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PURPOSE: There is a lack of real-world data in Asian populations for brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor for patients with non-small cell lung cancer (NSCLC). This study analysed real-world outcomes and dosing patterns for brigatinib in patients with crizotinib-refractory ALK+ NSCLC in South Korea. METHODS: This retrospective, non-interventional, cohort study used South Korean Health Insurance and Review Assessment claims data for adults with ALK+ NSCLC who initiated brigatinib between 19 April 2019 and 31 March 2021 after receiving prior crizotinib. Patients' characteristics, time to discontinuation (TTD), time to dose reduction, overall survival (OS) and treatment adherence were assessed. RESULTS: The study included 174 patients (56.9% male; 27.0% with a history of brain metastases). Median duration of prior crizotinib was 17 (range 0.3-48) months. Median follow-up after brigatinib initiation was 18 (range 0-34) months. Overall, 88.5% of patients received full-dose brigatinib (180 mg/day) and 93.1% of patients were adherent (proportion of days covered ≥0.8). The median TTD was 24.9 months (95% CI 15.2-not reached). The probability of continuing treatment was 63.2% at 1 year and 51.5% at 2 years. The probability of continuing at full or peak dose was 79.7% at 1 year and 75.6% at 2 years. Median OS was not reached. The 2-year OS rate was 68.7%. CONCLUSIONS: In this first nationwide retrospective study using national insurance claim data, brigatinib demonstrated real-world clinical benefit as second-line treatment after prior crizotinib in ALK+ NSCLC patients in South Korea.
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Quinasa de Linfoma Anaplásico , Carcinoma de Pulmón de Células no Pequeñas , Crizotinib , Neoplasias Pulmonares , Compuestos Organofosforados , Pirimidinas , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Masculino , Femenino , República de Corea , Crizotinib/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Compuestos Organofosforados/uso terapéutico , Compuestos Organofosforados/administración & dosificación , Compuestos Organofosforados/efectos adversos , Estudios Retrospectivos , Quinasa de Linfoma Anaplásico/genética , Quinasa de Linfoma Anaplásico/antagonistas & inhibidores , Adulto , Pirimidinas/uso terapéutico , Pirimidinas/administración & dosificación , Anciano , Inhibidores de Proteínas Quinasas/uso terapéutico , Resultado del TratamientoRESUMEN
BACKGROUND: The standard-risk hepatoblastoma has a good prognosis in children; however, refractory or relapsed (R/R) hepatoblastoma has a poor prognosis and high mortality rate. This study aimed to demonstrate the efficacy of high-dose chemotherapy and autologous hematopoietic stem cell transplantation (HSCT) rescue in pediatric patients with R/R hepatoblastoma. METHODS: We retrospectively analyzed 6 pediatric patients with R/R hepatoblastoma who underwent autologous HSCT. The MEC conditioning regimen was used for all patients, comprising melphalan 140 mg/m 2 /day intravenously (IV) on day 7 and 70 mg/m 2 on day 6, etoposide 200 mg/m 2 IV on days 5 to 8, and carboplatin 400 mg/m 2 IV on days 5 to 8. One patient received a TopoThioCarbo regimen, comprising topotecan 2 mg/m 2 /day IV on days 4 to 8, thiotepa 300 mg/m 2 /day IV on days 6 to 8, and carboplatin 500 mg/m 2 /day IV on days 3 to 5, as the conditioning regimen for the first transplantation. This was followed by salvage chemotherapy for relapse, and the second transplantation was performed using MEC as the conditioning regimen. RESULTS: We report the retrospective results of 6 patients with a median age of 1.8 (range 0.4 to 10.2) years who had R/R hepatoblastoma and underwent autologous HSCT. The median follow-up period was 58 (range 28 to 113) months after diagnosis. The median stage at diagnosis was 2.0 (range 2 to 4). Two patients had lung metastases during diagnosis. The median initial alpha-fetoprotein level was 292,888 (range 28,831 to 2,406,942) ng/mL, and the median number of chemotherapy lines before autologous HSCT was 3.5 (range 2 to 7). The disease status before HSCT was complete remission (CR) for all patients. The engraftment rate was 100%. No treatment-related mortality was reported. The 3-year event-free survival and overall survival rates were 83.3% and 100%, respectively. One patient relapsed after the second HSCT and achieved CR after salvage chemotherapy. CONCLUSION: This study suggests autologous HSCT as an effective treatment in pediatric patients with R/R hepatoblastoma. Nevertheless, future large-scale prospective studies are warranted.
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Trasplante de Células Madre Hematopoyéticas , Hepatoblastoma , Neoplasias Hepáticas , Recurrencia Local de Neoplasia , Trasplante Autólogo , Humanos , Hepatoblastoma/terapia , Hepatoblastoma/mortalidad , Hepatoblastoma/patología , Trasplante de Células Madre Hematopoyéticas/métodos , Estudios Retrospectivos , Masculino , Femenino , Preescolar , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Recurrencia Local de Neoplasia/terapia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/mortalidad , Niño , Lactante , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tasa de Supervivencia , Terapia Recuperativa/métodos , Acondicionamiento Pretrasplante/métodos , Carboplatino/administración & dosificación , PronósticoRESUMEN
Traditionally, bone marrow (BM) has been preferred as a source of stem cells (SCs) in pediatric hematopoietic SC transplantation (HSCT); however, the use of peripheral blood SCs (PBSC) has recently increased. With advancing graft-versus-host disease (GVHD) prophylaxis, whether the BM is still a better SC source than PB in sibling donor HSCT remains controversial. Here, we compared the results of BM transplantation (BMT) and PBSC transplantation (PBSCT) in pediatric patients with malignant or non-malignant diseases receiving sibling HSCT using a total of 7.5 mg/kg of anti-thymocyte globulin (ATG). We retrospectively reviewed children who received HSCT from a sibling donor between 2005 and 2020 at Seoul National University Children's Hospital. Of the 86 patients, 40 underwent BMT, and 46 underwent PBSCT. Fifty- six patients had malignant diseases, whereas thirty patients had non-malignant diseases. All conditioning regimens comprised ATG. Busulfan-based myeloablative conditioning regimens were administered to patients with malignant diseases and approximately half of those with non-malignant diseases. The remaining half of the patients with non-malignant diseases were administered cyclophosphamide-based reduced- intensity conditioning regimens. According to studies conducted at our center, all BM donors received G-CSF before harvest to achieve early engraftment. In all 86 patients (47 males and 39 females), the median age at the time of HSCT was 11.4 (range, 0.7 - 24.6) years. The median follow-up period was 57.9 (range, 0.9-228.6) months, and the corresponding values for those with BM and PBSC were 77 (range, 2.4-228.6) months and 48.7 (range, 0.9-213.2) months, respectively. Engraftment failure occurred in one patient with BM and no patient with PBSC. The cumulative incidence of acute GVHD with grades II-IV was higher in PBSC (BM 2.5%, PBSC 26.1%, p = 0.002), but there was no significant difference in those with grades III-IV acute GVHD (BM 0%, PBSC 6.5%, p = 0.3703) and extensive chronic GVHD (BM 2.5%, PBSC 11.6%, p = 0.1004). There were no significant differences in treatment-related mortality (TRM) (BM 14.2%, PBSC 6.8%, p = 0.453), 5-year event-free survival (EFS) (BM 71.5%, PBSC 76.2%, p = 0.874), and overall survival (OS) rates (BM 80.8%, PBSC 80.3%, p = 0.867) between BM and PBSC in the univariate analysis. In the multivariate analysis, which included all factors with p < 0.50 in the univariate analysis, there was no significant prognostic factor for EFS or OS. There was no significant difference in the relapse incidence between BM and PBSC among patients with malignant diseases (BM 14.2%, PBSC 6.8%, p = 0.453). Additionally, there were no significant differences in the TRM, 5-year EFS, and OS rates between malignant and non-malignant diseases nor between the busulfan-based myeloablative regimen and reduced-intensity chemotherapy using cyclophosphamide. In this study, we showed no significant differences in EFS, OS, TRM, and GVHD, except for acute GVHD grades II-IV, between BMT and PBSCT from sibling donors, using ATG (a total of 7.5 mg/kg). Therefore, PB collection, which is less invasive for donors and less labor-intensive for doctors, could also be considered an acceptable SC source for sibling donor HSCT in children.
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Trasplante de Médula Ósea , Enfermedad Injerto contra Huésped , Trasplante de Células Madre de Sangre Periférica , Hermanos , Humanos , Niño , Masculino , Femenino , Preescolar , Adolescente , Estudios Retrospectivos , Trasplante de Médula Ósea/métodos , Lactante , Enfermedad Injerto contra Huésped/prevención & control , Acondicionamiento Pretrasplante/métodos , Trasplante de Células Madre Hematopoyéticas/métodos , Donantes de Tejidos , Resultado del Tratamiento , Suero Antilinfocítico/uso terapéutico , Suero Antilinfocítico/administración & dosificación , Trasplante HomólogoRESUMEN
Background: Rapid reduction of leukemic cells in the bone marrow during remission induction chemotherapy (RIC) can lead to significant complications such as tumor lysis syndrome (TLS). We investigated whether prephase steroid treatment before RIC could decrease TLS incidence and improve overall survival in pediatric patients with acute lymphoblastic leukemia (ALL). Methods: Data were extracted from the Common Data Model databases in two tertiary-care hospitals in Seoul, South Korea. Patients were classified into the treated or untreated group if they had received RIC with prephase steroid treatment ≥7 days before RIC in 2012-2021 or not, respectively. Stabilized Inverse Probability of Treatment Weighting (sIPTW) was applied to ensure compatibility between the treated and untreated groups. The incidence of TLS within 14 days of starting RIC, overall survival (OS), and the incidence of adverse events of special interest were the primary endpoints. Multiple sensitivity analyses were performed. Results: Baseline characteristics were effectively balanced between the treated (n=308.4) and untreated (n=246.6) groups after sIPTW. Prephase steroid treatment was associated with a significant 88% reduction in the risk of TLS (OR 0.12, 95% CI: 0.03-0.41). OS was numerically greater in the treated group than in the untreated group although the difference was not statistically significant (HR 0.64, 95% CI 0.25-1.64). The treated group experienced significantly elevated risks for hyperbilirubinemia and hyperglycemia. The reduction in TLS risk by prephase steroid treatment was maintained in all of the sensitivity analyses. Conclusion: Prephase steroid treatment for ≥7 days before RIC in pediatric patients with ALL reduces the risk of TLS, while careful monitoring for toxicities is necessary. If adequately analyzed, real-world data can provide crucial effectiveness and safety information for proper management of pediatric patients with ALL, for whom prospective randomized studies may be difficult to perform for ethical and practical reasons.
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BACKGROUND: This paper describes the protocols for a randomized controlled trial using a parallel-group trial design that includes an intervention designed to address social isolation and loneliness among people experiencing homelessness known as Miracle Friends and an intervention that combines Miracles Friends with an economic poverty-reduction intervention known as Miracle Money. Miracle Friends pairs an unhoused person with a volunteer "phone buddy." Miracle Money provides guaranteed basic income of $750 per month for 1 year to Miracle Friends participants. The study will examine whether either intervention reduces social isolation or homelessness compared to a waitlist control group. METHODS: Unhoused individuals who expressed interest in the Miracle Friends program were randomized to either receive the intervention or be placed on a waitlist for Miracle Friends. Among those randomized to receive the Miracle Friends intervention, randomization also determined whether they would be offered Miracle Money. The possibility of receiving basic income was only disclosed to study participants if they were randomly selected and participated in the Miracle Friends program. All study participants, regardless of assignment, were surveyed every 3 months for 15 months. RESULTS: Of 760 unhoused individuals enrolled in the study, 256 were randomized to receive Miracle Friends, 267 were randomized to receive Miracle Money, and 237 were randomized to the waitlist control group. In the two intervention groups, 360 of 523 unhoused individuals were initially matched to a phone buddy. Of the 191 study participants in the Miracle Money group who had been initially matched to a volunteer phone buddy, 103 were deemed to be participating in the program and began receiving monthly income. DISCUSSION: This randomized controlled trial will determine whether innovative interventions involving volunteer phone support and basic income reduce social isolation and improve housing outcomes for people experiencing homelessness. Although we enrolled unhoused individuals who initially expressed interest in the Miracle Friends program, the study team could not reach approximately 30% of individuals referred to the study. This may reflect the general lack of stability in the lives of people who are unhoused or limitations in the appeal of such a program to some portion of the unhoused population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05408884 (first submitted on May 26, 2022).
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Personas con Mala Vivienda , Renta , Soledad , Aislamiento Social , Apoyo Social , Humanos , Personas con Mala Vivienda/psicología , California , Masculino , Femenino , Adulto , Factores de Tiempo , Pobreza , Ensayos Clínicos Controlados Aleatorios como Asunto , Amigos , Persona de Mediana Edad , Voluntarios/psicologíaRESUMEN
Cerium oxide nanoparticles (CeO2 NPs, NM-212) are well-known for their catalytic properties and antioxidant potential, and have many applications in various industries, drug delivery, and cosmetic formulations. CeO2 NPs exhibit strong antimicrobial activity and can be used to efficiently remove pathogens from different environments. However, knowledge of the toxicological evaluation of CeO2 NPs is too limited to support their safe use. In this study, CeO2 NPs were orally administered to Sprague Dawley rats for 13 weeks at the doses of 0, 10, 100, and 1000 mg/kg bw/day, followed by a four week recovery period. The hematology values for the absolute and relative reticulocyte counts in male rats treated with 1000 mg/kg bw/day CeO2 NPs were lower than those in control rats. The clinical chemistry values for sodium and chloride in the treated male rat groups (100 and 1000 mg/kg/day) and total protein and calcium in the treated female rat groups (100 mg/kg/day) were higher than those in the control groups. However, these changes were not consistent in both sexes, and no abnormalities were found in the corresponding pathological findings. The results showed no adverse effects on any of the parameters assessed. CeO2 NPs accumulated in the jejunum, colon, and stomach wall of rats administered 1000 mg/kg CeO2 NPs for 90 days. However, these changes were not abnormal in the corresponding histopathological and immunohistochemical examinations. Therefore, 1000 mg/kg bw/day may be considered the "no observed adverse effect level" of CeO2 NPs (NM-212) in male and female SD rats under the present experimental conditions.
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Cerio , Nanopartículas del Metal , Nanopartículas , Ratas , Masculino , Femenino , Animales , Ratas Sprague-Dawley , Nanopartículas/química , Cerio/toxicidad , Cerio/química , Sistemas de Liberación de Medicamentos , Nanopartículas del Metal/toxicidad , Nanopartículas del Metal/químicaRESUMEN
Gallic acid (GA), a phenolic compound naturally found in many plants, exhibits potential preventive and therapeutic roles. However, the underlying molecular mechanisms of its diverse biological activities remain unclear. Here, we investigated possible mechanisms of GA function through a transcriptome-based analysis using LINCS L1000, a publicly available data resource. We compared the changes in the gene expression profiles induced by GA with those induced by FDA-approved drugs in three cancer cell lines (A549, PC3, and MCF7). The top 10 drugs exhibiting high similarity with GA in their expression patterns were identified by calculating the connectivity score in the three cell lines. We specified the known target proteins of these drugs, which could be potential targets of GA, and identified 19 potential targets. Next, we retrieved evidence in the literature that GA likely binds directly to DNA polymerase ß and ribonucleoside-diphosphate reductase. Although our results align with previous studies suggesting a direct and/or indirect connection between GA and the target proteins, further experimental investigations are required to fully understand the exact molecular mechanisms of GA. Our study provides insights into the therapeutic mechanisms of GA, introducing a new approach to characterizing therapeutic natural compounds using transcriptome-based analyses.
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Neoplasias , Transcriptoma , Humanos , Ácido Gálico/farmacología , Ácido Gálico/metabolismo , Perfilación de la Expresión GénicaRESUMEN
Cytochrome b5 reductase 3 (CYB5R3) is involved in various cellular metabolic processes, including fatty acid synthesis and drug metabolism. However, the role of CYB5R3 in cancer development remains poorly understood. Here, we show that CYB5R3 expression is downregulated in human lung cancer cell lines and tissues. Adenoviral overexpression of CYB5R3 suppresses lung cancer cell growth in vitro and in vivo. However, CYB5R3 deficiency promotes tumorigenesis and metastasis in mouse models. Transcriptome analysis revealed that apoptosis- and endoplasmic reticulum (ER) stress-related genes are upregulated in CYB5R3-overexpressing lung cancer cells. Metabolomic analysis revealed that CYB5R3 overexpression increased the production of nicotinamide adenine dinucleotide (NAD+) and oxidized glutathione (GSSG). Ectopic CYB5R3 is mainly localized in the ER, where CYB5R3-dependent ER stress signaling is induced via activation of protein kinase RNA-like ER kinase (PERK) and inositol-requiring enzyme 1 alpha (IRE1α). Moreover, NAD+ activates poly (ADP-ribose) polymerase16 (PARP16), an ER-resident protein, to promote ADP-ribosylation of PERK and IRE1α and induce ER stress. In addition, CYB5R3 induces the generation of reactive oxygen species and caspase-9-dependent intrinsic cell death. Our findings highlight the importance of CYB5R3 as a tumor suppressor for the development of CYB5R3-based therapeutics for lung cancer.
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Neoplasias Pulmonares , Proteínas Serina-Treonina Quinasas , Animales , Humanos , Ratones , Factor de Transcripción Activador 4/genética , Factor de Transcripción Activador 4/metabolismo , Apoptosis/genética , Citocromo-B(5) Reductasa/metabolismo , Estrés del Retículo Endoplásmico/genética , Endorribonucleasas/genética , Endorribonucleasas/metabolismo , Neoplasias Pulmonares/genética , Sistema de Señalización de MAP Quinasas , NAD/metabolismo , Poli(ADP-Ribosa) Polimerasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismoRESUMEN
BACKGROUND: Recently, the fine dust problem caused by rapid industrialization and science and technological development has emerged as a severe social issue worldwide. This also increases the interest in its effect on human life. In particular, there is a growing concern about the harm of fine dust in Korea. METHODS: This study is based on the PM 2.5 data from 2017 to 2021 provided by Air Korea to estimate changes in ultrafine dust. In addition, the data from the Community Health Survey provided by the Korea Centers for Disease Control and Prevention (KCDC) from 2017 to 2021 were used to examine the effect between the change in ultra-fine dust and the prevalence of depression. A total of 229 local governments were included in the analysis. The Latent Growth Modeling was carried out to estimate the change in ultra-fine dust and the prevalence of depressions and verify the relationship between ultra-fine dust and the prevalence of depression. RESULTS: The analysis result revealed that the ultra-fine dust concentration continued to decrease from 2017 to 2021. However, the depression prevalence increased from an average of 2.60% in 2017 to an average of 3.12% in 2021, suggesting the need for adequate and sufficient welfare policies for depression treatment. As a result of estimating the initial value and change rate of ultra-fine dust and depression prevalence, the higher the initial value of ultra-fine dust, the greater the decrease in ultra-fine dust. In terms of depression, the lower the initial value of the prevalence of depression, the larger the increase in depression prevalence. CONCLUSIONS: This study is significant in that it revealed the strong association of the longitudinal relationship between ultra-fine dust and depression, one of the biggest issues in Korea, by utilizing large-scale longitudinal data.
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Contaminantes Atmosféricos , Polvo , Humanos , Polvo/análisis , Depresión/epidemiología , Prevalencia , Tamaño de la Partícula , Contaminantes Atmosféricos/análisis , Monitoreo del AmbienteRESUMEN
BACKGROUND: The optimal conditioning regimen of tandem high-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) for high-risk neuroblastoma (HR-NBL) has not been established. The efficacy of 131I-MIBG therapy is under exploration in newly diagnosed HR-NBL patients. Here, we compared the outcomes of tandem HDC/ASCT between the 131I-MIBG combination and non-MIBG groups. METHODS: We retrospectively analyzed the clinical data of 33 HR-NBL patients who underwent tandem HDC/ASCT between 2007 and 2021 at the Seoul National University Children's Hospital. RESULTS: The median age at diagnosis was 3.6 years. 131I-MIBG was administered to 13 (39.4%) of the patients. Thirty patients (90.9%) received maintenance therapy after tandem HDC/ASCT, twenty-two were treated with isotretinoin ± interleukin-2, and eight received salvage chemotherapy. The five-year overall survival (OS) and event-free survival (EFS) rates of all patients were 80.4% and 69.4%, respectively. Comparing the 131I-MIBG combined group and other groups, the five-year OS rates were 82.1% and 79.7% (p = 0.655), and the five-year EFS rates were 69.2% and 69.6% (p = 0.922), respectively. Among the adverse effects of grade 3 or 4, the incidence of liver enzyme elevation was significantly higher in the non-131I-MIBG group. CONCLUSIONS: Although tandem HDC/ASCT showed promising outcomes, the 131I-MIBG combination did not improve survival rates.
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Background: Managing complex vascular anomalies in pediatric care requires comprehensive approaches. Sirolimus, an mTOR inhibitor with immunosuppressive and anti-angiogenic properties, offers promise. We evaluated sirolimus's effectiveness and safety in pediatric patients with complex vascular anomalies at a tertiary children's hospital. Methods: Our study included 20 patients, aged 1 month to 19 years, with diverse vascular anomalies resistant to conventional therapies or located in high-risk areas precluding surgery. The evaluation of response encompassed measuring the reduction in the size of the targeted vascular or lymphatic lesions as observed on radiologic imaging, along with considering improvements reported by the patients. Results: Patients used sirolimus for a median of 2.1 years, ranging from 0.6-4.3 years. Results indicated that 60% of patients achieved complete or partial response (CR/PR), whereas 40% had stable disease (SD). Notably, no disease progression occurred. Lesion size assessment was complex, yet patients' self-reported improvements were considered. Three patients reinitiated sirolimus after discontinuation due to worsening lesions. Sirolimus treatment demonstrated good tolerability, with minor complications except for one case of Pneumocystis jiroveci pneumonia. Group comparisons based on response highlighted better outcomes in patients with vascular tumors (CR/PR group 58.0% vs. SD group 0.0%, P = 0.015) or localized measurable lesions (83.3% vs. 12.5%, P = 0.005). Conclusion: Our study underscores sirolimus's potential for treating complex vascular anomalies in pediatric patients. Challenges associated with optimal treatment duration and concurrent interventions necessitate a comprehensive approach and genetic testing to optimize outcomes.
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(1) Background: Hospitalists are healthcare providers who focus on hospitalized patients, but research on the roles of pediatric hospitalists is lacking. This study investigates the role of a supervisor-type hospitalist in a pediatric hematology/oncology ward at a tertiary children's hospital, assessing the impact on satisfaction levels among patient caregivers, resident physicians, and nurses. (2) Methods: A retrospective analysis and online surveys were conducted to assess satisfaction levels before and after the introduction of hospitalists in the Department of Pediatric Hematology/Oncology at Seoul National University Children's Hospital in the Republic of Korea. (3) Results: The introduction of hospitalists led to a 19.3% reduction in prescription error interventions over six months. Unexpected transfers to the intensive care unit decreased from 1.4% to 0.7% (p = 0.229). Patient caregivers reported elevated satisfaction levels with physicians (rated 8.47/10), and there was a significant enhancement in overall satisfaction among nurses (increasing from 3.23 to 4.23/5, p < 0.001). The majority of resident physicians (83.3%) expressed contentment with the hospitalist system, with 77% indicating an interest in transitioning to a hospitalist role. However, these resident physicians also expressed concerns regarding job stability. (4) Conclusions: Supervisor-type pediatric hospitalists have the potential to elevate satisfaction levels not only among patient caregivers but also among nurses and resident physicians, showing promise in improving medical care quality. Nonetheless, ensuring favorable perception and securing job stability within the hospitalist system are pivotal for achieving successful implementation.
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Although extant research suggests that power without status, but not status without power, induces interpersonal conflict, we are yet to fully understand the asymmetric effects of holding power or status on psychological processes and group functioning. The present research attempts to fill this gap by arguing that holding power would heighten the motivation for status, whereas holding status may not necessarily have an equivalent effect on the motivation for power. We further proposed that power-status misalignment within a group would lead powerholders to be competitive toward statusholders due to heightened status motive and (upon failure to attain status) invest less in their group due to greater emotional distress. Across four (and one Supplemental) studies, we found support for our hypotheses. Our findings not only shed further light on the interactive effects of power and status, but also help better explain why power without status is particularly related to negative outcomes.
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The compositions of organic carbon could be important in determining biological carbon pump efficiency. However, little information on them in relation to each algal assemblage is currently available in the Ross Sea. Here, we investigated the seasonal variations in organic carbon composition and the relative abundance of each organic carbon, including particulate organic carbon (POC), dissolved organic carbon (DOC), and transparent exopolymer particles (TEPs), characterized by different algal groups in the Ross Sea. The average POC and DOC contributions to the total organic carbon (TOC = POC + DOC) were 13.8 ± 3.7 % and 86.2 ± 3.7 % in mid-January 2019 and 20.9 ± 4.1 % and 79.1 ± 4.1 % in February-March 2018, respectively. The carbon content of TEP (TEP-C) contributed 19.6 ± 11.7 % and 4.6 ± 7.0 % of POC and TOC in mid-January and 36.2 ± 14.8 % and 9.0 ± 6.7 % in February-March, respectively. We found that the organic carbon compositions were affected by seasonal variations in the phytoplankton bloom phase, physical characteristics, and phytoplankton community structure. DOC concentrations and contributions to the TOC increased as phytoplankton cells became senescent in mid-January and decreased in February-March when phytoplankton were relatively active. From February-March, the deepened mixed layer depth encouraged TEP formation, subsequently increasing the TEP contributions. Regardless of the sampling season, all organic carbon concentrations per unit Chl-a were significantly higher in P. antarctica-abundant groups. The DOC contributions to the TOC were correspondingly higher at the P. antarctica-abundant stations in mid-January, which indicates that P. antarctica could be also important in the DOC contributions in the Ross Sea. The rapid alteration in environmental characteristics and phytoplankton community structures in the Ross Sea due to climate change could affect the organic carbon pool at the euphotic layer which consequently could determine the efficiency of the biological pump.
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Carbono , Monitoreo del Ambiente , Fitoplancton , Materia Orgánica Disuelta , Análisis Espacio-TemporalRESUMEN
School-based, universal social and emotional learning (SEL) has been widely practiced and promoted as a promising approach to prevent youth mental, emotional, and behavioral problems. Although prior research has accumulated robust evidence of the average effects of universal SEL, it remains unclear whether it works similarly or differentially across diverse sociocultural subgroups of students. Investigating subgroup effects has implications for understanding the impact of universal SEL on possible subgroup disparities in student social-emotional competence (SEC). This study examined whether the effects of a universal SEL program on student SEC development differed across diverse student subgroups classified by gender, race, ethnicity, socioeconomic status, disability status, and English learner status. Data came from student SEC progress monitoring collected during a 1-year quasi-experimental study of a universal SEL program (N = 1592; Grades K-2). The results of multigroup latent growth modeling suggest that (a) the intervention effects were slightly larger for Black students, compared to White or other racial-ethnic subgroups, and (b) the effects were not different across other examined subgroups. This study also found that in the comparison condition, the SEC disparities between Black and White students tended to widen throughout the year, whereas in the intervention condition, Black students showed a similar rate of growth as their White peers. Findings suggest that universal SEL may be similarly beneficial across many diverse student subgroups, while it may yield larger benefits among some racially marginalized subgroups, preventing racial disparities from further widening. Yet the benefits of SEL may not be sufficient to reduce existing subgroup disparities. These findings suggest a need for more studies to examine differential effects of universal preventive programs by diverse subgroups to better inform practices that enhance equity in youth outcomes.
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Aprendizaje , Aprendizaje Social , Adolescente , Humanos , Emociones , Estudiantes/psicología , Instituciones AcadémicasRESUMEN
Juvenile myelomonocytic leukemia (JMML) is a life-threatening myeloproliferative neoplasm. The chemotherapeutic effect on survival remains unclear, and feasible standardized response criteria are yet to be established. We aimed to evaluate the chemotherapeutic response and its effect on survival in patients with JMML. A retrospective registry was reviewed for children diagnosed with JMML between 2000 and 2019. Response was assessed according to the criteria proposed by the International JMML Symposium in 2007 (criteria I) and the updated version in 2013 with its modifications (criteria II). A total of 73 patients were included in this study. Complete response (CR) rates were 46.6% and 28.8% using the criteria I and criteria II, respectively. A platelet count ≥ 40 × 109/L at diagnosis was associated with higher CR rates using the criteria II. Patients with criteria I-based CR had a better overall survival (OS) than those without CR (81.1% vs. 49.1% at 5 years). Patients with criteria II-based CR showed better OS (85.7% vs. 55.5% at 5 years) and event-free survival (EFS) (71.1% vs. 44.7% at 5 years) than those without CR. Additionally, a trend toward better EFS was observed in patients with criteria II-based CR than in those with criteria I-based CR but without criteria II-based CR (71.1% vs. 53.8% at 5 years). Chemotherapeutic response is associated with better survival outcomes. Along with splenomegaly, the addition of platelet count recovery, existence of extramedullary leukemic infiltration, and more stringent leukocyte counts to the response criteria allows for a more sensitive prediction of survival outcomes.
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Hematología , Leucemia Mielomonocítica Juvenil , Niño , Humanos , Leucemia Mielomonocítica Juvenil/tratamiento farmacológico , Leucemia Mielomonocítica Juvenil/diagnóstico , Estudios Retrospectivos , Supervivencia sin Progresión , República de Corea/epidemiologíaRESUMEN
Increasing evidence indicates that DNA damage-induced apoptosis suppressor (DDIAS) is an oncogenic protein that is highly expressed in a variety of cancers, including colorectal cancer, lung cancer, breast cancer, and hepatocellular carcinoma (HCC). The discovery of DDIAS as a novel therapeutic target and its role in human cancer biology is fascinating and noteworthy. Recent studies have shown that DDIAS is involved in tumorigenesis, metastasis, DNA repair and synthesis, and drug resistance and that it plays multiple roles with distinct binding partners in several human cancers. This review focuses on the function of DDIAS and its regulatory proteins in human cancer as potential targets for cancer therapy, as well as the development and future prospects of DDIAS inhibitors.
Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Apoptosis/genética , Neoplasias Pulmonares/genética , Daño del ADNRESUMEN
Nucleocytoplasmic large DNA viruses (NCLDVs) infect various marine eukaryotes. However, little is known about NCLDV diversity and their relationships with eukaryotic hosts in marine environments, the elucidation of which will advance the current understanding of marine ecosystems. This study characterizes the interplay between NCLDVs and the eukaryotic plankton community (EPC) in the sub-Arctic area using metagenomics and metabarcoding to investigate NCLDVs and EPC, respectively, in the Kongsfjorden ecosystem of Svalbard (Norway) in April and June 2018. Gyrodinium helveticum (Dinophyceae) is the most prevalent eukaryotic taxon in the EPC in April, during which time Mimiviridae (31.8%), Poxviridae (25.1%), Phycodnaviridae (14.7%) and Pandoraviridae (13.1%) predominate. However, in June, the predominant taxon is Aureococcus anophagefferens (Pelagophyceae), and the NCLDVs, Poxviridae (32.9%), Mimiviridae (29.1%), and Phycodnaviridae (18.5%) appear in higher proportions with an increase in Pelagophyceae, Bacillariophyceae, and Chlorophyta groups. Thus, differences in NCLDVs may be caused by changes in EPC composition in response to environmental changes, such as increases in water temperature and light intensity. Taken together, these findings are particularly relevant considering the anticipated impact of NCLDV-induced EPC control mechanisms on polar regions and, therefore, improve the understanding of the Sub-Arctic Kongsfjorden ecosystem.