stepwise logistic regression analysis showed that patients with obliteration of basal cistern on initial brain CT scan had an odds ratio (OR) of 9.17 (p = 0.002; 95% confidence interval (CI): 0.026 to 0.455) adjusted risk of neurologic deterioration compared with those without obliteration of basal cistern. An increase of 1 point in the ICH score on admission would increase the neurologic deterioration rate by 83.2% (p = 0.010; 95% CI: 1.153 to 2.912). The ROC curves showed that the AUC for ICH score on presentation was 0.719 (p = 0.000; 95% CI: 0.613-0.826) and the cutoff value was 2.5 (sensitivity 80.5% and specificity 73.7%). CONCLUSION: Patients had obliteration of basal cistern on initial brain CT and ICH score greater or equal to 3 at admission implies a greater danger of neurologic deterioration during hospitalization. Cautious clinical assessments and repeated brain images study are mandatory for those high-risk patients to prevent neurologic deterioration during hospitalization.

Using Xenopus tissue cultures for the study of myasthenia gravis pathogenesis.

Myasthenia gravis (MG), the most common autoimmune disease of neuromuscular junction (NMJ), is heterogeneous in terms of pathophysiology, which is determined by the pathogenic antigen of autoantibodies targeting to synaptic proteins at the NMJs. Currently, patients suspected with MG are routinely screened for the presence of autoantibodies against acetylcholine receptor (AChR) or muscle-specific kinase (MuSK) using a cell-based assay (CBA) that involves the expression of target synaptic membrane protein in heterologous cell lines. However, some autoantibodies may only show reactivity for binding to densely clustered AChR in the physiological conformation, while AChR clustering is known to involve signaling events orchestrated by over a dozen of postsynaptic proteins. To improve the existing serological diagnosis of MG, this study explored the possibility of using the well-established Xenopus primary culture system as a novel CBA for MG. Here, by examining the pathogenic effects of four MG human plasma samples, we found that the samples from both seropositive and seronegative MG patients effectively induced the disassembly of aneural AChR clusters in cultured Xenopus muscle cells, as well as the nerve-induced AChR clusters in the nerve-muscle co-cultures. Importantly, the disassembly of AChR clusters was spatio-temporally correlated to the disappearance of actin depolymerizing factor (ADF)/cofilin, an actin regulator involved in AChR trafficking and clustering. Taken together, this study develops a reliable CBA using Xenopus primary cultures for screening the pathogenicity of human MG plasma samples, and providing a platform for investigating the pathogenic mechanisms underlying the endocytic trafficking and degradation of AChRs at NMJs in MG patients.

Physician Risk Tolerance and Head Computed Tomography Use for Patients with Isolated Headaches.

BACKGROUND: Headaches are one of the most common afflictions in adults and reasons for emergency department (ED) visits. OBJECTIVE: We sought to determine the association between physician risk tolerance and head computed tomography (CT) use in patients with headaches in the ED. METHODS: We performed a retrospective study of patients with nontraumatic isolated headaches in the ED and then administered two instruments (Risk-Taking subscale [RTS] of the Jackson Personality Index and a Malpractice Fear Scale [MFS]) to attending physicians who had evaluated these patients and made decisions regarding head CT scans. Outcomes were head CT use during ED evaluation and hospital admission. A hierarchical logistic regression was used to determine the effect of risk scales on head CT use. RESULTS: Of the 1328 patients with headaches, 521 (39.2%) received brain CTs and 83 (6.9%) were admitted; 33 (2.5%) patients received a final diagnosis that the central nervous system was the origin of the disease. Among the 17 emergency physicians (EPs), the median of the MFS and RTS was 23 (interquartile range [IQR] 19-25) and 21 (IQR 20-23), respectively. EPs who were relatively risk-averse and those who possessed a higher level of malpractice fear were not more likely to order brain CTs for patients with isolated headaches. CONCLUSIONS: Individual EP risk tolerance, as measured by RTS, and malpractice concerns, measured by MFS, were not predictive of CT use in patients with isolated headaches.

The diversity of human papillomavirus infection among human immunodeficiency virus-infected women in Yunnan, China.

BACKGROUND: Yunnan has one of the oldest and the most severe human immunodeficiency virus (HIV) epidemics in China. We conducted an observational study to evaluate the human papillomavirus (HPV) genotype distribution in relation to cervical neoplastic disease risk among HIV-infected women in Yunnan. METHODS: We screened 301 HIV-infected non-pregnant women in Mangshi prefecture in Yunnan province. All consenting participants underwent simultaneous and independent assessment by cervical cytology, colposcopy-histopathology, and HPV genotyping. Unadjusted and multivariable-adjusted multinomial logistic regression analysis was conducted to evaluate factors associated with single or multiple carcinogenic HPV genotypes. RESULTS: HPV genotypes were present in 43.5% (131/301) overall, and carcinogenic HPV genotypes were present in 37.5% (113/301) women. Among women with carcinogenic HPV genotypes, 80 (70.8% of 113) had a single carcinogenic HPV type, while 33 (29.2%) women had multiple (2 or more) carcinogenic HPV types. Overall, the most common carcinogenic HPV types were HPV52 (7.3%), HPV58 (6.6%), HPV18 (6.3%), HPV16 (6.0%), and HPV33 (5.3%). In women with cervical precancerous lesions (i.e., high-grade squamous intraepithelial lesions [HSIL] on cytology or cervical intraepithelial neoplasia grade 2 or worse [CIN2+] detected on colposcopy-histology), the most commonly detected genotypes were HPV16 (28.6%), HPV52 (25.0%), HPV58 (17.9%), HPV18 (10.7%) and HPV31 (10.7%). Increasing age was an independent risk factor associated with presence of single carcinogenic HPV types (adjusted odds ratio: 1.04, 95%CI: 1.01-1.07, p = 0.012) but not with the presence of multiple carcinogenic types in the multivariable-adjusted models. CONCLUSIONS: As HIV-infected women continue to live longer on antiretroviral therapy in China, it will be increasingly important to screen for, and prevent, HPV-associated cervical cancer in this population, especially given the wide diversity and multiplicity of HPV genotypes.

Minimum Minutes Machine-Learning Microfluidic Microbe Monitoring Method (M7).

Frequent outbreaks of viral diseases have brought substantial negative impacts on society and the economy, and they are very difficult to detect, as the concentration of viral aerosols in the air is low and the composition is complex. The traditional detection method is manually collection and re-detection, being cumbersome and time-consuming. Here we propose a virus aerosol detection method based on microfluidic inertial separation and spectroscopic analysis technology to rapidly and accurately detect aerosol particles in the air. The microfluidic chip is designed based on the principles of inertial separation and laminar flow characteristics, resulting in an average separation efficiency of 95.99% for 2 µm particles. We build a microfluidic chip composite spectrometer detection platform to capture the spectral information on aerosol particles dynamically. By employing machine-learning techniques, we can accurately classify different types of aerosol particles. The entire experiment took less than 30 min as compared with hours by PCR detection. Furthermore, our model achieves an accuracy of 97.87% in identifying virus aerosols, which is comparable to the results obtained from PCR detection.

A novel dual polarization multiplexing RoF system integrating optical fiber and FSO channel with AMI downlink signals.

Using dual polarization multiplexing alternate mark inversion (AMI) downlink signals, a novel radio over fiber (RoF) system integrating optical fiber and FSO channel is designed to adapt to applications in mountainous areas and other complex terrain areas. Optical heterodyne technology and self-mixing homodyne detection method are used to realize high sensitivity detection of the received signals after 25.1 km channel (including 1 km single-mode fiber and 100 m free space link) transmission. Moreover, polarization multiplexing technology is introduced to exponentially increase the transmission capacity of downlink signals. This scheme not only can be compatible with traditional optical fiber transmission systems, but also support the wireless optical access application of millimeter wave signals in RoF systems.

Muscle-origin creatinine-cystatin C ratio is an osteoporosis marker in individuals with normal renal function: evidence from observational and Mendelian randomization analysis.

Background: Creatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function. Methods: We selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively. Results: Amongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P<0.05). The multivariable logistic regression model showed that the decrease in CCR was associated with a higher risk of osteoporosis/fracture in all models (all P<0.05). In the multivariable Cox regression analysis with adjustment for potential confounders, reduced CCR is associated with the incidence of osteoporosis and fracture in both total subjects and gender-stratified subjects (all P<0.05). A significant non-linear dose-response was observed between CCR and osteoporosis/fracture risk (P non-linearity < 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P<5×10-8). MR analyses indicated the causal effect from CCR to osteoporosis/fracture. Conclusions: Reduced CCR predicted increased risks of osteoporosis/fracture, and significant causal effects support their associations. These findings indicated that the muscle-origin serum CCR was a potential biomarker to assess the risks of osteoporosis and fracture.

Exploring human resource management in the top five global hospitals: a comparative study.

Background: The pivotal role of Human Resource Management (HRM) in hospital administration has been acknowledged in research, yet the examination of HRM practices in the world's premier hospitals has been scant. Objective: This study explored how the world's leading hospitals attain operational efficiency by optimizing human resource allocation and melding development strategies into their HRM frameworks. A comparative analysis of the HRM frameworks in the top five global hospitals was undertaken to offer a reference model for other hospitals. Methods: This research offers a comparative exploration of the HRM frameworks utilized by the top five hospitals globally, underscoring both shared and distinct elements. Using a multi-case study methodology, the research scrutinized each hospital's HRM framework across six modules, drawing literature from publicly accessible sources, including websites, annual reports, and pertinent English-language scholarly literature from platforms such as Google Scholar, PubMed, Medline, and Web of Science. Results: The analyzed hospitals exhibited inconsistent HRM frameworks, yet all manifested potent organizational cultural attributes and maintained robust employee training and welfare policies. The design of the HR systems was strategically aligned with the hospitals' objectives, and the study established that maintaining a sustainable talent system is pivotal to achieving hospital excellence. Conclusion: The HRM frameworks of the five analyzed hospitals align with their developmental strategies and exhibit unique organizational cultural attributes. All five hospitals heavily prioritize aligning employee development with overall hospital growth and place a spotlight on fostering a healthy working environment and nurturing employees' sense of achievement. While compensation is a notable performance influencer, it is not rigorously tied to workload in these hospitals, with employees receiving mid-to-upper industry-range compensation. Performance assessment criteria focus on job quality and aligning employee actions with organizational values. Comprehensive welfare and protection are afforded to employees across all five hospitals.

Organisational Culture Research in Healthcare: A Big Data Bibliometric Study.

Across international healthcare, organisational culture and work environment have become central to all patient safety. However, there is a lack of comprehensive overview to assess and track the evolution of the literature on organisational culture in healthcare. This study aims to describe the current situation and global trends in organisational culture research in healthcare. The methodology is based on bibliometric mapping using scientific visualisation software (CiteSpace and VOSviewer). The big data were collected from the Web of Science core citation database. After applying the search criteria, we retrieved 1559 publications, which have steadily increased over the last two decades. In addition, 92 countries and regions have published studies on organisational culture in healthcare. The United States has made significant contributions to this field. In particular, organisational culture occupies an important position in the quality management of different types of care and caregiving. At the same time, organisational culture in healthcare may be inadequately researched in terms of theoretical underpinnings, which in turn leads to a lack of widespread dissemination of practice, and research on organisational culture in healthcare through evidence-based medicine may remain a significant focus and hot topic throughout the research field in the coming years.

Deep learning-derived spatial organization features on histology images predicts prognosis in colorectal liver metastasis patients after hepatectomy.

Histopathological images of colorectal liver metastases (CRLM) contain rich morphometric information that may predict patients' outcomes. However, to our knowledge, no study has reported any practical deep learning framework based on the histology images of CRLM, and their direct association with prognosis remains largely unknown. In this study, we developed a deep learning-based framework for fully automated tissue classification and quantification of clinically relevant spatial organization features (SOFs) in H&E-stained images of CRLM. The SOFs based risk-scoring system demonstrated a strong and robust prognostic value that is independent of the current clinical risk score (CRS) system in independent clinical cohorts. Our framework enables fully automated tissue classification of H&E images of CRLM, which could significantly reduce assessment subjectivity and the workload of pathologists. The risk-scoring system provides a time- and cost-efficient tool to assist clinical decision-making for patients with CRLM, which could potentially be implemented in clinical practice.

Complementary Fe(3+)- and Ti(4+)-immobilized metal ion affinity chromatography for purification of acidic and basic phosphopeptides.

RATIONALE: Despite advances in mass spectrometry (MS)-based identification, effective phosphopeptide enrichment is a prerequisite towards comprehensive phosphoproteomic analysis. Based on the different binding affinities and coordination geometries of the Ti(4+) and Fe(3+) ions with the phosphate group, we report a complementary metal-directed immobilized metal ion affinity chromatography (IMAC) method to increase the identification coverage of a phosphoproteome. METHODS: Phosphopeptides from standard phosphoproteins and Raji B cells were enriched from Ti(4+)-IMAC and Fe(3+)-IMAC methods, followed by matrix-assisted laser desorption/ionization (MALDI) MS and Orbitrap MS analysis. Optimal enrichment specificity was achieved by selection of acid structure/concentration and organic solvent to compete with non-phosphopeptides. The effect of the metal ion and the chelating compound was evaluated by the comparison of the characteristics of enriched phosphopeptides between Ti(4+)-IMAC, Fe(3+)-IMAC and TiO(2) methods. RESULTS: To address the low enrichment specificity of the Ti(4+)-IMAC method, a simple one-step acid/solvent controlled IMAC method was developed with significantly improved specificity (88%) and recovery (93%). The most striking discovery is that the optimal Ti(4+)-IMAC and Fe(3+)-IMAC methods have low overlapping percentage (10%) among the 2905 enriched phosphopeptides from Raji cells, comprised of the distinct characteristics including hydrophobicity, amino acid compositions, and frequency of multiple phosphorylation of the phosphopeptides. CONCLUSIONS: The reported Fe(3+)-IMAC and Ti(4+)-IMAC methods can complementarily enrich acidic and basic phosphopeptides to effectively increase the identification coverage of an heterogeneous phosphoproteome (twice than the single approach). Given the reproducibility and low sample loss, the combination of our enrichment strategy with a quantitative technique could be feasible for quantitative phosphoproteomics.

IL-33 induces IL-13-dependent cutaneous fibrosis.

IL-33 is constitutively expressed in epithelial barrier tissues, such as skin. Although increased expression of IL-33/IL-33R has been correlated with fibrotic disorders, such as scleroderma and progressive systemic sclerosis, the direct consequences of IL-33 release in skin has not been reported. To determine the effects of dysregulated IL-33 signaling in skin, we administered IL-33 s.c. and monitored its effects at the injection site. Administration of IL-33 resulted in IL-33R-dependent accumulation of eosinophils, CD3(+) lymphocytes, F4/80(+) mononuclear cells, increased expression of IL-13 mRNA, and the development of cutaneous fibrosis. Consistent with extensive cutaneous tissue remodeling, IL-33 resulted in significant modulation of a number of extracellular matrix-associated genes, including collagen VI, collagen III, and tissue inhibitor of metalloproteases-1. We establish that IL-33-induced fibrosis requires IL-13 using IL-13 knockout mice and eosinophils using Delta dblGATA mice. We show that bone marrow-derived eosinophils secrete IL-13 in response to IL-33 stimulation, suggesting that eosinophil-derived IL-13 may promote IL-33-induced cutaneous fibrosis. Collectively, our results identify IL-33 as a previously unrecognized profibrotic mediator in skin and highlight the cellular and molecular pathways by which this pathology develops.