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Child: Care, Health and Development Jul 2024In the digital age, bullying manifests in two distinct forms: traditional bullying and cyberbullying. Children's peer relationships are important predictors of bullying,...
BACKGROUND
In the digital age, bullying manifests in two distinct forms: traditional bullying and cyberbullying. Children's peer relationships are important predictors of bullying, and bullying in turn predicts peer relationships. However, few researchers have noted the bidirectional relationship between peer relationships and bullying.
METHODS
The present study used a two-wave cross-lagged longitudinal design to fill this gap. The potential sex differences were also examined in this relationship. The sample consisted of 527 Chinese children aged 8 to 12 years (M = 9.69, SD = .96; 53.5% female). Participants completed peer nominations for peer acceptance, peer rejection and social dominance, as well as self-reports of traditional bullying and cyberbullying.
RESULTS
Results showed that peer rejection at the first time point (T1) significantly and positively predicted traditional bullying perpetration, cyberbullying perpetration and cyberbullying victimization at the second time point (T2). Traditional bullying victimization at T1 significantly and negatively predicted peer acceptance and social dominance at T2. The results also revealed significant male and female differences. For instance, among boys, peer acceptance at T1 significantly and negatively predicted cyberbullying victimization at T2. In contrast, this relationship was not observed among girls. The present findings have important implications for understanding the cyclical relationship between peer relationships and bullying and providing practical guidance for improving peer relationships and reducing bullying.
Topics: Humans; Male; Female; Child; Peer Group; Bullying; China; Crime Victims; Interpersonal Relations; Longitudinal Studies; Sex Factors; Cyberbullying; Social Dominance; Child Behavior; East Asian People
PubMed: 38953565
DOI: 10.1111/cch.13302 -
FASEB Journal : Official Publication of... Jul 2024Age-related macular degeneration (AMD) is a common cause of vision loss. The aggressive form of AMD is associated with ocular neovascularization and subretinal fibrosis,...
Age-related macular degeneration (AMD) is a common cause of vision loss. The aggressive form of AMD is associated with ocular neovascularization and subretinal fibrosis, representing a responsive outcome against neovascularization mediated by epithelial-mesenchymal transition of retinal pigment epithelium (RPE) cells. A failure of the current treatment (anti-vascular endothelial growth factor therapy) has also been attributed to the progression of subretinal fibrosis. Hypoxia-inducible factors (HIFs) increase gene expressions to promote fibrosis and neovascularization. HIFs act as a central pathway in the pathogenesis of AMD. HIF inhibitors may suppress ocular neovascularization. Nonetheless, further investigation is required to unravel the aspects of subretinal fibrosis. In this study, we used RPE-specific HIFs or von Hippel-Lindau (VHL, a regulator of HIFs) conditional knockout (cKO) mice, along with pharmacological HIF inhibitors, to demonstrate the suppression of subretinal fibrosis. Fibrosis was suppressed by treatments of HIF inhibitors, and similar suppressive effects were detected in RPE-specific Hif1a/Hif2a- and Hif1a-cKO mice. Promotive effects were observed in RPE-specific Vhl-cKO mice, where fibrosis-mediated pathologic processes were evident. Marine products' extracts and their component taurine suppressed fibrosis as HIF inhibitors. Our study shows critical roles of HIFs in the progression of fibrosis, linking them to the potential development of therapeutics for AMD.
Topics: Animals; Mice; Fibrosis; Retinal Pigment Epithelium; Von Hippel-Lindau Tumor Suppressor Protein; Mice, Knockout; Hypoxia-Inducible Factor 1, alpha Subunit; Basic Helix-Loop-Helix Transcription Factors; Macular Degeneration; Retina; Epithelial-Mesenchymal Transition; Mice, Inbred C57BL
PubMed: 38953555
DOI: 10.1096/fj.202400540RRR -
Melanoma Research Jun 2024Mucosal melanoma is a rare melanoma subtype, accounting for about 1% of all diagnosed melanomas. It is characterized by an aggressive phenotype with a poor prognosis and...
Mucosal melanoma is a rare melanoma subtype, accounting for about 1% of all diagnosed melanomas. It is characterized by an aggressive phenotype with a poor prognosis and a low response rate to approved treatments. We retrospectively analyzed the clinical features, treatments, and outcomes of patients diagnosed with mucosal melanoma treated with axitinib ± anti-programmed cell death protein 1 (PD-1) therapy at a single US referral center between 2018 and 2021. Radiologic response was assessed according to Response Evaluation Criteria in Solid Tumors (RECIST), v1.1. Twenty-three patients were included in this study. In all, 78% were females with a median age of 62 years. The originating site of mucosal melanoma was the sinonasal (35%), genitourinary (35%), and gastrointestinal (30%) tracts. Sixty-five percent of patients had M1c or M1d disease and 0% had BRAF V600 mutations detected. The majority (96%) had prior treatment inclusive of anti-PD-1, with a median of 2 prior lines, and 78% of patients received a combination of axitinib and PD-1 and the median duration of treatment was 3.2 months. The overall response rate was 13% and the disease control rate was 26%. The median progression-free survival was 3.2 months, and the median overall survival was 8.2 months. Overall, the regimen was well tolerated with 39% of patients requiring dose reduction and 9% requiring treatment cessation. Axitinib with anti-PD-1 therapy has modest clinical activity in heavily pretreated patients with mucosal melanoma outside of Asia, including some with long-term benefits. This data supports the worldwide clinical trials evaluating this combination and the role of incorporating vascular endothelial growth factor-based therapy in the therapeutic paradigm for patients with mucosal melanoma.
PubMed: 38953532
DOI: 10.1097/CMR.0000000000000988 -
Histology and Histopathology Jun 2024Gastric cancer represents an aggressive malignancy and a leading contributor to cancer death. Ephrin-A4 (EFNA4) has been proposed to be related to the immune...
Gastric cancer represents an aggressive malignancy and a leading contributor to cancer death. Ephrin-A4 (EFNA4) has been proposed to be related to the immune microenvironment and prognosis of gastric cancer. This study was undertaken to discuss the participation and mechanism of EFNA4 in the development of gastric cancer. RT-qPCR and western blot examined EFNA4 and Pygopus2 (Pygo2) expression in gastric cancer cells. After transfection of EFNA4 interference plasmids or co-transfection of EFNA4 interference plasmids and Pygo2 overexpression plasmids, cell proliferation was detected by the CCK-8 method and EDU staining. Wound healing, Transwell, TUNEL, and endothelial cell tube formation assays detected cell migration, invasion, apoptosis, and angiogenesis, respectively. Western blot examined the expression of metastasis-, apoptosis-, angiogenesis-, and Wnt signaling-associated proteins. Cell stemness was estimated by the sphere formation assay, RT-qPCR, and western blot. Through the experimental data, it was noticed that EFNA4 expression was increased in gastric cancer cells. Knockdown of EFNA4 suppressed the proliferation, migration, invasion, angiogenesis as well as stemness while aggravating the apoptosis of gastric cancer cells. Also, EFNA4 depletion reduced Pygo2 protein expression and then inactivated Wnt/β-catenin signaling. Further elevation of Pygo2 reversed the impacts of EFNA4 silencing on Wnt/β-catenin signaling, cell proliferation, apoptosis, migration, invasion, angiogenesis as well as stemness in gastric cancer. Accordingly, the knockdown of EFNA4 might downregulate Pygo2 and inactivate Wnt/β-catenin signaling to exert protective effects against gastric cancer.
PubMed: 38953488
DOI: 10.14670/HH-18-779 -
American Journal of Hematology Jul 2024Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM). We identified 54/4352 MM patients (1.2%), who developed CNS-MM...
Central nervous system (CNS) involvement is a rare and aggressive complication of multiple myeloma (MM). We identified 54/4352 MM patients (1.2%), who developed CNS-MM between 2000 and 2022. A matched-control group of MM patients without CNS-MM was used for comparisons. Median age was 63 years. Median time to CNS-MM was 28 months; 6/54 experienced CNS-MM at MM diagnosis. Abnormal lactate dehydrogenase (LDH), high-risk cytogenetics, and extramedullary involvement (EMI), that is, soft tissue plasmacytomas and/or plasma cell leukemia (PCL), were more frequent in CNS-MM versus controls (p < .05); 13/54 had PCL at CNS-MM. The majority had leptomeningeal infiltration (LMI) (66%); 26% had CNS-MM without systemic myeloma; EMI was the strongest predictor for CNS-MM (OR: 6.3). Median overall survival (OS) of CNS-MM patients versus controls was 43 months (95% CI: 32-54) versus 60 months (95% CI: 38-82) (p < .001); treatment of CNS-MM included mainly bortezomib/thalidomide/chemotherapy whereas 20% received novel drugs/immunotherapy combinations; 28 patients underwent cerebrospinal fluid infusions; EMI was the strongest negative predictor for post CNS-MM OS (p = .005; HR: 2.9). Treatment after 2016 predicted significantly for OS (p = .002; HR: 0.27). Median post CNS-MM OS was 4 months (95% CI: 2.6-5.4); in patients treated after 2016 median OS was 12 months. In conclusion, we have demonstrated in this large real-world series that survival of CNS-MM remains poor; however, there is a positive impact of treatment after 2016, related to the efficacy of modern anti-myeloma therapy; EMI significantly increases the probability to develop CNS-MM and the risk of post CNS-MM death, indicating a potential need for CNS prophylaxis for those patients.
PubMed: 38953456
DOI: 10.1002/ajh.27425 -
American Journal of Hematology Jul 2024Myeloproliferative neoplasms represent a group of clonal hematopoietic disorders of which myelofibrosis (MF) is the most aggressive. In the context of myeloid neoplasms,...
Myeloproliferative neoplasms represent a group of clonal hematopoietic disorders of which myelofibrosis (MF) is the most aggressive. In the context of myeloid neoplasms, there is a growing recognition of the dysregulation of immune response and T-cell function as significant contributors to disease progression and immune evasion. We investigated cytotoxic T-cell exhaustion in MF to restore immune response against malignant cells. Increased expression of inhibitory receptors like CTLA-4 was observed on cytotoxic T cells from MF patients together with a reduced secretion of IFNɣ and TNFɑ. CTLA-4 ligands CD80 and CD86 were increased on MF granulocytes and monocytes highlighting a possible role for myeloid cells in suppressing T-cell activation in MF patients. Unlike healthy donors, the activation of cytotoxic T cells from MF patients was attenuated in the presence of myeloid cells and restored when T cells were cultured alone or treated with anti-CTLA-4. Moreover, anti-CTLA-4 treatment promoted elimination of neoplastic monocytes and granulocytes in a co-culture system with cytotoxic T cells. To test CTLA-4 inhibition in vivo, patient-derived xenografts were generated by transplanting MF CD34+ cells and by infusing homologous T cells in NSGS mice. CTLA-4 blockade reduced human myeloid chimerism and led to T-cell expansion in spleen and bone marrow. Overall, these findings shed light on T-cell dysfunction in MF and suggest that CTLA-4 blockade can boost the cytotoxic T cell-mediated immune response against tumor cells.
PubMed: 38953347
DOI: 10.1002/ajh.27428 -
Cureus May 2024Desmoid tumors, also referred to as aggressive fibromatosis, represent an uncommon form of fibroblastic proliferation. These neoplasms may arise within any...
Desmoid tumors, also referred to as aggressive fibromatosis, represent an uncommon form of fibroblastic proliferation. These neoplasms may arise within any musculoaponeurotic structure throughout the body. They are classified as benign due to several distinctive features: histologically, they exhibit regular mitotic activity and are devoid of metastatic potential. Computed tomography (CT) remains the definitive modality for precise diagnosis, and surgical excision is strongly advised. This account details the manifestation of a desmoid tumor located in the anterior abdominal wall of a 31-year-old female patient who notably lacks any prior surgical interventions. The surgical intervention entailed the excision of the neoplasm and subsequent reconstruction of the abdominal wall utilizing a polypropylene mesh. Postoperatively, the patient was released from the medical facility after a period of three days, having experienced no post-surgical complications. This was followed by a six-month interval free of any adverse events.
PubMed: 38953071
DOI: 10.7759/cureus.61383 -
Risk Management and Healthcare Policy 2024The Sars-CoV-2 pandemic imposed unprecedented and drastic changes in health care organizations all over the world.
BACKGROUND
The Sars-CoV-2 pandemic imposed unprecedented and drastic changes in health care organizations all over the world.
PURPOSE
To evaluate the impact of the pandemic on hospitalizations in an acute psychiatric ward.
PATIENTS AND METHODS
We retrospectively identified and compared acute psychiatric hospitalizations in the Service for Psychiatric Diagnosis and Care (SPDC) of AUSL-Modena during the pre-pandemic (n = 1858) and pandemic period (n = 1095), from 01/01/2017 to 31/12/2022. Data were statistically analyzed using STATA12.
RESULTS
We collected 1858 hospitalizations in the pre-pandemic and 1095 in the pandemic. During the pandemic, we observed a progressively sharp reduction in voluntary hospitalizations, whereas involuntary ones remained stable with an increase in 2022 (p < 0.001), longer hospital stays (12.32 mean days vs 10.03; p < 0.001), longer periods of involuntary hospitalizations (8.45 mean days vs 5.72; p < 0.001), more frequent aggressive behaviour (16.10% vs 9.12%; p < 0.001) and referral to psychiatric communities at discharge (11.04% vs 6.13%; p < 0.001); non-Italians (p = 0.001), people with disability pension (p < 0.001) and Support Administrator (p < 0.001) were more frequently hospitalized.
CONCLUSION
During the pandemic, voluntary psychiatric hospitalizations decreased, but not involuntary ones, and the most vulnerable people in serious clinical conditions were hospitalized.
PubMed: 38953036
DOI: 10.2147/RMHP.S465858 -
Frontiers in Immunology 2024Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of...
BACKGROUND
Chimeric antigen receptor T (CAR-T) cell therapies have achieved remarkable success in the treatment of hematological tumors. However, given the distinct features of solid tumors, particularly heterogeneity, metabolic aggressiveness, and fewer immune cells in tumor microenvironment (TME), the practical utility of CAR-T cells for solid tumors remains as a challenging issue. Meanwhile, although anti-PD-1 monoclonal antibody (mAb) has shown clinical efficacy, most mAbs also show limited clinical benefits for solid tumors due mainly to the issues associated with the lack of immune cells in TME. Thus, the infiltration of targeted immunological active cells into TME could generate synergistic efficacy for mAbs.
METHODS
We present a combinational strategy for solid tumor treatment, which combines armored-T cells to express Fc-gamma receptor I (FcγRI) fragment on the surfaces for targeting various tumors with therapeutically useful mAbs. Choosing CD20 and HER-2 as the targets, we characterized the and efficacy and latent mechanism of the combination drug by using flow cytometry, ELISA and other methods.
RESULTS
The combination and preprocessing of armored T-cells with corresponding antibody of Rituximab and Pertuzumab exerted profound anti-tumor effects, which is demonstrated to be mediated by synergistically produced antibody-dependent cellular cytotoxicity (ADCC) effects. Meanwhile, mAb was able to carry armored-T cell by preprocessing for the infiltration to TME in cell derived xenograft (CDX) model.
CONCLUSIONS
This combination strategy showed a significant increase of safety profiles from the reduction of antibody doses. More importantly, the present strategy could be a versatile tool for a broad spectrum of cancer treatment, with a simple pairing of engineered T cells and a conventional antibody.
Topics: Receptors, IgG; Humans; Animals; Mice; Neoplasms; T-Lymphocytes; Tumor Microenvironment; Antibodies, Monoclonal; Cell Line, Tumor; Xenograft Model Antitumor Assays; Immunotherapy, Adoptive; Receptor, ErbB-2; Antineoplastic Agents, Immunological; Receptors, Chimeric Antigen; Female; Antigens, CD20
PubMed: 38953027
DOI: 10.3389/fimmu.2024.1400177 -
Pathology Oncology Research : POR 2024Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the... (Review)
Review
Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the gradual cut of smoking prevalence. Consequently, the relative frequency of adenocarcinoma increased while that of squamous and small cell carcinomas declined. During the last two decades a plethora of targeted drug therapies have appeared for the treatment of metastasizing non-small cell lung carcinomas (NSCLC). Personalized oncology aims to precisely match patients to treatments with the highest potential of success. Extensive research is done to introduce biomarkers which can predict the effectiveness of a specific targeted therapeutic approach. The EGFR signaling pathway includes several sufficient targets for the treatment of human cancers including NSCLC. Lung adenocarcinoma may harbor both activating and resistance mutations of the EGFR gene, and further, mutations of KRAS and BRAF oncogenes. Less frequent but targetable genetic alterations include ALK, ROS1, RET gene rearrangements, and various alterations of MET proto-oncogene. In addition, the importance of anti-tumor immunity and of tumor microenvironment has become evident recently. Accumulation of mutations generally trigger tumor specific immune defense, but immune protection may be upregulated as an aggressive feature. The blockade of immune checkpoints results in potential reactivation of tumor cell killing and induces significant tumor regression in various tumor types, such as lung carcinoma. Therapeutic responses to anti PD1-PD-L1 treatment may correlate with the expression of PD-L1 by tumor cells. Due to the wide range of diagnostic and predictive features in lung cancer a plenty of tests are required from a single small biopsy or cytology specimen, which is challenged by major issues of sample quantity and quality. Thus, the efficacy of biomarker testing should be warranted by standardized policy and optimal material usage. In this review we aim to discuss major targeted therapy-related biomarkers in NSCLC and testing possibilities comprehensively.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Biomarkers, Tumor; Proto-Oncogene Mas
PubMed: 38953007
DOI: 10.3389/pore.2024.1611733