Identification and validation of calcium extrusion-related genes prognostic signature in colon adenocarcinoma.

Background: Disruptions in calcium homeostasis are associated with a wide range of diseases, and play a pivotal role in the development of cancer. However, the construction of prognostic models using calcium extrusion-related genes in colon adenocarcinoma (COAD) has not been well studied. We aimed to identify whether calcium extrusion-related genes serve as a potential prognostic biomarker in the COAD progression. Methods: We constructed a prognostic model based on the expression of calcium extrusion-related genes (SLC8A1, SLC8A2, SLC8A3, SLC8B1, SLC24A2, SLC24A3 and SLC24A4) in COAD. Subsequently, we evaluated the associations between the risk score calculated by calcium extrusion-related genes and mutation signature, immune cell infiltration, and immune checkpoint molecules. Then we calculated the immune score, stromal score, tumor purity and estimate score using the Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm. The response to immunotherapy was assessed using tumor immune dysfunction and exclusion (TIDE). Finally, colorectal cancer cells migration, growth and colony formation assays were performed in RKO cells with the overexpression or knockdown SLC8A3, SLC24A2, SLC24A3, or SLC24A4. Results: We found that patients with high risk score of calcium extrusion-related genes tend to have a poorer prognosis than those in the low-risk group. Additionally, patients in high-risk group had higher rates of KRAS mutations and lower MUC16 mutations, implying a strong correlation between KRAS and MUC16 mutations and calcium homeostasis in COAD. Moreover, the high-risk group showed a higher infiltration of regulatory T cells (Tregs) in the tumor microenvironment. Finally, our study identified two previously unreported model genes (SLC8A3 and SLC24A4) that contribute to the growth and migration of colorectal cancer RKO cells. Conclusions: Altogether, we developed a prognostic risk model for predicting the prognosis of COAD patients based on the expression profiles of calcium extrusion-related genes, Furthermore, we validated two previously unreported tumor suppressor genes (SLC8A3 and SLC24A4) involved in colorectal cancer progression.

Predictive value of total cholesterol to high-density lipoprotein cholesterol ratio for chronic kidney disease among adult male and female in Northwest China.

Background: Studies have found that the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) was associated with the development of chronic kidney disease (CKD). However, the relationship in different genders was rarely discussed. The aim of this study was to explore this relationship and assess its predictive power for both males and females. Methods: Based on a prospective cohort platform in northwest China, 32,351 participants without CKD were collected in the baseline and followed up for approximately 5 years. Cox proportional hazard model and restricted cubic spline regression analysis were performed to investigate the association between TC, HDL-C, TC/HDL-C and CKD in adult female and male. The clinical application value of the indicators in predicting CKD was evaluated by the receiver operator characteristic curve. Results: During a mean follow-up of 2.2 years, 484 males and 164 females developed CKD. After adjusted for relevant confounders, for every one standard deviation increase in TC, HDL-C and TC/HDL-C, the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for CKD were 1.17 (1.05-1.31), 0.84 (0.71-0.99), and 1.15 (1.06-1.25) for males, 0.94 (0.78-1.13), 0.58 (0.35-0.95), and 1.19 (1.01-1.40) for females, respectively. The results also showed that TC, HDL-C, and TC/HDL-C were associated with CKD in a linear dose-response relationship. The TC/HDL-C had the largest area under the curve (AUC) compared to TC and HDL-C, and the AUC among the females was larger than that among males. Conclusions: The TC/HDL-C was significantly associated with CKD in adult males and females and has better clinical value in predicting CKD than TC and HDL-C, especially in females.

[Effects of reductive soil disinfestation and organic fertilizer application on microbial community stability in a facility vegetable soil]. / 强还原处理和施用有机肥对设施蔬菜地土壤微生物群落稳定性的影响.

Reductive soil disinfestation (RSD) is an effective method for remediating degraded facility vegetable soils. However, the effectiveness of RSD using green manure as a carbon source in the field has not yet been clarified. We investigated the effects of RSD and organic fertilizer application on soil microbial community composition, diversity, and stability in a degraded facility vegetable soil. There were six treatments, including no fertilization (CK), no fertilization and soil flooded and mulched with plastic film (FF), soil amended with chicken manure (OM), soil amended with chicken manure and flooded and mulched with plastic film (OMR), soil amended with Sesbania cannabina (TF), and soil amended with S. cannabina and flooded and mulched with plastic film (TR). The results showed that the OMR and TR treatments significantly decreased bacterial Chao1 index, altered bacterial and fungal community structure, and increased the relative abundances of Bacillus, Rhodococcus, Clostridium, and Penicillium. The TR treatment significantly reduced the relative abundance of Fusarium. Results of redundancy analysis and Mantel test analysis suggested that soil ammonium nitrogen and dissolved organic carbon contents were the key factors influencing bacterial community composition, and soil pH was the key factor affecting fungal community composition. Results of cohesion analysis showed that the OMR and TR treatments significantly improved bacterial community stability, and that there was no difference between OMR and TR treatments. The TR treatment enhanced fungal community stability, which was significantly higher than the OMR treatment. Therefore, the RSD with green manure as carbon source could be effective remediation practice to improve soil health.

Associations between transfusion reactions and thromboembolism development in blood-transfused patients: A retrospective cohort study.

BACKGROUND: Blood transfusion (BT) may be associated with an increased risk of thromboembolism. The associations between transfusion reactions (TRs) during BTs and potential risk factors for the development of thromboembolism in patients underwent blood transfusion have not been analyzed. Therefore, this study aimed to compare risk factors associated with the development of venous thromboembolism (VTE) or pulmonary embolism (PE) between patients underwent blood transfusion with and without TRs. STUDY DESIGNS AND METHODS: The retrospective study was conducted between April 1, 2017, and March 31, 2020, at a medical center in Taiwan. Blood-transfused patients were grouped into two cohorts as follows: those who experienced TRs and those who did not experience TRs. Both cohorts were subjected to follow-up until March 31, 2021. The endpoints for both groups were the occurrence of VTE or PE or the date of March 31, 2021. To investigate between-cohort risk differences, a Kaplan-Meier survival analysis and multiple Cox proportional hazard model was used. RESULTS: A total of 10,759 patients underwent 59,385 transfusion procedures, with 703 patients in the TR group, and 10,056 patients in the non-TR group. The risk of VTE or PE was twice as high in the TR group than in the non-TR group (adjusted hazard ratio 2.53, 95% confidence interval 1.49-4.29, p = .001). Meanwhile, age, female sex, transfusion frequency increment, and being nondiabetic was associated with an increased risk of developing thromboembolism. CONCLUSION: TRs are associated with increased long-term thromboembolism risk in patients underwent blood transfusion. It is imperative for clinicians to acknowledge this and maintain rigorous follow-up.

Large-Dynamic-Range Ocular Aberration Measurement Based on Deep Learning with a Shack-Hartmann Wavefront Sensor.

The Shack-Hartmann wavefront sensor (SHWFS) is widely utilized for ocular aberration measurement. However, large ocular aberrations caused by individual differences can easily make the spot move out of the range of the corresponding sub-aperture in SHWFS, rendering the traditional centroiding method ineffective. This study applied a novel convolutional neural network (CNN) model to wavefront sensing for large dynamic ocular aberration measurement. The simulation results demonstrate that, compared to the modal method, the dynamic range of our method for main low-order aberrations in ocular system is increased by 1.86 to 43.88 times in variety. Meanwhile, the proposed method also has the best measurement accuracy, and the statistical root mean square (RMS) of the residual wavefronts is 0.0082 ± 0.0185 λ (mean ± standard deviation). The proposed method generally has a higher accuracy while having a similar or even better dynamic range as compared to traditional large-dynamic schemes. On the other hand, compared with recently developed deep learning methods, the proposed method has a much larger dynamic range and better measurement accuracy.

Molecular and immunological characteristics of postoperative relapse in lymph node-positive esophageal squamous cell cancer.

BACKGROUND: The molecular and immunological characteristics of primary tumors and positive lymph nodes in esophageal squamous cell carcinoma (ESCC) are unknown and the relationship with recurrence is unclear, which this study attempted to explore. METHODS: A total of 30 ESCC patients with lymph node positive (IIB-IVA) were enrolled. Among them, primary tumor and lymph node specimens were collected from each patient, and subjected to 551-tumor-targeted DNA sequencing and 289-immuno-oncology RNA panel sequencing to identify the different molecular basis and immunological features, respectively. RESULTS: The primary tumors exhibited a higher mutation burden than lymph nodes (p < 0.001). One-year recurrent ESCC exhibited a higher Mucin16 (MUC16) mutation rate (p = 0.038), as well as univariate and multivariate analysis revealed that MUC16 mutation is independent genetic factor associated with reduced relapse-free survival (univariate, HR: 5.39, 95% CI: 1.67-17.4, p = 0.005; multivariate, HR: 7.36, 95% CI: 1.79-30.23, p = 0.006). Transcriptomic results showed non-relapse group had higher cytolytic activity (CYT) score (p = 0.025), and was enriched in the IFN-α pathway (p = 0.036), while those in the relapsed group were enriched in the TNF-α/NF-κB (p = 0.001) and PI3K/Akt pathway (p = 0.014). CONCLUSION: The difference in molecular characteristics between primary lesions and lymph nodes may be the cause of the inconsistent clinical outcomes. Mutations of MUC16 and poor immune infiltration are associated with rapid relapse of nodes-positive ESCC.

Identification of key sensory and chemical factors determining flavor quality of Xinyu mandarin during ripening and storage.

Xinyu mandarin is popular for its good flavor, but its flavor deteriorates during postharvest storage. To better understand the underlying basis of this change, the dynamics of the sensory profiles were investigated throughout fruit ripening and storage. Sweetness and sourness, determined especially by sucrose and citric acid content, were identified as the key sensory factors in flavor establishment during ripening, but not in flavor deterioration during storage. Postharvest flavor deterioration is mainly attributed to the reduction of retronasal aroma and the development of off-flavor. Furthermore, sugars, acids and volatile compounds were analyzed. Among the 101 detected volatile compounds, 10 changed significantly during the ripening process. The concentrations of 15 volatile components decreased during late postharvest storage, among which α-pinene and d-limonene were likely to play key roles in the reduction of aroma. Three volatile compounds were found to increase during storage, associated with off-flavor development.

Widespread Adoption of Microincision Vitrectomy Surgery Improves Visual Outcomes in Endogenous Endophthalmitis with Poor Initial Vision: A 21-Year Experience in Taiwan.

PURPOSE: To review the presentation and visual prognostic factors of patients with endogenous endophthalmitis before and after the introduction of microincision vitrectomy surgery (MIVS), at a tertiary referral hospital in Taiwan, over a 21-year period. METHODS: We retrospectively analyzed medical records of patients diagnosed with endogenous endophthalmitis before and after the introduction of MIVS between January 2002 and December 2022. RESULTS: Data were collected from 147 patients. Diabetes mellitus was the most common comorbidity (59.9%). Liver abscess (32.7%) was the leading source of infection, followed by urinary tract infection (15.0%), and infective endocarditis (5.4%). Klebsiella pneumoniae (50.4%) was the most common pathogen, followed by Staphylococcus aureus (13.5%), and Candida albicans (8.3%). Poor initial visual acuity worse than counting fingers (CF) (p < 0.001) and diabetes mellitus (p = 0.008) were significantly associated with poor visual outcomes. In the treatment of 98 patients with poor initial visual acuity worse than CF, the proportion of vitrectomy surgeries performed increased from 13/56 (23.2%) to 24/42 (57.1%) (p = 0.001) after the introduction of MIVS. Final visual acuity of CF or better increased from 7/56 (12.5%) to 12/42 (28.6%) after the introduction of MIVS (p = 0.046). Vitrectomy was a better prognostic factor for final visual outcome in patients with poor initial visual acuity of worse than CF (p = 0.011) than other factors. CONCLUSION: In endogenous endophthalmitis patients presenting with poor initial visual acuity, vitrectomy was a better visual prognostic factor. MIVS has allowed more patients to undergo vitrectomy and improved visual outcomes.

The association of socioeconomic status on kidney transplant access and outcomes: a nationwide cohort study in Taiwan.

BACKGROUND: Conflicting evidence exists regarding the relationship between socioeconomic status and access to or outcomes after kidney transplantation. This study analyzed the effects of individual and neighborhood socioeconomic status on kidney transplant access and outcomes in Taiwan. METHODS: We used a retrospective cohort study design and performed comparisons using the Cox proportional hazards model after adjusting for risk factors. Data were collected from the National Health Insurance Bureau of Taiwan data (2003-2012). RESULTS: Patients with high individual and neighborhood socioeconomic status had higher chances of receiving kidney transplants than those with low individual and neighborhood socioeconomic status [adjusted hazard ratio (aHR) = 2.04; 95% CI: (1.81-2.31), p < 0.001]. However, there were no significant differences in post-transplant graft failure or patient mortality in Taiwan between individuals of varying socioeconomic status after five years. When we stratified kidney transplants by domestic and overseas transplantation, there were no significant differences in post-transplant mortality and graft failure, but individuals who received a kidney graft in Taiwan with high individual and neighborhood socioeconomic status experienced lower risks of graft failure (aHR = 0.55; [95% CI 0.33-0.89], p = 0.017). CONCLUSION: A relevant disparity exists in accessing kidney transplantation in Taiwan, depending on individual and neighborhood socioeconomic status. However, results post transplantation were not different after five years. Improved access to waitlisting, education, and welfare support may reduce disparities.

A Retrospective Analysis: Investigating Factors Linked to High Lung-RADS Scores in a Nonsmoking, Non-Family History Population.

Low-dose computed tomography screening for lung cancer is currently targeted at heavy smokers or those with a family history of lung cancer. This study aimed to identify risk factors for lung cancer in individuals who do not meet the current lung cancer screening criteria as stipulated by the Taiwan Health Promotion Agency's low-dose computed tomography (LDCT) screening policy. A cohort analysis was conducted on 12,542 asymptomatic healthy subjects aged 20-80 years old who voluntarily underwent LDCT scans from January 2016 to December 2021. Logistic regression demonstrated that several factors, including age over 55 years, female gender, a body mass index (BMI) less than 23, a previous history of respiratory diseases such as tuberculosis or obstructive respiratory diseases (chronic obstructive pulmonary disease [COPD], asthma), and previous respiratory symptoms such as cough or dyspnea, were associated with high-risk lung radiology scores according to LDCT scans. These findings indicate that risk-based assessments using primary data and questionnaires to identify risk factors other than heavy smoking and a family history of lung cancer may improve the efficiency of lung cancer screening.

Association between per- and poly-fluoroalkyl substances and nonalcoholic fatty liver disease: A nested case-control study in northwest China.

Per- and poly-fluoroalkyl substances (PFAS) have been reported to have hepatotoxic effects. However, it is unclear whether they are linked to non-alcoholic fatty liver disease (NAFLD). This nested case-control study focused on the epidemiological links between PFAS and the prevalence of NAFLD. We selected 476 new cases of NAFLD and 952 age- and sex-matched controls from the Jinchang cohort population between 2014 and 2019. Serum concentrations of PFAS were measured using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Only PFAS with a detection rate of ≥90 % were included for analysis, which included PFPeA, PFOA, PFNA, PFHxS, PFOS, and 9Cl-PF3ONS. The relationship between single and co-exposure to PFAS and the occurrence of NAFLD was evaluated using conditional logistic regression, Quantile g-computation (QgC), and Bayesian kernel machine regression (BKMR) model. Logistic regression indicated that PFPeA, PFOA, and 9Cl-PF3ONS were positive correlation with the incidence of NAFLD after adjusting for confounders, with odds ratios (OR) and 95 % confidence interval (CI) of 3.13 (95 % CI: 2.53, 3.86), 1.39 (95 % CI: 1.12, 1.73), and 1.41 (95 % CI: 1.20, 1.66), respectively. PFNA, PFHxS, and PFOS were nonlinearly and negatively associated with the incidence of NAFLD, with OR (95 % CI) of 0.53 (0.46, 0.62), 0.83 (0.73, 0.95), and 0.52 (0.44, 0.61), respectively. QgC showed a significant joint effect of PFAS mixture on NAFLD onset (OR: 1.52, 95 % CI: 1.24, 1.88). BKMR showed a weak positive trend between PFAS mixtures and NAFLD incidence. Positive correlations were primarily driven by PFPeA and 9Cl-PF3ONS, while negative correlations were mainly influenced by PFNA and PFOS. The BKMR model also suggested that there was an interaction between PFOS and PFNA and other four PFAS compounds. In conclusion, our findings suggest that individual and co-exposure to PFAS is associated with a risk of NAFLD onset.

Association between blood culture turnaround time and clinical prognosis in emergency department patients with community acquired bloodstream infection: A retrospective study based on electronic medical records.

Importance: Previous investigations have found that time to positive blood culture (TTP) is a prognostic factor for clinical outcomes. In fact, what the emergency physician sees from the medical information system is TAT (turnaround time) defined as time required to post a bacterial culture report. We propose a definition of blood culture TAT that more closely aligns with clinical considerations by measuring the time from starting specimen culture to the release of an official blood culture report.We were curious to know whether the duration of TAT is as intricately linked to the prognosis of bacteremia as TTP. Objectives: To examine the association between TAT and outcomes of adult patients who present to the ED with community acquired bacteremia. Design: Setting, and Participants: This retrospective study utilized electronic medical records from Kaohsiung Veterans General Hospital (KVGH), a 1000-bed tertiary medical center in Taiwan. Patients were adults aged 18 years and older who presented to ED (Emergency department) for initial diagnosis of community acquired bacteremia from January 1, 2016 to March 31, 2021. Data analysis was performed from December 2022 to January 2023.Main outcomes and measures.The primary outcomes included mortality in the ED, all-cause in-hospital mortality, length of hospital stay, and all-cause 30-day mortality in relation to the individual first report of positive blood culture TAT. Results: A total of 4011 eligible patients with bacteremia were evaluated, of which 207 patients had a blood culture TAT of ≤48 h. The overall 30-day all-cause mortality rate was 13%. Contrary to expectation, no statistically significant differences were observed in clinical prognosis between the TAT groups (≤48 versus >48 h). Subgroup analyses indicated that the length of TAT did not have a significant effect on clinical prognosis in patients who underwent lactate level assessment. Furthermore, no difference in clinical outcome was noted between TAT groups (≤48 versus >48 h) in terms of Gram-negative bacilli or Gram-positive cocci bacteremia. However, in patients with delayed antibiotic treatment (>3 h), a shorter TAT was significantly associated with a fatal outcome. Conclusion: In adults with community-acquired bacteremia, this study did not observe a significant association between blood culture TAT and clinical prognosis, except in cases of delayed antibiotic treatment.

Comprehensive analysis of T cell exhaustion related signature for predicting prognosis and immunotherapy response in HNSCC.

BACKGROUND: T cell exhaustion (TEX) signifies a condition of T cell disorder which implicate the therapeutic benefits and prognostic significance in patients with cancer. However, its role in the Head and Neck Squamous Carcinoma (HNSCC) remains incompletely understood. METHODS: The detailed data of HNSCC samples were obtained from The Cancer Genome Atlas (TCGA) database and two Gene Expression Omnibus (GEO) datasets. We computed the expression scores of four TEX-related pathways and detected gene modules closely linked to these pathways, indicating prognostic significance. Following this, regression analyses were performed to select eight genes for the development of a predictive signature. The predictive capacity of this signature was evaluated. Additionally, we examined the relationships between TEX-related signature risk scores and the effectiveness of immunotherapy as well as drug sensitivity. RESULTS: A novel prognostic model, comprising eight TEX-related genes, was established for patients with HNSCC. The prognostic value was further confirmed using additional GEO datasets: GSE65858 and GSE27020. This signature enables the stratification of patients into high- and low- risk groups, each showing distinct survival outcomes and responsiveness to immunotherapy. The low-risk group demonstrated improved prognosis and enhanced efficacy of immunotherapy. In addition, AZD6482, TAF1, Ribociclib, LGK974, PF4708671 and other drugs showed increased sensitivity in the high-risk group based on drug sensitivity values, offering tailored therapeutic recommendations for individuals with various risks profiles. CONCLUSION: In conclusion, we developed a novel T cell exhaustion-associated signature, which holds considerable predictive value for both the prognosis of patients with HNSCC and the effectiveness of tumor immunotherapy.

Science at risk? Considering the importance of academic freedom for STEM research production across 17 OECD countries.

Since 2011, a declining trend in academic freedom globally has paralleled a rising tide of neo-nationalism. We use fixed effects models to examine data from the Varieties of Democracy (V-DEM) academic freedom index and bibliometric data for 17 OECD countries across nearly three decades (1981-2007) that precede the recent decline in academic freedom. We find substantial, statistically significant, positive relationships between cross-nationally comparable and longitudinal measures of academic freedom and volume of STEM publications. Additionally, academic freedom positively influenced the quality of STEM publications as measured by journal rankings. Our findings were relatively consistent across various measures of academic freedom and model specifications. We discuss implications for safeguarding academic freedom, applying neo-institutional theory, and identifying directions for future research.

Inner sense of rhythm: percussionist brain activity during rhythmic encoding and synchronization.

Introduction: The main objective of this research is to explore the core cognitive mechanisms utilized by exceptionally skilled percussionists as they navigate complex rhythms. Our specific focus is on understanding the dynamic interactions among brain regions, respectively, related to externally directed cognition (EDC), internally directed cognition (IDC), and rhythm processing, defined as the neural correlates of rhythm processing (NCRP). Methods: The research involved 26 participants each in the percussionist group (PG) and control group (CG), who underwent task-functional magnetic resonance imaging (fMRI) sessions focusing on rhythm encoding and synchronization. Comparative analyses were performed between the two groups under each of these conditions. Results: Rhythmic encoding showed decreased activity in EDC areas, specifically in the right calcarine cortex, left middle occipital gyrus, right fusiform gyrus, and left inferior parietal lobule, along with reduced NCRP activity in the left dorsal premotor, right sensorimotor cortex, and left superior parietal lobule. During rhythmic synchronization, there was increased activity in IDC areas, particularly in the default mode network, and in NCRP areas including the left inferior frontal gyrus and bilateral putamen. Conversely, EDC areas like the right dorsolateral prefrontal gyrus, right superior temporal gyrus, right middle occipital gyrus, and bilateral inferior parietal lobule showed decreased activity, as did NCRP areas including the bilateral dorsal premotor cortex, bilateral ventral insula, bilateral inferior frontal gyrus, and left superior parietal lobule. Discussion: PG's rhythm encoding is characterized by reduced cognitive effort compared to CG, as evidenced by decreased activity in brain regions associated with EDC and the NCRP. Rhythmic synchronization reveals up-regulated IDC, down-regulated EDC involvement, and dynamic interplay among regions with the NCRP, suggesting that PG engages in both automatic and spontaneous processing simultaneously. These findings provide valuable insights into expert performance and present opportunities for improving music education.

Price for waiting: the adverse outcomes of boarding critically ill elderly medical patients in the emergency department.

PURPOSE: Boarding, the period in which a patient spends in the emergency department (ED) before admission, may be hazardous to critically ill patients, particularly the elderly. This study investigated the associations of boarding with hospital course, prognosis, and medical expenditure in older patients. METHODS: From January 2019 to December 2021, the medical records of older patients (age ≥ 65) visiting the ED of a tertiary referral hospital who were admitted to the medical intensive care unit (ICU) were retrospectively reviewed. Eligible patients were categorized into two groups according to boarding time with a cutoff set at 6 h. Primary outcomes were in-hospital mortality, ICU/hospital length of stay, and total/average hospitalization cost. Subgroup analyses considered age and disease type. RESULTS: Among 1318 ICU admissions from the ED, 36% were subjected to boarding for over 6 h. Prolonged boarding had a longer ICU (8.9 ± 8.8 vs. 11.2 ± 12.2 days, P < .001) and hospital (17.8 ± 20.1 vs. 22.8 ± 23.0 days, P < .001) stay, higher treatment cost (10.4 ± 13.9 vs. 13.2 ± 16.5 thousands of USD, P = .001), and hospital mortality (19% vs. 25% P = .020). Multivariate regression analysis showed a longer ICU stay in patients aged 65-79 (8.3 ± 8.4 vs. 11.8 ± 14.2 days, P < .001) and cardiology patients (6.9 ± 8.4 vs. 8.8 ± 9.7 days, P = .001). Besides, the treatment cost was also higher for both groups (10.4 ± 14.6 vs. 13.7 ± 17.7 thousands of USD, P = .004 and 8.4 ± 14.0 vs. 11.7 ± 16.6 thousands of USD, P < .001, respectively). CONCLUSION: Extended ED boarding for critically ill medical patients over 65 years old was associated with negative outcomes, including longer ICU/hospital stays, higher treatment costs, and hospital mortality.

The Regulatory Mechanism of Hypoxia-inducible Factor 1 and its Clinical Significance.

Hypoxia-inducible factor (HIF) is a nuclear protein that plays a crucial role in oxygen homeostasis through its transcriptional activity and thousands of target gene profiles. Through transcriptional and post-transcriptional regulation, the downstream target genes of HIF can trigger multiple pathological responses in the body, including energy metabolism, cytopenia, and angiogenesis. There are three distinct subtypes of HIF: HIF-1, HIF-2, and HIF-3. HIF-1 is a significant regulator of the cellular response to hypoxia, and the balance between its production and degradation is critical for this response. As hypoxia is linked to several disorders, understanding HIF can open up novel avenues for the treatment of many diseases. This review describes the regulatory mechanisms of HIF-1 synthesis and degradation and the clinical significance of the hypoxia-inducible factor pathway in lung injury, kidney disease, hematologic disorders, and inflammation-related diseases.

Early enteral nutrition in patients with out-of-hospital cardiac arrest under target temperature management was associated with a lower 7-day bacteremia rate: A post-hoc analysis of a retrospective cohort study.

INTRODUCTION: Early enteral nutrition (EN) is a nutritional strategy for reducing the incidence of in-hospital infections. However, the benefits of early EN, under targeted temperature management (TTM) in patients with out-of-hospital cardiac arrest (OHCA), remain unclear. We aimed to evaluate the effect of early EN on the infective complications of OHCA patients who underwent TTM. METHODS: We retrospectively searched the clinical databases of two adult emergency tertiary referral hospitals in southern Taiwan and identified patients admitted for OHCA who underwent TTM between 2017 and 2022. The 85 enrolled patients were divided into two groups based on timing: early EN (EN within 48 h of admission) and delayed EN (EN > 48 h after admission). Clinical outcomes of 7-day infective complications between the two groups were analyzed. RESULTS: Early EN was provided to 57 (67 %) of 85 patients and delayed EN was provided to the remaining 28 (33 %) patients. No significant differences in baseline patient characteristics were observed between the two groups. In addition, no differences in clinical outcomes were observed, except that the early EN group had a lower 7-day bacteremia rate (5.3 % vs. 26.9 %, p = 0.013). Gram-negative bacteria were the major pathogen among the 7-day infective complications. CONCLUSION: In OHCA patients treated with TTM, early EN was associated with a lower 7-day bacteremia rate. Furthermore, the application of early EN in this population was well tolerated without significant adverse events.

Preoperative systemic inflammation response index: Clinicopathologic predictor of pathological complete response in HER2-positive breast cancer patients receiving neoadjuvant systemic therapy.

BACKGROUND: Multiple pretreatment systemic inflammatory markers (SIMs) have been reported as predictors of pathological complete response (pCR) after neoadjuvant systemic therapy (NST) in patients with breast cancer (BC). However, the most significant SIM remains to be conclusively identified, and variations among different molecular subtypes remain unknown. The objective of the study was to identify the most significant SIM in patients with human epidermal growth factor receptor 2 (HER2) positive BC, to construct a pCR-predictive nomogram combining it with other clinicopathologic factors, and to evaluate its prognostic value on survival. METHODS: We retrospectively reviewed the findings for 240 patients with stage I-III HER2-positive BC who underwent NST and subsequent surgery at Kaohsiung and Taichung Veterans General Hospital from 2011 to 2021. Clinicopathologic factors were analyzed by stepwise logistic regression with backward selection. The data were used to construct a nomogram plot for determining the pCR probability. Kaplan-Meier curves and log-rank test were used to evaluate disease-free survival (DFS) and overall survival (OS). RESULTS: Among the pretreatment SIMs, only the systemic inflammation response index (SIRI) was significantly related to pCR, with an optimal cutoff value of 1.27 × 10 9 /L. Stepwise logistic analyses indicated that clinical N stage, HER2 immunohistochemistry score, hormone receptor status, targeted therapy regimen, and SIRI were independent predictors of pCR, with an area under the curve of 0.722. The Hosmer-Lemeshow test and calibration curve revealed that the predictive ability was a good fit to actual observations. A nomogram was constructed based on the logistic model. The external validation of the model also revealed satisfactory discrimination and calibration. Kaplan-Meier analysis showed that patients with SIRI <1.27 had longer DFS and OS. CONCLUSION: Pretreatment SIRI <1.27 is predictive of pCR, DFS, and OS in HER2-positive BC. Our nomogram could efficiently predict pCR and facilitate clinical decision-making before neoadjuvant treatment.