Long-Term Temporal Trends of Real-World Healthcare Costs Associated with Nivolumab Plus Ipilimumab and Pembrolizumab Plus Axitinib as First-Line Treatment for Advanced or Metastatic Renal Cell Carcinoma.

INTRODUCTION: Nivolumab plus ipilimumab (NIVO + IPI) and pembrolizumab plus axitinib (PEM + AXI) are first-line (1L) treatments for advanced or metastatic renal cell carcinoma (aRCC), although the long-term trends in their associated real-world healthcare costs are not well defined. We compared the real-world healthcare costs of patients with aRCC who received 1L NIVO + IPI or PEM + AXI over 24 months. METHODS: Adults with RCC and secondary malignancy who initiated 1L NIVO + IPI or PEM + AXI were identified in the Merative MarketScan Commercial and Medicare Supplemental Databases (01/01/2004 to 09/30/2021). All-cause and RCC-related healthcare costs (unadjusted and adjusted) were assessed per patient per month (PPPM) at 6-month intervals post-treatment initiation (index date) up to 24 months, and differences between the NIVO + IPI and PEM + AXI cohorts were compared. RESULTS: Of 325 patients with aRCC, 219 received NIVO + IPI and 106 received PEM + AXI as the 1L treatment. According to patients' follow-up length, the analyses for months 7-12 included 210 patients in the NIVO + IPI cohort and 103 in the PEM + AXI cohort; months 13-18 included 119 and 48 patients, respectively; and months 19-24 included 81 and 25 patients. PPPM unadjusted all-cause total costs were $46,348 for NIVO + IPI and $38,097 for PEM + AXI in months 1-6; $26,840 versus $27,983, respectively, in months 7-12; $22,899 versus $25,137 in months 13-18; and $22,279 versus $27,947 in months 19-24. PPPM unadjusted RCC-related costs were $44,059 for NIVO + IPI and $36,456 for PEM + AXI in months 1-6; $25,144 versus $26,692, respectively, in months 7-12; $21,645 versus $23,709 in months 13-18; and $20,486 versus $25,515 in months 19-24. PPPM costs declined more rapidly for patients receiving NIVO + IPI compared to those receiving PEM + AXI, resulting in significantly lower all-cause costs associated with NIVO + IPI during months 19-24 (difference - $10,914 [95% confidence interval - $21,436, - $1091]) and RCC-related costs during months 7-12 (- $4747 [(- $8929, - $512]) and 19-24 (- $10,261 [- $20,842, - $421]) after adjustment. Cost savings for NIVO + IPI versus PEM + AXI were driven by differences in drug costs which, after adjustment, were significantly lower in months 7-12 (difference - $5555 [all-cause], - $5689 [RCC-related]); 13-18 (- $7217 and - $6870, respectively); and 19-24 (- $16,682 and - $16,125). CONCLUSION: Although the real-world PPPM healthcare costs of 1L NIVO + IPI were higher compared with PEM + AXI in the first 6 months of treatment, the costs associated with NIVO + IPI rapidly declined thereafter, resulting in significantly lower costs vs. PEM + AXI from months 7 to 24.

Pseudomonas paeninsulae sp. nov. and Pseudomonas svalbardensis sp. nov., isolated from Antarctic intertidal sediment and Arctic soil, respectively.

Two Gram-stain-negative, aerobic, rod-shaped, non-endospore-forming and motile bacterial strains, designated IT1137T and S025T, were isolated from an intertidal sediment sample collected from the Fildes Peninsula (King George Island, Maritime Antarctica) and a soil sample under red snow in the Ny-Ålesund region (Svalbard, High Arctic), respectively. The 16S rRNA gene sequence similarity values grouped them in the genus Pseudomonas. The two strains were characterized phenotypically using API 20E, API 20NE, API ZYM and Biolog GENIII tests and chemotaxonomically by their fatty acid contents, polar lipids and respiratory quinones. Multilocus sequence analysis (concatenated 16S rRNA, gyrB, rpoB and rpoD sequences), together with genome comparisons by average nucleotide identity and digital DNA-DNA hybridization, were performed. The results showed that the similarity values of the two isolates with the type strains of related Pseudomonas species were below the recognized thresholds for species definition. Based on polyphasic taxonomy analysis, it can be concluded that strains IT1137T and S025T represent two novel species of the genus Pseudomonas, for which the names Pseudomonas paeninsulae sp. nov. (type strain IT1137T=PMCC 100533T=CCTCC AB 2023226T=JCM 36637T) and Pseudomonas svalbardensis sp. nov. (type strain S025T=PMCC 200367T= CCTCC AB 2023225T=JCM 36638T) are proposed.

Global siRNA Screen Reveals Critical Human Host Factors of SARS-CoV-2 Multicycle Replication.

Defining the subset of cellular factors governing SARS-CoV-2 replication can provide critical insights into viral pathogenesis and identify targets for host-directed antiviral therapies. While a number of genetic screens have previously reported SARS-CoV-2 host dependency factors, these approaches relied on utilizing pooled genome-scale CRISPR libraries, which are biased towards the discovery of host proteins impacting early stages of viral replication. To identify host factors involved throughout the SARS-CoV-2 infectious cycle, we conducted an arrayed genome-scale siRNA screen. Resulting data were integrated with published datasets to reveal pathways supported by orthogonal datasets, including transcriptional regulation, epigenetic modifications, and MAPK signalling. The identified proviral host factors were mapped into the SARS-CoV-2 infectious cycle, including 27 proteins that were determined to impact assembly and release. Additionally, a subset of proteins were tested across other coronaviruses revealing 17 potential pan-coronavirus targets. Further studies illuminated a role for the heparan sulfate proteoglycan perlecan in SARS-CoV-2 viral entry, and found that inhibition of the non-canonical NF-kB pathway through targeting of BIRC2 restricts SARS-CoV-2 replication both in vitro and in vivo. These studies provide critical insight into the landscape of virus-host interactions driving SARS-CoV-2 replication as well as valuable targets for host-directed antivirals.

A telomere-to-telomere gap-free reference genome assembly of avocado provides useful resources for identifying genes related to fatty acid biosynthesis and disease resistance.

Avocado (Persea americana Mill.) is an economically valuable plant because of the high fatty acid content and unique flavor of its fruits. Its fatty acid content, especially the relatively high unsaturated fatty acid content, provides significant health benefits. We herein present a telomere-to-telomere gapless genome assembly (841.6 Mb) of West Indian avocado. The genome contains 40 629 predicted protein-coding genes. Repeat sequences account for 57.9% of the genome. Notably, all telomeres, centromeres, and a nucleolar organizing region are included in this genome. Fragments from these three regions were observed via fluorescence in situ hybridization. We identified 376 potential disease resistance-related nucleotide-binding leucine-rich repeat genes. These genes, which are typically clustered on chromosomes, may be derived from gene duplication events. Five NLR genes (Pa11g0262, Pa02g4855, Pa07g3139, Pa07g0383, and Pa02g3196) were highly expressed in leaves, stems, and fruits, indicating they may be involved in avocado disease responses in multiple tissues. We also identified 128 genes associated with fatty acid biosynthesis and analyzed their expression patterns in leaves, stems, and fruits. Pa02g0113, which encodes one of 11 stearoyl-acyl carrier protein desaturases mediating C18 unsaturated fatty acid synthesis, was more highly expressed in the leaves than in the stems and fruits. These findings provide valuable insights that enhance our understanding of fatty acid biosynthesis in avocado.

Application of Multi-Rod Constructs for the Revision of Thoracolumbar Fractures.

OBJECTIVE: The revision procedure for failure of internal fixation after thoracolumbar fracture is controversial. Combined anterior and posterior surgery is associated with higher risk more intraoperative bleeding and tissue damage. The success rate of simple anterior surgery needs further confirmation, and posterior surgery lacks stability of internal fixation. This study evaluates the feasibility and surgical effect of multi-rod constructs in the revision of thoracolumbar fractures. METHODS: Eleven patients with thoracolumbar fractures who underwent previous construct failure and were treated with revision and internal fixation with the multi-rod technique from March 2017 to September 2018 were analyzed. The original internal fixation was removed and replaced in the medial insertion of satellite rods and bone graft. The average follow-up time was 15.97 months. The intraoperation blood loss, the time of the operation, activation and discharge and the rate of rod fracture were calculated. The sagittal Cobb angle before revision, after revision and at the last follow-up were compared. The clinical effect was evaluated by visual analogue scale (VAS) and Oswestry Disability Index questionnaire (ODI). RESULTS: The average operation time was 107 min, the intraoperative blood loss was 131.81 mL, the active time was 1.59 days, and the discharge time was 10.89 days. No rod fractured again during the follow-up period. The paired t-test was used to compare the Cobb angle, VAS score, and ODI before and after surgery. There was significant difference in the sagittal Cobb angle between the pre-revision and the posterior sagittal position (p = 0.000), and no significant difference was found between post-revision and last follow-up (p = 0.551). VAS and ODI were greatly improved at the last follow-up. CONCLUSION: The literature on revision of thoracolumbar fractures is insufficient and comprises varying opinions. This paper proposes a new treatment option. The application of the multi-rod constructs in the revision of thoracolumbar fractures is safe, simple, and effective and might provide guidance for future clinical work.

Research progress on the mechanism of action and clinical application of remote ischemic post-conditioning for acute ischemic stroke.

Remote ischemic post-conditioning (RIPostC) can reduce cerebral ischemia reperfusion injury (IRI) by inducing endogenous protective effects, the distal limb ischemia post-treatment and in situ ischemia post-treatment were classified according to the site of intervention. And in the process of clinical application distal limb ischemia post-treatment is more widely used and more conducive to clinical translation. Therefore, in this paper, we review the mechanism of action and clinical application of RIPostC in cerebral ischemia, hoping to provide reference help for future experimental directions and clinical translation.

DDR2/STAT3 Positive Feedback Loop Mediates the Immunosuppressive Microenvironment by Upregulating PD-L1 and Recruiting MDSCs in Oxaliplatin-Resistant HCC.

BACKGROUND AND AIMS: Transcriptome sequencing revealed high expression of DDR2 in oxaliplatin-resistant hepatocellular carcinoma (HCC). This study aimed to explore the role of DDR2 in oxaliplatin resistance and immune evasion in HCC. METHODS: Oxaliplatin-resistant HCC cell lines were established. The interaction between DDR2 and STAT3 was investigated, along with the mechanisms involved in DDR2/STAT3-mediated PD-L1 upregulation and polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) accumulation both in vitro and in vivo. RESULTS: DDR2 was found to induce the phosphorylation of STAT3, leading to its nuclear translocation. Conversely, the activation of STAT3 enhanced DDR2 expression. A positive feedback loop involving DDR2/STAT3 was identified in oxaliplatin-resistant HCC and associated with PD-L1 upregulation, and PMN-MDSCs accumulation was identified in oxaliplatin-resistant HCC. Knockdown of DDR2 and STAT3 sensitized oxaliplatin-resistant HCC cells to oxaliplatin and resulted in decreased PMN-MDSCs and increased CD8+ T cells in the tumor microenvironment. Enzyme-linked immunosorbent array and MDSC transwell migration assays indicated that oxaliplatin-resistant HCC cells recruited PMN-MDSCs through CCL20. Dual luciferase reporter assays demonstrated that STAT3 can directly enhance the transcription of PD-L1 and CCL20. Furthermore, treatment with a PD-L1 antibody in combination with CCL20 blockade had significant antitumor effects on oxaliplatin-resistant HCC. CONCLUSIONS: Our findings revealed a positive feedback mechanism involving DDR2 and STAT3 that mediates the immunosuppressive microenvironment and promotes oxaliplatin resistance and immune evasion via PD-L1 upregulation and PMN-MDSC recruitment. Targeting the DDR2/STAT3 pathway may be a promising therapeutic strategy to overcome immune escape and chemoresistance in HCC.

The different serum albumin assays influence the prescriptions in children with primary nephrotic syndrome.

The differences between the serum albumin determined by bromocresol green (BCG) and immunonephelometry (IN) were inconsistent in past studies, and the samples were all adults. We sought to determine the differences in children and reveal the impacts of these differences on the clinical diagnosis and treatments of primary nephrotic syndrome (PNS). Repeated measurements from 576 PNS children showed that albumin measured by BCG and IN (ALB-B and ALB-I) were 19.95 (11.15) g/L and 15.30 (11.05) g/L, respectively, and the mean difference was 4.68 g/L (P < 0.001). The cut-offs we calculated for hypoalbuminemia and severe hypoalbuminemia based on the IN were 25 and 15 g/L, which were 5 g/L lower than the cut-offs recommended by KIDGO, respectively. A pair of historical control samples (206 vs. 216) with ALB-B or ALB-I showed that the proportion of severe hypoalbuminemia was 14.60% greater in IN group (75.20% vs. 60.60%, P < 0.001). The misdiagnosis rate of severe hypoalbuminemia by IN was 33.77% when 20 g/L rather than 15 g/L was used as the cut-off. Furthermore, the proportion of patients receiving albumin injections increased by 10.20%, and the average consumption increased by 97.06% (P = 0.01) along with the use of IN. So, our results suggested that the difference between ALB-B and ALB-I led to misdiagnosis and prescription abuse in PNS children.

Infection and chronic disease activate a systemic brain-muscle signaling axis.

Infections and neurodegenerative diseases induce neuroinflammation, but affected individuals often show nonneural symptoms including muscle pain and muscle fatigue. The molecular pathways by which neuroinflammation causes pathologies outside the central nervous system (CNS) are poorly understood. We developed multiple models to investigate the impact of CNS stressors on motor function and found that Escherichia coli infections and SARS-CoV-2 protein expression caused reactive oxygen species (ROS) to accumulate in the brain. ROS induced expression of the cytokine Unpaired 3 (Upd3) in Drosophila and its ortholog, IL-6, in mice. CNS-derived Upd3/IL-6 activated the JAK-STAT pathway in skeletal muscle, which caused muscle mitochondrial dysfunction and impaired motor function. We observed similar phenotypes after expressing toxic amyloid-ß (Aß42) in the CNS. Infection and chronic disease therefore activate a systemic brain-muscle signaling axis in which CNS-derived cytokines bypass the connectome and directly regulate muscle physiology, highlighting IL-6 as a therapeutic target to treat disease-associated muscle dysfunction.

The chromosome-level genome assembly of Cananga odorata provides insights into its evolution and terpenoid biosynthesis.

Cananga odorata is known as a natural perfume tree of the Annonaceae family in Magnoliales. However, its phylogenetic position and the molecular mechanisms involved in the biosynthesis of the floral volatile organic compounds (VOCs) remain unclear. Here, by combining a variety of sequencing platforms, we present a telomere-to-telomere (T2T) genome of C. odorata with 735.83 Mb, which represents the highest integrity and assembly quality of genome in magnoliid plants reported to date. Phylogenetic analysis based on multiple datasets and approaches showed that C. odorata, as a member of magnoliids, is sister to eudicots, after their divergence from monocots. Metabolomic of VOCs in the essential oil and flowers scent showed that sesquiterpenes, especially ß-caryophyllene, were the major compounds. Two CoTPS21 homologues derived from tandem duplication events were highly expressed during flower development and were identified as the key sesquiterpene synthases for the production of ß-caryophyllene. In addition, CoSPL3 and CoSPL9 were considered as potential transcription factors for activating the expression of CoTPS21 homologues. Our results shed light on the molecular mechanisms underlying the biosynthesis of the unique floral fragrance in C. odorata and provide new insights into the phylogenetic position of magnoliids.

Association between chronic pain and risk of cardiometabolic multimorbidity: a prospective cohort study.

BACKGROUND: Although chronic pain was deleteriously related to single cardiometabolic diseases, the relationship between chronic pain and cardiometabolic multimorbidity remains unclear. The purpose of this study was to investigate the association between chronic pain with the risk of cardiometabolic multimorbidity. METHODS: A prospective cohort study included 452 818 participants who were free of cardiometabolic multimorbidity at baseline. Chronic pain was assessed in diverse anatomical sites including the head, face, neck/shoulder, stomach/abdominal area, back, hip and knee or 'all over the body'. Participants were classified into six groups according to the amount of chronic pain sites: no chronic pain, chronic pain at one, two, three and four or more sites, and those reporting pain 'all over the body'. Cardiometabolic multimorbidity was defined as the occurrence of at least two cardiometabolic diseases, involving type 2 diabetes, ischaemic heart disease and stroke. RESULTS: After a median follow-up of 13.7 years, 4445 participants developed cardiometabolic multimorbidity. Compared with individuals without chronic pain, those experiencing chronic pain in four or more sites were associated with a 1.82-fold (HR: 1.82, 95% CI: 1.61, 2.06) higher risk of cardiometabolic multimorbidity. Pain distributed 'all over the body' was associated with a 59% (HR: 1.59, 95% CI: 1.30, 1.93) increased risk of cardiometabolic multimorbidity Additionally, individuals who had chronic pain in both the head and stomach/abdomen showed the highest risk with cardiometabolic multimorbidity (HR: 1.88, 95% CI: 1.60, 2.20). CONCLUSIONS: Our findings suggested that there was an elevated risk of cardiometabolic multimorbidity associated with an increased amount of chronic pain sites.

Complete genome sequence of a novel Pseudomonas sp. IT1137 isolated from Antarctic intertidal sediment showing potential for alkane degradation at low temperatures.

Pseudomonas species are known for their diverse metabolic abilities and broad ecological distribution. They are fundamental components of bacterial communities and perform essential ecological functions in the environment. A psychrotrophic Pseudomonas sp. IT1137 was isolated from intertidal sediment in the coastal region of the Fildes Peninsula, King George Island, Antarctica. The strain contained a circular chromosome of 5,346,697 bp with a G + C content of 61.66 mol% and one plasmid of 4481 bp with a G + C content of 64.61 mol%. A total of 4848 protein-coding genes, 65 tRNA genes and 15 rRNA genes were obtained. Genome sequence analysis revealed that strain IT1137 not only is a potentially novel species of the genus Pseudomonas but also harbors functional genes related to nitrogen, sulfur and phosphorus cycling. In addition, genes involved in alkane degradation, ectoine synthesis and cyclic lipopeptide (CLP) production were detected in the bacterial genome. The results indicate the potential of the strain Pseudomonas sp. IT1137 for biotechnological applications such as bioremediation and secondary metabolite production and are helpful for understanding bacterial adaptability and ecological function in cold coastal environments.

Optimization of immunosuppression strategies for the establishment of chronic hepatitis E virus infection in rabbits.

Chronic hepatitis E mostly occurs in organ transplant recipients and can lead to rapid liver fibrosis and cirrhosis. Previous studies found that the development of chronic hepatitis E virus (HEV) infection is linked to the type of immunosuppressant used. Animal models are crucial for the study of pathogenesis of chronic hepatitis E. We previously established a stable chronic HEV infection rabbit model using cyclosporine A (CsA), a calcineurin inhibitor (CNI)-based immunosuppressant. However, the immunosuppression strategy and timing may be optimized, and how different types of immunosuppressants affect the establishment of chronic HEV infection in this model is still unknown. Here, we showed that chronic HEV infection can be established in 100% of rabbits when CsA treatment was started at HEV challenge or even 4 weeks after. Tacrolimus or prednisolone treatment alone also contributed to chronic HEV infection, resulting in 100% and 77.8% chronicity rates, respectively, while mycophenolate mofetil (MMF) only led to a 28.6% chronicity rate. Chronic HEV infection was accompanied with a persistent activation of innate immune response evidenced by transcriptome analysis. The suppressed adaptive immune response evidenced by low expression of genes related to cytotoxicity (like perforin and FasL) and low anti-HEV seroconversion rates may play important roles in causing chronic HEV infection. By analyzing HEV antigen concentrations with different infection outcomes, we also found that HEV antigen levels could indicate chronic HEV infection development. This study optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits and highlighted the potential association between the development of chronic HEV infection and immunosuppressants.IMPORTANCEOrgan transplant recipients are at high risk of chronic hepatitis E and generally receive a CNI-based immunosuppression regimen containing CNI (tacrolimus or CsA), MMF, and/or corticosteroids. Previously, we established stable chronic HEV infection in a rabbit model by using CsA before HEV challenge. In this study, we further optimized the immunosuppression strategies for establishing chronic HEV infection in rabbits. Chronic HEV infection can also be established when CsA treatment was started at the same time or even 4 weeks after HEV challenge, clearly indicating the risk of progression to chronic infection under these circumstances and the necessity of HEV screening for both the recipient and the donor preoperatively. CsA, tacrolimus, or prednisolone instead of MMF significantly contributed to chronic HEV infection. HEV antigen in acute infection phase indicates the development of chronic infection. Our results have important implications for understanding the potential association between chronic HEV infection and immunosuppressants.

Flavonoid localization in soybean seeds: Comparative analysis of wild (Glycine soja) and cultivated (Glycine max) varieties.

Wild soybean (Glycine soja) is known for its high flavonoid contents, yet the distribution of flavonoids in the seeds is not well understood. Herein, we utilized matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and metabolomics methods to systematically investigate flavonoid differences in the seed coats and embryos of G. soja and G. max. The results of flavonoid profiles and total flavonoid content analyses revealed that flavonoid diversity and abundance in G. soja seed coats were significantly higher than those in G. max whereas the levels were similar in embryos. Specifically, 23 unique flavonoids were identified in the seed coats of G. soja, including procyanidins, epicatechin derivatives, and isoflavones. Using MALDI-MSI, we further delineated the distribution of the important flavonoids in the cotyledons, hypocotyls, and radicles of the two species. These findings imply that G. soja holds considerable breeding potential to enhance the nutritional and stress resistance traits of G. max.

Novel insights into necrozoospermia from a single-center study: reference ranges, possible etiology, and impact on male fertility.

ABSTARCT: Necrozoospermia is a poorly documented condition with a low incidence, and its definition and clinical significance are unclear. Herein, we provide a reference range for necrozoospermia and discuss its possible etiology and impact on male fertility and assisted reproductive outcomes. We extracted relevant information from 650 Chinese male partners of infertile couples and statistically analyzed sperm vitality. Necrozoospermia was present in 3.4% (22/650) of our study population, and the lower cut-off value for sperm vitality was 75.3%. We compared two methods for assessing sperm vitality (eosin-nigrosin head staining and hypo-osmotic swelling test [HOST]), for which the percentage in the eosin-nigrosin group (mean ± standard deviation [s.d.]: 77.5% ± 10.5%) was significantly higher than that in the HOST group (mean ± s.d.: 58.1% ± 6.7% [5-10 min after incubation] and 55.6% ± 8.2% [25-30 min after incubation]; both P < 0.001). The incidence of necrozoospermia increased with age (odds ratio [OR] = 1.116, 95% confidence interval [CI]: 1.048-1.189, P = 0.001), while the percentage of normal sperm morphology and DNA fragmentation index (DFI) were significantly associated with necrozoospermia, with ORs of 0.691 (95% CI: 0.511-0.935, P = 0.017) and 1.281 (95% CI: 1.180-1.390, P < 0.001), respectively. In the following 6 months, we recruited 166 patients in the nonnecrozoospermia group and 87 patients in the necrozoospermia group to compare intracytoplasmic sperm injection (ICSI) and pregnancy outcomes between the two groups. The necrozoospermia group had a significantly lower normal fertilization rate (74.7% vs 78.2%, P = 0.041; OR = 0.822; 95% CI: 0.682-0.992) than that in the nonnecrozoospermia group. This study presents substantial information on necrozoospermia to establish comprehensive and applicable reference values for sperm vitality for spontaneous conception and artificially assisted reproductive management.

Dyadic effects of financial toxicity and social support on the fear of cancer recurrence in breast cancer patients and caregivers: an actor-partner interdependence mediation model.

PURPOSE: In this study, the actor-partner interdependence mediation model (APIMeM) was applied to breast cancer patients and their caregivers to assess the factors that affect the fear of cancer recurrence. In particular, the purpose of this study was to evaluate the mediating effect of social support on financial toxicity and the fear of cancer recurrence, providing an effective basis for developing plans to reduce the level of fear of cancer recurrence. METHODS: This study employed a cross-sectional design, and 405 dyads of breast cancer patients and their caregivers were enrolled. Financial toxicity, social support, and fear of cancer recurrence were assessed by computing comprehensive scores for financial toxicity based on patient-reported outcome measures, the Social Support Rating Scale, and the Fear of Cancer Recurrence Inventory Short Form, respectively. The data were analysed using SPSS 24.0 and AMOS 23.0. RESULTS: The results showed that the fear of cancer recurrence of breast cancer patients and their caregivers was significantly related to dyadic financial toxicity and social support. In addition, the financial toxicity of breast cancer patients and their caregivers had significant actor effects and partner effects on the fear of cancer recurrence through dyadic social support. CONCLUSIONS: The financial toxicity of breast cancer patients and their caregivers could produce actor and partner effects on the fear of cancer recurrence through the mediation of social support, which provided empirical support for improving reducing the level of fear of cancer recurrence among patients and caregivers at the dyadic level.

Adolescent Patients'experiences of Mental Disorders Related to School Bullying.

Objective: The purpose of this study was to explore the real inner experience and nursing needs of adolescent patients who suffered from school bullying, and to develop a treatment plan to restore adolescent mental health. Methods: Using the maximum difference sampling method, 15 adolescent patients were interviewed by psychologists and nurses, and the interview results were analyzed by topic induction. Results: Among the 15 participants, 12 (80%) felt helpless, 13 (86.7%) had serious negative emotions, and 10 (66.7%) felt anxious about personal growth. Based on the semi-structured interviews, the psychological states of participants were summarized into three themes: Helplessness, Severe negative emotions, and Anxiety about personal growth. Under the theme of serious negative emotions, it was further divided into three sub-themes: Frustration and Distrust, Rebellion, Insecurity and depression. These themes reflected the significant impact of school bullying on the psychological status of the participants. Conclusion: The internal experience of adolescent patients with mental disorders caused by school bullying mainly includes helplessness, serious negative emotions and anxiety about personal growth. It is recommended to evaluate and diagnose patients' existing and potential health problems individually during clinical treatment and care. On the basis of comprehensive assessment, psychological counseling should be provided and support from family and school should be sought to promote positive mental health and personal growth of adolescents.

How does psychosocial safety climate cross-level influence work engagement and job burnout: the roles of organization-based self-esteem and psychological detachment.

BACKGROUND: Existing researches on nurses' work engagement and job burnout have mostly stayed at the individual level, and limited researches test the cross-level effects of psychosocial safety climate (PSC). The study aimed to explore the cross-level mediating effect of organization-based self-esteem (OBSE) and the moderating effect of psychological detachment between the relationship of PSC and work engagement and job burnout in nurses. METHODS: The cross-sectional study was conducted during November to December 2022 at a tertiary hospital in a northeastern province of China. Data was collected from 1832 nurses through an online questionnaire. Correlation analyses and hierarchical linear modeling were used to test study hypotheses. RESULTS: The results showed that PSC was positively associated with work engagement, and negatively associated with job burnout. OBSE mediated the effect of PSC on work engagement, as well as job burnout. Additionally, psychological detachment played a moderating role between PSC and work engagement, but no moderating effect was found between PSC and job burnout. CONCLUSIONS: PSC at the organizational level increases work engagement and reduces job burnout by stimulating nurses' high levels of OBSE. Psychological detachment, as a situational factor, enhances the positive influence of PSC on work engagement. The implementation of measures to improve the PSC levels of the organization, and the levels of OBSE and psychological detachment among nurses could help to promote their good work performance.

The mechanism of resveratrol stabilization and degradation by synergistic interactions between constituent proteins of whey protein.

Whey protein isolate (WPI) is mainly composed of ß-lactoglobulin (ß-LG), α-lactalbumin (α-LA) and bovine serum albumin (BSA). The aim of this study was to compare and analyze the influence of WPI and its three main constituent proteins, as well as proportionally reconstituted WPI (R-WPI) on resveratrol. It was found that the storage stability of resveratrol was protected by WPI, not affected by R-WPI, but reduced by individual whey proteins at 45°C for 30 days. The rank of accelerated degradation of resveratrol by individual whey proteins was BSA > α-LA > ß-LG. The antioxidant activity, localization of resveratrol and oxidation of carrier proteins were determined by ABTS, H2O2 assay, synchronous fluorescence, carbonyl and circular dichroism. The non-covalent interactions and disulfide bonds between constituent proteins improved the antioxidant activity of the R-WPI-resveratrol complex, the oxidation stability of the carrier and the solvent shielding effect on resveratrol, which synergistically inhibited the degradation of resveratrol in R-WPI system. The results gave insight into elucidating the interaction mechanism of resveratrol with protein carriers.

Assessment of monthly runoff simulations based on a physics-informed machine learning framework: The effect of intermediate variables in its construction.

Hydrological forecasting is of great importance for water resources management and planning, especially given the increasing occurrence of extreme events such as floods and droughts. The physics-informed machine learning (PIML) models effectively integrate conceptual hydrologic models with machine learning (ML) models. In this process, the intermediate variables of PIML models serve as bridges between inputs and outputs, while the impact of intermediate variables on the performance of PIML models remains unclear. To fill this knowledge gap, this study aims to encompass the construction of PIML models based on various hydrologic models, conduct comparative analyses of different intermediate variables based on a case study of 205 CAMELS basins, and further explore the relationship between the performance of PIML models and catchment characteristics. The optimal ML model for constructing PIML is first selected among four ML models within the 205 basins. The PIML models are then developed based on five monthly water balance models, namely TM, XM, MEP, SLM, and TVGM. To quantify the potential impact of difference in intermediate variables, two sets of experiments are further designed and performed, namely S1 with actual evapotranspiration as the intermediate variable and S2 with soil moisture as the intermediate variable. Results show that five PIML models generally outperformed the optimal standalone ML models, i.e., the Lasso model. Specifically, regardless of the choice of intermediate variables, the PIML-XM model consistently outperformed the other models within the same basins. Almost all constructed PIML models are affected by the intermediate variables in monthly runoff simulations. Typically, S1 exhibited better performance compared to S2. A greater impact of aridity index, forest fraction, and catchment area on model performance is observed in S2. These findings improve our understanding of constructing PIML models in hydrology by emphasizing their excellent performance in runoff simulations and highlighting the importance of intermediate variables.