-
Journal of Hazardous Materials Jun 2024Neonicotinoids (NEOs) are currently the fastest-growing and most widely used insecticide class worldwide. Increasing evidence suggests that long-term NEO residues in the...
Neonicotinoids (NEOs) are currently the fastest-growing and most widely used insecticide class worldwide. Increasing evidence suggests that long-term NEO residues in the environment have toxic effects on non-target soil animals. However, few studies have conducted surveys on the effects of NEOs on soil animals, and only few have focused on global systematic reviews or meta-analysis to quantify the effects of NEOs on soil animals. Here, we present a meta-analysis of 2940 observations from 113 field and laboratory studies that investigated the effects of NEOs (at concentrations of 0.001-78,600.000 mg/kg) on different soil animals across five indicators (i.e., survival, growth, behavior, reproduction, and biochemical biomarkers). Furthermore, we quantify the effects of NEOs on different species of soil animals. Results show that NEOs inhibit the survival, growth rate, behavior, and reproduction of soil animals, and alter biochemical biomarkers. Both the survival rate and longevity of individuals decreased by 100 % with NEO residues. The mean values of juvenile survival, cocoon number, and egg hatchability were reduced by 97 %, 100 %, and 84 %, respectively. Both individual and cocoon weights were reduced by 82 %, while the growth rate decreased by 88 % with NEO residues. Our meta-analysis confirms that NEOs pose significant negative impacts on soil animals.
PubMed: 38941834
DOI: 10.1016/j.jhazmat.2024.135022 -
Journal of Thermal Biology Jun 2024Phenotypic links are the potential for "carryover" of effects of experience during one life history stage into performance and selection at subsequent stages. They...
Phenotypic links are the potential for "carryover" of effects of experience during one life history stage into performance and selection at subsequent stages. They reflect plastic responses to the environment experienced during an early phase on the phenotype of subsequent phases. We are studying these effects by following individuals of the shrimp Palaemon serratus from the embryonic (eggs carried by females) through the larval phase (pelagic) to the juvenile phase (benthic). In experiment 1, we investigated the effects of larval prey concentration (10, 4 and 2 Artemia/mL) and larval incubation temperature (16 and 22 °C) on larval performance (metamorphosis rate, developmental duration and growth) and then on juvenile performance (survival and Specific Growth Rate, SGR, at 18 and 24 °C in 14 days). In experiment 2, we investigated the effects of embryonic incubation temperature (larval biomass and lipid content of newly hatched larvae from embryos incubated at 12 and 18 °C) and larval prey concentration on larval performance and then on juvenile performance. In both experiments, the larvae plastically increased their development time in response to the reduction in temperature and prey concentration, whereas their survival decreased with temperature and prey concentration. The quantity of lipids available at hatching decreased with decreasing embryonic incubation temperature, which reduced the larval performance, particularly with a low concentration of prey. Survival at 14 days post-metamorphosis was significantly reduced when the embryos were incubated at 12 °C compared with those incubated at 18 °C, regardless of the subsequent larval incubation conditions, revealing phenotypic links between overconsumption of embryonic yolk reserves and post-metamorphic fitness. Overall, juveniles had a better SGR at 24 than at 18 °C, and even better when incubated under stressful embryo-larval conditions (temperature and prey concentration). This study highlighted phenotypic links between developmental stages and over developmental periods of several months.
PubMed: 38941824
DOI: 10.1016/j.jtherbio.2024.103892 -
International Immunopharmacology Jun 2024Immune checkpoint therapy (ICT) has been shown to produce durable responses in various cancer patients. However, its efficacy is notably limited in hepatocellular...
Immune checkpoint therapy (ICT) has been shown to produce durable responses in various cancer patients. However, its efficacy is notably limited in hepatocellular carcinoma (HCC), with only a small percentage of patients responding positively to treatment. The mechanism underlying resistance to ICT in HCC remains poorly understood. Here, we showed that combination treatment of ICG-001, an inhibitor of the Wnt/β-catenin signaling pathway, with anti-PD-1 antibody effectively suppresses tumor growth and promotes the infiltration of immune cells such as DCs and CD8 T cells in the tumor microenvironment (TME). By inhibiting the activity of β-catenin and blocking its binding to the transcription factor IKAROS family zinc finger 1 (IKZF1), ICG-001 upregulated the expression of CCL5. Moreover, IKZF1 regulated the activity of the CCL5 promoter and its endogenous expression. Through inhibition of the WNT/β-catenin signaling pathway, upregulation of the expression of CCL5 was achieved, which subsequently recruited more DCs into the TME via C-C motif chemokine receptor 5 (CCR5). This, in turn, resulted in an increase in the infiltration of CD8 T cells in the TME, thereby enhancing the antitumor immune response. Analysis of a tissue microarray derived from HCC patient samples revealed a positive correlation between survival rate and prognosis and the expression levels of CCL5/CD8. In conclusion, our findings suggest that combined application of ICG-001 and anti-PD-1 antibody exhibits significantly enhanced antitumor efficacy. Hence, combining a WNT/β-catenin signaling pathway inhibitor with anti-PD-1 therapy may be a promising treatment strategy for patients with HCC.
PubMed: 38941667
DOI: 10.1016/j.intimp.2024.112534 -
International Immunopharmacology Jun 2024This study aims to analyze the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) blockade plus chemotherapy in real-world applications. Additionally, we...
BACKGROUND
This study aims to analyze the efficacy and safety of neoadjuvant programmed cell death-1 (PD-1) blockade plus chemotherapy in real-world applications. Additionally, we report survival outcomes with a median follow-up of 40.1 months.
METHODS
From January 2018 to October 2022, we retrospectively recruited patients with esophageal squamous cell carcinoma (ESCC) who underwent surgery after receiving PD-1 blockade (immunotherapy) plus chemotherapy at Jiangsu Cancer Hospital.
RESULTS
A total of 132 eligible ESCC patients were included, and R0 resection was achieved in 131 cases (99.2 %). A complete pathological response rate (ypT0N0) was observed in 32 patients (24.2 %), and the objective response rate was 59.1 %. The most common grade 3-4 treatment-related adverse events (TRAEs) were leukopenia (18.2 %) and neutropenia (15.9 %). Three cases (2.3 %) of grade 3 immune-related AEs were observed, including increased ALT (0.8 %), rash (0.8 %), and encephalitis (0.8 %). The 1-year disease-free survival (DFS) and overall survival (OS) rates were 68.2 % and 89.4 %, respectively, and the 2-year DFS and OS rates were 55.1 % and 78.6 %, respectively. The pathological responses of 103 cases (94.5 % of 109) of the index lymph node (ILN) were categorized as the worst regression subgroup. In these cases, using the pathological response of the ILN to indicate the status of other lymph nodes would not result to a missed therapeutic lymph node dissection.
CONCLUSIONS
Neoadjuvant immunotherapy plus chemotherapy is safe and effective for ESCC, with observable survival benefits. The pathological response of the ILN after neoadjuvant therapy may have important value in guiding therapeutic lymph node dissection.
PubMed: 38941666
DOI: 10.1016/j.intimp.2024.112558 -
Colloids and Surfaces. B, Biointerfaces Jun 2024In cancer research, circulating tumor cells (CTCs) were identified as the main drivers of metastasis. They are vital for early detection and prevention of metastasis...
In cancer research, circulating tumor cells (CTCs) were identified as the main drivers of metastasis. They are vital for early detection and prevention of metastasis during cancer treatment. Even though continuous progress in research offers more and more tools to combat cancer, we still lack a proper arsenal of therapeutics. Especially in tumors with close to no targeting options, like triple-negative breast cancer, early detection is often the main difference between successful and failed therapy. When such tumors are detected too late, they may have already produced plenty of CTCs, likely causing metastasis, which is the primary reason for tumor-associated deaths. Detecting those CTCs early on could substantially impact therapy outcomes and the 5-year survival rate. In our study, we developed and evaluated a reliable and affordable CTC screening method based on flow cytometry and 5-aminolevulinic acid (5-ALA) staining. We successfully established a circulation model for 5-ALA and CTCs research and demonstrated that the method can detect an average of 11 ± 3.3 CTCs out of 10,000 peripheral blood mononuclear cells, representing as low as approximately 0.1 % with a reasonable number of false positive events. Additionally, we present initial results on a theranostic approach using 5-ALA converted to protoporphyrin IX. The outcomes of this study might contribute significantly to the further development of CTC detection and the overall detection and treatment of cancer.
PubMed: 38941652
DOI: 10.1016/j.colsurfb.2024.114059 -
Medicine Jun 2024Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding... (Observational Study)
Observational Study
Idiopathic inflammatory myopathies, especially antisynthetase syndrome, often appear outside of the muscles as interstitial lung disease (ILD). Another typical finding is the presence of mechanic's hands. The aim of the present study was to describe the clinical, functional, tomographic, and serological data of patients with ILD and mechanic's hands and their response to treatment and survival rates. This is a retrospective study of ILD with concurrent myopathy. Among the 119 patients initially selected, 51 had mechanic's hands. All the patients were screened for anti-Jo-1 antibodies. An expanded panel of myopathy autoantibodies was also performed in 27 individuals. Of the 51 patients, 35 had 1 or more antibodies. The most common were anti-Jo-1, anti-PL-7, and anti-PL-12, while of the associated antibodies, anti-Ro52 was present in 70% of the 27 tested individuals. A significant response to treatment was characterized by an increase in predicted forced vital capacity (FVC) of at least 5% in the last evaluation done after 6 to 24 months of treatment. A decrease in predicted FVC of at least 5%, the need for oxygen therapy, or death were all considered treatment failures. All patients were treated with corticosteroids, and 71% with mycophenolate. After 24 months, 18 patients had an increase in FVC, 11 had a decrease, and 22 remained stable. After a median follow-up of 58 months, 48 patients remained alive and three died. Patients with honeycombing on high-resolution chest tomography (log-rank = 34.65; P < .001) and a decrease in FVC ≥5% (log-rank = 18.28, P < .001) had a poorer survival rate. Patients with ILD and mechanic's hands respond well to immunosuppressive treatment.
Topics: Humans; Lung Diseases, Interstitial; Retrospective Studies; Male; Female; Middle Aged; Myositis; Aged; Treatment Outcome; Adult; Autoantibodies; Outpatients; Adrenal Cortex Hormones; Vital Capacity
PubMed: 38941439
DOI: 10.1097/MD.0000000000038642 -
Medicine Jun 2024Evidence on real-world clinical and economic outcomes in patients with multiple myeloma (MM) and renal impairment (RI) is limited in the United States. This... (Observational Study)
Observational Study
Evidence on real-world clinical and economic outcomes in patients with multiple myeloma (MM) and renal impairment (RI) is limited in the United States. This retrospective study aimed to generate an updated comprehensive assessment of the clinical and economic outcomes of MM patients with RI using the Medicare research identifiable files data with Part D linkage, which might assist in assessing the total clinical and socioeconomic burden of these high-risk and challenging-to-treat patients. Treatment patterns and clinical and economic outcomes in first line (1L) to fourth line (4L) therapy were described in Medicare beneficiaries (2012 to 2018) for MM patients with RI (RI MM cohort). For reference purposes, information on a general cohort of MM patients was generated and reported to highlight the clinical and economic burden of RI. Since the goal was to describe the burden of these patients, this study was not designed as a comparison between the 2 cohorts. Compared with the general MM cohort (n = 13,573), RI MM patients (24.9%) presented high MM-associated comorbidities. In the RI MM cohort, bortezomib-dexamethasone (45.7%), bortezomib-lenalidomide (18.6%), lenalidomide (12.3%), and bortezomib-cyclophosphamide (12.1%) were the most prevalent regimens in 1L; carfilzomib and pomalidomide were mostly received in 3L to 4L; and daratumumab in 4L. Across 1L to 4L, the RI MM cohort presented shorter median real-world progression-free survival (1L: 12.9 and 16.4 months) and overall survival (1L: 31.1 and 46.8 months) and higher all-cause healthcare resource utilization (1L incidence rate of inpatient days: 12.1 and 7.8 per person per year) than the general MM cohort. In the RI MM cohort, the mean all-cause total cost increased from 1L to 4L ($14,549-$18,667 per person per month) and was higher than that of the general MM cohort. RI MM patients presented higher clinical and economic burdens across 1L to 4L than the general MM patients in real-world clinical practice.
Topics: Humans; Multiple Myeloma; United States; Male; Female; Aged; Retrospective Studies; Medicare; Aged, 80 and over; Renal Insufficiency; Cost of Illness; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38941411
DOI: 10.1097/MD.0000000000038609 -
Medicine Jun 2024Ferroptosis was reported to possess the therapeutic potentials in various human cancers. In the present study, we explored the expression, clinical significance and the...
BACKGROUND
Ferroptosis was reported to possess the therapeutic potentials in various human cancers. In the present study, we explored the expression, clinical significance and the molecular mechanism of FK506 binding protein 3 (FKBP3) in the progression of lung adenocarcinoma (LUAD).
MATERIAL AND METHOD
Cox regression was performed to obtain the prognosis related to differentially expressed genes (DEGs) in LUAD datasets from TCGA. We also downloaded the ferroptosis-related gene datasets from GeneCards. Venn diagram was performed to find the intersecting genes and FKBP3 was selected as the targeted gene by analyzing the diagnostic and prognostic values of Top10 intersecting genes. Moreover, univariate and multivariate analyses were performed to evaluate the association between clinicopathological factors and survival rates. GO/KEGG and GSEA analysis was performed to explore the function of FKBP3 in LUAD progression. Protein-protein interaction (PPI) network was performed via STRING database and the top10 hub genes were selected. Finally, the relationship between FKBP3 and immune infiltration was explored by ssGSEA analysis.
RESULTS
Firstly, 184 genes associated with the prognosis of LUAD and ferroptosis were obtained. FKBP3 was found to be significantly associated with a poor overall survival rate of LUAD patients. Immunohistochemical staining results showed that FKBP3 was highly located in cytoplasm and membrane of cells in LUAD tissues. PPI network analysis results showed that HDAC1, YY1, HDAC2, MTOR, PSMA3, PIN1, NCL, C14orf166, PIN4, and LARP6 were the top10 hub genes. Furthermore, spearman analysis results showed that the expression of FKBP3 was positively correlated with the abundance of Th2 cells and T helper cells.
CONCLUSION
High level of FKBP3 was associated with poor prognostic outcomes of LUAD patients, which also inhibited immune infiltration in LUAD tissues. Additionally, FKBP3 was involved in regulating the ferroptosis process in LUAD patients. Thus, FKBP3 possessed the tumor promotion role might be involving in regulating ferroptosis and immune infiltration in LUAD progression.
Topics: Humans; Ferroptosis; Prognosis; Female; Disease Progression; Male; Adenocarcinoma of Lung; Lung Neoplasms; Middle Aged; Tacrolimus Binding Proteins; Biomarkers, Tumor; Aged; Gene Expression Regulation, Neoplastic; Protein Interaction Maps
PubMed: 38941396
DOI: 10.1097/MD.0000000000038606 -
Journal of Primary Health Care Jun 2024Introduction The inability to afford a consultation with a general practitioner may lead to delays in accessing care pathways. Aim This study aimed to explore the...
Introduction The inability to afford a consultation with a general practitioner may lead to delays in accessing care pathways. Aim This study aimed to explore the characteristics of people by their unmet need for a general practitioner consultation because of cost, and the characteristics of subsequent inpatient hospitalisations. Methods From the New Zealand Health Surveys (2013/14-2018/19), two groups were formed based on their unmet need for a general practitioner consultation due to cost. These groups were compared by socio-demographic factors and subsequent inpatient hospitalisation characteristics during follow-up. Time to an inpatient hospitalisation was the outcome in a proportional hazards regression model with need status as the key variable. The model was expanded to include confounding variables: sex, age group, ethnicity, the New Zealand Deprivation Index and self-rated health. Results The need group, characterised by having a higher proportion of females, younger adults, Māori, increased socioeconomic deprivation and poorer self-rated health experienced a greater chance of hospitalisation, a similar number of visits during follow-up, shorter stays and a quicker time to hospitalisation compared to the no-need group. Proportional hazards survival models gave a 28% higher hazard rate for the time to an inpatient hospitalisation for the need group compared to the no-need group. The inclusion of all the confounders in the model gave a similar hazard ratio. Discussion Although consultation fees vary across general practices, it is evident that this may not eliminate the cost barriers to accessing care for some groups. Needing multiple consultations may contribute to persistent unmet needs.
Topics: Humans; New Zealand; Male; Female; Hospitalization; Middle Aged; Adult; Primary Health Care; Aged; Young Adult; Adolescent; Socioeconomic Factors; Health Services Needs and Demand; Age Factors; Sex Factors; Cohort Studies; Health Services Accessibility; Proportional Hazards Models; Native Hawaiian or Other Pacific Islander; Sociodemographic Factors
PubMed: 38941253
DOI: 10.1071/HC24018 -
The International Journal of Oral &... Jun 2024To retrospectively evaluate the long-term clinical, technical, biological, and esthetic outcomes of implant supported single zirconia crowns (ISCs) intraorally cemented...
Retrospective, Multi-center, Cohort Study Evaluating Clinical, Technical, Biological, and Esthetic Outcomes of Implant Supported Zirconia Single Crowns Cemented on Titanium-base Abutments: 7-year Mean Follow-up.
PURPOSE
To retrospectively evaluate the long-term clinical, technical, biological, and esthetic outcomes of implant supported single zirconia crowns (ISCs) intraorally cemented to Ti-base hybrid-abutments up to 16 years after placement.
MATERIALS AND METHODS
A total of 63 ISCs (Xive S, Camlog Screw Line, Replace Select TC NP, Branemark MK II, and 3i Osseotite) were evaluated in 36 patients at two different centers. Original Ti-bases were selected and zirconia meso structures and zirconia crowns were designed using CAD/CAM software and then milled from partially stabilized zirconia blocks. After the meso structures were cemented extraorally onto the Ti-bases, the ceramic crowns were intraorally luted to the hybrid abutments. The Ti-base ISC restorations were followed up for up to 16 years, and their clinical, biological, and esthetic outcomes were recorded at distinct time points (T1; T2) at three-year intervals.
RESULTS
36 patients (18 men, 18 women) received 32 ISCs in the anterior region and 31 in the posterior region of the maxilla and mandible. The mean follow-up of the Ti-base ISCs was 6.93 ± 2.60 years. The mean follow-up of the implants amounted to 8.11 ± 3.26 years. No implants were lost during follow-up, resulting in a cumulative implant survival rate of 100%. Abutment screw loosening was observed in two ISCs after one year in service. The overall cumulative restorative survival rate of the Ti-base restorations reached thus 96.83%. At T2 follow-up 24% of the ISCs exhibited an increase in PD despite maintaining clinically healthy peri-implant tissue. An 11% increase in BOP and a 3.17% decrease in PI were recorded. Despite spectrophotometrically measured ΔE values indicating visible discoloration of some restorations and their peri-implant soft tissue, a low incidence of esthetic complications was observed with an average PES/WES score of ≥ 12. No correlation was found between PES (R = -0.25; p = 0.27) and WES (R = -0.18; p = 0.43) scores and digital shade determination.
CONCLUSIONS
The results of the present retrospective, multicenter, cohort study indicate satisfactory clinical outcomes for intraorally cemented single zirconia crowns (ISCs) supported by Ti-base hybrid abutments. An overall esthetic superiority of Ti-base ISCs could not be confirmed.
PubMed: 38941168
DOI: 10.11607/jomi.11039