Development and Validation of a Community-Based Prediction Model for Depression in Elderly Patients with Diabetes: A Cross-Sectional Study.

Background: In elderly diabetic patients, depression is often overlooked because professional evaluation requires psychiatrists, but such specialists are lacking in the community. Therefore, we aimed to create a simple depression screening model that allows earlier detection of depressive disorders in elderly diabetic patients by community health workers. Methods: The prediction model was developed in a primary cohort that consisted of 210 patients with diabetes, and data were gathered from December 2022 to February 2023. The independent validation cohort included 99 consecutive patients from February 2023 to March 2023. Multivariable logistic regression analysis was used to develop the predictive model. We incorporated common demographic characteristics, diabetes-specific factors, family structure characteristics, the self-perceived burden scale (SPBS) score, and the family APGAR (adaptation, partnership, growth, affection, resolution) score. The performance of the nomogram was assessed with respect to its calibration (calibration curve, the Hosmer-Lemeshow test), discrimination (the area under the curve (AUC)), and clinical usefulness (Decision curve analysis (DCA)). Results: The prediction nomogram incorporated 5 crucial factors such as glucose monitoring status, exercise status, monthly income, sleep disorder status, and the SPBS score. The model demonstrated strong discrimination in the primary cohort, with an AUC of 0.839 (95% CI, 0.781-0.897). This discriminative ability was further validated in the validation cohort, with an AUC of 0.857 (95% CI, 0.779-0.935). Moreover, the nomogram exhibited satisfactory calibration. DCA suggested that the prediction of depression in elderly patients with diabetes mellitus was of great clinical value. Conclusion: The prediction model provides precise and user-friendly guidance for community health workers in preliminary screenings for depression among elderly patients with diabetes.

Exploring the potential biological significance of KDELR family genes in lung adenocarcinoma.

The Lys-Asp-Glu-Leu receptor (KDELR) family genes play critical roles in a variety of biological processes in different tumors. Our study aimed to provide a comprehensive analysis of the potential roles of KDELRs in lung adenocarcinoma (LUAD). Utilizing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, as well as clinical samples, we conducted a series of analyses and validations using R software tools and various online resources. The results showed that KDELR family genes and proteins were highly expressed and associated with a poor prognosis of LUAD. Promoter hypomethylation and the competing endogenous RNA (ceRNA) network of PCAT6/hsa-miR-326/KDELR1 might be potential causes of aberrant KDELR1 overexpression in LUAD. Three key Transcription factors (TFs) (SPI1, EP300, and MAZ) and a TFs-miRNAs-KDELRs network (involving 11 TFs) might be involved in modulating KDELRs expression abnormalities. Gene Set Enrichment Analysis (GSEA) indicated enrichment of genes highly expressing KDELR1, KDELR2, and KDELR3 in MTORC1_SIGNALING, P53_PATHWAY, and ANGIOGENESIS. Negative correlations between KDELRs expression and CD8 + T cell infiltration, as well as CTLA-4 expression. Our multiple analyses suggested that the KDELRs are important signaling molecules in LUAD. These results provided novel insights for developing prognostic markers and novel therapies of LUAD.

Ag-thiolate interactions to enable an ultrasensitive and stretchable MXene strain sensor with high temporospatial resolution.

High-sensitivity strain sensing elements with a wide strain range, fast response, high stability, and small sensing areas are desirable for constructing strain sensor arrays with high temporospatial resolution. However, current strain sensors rely on crack-based conductive materials having an inherent tradeoff between their sensing area and performance. Here, we present a molecular-level crack modulation strategy in which we use layer-by-layer assembly to introduce strong, dynamic, and reversible coordination bonds in an MXene and silver nanowire-matrixed conductive film. We use this approach to fabricate a crack-based stretchable strain sensor with a very small sensing area (0.25 mm2). It also exhibits an ultrawide working strain range (0.001-37%), high sensitivity (gauge factor ~500 at 0.001% and >150,000 at 35%), fast response time, low hysteresis, and excellent long-term stability. Based on this high-performance sensing element and facile assembly process, a stretchable strain sensor array with a device density of 100 sensors per cm2 is realized. We demonstrate the practical use of the high-density strain sensor array as a multichannel pulse sensing system for monitoring pulses in terms of their spatiotemporal resolution.

Effects of mindfulness-based cognitive therapy for Chinese adults with PTSD symptoms: protocol for a randomised controlled trial.

INTRODUCTION: Emerging evidence supports mindfulness as a potential psychotherapy for post-traumatic stress disorder (PTSD). Individuals with subthreshold PTSD experience significant impairment in their daily life and functioning due to PTSD symptoms, despite not meeting the full diagnostic criteria for PTSD in DSM-5. Mindfulness skills, including non-judgmental acceptance, attentional control and openness to experiences may help alleviate PTSD symptoms by targeting characteristics such as intensified memory processing, dysregulated hyperarousal, avoidance, and thought suppression. This trial aims to test the effects of mindfulness-based cognitive therapy (MBCT) when compared to an active control. METHOD AND ANALYSIS: This 1:1 randomised controlled trial will enroll 160 participants with PTSD symptoms in 2 arms (MBCT vs. Seeking Safety), with both interventions consisting of 8 weekly sessions lasting 2 h each week and led by certified instructors. Assessments will be conducted at baseline (T0), post-intervention (T1), and 3 months post-intervention (T2), with the primary outcome being PTSD symptoms measured by the PTSD checklist for DSM-5 (PCL-5) at T1. Secondary outcomes include depression, anxiety, attention, experimental avoidance, rumination, mindfulness, and coping skills. Both intention-to-treat and per-protocol analyses will be performed. Mediation analysis will investigate whether attention, experimental avoidance, and rumination mediate the effect of mindfulness on PTSD symptoms. DISCUSSION: The proposed study will assess the effectiveness of MBCT in improving PTSD symptoms. The findings are anticipated to have implications for various areas of healthcare and contribute to the enhancement of existing intervention guidelines for PTSD. TRIAL REGISTRATION NUMBER: ChiCTR2200061863.

Multi-metallic Layered Catalysts for Stable Electrochemical CO2 Reduction to Formate and Formic Acid.

Electrochemical CO2 reduction (ECR) to value-added products such as formate/formic acid is a promising approach for CO2 mitigation. Practical ECR requires long-term stability at industrially relevant reduction rates, which is challenging due to the rapid degradation of most catalysts at high current densities. Herein, we report the development of a bismuth (Bi) gas diffusion electrode on a polytetrafluoroethylene-based electrically conductive silver (Ag) substrate (Ag@Bi), which exhibits high Faradaic efficiency (FE) for formate of over 90 % in 1 M KOH and 1 M KHCO3 electrolytes. The catalyst also shows high selectivity of formic acid above 85 % in 1 M NaCl catholyte, which has a bulk pH of 2-3 during ECR, at current densities up to 300 mA cm-2. In 1 M KHCO3 condition, Ag@Bi maintains formate FE above 90 % for at least 500 hours at the current density of 100 mA cm-2. We found that the Ag@Bi catalyst degrades over time due to the leaching of Bi in the NaCl catholyte. To overcome this challenge, we deposited a layer of Ag nanoparticles on the surface of Ag@Bi to form a multi-layer Ag@Bi/Ag catalyst. This designed catalyst exhibits 300 hours of stability with FE for formic acid ≥70 % at 100 mA cm-2. Our work establishes a new strategy for achieving the operational longevity of ECR under wide pH conditions, which is critical for practical applications.

The association between organised colorectal cancer screening strategies and reduction of its related mortality: a systematic review and meta-analysis.

BACKGROUND: To assess the long-term association between organised colorectal cancer (CRC) screening strategies and CRC-relate mortality. METHODS: We systematically reviewed studies on organised CRC screening through PubMed, Ovid Medline, Embase and Cochrane from the inception. We retrieved characteristics of organised CRC screening from included literature and matched mortality (over 50 years) of those areas from the International Agency for Research on Cancer in May 2023. The variations of mortality were reported via the age-standardised mortality ratio. A random-effects model was used to synthesis results. RESULTS: We summarised 58 organised CRC screening programmes and recorded > 2.7 million CRC-related deaths from 22 countries where rollout screening programmes were performed. The CRC screening strategy with faecal tests (guaiac faecal occult blood test (gFOBT) or faecal immunochemical tests (FIT)) or colonoscopy as the primary screening offer was associated with a 41.8% reduction in mortality, which was higher than those offered gFOBT (4.4%), FIT (16.7%), gFOBT or FIT (16.2%), and faecal tests (gFOBT or FIT) or flexible sigmoidoscopy (16.7%) as primary screening test. The longer duration of screening was associated with a higher reduction in the pooled age-standardised mortality ratio. In particular, the pooled age-standardised mortality ratio became non-significant when the screening of FIT was implemented for less than 5 years. CONCLUSIONS: A CRC screening programme running for > 5 years was associated with a reduction of CRC-related mortality. Countries with a heavy burden of CRC should implement sustainable, organised screening providing a choice between faecal tests and colonoscopy as a preferred primary test.

Realization of white-light-emitting diodes from a high-brightness zirconium-based metal-organic gel driven by the AIE effect.

Developing luminescent materials with suitable correlated color temperature (CCT) and sufficient color-rendering index (CRI) is a challenging problem in the field of commercialized warm white LED lighting. Herein, a novel metal-organic gel (MOG) material named YTU-G-1(SE) was synthesized, consisting of zirconium metal coordinated with 1,1,2,2-tetrakis(4-carboxyphenyl) ethylene. YTU-G-1(SE) exhibits strong fluorescent properties with an aggregation-induced emission (AIE) effect, emitting yellow-green fluorescence at 515 nm. The internal and external quantum efficiencies (IQE/EQE) of YTU-G-1(SE) are close to unity, with values of 95.74 ± 0.5% and 88.67 ± 0.5%, respectively. Finally, we combined YTU-G-1(SE) with a commercial blue chip and a commercial red phosphor (Sr,Ca)AlSiN3:Eu2+ to fabricate a warm white light LED with a color temperature of 3736 K, a color-rendering index Ra of 88.2, and a lumen efficiency of 79.42 lm W-1. This work provides a new approach to regulating the emission of AIE and offers a novel idea for developing high-performance warm-white pc-WLEDs.

Nanocellulose based ultra-elastic and durable foams for smart packaging applications.

Foams with advanced sensing properties and excellent mechanical properties are promising candidates for smart packaging materials. However, the fabrication of ultra-elastic and durable foams is still challenging. Herein, we report a universal strategy to obtain ultra-elastic and durable foams by crosslinking cellulose nanofiber and MXene via strong covalent bonds and assembling the composites into anisotropic cellular structures. The obtained composite foam shows an excellent compressive strain of up to 90 % with height retention of 97.1 % and retains around 90.3 % of its original height even after 100,000 compressive cycles at 80 % strain. Their cushioning properties were systematically investigated, which are superior to that of wildly-used petroleum-based expanded polyethylene and expanded polystyrene. By employing the foam in a piezoelectric sensor, a smart cushioning packaging and pressure monitoring system is constructed to protect inner precision cargo and detect endured pressure during transportation for the first time.

Identification and validation of necroptosis-related gene signatures to predict clinical outcomes and therapeutic responses in acute myeloid leukemia.

BACKGROUND: Necroptosis is a tightly regulated form of necrotic cell death that promotes inflammation and contributes to disease development. However, the potential roles of necroptosis-related genes (NRGs) in acute myeloid leukemia (AML) have not been elucidated fully. METHODS: We conducted a study to identify a robust biomarker signature for predicting the prognosis and immunotherapy efficacy based on NRGs in AML. We analyzed the genetic and transcriptional alterations of NRGs in 151 patients with AML. Then, we identified three necroptosis clusters. Moreover, a necroptosis score was constructed and assessed based on the differentially expressed genes (DEGs) between the three necroptosis clusters. RESULTS: Three necroptosis clusters were correlated with clinical characteristics, prognosis, the tumor microenvironment, and infiltration of immune cells. A high necroptosis score was positively associated with a poor prognosis, immune-cell infiltration, expression of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1), immune score, stromal score, interferon-gamma (IFNG), merck18, T-cell dysfunction-score signatures, and cluster of differentiation-86, but negatively correlated with tumor immune dysfunction and exclusion score, myeloid-derived suppressor cells, and M2-type tumor-associated macrophages. Our observations indicated that a high necroptosis score might contribute to immune evasion. More interestingly, AML patients with a high necroptosis score may benefit from treatment based on immune checkpoint blockade. CONCLUSIONS: Consequently, our findings may contribute to deeper understanding of NRGs in AML, and facilitate assessment of the prognosis and treatment strategies.

Detection of NPM1 Mutations in Acute Myeloid Leukemia by using Drop-Off Droplet Digital PCR and its Clinical Application.

BACKGROUND: Nucleophosmin 1 (NPM1) mutations, which occur in 25 - 30% of acute myeloid leukemia (AML) and 50 - 60% of AML with normal karyotype, have been identified as an important marker for stratification of prog-nosis in AML. This study aimed to establish a new quantitative polymerase chain reaction (PCR) technique, the drop-off droplet digital PCR (ddPCR), for rapid and sensitive detection of NPM1 mutations in AML. METHODS: We established the drop-off ddPCR system and verified its performance. NPM1 mutations were screened in 130 AML patients by drop-off ddPCR and were validated by Sanger sequencing and next-generation sequencing (NGS). Then, the NPM1 mutation burden was dynamically monitored in five patients. RESULTS: The limit of blank (LOB) of drop-off ddPCR established for NPM1 mutation was 3.36 copies/µL, and the limit of detection (LOD) was 5.00 - 5.37 copies/µL in 50 ng DNA, and the sensitivity was about 0.05%, which had good linearity. Drop-off ddPCR identified 33/130 (25.4%) NPM1 mutated cases, consistent with Sanger sequencing. In 18 NPM1 positive cases selected randomly, NGS identified fourteen with type A mutation, two with type D mutation, and two with rare type mutations. The mutation burden of NPM1 mutation analyzed by NGS was consistent with the drop-off ddPCR. The sequential samples were detected for measurable residual disease (MRD) monitoring in 5 patients showed that the NPM1 mutation burden was consistent with clinical remission and recurrence. Compared with traditional ddPCR, drop-off ddPCR was also suitable for MRD monitoring. CONCLUSIONS: In this study, we established a drop-off ddPCR method for detecting three common mutations in AML with good sensitivity and repeatability, which can be used to screen mutations in newly diagnosed AML patients and for MRD monitoring after remission to guide treatment.

Comprehensive characterization of TGFB1 across hematological malignancies.

TGFB1, which encodes TGF-ß1, a potent cytokine regulating varies cellular processes including immune responses. TGF-ß1 plays context-dependent roles in cancers and is increasingly recognized as a therapeutic target to enhance immunotherapy responses. We comprehensively evaluated expression of TGFB1 and its clinical and biological effects across hematological malignancies. TGFB1 expression was first explored using data from the GTEx, CCLE, and TCGA databases. The expression and clinical significances of TGFB1 in hematological malignancies were analyzed using Hemap and our In Silico curated datasets. We also analyzed the relationship between TGFB1 with immune scores and immune cell infiltrations in Hemap. We further assessed the value of TGFB1 in predicting immunotherapy response using TIDE and real-world immunotherapy datasets. TGFB1 showed a hematologic-tissue-specific expression pattern both across normal tissues and cancer types. TGFB1 expression were broadly dysregulated in blood cancers and generally associated with adverse prognosis. TGFB1 expression were associated with distinct TME properties among different blood cancer types. In addition, TGFB1 expression was found to be a useful marker in predicting immunotherapy responses. Our results suggest that TGFB1 is broadly dysregulated in hematological malignancies. TGFB1 might regulate the immune microenvironment in a cancer-type-specific manner, which could be applied in the development of new targeted drugs for immunotherapy.

ALOX5AP is a new prognostic indicator in acute myeloid leukemia.

BACKGROUND: The overexpression of ALOX5AP has been observed in many types of cancer and has been identified as an oncogene. However, its role in acute myeloid leukemia (AML) has not been extensively studied. This study aimed to identify the expression and methylation patterns of ALOX5AP in bone marrow (BM) samples of AML patients, and further explore its clinical significance. METHODS: Eighty-two de novo AML patients and 20 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the alteration of ALOX5AP. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of ALOX5AP expression to discriminate AML. The prognostic value of ALOX5AP was identified by the Kaplan-Meier method and log-rank test. It was further validated in four independent cohorts (n = 1186). Significantly different genes associated with ALOX5AP expression were subsequently compared by LinkedOmics, and Metascape database. RESULTS: The level of ALOX5AP expression was significantly increased in bone marrow cells of AML patients compared with healthy donors (P < 0.05). ROC curve analysis suggested that ALOX5AP expression might be a potential biomarker to discriminate AML from controls. ALOX5AP overexpression was associated with decreased overall survival (OS) in AML according to the TCGA data (P = 0.006), which was validated by other four independent cohorts. DNA methylation levels of ALOX5AP were significantly lower in AML patients compared to normal samples (P < 0.05), as confirmed in the Diseasemeth database and the independent cohort GSE63409. ALOX5AP level was positively associated with genes with proleukemic effects such as PAX2, HOX family, SOX11, H19, and microRNAs that act as oncogenes in leukemia, such as miR125b, miR-93, miR-494, miR-193b, while anti-leukemia-related genes and tumor suppressor microRNAs such as miR-582, miR-9 family and miR-205 were negatively correlated. CONCLUSION: ALOX5AP overexpression, associated with its hypomethylation, predicts poorer prognosis in AML.

Litter decomposition and nutrient release are faster under secondary forests than under Chinese fir plantations with forest development.

In terrestrial ecosystems, leaf litter is the main source of nutrients returning to the soil. Understanding how litter decomposition responds to stand age is critical for improving predictions of the effects of forest age structure on nutrient availability and cycling in ecosystems. However, the changes in this critical process with stand age remain poorly understood due to the complexity and diversity of litter decomposition patterns and drivers among different stand ages. In this study, we examined the effects of stand age on litter decomposition with two well-replicated age sequences of naturally occurring secondary forests and Chinese fir (Cunninghamia lanceolata) plantations in southern China. Our results showed that the litter decomposition rates in the secondary forests were significantly higher than those in the Chinese fir plantations of the same age, except for 40-year-old forests. The litter decomposition rate of the Chinese fir initially increased and then decreased with stand age, while that of secondary forests gradually decreased. The results of a structural equation model indicated that stand age, litter quality and microbial community were the primary factors driving nutrient litter loss. Overall, these findings are helpful for understanding the effects of stand age on the litter decomposition process and nutrient cycling in plantation and secondary forest ecosystems.

Assembled one-dimensional nanowires for flexible electronic devices via printing and coating: Techniques, applications, and perspectives.

The rapid progress in flexible electronic devices has necessitated continual research into nanomaterials, structural design, and fabrication processes. One-dimensional nanowires, characterized by their distinct structures and exceptional properties, are considered essential components for various flexible electronic devices. Considerable attention has been directed toward the assembly of nanowires, which presents significant advantages. Printing and coating techniques can be used to assemble nanowires in a relatively simple, efficient, and cost-competitive manner and exhibit potential for scale-up production in the foreseeable future. This review aims to provide an overview of nanowire assembly using printing and coating techniques, such as bar coating, spray coating, dip coating, blade coating, 3D printing, and so forth. The application of assembled nanowires in flexible electronic devices is subsequently discussed. Finally, further discussion is presented on the potential and challenges of flexible electronic devices based on assembled nanowires via printing and coating.

Machine-learning analysis to predict the fluorescence quantum yield of carbon quantum dots in biochar.

Biochar nanoparticles have recently attracted attention, owing to their environmental behavior and ecological effects. However, biochar has not been shown to contain carbon quantum dots (< 10 nm) with unique photovoltaic properties. Therefore, this study utilized several characterization techniques to demonstrate the generation of carbon quantum dots in biochar produced from 10 types of farm waste. The generated carbon quantum dots had a quasi-spherical morphology and high-resolution lattice stripes with lattice spacings of 0.20-0.23 nm. Moreover, they contained functional groups with good hydrophilic properties, such as amino and hydroxyl groups, and elemental O, C, and N on the surface. A crucial determinant of the photoluminescence properties of carbon quantum dots is their fluorescence quantum yield. Therefore, the relationship between the biochar preparation parameters and the fluorescence quantum yield was investigated using six machine learning analytical models based on 480 samples. Among the models, the gradient-boosting decision-tree regression model exhibited the best predictive performance (R2 > 0.9, RMSE <0.02, and MAPE <3), and was used for the analysis of feature importance; compared to the properties of the raw material, the production parameters had a greater effect on the fluorescence quantum yield. Additionally, four key features were identified: pyrolysis temperature, residence time, N content, and C/N ratio, which were independent of farm waste type. These features can be used to accurately predict the fluorescence quantum yield of carbon quantum dots in biochar. The relative error range between the predicted and the experimental value of fluorescence quantum yield is 0.00-4.60 %. Thus, the prediction model has the potential to predict the fluorescence quantum yield of carbon quantum dots in other types of farm waste biochar, and provides fundamental information for the study of biochar nanoparticles.

Use, satisfaction, and preference of online health services among older adults with multimorbidity in Hong Kong primary care during COVID-19.

BACKGROUND: The use of online and mobile internet and social media has been increasing in healthcare service delivery. However, there is limited literature on the acceptance and use of online health services for older adults with multimorbidity who require more medical care and assistance. This study aims to explore the use of social media in older adults with multimorbidity in Hong Kong primary care and to assess the feasibility and usage of online health services in this population, including satisfaction, preference, and problems encountered. METHODS: This is a cross-sectional study among older adults with multimorbidity conducted between November 2020 and March 2021 in a Hong Kong primary care programme. Online and face-to-face services were offered based on the needs of the participants. Demographic characteristics and health conditions were assessed at baseline. Participants using online services were invited to complete a feedback questionnaire. RESULTS: The study included 752 participants, of which 66.1% use social media every day. Participants who declined to use online services were found to be significantly older, live alone, have lower income, have social security assistance, have greater cognitive decline, and be less depressed (p < 0.05). Non-responders to the online questionnaire had fewer years of education and greater cognitive decline (p < 0.05). The median satisfaction with the online services was 8 (interquartile range: 7, 9), and 14.6% of the participants preferred online more than face-to-face services. Lower education levels, fewer internet connection issues, and more self-efficacy on mobile apps were associated with a higher level of online satisfaction after adjustment (p < 0.05). Fewer internet connection issues and more self-efficacy on mobile apps were associated with participants' preference for online services (p < 0.05). CONCLUSIONS: More than half of Hong Kong older adults with multimorbidity in primary care use social media daily. Internet connection issues can be a significant barrier to the usage of online services in this population. Prior use and training can be beneficial to enhance use and satisfaction in older adults.

A Natural-Position X-Ray for Evaluating Cervical Vertebra Physiology Curvature Before and After Conservative Treatment.

BACKGROUND Abnormal physiological curvature is one of the symptoms of early cervical spondylosis. An X-ray taken with the patient standing in a natural position can best reflect the real cervical vertebra physiological curvature. The purpose of this research was to study the value of natural-position X-ray in evaluating cervical vertebra physiology curvature before and after conservative treatment. MATERIAL AND METHODS This study included 135 participants of different ages diagnosed with cervical disease and who received conservative treatment for more than 12 months. The natural- and regular-position X-rays were performed before and after treatment. The positive change of D value in Borden's measurement and C2~7 Cobb angle should be recognized as an improvement of cervical vertebra physiology curvature. RESULTS Before treatment, the C2~7 Cobb angle of the regular-position group was larger than that of natural-position group. After treatment, the C2~7 Cobb angle of the natural-position group was larger than that of the regular-position group, and the D value increased after treatment in both groups. The effective rate of cervical physiological curvature of the natural-position group was higher than that of the regular-position group. CONCLUSIONS Natural-position X-ray has greater accuracy in evaluating cervical vertebra physiology curvature before and after conservative treatment compared with regular-position X-ray.

A novel methionine metabolism-related signature predicts prognosis and immunotherapy response in lung adenocarcinoma.

Recent research revealed methionine metabolism as a key mediator of tumor initiation and immune evasion. However, the relationship between methionine metabolism and tumor microenvironment (TME) in lung adenocarcinoma (LUAD) remains unknown. Here, we comprehensively analyzed the genomic alterations, expression patterns, and prognostic values of 68 methionine-related regulators (MRGs) in LUAD. We found that most MRGs were highly prognostic based on 30 datasets including 5024 LUAD patients. Three distinct MRG modification patterns were identified, which showed significant differences in clinical outcomes and TME characteristics: The C2 subtype was characterized by higher immune score, while the C3 subtype had more malignant cells and worse survival. We developed a MethScore to measure the level of methionine metabolism in LUAD. MethScore was positively correlated with T-cell dysfunction and tumor-associated macrophages (TAMs), indicating a dysfunctional TME phenotype in the high MethScore group. In addition, two immunotherapy cohorts confirmed that patients with a lower MethScore exhibited significant clinical benefits. Our study highlights the important role of methionine metabolism in modeling the TME. Evaluating methionine modification patterns will enhance our understanding of TME characteristics and can guide more effective immunotherapy strategies.

Determinants of post-COVID-19 symptoms among adults aged 55 or above with chronic conditions in primary care: data from a prospective cohort in Hong Kong.

Background: Primary care patients, especially those with an older age, are one of the most vulnerable populations for post-COVID-19 symptoms. Identifying predictors of post-COVID symptoms can help identify high-risk individuals for preventive care. Methods: Out of 977 primary care patients aged 55 years or above with comorbid physical and psychosocial conditions in a prospective cohort in Hong Kong, 207 patients infected in the previous 5-24 weeks were included. The three most common post-COVID-19 symptoms (breathlessness, fatigue, cognitive difficulty), which lasted beyond the 4-week acute infection period, were assessed using items from the COVID-19 Yorkshire Rehabilitation Scale (C19-YRS), together with other self-reported symptoms. Multivariable analyses were conducted to identify predictors of post-acute and long COVID-19 symptoms (5-24 weeks after infection). Results: The 207 participants had a mean age of 70.8 ± 5.7 years, 76.3% were female, and 78.7% had ≥2 chronic conditions. In total, 81.2% reported at least one post-COVID symptom (mean: 1.9 ± 1.3); 60.9, 56.5 and 30.0% reported fatigue, cognitive difficulty, and breathlessness respectively; 46.1% reported at least one other new symptom (such as other respiratory-related symptoms (14.0%), insomnia or poor sleep quality (14.0%), and ear/nose/throat symptoms (e.g., sore throat) (10.1%), etc.). Depression predicted post-COVID-19 fatigue. The female sex predicted cognitive difficulty. Receiving fewer vaccine doses (2 doses vs. 3 doses) was associated with breathlessness. Anxiety predicted a higher overall symptom severity level of the three common symptoms. Conclusion: Depression, the female sex, and fewer vaccine doses predicted post-COVID symptoms. Promoting vaccination and providing intervention to those at high-risk for post-COVID symptoms are warranted.

The validation and clinical significance of LPCAT1 down-regulation in acute myeloid leukemia.

BACKGROUND: Overexpression of lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been found in various solid cancers and is associated with disease progression, metastasis, and recurrence. However, the expression pattern of LPCAT1 in acute myeloid leukemia (AML) bone marrow remains unknown. The present study aimed to compare LPCAT1 expression differences in bone marrow samples from AML patients and healthy controls and assess the clinical relevance of LPCAT1 in AML. METHODS AND RESULTS: LPCAT1 expression in bone marrow was significantly lower in AML than in healthy controls predicted by public databases. Furthermore, real-time quantitative PCR (RQ-PCR) validated that LPCAT1 expression in bone marrow was significantly down-regulated in AML compared to healthy controls [0.056 (0.000-0.846) vs 0.253 (0.031-1.000)]. The DiseaseMeth version 2.0 and The Cancer Genome Atlas analysis revealed that the LPCAT1 promoter was hypermethylated in AML, and there was a strong negative correlation between LPCAT1 expression and methylation (R = - 0.610, P < 0.001). RQ-PCR revealed that the frequency of LPCAT1 low expression was lower in the FAB-M4/M5 subtype than in the other subtypes (P = 0.018). The ROC curve revealed that LPCAT1 expression could serve as a potential diagnostic marker for differentiating AML from controls with an area under the ROC curve of 0.819 (95% CI 0.743-0.894, P < 0.001). In cytogenetically normal AML, patients with LPCAT1 low expression had significantly longer overall survival than those without LPCAT1 low expression (median 19 versus 5.5 months, P = 0.036). CONCLUSIONS: LPCAT1 is down-regulated in AML bone marrow, and LPCAT1 down-regulation could be used as a potential biomarker for AML diagnosis and prognosis.