Inhibiting SHP2 reduces glycolysis, promotes microglial M1 polarization, and alleviates secondary inflammation following spinal cord injury in a mouse model.

JOURNAL/nrgr/04.03/01300535-202503000-00030/figure1/v/2024-06-17T092413Z/r/image-tiff Reducing the secondary inflammatory response, which is partly mediated by microglia, is a key focus in the treatment of spinal cord injury. Src homology 2-containing protein tyrosine phosphatase 2 (SHP2), encoded by PTPN11, is widely expressed in the human body and plays a role in inflammation through various mechanisms. Therefore, SHP2 is considered a potential target for the treatment of inflammation-related diseases. However, its role in secondary inflammation after spinal cord injury remains unclear. In this study, SHP2 was found to be abundantly expressed in microglia at the site of spinal cord injury. Inhibition of SHP2 expression using siRNA and SHP2 inhibitors attenuated the microglial inflammatory response in an in vitro lipopolysaccharide-induced model of inflammation. Notably, after treatment with SHP2 inhibitors, mice with spinal cord injury exhibited significantly improved hind limb locomotor function and reduced residual urine volume in the bladder. Subsequent in vitro experiments showed that, in microglia stimulated with lipopolysaccharide, inhibiting SHP2 expression promoted M2 polarization and inhibited M1 polarization. Finally, a co-culture experiment was conducted to assess the effect of microglia treated with SHP2 inhibitors on neuronal cells. The results demonstrated that inflammatory factors produced by microglia promoted neuronal apoptosis, while inhibiting SHP2 expression mitigated these effects. Collectively, our findings suggest that SHP2 enhances secondary inflammation and neuronal damage subsequent to spinal cord injury by modulating microglial phenotype. Therefore, inhibiting SHP2 alleviates the inflammatory response in mice with spinal cord injury and promotes functional recovery postinjury.

Prospective observational study of Trichomonas tenax infection in patients with pneumonia.

Trichomonas tenax, an oral commensal parasite commonly found in the human mouth, is associated with periodontitis and poor oral hygiene. However, it has also been identified in the bronchoalveolar lavage fluid (BALF) of individuals with lung diseases. Notably, significant quantities of T. tenax have been isolated following bronchoscopy in cases of empyema and acute respiratory distress syndrome (ARDS). Furthermore, research has demonstrated its ability to induce inflammation in pulmonary epithelial cells. To comprehend the potential role of T. tenax in pneumonia, it is crucial to elucidate the relationship between the parasite and the disease. We investigated the clinical factors associated with T. tenax infection in patients with pneumonia. Employing nested polymerase chain reactions, we amplified nucleic acids from BALF and analyzed the relationships between T. tenax and various clinical factors. Our data revealed a significant association between T. tenax and bacterial infections, high pneumonia severity index (PSI) scores, nasogastric tube feeding, and pulmonary complications. Logistic regression analyses also showed strong associations between T. tenax and these clinical factors in pneumonia patients. These findings suggest that T. tenax infection in pneumonia is accompanied by bacterial infection and severe clinical manifestations.

Benefits of Hepatitis C Viral Eradication: A Real-World Nationwide Cohort Study in Taiwan.

BACKGROUND: Chronic hepatitis C (CHC) increases the risk of liver cirrhosis (LC) and hepatocellular carcinoma (HCC). This nationwide cohort study assessed the effectiveness of viral eradication of CHC. METHODS: The Taiwanese chronic hepatitis C cohort and Taiwan hepatitis C virus (HCV) registry are nationwide HCV registry cohorts incorporating data from 23 and 53 hospitals in Taiwan, respectively. This study included 27,577 individuals from these cohorts that were given a diagnosis of CHC and with data linked to the Taiwan National Health Insurance Research Database. Patients received either pegylated interferon and ribavirin or direct-acting antiviral agent therapy for > 4 weeks for new-onset LC and liver-related events. RESULTS: Among the 27,577 analyzed patients, 25,461 (92.3%) achieved sustained virologic response (SVR). The mean follow-up duration was 51.2 ± 48.4 months, totaling 118,567 person-years. In the multivariable Cox proportional hazard analysis, the hazard ratio (HR) for incident HCC was 1.39 (95% confidence interval [CI]: 1.00-1.95, p = 0.052) among noncirrhotic patients without SVR compared with those with SVR and 1.82 (95% CI 1.34-2.48) among cirrhotic patients without SVR. The HR for liver-related events, including HCC and decompensated LC, was 1.70 (95% CI 1.30-2.24) among cirrhotic patients without SVR. Patients with SVR had a lower 10-year cumulative incidence of new-onset HCC than those without SVR did (21.7 vs. 38.7% in patients with LC, p < 0.001; 6.0 vs. 18.4% in patients without LC, p < 0.001). CONCLUSION: HCV eradication reduced the incidence of HCC in patients with and without LC and reduced the incidence of liver-related events in patients with LC.

Mild hypothermia pretreatment improves hepatic ischemia-reperfusion injury: A systematic review and meta-analysis of animal experiments.

BACKGROUND AND AIM: Mild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury. METHODS: We systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32-34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software. RESULTS: Eight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), P<0.001], and AST levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.45, 95% CI (-6.10, -2.78), P<0.001]. The hepatocyte apoptosis rate in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -6.86, 95% CI (-10.38, -3.33), P<0.001]. Hepatocyte pathology score in the mild hypothermia pretreatment group was significantly lower than that in the normothermic control group [SMD = -4.36, 95% CI (-5.78, -2.95), P<0.001]. There was no significant difference in MPO levels between the mild hypothermia preconditioning group and the normothermic control group [SMD = -4.83, 95% CI (-11.26, 1.60), P = 0.14]. SOD levels in the mild hypothermia preconditioning group were significantly higher than those in the normothermic control group [SMD = 3.21, 95% CI (1.27, 5.14), P = 0.001]. MDA levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [SMD = -4.06, 95% CI (-7.06, -1.07) P = 0.008]. CONCLUSION: Mild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function.

Targeting CK1δ and CK1ε as a new therapeutic approach for clear cell renal cell carcinoma.

INTRODUCTION: Kidney cancer ranks as the ninth most common cancer in men and the fourteenth in women globally, with renal cell carcinoma (RCC) being the most prevalent type. Despite advances in therapeutic strategies targeting angiogenesis and immune checkpoints, the absence of reliable markers for patient selection and limited duration of disease control underline the need for innovative approaches. CK1δ and CK1ε are highly conserved serine/threonine kinases involved in cell cycle regulation, apoptosis, and circadian rhythm. While CK1δ dysregulation is reportedly associated with breast and bladder cancer progression, their role in RCC remains elusive. This study aims to investigate the feasibility of CK1δ/ε as new therapeutic targets for RCC patients. METHODS: The relationship between CK1δ/ε and RCC progression was evaluated by the analysis of microarray dataset and TCGA database. The anticancer activity of CK1δ/ε inhibitor was examined by MTT/SRB assay , and apoptotic cell death was analyzed by flow cytometry and western blotting. RESULTS: Our data demonstrate that the gene expression of CSNK1D and CSNK1E is significantly higher in clear cell RCC (ccRCC) tissues compared to normal kidney samples, which is correlated with lower survival rates in ccRCC patients. SR3029, a selective inhibitor targeting CK1δ/ε, significantly suppresses the viability and proliferation of ccRCC cell lines regardless of the status of VHL deficiency. Importantly, the inhibitor promotes the population of subG1 cells and induces apoptosis, and ectopically expression of CK1δ partially rescued SR3029-induced apoptosis in ccRCC cells. CONCLUSION: These findings underscore the crucial role of CK1δ and CK1ε in ccRCC progression, suggesting CK1δ/ε inhibitors as new therapeutic options for ccRCC patients.

Transoral Ultrasound-Guided Core Biopsy for Minimally Invasive Sampling of Hard-to-Access Oropharyngeal Cancers.

Pathological diagnosis plays a pivotal role in risk classification and personalized treatment planning for patients with oropharyngeal cancers. However, challenges arise in cases involving trismus and tumors with submucosal spread, hindering traditional endoscopic biopsies and open incisional biopsies. In this study, we examined the clinical and pathological data of patients with trismus who underwent transoral ultrasound-guided core biopsy (USCB) for their oropharyngeal tumors, comparing this method with existing diagnostic approaches. Seventeen patients presenting with oropharyngeal tumors and trismus underwent transoral USCB for diagnosis. Of these, 14 patients were diagnosed with squamous cell carcinoma, while the remaining 3 were diagnosed with lymphoma. The procedure resulted in minimal wound size and effective bleeding control through compression, without encountering any complications. In conclusion, transoral USCB emerges as a precise diagnostic tool for patients with oropharyngeal tumors and trismus, offering a valuable adjunct to conventional open and endoscopic biopsies.

Impact of Esophageal Motility on Microbiome Alterations in Symptomatic Gastroesophageal Reflux Disease Patients With Negative Endoscopy: Exploring the Role of Ineffective Esophageal Motility and Contraction Reserve.

Background/Aims: Ineffective esophageal motility (IEM) is common in patients with gastroesophageal reflux disease (GERD) and can be associated with poor esophageal contraction reserve on multiple rapid swallows. Alterations in the esophageal microbiome have been reported in GERD, but the relationship to presence or absence of contraction reserve in IEM patients has not been evaluated. We aim to investigate whether contraction reserve influences esophageal microbiome alterations in patients with GERD and IEM. Methods: We prospectively enrolled GERD patients with normal endoscopy and evaluated esophageal motility and contraction reserve with multiple rapid swallows during high-resolution manometry. The esophageal mucosa was biopsied for DNA extraction and 16S ribosomal RNA gene V3-V4 (Illumina)/full-length (Pacbio) amplicon sequencing analysis. Results: Among the 56 recruited patients, 20 had normal motility (NM), 19 had IEM with contraction reserve (IEM-R), and 17 had IEM without contraction reserve (IEM-NR). Esophageal microbiome analysis showed a significant decrease in microbial richness in patients with IEM-NR when compared to NM. The beta diversity revealed different microbiome profiles between patients with NM or IEM-R and IEM-NR (P = 0.037). Several esophageal bacterial taxa were characteristic in patients with IEM-NR, including reduced Prevotella spp. and Veillonella dispar, and enriched Fusobacterium nucleatum. In a microbiome-based random forest model for predicting IEM-NR, an area under the receiver operating characteristic curve of 0.81 was yielded. Conclusions: In symptomatic GERD patients with normal endoscopic findings, the esophageal microbiome differs based on contraction reserve among IEM. Absent contraction reserve appears to alter the physiology and microbiota of the esophagus.

Ultrafast 2D Nanosheet Assembly via Spontaneous Spreading Phenomenon.

In 2D materials, a key engineering challenge is the mass production of large-area thin films without sacrificing their uniform 2D nature and unique properties. Here, it is demonstrated that a simple fluid phenomenon of water/alcohol solvents can become a sophisticated tool for self-assembly and designing organized structures of 2D nanosheets on a water surface. In situ, surface characterizations show that water/alcohol droplets of 2D nanosheets with cationic surfactants exhibit spontaneous spreading of large uniform monolayers within 10 s. Facile transfer of the monolayers onto solid or flexible substrates results in high-quality mono- and multilayer films with high coverages (>95%) and homogeneous electronic/optical properties. This spontaneous spreading is quite general and can be applied to various 2D nanosheets, including metal oxides, graphene oxide, h-BN, MoS2, and transition metal carbides, enabling on-demand smart manufacture of large-size (>4 inchϕ) 2D nanofilms and free-standing membranes.

Radical resection in a patient with stage IIIA non-small cell lung cancer with the EGFR exon 19 deletion mutation after neoadjuvant targeted therapy with osimertinib: a case report.

Background: With the advent of targeted therapies, the survival rates of patients with locally advanced lung cancer have significantly improved. However, there is limited research on the efficacy of neoadjuvant targeted therapy in resectable advanced non-small cell lung cancer (NSCLC) patients with positive driver genes. This article reports a case of stage IIIA NSCLC with an epidermal growth factor receptor (EGFR) 19del mutation that successfully underwent radical lung cancer surgery following neoadjuvant targeted therapy. By observing the perioperative treatment outcomes and side effects in this patient, we aimed to provide insights and summarize experiences for treating similar cases in the future. Case Description: We report a case of a 54-year-old female diagnosed preoperatively with stage IIIA adenocarcinoma of the left upper lung (cT1cN2M0). The patient's course was complicated by acute sick sinus syndrome and was cured by implanting a permanent pacemaker. After multidisciplinary discussion, it was decided to administer neoadjuvant targeted therapy with osimertinib. Following 6 weeks of treatment, the tumor assessment showed partial response (PR), making the patient eligible for surgery. The patient underwent single-port thoracoscopic left upper lobectomy + mediastinal lymphadenectomy. Intraoperatively, the left hilar lymph nodes were found to be tightly adherent to the apical-anterior branch of the left upper pulmonary artery. The main trunk of the left pulmonary artery was temporarily occluded with a vascular clamp to safely dissect the left upper pulmonary artery. The procedure was completed without conversion to open thoracotomy, achieving an R0 resection. Postoperative pathology confirmed stage IIIA (ypT1bN2M0), and the patient continued adjuvant therapy with osimertinib. Conclusions: Neoadjuvant targeted therapy with osimertinib is expected to become one of the options for neoadjuvant therapy in locally advanced NSCLC with sensitizing EGFR mutations. And for those with advanced lung cancer involving tumors close to the hilum or mediastinal lymph node metastasis, preblocking of the left upper pulmonary artery can help improve surgical safety and better ensure R0 resection.

Development and validation of a preoperative radiomics-based nomogram to identify patients who can benefit from splenic hilar lymphadenectomy: a pooled analysis of three prospective trials.

BACKGROUND: We aimed to use preoperative computed tomography images to develop a radiomic nomogram to select patients who would benefit from spleen-preserving splenic hilar (No.10) lymphadenectomy (SPSHL). METHODS: A pooled analysis of three distinct prospective studies was performed. The splenic hilar lymph node (SHLN) ratio (sLNR) was established as the quotient of the number of metastatic SHLN to the total number of SHLN. Radiomic features reflecting the phenotypes of the primary tumor (RS1) and SHLN region (RS2) were extracted and used as predictive factors for sLNR. RESULTS: This study included 733 patients: 301 in the D2 group and 432 in the D2+No.10 group. The optimal sLNR cutoff value was set at 0.4, and the D2+No.10 group was divided into three groups: sLNR=0, sLNR≤0.4, and sLNR>0.4. Patients in the D2+No. 10 group were randomly divided into the training (n=302) and validation (n=130) cohorts. The AUCs value of the nomogram, including RS1 and RS2, were 0.952 in the training cohort and 0.888 in the validation cohort. The entire cohort was divided into three groups based on the nomogram scores: low, moderate and high SHLN metastasis burden groups (LMB, MMB and HMB, respectively). A similar 5-year OS rate was found between the D2 and D2+No. 10 groups in the LMB and HMB groups. In the MMB group, the 5-year OS of the D2+No. 10 group (73.4%) was significantly higher than that of the D2 group (37.6%) (P<0.001). CONCLUSIONS: The nomogram showed good predictive ability for distinguishing patients with various SHLN metastasis burdens. It can accurately identify patients who would benefit from SPSHL.

Impact of English proficiency on use of Glasgow Coma Scale in geriatric patients with traumatic brain injury.

Background: The relationship between English proficiency (EP), Glasgow Coma Scale (GCS) and traumatic brain injury (TBI) is not well characterized. We aimed to understand the impact of limited English proficiency (LEP) on the evaluation and outcomes of TBI. Methods: Retrospective comparative study in a single institution of patients aged ⪰65 who presented to the emergency department after a fall with head strike between January 2018 and December 2021. TBI was defined as documented loss of consciousness or intracranial hemorrhage (ICH). Relationships between EP, GCS, and TBI were analyzed with multivariable and propensity score-matched models. Results: Of the 2905 included, 1233 (42%) had LEP. Most LEP patients were Asian (60%) while the majority of EP patients were non-Hispanic Caucasians (72%). In a univariate analysis, LEP had higher incidence of decreased GCS and was strongly correlated with risk of TBI (OR 1.47, CI 1.26 to 1.71). After adjusting for multiple covariates including race, LEP did not have a significantly increased risk for GCS score <13 (OR 1.66, CI 0.99 to 2.76) or increased risk of TBI. In the matched analysis, LEP had a small but significantly higher risk of GCS score <13 (OR 1.03, CI 1.02 to 1.05) without an increased risk in TBI. Decreased GCS remained strongly correlated with presence of ICH in LEP patients in the adjusted model (OR 1.39, CI 1.30 to 1.50). Conclusions: LEP correlated with lower GCS in geriatric patients with TBI. This association weakened after adjusting for factors like race, suggesting racial disparities may have more influence than language differences. Moreover, GCS remained effective for predicting ICH in LEP individuals, highlighting its value with suitable translation resources. Level of evidence: This is a Level III evidence restrospective comparative study.

Chemical Reaction Modulated Low-Dimensional Phase Toward Highly Efficient Sky-Blue Perovskite Light-Emitting Diodes.

Blue perovskite light-emitting diodes (PeLEDs) are crucial avenues for achieving full-color displays and lighting based on perovskite materials. However, the relatively low external quantum efficiency (EQE) has hindered their progression towards commercial applications. Quasi-two-dimensional (quasi-2D) perovskites stand out as promising candidates for blue PeLEDs, with optimized control over low-dimensional phases contributing to enhanced radiative properties of excitons. Herein, the impact of organic molecular dopants on the crystallization of various n-phase structures in quasi-2D perovskite films. The results reveal that the highly reactive bis(4-(trifluoromethyl)phenyl)phosphine oxide (BTF-PPO) molecule could effectively restrain the formation of organic spacer cation-ordered layered perovskite phases through chemical reactions, simultaneously passivate those uncoordinated Pb2+ defects. Consequently, the prepared PeLEDs exhibited a maximum EQE of 16.6% (@ 490 nm). The finding provides a new route to design dopant molecules for phase modulation in quasi-2D PeLEDs.

Characterization of Sesquiterpene Dimers from the Flowers of Inula japonica and the Structural Revisions of Related Compounds.

Sesquiterpene dimers are mainly found in the Asteraceae family. However, conflicting reports on the structures of these compounds can be found in the literature. Herein, we describe ten sesquiterpene dimers isolated from the flowers of Inula japonica, including configurational revisions of japonicone H (1-1), japonicone D (2-1), inulanolide A (4-1), japonicone X (5-1), and inulanolide F (5-2) to compounds 1, 2, 4, and 5, respectively. Five new related metabolites (3 and 6-9) are also described. Application of GIAO NMR/DP4+ analyses and ECD/OR calculations enabled us to revise the absolute configurations of an additional 13 sesquiterpene dimers isolated from plants of the genus Inula. Compounds 1, 2, 4, and 6 exhibited inhibition of nitric oxide production in lipopolysaccharide activated RAW264.7 macrophages with IC50 values of 4.07-10.00 µM.

Intermittent Fasting Targets Osteocyte Neuropeptide Y to Relieve Osteoarthritis.

Osteoarthritis is a highly prevalent progressive joint disease that still requires an optimal therapeutic approach. Intermittent fasting is an attractive dieting strategy for improving health. Here this study shows that intermittent fasting potently relieves medial meniscus (DMM)- or natural aging-induced osteoarthritic phenotypes. Osteocytes, the most abundant bone cells, secrete excess neuropeptide Y (NPY) during osteoarthritis, and this alteration can be altered by intermittent fasting. Both NPY and the NPY-abundant culture medium of osteocytes (OCY-CM) from osteoarthritic mice possess pro-inflammatory, pro-osteoclastic, and pro-neurite outgrowth effects, while OCY-CM from the intermittent fasting-treated osteoarthritic mice fails to induce significant stimulatory effects on inflammation, osteoclast formation, and neurite outgrowth. Depletion of osteocyte NPY significantly attenuates DMM-induced osteoarthritis and abolishes the benefits of intermittent fasting on osteoarthritis. This study suggests that osteocyte NPY is a key contributing factor in the pathogenesis of osteoarthritis and intermittent fasting represents a promising nonpharmacological antiosteoarthritis method by targeting osteocyte NPY.

A Single Lung Abscess Caused by Panton-Valentine Leukocidin-Producing Methicillin-Resistant Staphylococcus aureus.

This case report presents a rare occurrence of a single lung abscess caused by Panton-Valentine leukocidin (PVL)-producing methicillin-resistant Staphylococcus aureus (MRSA) in a 38-year-old immunocompetent man. The patient, of Southeast Asian origin, presented with symptoms of fever, chest pain, cough, and shortness of breath following a recent flu-like illness. Imaging indicated a cavitary lung lesion in the left lower lobe, suggestive of a lung abscess. Initial antibiotic treatment failed, and drainage of the abscess confirmed MRSA with the PVL gene, indicating a community-acquired MRSA infection. The patient received intravenous vancomycin followed by oral linezolid, leading to the resolution of the abscess. Contact tracing and decolonization measures were implemented. This case highlights the importance of considering PVL-producing S. aureus as a potential pathogen in severe necrotizing pneumonia or sepsis and underscores the need for prompt diagnosis, appropriate antibiotic therapy, and infection control measures in managing such infections.

Integrating proximal soil sensing data and environmental variables to enhance the prediction accuracy for soil salinity and sodicity in a region of Xinjiang Province, China.

Soil salinization and sodification, the primary causes of land degradation and desertification in arid and semi-arid regions, demand effective monitoring for sustainable land management. This study explores the utility of partial least square (PLS) latent variables (LVs) derived from visible and near-infrared (Vis-NIR) spectroscopy, combined with remote sensing (RS) and auxiliary variables, to predict electrical conductivity (EC) and sodium absorption ratio (SAR) in northern Xinjiang, China. Using 90 soil samples from the Karamay district, machine learning models (Random Forest, Support Vector Regression, Cubist) were tested in four scenarios. Modeling results showed that RS and Land use alone were unreliable predictors, but the addition of topographic attributes significantly improved the prediction accuracy for both EC and SAR. The incorporation of PLS LVs derived from Vis-NIR spectroscopy led to the highest performance by the Random Forest model for EC (CCC = 0.83, R2 = 0.80, nRMSE = 0.48, RPD = 2.12) and SAR (CCC = 0.78, R2 = 0.74, nRMSE = 0.58, RPD = 2.25). The variable importance analysis identified PLS LVs, certain topographic attributes (e.g., valley depth, elevation, channel network base level, diffuse insolation), and specific RS data (i.e., polarization index of VV + VH) as the most influential predictors in the study area. This study affirms the efficiency of Vis-NIR data for digital soil mapping, offering a cost-effective solution. In conclusion, the integration of proximal soil sensing techniques and highly relevant topographic attributes with the RF model has the potential to yield a reliable spatial model for mapping soil EC and SAR. This integrated approach allows for the delineation of hazardous zones, which in turn enables the consideration of best management practices and contributes to the reduction of the risk of degradation in salt-affected and sodicity-affected soils.

Synergistic Effect of Human Papillomavirus and Environmental Factors on Skin Squamous Cell Carcinoma, Basal Cell Carcinoma, and Melanoma: Insights from a Taiwanese Cohort.

Human papillomavirus (HPV) has been implicated in various cancers, including those affecting the skin. The study assessed the long-term risk of skin cancer associated with HPV infection in Taiwan region, using data from the National Health Insurance Research Database between 2007 and 2015. Our analysis revealed a significant increase in skin cancer risk among those with HPV, particularly for squamous cell carcinoma (SCC), the subtype with the highest observed adjusted hazard ratio (aHR) = 5.97, 95% CI: 4.96-7.19). The overall aHR for HPV-related skin cancer was 5.22 (95% CI: 4.70-5.80), indicating a notably higher risk in the HPV-positive group. The risk of skin cancer was further stratified by type, with basal cell carcinoma (aHR = 4.88, 95% CI: 4.14-5.74), and melanoma (aHR = 4.36, 95% CI: 2.76-6.89) also showing significant associations with HPV. The study also highlighted regional variations, with increased risks in southern Taiwan and the Kaohsiung-Pingtung area. Key findings emphasize the importance of sun protection, particularly in regions of high UV exposure and among individuals in high-risk occupations. This research contributes to a better understanding of the complex interactions between HPV and skin cancer risk, reinforcing the importance of preventive strategies in public health.

Liver fibrosis detected by diffusion-weighted magnetic resonance imaging and its functional correlates in Fontan patients.

OBJECTIVES: The evaluation of Fontan-associated liver disease is often challenging. Diffusion-weighted magnetic resonance imaging can detect hepatic fibrosis from capillary perfusion and diffusion abnormalities from extracellular matrix accumulation. This study investigated its role in the evaluation of liver disease in Fontan patients and explored possible diagnostic methods for early detection of advanced liver fibrosis. METHODS: Stable adult Fontan patients who could safely be examined with magnetic resonance imaging were enrolled, and blood biomarkers, transient elastography were also examined. RESULTS: Forty-six patients received diffusion-weighted imaging; and 58.7% were diagnosed with advanced liver fibrosis (severe liver fibrosis, 37.0%, and cirrhosis 21.7%). Two parameters of hepatic dysfunction, platelet counts (Spearman's ρ: -0.456, P = 0.001) and cholesterol levels (Spearman's ρ: -0.383, P = 0.009), decreased with increasing severity of fibrosis. Using transient elastography, a cut-off value of 14.2 kPa predicted the presence of advanced liver fibrosis, but with a low positive predictive value. When we included platelet count, cholesterol, post-Fontan years and transient elastography values as a composite, the capability of predicting advanced liver fibrosis was the most satisfactory (C statistic 0.817 ± 0.071, P < 0.001). A cut-off value of 5.0 revealed a sensitivity of 78% and a specificity of 82%. CONCLUSIONS: In Fontan patients, diffusion-weighted imaging was helpful in detecting liver fibrosis that was correlated with hepatic dysfunction. A simple score was proposed for long-term surveillance and early detection of advanced liver disease in adult Fontan patients. For adult Fontan patients with a calculated score > 5.0, we may consider timely diffusion-weight imaging and early management for liver complications.

Enhancing the Efficiency and Stability of Inverted Formamidinium-Cesium Lead-Triiodide Perovskite Solar Cells through Lewis Base Pretreatment of Buried Interfaces.

Mixed components of formamidinium(FA) and cesium (Cs)-based perovskite solar cells are the most hopeful for commercialization owing to their excellent operational and phase stabilities, especially for devices with inverted structure. The nonradiative recombination of carriers can be effectively suppressed through interface optimization, therefore, the performance of devices can be improved. Notably, the buried interface emerges as critical aspects such as charge transport, charge recombination kinetics, and morphology of perovskite films. This study focuses on a straightforward yet effective approach to overcome buried interface challenges between organic polymers (poly(-triarylamine) (PTAA) and FACs-based perovskite films. The PTAA substrate is pretreated with a Lewis base known as 2-butynoic acid (BA) with a C═O functional group. First, it can be an interfacial buffering layer, harmonizing stress mismatch between the perovskite and PTAA layers, consequently optimizing crystallization and improving perovskite film quality. Second, Pb2+ defect can be passivated at the buried interface of the perovskite film through binding with the C═O group of the BA molecule. This dual-function strategy leads to a substantial enhancement in both photoelectric conversion efficiency (PCE) and stability of devices. Finally, the PCE of the device-modified buried interface with BA reaches an impressive 23.33%. Furthermore, unencapsulated devices with BA treatment maintain approximately 94% of their initial efficiency after aging at maximum power point tracking for 1000 h.

Sex differences in clinical characteristics and long-term clinical outcomes in Asian hospitalized heart failure patients.

AIMS: Sex differences in long-term post-discharge clinical outcomes in Asian patients hospitalized for acute decompensated heart failure (HF) persist despite the world-wide implementation of guideline-directed medical therapy for decades. The present study aims to elucidate the puzzling dilemma and to depict the directions of solution. METHODS AND RESULTS: Between 2011 and 2020, a total of 12 428 patients (6518 men and 5910 women, mean age 73.50 ± 14.85) hospitalized for acute decompensated HF were retrospectively enrolled from a university HF cohort. Compared with men, women hospitalized for acute decompensated HF were older in age (76.40 ± 13.43 vs. 71.20 ± 15.67 years old, P < 0.0001) with more coexisting hypertension, diabetes, hyperlipidaemia and moderate to severe chronic kidney disease, but less with ischaemic heart disease, cerebrovascular disease and chronic obstructive pulmonary disease (P < 0.0001). In echocardiography measurement parameters, women had smaller left ventricular and left atrial dimensions, higher left ventricular mass index, higher left ventricular ejection fraction (LVEF) and more in HF with preserved ejection fraction (EF) category (LVEF > 50%) than men (P < 0.0001). In HF therapy, women compared with men received more guideline-directed medical HF therapies including angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, angiotensin receptor-neprilysin inhibitors and sodium-glucose cotransporter-2 inhibitors, but similar beta-blockers and mineralocorticoid receptor antagonists (P < 0.0001). Post-discharge long-term clinical outcomes after multivariate-adjusted analysis revealed that women compared with men had lower all-cause mortality [adjusted hazard ratio (aHR): 0.89, 95% confidence interval (CI): 0.84-0.93], lower cardiovascular mortality (aHR: 0.89, 95% CI: 0.80-0.99) and lower 1 year mortality (aHR: 0.91, 95% CI: 0.84-0.99) but similar HF rehospitalization rate (aHR: 1.02, 95% CI: 0.95-1.09) over 8 years of follow-up. The superiority of women over men in all-cause mortality was shown in HF with preserved EF (>50%) and HF with mildly reduced EF (40%-50%), but not in HF with reduced EF (<40%) category. Subgroup forest plot analysis showed body mass index, coexisting hypertension and chronic obstructive pulmonary disease as significant interacting factors. CONCLUSIONS: With more coronary risk factors and medical comorbidities, less cardiac remodelling and better adherence to guideline-directed HF therapy, women hospitalized for acute decompensated HF demonstrated superiority over men in long-term post-discharge clinical outcomes, including all-cause mortality, cardiovascular mortality and 1 year mortality, and mainly in HF with preserved and mid-range EF categories, in the Asian HF cohort.