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Background: Predicting long-term survival in intensive care unit patients with intracerebral hemorrhage (ICH) is crucial. This study aimed to develop a platelet-to-white blood cell ratio (PWR) incorporated nomogram for long-term survival prediction. Methods: A retrospective analysis was conducted on 1,728 ICH patients in the MIMIC-IV 2.2 database. The independent prognostic value of PWR for 1- year mortality was assessed. A nomogram was developed using LASSO and Cox regression to predict 1-year survival, incorporating PWR and other factors. The performance of the nomogram was evaluated through calibration curves, area under the curve, Delong test, net reclassification index, integrated discrimination improvement, and decision curve analysis. Results: The nomogram, which included age, weight, Glasgow Coma Scale (GCS) score, mechanical ventilation, glucose, red blood cell (RBC) count, blood urea nitrogen (BUN), and PWR, showed good predictive performance for 1-year survival. The C-index was 0.736 (95% CI = 0.716--0.756) for the training set and 0.766 (95% CI = 0.735--0.797) for the testing set. Higher age and ventilation increased mortality risk, while higher weight, GCS score, RBC count, and PWR decreased risk. The nomogram outperformed conventional scores. Conclusions: A nomogramincorporating PWR as a prognostic factor accurately predicts long-term survival in ICH patients. However, validation in large-scale multicenter studies and further exploration of biomarkers are needed. [ABSTRACT FROM AUTHOR]

Background: The association between fibrinogen-to-albumin ratio (FAR) and in-hospital mortality in patients with spontaneous intracerebral hemorrhage (ICH) has been established. However, the association with long-term mortality in spontaneous ICH remains unclear. This study aims to investigate the association between FAR and long-term mortality in these patients. Methods: Our retrospective study involved 3,538 patients who were diagnosed with ICH at West China Hospital, Sichuan University. All serum fibrinogen and serum albumin samples were collected within 24 h of admission and participants were divided into two groups according to the FAR. We conducted a Cox proportional hazard analysis to evaluate the association between FAR and long- term mortality. Results: Out of a total of 3,538 patients, 364 individuals (10.3%) experienced in-hospital mortality, and 750 patients (21.2%) succumbed within one year. The adjusted hazard ratios (HR) showed significant associations with in-hospital mortality (HR 1.61, 95% CI 1.31-1.99), 1-year mortality (HR 1.45, 95% CI 1.25-1.67), and long-term mortality (HR 1.45, 95% CI 1.28-1.64). Notably, the HR for long-term mortality remained statistically significant at 1.47 (95% CI, 1.15-1.88) even after excluding patients with 1-year mortality. Conclusion: A high admission FAR was significantly correlated with an elevated HR for long-term mortality in patients with ICH. The combined assessment of the ICH score and FAR at admission showed higher predictive accuracy for long-term mortality than using the ICH score in isolation. [ABSTRACT FROM AUTHOR]

The surface morphology of perovskite films significantly influences the performance of perovskite light-emitting diodes (PeLEDs). However, the thin perovskite thickness (~10 nm) results in low surface coverage on the substrate, limiting the improvement of photoelectric performance. Here, we propose a molecular additive strategy that employs pentafluorophenyl diphenylphosphinate (FDPP) molecules as additives. P=O and Pentafluorophenyl (5F) on FDPP can coordinate with Pb2+ to slow the crystallization process of perovskite and enhance surface coverage. Moreover, FDPP reduces the defect density of perovskite and enhances the crystalline quality. The maximum brightness, power efficiency (PE), and external quantum efficiency (EQE) of the optimal device reached 24,230 cd m−2, 82.73 lm W−1, and 21.06%, respectively. The device maintains an EQE of 19.79% at 1000 cd m−2 and the stability is further enhanced. This study further extends the applicability of P=O-based additives. [ABSTRACT FROM AUTHOR]

Objective: Blood-blister aneurysms (BBAs) of the internal carotid artery (ICA) are challenging lesions with high morbidity and mortality rates. Although research on BBAs is well documented in different populations, the study of BBAs in the Tibetan population is extremely rare. This study aimed to evaluate the characteristics of BBAs and analyze the treatment modalities and long-term outcomes in the Tibetan population in comparison with the Han population. Methods: The characteristics of patients with BBAs of the ICA from January 2009 to January 2021 at our institution were reviewed. The features of aneurysms, treatment modalities, complications, and follow-up outcomes were retrospectively analyzed. Results: A total of 130 patients (41 Tibetan and 89 Han patients) with BBAs of the ICA who underwent treatment were enrolled. Compared with the Han group, the Tibetan group significantly demonstrated a high ratio of BBAs among ICAs (8.6%, 41/477 vs. 1.6%, 89/5563; p<0.05), a high ratio of vasospasm (34.1%, 14/41 vs. 6.7%, 6/89; p=0.001), a high risk of ischemic events (43.9%, 18/41 vs. 22.5%, 20/89; p<0.05), and a low ratio of good outcomes (modified Rankin scale, 0-2) at the 1-year follow-up (51.2%, 21/41 vs. 74.2%, 66/89; p<0.05). The multivariate regression model showed that ischemic events significantly contributed to the prediction of outcomes at 1 year. Further analysis revealed that microsurgery and vasospasm were associated with ischemic events. Conclusion: In comparison with Han patients, the Tibetan population had a high ratio of BBA occurrence, a high incidence of ischemic events, and a high ratio of poor outcomes. The endovascular approach showed more benefits in BBA patients. [ABSTRACT FROM AUTHOR]

Triple-negative breast cancer (TNBC) is the most challenging breast cancer subtype. Molecular stratification and target therapy bring clinical benefit for TNBC patients, but it is difficult to implement comprehensive molecular testing in clinical practice. Here, using our multi-omics TNBC cohort (N = 425), a deep learning-based framework was devised and validated for comprehensive predictions of molecular features, subtypes and prognosis from pathological whole slide images. The framework first incorporated a neural network to decompose the tissue on WSIs, followed by a second one which was trained based on certain tissue types for predicting different targets. Multi-omics molecular features were analyzed including somatic mutations, copy number alterations, germline mutations, biological pathway activities, metabolomics features and immunotherapy biomarkers. It was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation, germline BRCA2 mutation and PD-L1 protein expression (area under the curve [AUC]: 0.78, 0.79 and 0.74 respectively). The molecular subtypes of TNBC can be identified (AUC: 0.84, 0.85, 0.93 and 0.73 for the basal-like immune-suppressed, immunomodulatory, luminal androgen receptor, and mesenchymal-like subtypes respectively) and their distinctive morphological patterns were revealed, which provided novel insights into the heterogeneity of TNBC. A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes (log-rank P < 0.001). Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA (N = 143) and appeared robust to the changes in patient population. For potential clinical translation, we built a novel online platform, where we modularized and deployed our framework along with the validated models. It can realize real-time one-stop prediction for new cases. In summary, using only pathological WSIs, our proposed framework can enable comprehensive stratifications of TNBC patients and provide valuable information for therapeutic decision-making. It had the potential to be clinically implemented and promote the personalized management of TNBC. [ABSTRACT FROM AUTHOR]

Climate varies along geographic gradients, causing spatial variations in the effects of energy and water on species richness and the explanatory power of different climatic factors. Species of the Quercus genus are important tree species in China with high ecological and socioeconomic value. To detect whether the effects of energy and water on species richness change along climatic gradients, this study built geographically weighted regression models based on species richness and climatic data. Variation partition analysis and hierarchical partitioning analysis were used to further explore the main climatic factors shaping the richness distribution pattern of Quercus in China. The results showed that Quercus species were mainly distributed in mountainous areas of southwestern China. Both energy and water were associated with species richness, with global slopes of 0.17 and 0.14, respectively. The effects of energy and water on species richness gradually increased as energy and water in the environment decreased. The interaction between energy and water altered the effect of energy, and in arid regions, the effects of energy and water were relatively stronger. Moreover, energy explained more variation in species richness in both the entire study area (11.5%) and different climate regions (up to 19.4%). The min temperature of coldest month was the main climatic variable forming the richness distribution pattern of Quercus in China. In conclusion, cold and drought are the critical climatic factors limiting the species richness of Quercus, and climate warming will have a greater impact in arid regions. These findings are important for understanding the biogeographic characteristics of Quercus and conserving biodiversity in China. [ABSTRACT FROM AUTHOR]

Objective: Intracerebral hemorrhage (ICH) is a significant cause of global mortality and morbidity. This study aimed to analyze the burden of ICH and its variation trends across 204 countries and territories from 1990 to 2019. Materials and methods: The study population comprised individuals of all ages and genders with ICH in 204 countries and regions between 1990 and 2019. Utilizing data from the Global Burden of Disease (GBD) study 2019, we collected information on age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and disability-adjusted life-years (DALYs) rate, which were compared by age, gender, and socio-demographic index (SDI). Results: In 2019, there were an estimated 3.4 million (3.0–3.9) incident cases, resulting in 2.8 million (2.6–3.0) deaths and 68.5 million (63.2–73.6) DALYs due to ICH. Between 1990 and 2019, the absolute number of incident cases, deaths, and DALYs increased by 43.0% (41.0–45.0), 37.0% (22.0–51.0), and 25.0% (12.0–36.0), respectively. However, the ASIR, ASDR, and DALYs showed a decreasing trend of- 29.0% (−28.0 to −30.0), −36.0% (−29.0 to −43.0), and − 37.0% (−43.0 to −31.0), respectively. Countries with lower SDI tended to have higher ASIR, ASDR, and DALY rates. Conclusion: While the ASDR and DALY rates decreased from 1990 to 2019, the decline in ASIR was less pronounced. The global burden of ICH remains high, exhibiting significant variation across different genders, age groups, and SDI levels. [ABSTRACT FROM AUTHOR]

Immunotherapy has rejuvenated cancer therapy, especially after anti-PD-(L)1 came onto the scene. Among the many therapeutic options, therapeutic cancer vaccines are one of the most essential players. Although great progress has been made in research on tumor antigen vaccines, few phase III trials have shown clinical benefits. One of the reasons lies in obstruction from the tumor microenvironment (TME). Meanwhile, the therapeutic cancer vaccine reshapes the TME in an ambivalent way, leading to immune stimulation or immune escape. In this review, we summarize recent progress on the interaction between therapeutic cancer vaccines and the TME. With respect to vaccine resistance, innate immunosuppressive TME components and acquired resistance caused by vaccination are both involved. Understanding the underlying mechanism of this crosstalk provides insight into the treatment of cancer by directly targeting the TME or synergizing with other therapeutics. [ABSTRACT FROM AUTHOR]

Background: Abnormal hematocrit values, including anemia and polycythemia, are common in patients undergoing craniotomy, but the extent to which preoperative anemia or polycythemia independently increases the risk of mortality is unclear. This retrospective cohort study aimed to examine the association between preoperative anemia and polycythemia and postoperative mortality in patients who underwent craniotomy for brain tumor resection. Methods: We retrospectively analyzed data from 12,170 patients diagnosed with a brain tumor who underwent cranial surgery at West China Hospital between January 2011 and March 2021. The preoperative hematocrit value was defined as the last hematocrit value within 7 days before the operation, and patients were grouped according to the severity of their anemia or polycythemia. We assessed the primary outcome of 30-day postoperative mortality using logistic regression analysis adjusted for potential confounding factors. Results: Multivariable logistic regression analysis reported that the 30-day mortality risk was raised with increasing severity of both anemia and polycythemia. Odds ratios for mild, moderate, and severe anemia were 1.12 (95% CI: 0.79--1.60), 1.66 (95% CI: 1.06--2.58), and 2.24 (95% CI: 0.99--5.06), respectively. Odds ratios for mild, moderate, and severe polycythemia were 1.40 (95% CI: 0.95--2.07), 2.81 (95% CI: 1.32--5.99), and 14.32 (95% CI: 3.84--53.44), respectively. Conclusions: This study demonstrated that moderate to severe anemia and polycythemia are independently associated with increased postoperative mortality in patients undergoing craniotomy for brain tumor resection. These findings underscore the importance of identifying and managing abnormal hematocrit values before craniotomy surgery. [ABSTRACT FROM AUTHOR]

Background: To date, optimal agents for low-density lipoprotein cholesterol (LDL-C) reduction in patients with established atherosclerotic cardiovascular disease are still being explored. Thus, we evaluated the efficiency of novel LDL-C-lowering therapies in the secondary prevention of cardiovascular events. Methods: We included randomized clinical trials (RCTs) that explored the effects of different LDL-C lowering agents including alirocumab, evolocumab, and bempedoic acid in adult patients with cardiovascular disease. Several databases were searched from inception through 2022. The safety endpoint includes new-onset diabetes, serious adverse events, and neurocognitive disorders with at least 1 year of follow-up. The efficacy outcomes included composite adverse cardiovascular outcomes, all-cause death, and cardiovascular death. Results: Seven RCTs comprising 53,106 patients were included in this research. Bempedoic acid ranked first in reducing the risk of new-onset diabetes (risk ratio [RR] 0.72, 95% credible interval [CrI] 0.52–0.99) and risk of the composite cardiovascular outcome (RR 0.75, 95% CrI 0.57–0.99). Meta-regression analysis demonstrated that elevated risk of new-onset diabetes was positively correlated with a significant reduction in LDL-C levels (p = 0.03). All treatment agents were associated with a decreased risk of a composite adverse cardiovascular outcome. Conclusions: The present analysis showed that bempedoic acid ranked first in reducing the risk of a composite cardiovascular outcome. In addition, it ranked first in reducing the risk of new-onset diabetes compared with placebo and evolocumab. Our analysis also suggests that the increased risk of new-onset diabetes might be associated with a reduction in LDL-C levels. Besides, the present analysis found that alirocumab ranked first in decreasing all-cause mortality and cardiovascular mortality. [ABSTRACT FROM AUTHOR]

The increase of nitrogen (N) deposition and the diversity of its components lead to significant changes in the structure and function of temperate meadow steppe, which could affect plant nutrient uptake, nutrient resorption and litter decomposition, thus affecting the biogeochemical cycle process. The distribution and metabolism of nitrogen and phosphorus in plants determine the growth process and productivity of plants. Plant nutrient uptake, nutrient resorption and litter decomposition play an important role in the nutrient cycling process of ecosystem. This study closely combined these three processes to carry out experiments with different nitrogen dosages and types, and systematically explored the response of nitrogen and phosphorus nutrient cycling to nitrogen deposition. The results showed that nitrogen deposition can greatly affect ecosystem nutrient cycle of nitrogen and phosphorus. Firstly, Nitrogen deposition has significant effect on plant nutrient uptake. Nitrogen uptake of stems and leaves increased with the increase of nitrogen addition dosage, while phosphorus uptake of stems and leaves showed a downward trend or no significant effect. Besides, nitrogen addition type had a significant effect on nitrogen and phosphorus content of stems. Secondly, Nitrogen addition dosage had a significant effect on plant nutrient resorption, while nitrogen addition type had no significant effect on it. Thirdly, nitrogen deposition has significant effect on litter decomposition. With the increase of nitrogen addition dosage, the initial nitrogen content of litters increased and the decomposition rate of litters accelerated. Nitrogen application type had significant effect on stem litter decomposition. These results indicated that nitrogen deposition significantly affects plant nutrient cycling, and thus affects the structure and function of grassland ecosystem. [ABSTRACT FROM AUTHOR]

Background: Extrahepatic metastasis of hepatocellular carcinoma (HCC) is common. However, pituitary metastasis of HCC is extremely rare. Our case may be helpful to extend the understanding of the disease. Case presentation: A 65-year-old man presented to the outpatient department for unexplained headache and ptosis for 1 month. Brain imaging showed a slight enhancement tumor in the pituitary fossa, and the endocrinological assessment showed normal results. We considered the tumor as a non-functioning pituitary adenoma before surgery. Then, the tumor was resected by an endonasal endoscopic transsphenoidal approach. The histopathological examination results revealed the pituitary metastasis of HCC. Additional abdominal imaging revealed tumors were located in the left and right liver lobes with portal vein invasion and bilateral ilium metastases. After multidisciplinary cooperation, the patient chose chemotherapy. Conclusion: We report a case of HCC metastasis to the pituitary gland that initially presented with neurological symptoms. We should consider the possibility of pituitary metastasis in HCC patients. [ABSTRACT FROM AUTHOR]

Background: Despite the widespread use of intraoperative steroids in various neurological surgeries to reduce cerebral edema and other adverse symptoms, there is sparse evidence in the literature for the optimal and safe usage of intraoperative steroid administration in patients undergoing craniotomy for brain tumors. We aimed to investigate the effects of intraoperative steroid administration on postoperative 30-day mortality in patients undergoing craniotomy for brain tumors. Methods: Adult patients who underwent craniotomy for brain tumors between January 2011 to January 2020 were included at West China Hospital, Sichuan University in this retrospective cohort study. Stratified analysis based on the type of brain tumor was conducted to explore the potential interaction. Results: This study included 8,663 patients undergoing craniotomy for brain tumors. In patients with benign brain tumors, intraoperative administration of steroids was associated with a higher risk of postoperative 30-day mortality (adjusted OR 1.98, 95% CI 1.09-3.57). However, in patients with malignant brain tumors, no significant association was found between intraoperative steroid administration and postoperative 30-day mortality (adjusted OR 0.86, 95% CI 0.55-1.35). Additionally, administration of intraoperative steroids was not associated with acute kidney injury (adjusted OR 1.11, 95% CI 0.71-1.73), pneumonia (adjusted OR 0.89, 95% CI 0.74-1.07), surgical site infection (adjusted OR 0.78, 95% CI 0.50-1.22) within 30 days, and stress hyperglycemia (adjusted OR 1.05, 95% CI 0.81-1.38) within 24 h after craniotomy for brain tumor. Conclusion: In patients undergoing craniotomy for benign brain tumors, intraoperative steroids were associated with 30-day mortality, but this association was not significant in patients with malignant brain tumors. [ABSTRACT FROM AUTHOR]

Introduction: It is of great significance to understand the characteristics and influencing factors of vegetation coverage variation in the warm temperate zone. As a typical region of the warm temperate zone in eastern China, the mountainous and hilly region in central-south Shandong Province has fragile ecological environment and soil erosion problem. Studying on vegetation dynamics and its influencing factors in this region will help to better understand the relationship between climate change and vegetation cover change in the warm temperate zone of eastern China, and the influence of human activities on vegetation cover dynamics. Methods: Based on dendrochronology, a standard tree-ring width chronology was established in the mountainous and hilly region of central-south Shandong Province, and the vegetation coverage from 1905 to 2020 was reconstructed to reveal the dynamic change characteristics of vegetation cover in this region. Secondly, the influence of climate factors and human activities on the dynamic change of vegetation cover was discussed through correlation analysis and residual analysis. Results and discussion: In the reconstructed sequence, 23 years had high vegetation coverage and 15 years had low vegetation coverage. After low-pass filtering, the vegetation coverage of 1911–1913, 1945–1951, 1958–1962, 1994–1996, and 2007– 2011 was relatively high, while the vegetation coverage of 1925–1927, 1936–1942, 2001–2003, and 2019–2020 was relatively low. Although precipitation determined the variation of vegetation coverage in this study area, the impacts of human activities on the change of vegetation coverage in the past decades cannot be ignored. With the development of social economy and the acceleration of urbanization, the vegetation coverage declined. Since the beginning of the 21st century, ecological projects such as Grain-for-Green have increased the vegetation coverage. [ABSTRACT FROM AUTHOR]

Objective: Many peripheral inflammatory markers were reported to be associated with the prognosis of aneurysmal subarachnoid hemorrhage (aSAH). We aimed to identify the most promising inflammatory factor that can improve existing predictive models. Methods: The study was based on data from a 10 year retrospective cohort study at Sichuan University West China Hospital. We selected the well-known SAFIRE and Subarachnoid Hemorrhage International Trialists' (SAHIT) models as the basic models. We compared the performance of the models after including the inflammatory markers and that of the original models. The developed models were internally and temporally validated. Results: A total of 3,173 patients were included in this study, divided into the derivation cohort (n = 2,525) and the validation cohort (n = 648). Most inflammatory markers could improve the SAH model for mortality prediction in patients with aSAH, and the neutrophil-to-albumin ratio (NAR) performed best among all the included inflammatory markers. By incorporating NAR, the modified SAFIRE and SAHIT models improved the area under the receiver operator characteristics curve (SAFIRE+NAR vs. SAFIRE: 0.794 vs. 0.778, p = 0.012; SAHIT+NAR vs. SAHIT: 0.831 vs. 0.819, p = 0.016) and categorical net reclassification improvement (SAFIRE+NAR: 0.0727, p = 0.002; SAHIT+NAR: 0.0810, p < 0.001). Conclusion: This study illustrated that among the inflammatory markers associated with aSAH prognosis, NAR could improve the SAFIRE and SAHIT models for 3 month mortality of aSAH. [ABSTRACT FROM AUTHOR]

Background and purpose: Though hypertension disorders of pregnancy (HDP) are recognized as independent pregnancy-associated stroke risk factors, few studies have considered their impact on stroke prognosis. Therefore, we intended to evaluate the impact of HDP on short- and long-term outcomes of pregnancy-associated hemorrhagic stroke (HS). Methods: We conducted a retrospective analysis of patients admitted to our hospital from May 2009 to December 2021 with a diagnosis of pregnancy-associated HS. After dividing patients into two groups by the presence of a diagnosis of HDP or not, the short-(at the time of discharge) and long-term (after discharge follow-up) outcomes were compared by mRS (modified Rankin Scale) scores, and poor functional outcome defined as mRS > 2. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were reported. Results: Twenty-two HDP and 72 non-HDP pregnancy-associated HS patients were enrolled and follow-up after 4.7 ± 3.6 years. There was no significant difference between the two groups regarding short-term outcomes, but patients with HDP were more likely to reach poor functional outcomes at long-term follow-up (aOR = 4.47, 95% CI = 1.28-15.67, p = 0.019). Conclusions: In this retrospective study, women with hypertension disorders of pregnancy did not show worse short-term outcomes of pregnancy-associated hemorrhagic stroke compared to those without but had poorer long-term functional outcomes. This underlines the importance of prevention, recognition, and treatment of hypertension disorders in these women. [ABSTRACT FROM AUTHOR]

Background: Schwannomas of the trochlear nerve with the absence of systemic neurofibromatosis are considerably uncommon, especially complicated by intra-tumoral hemorrhage. Due to the lack of typical clinical manifestations and imaging findings, a definite diagnosis of trochlear schwannomas before surgery is particularly difficult. Case presentation: We report the case of a 64-year-old female patient who presented with a unilaterally intermittent headache of 2-month duration and without a remarkable neurological deficit at admission. Imaging studies revealed a well-demarcated cystic-solid lesion with mixed signals beside the brainstem and suprasellar cisterna. The patient underwent a surgical operation with total resection of the tumor by a subtemporal surgical approach. The tumor was intraoperatively found to originate from the trochlear nerve and was pathologically confirmed as a hemorrhagic schwannoma with cystic degeneration. Conclusions: We describe this case in detail and conduct a concomitant survey of the literature, summarizing the clinical presentations, radiological features, surgical treatment, and the possible mechanisms of hemorrhage in relevance to trochlear nerve schwannoma. [ABSTRACT FROM AUTHOR]

Background: Heme oxygenase one (HO-1) is considered a poor prognostic factor for survival in patients with severe-to-critical coronavirus disease (COVID-19), but the clinical correlation between heme catabolism biomarkers and COVID-19-related sepsis is unknown. The etiopathogenetic hypothesis of HO-1 response during sepsis in patients with poor prognosis should be clarified. This study aimed to investigate sepsis development within 48 h following moderate-to-critical COVID-19 and examined heme/HO-1 catabolism biomarkers associated with sepsis. We also studied the HO-1 and traditional prognostic factors for predicting survival in patients with COVID-19. Methods: This retrospective observational study included patients unvaccinated for COVID-19 with moderate-to-critical COVID-19 (n = 156) who had been admitted to Taipei Tzu Chi Hospital in 2021. All COVID-19 patients were diagnosed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse transcriptase polymerase chain reaction. For analysis of heme catabolism in SARS-CoV-2-induced sepsis, we excluded patients with co-infection and severe anemia. Heme catabolism biomarkers were compared between groups of patients with COVID-19 and sepsis (sepsis) and those with COVID-19 without sepsis (no sepsis), and a control group comprising 100 healthy individuals. All clinical and laboratory data were collected retrospectively and blood specimens were collected from Biobank. Multivariable logistic regression analysis was used to compare all variables between the sepsis and no-sepsis groups. Cox regression analysis was used to determine predictors of survival in patients with COVID-19. Results: There were 71 and 85 patients with and without sepsis, respectively. Heme and HO-1 levels differed significantly between the sepsis, no sepsis, and control groups. In multivariate analysis, confusion, blood urea nitrogen, respiration, blood pressure in patients aged > 65 years (CURB-65) (adjusted odds ratio [aOR] 5.331, 95% confidence interval [CI] 2.587–10.987; p < 0.001), albumin (aOR 0.139, 95% CI 0.003–0.636; p = 0.01), d-dimer (aOR 1.001, 95% CI 1.000–1.002; p = 0.032), and HO-1 (aOR 1.116, 95% CI 1.055–1.180; p < 0.001) were significantly associated with 48-h sepsis episodes after adjusting for other confounding factors. HO-1 levels were also significantly associated with 48-h Sequential Organ Failure Assessment Score (SOFA) scores. However, HO-1 did not significantly increase the hazard of in-hospital mortality in moderate-to-critical COVID-19 by Cox regression analysis. Conclusions: HO-1 levels increased with sepsis development within 48 h of admission for COVID-19 after adjusting for other risk factors, but no significant association was observed between HO-1 and COVID-19 mortality. We suppose that HO-1 may have protective effect in early sepsis, but further clinical multicenter prospective studies are needed. [ABSTRACT FROM AUTHOR]

Background: Multiple risk factors of stroke have been identified in previous studies; however, the causal role of snoring in the onset of stroke is less investigated. To clarify the causal association of snoring on stroke and its subtypes, this study is performed. Methods: The single nucleotide polymorphisms in relation to snoring were retrieved from the UK biobank cohort with 408,317 participants. The data for stroke and its subtypes of European ancestry (67,162 cases and 453,702 controls) were obtained fromtheMEGASTROKE consortium. In single-variable Mendelian randomization (SVMR) and multivariable MR (MVMR) analyses, inverse variance weighting was used as the primary estimate, complemented with sensitivity analyses more robust to pleiotropy. Results: Genetically predicted snoring increased the risk of stroke (odds ratio [OR] = 2.69, 95% confidence interval [CI] = 1.19-6.08, P = 0.016) and ischemic stroke (IS) (OR = 2.82, 95% CI = 1.23-6.44, P = 0.013), but not large artery stroke (LAS) (OR = 3.02, 95% CI = 0.31-29.44, P = 0.339), cardioembolic stroke (CES) (OR = 1.51, 95% CI = 0.58-3.92, P = 0.395). We provide novel genetic evidence that snoring increases the risk of stroke and IS, but not LAS, CES, and SVS. Conclusion: Our findings provide novel genetic evidence that snoring increases the risk of stroke and IS, but not LAS, CES, and SVS. [ABSTRACT FROM AUTHOR]

Among previously uninfected healthcare workers in Taiwan, mRNA COVID-19 booster vaccine was associated with lower odds of COVID-19 after primary recombinant vaccine. Symptom-triggered testing revealed that tetravalent influenza vaccine was associated with higher odds of SARS-CoV-2 infection. COVID-19 vaccination continues to be most effective against SARS-CoV-2. [ABSTRACT FROM AUTHOR]

Purpose: Psychological distress is common among patients with acute diseases and is associated with a poorer prognosis. Early detection and intervention are important for high‐risk individuals. Design and Methods: This retrospective study used the five‐item Brief Symptom Rating Scale (BSRS‐5) to assess psychological distress and evaluate whether proactive intervention may reduce distress levels among hospitalized patients in a single medical center in northern Taiwan. Findings: Of the patients, 10.7% were found to have varying degrees of emotional distress (BSRS‐5 ≥ 6). After providing integrated medical care for patients with psychological distress, the degree of stress decreased significantly (p < 0.001). These results were consistent across subgroups. Practice Implications: The results highlight that proactive assessment and appropriate interventions may reduce patients' psychological distress during their course of hospitalization. [ABSTRACT FROM AUTHOR]

This study aims to construct a Macrophage-Related Gene Prognostic Index (MRGPI) for glioblastoma (GBM) and explore the underlying molecular, metabolic, and immunological features. Based on the GBM dataset from The Cancer Genome Atlas (n = 156), 13 macrophage-related hub genes were identified by weighted gene co-expression network (WGCNA) analysis. 5 prognostic genes screened by Kaplan-Meire (K-M) analysis and Cox regression model were used to construct the MRGPI, including GPR84, NCF2, HK3, LILRB2, and CCL18. Multivariate Cox regression analysis found that the MRGPI was an independent risk factor (HR = 2.81, CI95: 1.13-6.98, p = 0.026), leading to an unfavorable outcome for the MRGPI-high group, which was further validated by 4 validation GBM cohorts (n = 728). Thereafter, the molecular, metabolic, and immune features and the clinical implications of the MRGPI-based groups were comprehensively characterized. Gene set enrichment analysis (GSEA) found that immune-related pathways, including inflammatory and adaptive immune response, and activated eicosanoid metabolic pathways were enriched in the MRGPI-high group. Besides, genes constituting the MRGPI was primarily expressed by monocytes and macrophages at single-cell scope and was associated with the alternative activation of macrophages. Moreover, correlation analysis and receiver operating characteristic (ROC) curves revealed the relevance between the MRGPI with the expression of immune checkpoints and T cell dysfunction. Thus, the responsiveness of samples in the MRGPI-high group to immune checkpoint inhibitors (ICI) was detected by algorithms, including Tumor Immune Dysfunction and Exclusion (TIDE) and Submap. In contrast, the MRGPI-low group had favorable outcome, was less immune active and insensitive to ICI. Together, we have developed a promising biomarker to classify the prognosis, metabolic and immune features for GBM, and provide references for facilitating the personalized application of ICI in GBM. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a major cause of death and morbidity worldwide, often due to rupture of intracranial aneurysms (IAs). Immune infiltration and inflammatory activation play key roles in the process of aneurysmal SAH (aSAH). This study aimed to elaborate the immune infiltration and identify related biomarkers both in blood and tissue samples from patients with aSAH. Expression data of aSAH and healthy control samples were obtained from gene expression omnibus (GEO) database. Overall, a blood sample dataset GSE36791 and a tissue sample dataset GSE122897 were included. Differentially expressed genes (DEGs) between aSAH and healthy samples were explored. We applied GO biological and Gene Set Enrichment Analyses (GSEA) processes to access the functional enrichment. Then feature elimination algorithms based on random forest were used to screen and verify the biomarkers of aSAH. We performed three computational algorithms including Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT), Microenvironment Cell Populations-counter (MCPcounter), and xcell to evaluate the immune cell infiltration landscape to identify the unique infiltration characteristics associated with rupturing. We found 2,220 DEGs (856 upregulated and 1,364 downregulated) in the original dataset. Functional analysis revealed most of these genes are enriched in immunological process, especially related with neutrophil response. Similar signaling pathway enrichment patterns were observed in tissue sample dataset and ClueGo. Analysis of immune microenvironment infiltration suggested neutrophils were abnormally upregulated in aSAH compared with those in the control group. Key gene SRPK1 was then filtered based on feature elimination algorithms, and transcription factor (TF) ZNF281 is assumed to participate in immunomodulation by regulating expression of SRPK1. Several immunomodulators such as CXCR1 and CXCR2 also appear to be involved in the progression of aSAH. In the present study, we performed a comprehensive stratification and quantification of the immune infiltration status of aSAH. By exploring the potential mechanism for aSAH based on several computational algorithms, key genes including SRPK1 and ZNF281 were filtered. This study may be of benefit to patients who are at high risk of suffering aSAH which allows for early diagnosis and potential therapy. [ABSTRACT FROM AUTHOR]

The pathological implications of tumor-associated macrophages in the glioma microenvironment have been highlighted, while there lacks a gene signature to characterize the functional status and clinical implications of these cells. Comprehensive bioinformatics approaches were employed to develop an M2 macrophage-associated gene signature at bulk-tumor and single-cell levels and explore immunological and metabolic features. Consequently, the PI3K pathway and fatty acid metabolism were correlated with the M2 fraction. Further distilling the pathway members resulted in a leukotriene synthesisrelated gene signature (Macro index), including PIK3R5, PIK3R6, ALOX5, ALOX5AP, and ALOX15B, that was primarily expressed by monocytes/macrophages. Increased Macro index predicted IL13-induced macrophages, and was associated with T-cell dysfunction at both transcriptional and epigenetic levels and predicted an unfavorable outcome. Besides, the Macro index was proportional with PAI1 at the protein level, with high levels of the latter suggesting a decreased progression-free interval of glioblastoma. Notably, the monocytes/macrophages in the glioma environment contribute to the expression of immune checkpoints and the Macro index predicts glioma responsiveness to anti-PD1 treatment. Together, our study proposed a leukotriene synthesis-related M2 macrophage gene signature, which may provide insights into the role of these cells in the glioma microenvironment and facilitate individually tailored therapeutic strategies for the disease. [ABSTRACT FROM AUTHOR]

Background: Though acute kidney injury (AKI) in the context of aneurysmal subarachnoid hemorrhage (aSAH) worsens short-term outcomes, its impact on long-term survival is unknown. Aim: We aimed to evaluate the association between long-term mortality and AKI during hospitalization for aSAH. Methods: This was a retrospective study of patients who survived >12 months after aSAH. All patients were evaluated atWest China Hospital, Sichuan University, between December 2013 and June 2019. The minimum follow-up time was over 1 year. the maximum follow-up time was about 7.3 years. AKI was defined by the KDIGO (The Kidney Disease Improving Global Outcomes) guidelines, which stratifies patients into three stages of severity. The primary outcome was long-term mortality, which was analyzed with Kaplan-Meier curves and Cox proportional hazards models. Results: During this study period, 238 (9.2%) patients had AKI among 2,592 patients with aSAH. We confirmed that AKI during care for aSAH significantly increased long-term mortality (median 4.3 years of follow-up) and that risk increased with the severity of the kidney failure, with an adjusted hazard ratio (HR) of 2.08 (95% CI 1.49-2.89) for stage 1 AKI, 2.15 (95% CI 1.05-4.43) for stage 2 AKI, and 2.66 (95% CI 1.08-6.53) for stage 3 AKI compared with patients without AKI. Among patients with an AKI episode, those with renal recovery still had increased long-termmortality (HR 1.96; 95% CI 1.40-2.74) compared with patients without AKI but had better long-term outcomes than those without renal recovery (HR 0.51, 95% CI 0.27-0.97). Conclusions: Among 12-month survivors of aSAH, AKI during their initial hospitalization for aSAH was associated with increased long-term mortality, even for patients who had normal renal function at the time of hospital discharge. Longer, multidisciplinary post-discharge follow-up may be warranted for these patients. [ABSTRACT FROM AUTHOR]

Erythrocytes undergo certain morphological changes resembling apoptosis during senescence or in an abnormal state/site, which is termed eryptosis. This process is characterized by phosphatidylserine (PS) exposure, membrane blebbing, and cell shrinkage. Eryptotic erythrocytes are subsequently removed via macrophage-mediated efferocytosis. In hemorrhagic stroke (HS), blood within an artery rapidly bleeds into the brain tissue or the subarachnoid space, resulting in severe neurological deficits. A hypoxic, over-oxidative, and pro-inflammatory microenvironment in the hematoma leads to oxidative stress, hyperosmotic shock, energy depletion, and Cl􀀀 removal in erythrocytes, which eventually triggers eryptosis. In addition, eryptosis following intracerebral hemorrhage favors hematoma clearance, which sheds light on a common mechanism of intrinsic phagocytosis. In this review, we summarized the canonical mechanisms of eryptosis and discussed its pathological conditions associated with HS. Understanding the role of eryptosis in HS may uncover additional potential interventions for further translational clinical research. [ABSTRACT FROM AUTHOR]

Background: Intracranial non-branching site blood blister-like aneurysms (BBA) are extremely rare and vicious. Their etiology remains elusive, and no molecular study has been carried out to reveal its pathogenic relevance to intracranial atherosclerosis. To investigate its transcriptomic landscape and underlying potential pathogenesis, we performed single-cell RNA sequencing with extensive pathological validation. Methods: In total, 12,245 cells were recovered for single-cell RNA sequencing analysis from 1 BBA and 2 saccular intracranial aneurysms (IAs). Unbiased clustering using Seuratbased pipeline was used for cellular landscape profiling. Cell chat was used to understand intracellular communications. Furthermore, 10 BBAs and 30 IAs were retrospectively collected for pathological validations like scanning electron microscopy, H&E stain, Masson stain, Verhoeff Van Gielson stain, and immunofluorescence. Results: Single-cell transcriptome profiled 14 total subclusters in 6 major groups, namely, 6 monocyte/macrophage clusters, 2 T&NK clusters, 3 vascular smooth muscle cell (VSMC) clusters, 1 dendritic cell, 1 B cell, and 1 endothelial cell cluster. The only mural cell identified in BBAs was VSMC-2 cluster, while mural cells in IAs comprise most clusters of VSMCs and endothelial cells. Upregulated genes in BBA-derived VSMCs are related to arterial mineralization and atherosclerosis, such as PTX3, SPP1, LOX, etc., whereas vasodilation and physiological regulatory genes such as MGP, ACTA2, and MYL9 were conversely enriched in conventional IA-derived VSMCs. Immune cells in the BBA were predominantly macrophages, with a low fraction of T&NK cells, while conventional IAs had a higher percentage of T&NK. Gene enrichment analysis suggested that macrophages in BBA were highly enriched in lipid metabolism as well as atherosclerosis. Ligand–receptor interaction suggested that secretory phosphoprotein 1 (also known as osteopontin) played a major role in mediating the intracellular communication between VSMC and macrophages, especially in BBA. Pathological experiments corroborate with the bioinformatic findings and further characterized BBAs as a thin-walled thrombotic aneurysm with severe atherosclerotic lesions, where ApoE+ macrophages and OPN+ mural cells are intimately involved in the inflammation process. Conclusions: The preexisting intracranial atherosclerosis might predispose the parent artery to the pathogenic occurrence of BBAs. These data shed light on the pathophysiology of intracranial aneurysms and might assist in the further resolution of the complexity in aneurysm pathogenesis. [ABSTRACT FROM AUTHOR]

We present optically tunable operations of deoxyribonucleic acid (DNA) biopolymer devices, where a single high-resistance state, write-once read-many-times memory state, write-read-erase memory state, and single low-resistance state can be achieved by controlling UV irradiation time. The device is a simple sandwich structure with a spin-coated DNA biopolymer layer sandwiched by two electrodes. Upon irradiation, the electrical properties of the device are adjusted owing to a phototriggered synthesis of silver nanoparticles in DNA biopolymer, giving rise to multiple switching scenarios. This technique, distinct from the strategy of doping of pre-formed nanoparticles, enables a post-film fabrication process for achieving optically controlled memory device operations, which provides a more versatile platform to fabricate organic memory and optoelectronic devices. [ABSTRACT FROM AUTHOR]

Dust is the major aerosol type over the Tibetan Plateau (TP), and the TP plays an important role in forming the spring dust belt across the Northern Hemisphere in the upper troposphere. Estimated spring dust mass flux (DMF) showed a significant declining trend over the TP during 2007-19. The total spring DMF across the TP (TDMFTP) was mainly affected by DMFs over the Tarim Basin, while the spring DMF across the TP in the midtroposphere was also connected with DMFs over the northwest Indian Peninsula and central Asia. Interannual variability of springTDMFTP was strongly correlated with the North Atlantic winter sea surface temperature (SST) tripole. A cold preceding winter induced by the North Atlantic winter SST tripole over midlatitude Eurasia promotes dust activities in the subsequent spring. The North Atlantic winter SST tripole anomalies persist into the subsequent spring and induce a corresponding atmosphere response. Enhanced atmospheric baroclinicity develops over northwest China and the northern Indian Peninsula during spring, which is attributed to surface thermal forcing induced by the positive winter SST tripole phase. A strong positive North Atlantic winter SST tripole anomaly strengthens the upper-level westerly jets, enhancing airflow toward the TP midtroposphere; together, these circulation patterns cause anomalous cyclonic conditions in the lower troposphere, especially over the Tarim Basin, via the eastward propagation of a Rossby wave train. These atmospheric circulation conditions are likely to increase the frequency of dust occurrence and promote the transport of dust onto the TP. [ABSTRACT FROM AUTHOR]