Latent space representation of electronic health records for clustering dialysis-associated kidney failure subtypes.

OBJECTIVE: Kidney failure manifests in various forms, from sudden occurrences such as Acute Kidney Injury (AKI) to progressive like Chronic Kidney Disease (CKD). Given its intricate nature, marked by overlapping comorbidities and clinical similarities-including treatment modalities like dialysis-we sought to design and validate an end-to-end framework for clustering kidney failure subtypes. MATERIALS AND METHODS: Our emphasis was on dialysis, utilizing a comprehensive dataset from the UK Biobank (UKB). We transformed raw Electronic Health Record (EHR) data into standardized matrices that incorporate patient demographics, clinical visit data, and the innovative feature of visit time-gaps. This matrix structure was achieved using a unique data cutting method. Latent space transformation was facilitated using a convolution autoencoder (ConvAE) model, which was then subjected to clustering using Principal Component Analysis (PCA) and K-means algorithms. RESULTS: Our transformation model effectively reduced data dimensionality, thereby accelerating computational processes. The derived latent space demonstrated remarkable clustering capacities. Through cluster analysis, two distinct groups were identified: CKD-majority (cluster 1) and a mixed group of non-CKD and some CKD subtypes (cluster 0). Cluster 1 exhibited notably low survival probability, suggesting it predominantly represented severe CKD. In contrast, cluster 0, with substantially higher survival probability, likely to include milder CKD forms and severe AKI. Our end-to-end framework effectively differentiates kidney failure subtypes using the UKB dataset, offering potential for nuanced therapeutic interventions. CONCLUSIONS: This innovative approach integrates diverse data sources, providing a holistic understanding of kidney failure, which is imperative for patient management and targeted therapeutic interventions.

Four-party evolutionary game analysis of enterprise environmental behavior.

With the implementation of the "Rural Revitalization Strategy" in China, it is common for enterprises to go to the countryside to develop business. However, enterprises often neglect the local environmental protection in rural areas while developing the economy to pursue profits. As the end of the national administrative system and the villagers' autonomous organization, the village committee needs to participate in monitoring enterprises' environmental behavior. With this in mind, this paper builds a game model of enterprises, grass-roots governments, farmers, and village committees and analyzes the impact of village committees, grass-roots governments, and farmers on enterprise environmental behavior. The conclusions are as follows: (i) it is difficult for the village committee to promote the positive environmental behavior of enterprises, which needs the supervision of the grass-roots government; (ii) Improving the coordination ability of village committees is conducive to reducing the burden of government supervision; (iii) Farmers' awareness of environmental protection can affect the environmental behavior of enterprises through the rights protection mechanism and reputation mechanism.

Global burden and health inequality of nutritional deficiencies from 1990 to 2019.

Introduction: Nutritional deficiencies (NDs) manifest in various forms and are widespread globally. However, a systematic evaluation of the epidemiology of NDs across all causes and age groups in different countries and regions has not been conducted. Materials and methods: This study aimed to utilize data from the 2019 Global Burden of Disease (GBD) study to assess the burden and trends of NDs, including their incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Additionally, the study evaluated health inequalities at global, regional, and national levels from 1990 to 2019. Result: In 2019, the age-standardized incidence rate of NDs was 2,207.71 per 100,000 individuals (95% UI 1,863.04-2,604.67), and the age-standardized DALYs (ASR-DALYs) was 680.12 per 100,000 individuals (95% UI 507.21-894.89). Among the causes of NDs, dietary iron deficiency had the highest ASR-DALYs and exhibited minimal variation. Children under the age of 5 years faced the greatest risk of NDs. Sex disparity was evident, with males having lower rates than females. Although the gap in the burden of NDs between regions classified as poor and wealthy decreased, disparities persist. Conclusion: These findings provide critical insights for the development of global health strategies aimed at mitigating NDs and may guide policymakers in implementing effective and economically viable interventions.

Isolation, characterization, and application of a novel Pseudomonas fluorescens phage vB_PF_Y1-MI in contaminated milk.

The food industry has incurred substantial losses from contamination by Pseudomonas fluorescens, emphasizing the critical importance of implementing effective control strategies. Phages are potential sterilizers due to their specific killing abilities and the difficulty bacteria face in developing resistance. However, a significant barrier to their development is the lack of diversity among phage types. In this study, we characterized a novel lytic P. fluorescens phage, named vB_PF_Y1-MI. Phage vB_PF_Y1-MI displayed a latent period of nearly 10 min and a high burst size of 1493 PFU/cell. This phage showed good activity over a wide range of temperature (up to 70 °C) and pH (3-12). The genome of phage vB_PF_Y1-MI spans 93,233 bp with a GC content of 45%. It encompasses 174 open-reading frames and 19 tRNA genes, while no lysogeny or virulence-associated genes were detected. Phylogenetic analysis positions it as a novel unassigned evolutionary lineage within the Caudoviricetes class among related dsDNA phages. Our study provides foundational insights into vB_PF_Y1-MI and emphasizes its potential as an effective biological control agent against P. fluorescens. This research offers crucial theoretical groundwork and technical support for subsequent efforts in preventing and controlling P. fluorescens contamination.

The association of ideal cardiovascular health and its change with subclinical atherosclerosis according to glucose status: A prospective cohort study.

BACKGROUND: An updated definition was developed to better evaluate cardiovascular health (CVH). We aimed to investigate whether optimal or improvement of six CVH metrics defined by new Life's Essential 8 (LE8) may counteract the risk of subclinical atherosclerosis among patients with hyperglycemia. METHODS: We conducted a prospective analysis of 5225 participants without prior cardiovascular diseases, of whom 4768 had complete data on CVH change. Subjects with CVH scores of 0-49, 50-79, and 80-100 points were categorized as having low, moderate, or high CVH, respectively. Subclinical atherosclerosis was evaluated by brachial-ankle pulse wave velocity, pulse pressure and albuminuria, both separately and in combination. RESULTS: Of the 5225 participants, 1937 (37.1%) had normal glucose regulation, while 3288 (62.9%) had hyperglycemia. The multivariable-adjusted odds ratio (OR) for composite subclinical atherosclerosis was 2.34 (95% confidence interval [CI], 1.88-2.91), 1.43 (95% CI, 1.21-1.70), and 0.74 (95% CI, 0.46-1.18), for participants with hyperglycemia who had low, moderate, or high overall CVH scores, respectively, compared with participants with normal glucose regulation. In addition, compared with those with stable CVH and normal glucose regulation, participants who exhibited greater improvements in overall CVH from 2010 to 2014 had a reduced risk of composite subclinical atherosclerosis with an OR of 0.72 (95% CI, 0.53-0.98) for those with normal glucose regulation, and 1.13 (95% CI, 0.87-1.48) for those with hyperglycemia. CONCLUSIONS: The novel defined CVH using six metrics was inversely associated with subsequent risk of subclinical atherosclerosis. Both the status of CVH and its changes modified the relationship between hyperglycemia and subclinical atherosclerosis.

Clustering-based risk stratification of prediabetes populations: Insights from the Taiwan and UK Biobanks.

AIMS/INTRODUCTION: This study aimed to identify low- and high-risk diabetes groups within prediabetes populations using data from the Taiwan Biobank (TWB) and UK Biobank (UKB) through a clustering-based Unsupervised Learning (UL) approach, to inform targeted type 2 diabetes (T2D) interventions. MATERIALS AND METHODS: Data from TWB and UKB, comprising clinical and genetic information, were analyzed. Prediabetes was defined by glucose thresholds, and incident T2D was identified through follow-up data. K-means clustering was performed on prediabetes participants using significant features determined through logistic regression and LASSO. Cluster stability was assessed using mean Jaccard similarity, silhouette score, and the elbow method. RESULTS: We identified two stable clusters representing high- and low-risk diabetes groups in both biobanks. The high-risk clusters showed higher diabetes incidence, with 15.7% in TWB and 13.0% in UKB, compared to 7.3% and 9.1% in the low-risk clusters, respectively. Notably, males were predominant in the high-risk groups, constituting 76.6% in TWB and 52.7% in UKB. In TWB, the high-risk group also exhibited significantly higher BMI, fasting glucose, and triglycerides, while UKB showed marginal significance in BMI and other metabolic indicators. Current smoking was significantly associated with increased diabetes risk in the TWB high-risk group (P < 0.001). Kaplan-Meier curves indicated significant differences in diabetes complication incidences between clusters. CONCLUSIONS: UL effectively identified risk-specific groups within prediabetes populations, with high-risk groups strongly associated male gender, higher BMI, smoking, and metabolic markers. Tailored preventive strategies, particularly for young males in Taiwan, are crucial to reducing T2D risk.

cNEK6 induces gemcitabine resistance by promoting glycolysis in pancreatic ductal adenocarcinoma via the SNRPA/PPA2c/mTORC1 axis.

Resistance to gemcitabine in pancreatic ductal adenocarcinoma (PDAC) leads to ineffective chemotherapy and, consequently, delayed treatment, thereby contributing to poor prognosis. Glycolysis is an important intrinsic reason for gemcitabine resistance as it competitively inhibits gemcitabine activity by promoting deoxycytidine triphosphate accumulation in PDAC. However, biomarkers are lacking to determine which patients can benefit significantly from glycolysis inhibition under the treatment of gemcitabine activity, and a comprehensive understanding of the molecular mechanisms that promote glycolysis in PDAC will contribute to the development of a strategy to sensitize gemcitabine chemotherapy. In this study, we aimed to identify a biomarker that can robustly indicate the intrinsic resistance of PDAC to gemcitabine and guide chemotherapy sensitization strategies. After establishing gemcitabine-resistant cell lines in our laboratory and collecting pancreatic cancer and adjacent normal tissues from gemcitabine-treated patients, we observed that circRNA hsa_circ_0008383 (namely cNEK6) was highly expressed in the peripheral blood and tumor tissues of patients and xenografts with gemcitabine-resistant PDAC. cNEK6 enhanced resistance to gemcitabine by promoting glycolysis in PDAC. Specifically, cNEK6 prevented K48 ubiquitination of small ribonucleoprotein peptide A from the BTRC, a ubiquitin E3 ligase; thus, the accumulated SNRPA stopped PP2Ac translation by binding to its G-quadruplexes in 5' UTR of mRNA. mTORC1 pathway was aberrantly phosphorylated and activated owing to the absence of PP2Ac. The expression level of cNEK6 in the peripheral blood and tumor tissues correlated significantly and positively with the activation of the mTORC1 pathway and degree of glycolysis. Hence, the therapeutic effect of gemcitabine is limited in patients with high cNEK6 levels, and in combination with the mTORC1 inhibitor, rapamycin, can enhance sensitivity to gemcitabine chemotherapy.

Dose advantage of abdominal deep inspiratory breath-hold (aDIBH) in postoperative adjuvant radiotherapy for left breast cancer.

PURPOSE: We explored the dosimetric efficacy of the abdominal deep inspiration breath hold (aDIBH) technique using an audio-guided device in patients with left breast cancer undergoing postoperative adjuvant radiotherapy compared to free breathing (FB). METHODS: A total of 35 patients with early stage left breast cancer underwent two computed tomography simulation scans each with aDIBH and FB after breast-conserving surgery. Treatment planning was optimized using the Pinnacle3 9.10 planning system. The heart, left anterior descending coronary artery (LADCA), and left lung was defined as organs at risk (OARs). The dosimetric differences in the planning target volume (PTV) and OARs were compared between aDIBH and FB. RESULTS: Compared with FB, the heart moved farther caudally and away from the chest wall, and the volume of heart became smaller under aDIBH due to expansion of the lungs. The D mean of the heart, LADCA and left lung of aDIBH were respectively reduced by 332.79 ± 264.61 cGy (P < 0.001), 1290.37 ± 612.09 cGy (P < 0.047) and 69.94 ± 117.73 cGy (P < 0.001). The V20 and V30 of the OARs were also significantly reduced with statistical differences (P < 0.05). In addition, there was no significant difference in the dosimetric parameters of the PTV between the two groups (P > 0.05). CONCLUSIONS: Implementation of the aDIBH technique for postoperative radiotherapy after breast-conserving surgery of the left breast cancer could reduce irradiation of the heart dose, LADCA dose and left lung dose, without compromising target coverage.

Sex difference and socioeconomic inequity in hypertension: a national survey study of 98,658 adults from 162 study sites.

BACKGROUND: Sex differences in blood pressure (BP) levels and hypertension are important and the role of socioeconomic status (SES) in sex differences of hypertension remains unclear. OBJECTIVE: We aimed to evaluate the impact of SES on sex differences of hypertension in a nationally representative survey study. METHODS: A total of 98,658 participants aged ≥18 years who have lived in their current residence for ≥6 months were recruited from 162 study sites across mainland China. Sex was self-reported. Individual-level SES included the highest level of education and annual household income. Area-level SES included economic development status, urban/rural residency, and north/south location. Outcomes included levels of systolic and diastolic BP, and hypertension. Linear and Cox regression models were used to examine the associations between sex (women vs. men) and BP characteristics stratified by individual or combined SES indicators. RESULTS: Systolic and diastolic BP levels and prevalence of hypertension were higher in men than women. This sex difference was found across categories of SES with widened sex disparities in participants having more favorable SES. Significant multiplicative interaction effects of SES on the association of sex with BP characteristics were found. Women with improving SES were associated with lower BP and hypertension prevalence compared with men. For combined SES, a 9% (prevalence ratio (PR)=0.91, 95% confidence interval (CI)=0.83, 0.98) and a 30% lower probability (PR=0.70, 95% CI=0.63, 0.78) of having hypertension were found in women with an overall intermediate SES and high SES, respectively compare with low SES while no significant reduction was found in men. CONCLUSIONS: There are significant sex differences in BP characteristics and SES has a potent impact on the disparities. Sex-specific public health policies to alleviate socioeconomic inequalities, especially in women are important for the prevention of hypertension.

Circular RNAs in programmed cell death: Regulation mechanisms and potential clinical applications in cancer: A review.

Circular RNAs (circRNAs) are a novel class of non-coding RNAs with covalently closed structures formed by reverse splicing of precursor mRNAs. The widespread expression of circRNAs across species has been revealed by high-throughput sequencing and bioinformatics approaches, indicating their unique properties and diverse functions including acting as microRNA sponges and interacting with RNA-binding proteins. Programmed cell death (PCD), encompassing various forms such as apoptosis, necroptosis, pyroptosis, autophagy, and ferroptosis, is an essential process for maintaining normal development and homeostasis in the human body by eliminating damaged, infected, and aging cells. Many studies have demonstrated that circRNAs play crucial roles in tumourigenesis and development by regulating PCD in tumor cells, showing that circRNAs have the potential to be biomarkers and therapeutic targets in cancer. This review aims to comprehensively summarize the intricate associations between circRNAs and diverse PCD pathways in tumor cells, which play crucial roles in cancer development. Additionally, this review provides a detailed overview of the underlying mechanisms by which circRNAs modulate various forms of PCD for the first time. The ultimate objective is to offer valuable insights into the potential clinical significance of developing novel strategies based on circRNAs and PCD for cancer diagnosis, prognosis, and treatment.

Periodic Domain Inversion in Single Crystal Barium Titanate-on-Insulator Thin Film.

Experimentally achieving the first-ever electric field periodic poling of single crystal barium titanate oxide (BTO, or BaTiO3) thin film on-insulator is reported. Owing to the outstanding optical nonlinearities of BTO, this result is a key step toward achieving quasi-phase-matching (QPM). First, the BTO thin film is grown on a dysprosium scandate substrate using pulsed laser deposition with a thin layer of strontium ruthenate later serving as the bottom electrode for poling. The characterization of the BTO thin film using x-ray diffraction (XRD) and piezo-response force microscopy to demonstrate single crystal, single domain growth of the film that enables the desired periodic poling, are presented. To investigate the poling quality, both non-destructive piezo force response microscopy and destructive etching-assisted scanning electron microscopy (SEM) are applied, and it is shown that high quality, uniform, and intransient poling with 50% duty cycle and periods ranging from 2 µm to 10 µm is achieved. The successful realization of periodic poling in BTO thin film unlocks the potential for highly efficient nonlinear processes under QPM that seemed far-fetched with prior polycrystalline BTO thin films which predominantly relied on efficiency-limited random or non-phase matching conditions and is a key step toward integration of BTO photonic devices.

Sustainable development between sports facilities and ecological environment based on the dual carbon background.

The sustainable development of sports facilities and their integration with the ecological environment are crucial in addressing global environmental challenges. This study examines the coupling coordination between sports facilities and the ecological environment in nine prefecture-level cities in Fujian Province, China, from 2013 to 2020, within the framework of China's "Dual Carbon" strategy. Using a multidisciplinary approach that integrates economics, sociology, and geography, the study employs the entropy method and coupling coordination models to analyze the temporal evolution and spatial distribution of the coupling coordination between sports facilities and the ecological environment. The findings reveal that the overall trend of coupling coordination is positive, with the degree of coordination improving over time from severe imbalance in 2013 to high-quality coordination by 2020. Economic factors, such as per capita GDP, positively influence the coupling coordination, while factors like population density and regional GDP have a negative impact. Coastal cities, such as Xiamen and Zhangzhou, demonstrate stronger regional correlations and play a critical role in improving the overall coupling level of the province. This research provides several recommendations for promoting orderly and optimal development, considering the distinct characteristics of sports facilities and the ecological environment.

Sulindac (K-80003) with nab-paclitaxel and gemcitabine overcomes drug-resistant pancreatic cancer.

The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance's core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.

Impact of Postoperative Chemotherapy on Survival in Patients with Primary Central Nervous System Lymphoma: A Study Based on the SEER Database.

Aims/Background We aimed to investigate the impact of postoperative chemotherapy (POCT) on survival in patients with primary central nervous system lymphoma (PCNSL) using data from the Surveillance, Epidemiology, and End Results (SEER) database. Methods This study included 786 PCNSL patients, of which 605 received chemotherapy after surgery, and 181 did not. Data from the SEER registry database (2007-2020) were used to analyze PCNSL. Baseline information, including age, sex, race, marital status, primary tumour site, histological type, summary stage, surgical procedures, chemotherapy, and radiotherapy, was analyzed. Propensity Score Matching (PSM) (1:1) was employed to balance the effects of confounding variables between the two groups. Subsequently, Cox regression and bidirectional stepwise regression were used to identify independent prognostic factors. Kaplan-Meier (K-M) survival curves were constructed to assess the impact of POCT on patient prognosis. Additionally, two cases of PCNSL with typical magnetic resonance imaging appearances were presented. Results Multivariate Cox regression results revealed that age older than 60 years (hazard ratio [HR] = 1.786; 95% confidence interval [CI]: 1.272-2.509; p = 0.001) and absence of POCT (HR = 2.841; 95% CI: 2.159-3.738; p < 0.001) were independent prognostic risk factors, while primary tumour locations in the meninges (HR = 0.136; 95% CI: 0.032-0.569; p = 0.006) and other nervous system regions (HR = 0.552; 95% CI: 0.326-0.936; p = 0.027), as well as histological morphologies such as diffuse large B-cell lymphoma (HR = 0.233; 95% CI: 0.128-0.425; p < 0.001) and non-Hodgkin lymphoma (HR = 0.559; 95% CI: 0.356-0.876; p = 0.011), were associated with favourable patient outcomes. K-M curves demonstrated that the group undergoing POCT had a significantly more favourable prognosis compared to the non-POCT group, before (HR = 0.454; 95% CI: 0.343-0.600; p < 0.0001) or after PSM (HR = 0.580; 95% CI: 0.431-0.780; p < 0.0001). For patients with PCNSL, those with tumours located in the infratentorial region (HR = 0.231; 95% CI: 0.078-0.682; p = 0.046), supratentorial region (HR = 0.250; 95% CI: 0.163-0.383; p < 0.0001), overlapping brain regions (HR = 0.201; 95% CI: 0.056-0.727; p = 0.0058), and those who underwent biopsy (HR = 0.740; 95% CI: 0.463-1.182; p = 0.003), subtotal resection (STR) (HR = 0.490; 95% CI: 0.265-0.906; p = 0.0064), or gross total resection (GTR) (HR = 0.613; 95% CI: 0.292-1.287; p = 0.0003) had better prognoses in the postoperative chemotherapy group compared to the non-chemotherapy group. Conclusion POCT significantly improves the prognosis of PCNSL patients and identifies the characteristics of the benefiting population. This information aids clinical practitioners in designing personalized treatment plans for individuals and advancing precise treatment.

[Treatment of massive rotator cuff tears with modified Chinese-way technique].

OBJECTIVE: To explore clinical effect of modified Chinese-way technique under shoulder arthroscopy in treating massive rotator cuff tears. METHODS: From January 2019 to June 2022, 22 patients with massive rotator cuff tears who underwent arthroscopic rotator cuff repair with improved Chinese-way technique, including 10 males and 12 females, aged from 46 to 76 years old with an average of(64.14±7.45) years old;the courses of disease ranged from 5 to 14 months with an average of(8.32±2.42) months;19 patients were complete repaired, and 3 patients were partial repaired. Visual analogue scale (VAS) and University of California at Los Angeles (UCLA) scale were used to evaluate pain and function of shoulder joint preoperatively and 1 year postoperatively. Postoperative complications, the integrity of reconstructed tissue structure and the size of subacromial space were observed. RESULTS: All patients were followed up from 12 to 34 months with an average of (17.14±5.93) months. Re-tear were occurred in 4 patients during MRI follow-up, but clinical symptoms of patients were improved significantly and they were satisfied with the treatment, the others were no complications such as incision infection, peripheral nerve injury, loosening and falling off of internal fixation anchors. Preoperative and 1 year after operation VAS were (8.05±1.12) and (1.82±1.50), UCLA scores were (7.45±1.65) and (31.41±2.87) respectively, and the difference was statistically significant (P<0.05). CONCLUSION: The modified Chinese-way technique under shoulder arthroscopy for the massive rotator cuff tear could relieve pain obviously and recovery postoperative function well, with satisfactory curative effect.

Electrochemical promoted three-component reaction to unsymmetric thiosulfonates.

Compounds comprising S-S bonds serve as significant pharmacological scaffolds in medicinal chemistry and natural products. We have devised an efficient electrochemical method for the construction of asymmetric disulfide bonds, leading to the synthesis of unsymmetric thiosulfonates. Compared with existing synthesis methods, our work not only avoids the use of metals and oxidants, but also realizes the operation of a one-pot three-component method, which makes this strategy extremely attractive.

Genetic complexity of killer-cell immunoglobulin-like receptor genes in human pangenome assemblies.

The killer-cell immunoglobulin-like receptor (KIR) gene complex, a highly polymorphic region of the human genome that encodes proteins involved in immune responses, poses strong challenges in genotyping owing to its remarkable genetic diversity and structural intricacy. Accurate analysis of KIR alleles, including their structural variations, is crucial for understanding their roles in various immune responses. Leveraging the high-quality genome assemblies from the Human Pangenome Reference Consortium (HPRC), we present a novel bioinformatic tool, the structural KIR annoTator (SKIRT), to investigate gene diversity and facilitate precise KIR allele analysis. In 47 HPRC-phased assemblies, SKIRT identifies a recurrent novel KIR2DS4/3DL1 fusion gene in the paternal haplotype of HG02630 and maternal haplotype of NA19240. Additionally, SKIRT accurately identifies eight structural variants and 15 novel nonsynonymous alleles, all of which are independently validated using short-read data or quantitative polymerase chain reaction. Our study has discovered a total of 570 novel alleles, among which eight haplotypes harbor at least one KIR gene duplication, six haplotypes have lost at least one framework gene, and 75 out of 94 haplotypes (79.8%) carry at least five novel alleles, thus confirming KIR genetic diversity. These findings are pivotal in providing insights into KIR gene diversity and serve as a solid foundation for understanding the functional consequences of KIR structural variations. High-resolution genome assemblies offer unprecedented opportunities to explore polymorphic regions that are challenging to investigate using short-read sequencing methods. The SKIRT pipeline emerges as a highly efficient tool, enabling the comprehensive detection of the complete spectrum of KIR alleles within human genome assemblies.

Androgen receptor expression and clinical characteristics in breast cancer.

OBJECTIVE: To investigate the relationship between the expression of androgen receptor (AR) and clinical characteristics in breast cancer. PATIENTS AND METHODS: The clinical records of all 432 patients tested for AR in our institution between January 2020 and May 2023 were reviewed. Clinical characteristics, age, menopausal status, tumor node metastasis (TNM) stage, distant metastasis, pathological complete response (pCR), histopathological features histological grade, estrogen receptor (ER), progesterone receptor, Her-2, Ki-67, and molecular subtype were registered for all patients. RESULTS: About 377 (87.27%) of the 432 patients had AR expression. No significant difference in AR expression was found with age, menopausal status, TNM stage of primary tumor, or pCR. AR was positively and significantly associated with the histological grade, and recurrence. The AR expression was significantly related with molecular subtypes, including ER, PR Her-2, Ki67 and molecular subtype. ER (OR = 10.489, 95%CI: 5.470-21.569), PR (OR = 7.690, 95%CI: 3.974-16.129, Her-2 (OR = 10.489, 95%CI: 2.779-23.490 and tumor recurrence (OR = 0.110, 95%CI: 0.031-0.377 were significant independent risk factors affecting AR expression. CONCLUSIONS: AR expression can serve as a reliable basis for judging the clinical molecular types and poor prognosis for breast cancer. AR may be a novel biomarker and target in AR-positive breast cancer depending on significant difference in AR expression among different molecular types of breast cancer.

Rapid transformation of nanobodies affinity based on AlphaFold2's high-accuracy predictions and interaction analysis for enrofloxacin detection in coastal fish.

High-affinity antibodies are crucial in biosensors, disease diagnostics, therapeutic drug development, and immunological analysis, making the enhancement of antibody affinity a key research focus within the field. Computer-aided design is recognized as a time-saving and labor-efficient method for nanobodies in vitro affinity maturation. Compared to experimental mutagenesis techniques, it is advantageous due to the elimination of the need for laborious library construction and screening processes. However, these approaches are constrained by structural prediction since inaccuracy in structure could readily result in maturation failures. Herein, a novel nanobodies modification method for in vitro affinity maturation, utilizing the high accuracy prediction of AlphaFold2, was employed to rapidly transform a low affinity nanobody against enrofloxacin (ENR) into one with high affinity. The molecular docking results revealed a 1.5- to 2.5-fold increase in the number of noncovalent interactions of modified nanobodies, accompanied by a reduction in binding free energy ranging from 14.1 to 62.6%. The evaluation results from ELISA and BLI indicated that the affinity of the modified nanobodies had been enhanced by 6.2-91.6 times compared to the template nanobody. Furthermore, the modified nanobodies were employed for the detection of ENR-spiked coastal fish samples. In summary, this research proposed a nanobodies modification method from a new perspective, endowing its great application potential in biosensors, food safety, and environmental monitoring.