Intracardiac leakage of cement during artificial femoral head replacement: a case report and review.

Bone cement leakage from the femoral medullary cavity is a rare complication following hip replacement. Currently, there are no reports of bone cement leakage into the heart. Here, we report an 81-year-old female patient with right femoral neck fracture. A thorough preoperative examination showed that bone cement had leaked into the heart during right femoral head replacement, leading to the death of the patient that night. Postoperative cardiac ultrasound showed that bone cement entered the vascular system through the femoral medullary cavity and subsequently entered the heart. Extreme deterioration in the patient's condition resulted in death that night. Unfortunately, the patient's family abandoned the idea of surgical removal of foreign bodies, leading to inevitable death. This case emphasizes the risk of clinical manifestations of cardiac embolism of bone cement after artificial femoral head replacement, suggesting that the risk of such embolism might be underestimated. We propose routine real-time C-arm X-ray guidance and injection of an appropriate amount of bone cement to prevent serious cardiopulmonary failure.

A dual-mode fluorometric/colorimetric sensor for sulfadimethoxine detection based on Prussian blue nanoparticles and carbon dots.

A dual-mode (colorimetric/fluorescence) nanoenzyme-linked immunosorbent assay (NLISA) was developed based on Au-Cu nanocubes generating Prussian blue nanoparticles (PBNPs). It is expected that this method can be used to detect the residues of sulfonamides in the field, and solve the problem of long analysis time and high cost of the traditional method. Sulfadimethoxine (SDM) was selected as the proof-of-concept target analyte. The Au-Cu nanocubes were linked to the aptamer by amide interaction, and the Au-Cu nanocubes, SDM and antibody were immobilized on a 96-well plate using the sandwich method. The assay generates PBNPs by oxidising the Cu shells on the Au-Cu nanocubes in the presence of hydrochloric acid, Fe3+ and K3[Fe (CN)6]. In this process, the copper shell undergoes oxidation to Cu2+ and subsequently Cu2 + further quenches the fluorescence of the carbon point. PBNPs exhibit peroxidase-like activity, oxidising 3,3',5,5'-tetramethylbenzidine (TMB) to OX-TMB in the presence of H2O2, which alters the colorimetric signal. The dual-mode signals are directly proportional to the sulfadimethoxine concentration within the range 10- 3~10- 7 mg/mL. The limit of detection (LOD) of the assay is 0.023 ng/mL and 0.071 ng/mL for the fluorescent signal and the colorimetric signal, respectively. Moreover, the assay was successfully applied to determine sulfadimethoxine in silver carp, shrimp, and lamb samples with satisfactory results.

Moral Dilemmas Regarding Physical Restraints in Intensive Care Units: Understanding Autonomy, Beneficence, Non-Maleficence and Justice in the Use of Physical Restraints.

In intensive care units, patients are often restrained to ensure their safety, with physical restraints being the most commonly used method. However, physical restraints compromises the patient's freedom, health and comfort, and nurses often face moral dilemmas when deciding whether to use physical restraints. This article examines physical restraints through the four universal principles of autonomy, beneficence, non-maleficence and justice. Through these principles, the authors will critically explore whether the physical restraints of patients by nurses is ethical in practice and what moral issues exist. This paper also explores conflicts and moral dilemmas for nurses in this context. Finally, suggestions are made on changes to education and clinical practice.

Fraction dose escalation of hypofractionated radiotherapy with concurrent chemotherapy and subsequent consolidation immunotherapy in locally advanced non-small cell lung cancer: a phase 1 study.

PURPOSE: This phase 1 trial aimed to determine the maximum tolerated fraction dose (MTFD) of hypofractionated radiotherapy (hypo-RT) combined with concurrent chemotherapy and subsequent consolidation immune checkpoint inhibitors (cICI) for patients with locally advanced non-small cell lung cancer (LA-NSCLC). PATIENTS AND METHODS: Split-course hypo-RT and hypo-boost combined with concurrent chemotherapy were administered at three dose levels (DLs), using a stepwise dose-escalation protocol. The sophisticated esophagus-sparing technique was implemented to restrict the dose to the esophagus. Patients who did not experience disease progression or unresolved G2+ toxicities after radiotherapy received cICI. Each DL aimed to treat 6 patients. The MTFD was defined as the highest DL at which <=2 patients of the 6 who were treated experienced treatment-related G3+ toxicity and <=1 patient experienced G4+ toxicity within 12 months post-radiotherapy. RESULTS: Eighteen patients were enrolled with 6 patients in each DL. All patients completed hypo-RT and concurrent chemotherapy, and 16 (88.9%) received at least one infusion of cICI, with a median of 10 infusions. Within the 12-month assessment period, one patient in DL1 experienced G3 pneumonitis, and one patient in DL3 developed G3 tracheobronchitis. The MTFD was not reached. The objective response rate (ORR) was 100%. With a median follow-up of 20.9 months, the 1-year overall survival and progression-free survival rate were 94.4% and 83.3%, respectively. CONCLUSIONS: Utilizing the split-course hypo-RT and hypo-boost approach, a fraction dose of 5Gy to a total dose of 60Gy, combined with concurrent chemotherapy and subsequent cICI, was well-tolerated, and yielded promising ORR and survival outcomes.

Stress responses and Physiological Changes of Salmonella enterica Serovar Enteritidis on Short-Term and Long-Term Benzalkonium Bromide Adaptation.

Salmonella enterica is a common foodborne pathogen that poses significant safety risks across the world. And benzalkonium bromide (BK) is widely used as a disinfectant to sterilize the food processing equipment. It has been reported that sub-lethal concentration of disinfectants induced not only the homologous resistance but also cross-resistances. This work analyzed the induced resistances of Salmonella Enteritidis by short-term adaptation (STA) and long-term adaptation (LTA) to BK. We have demonstrated that inefficient sterilization exposes Salmonella Enteritidis to sub-lethal concentrations of BK, and adapts bacteria to a higher minimum inhibitory concentration and minimum bactericidal concentration. In addition, STA, but not LTA, to BK induced heterogeneous resistance to sodium hypochlorite, and cross-resistance to freezing, desiccation, and heating, which may be caused by the membrane composition change of Salmonella Enteritidis. This work could be useful to the optimization of cleaning protocol.

From stem cells to pancreatic ß-cells: strategies, applications, and potential treatments for diabetes.

Loss and functional failure of pancreatic ß-cells results in disruption of glucose homeostasis and progression of diabetes. Although whole pancreas or pancreatic islet transplantation serves as a promising approach for ß-cell replenishment and diabetes therapy, the severe scarcity of donor islets makes it unattainable for most diabetic patients. Stem cells, particularly induced pluripotent stem cells (iPSCs), are promising for the treatment of diabetes owing to their self-renewal capacity and ability to differentiate into functional ß-cells. In this review, we first introduce the development of functional ß-cells and their heterogeneity and then turn to highlight recent advances in the generation of ß-cells from stem cells and their potential applications in disease modeling, drug discovery and clinical therapy. Finally, we have discussed the current challenges in developing stem cell-based therapeutic strategies for improving the treatment of diabetes. Although some significant technical hurdles remain, stem cells offer great hope for patients with diabetes and will certainly transform future clinical practice.

[Alcohol Abstinence and Accelerated Biological Aging Among Middle-Aged and Older Adults: Evidence From the UK Biobank]. / ä¸­è€å¹´ç¾¤ä½“é ’ç²¾æˆ’æ–­ä¸Žç”Ÿç‰©è¡°è€åŠ é€Ÿçš„å ³ç³»ï¼šåŸºäºŽè‹±å›½ç”Ÿç‰©é“¶è¡Œæ•°æ®åº“çš„ç ”ç©¶.

Objective: To investigate the longitudinal association between alcohol abstinence and accelerated biological aging among middle-aged and older adults and to explore the potential effect modifiers influencing the association. Methods: Utilizing the clinico-biochemical and anthropometric data from the baseline and first repeat survey of the UK Biobank (UKB), we employed the Klemera and Doubal method (KDM) to construct the biological age (BA) and calculate BA acceleration. Change analysis based on multivariate linear regression models was employed to explore the association between changes in alcohol abstinence and changes in BA acceleration. Age, sex, smoking status, tea and coffee consumption, and body mass index were considered as the stratification factors for conducting stratified analysis. Results: A total of 5 412 participants were included. Short-term alcohol abstinence (ß=1.00, 95% confidence interval [CI]: 0.15-1.86) was found to accelerate biological aging when compared to consistent never drinking, while long-term abstinence (ß=-0.20, 95% CI: -1.12-0.71) did not result in a significant acceleration of biological aging. Body mass index may be a potential effect modifier. Conclusion: Short-term alcohol abstinence was associated with accelerated biological aging, but the effect gradually diminishes over extended periods of abstinence.

Identification of an immune-related gene signature for predicting prognosis and immunotherapy efficacy in liver cancer via cell-cell communication.

BACKGROUND: Liver cancer is one of the deadliest malignant tumors worldwide. Immunotherapy has provided hope to patients with advanced liver cancer, but only a small fraction of patients benefit from this treatment due to individual differences. Identifying immune-related gene signatures in liver cancer patients not only aids physicians in cancer diagnosis but also offers personalized treatment strategies, thereby improving patient survival rates. Although several methods have been developed to predict the prognosis and immunotherapeutic efficacy in patients with liver cancer, the impact of cell-cell interactions in the tumor microenvironment has not been adequately considered. AIM: To identify immune-related gene signals for predicting liver cancer prognosis and immunotherapy efficacy. METHODS: Cell grouping and cell-cell communication analysis were performed on single-cell RNA-sequencing data to identify highly active cell groups in immune-related pathways. Highly active immune cells were identified by intersecting the highly active cell groups with B cells and T cells. The significantly differentially expressed genes between highly active immune cells and other cells were subsequently selected as features, and a least absolute shrinkage and selection operator (LASSO) regression model was constructed to screen for diagnostic-related features. Fourteen genes that were selected more than 5 times in 10 LASSO regression experiments were included in a multivariable Cox regression model. Finally, 3 genes (stathmin 1, cofilin 1, and C-C chemokine ligand 5) significantly associated with survival were identified and used to construct an immune-related gene signature. RESULTS: The immune-related gene signature composed of stathmin 1, cofilin 1, and C-C chemokine ligand 5 was identified through cell-cell communication. The effectiveness of the identified gene signature was validated based on experimental results of predictive immunotherapy response, tumor mutation burden analysis, immune cell infiltration analysis, survival analysis, and expression analysis. CONCLUSION: The findings suggest that the identified gene signature may contribute to a deeper understanding of the activity patterns of immune cells in the liver tumor microenvironment, providing insights for personalized treatment strategies.

The efficacy and safety of PD-1 inhibitor combined with TACE in the first-line treatment of unresectable hepatocellular carcinoma.

The application of immune checkpoint inhibitors (ICIs) has changed the treatment of advanced hepatocellular carcinoma. Transcatheter arterial chemoembolization (TACE) is a first-line treatment for intermediate hepatocellular carcinoma. Serving as a local treatment modality that can induce immunogenic cell death, the efficacy and safety of combined use with ICI have not been evaluated. Although there have been prospective studies aimed at evaluating the efficacy and safety of ICI combined with TACE in BCLC stage B HCC patients, there are few reports on the evaluation of BCLC stage C patients with distant metastasis or portal vein cancer thrombus. Data of unresectable hepatocellular carcinoma patients received PD-1 inhibitor and TACE were collected in Xijing Hospital from June 2019 to December 2022. The tumor response was evaluated according to the Solid Tumor Modified Response Evaluation Standard (mRECIST), including complete response (CR), partial response (PR), disease stability (SD), disease progression (PD), objective response rate (ORR), and disease control rate (DCR). The progression-free survival (PFS) and overall survival (OS) were used to estimate therapy efficacy. The treatment-related adverse events were evaluated based on National Cancer Institute Common Adverse Event Evaluation Criteria (CTCAE) version 5.0. A total of 42 patients with unresectable hepatocellular carcinoma were included in this study, including 34 males (80.5%) and 8 females (19.5%). The average age is 54.5 years, ranging from 34 to 72. The median follow-up time was 12.3 months, with an ORR of 42.9% and a DCR of 90.5% as of the follow-up time. The median PFS is 7.5 months (95% CI: 5.76-9.23), and the median OS has not yet been reached; 6-month PFS was 62.2%. Safety analysis showed that 41 (97.6%) patients experienced treatment-related adverse reactions, mainly including elevated AST and ALT, fever, elevated bilirubin, hypothyroidism, nausea, abdominal pain, and rash. 40 patients had grade 1/2 adverse reactions, and only one patient had grade 3 adverse reactions, manifested as intolerable rash, nausea, and vomiting. Treatment is terminated when symptomatic treatment and drug suspension cannot be alleviated. In this study, thre patients with unresectable hepatocellular carcinoma were treated with PD-1 inhibitor combined with TACE to achieve good tumor reduction effect and underwent liver cancer resection surgery. For patients with unresectable hepatocellular carcinoma, whether in BCLC stage B or stage C, effective systemic therapy (PD-1 inhibitor) combined with local therapy (TACE) can achieve a high rate of tumor regression and objective response. Some patients may even pursue surgical treatment opportunities, and the treatment-related adverse reactions are controllable, which is expected to provide new options for extending the survival of unresectable hepatocellular carcinoma patients.

Sugar-coated bullets: Unveiling the enigmatic mystery 'sweet arsenal' in osteoarthritis.

Glycosylation is a crucial post-translational modification process where sugar molecules (glycans) are covalently linked to proteins, lipids, or other biomolecules. In this highly regulated and complex process, a series of enzymes are involved in adding, modifying, or removing sugar residues. This process plays a pivotal role in various biological functions, influencing the structure, stability, and functionality of the modified molecules. Glycosylation is essential in numerous biological processes, including cell adhesion, signal transduction, immune response, and biomolecular recognition. Dysregulation of glycosylation is associated with various diseases. Glycation, a post-translational modification characterized by the non-enzymatic attachment of sugar molecules to proteins, has also emerged as a crucial factor in various diseases. This review comprehensively explores the multifaceted role of glycation in disease pathogenesis, with a specific focus on its implications in osteoarthritis (OA). Glycosylation and glycation alterations wield a profound influence on OA pathogenesis, intertwining with disease onset and progression. Diverse studies underscore the multifaceted role of aberrant glycosylation in OA, particularly emphasizing its intricate relationship with joint tissue degradation and inflammatory cascades. Distinct glycosylation patterns, including N-glycans and O-glycans, showcase correlations with inflammatory cytokines, matrix metalloproteinases, and cellular senescence pathways, amplifying the degenerative processes within cartilage. Furthermore, the impact of advanced glycation end-products (AGEs) formation in OA pathophysiology unveils critical insights into glycosylation-driven chondrocyte behavior and extracellular matrix remodeling. These findings illuminate potential therapeutic targets and diagnostic markers, signaling a promising avenue for targeted interventions in OA management. In this comprehensive review, we aim to thoroughly examine the significant impact of glycosylation or AGEs in OA and explore its varied effects on other related conditions, such as liver-related diseases, immune system disorders, and cancers, among others. By emphasizing glycosylation's role beyond OA and its implications in other diseases, we uncover insights that extend beyond the immediate focus on OA, potentially revealing novel perspectives for diagnosing and treating OA.

Role of NF-κB p65/TNF-α in Cell Apoptosis in the Fetal Membranes of Pregnant Women with Preterm Premature Rupture of Membranes.

OBJECTIVE: This study aimed to investigate the roles of nuclear factor-kappa B p65 (NF-[Formula: see text]B p65) and tumor necrosis factor-α (TNF-α) in cell apoptosis occurring in the fetal membranes of pregnant women who experience preterm premature rupture of membranes (PPROM). METHODS: This was a case-control study involving 57 pregnant women who delivered in the obstetric department of Affiliated Loudi Hospital, Hengyang Medical School, University of South China, from June 2021 to June 2022. Samples of fetal membrane tissue were collected from pregnant women with PPROM (n=27) and pregnant women who had normal deliveries (control group; n=30). The membrane tissue morphology of both groups was observed, and the expression of NF-[Formula: see text]B p65, p-NF-[Formula: see text]B p65, TNF-α, and caspase-3 was detected. Apoptosis in fetal membranes was examined. RESULTS: Morphological evaluation of the fetal membrane tissues obtained from patients with PPROM revealed an abnormal structure with a thin collagen fiber layer and cells with a largely vacuolar cytoplasm. There was a positive correlation between the expression of p-NF-[Formula: see text]B p65/NF-[Formula: see text]B p65 and cell apoptosis (r1 =0.89, R2 =0.805, P=0.00). Furthermore, TNF-α was positively correlated with fetal membrane cell apoptosis (r2 =0.93, R2=0.881, P=0.00). CONCLUSION: NF-[Formula: see text]B p65 is involved in the occurrence of PPROM by promoting the expression of TNF-α, which upregulates caspase-3 to cause apoptosis of fetal membrane cells.

Mediating effect of psychological capital on the relationship between mental health literacy and coping styles among newly recruited nurses.

BACKGROUND: Newly recruited nurses face multiple sources of stress and their coping styles need to be focused on to ensure good mental health. This study aimed to examine the relationship among mental health literacy, psychological capital and coping styles in newly recruited nurses. METHODS: A cross-sectional study was conducted in August and September 2022. A total of 315 newly recruited nurses were recruited in a tertiary hospital in Henan Province, central China, employing the convenience sampling method. The self-reported questionnaires were sent through a QR code, including the Mental Health Literacy Scale for Healthcare Students, Psychological Capital Questionnaire, and Simplified Coping Style Questionnaire. Pearson correlation analysis was used to evaluate the relationships among the variables. Mediation analysis was performed to identify the mediating effect of psychological capital on the relationship between mental health literacy and coping styles. RESULTS: Positive coping showed a positive relationship with psychological capital and mental health literacy, while negative coping showed a negative relationship with psychological capital and mental health literacy. For positive coping, psychological capital was a partial mediator with an effect of 0.140, accounting for 62.8%. For negative coping, a full mediating effect was shown by psychological capital between mental health literacy and negative coping, with an indirect effect of -0.048. CONCLUSION: Psychological capital plays a partial and complete mediating role between mental health literacy and different coping styles among newly recruited nurses. Diversified training and personalized guidance in improving mental health literacy and increasing psychological capital simultaneously can be provided to newly recruited nurses continuously to adjust their coping styles.

Comparisons of different extraction methods and solvents for saliva samples.

INTRODUCTION: Changes in the categories and concentrations of salivary metabolites may be closely related to oral, intestinal or systemic diseases. To study salivary metabolites, the first analytical step is to extract them from saliva samples as much as possible, while reducing interferences to a minimum. Frequently used extraction methods are protein precipitation (PPT), liquid-liquid extraction (LLE) and solid-phase extraction (SPE), with various organic solvents. The types and quantities of metabolites extracted with different methods may vary greatly, but few studies have systematically evaluated them. OBJECTIVES: This study aimed to select the most suitable methods and solvents for the extraction of saliva according to different analytical targets. METHODS: An untargeted metabolomics approach based on liquid chromatography-mass spectrometry was applied to obtain the raw data. The numbers of metabolites, repeatability of the data and intensities of mass spectrometry signals were used as evaluation criteria. RESULTS: PPT resulted in the highest coverage. Among the PPT solvents, acetonitrile displayed the best repeatability and the highest coverage, while acetone resulted in the best signal intensities for the extracted compounds. LLE with the mixture of chloroform and methanol was the most suitable for the extraction of small hydrophobic compounds. CONCLUSION: PPT with acetonitrile or acetone was recommended for untargeted analysis, while LLE with the mixture of chloroform and methanol was recommended for small hydrophobic compounds.

Pancreatic ß-cell failure, clinical implications, and therapeutic strategies in type 2 diabetes.

ABSTRACT: Pancreatic ß-cell failure due to a reduction in function and mass has been defined as a primary contributor to the progression of type 2 diabetes (T2D). Reserving insulin-producing ß-cells and hence restoring insulin production are gaining attention in translational diabetes research, and ß-cell replenishment has been the main focus for diabetes treatment. Significant findings in ß-cell proliferation, transdifferentiation, pluripotent stem cell differentiation, and associated small molecules have served as promising strategies to regenerate ß-cells. In this review, we summarize current knowledge on the mechanisms implicated in ß-cell dynamic processes under physiological and diabetic conditions, in which genetic factors, age-related alterations, metabolic stresses, and compromised identity are critical factors contributing to ß-cell failure in T2D. The article also focuses on recent advances in therapeutic strategies for diabetes treatment by promoting ß-cell proliferation, inducing non-ß-cell transdifferentiation, and reprograming stem cell differentiation. Although a significant challenge remains for each of these strategies, the recognition of the mechanisms responsible for ß-cell development and mature endocrine cell plasticity and remarkable advances in the generation of exogenous ß-cells from stem cells and single-cell studies pave the way for developing potential approaches to cure diabetes.

The Implication of Diabetes-Specialized Nurses in Aiming for the Better Treatment and Management of Patients with Diabetes Mellitus: A Brief Narrative Review.

Diabetes mellitus (DM) is regarded as one of the most critical public health challenges of the 21st century. It has evolved into a burgeoning epidemic since the last century, and today ranks among the major causes of mortality worldwide. Diabetes specialist nurses (DSNs) are central to good patient care and outcomes including confident self-care management. Evidence shows that DSNs are cost-effective, improve clinical outcomes, and reduce length of stay in hospital. In this brief narrative review, we aim to describe the roles of DSNs and their contribution in the treatment and management of patients with DM. This narrative review describes the importance of DSNs in healthcare practice, in the inpatient and outpatient departments, in the pediatrics department, in managing diabetic foot ulcers, in the treatment and management of gestational diabetes, in prescribing medications for DM and in diabetes self-management education on glycosylated hemoglobin, and cardiovascular risk factors. To conclude, DSNs have a crucial role in the treatment and management of patients with DM and its complications. DSNs have a great impact on diabetes therapy, and hence implementation of DSNs and nurse-led diabetic clinics might be beneficial for the health care system. Finally, having DSNs might significantly contribute to good healthcare practice and support. Even though DSNs are not available in several regions around the globe, and even though this post is still new to several health care institutions, the presence of DSNs recognized and certified by the various healthcare systems would be very useful.

Sleep disorders and cancer incidence: examining duration and severity of diagnosis among veterans.

Introduction: Sleep disruption affects biological processes that facilitate carcinogenesis. This retrospective cohort study used de-identified data from the Veterans Administration (VA) electronic medical record system to test the hypothesis that patients with diagnosed sleep disorders had an increased risk of prostate, breast, colorectal, or other cancers (1999-2010, N=663,869). This study builds upon existing evidence by examining whether patients with more severe or longer-duration diagnoses were at a greater risk of these cancers relative to those with a less severe or shorter duration sleep disorder. Methods: Incident cancer cases were identified in the VA Tumor Registry and sleep disorders were defined by International Classification of Sleep Disorder codes. Analyses were performed using extended Cox regression with sleep disorder diagnosis as a time-varying covariate. Results: Sleep disorders were present among 56,055 eligible patients (8% of the study population); sleep apnea (46%) and insomnia (40%) were the most common diagnoses. There were 18,181 cancer diagnoses (41% prostate, 12% colorectal, 1% female breast, 46% other). The hazard ratio (HR) for a cancer diagnosis was 1.45 (95% confidence interval [CI]: 1.37, 1.54) among those with any sleep disorder, after adjustment for age, sex, state of residence, and marital status. Risks increased with increasing sleep disorder duration (short [<1-2 years] HR: 1.04 [CI: 1.03-1.06], medium [>2-5 years] 1.23 [1.16-1.32]; long [>5-12 years] 1.52 [1.34-1.73]). Risks also increased with increasing sleep disorder severity using cumulative sleep disorder treatments as a surrogate exposure; African Americans with more severe disorders had greater risks relative to those with fewer treatments and other race groups. Results among patients with only sleep apnea, insomnia, or another sleep disorder were similar to those for all sleep disorders combined. Discussion: The findings are consistent with other studies indicating that sleep disruption is a cancer risk factor. Optimal sleep and appropriate sleep disorder management are modifiable risk factors that may facilitate cancer prevention.

The impact of caregiver burden on quality of life in family caregivers of patients with advanced cancer: a moderated mediation analysis of the role of psychological distress and family resilience.

BACKGROUND: The caregiver burden frequently experienced by family members tending to advanced cancer patients significantly impacts their psychological well-being and quality of life (QoL). Although family resilience might function as a mitigating factor in this relationship, its specific role remains to be elucidated. This study aims to probe the mediating effect of psychological distress on the relationship between caregiver burden and QoL, as well as the moderating effect of family resilience. METHODS: A cross-sectional study was conducted between June 2020 and March 2021 in five tertiary hospitals in China. Data were collected on caregiver burden, family resilience, psychological distress (including anxiety and depression), and QoL. Moderated mediation analysis was performed. RESULTS: Data analysis included 290 caregivers. It confirmed the mediating role of psychological distress in the caregiver burden-QoL relationship (P < 0.001). Both overall family resilience and the specific dimension of family communication and problem-solving (FCPS) demonstrated significant moderating effects on the "psychological distress/anxiety-QoL" paths (P < 0.05). The utilization of social and economic resources (USER) significantly moderated the association between depression and QoL (P < 0.05). CONCLUSIONS: The study corroborates psychological distress's mediation between caregiver burden and QoL and family resilience's moderation between psychological distress and QoL. It underscores the need for minimizing psychological distress and bolstering family resilience among caregivers of advanced cancer patients. Accordingly, interventions should be tailored, inclusive of psychological assistance and promotion of family resilience, particularly focusing on FCPS and USER, to augment the caregivers' well-being and QoL.

Epigenetic Features in Newborns Associated with Preadolescence Lung Function and Asthma Acquisition during Adolescence.

The association between newborn DNA methylation (DNAm) and asthma acquisition (AA) during adolescence has been suggested. Lung function (LF) has been shown to be associated with asthma risk and its severity. However, the role of LF in the associations between DNAm and AA is unclear, and it is also unknown whether the association between DNAm and AA is consistent with that between DNAm and LF. We address this question through assessing newborn epigenetic features of preadolescence LF and of AA during adolescence, along with their biological pathways and processes. Our study's primary medical significance lies in advancing the understanding of asthma's early life origins. By investigating epigenetic markers in newborns and their association with lung function in preadolescence, we aim to uncover potential early biomarkers of asthma risk. This could facilitate earlier detection and intervention strategies. Additionally, exploring biological pathways linking early lung function to later asthma development can offer insights into the disease's pathogenesis, potentially leading to novel therapeutic targets. METHODS: The study was based on the Isle of Wight Birth cohort (IOWBC). Female subjects with DNAm data at birth and with no asthma at age 10 years were included (n = 249). The R package ttScreening was applied to identify CpGs potentially associated with AA from 10 to 18 years and with LF at age 10 (FEV1, FVC, and FEV1/FVC), respectively. Agreement in identified CpGs between AA and LF was examined, along with their biological pathways and processes via the R function gometh. We tested the findings in an independent cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC), to examine overall replicability. RESULTS: In IOWBC, 292 CpGs were detected with DNAm associated with AA and 1517 unique CpGs for LF (514 for FEV1, 436 for FVC, 408 for FEV1/FVC), with one overlapping CpG, cg23642632 (NCKAP1) between AA and LF. Among the IOWBC-identified CpGs, we further tested in ALSPAC and observed the highest agreement between the two cohorts in FVC with respect to the direction of association and statistical significance. Epigenetic enrichment analyses indicated non-specific connections in the biological pathways and processes between AA and LF. CONCLUSIONS: The present study suggests that FEV1, FVC, and FEV1/FVC (as objective measures of LF) and AA (incidence of asthma) are likely to have their own specific epigenetic features and biological pathways at birth. More replications are desirable to fully understand the complexity between DNAm, lung function, and asthma acquisition.

Development of KASP markers assisted with soybean drought tolerance in the germination stage based on GWAS.

Soybean [Glycine max(L.)Merr.] is a leading oil-bearing crop and cultivated globally over a vast scale. The agricultural landscape in China faces a formidable challenge with drought significantly impacting soybean production. In this study, we treated a natural population of 264 Chinese soybean accessions using 15% PEG-6000 and used GR, GE, GI, RGR, RGE, RGI and ASFV as evaluation index. Using the ASFV, we screened 17 strong drought-tolerant soybean germplasm in the germination stage. Leveraging 2,597,425 high-density SNP markers, we conducted Genome-Wide Association Studies (GWAS) and identified 92 SNPs and 9 candidate genes significantly associated with drought tolerance. Furthermore, we developed two KASP markers for S14_5147797 and S18_53902767, which closely linked to drought tolerance. This research not only enriches the pool of soybean germplasm resources but also establishes a robust foundation for the molecular breeding of drought tolerance soybean varieties.

Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions.

BACKGROUND: DNA methylation is a biochemical process in which a methyl group is added to the cytosine-phosphate-guanine (CpG) site on DNA molecules without altering the DNA sequence. Multiple CpG sites in a certain genome region can be differentially methylated across phenotypes. Identifying these differentially methylated CpG regions (DMRs) associated with the phenotypes contributes to disease prediction and precision medicine development. RESULTS: We propose a novel DMR detection algorithm, gbdmr. In contrast to existing methods under a linear regression framework, gbdmr assumes that DNA methylation levels follow a generalized beta distribution. We compare gbdmr to alternative approaches via simulations and real data analyses, including dmrff, a new DMR detection approach that shows promising performance among competitors, and the traditional EWAS that focuses on single CpG sites. Our simulations demonstrate that gbdmr is superior to the other two when the correlation between neighboring CpG sites is strong, while dmrff shows a higher power when the correlation is weak. We provide an explanation of these phenomena from a theoretical perspective. We further applied the three methods to multiple real DNA methylation datasets. One is from a birth cohort study undertaken on the Isle of Wight, United Kingdom, and the other two are from the Gene Expression Omnibus database repository. Overall, gbdmr identifies more DMR CpGs linked to phenotypes than dmrff, and the simulated results support the findings. CONCLUSIONS: Gbdmr is an innovative method for detecting DMRs based on generalized beta regression. It demonstrated notable advantages over dmrff and traditional EWAS, particularly when adjacent CpGs exhibited moderate to strong correlations. Our real data analyses and simulated findings highlight the reliability of gbdmr as a robust DMR detection tool. The gbdmr approach is accessible and implemented by R on GitHub: https://github.com/chengzhouwu/gbdmr .